WorldWideScience

Sample records for future drug design

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

    Science.gov (United States)

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

    2015-12-01

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

  2. 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.

  3. 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.

  4. [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.

  5. Designing the molecular future

    OpenAIRE

    Schneider Gisbert

    2011-01-01

    Approximately 25 years ago the first computer applications were conceived for the purpose of automated 'de novo' drug design prominent pioneering tools being ALADDIN CAVEAT GENOA and DYLOMMS. Many of these early concepts were enabled by innovative techniques for ligand receptor interaction modeling like GRID MCSS DOCK and CoMFA which still provide the theoretical framework for several more recently developed molecular design algorithms. After a first wave of software tools and groundbreaking ...

  6. Designing the Future

    Directory of Open Access Journals (Sweden)

    Friso de Zeeuw

    2010-04-01

    Full Text Available The Netherlands has a tradition in public spatial planning and design. In the past 20 years, we have seen an increasing role for the market in this field, and more recently, growing attention for sustainability. Sustainability has become an economic factor. Not only at the building level, but also on the level of large-scale area development projects. More and more local governments have high ambitions for sustainable development. Increasingly, during project development, buildings are developed on a sustainable basis. Most of the time, the focus in this approach is on energy. However, sustainability also comprises social aspects. Energy measures have a direct relation to an economic factor such as investment costs, and payback time can be calculated. The economic aspects of social sustainability are more complex. Therefore, for all sustainability development projects, especially in large-scale projects planned over a longer period, it is necessary to make presumptions, which are less reliable as the planning period is extended. For future larger-scale developments, experience in the Netherlands points to two design approaches: ‘backcasting’, or using a growth model (or a combination of these two. The power of design is the ability to imagine possible scenarios for the future. The layer approach helps to integrate sustainability into public spatial planning. And more specifically, Urban Design Management (UDM supports an integrative and collaborative approach also on the operational level of a project in which public and market partners work together. This article outlines how design, based on these approaches, can contribute to sustainable development based on the ‘new playing field’, where spatial problems should be solved in networks. Dutch projects in Almere (Benoordenhout and Rijswijk are used to illustrate this approach.

  7. Projecting future drug expenditures--2009.

    Science.gov (United States)

    Hoffman, James M; Shah, Nilay D; Vermeulen, Lee C; Doloresco, Fred; Martin, Patrick K; Blake, Sharon; Matusiak, Linda; Hunkler, Robert J; Schumock, Glen T

    2009-02-01

    Drug expenditure trends in 2007 and 2008, projected drug expenditures for 2009, and factors likely to influence drug expenditures are discussed. Various factors are likely to influence drug expenditures in 2009, including drugs in development, the diffusion of new drugs, drug safety concerns, generic drugs, Medicare Part D, and changes in the drug supply chain. The increasing availability of important generic drugs and drug safety concerns continue to moderate growth in drug expenditures. The drug supply chain remains dynamic and may influence drug expenditures, particularly in specialized therapeutic areas. Initial data suggest that the Medicare Part D benefit has influenced drug expenditures, but the ultimate impact of the benefit on drug expenditures remains unclear. From 2006 to 2007, total U.S. drug expenditures increased by 4.0%, with total spending rising from $276 billion to $287 billion. Drug expenditures in clinics continue to grow more rapidly than in other settings, with a 9.9% increase from 2006 to 2007. Hospital drug expenditures increased at a moderate rate of only 1.6% from 2006 to 2007; through the first nine months of 2008, hospital drug expenditures increased by only 2.8% compared with the same period in 2007. In 2009, we project a 0-2% increase in drug expenditures in outpatient settings, a 1-3% increase in expenditures for clinic-administered drugs, and a 1-3% increase in hospital drug expenditures.

  8. 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.

  9. 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.

  10. The national drug abuse treatment clinical trials network data share project: website design, usage, challenges, and future directions.

    Science.gov (United States)

    Shmueli-Blumberg, Dikla; Hu, Lian; Allen, Colleen; Frasketi, Michael; Wu, Li-Tzy; Vanveldhuisen, Paul

    2013-01-01

    There are many benefits of data sharing, including the promotion of new research from effective use of existing data, replication of findings through re-analysis of pooled data files, meta-analysis using individual patient data, and reinforcement of open scientific inquiry. A randomized controlled trial is considered as the 'gold standard' for establishing treatment effectiveness, but clinical trial research is very costly, and sharing data is an opportunity to expand the investment of the clinical trial beyond its original goals at minimal costs. We describe the goals, developments, and usage of the Data Share website (http://www.ctndatashare.org) for the National Drug Abuse Treatment Clinical Trials Network (CTN) in the United States, including lessons learned, limitations, and major revisions, and considerations for future directions to improve data sharing. Data management and programming procedures were conducted to produce uniform and Health Insurance Portability and Accountability Act (HIPAA)-compliant de-identified research data files from the completed trials of the CTN for archiving, managing, and sharing on the Data Share website. Since its inception in 2006 and through October 2012, nearly 1700 downloads from 27 clinical trials have been accessed from the Data Share website, with the use increasing over the years. Individuals from 31 countries have downloaded data from the website, and there have been at least 13 publications derived from analyzing data through the public Data Share website. Minimal control over data requests and usage has resulted in little information and lack of control regarding how the data from the website are used. Lack of uniformity in data elements collected across CTN trials has limited cross-study analyses. The Data Share website offers researchers easy access to de-identified data files with the goal to promote additional research and identify new findings from completed CTN studies. To maximize the utility of the website

  11. Designing Futures in Indonesia

    OpenAIRE

    Alexandra Crosby

    2016-01-01

    Design is a wide reaching and unruly idea, often associated with seamless global mobility, ubiquitous consumerism, elite urban tastes, and fast paced economic growth. But design is also increasingly understood to be operating at edges, as a necessary response to the ethical and political challenges of advanced global capitalism. Design is both the problem and the solution, and effects everything. As Tony Fry writes ‘Design–the designer and designed objects, images, systems and things–shapes t...

  12. Future product design

    DEFF Research Database (Denmark)

    Andreasen, Mogens Myrup

    1997-01-01

    This paper (in form of overheads) formulate new challenges and possibilities for engineering design, utilizing rationalization effect from modularisation, re-use and transparaency.......This paper (in form of overheads) formulate new challenges and possibilities for engineering design, utilizing rationalization effect from modularisation, re-use and transparaency....

  13. Future integrated design environments

    DEFF Research Database (Denmark)

    Christiansson, Per; Svidt, Kjeld; Sørensen, Kristian Birch

    2009-01-01

    and modeling of explicit and implicit end-user needs and requirements on both the building to be designed and the supporting design tools. The paper provides grounds to higher success rate in capture of explicit and implicit end user needs and requirements on functional performance in use and re...

  14. Designing the future

    NARCIS (Netherlands)

    De Zeeuw, F.; Franzen, A.; Aalbers, K.; Van Hal, A.; Dulski, B.

    2010-01-01

    The Netherlands has a tradition in public spatial planning and design. In the past 20 years, we have seen an increasing role for the market in this field, and more recently, growing attention for sustainability. Sustainability has become an economic factor. Not only at the building level, but also

  15. Designing Futures in Indonesia

    Directory of Open Access Journals (Sweden)

    Alexandra Crosby

    2016-08-01

    This curated issue takes as its departure point Fry’s notion that design broadly shapes the world we occupy. To ask what happens when the world we occupy is not conceived simply in terms of local issues and solutions, but rather as a set of shared concerns that are localised and play out through global flows. To do so this issue presents ten contributions from Indonesia.

  16. Design for the future

    International Nuclear Information System (INIS)

    Antelo, R.

    1998-01-01

    Up until a few years ago, to be successful it was sufficient to have a product which was different from he competition's product in one of the following ways: price, quality, innovation design. With respect to other characteristics, it was sufficient just not to be outstandingly negative. The current scene is totally different. If a products is situated in the middle of the competition with respect to the above factors, only the Company's survival can be guaranteed (with difficulty). If on the other hand, it is situated below the competition with respect to some of the above characteristics, the Company may be in danger. If the product is situated above the competitive advantage will be guaranteed. The capacity to generate winning products is therefore a key factor to generating shareholder value: the success of the product and, therefore, the company's success is determined when the product is conceived and developed and on the selection of technological processes. In this context we have developed a model of reference to help companies attain excellence when developing products. (Author)

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. Crystallography and Drug Design

    Indian Academy of Sciences (India)

    IAS Admin

    is of immense help in developing drugs for specific diseases by targeting molecules ... tions, or selected from a large pool of available libraries and the binding strengths can ... was identified to be caused by a virus named later as the human.

  2. 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.

  3. Designing the Future of Democracy

    DEFF Research Database (Denmark)

    Pichlmair, Martin

    2015-01-01

    Creating a simulation of Democracy and its future challenges is a fruitful exercise in design. This short paper describes a different use of a simulation that the traditional training via playing. Instead of playing, the creation of the simulation is at the center of attention....

  4. 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...

  5. 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.

  6. Future steam generator designs. Single wall designs

    Energy Technology Data Exchange (ETDEWEB)

    Hayden, O [Nuclear Power Company Ltd, Warrington, Cheshire (United Kingdom)

    1978-10-01

    The easily removable 'U' tube design style adopted in the UK for the existing PFR Steam Generators, the Replacement Units now in production and for the future CDFR, gives the operator an extremely valuable option in the event of a water/steam leak occurring inside the Steam Generator. He can choose to shut-down, attempt to find the leak, assess damage, repair, revalidate and return to service in situ, or he can elect to remove the defect unit and replace with a 'proven' spare before returning the circuit to power. With the latter approach the resultant outage time is a known entity of about two weeks. If a repair is attempted in situ, predictions of outage time can become a matter of guesswork since one has no 'guaranteed' method of leak location and the assessment of secondary damage may be very time consuming, depending on the size and type of the original leak together with the particular design style of the Steam Generator. A further significant advantage of the removable 'U' tube design concept is that periodic interchanging of bundles with a spare enables routine chemical cleaning and thorough scheduled tube inspections, with specimen tube sample removal if required for monitoring purposes. If necessary, bundle decontamination can be undertaken to assess engineering deterioration to various degrees of thoroughness ranging from 100% equivalent factory final assembly inspection, to partial decontamination operating via a glovebox type of maintenance bag arrangement, examining local points of both shell and tube areas of the bundle. Many lessons from the last five years' experience of PFR will be incorporated into the design of the CDFR and PFR Steam Generators have two very good examples of how the designer can ease or severely handicap the operator in coping with sodium/water leakages. Good, quick access to tube ends is achieved in the existing PFR Evaporator by simply unbolting the steam/water closure head, but on the superheater and reheater hand-caps have

  7. Future steam generator designs. Single wall designs

    International Nuclear Information System (INIS)

    Hayden, O.

    1978-01-01

    The easily removable 'U' tube design style adopted in the UK for the existing PFR Steam Generators, the Replacement Units now in production and for the future CDFR, gives the operator an extremely valuable option in the event of a water/steam leak occurring inside the Steam Generator. He can choose to shut-down, attempt to find the leak, assess damage, repair, revalidate and return to service in situ, or he can elect to remove the defect unit and replace with a 'proven' spare before returning the circuit to power. With the latter approach the resultant outage time is a known entity of about two weeks. If a repair is attempted in situ, predictions of outage time can become a matter of guesswork since one has no 'guaranteed' method of leak location and the assessment of secondary damage may be very time consuming, depending on the size and type of the original leak together with the particular design style of the Steam Generator. A further significant advantage of the removable 'U' tube design concept is that periodic interchanging of bundles with a spare enables routine chemical cleaning and thorough scheduled tube inspections, with specimen tube sample removal if required for monitoring purposes. If necessary, bundle decontamination can be undertaken to assess engineering deterioration to various degrees of thoroughness ranging from 100% equivalent factory final assembly inspection, to partial decontamination operating via a glovebox type of maintenance bag arrangement, examining local points of both shell and tube areas of the bundle. Many lessons from the last five years' experience of PFR will be incorporated into the design of the CDFR and PFR Steam Generators have two very good examples of how the designer can ease or severely handicap the operator in coping with sodium/water leakages. Good, quick access to tube ends is achieved in the existing PFR Evaporator by simply unbolting the steam/water closure head, but on the superheater and reheater hand-caps have

  8. Designers predict a bright future

    International Nuclear Information System (INIS)

    Statton, T.D.

    1996-01-01

    As power plant designers and builders, there is a bright future for the industry. The demand for electricity will continue to grow, and the need for new plants will increase accordingly. But companies that develop and supply these plants must adapt to new ways of doing business if they expect to see the dawn of this new age. Several factors will have a profound effect on the generation and use of electricity in future years. Instant communications now reach all corners of the globe, making people everywhere aspire to a higher standard of living. The economic surge needed to satisfy these appetites will, in turn, be fed by a network of suppliers who are themselves restructuring to serve global markets, unimpeded by past nationalistic barriers to trade. The strong correlation between economic progress and the growing demand for electricity is well recognized. A ready supply of affordable electricity is a necessary underpinning for any economic expansion. As economies advance and jobs increase, electric demand grows geometrically, fueled by an ever-improving quality of life. Coupled with increasing demand is the worldwide trend toward privatization of the generation industry. The reasons may vary in different parts of the world, but the effect is the same--companies are battling intensely for the right to build or purchase generating facilities. Those companies, like the industry they serve, are themselves in a period of transition. Once a closed, monopolistic group of owners in a predominantly services-based market, they are, thanks to competitive forces, being driven steadily toward a product-based structure

  9. The Future of Organization Design

    OpenAIRE

    Jay R. Galbraith

    2012-01-01

    The type of organization design that I practice is strategic organization design. It has roots in Chandler's (1962) work which states, "Structure follows strategy." It applies to organizing at the enterprise, business unit, region, or functional levels. It is a top-down design methodology. The alternative is a bottom-up design approach such as the socio-technical systems approach. Bottom-up design methodologies build and design an organization around the technology being utilized and are most...

  10. 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.

  11. The Future of Organization Design

    Directory of Open Access Journals (Sweden)

    Jay R. Galbraith

    2012-05-01

    Full Text Available The type of organization design that I practice is strategic organization design. It has roots in Chandler's (1962 work which states, "Structure follows strategy." It applies to organizing at the enterprise, business unit, region, or functional levels. It is a top-down design methodology. The alternative is a bottom-up design approach such as the socio-technical systems approach. Bottom-up design methodologies build and design an organization around the technology being utilized and are most applicable at lower levels of the organization.

  12. Dosage design - past, present and future

    International Nuclear Information System (INIS)

    Ganderton, D.

    1982-01-01

    The design criteria to be considered in the formulation of drugs is discussed eg. the porosity, density, solubility and compressibility of tablets. Structure related to function. The absorbability of drug surfaces in the intestinal tract and the relationship of this to the pH of stomach contents. Particle size and the role of release of a drug for maximum therapeutic effect. Pharmacodynamic intensity and the use of polymers as matrix materials for slow-release drugs. Sites of administration and targeting of drugs, and the physiological response of the body are all important. (U.K.)

  13. [Development of antituberculous drugs: current status and future prospects].

    Science.gov (United States)

    Tomioka, Haruaki; Namba, Kenji

    2006-12-01

    latently infected with MTB. Unfortunately, no new drugs except rifabutin and rifapentine has been marketed for TB in the US and other countries during the 40 years after release of rifampicin. There are a number of constraints that have deterred companies from investing in new anti-TB drugs. The research is expensive, slow and difficult, and requires specialized facilities for handling MTB. There are few animal models that closely mimic the human TB disease. Development time of any anti-TB drug will be long. In fact, clinical trials will require the minimum six-month therapy, with a follow-up period of one year or more. In addition, it is hard to demonstrate obvious benefit of a new anti-TB agents over pre-existing drugs, since clinical trials involve multidrug combination therapy using highly effective ordinary anti-TB drugs. Finaly, there is the perceived lack of commercial return to companies engaged in the development of new anti-TB drugs, because over 95% of TB cases worldwide are in developing countries. In this symposium, we reviewed the following areas. 1. Critical new information on the entire genome of MTB recently obtained and increasing knowledge of various mycobacterial virulence genes are greatly promoting the identification of genes that code for new drug targets. In this context, Dr. Namba reviewed the status of new types of compounds which are being developed as anti-TB drug. He also discussed the development of new antimycobacterial drugs according to new and potential pharmacological targets and the best clinical development plans for new-TB drugs in relation to corporate strategy. 2. Using such findings for mycobacterial genomes, bioinformatics/genomics/proteomics-based drug design and drug development using quantitative structure-activity relationships may be possible in the near future. In this context, Dr. Suwa and Dr. Suzuki reviewed the usefulness of chemical genomics in searching novel drug targets for development of new antituberculous drugs. The

  14. Designing the future of healthcare.

    Science.gov (United States)

    Fidsa, Gianfranco Zaccai

    2009-01-01

    This paper describes the application of a holistic design process to a variety of problems plaguing current healthcare systems. A design process for addressing complex, multifaceted problems is contrasted with the piecemeal application of technological solutions to specific medical or administrative problems. The goal of this design process is the ideal customer experience, specifically the ideal experience for patients, healthcare providers, and caregivers within a healthcare system. Holistic design is shown to be less expensive and wasteful in the long run because it avoids solving one problem within a complex system at the cost of creating other problems within that system. The article applies this approach to the maintenance of good health throughout life; to the creation of an ideal experience when a person does need medical care; to the maintenance of personal independence as one ages; and to the enjoyment of a comfortable and dignified death. Virginia Mason Medical Center is discussed as an example of a healthcare institution attempting to create ideal patient and caregiver experiences, in this case by applying the principles of the Toyota Production System ("lean manufacturing") to healthcare. The article concludes that healthcare is inherently dedicated to an ideal, that science and technology have brought it closer to that ideal, and that design can bring it closer still.

  15. Designing Firms to Fit the Future

    Directory of Open Access Journals (Sweden)

    Raymond E. Miles

    2012-08-01

    Full Text Available Most firms identify market opportunities for their new technologies after they have been developed. This article discusses the design of a “futures group” which can help to synchronize a firm’s technology and market development. A futures group designed to span more than one organization could lead to simultaneous market development for multiple technologies.

  16. 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.

  17. "9th Annual Congress on Drug Formulation & Drug Design"

    OpenAIRE

    Monty Karl

    2017-01-01

    Conference Series has been instrumental in conducting international meetings for seven years, and very excited to expand Europe, America and Asia Pacific continents. Previous meetings were held in major cities like Belgium, Tokyo, Madrid, with success the meetings again scheduled in three continents. It’s time to announce 9th Annual Congress on Drug Formulation & Drug Design October 19-21, 2017 Seoul, South Korea . Drug Formulation 2017 is a 3-day event offering the Exhibition, at venue to sh...

  18. The impact of population ageing on future Danish drug expenditure

    DEFF Research Database (Denmark)

    Kildemoes, Helle Wallach

    expenditure among the elderly partly is due the high "costs of dying". Aims The aim of this study was to estimate the impact of the ageing Danish population on future total expenditures on out-of-hospital prescription drugs and to describe the association between age and drug expenditure among survivors......Background Population ageing is likely to place an increasing burden on future health care budgets. Several studies have demonstrated that the impact of ageing on future hospital expenditures will be overestimated when not accounting for proximity to death. This is because greater health care...... compared to that of decedents. Methods Taking expenditure during the last year of life and the changes in mortality rates into account, future drug expenditure was projected by multiplying estimated mean annual drug expenditure according to age, gender and survival status by the predicted future number...

  19. Meningococcal disease and future drug targets

    DEFF Research Database (Denmark)

    Gammelgaard, L K; Colding, H; Hartzen, S H

    2011-01-01

    recent data and current knowledge on molecular mechanisms of meningococcal disease and explains how host immune responses ultimately may aggravate neuropathology and the clinical prognosis. Within this context, particular importance is paid to the endotoxic components that provide potential drug targets...... for novel neuroprotective adjuvants, which are needed in order to improve the clinical management of meningoencephalitis and patient prognosis....

  20. Computer aided architectural design : futures 2001

    NARCIS (Netherlands)

    Vries, de B.; Leeuwen, van J.P.; Achten, H.H.

    2001-01-01

    CAAD Futures is a bi-annual conference that aims to promote the advancement of computer-aided architectural design in the service of those concerned with the quality of the built environment. The conferences are organized under the auspices of the CAAD Futures Foundation, which has its secretariat

  1. Future Challenges and Opportunities in Online Prescription Drug Promotion Research

    Science.gov (United States)

    Southwell, Brian G.; Rupert, Douglas J.

    2016-01-01

    Despite increased availability of online promotional tools for prescription drug marketers, evidence on online prescription drug promotion is far from settled or conclusive. We highlight ways in which online prescription drug promotion is similar to conventional broadcast and print advertising and ways in which it differs. We also highlight five key areas for future research: branded drug website influence on consumer knowledge and behavior, interactive features on branded drug websites, mobile viewing of branded websites and mobile advertisements, online promotion and non-US audiences, and social media and medication decisions. PMID:26927597

  2. Telomerase – future drug target enzyme?

    Directory of Open Access Journals (Sweden)

    Tomaž Langerholc

    2012-06-01

    Full Text Available Eucaryotic chromosome endings (telomeres replication problem was solved in the 1980’s by discovery of the telomerase enzyme. The Nobel Prize in Physiology or Medicine was awarded in 2009 for the discovery of telomerase. Altered telomerase expression in cancer, and human dream of eternal youth have accelerated the development of pharmacological telomerase inhibitors and activators. However, after 15 years of development they are still not available on the market. In the present article we reviewed pharmacological agents that target telomerase activity, which have entered clinical trials. Current drugs in development are mostly not intended to be used alone, as telomerase inhibitors under clinical trials are used in combination with the existing chemotherapeutics and anti-telomerase vaccines in combination with immuno-stimulants. Apart from cancer and aging, there are other diseases linked to deregulated activity of telomerase/telomeres and we also discuss technical and legal problems that researchers encounter in developing anti-telomerase therapy. Given the pace of development, first anti-telomerase drugs might appear on the market in the next 5 years.

  3. Psychiatry & the psychedelic drugs. Past, present & future.

    Science.gov (United States)

    Rucker, James J H; Iliff, Jonathan; Nutt, David J

    2017-12-25

    The classical psychedelic drugs, including psilocybin, lysergic acid diethylamide and mescaline, were used extensively in psychiatry before they were placed in Schedule I of the UN Convention on Drugs in 1967. Experimentation and clinical trials undertaken prior to legal sanction suggest that they are not helpful for those with established psychotic disorders and should be avoided in those liable to develop them. However, those with so-called 'psychoneurotic' disorders sometimes benefited considerably from their tendency to 'loosen' otherwise fixed, maladaptive patterns of cognition and behaviour, particularly when given in a supportive, therapeutic setting. Pre-prohibition studies in this area were sub-optimal, although a recent systematic review in unipolar mood disorder and a meta-analysis in alcoholism have both suggested efficacy. The incidence of serious adverse events appears to be low. Since 2006, there have been several pilot trials and randomised controlled trials using psychedelics (mostly psilocybin) in various non-psychotic psychiatric disorders. These have provided encouraging results that provide initial evidence of safety and efficacy, however the regulatory and legal hurdles to licensing psychedelics as medicines are formidable. This paper summarises clinical trials using psychedelics pre and post prohibition, discusses the methodological challenges of performing good quality trials in this area and considers a strategic approach to the legal and regulatory barriers to licensing psychedelics as a treatment in mainstream psychiatry. Copyright © 2017. Published by Elsevier Ltd.

  4. EcoDesign and future environmental impacts

    DEFF Research Database (Denmark)

    Jeswiet, Jack; Hauschild, Michael Zwicky

    2005-01-01

    This paper describes the relation between EcoDesign and Life Cycle Engineering; both include Product Engineering as a focal point. Product Engineering includes both product design and manufacture, two fields which are changing quickly. In addition, this paper shows where future changes can be exp...

  5. 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

  6. 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.

  7. Current situation and future usage of anticancer drug databases.

    Science.gov (United States)

    Wang, Hongzhi; Yin, Yuanyuan; Wang, Peiqi; Xiong, Chenyu; Huang, Lingyu; Li, Sijia; Li, Xinyi; Fu, Leilei

    2016-07-01

    Cancer is a deadly disease with increasing incidence and mortality rates and affects the life quality of millions of people per year. The past 15 years have witnessed the rapid development of targeted therapy for cancer treatment, with numerous anticancer drugs, drug targets and related gene mutations been identified. The demand for better anticancer drugs and the advances in database technologies have propelled the development of databases related to anticancer drugs. These databases provide systematic collections of integrative information either directly on anticancer drugs or on a specific type of anticancer drugs with their own emphases on different aspects, such as drug-target interactions, the relationship between mutations in drug targets and drug resistance/sensitivity, drug-drug interactions, natural products with anticancer activity, anticancer peptides, synthetic lethality pairs and histone deacetylase inhibitors. We focus on a holistic view of the current situation and future usage of databases related to anticancer drugs and further discuss their strengths and weaknesses, in the hope of facilitating the discovery of new anticancer drugs with better clinical outcomes.

  8. 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.

  9. Advanced materials and processing for drug delivery: the past and the future.

    Science.gov (United States)

    Zhang, Ying; Chan, Hon Fai; Leong, Kam W

    2013-01-01

    Design and synthesis of efficient drug delivery systems are of vital importance for medicine and healthcare. Materials innovation and nanotechnology have synergistically fueled the advancement of drug delivery. Innovation in material chemistry allows the generation of biodegradable, biocompatible, environment-responsive, and targeted delivery systems. Nanotechnology enables control over size, shape and multi-functionality of particulate drug delivery systems. In this review, we focus on the materials innovation and processing of drug delivery systems and how these advances have shaped the past and may influence the future of drug delivery. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. 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.

  11. 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.…

  12. 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.

  13. 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.

  14. LEGO-inspired drug design

    DEFF Research Database (Denmark)

    Thanh Tung, Truong; Dao, Trong Tuan; Grifell Junyent, Marta

    2018-01-01

    The fungal plasma membrane H+-ATPase (Pma1p) is a potential target for the discovery of new antifungal agents. Surprisingly, no structure-activity relationship studies for small molecules targeting Pma1p have been reported. Herein, we disclose a LEGO-inspired fragment assembly strategy for design...

  15. Adolescents' future orientation and nonmedical use of prescription drugs.

    Science.gov (United States)

    Steiger, Rena M; Stoddard, Sarah A; Pierce, Jennifer

    2017-02-01

    How adolescents think about their future (i.e., future orientation) impacts their risk-taking behavior. The purpose of the present analysis was to explore whether future orientation (future planning, perceived risk to future goals, and positive future expectations) was associated with nonmedical use of stimulants and analgesics in a sample of high school students. Information on future orientation and nonmedical use of prescription drugs (NMUPD) were collected using a paper-and-pencil survey from a sample of 9th-12th grade students in a Midwestern school. Higher perceived risk to future goals and positive future expectations were associated with a lower likelihood of self-reported nonmedical use of stimulants (n=250; OR=0.46, 95% CI: 0.26, 0.83; OR=0.15, 95% CI: 0.05, 0.47, respectively). Only higher perceived risk to future goals was associated with a lower likelihood of self-reported nonmedical use of analgesics (n=250; OR=0.40, 95% CI: 0.24, 0.68). In a follow-up analysis limited to students who endorsed alcohol or marijuana use, perceived risk to future goals remained associated with a lower likelihood of nonmedical use of stimulants and analgesics. Results suggest that risk perception might be a salient protective factor against both nonmedical use of stimulants and analgesics. Overall, the differential impact of conceptualizations of future orientation might depend on the class of prescription drug used, demonstrating a need to consider prescription drugs individually in the development of future studies and interventions. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Designing Adaptable Ships: Modularity and Flexibility in Future Ship Designs

    Science.gov (United States)

    2016-01-01

    with motors, belts, shafts , seals, valves, hose spindles , and switches. If ship installation is not installed, the system will be status quo. Ship...Impact: the current centrifugal purifiers (Alfa-Laval) have experienced frequent failures with motor, belts, shafts , seals, valves, hose spindles ... Designing Adaptable Ships Modularity and Flexibility in Future Ship Designs John F. Schank, Scott Savitz, Ken Munson, Brian Perkinson, James

  17. Drug resistance in leishmaniasis: current drug-delivery systems and future perspectives.

    Science.gov (United States)

    Yasinzai, Masoom; Khan, Momin; Nadhman, Akhtar; Shahnaz, Gul

    2013-10-01

    Leishmaniasis is a complex of diseases with numerous clinical manifestations for instance harshness from skin lesions to severe disfigurement and chronic systemic infection in the liver and spleen. So far, the most classical leishmaniasis therapy, despite its documented toxicities, remains pentavalent antimonial compounds. The arvailable therapeutic modalities for leishmaniasis are overwhelmed with resistance to leishmaniasis therapy. Mechanisms of classical drug resistance are often related with the lower drug uptake, increased efflux, the faster drug metabolism, drug target modifications and over-expression of drug transporters. The high prevalence of leishmaniasis and the appearance of resistance to classical drugs reveal the demand to develop and explore novel, less toxic, low cost and more promising therapeutic modalities. The review describes the mechanisms of classical drug resistance and potential drug targets in Leishmania infection. Moreover, current drug-delivery systems and future perspectives towards Leishmaniasis treatment are also covered.

  18. Classifying new anti-tuberculosis drugs: rationale and future perspectives

    Directory of Open Access Journals (Sweden)

    Simon Tiberi

    2017-03-01

    Full Text Available The classification of anti-tuberculosis (TB drugs is important as it helps the clinician to build an appropriate anti-TB regimen for multidrug-resistant (MDR and extensively drug-resistant (XDR TB cases that do not fulfil the criteria for the shorter MDR-TB regimen. The World Health Organization (WHO has recently approved a revision of the classification of new anti-TB drugs based on current evidence on each drug. In the previous WHO guidelines, the choice of drugs was based on efficacy and toxicity in a step-down manner, from group 1 first-line drugs and groups 2–5 second-line drugs, to group 5 drugs with potentially limited efficacy or limited clinical evidence. In the revised WHO classification, exclusively aimed at managing drug-resistant cases, medicines are again listed in hierarchical order from group A to group D. In parallel, a possible future classification is independently proposed. The aim of this viewpoint article is to describe the evolution in WHO TB classification (taking into account an independently proposed new classification and recent changes in WHO guidance, while commenting on the differences between them. The latest evidence on the ex-group 5 drugs is also discussed.

  19. Citizen involvement in future drug R&D

    DEFF Research Database (Denmark)

    Møldrup, Claus; Morgall, Janine Marie; Almarsdóttir, Anna Birna

    2000-01-01

    This article adopts a prospective approach in an attempt to explore the potential benefit of citizen involvement in decision making concerning future drug R&D. This is one of the first Delphi studies to fully utilize internet technology to collect and process data. The results show an increasing...... individual autonomy among respondents, which also affects the drug R&D process in general. Human, liberal and ethical values are reported as crucial values to citizens. On this basis, respondents reported that patient organizations, representative citizen groups and ethical councils can contribute...... with important input to ensure these values in decision making concerning future drug R&D. Paying attention to citizen needs, demands and ideas may protect the research, development and eventual marketing of unacceptable drugs on a societal and ethical level....

  20. The Future of Design: Unframed Problem Solving in Design Education

    DEFF Research Database (Denmark)

    Friis, Silje Alberthe Kamille; Gelting, Anne Katrine Gøtzsche

    2016-01-01

    The present paper sets out to investigate the impact and significance of a 3rd semester course in design methods, complex problem solving, and cross-disciplinary collaboration to the students within six design disciplines as experienced by the students three years later. The course reflects a shi......, society, and technology influencing the future disciplines and practices of design and thus the professional roles that they themselves might take....

  1. Molecular Rift: Virtual Reality for Drug Designers.

    Science.gov (United States)

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

    2015-11-23

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

  2. Clinic exam room design: present and future.

    Science.gov (United States)

    Freihoefer, Kara; Nyberg, Gary; Vickery, Christine

    2013-01-01

    This article aims to deconstruct various design qualities and strategies of clinic exam rooms, and discuss how they influence users' interaction and behavior in the space. Relevant literature supports the advantages and disadvantages of different design strategies. Annotated exam room prototypes illustrate the design qualities and strategies discussed. Advancements in technology and medicine, along with new legislative policies, are influencing the way care providers deliver care and ultimately clinic exam room designs. The patient-centered medical home model has encouraged primary care providers to make patients more active leaders of their health plan which will influence the overall functionality and configuration of clinic exam rooms. Specific design qualities discussed include overall size, location of doors and privacy curtains, positioning of exam tables, influence of technology in the consultation area, types of seating, and placement of sink and hand sanitizing dispensers. In addition, future trends of exam room prototypes are presented. There is a general lack of published evidence to support design professionals' design solutions for outpatient exam rooms. Future research should investigate such topics as the location of exam tables and privacy curtains as they relate to patient privacy; typical size and location of consultation table as it relates to patient connection and communication; and placement of sinks and sanitization dispensers as they relate to frequency and patterns of usage. Literature review, outpatient, technology, visual privacy.

  3. 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.

  4. 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)

  5. 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...

  6. Designing future learning. A posthumanist approach to researching design processes

    DEFF Research Database (Denmark)

    Juelskjær, Malou

    I investigate how a design process – leading up to the design of a new education building - enact, transform and highlight tacit everyday practices and experiences in an education setting, whereby becoming an art of managing. I apply a post-humanist performative perspective, highlighting entangled...... agencies rather than focusing on human agency. I focus on the design process rather than the designer. The design process accelerated and performed past and future experiences of schooling, learning, teaching. This called for analytical attention to agential forces of not only the material but also...... and temporalities matter in design processes. Furthermore, the analysis emphasise how design translate affective economies and that attention to those affective economies are vital for the result of the design process....

  7. 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.

  8. Participatory Design in Emergency Medical Service: Designing for Future Practice

    DEFF Research Database (Denmark)

    Kristensen, Margit; Kyng, Morten; Palen, Leysia Ann

    2006-01-01

    address challenges identified by disaster sociologists when designing for major incidents. Through qualitative research and participatory design, we have ex-amined the features of EMS work and technology use in different emergency situations from the perspective of mul-tiple actors. We conceptualize...... victims in incidents—and particularly in major incidents, where on-site medical as-sessments is highly incomplete—as boundary objects over which the complex and imperfect work of coordination is done. As an outcome of our participatory design approach, we describe a set of designs in support of future EMS...

  9. 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.

  10. Future Smart Cooking Machine System Design

    Directory of Open Access Journals (Sweden)

    Dewi Agushinta R.

    2013-11-01

    Full Text Available There are many tools make human task get easier. Cooking has become a basic necessity for human beings, since food is one of basic human needs. Until now, the cooking equipment being used is still a hand tool. However everyone has slightly high activity. The presence of cooking tools that can do the cooking work by itself is now necessary. Future Smart Cooking Machine is an artificial intelligence machine that can do cooking work automatically. With this system design, the time is minimized and the ease of work is expected to be achieved. The development of this system is carried out with System Development Life Cycle (SDLC methods. Prototyping method used in this system is a throw-away prototyping approach. At the end of this research there will be produced a cooking machine system design including physical design engine and interface design.

  11. Design Creativity: Future Directions for Integrated Visualisation

    Directory of Open Access Journals (Sweden)

    Jack Steven Goulding

    2015-11-01

    Full Text Available The Architecture, Engineering and Construction (AEC sectors are facing unprecedented challenges, not just with increased complexity of projects per se, but design-related integration. This requires stakeholders to radically re-think their existing business models (and thinking that underpins them, but also the technological challenges and skills required to deliver these projects. Whilst opponents will no doubt cite that this is nothing new as the sector as a whole has always had to respond to change; the counter to this is that design ‘creativity’ is now much more dependent on integration from day one. Given this, collaborative processes embedded in Building Information Modelling (BIM models have been proffered as a panacea solution to embrace this change and deliver streamlined integration. The veracity of design teams’ “project data” is increasingly becoming paramount - not only for the coordination of design, processes, engineering services, fabrication, construction, and maintenance; but more importantly, facilitate ‘true’ project integration and interchange – the actualisation of which will require firm consensus and commitment. This Special Issue envisions some of these issues, challenges and opportunities (from a future landscape perspective, by highlighting a raft of concomitant factors, which include: technological challenges, design visualisation and integration, future digital tools, new and anticipated operating environments, and training requirements needed to deliver these aspirations. A fundamental part of this Special Issue’s ‘call’ was to capture best practice in order to demonstrate how design, visualisation and delivery processes (and technologies affect the finished product viz: design outcome, design procedures, production methodologies and construction implementation. In this respect, the use of virtual environments are now particularly effective at supporting the design and delivery processes. In

  12. 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

  13. Antimalarial drug policy in India: past, present & future.

    Science.gov (United States)

    Anvikar, Anupkumar R; Arora, Usha; Sonal, G S; Mishra, Neelima; Shahi, Bharatendu; Savargaonkar, Deepali; Kumar, Navin; Shah, Naman K; Valecha, Neena

    2014-02-01

    The use of antimalarial drugs in India has evolved since the introduction of quinine in the 17 th century. Since the formal establishment of a malaria control programme in 1953, shortly after independence, treatments provided by the public sector ranged from chloroquine, the mainstay drug for many decades, to the newer, recently introduced artemisinin based combination therapy. The complexity of considerations in antimalarial treatment led to the formulation of a National Antimalarial Drug Policy to guide procurement as well as communicate best practices to both public and private healthcare providers. Challenges addressed in the policy include the use of presumptive treatment, the introduction of alternate treatments for drug-resistant malaria, the duration of primaquine therapy to prevent relapses of vivax malaria, the treatment of malaria in pregnancy, and the choice of drugs for chemoprophylaxis. While data on antimalarial drug resistance and both public and private sector treatment practices have been recently reviewed, the policy process of setting national standards has not. In this perspective on antimalarial drug policy, this review highlights its relevant history, analyzes the current policy, and examines future directions.

  14. Antimalarial drug policy in India: Past, present & future

    Directory of Open Access Journals (Sweden)

    Anupkumar R Anvikar

    2014-01-01

    Full Text Available The use of antimalarial drugs in India has evolved since the introduction of quinine in the 17 th century. Since the formal establishment of a malaria control programme in 1953, shortly after independence, treatments provided by the public sector ranged from chloroquine, the mainstay drug for many decades, to the newer, recently introduced artemisinin based combination therapy. The complexity of considerations in antimalarial treatment led to the formulation of a National Antimalarial Drug Policy to guide procurement as well as communicate best practices to both public and private healthcare providers. Challenges addressed in the policy include the use of presumptive treatment, the introduction of alternate treatments for drug-resistant malaria, the duration of primaquine therapy to prevent relapses of vivax malaria, the treatment of malaria in pregnancy, and the choice of drugs for chemoprophylaxis. While data on antimalarial drug resistance and both public and private sector treatment practices have been recently reviewed, the policy process of setting national standards has not. In this perspective on antimalarial drug policy, this review highlights its relevant history, analyzes the current policy, and examines future directions.

  15. 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.

  16. The impact of genetics on future drug discovery in schizophrenia.

    Science.gov (United States)

    Matsumoto, Mitsuyuki; Walton, Noah M; Yamada, Hiroshi; Kondo, Yuji; Marek, Gerard J; Tajinda, Katsunori

    2017-07-01

    Failures of investigational new drugs (INDs) for schizophrenia have left huge unmet medical needs for patients. Given the recent lackluster results, it is imperative that new drug discovery approaches (and resultant drug candidates) target pathophysiological alterations that are shared in specific, stratified patient populations that are selected based on pre-identified biological signatures. One path to implementing this paradigm is achievable by leveraging recent advances in genetic information and technologies. Genome-wide exome sequencing and meta-analysis of single nucleotide polymorphism (SNP)-based association studies have already revealed rare deleterious variants and SNPs in patient populations. Areas covered: Herein, the authors review the impact that genetics have on the future of schizophrenia drug discovery. The high polygenicity of schizophrenia strongly indicates that this disease is biologically heterogeneous so the identification of unique subgroups (by patient stratification) is becoming increasingly necessary for future investigational new drugs. Expert opinion: The authors propose a pathophysiology-based stratification of genetically-defined subgroups that share deficits in particular biological pathways. Existing tools, including lower-cost genomic sequencing and advanced gene-editing technology render this strategy ever more feasible. Genetically complex psychiatric disorders such as schizophrenia may also benefit from synergistic research with simpler monogenic disorders that share perturbations in similar biological pathways.

  17. Microdosing and drug development: past, present and future

    Science.gov (United States)

    Lappin, Graham; Noveck, Robert; Burt, Tal

    2015-01-01

    Introduction Microdosing is an approach to early drug development where exploratory pharmacokinetic data are acquired in humans using inherently safe sub-pharmacologic doses of drug. The first publication of microdose data was 10 years ago and this review comprehensively explores the microdose concept from conception, over the past decade, up until the current date. Areas covered The authors define and distinguish the concept of microdosing from similar approaches. The authors review the ability of microdosing to provide exploratory pharmacokinetics (concentration-time data) but exclude microdosing using positron emission tomography. The article provides a comprehensive review of data within the peer-reviewed literature as well as the latest applications and a look into the future, towards where microdosing may be headed. Expert opinion Evidence so far suggests that microdosing may be a better predictive tool of human pharmacokinetics than alternative methods and combination with physiologically based modelling may lead to much more reliable predictions in the future. The concept has also been applied to drug-drug interactions, polymorphism and assessing drug concentrations over time at its site of action. Microdosing may yet have more to offer in unanticipated directions and provide benefits that have not been fully realised to date. PMID:23550938

  18. Future Perspective : Design Process of Perfume Packaging

    OpenAIRE

    Anderson, Duncan

    2016-01-01

    In a world where technology develops at a rapid speed a packaging designer should have the ability to adapt to the challenges in a world where the packaging landscape might look far more different from today. This thesis will look at possible future scenarios relating to resources, infrastructure and consumer behaviour in the year 2050. It will then go on to discuss the emergence of new packaging materials pitted to replace plastic, as well as take a look at printed electronics in packaging a...

  19. 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.

  20. Use of prescription drugs and future delinquency among adolescent offenders.

    Science.gov (United States)

    Drazdowski, Tess K; Jäggi, Lena; Borre, Alicia; Kliewer, Wendy L

    2015-01-01

    Non-medical use of prescription drugs (NMUPD) by adolescents is a significant public health concern. The present study investigated the profile of NMUPD in 1349 adolescent offenders from the Pathways to Desistance project, and whether NMUPD predicted future delinquency using longitudinal data. Results indicated that increased frequency and recency of NMUPD in adolescent offenders are related to some demographic factors, as well as increased risk for violence exposure, mental health diagnoses, other drug use, and previous delinquency, suggesting that severity of NMUPD is important to consider. However, ANCOVA analyses found that NMUPD was not a significant predictor of drug-related, non-aggressive, or aggressive delinquency 12 months later beyond other known correlates of delinquency. Age, sex, exposure to violence, lower socioeconomic status, more alcohol use, and having delinquency histories were more important than NMUPD in predicting future delinquency. These findings suggest that although NMUPD is an important risk factor relating to many correlates of delinquency, it does not predict future delinquency beyond other known risk factors. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. 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.

  2. NRC policy on future reactor designs

    International Nuclear Information System (INIS)

    1985-07-01

    On April 13, 1983, the US Nuclear Regulatory Commission issued for public comment a ''Proposed Commission Policy Statement on Severe Accidents and Related Views on Nuclear Reactor Regulation'' (48 FR 16014). This report presents and discusses the Commission's final version of that policy statement now entitled, ''Policy Statement on Severe Reactor Accidents Regarding Future Designs and Existing Plants.'' It provides an overview of comments received from the public and the Advisory Committee on Reactor Safeguards and the staff response to these. In addition to the Policy Statement, the report discusses how the policies of this statement relate to other NRC programs including the Severe Accident Research Program; the implementation of safety measures resulting from lessons learned in the accident at Three Mile Island; safety goal development; the resolution of Unresolved Safety Issues and other Generic Safety Issues; and possible revisions of rules or regulatory requirements resulting from the Severe Accident Source Term Program. Also discussed are the main features of a generic decision strategy for resolving Regulatory Questions and Technical Issues relating to severe accidents; the development and regulatory use of new safety information; the treatment of uncertainty in severe accident decision making; and the development and implementation of a Systems Reliability Program for both existing and future plants to ensure that the realized level of safety is commensurate with the safety analyses used in regulatory decisions

  3. Accounting for the drug life cycle and future drug prices in cost-effectiveness analysis.

    Science.gov (United States)

    Hoyle, Martin

    2011-01-01

    Economic evaluations of health technologies typically assume constant real drug prices and model only the cohort of patients currently eligible for treatment. It has recently been suggested that, in the UK, we should assume that real drug prices decrease at 4% per annum and, in New Zealand, that real drug prices decrease at 2% per annum and at patent expiry the drug price falls. It has also recently been suggested that we should model multiple future incident cohorts. In this article, the cost effectiveness of drugs is modelled based on these ideas. Algebraic expressions are developed to capture all costs and benefits over the entire life cycle of a new drug. The lifetime of a new drug in the UK, a key model parameter, is estimated as 33 years, based on the historical lifetime of drugs in England over the last 27 years. Under the proposed methodology, cost effectiveness is calculated for seven new drugs recently appraised in the UK. Cost effectiveness as assessed in the future is also estimated. Whilst the article is framed in mathematics, the findings and recommendations are also explained in non-mathematical language. The 'life-cycle correction factor' is introduced, which is used to convert estimates of cost effectiveness as traditionally calculated into estimates under the proposed methodology. Under the proposed methodology, all seven drugs appear far more cost effective in the UK than published. For example, the incremental cost-effectiveness ratio decreases by 46%, from £61, 900 to £33, 500 per QALY, for cinacalcet versus best supportive care for end-stage renal disease, and by 45%, from £31,100 to £17,000 per QALY, for imatinib versus interferon-α for chronic myeloid leukaemia. Assuming real drug prices decrease over time, the chance that a drug is publicly funded increases over time, and is greater when modelling multiple cohorts than with a single cohort. Using the methodology (compared with traditional methodology) all drugs in the UK and New

  4. Electricity market design of the future

    International Nuclear Information System (INIS)

    Peek, Markus; Diels, Robert

    2016-01-01

    The transformation of the power generation system, to one in which renewable energies will form a cornerstone, will change the requirements for all market actors. To achieve the goals of the German Energiewende ('energy transition'), greater flexibility in production and consumption is of particular importance. Flexibility enables the cost-effective integration of the fluctuating actual feed-in of renewable energies. On the one hand, the technical options for reducing existing technical inflexibilities are given to a considerable extent. On the other hand, analyses of the transnational compensation effects of load and renewable energy supply (RES) feed-in show that flexibility requirements can be reduced significantly in a common electricity market. Electricity markets in which there is open technological competition are an appropriate instrument for the flexibilization of the power supply system. In the short term, the mechanisms of competitive electricity markets ensure an efficient synchronization of supply and demand. Over the medium and long term, the market creates efficient incentives to adapt the generation system and the behavior of consumers to future needs, resulting from the changes in the residual load structure. But at the same time, in recent years the occurrence of negative electricity prices in situations with significantly positive residual loads show that flexibility restraints exist. The causes of these restraints are at least partly due to the market design or the regulatory framework. On the one hand, there are barriers to market entry and, on the other hand, price signals from the electricity markets do not reach all market actors or reach them distortedly. To enable the cost effective development of the different flexibility options in an open technology competition, restraints resulting from market design and the regulatory framework (e. g. in the framework of grid charges, the market and product design of control power markets

  5. 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.

  6. Multimodal drugs and their future for Alzheimer's and Parkinson's disease.

    Science.gov (United States)

    Van der Schyf, Cornelis J; Geldenhuys, Werner J

    2011-01-01

    This chapter discusses the rationale for developing multimodal or multifunctional drugs (also called designed multiple ligands or DMLs) aimed at disease-modifying treatment strategies for the most common neurodegenerative diseases Alzheimer's and Parkinson's disease (AD and PD). Both the prevalence and incidence of AD and PD have seen consistent and dramatic increases, a disconcerting phenomenon which, ironically, has been attributed to extended life expectancy brought about by better health care globally. In spite of these statistics, the development and introduction to the clinic of new therapies proven to prevent or delay the onset of AD and PD have been disappointing. Evidence has accumulated to suggest that the etiopathology of these diseases is extremely complex, with an array of potential drug targets located within a number of deleterious biochemical pathways. Therefore, in these diseases, it is unlikely that the complex pathoetiological cascade leading to disease initiation or progression will be mitigated by any one drug acting on a single pathway or target. The pursuit of novel DMLs may offer far better outcomes. Although certainly not the only, and perhaps not even the best, approach but farthest along the drug development pipeline in the DML paradigm are drugs that combine inhibition of monoamine oxidase with associated etiological targets unique to either AD or PD. These compounds will constitute the major focus of this chapter, which will also explore radically new paradigms that seek to combine cognitive enhancers with proneurogenesis compounds. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. Medicinal chemistry in drug discovery in big pharma: past, present and future.

    Science.gov (United States)

    Campbell, Ian B; Macdonald, Simon J F; Procopiou, Panayiotis A

    2018-02-01

    The changes in synthetic and medicinal chemistry and related drug discovery science as practiced in big pharma over the past few decades are described. These have been predominantly driven by wider changes in society namely the computer, internet and globalisation. Thoughts about the future of medicinal chemistry are also discussed including sharing the risks and costs of drug discovery and the future of outsourcing. The continuing impact of access to substantial computing power and big data, the use of algorithms in data analysis and drug design are also presented. The next generation of medicinal chemists will communicate in ways that reflect social media and the results of constantly being connected to each other and data. Copyright © 2017. Published by Elsevier Ltd.

  8. Anti-obesity drugs: past, present and future

    Directory of Open Access Journals (Sweden)

    R. John Rodgers

    2012-09-01

    Full Text Available The ideal anti-obesity drug would produce sustained weight loss with minimal side effects. The mechanisms that regulate energy balance have substantial built-in redundancy, overlap considerably with other physiological functions, and are influenced by social, hedonic and psychological factors that limit the effectiveness of pharmacological interventions. It is therefore unsurprising that anti-obesity drug discovery programmes have been littered with false starts, failures in clinical development, and withdrawals due to adverse effects that were not fully appreciated at the time of launch. Drugs that target pathways in metabolic tissues, such as adipocytes, liver and skeletal muscle, have shown potential in preclinical studies but none has yet reached clinical development. Recent improvements in the understanding of peptidergic signalling of hunger and satiety from the gastrointestinal tract mediated by ghrelin, cholecystokinin (CCK, peptide YY (PYY and glucagon-like peptide-1 (GLP-1, and of homeostatic mechanisms related to leptin and its upstream pathways in the hypothalamus, have opened up new possibilities. Although some have now reached clinical development, it is uncertain whether they will meet the strict regulatory hurdles required for licensing of an anti-obesity drug. However, GLP-1 receptor agonists have already succeeded in diabetes treatment and, owing to their attractive body-weight-lowering effects in humans, will perhaps also pave the way for other anti-obesity agents. To succeed in developing drugs that control body weight to the extent seen following surgical intervention, it seems obvious that a new paradigm is needed. In other therapeutic arenas, such as diabetes and hypertension, lower doses of multiple agents targeting different pathways often yield better results than strategies that modify one pathway alone. Some combination approaches using peptides and small molecules have now reached clinical trials, although recent

  9. 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.

  10. 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

  11. 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.

  12. ETF design activities: status and future direction

    International Nuclear Information System (INIS)

    Steiner, D.

    1980-01-01

    The nature of the device to follow TFTR has been evolving over the past six years. The most recent design activities have been directed to the Engineering Test Facility (ETF) concept. In order to address the design of the ETF a centralized laboratory/industry design team was established and hosted at ORNL. This Design Center began ETF Preconceptual design in October, 1979. The ETF design effort has been judged to be sound. However, the ETF mission has been judged to be overly ambitious. It has been recommended that the device to follow TFTR be dedicated to the investigation of engineering feasibility and that device has been designated the Fusion Engineering Device (FED). The ETF design activities provide a basis for developing the FED design. This will be accomplished under the direction of the newly formed FED Technical Management Board

  13. Trial discontinuation: lessons for future trial design?

    NARCIS (Netherlands)

    V.J.A.A. Nuij (Veerle); C.J. de Haar (Colin); C.J. van der Woude (Janneke)

    2012-01-01

    textabstractBackground: The current therapeutic arsenal still does not fulfill the therapeutic needs of inflammatory bowel disease patients. Although new drugs are constantly being developed, many will never reach the market. In this review we will search for reasons for discontinuing promising

  14. 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.

  15. Designing a Sustainable Future with Mental Models

    OpenAIRE

    Bernotat, Anke; Bertling, Jürgen; English, Christiane; Schanz, Judith

    2017-01-01

    Inspired by the question of the Club of Rome as to Design could help to translate the ubiquitous knowledge on sustainability into daily practise and Peter Senge's belief on mental models as a limiting factor to implementation of systemic insight (Senge 2006), we explored working with mental models as a sustainable design tool. We propose a definition for design uses. At the 7th Sustainable Summer School we collected general unsustainable mental models and "designed" sustainable ones. These me...

  16. Historical Spice as a Future Drug: Therapeutic Potential of Piperlongumine.

    Science.gov (United States)

    Prasad, Sahdeo; Tyagi, Amit K

    2016-01-01

    Spice and spice-derived compounds have been identified and explored for their health benefits since centuries. One of the spice long pepper has been traditionally used to treat chronic bronchitis, asthma, constipation, gonorrhea, paralysis of the tongue, diarrhea, cholera, malaria, viral hepatitis, respiratory infections, stomach ache, diseases of the spleen, cough, and tumors. In this review, the evidences for the chemopreventive and chemotherapeutic potential of piperlongumine have been described. The active component piperlonguime has shown effective against various ailments including cancer, neurogenerative disease, arthritis, melanogenesis, lupus nephritis, and hyperlipidemic. These beneficial effects of piperlongumine is attributed to its ability to modulate several signaling molecules like reactive oxygen species, kinases, proteasome, proto-oncogenes, transcription factors, cell cycle, inflammatory molecules and cell growth and survival molecules. Piperlongumine also chemosensitizes to drugs resistant cancer cells. Overall the consumption of long peppers is therefore recommended for the prevention and treatment of various diseases including cancer, and thus piperlongumine may be a promising future candidate drug against cancer.

  17. [Present status and future of hypnotic drug treatment for insomnia].

    Science.gov (United States)

    Uchiyama, Makoto; Konno, Michiko

    2012-07-01

    Pharmacological treatments of insomnia have become safer since the first benzodiazepine receptor agonist (BzRA) hypnotic was introduced in the 1960's. Though BzRAs could hardly cause a fatal condition even in cases of overdosing, they had inherited the arguments on addiction and withdrawal from the prior studies of barbiturate hypnotics that indicated they are strongly addictive. In the 2000s, it was repeatedly demonstrated that insomnia as well as sleep deprivation underlie the development and deterioration of comorbid diseases such as hypertension, cardiovascular diseases, diabetes and depression, and that the proper use of hypnotic drugs is unlikely to cause tolerance, addiction nor rebound phenomena, but likely to be associated with improvement of QOL. Thus, the 2005's consensus report on chronic insomnia by NIH has recommended general physicians to facilitate insomnia treatment to prevent the development of physical and/or mental disorders. The author reviewed in this article the efficacy and side effects of BzRA hypnotics, a hypnotic drug therapy combined with cognitive and behavioral interventions, uses of melatonin receptor agonist in general and sleep medicine practices, and future utilization of newly-developed orexin antagonists for insomnia treatment.

  18. Anti-chemokine small molecule drugs: a promising future?

    Science.gov (United States)

    Proudfoot, Amanda E I; Power, Christine A; Schwarz, Matthias K

    2010-03-01

    Chemokines have principally been associated with inflammation due to their role in the control of leukocyte migration, but just over a decade ago chemokine receptors were also identified as playing a pivotal role in the entry of the HIV virus into cells. Chemokines activate seven transmembrane G protein-coupled receptors, making them extremely attractive therapeutic targets for the pharmaceutical industry. Although there are now a large number of molecules targeting chemokines and chemokine receptors including neutralizing antibodies in clinical trials for inflammatory diseases, the results to date have not always been positive, which has been disappointing for the field. These failures have often been attributed to redundancy in the chemokine system. However, other difficulties have been encountered in drug discovery processes targeting the chemokine system, and these will be addressed in this review. In this review, the reader will get an insight into the hurdles that have to be overcome, learn about some of the pitfalls that may explain the lack of success, and get a glimpse of the outlook for the future. In 2007, the FDA approved maraviroc, an inhibitor of CCR5 for the prevention of HIV infection, the first triumph for a small-molecule drug acting on the chemokine system. The time to market, 11 years from discovery of CCR5, was fast by industry standards. A second small-molecule drug, a CXCR4 antagonist for hematopoietic stem cell mobilization, was approved by the FDA at the end of 2008. The results of a Phase III trial with a CCR9 inhibitor for Crohn's disease are also promising. This could herald the first success for a chemokine receptor antagonist as an anti-inflammatory therapeutic and confirms the importance of chemokine receptors as a target class for anti-inflammatory and autoimmune diseases.

  19. The impact of ageing and changing utilization patterns on future cardiovascular drug expenditure: a pharmacoepidemiological projection approach

    DEFF Research Database (Denmark)

    Kildemoes, Helle Wallach; Andersen, Morten; Støvring, Henrik

    2010-01-01

    To develop a method for projecting the impact of ageing and changing drug utilization patterns on future drug expenditure.......To develop a method for projecting the impact of ageing and changing drug utilization patterns on future drug expenditure....

  20. Design storytelling with future scenario development; envisioning "the museum"

    NARCIS (Netherlands)

    Eggink, Wouter; Albert de la Bruheze, Adri A.

    2015-01-01

    There are different ways to tell stories with design. This paper shows possibilities of telling stories by envisioning the future. Overall, design has the very ability to envision, visualize and express things that do not exist yet. We introduce the Future Scenario Development Design methodology as

  1. Educating engineering designers for a multidisciplinary future

    DEFF Research Database (Denmark)

    engineering design education. Educating engineering designers today significantly differs from traditional engineering education (McAloone, et.al., 2007). However, a broader view of design activities gains little attention. The project course Product/Service-Systems, which is coupled to the lecture based...... course Product life and Environmental issues at the Technical University of Denmark (DTU) and the master programme Product Development Processes at the Luleå University of Technology (LTU), Sweden, are both curriculums with a broader view than traditional (mechanical) engineering design. Based...... on these two representatives of a Scandinavian approach, the purpose in this presentation is to describe two ways of educating engineering designers to enable them to develop these broader competencies of socio-technical aspects of engineering design. Product Development Processes at LTU A process, called...

  2. The Future School: Designing for Student Success.

    Science.gov (United States)

    Ruck, Gary

    1993-01-01

    Three themes of change in school planning are the future school, outsourcing, and the reconstruction of existing facilities to accommodate technological and philosophical potential. Describes the technology and the house concept at a middle school and renovations at an elementary school. (MLF)

  3. Electricity market design for the future

    OpenAIRE

    robinson, david; Keay, Malcolm

    2017-01-01

    This paper explains why current electricity markets are not fit for purpose and propose a new market design. Electricity markets operating today were designed for the technical and economic conditions of the 1990's. These conditions have changed substantially, especially with increased penetration of intermittent renewables and the growing potential for distributed energy resources and consumer involvement. Today's markets are incompatible with these trends. They do not provide h...

  4. 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.

  5. 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

  6. Bioreactor design and optimization – a future perspective

    DEFF Research Database (Denmark)

    Gernaey, Krist

    2011-01-01

    Bioreactor design and optimisation are essential in translating the experience gained from lab or pilot scale experiments to efficient production processes in industrial scale bioreactors. This article gives a future perspective on bioreactor design and optimisation, where it is foreseen...

  7. Bioinformatics in cancer therapy and drug design

    International Nuclear Information System (INIS)

    Horbach, D.Y.; Usanov, S.A.

    2005-01-01

    One of the mechanisms of external signal transduction (ionizing radiation, toxicants, stress) to the target cell is the existence of membrane and intracellular proteins with intrinsic tyrosine kinase activity. No wonder that etiology of malignant growth links to abnormalities in signal transduction through tyrosine kinases. The epidermal growth factor receptor (EGFR) tyrosine kinases play fundamental roles in development, proliferation and differentiation of tissues of epithelial, mesenchymal and neuronal origin. There are four types of EGFR: EGF receptor (ErbB1/HER1), ErbB2/Neu/HER2, ErbB3/HER3 and ErbB4/HER4. Abnormal expression of EGFR, appearance of receptor mutants with changed ability to protein-protein interactions or increased tyrosine kinase activity have been implicated in the malignancy of different types of human tumors. Bioinformatics is currently using in investigation on design and selection of drugs that can make alterations in structure or competitively bind with receptors and so display antagonistic characteristics. (authors)

  8. Bioinformatics in cancer therapy and drug design

    Energy Technology Data Exchange (ETDEWEB)

    Horbach, D Y [International A. Sakharov environmental univ., Minsk (Belarus); Usanov, S A [Inst. of bioorganic chemistry, National academy of sciences of Belarus, Minsk (Belarus)

    2005-05-15

    One of the mechanisms of external signal transduction (ionizing radiation, toxicants, stress) to the target cell is the existence of membrane and intracellular proteins with intrinsic tyrosine kinase activity. No wonder that etiology of malignant growth links to abnormalities in signal transduction through tyrosine kinases. The epidermal growth factor receptor (EGFR) tyrosine kinases play fundamental roles in development, proliferation and differentiation of tissues of epithelial, mesenchymal and neuronal origin. There are four types of EGFR: EGF receptor (ErbB1/HER1), ErbB2/Neu/HER2, ErbB3/HER3 and ErbB4/HER4. Abnormal expression of EGFR, appearance of receptor mutants with changed ability to protein-protein interactions or increased tyrosine kinase activity have been implicated in the malignancy of different types of human tumors. Bioinformatics is currently using in investigation on design and selection of drugs that can make alterations in structure or competitively bind with receptors and so display antagonistic characteristics. (authors)

  9. 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.

  10. A Future in Fashion: Designing Wearable Art

    Science.gov (United States)

    Brew, Charl Anne

    2009-01-01

    Art instructors are ever mindful of the need to introduce and encourage the possibilities of careers in the art field. The longer the author has been teaching art, the more aware she has become of the many wonderful art-related jobs and careers that exist. Fashion design, marketing and retail are three areas in which many students--male and…

  11. Design of nursing homes of the future

    NARCIS (Netherlands)

    Joost van Hoof

    2014-01-01

    Purpose There is an increasing call in society for improvementof the well-being of nursing home residents and support of health care professionals through a wide array of architectural and technological solutions that are available in modern nursing homes. The design of nursing home facilities calls

  12. Challenges and Future in Vaccines, Drug Development, and Immunomodulatory Therapy

    Science.gov (United States)

    Nau, Gerard J.; Ross, Ted M.; Evans, Thomas G.; Chakraborty, Krishnendu; Empey, Kerry M.; Flynn, JoAnne L.

    2014-01-01

    Pulmonary diseases and infections are among the top contributors to human morbidity and mortality worldwide, and despite the successful history of vaccines and antimicrobial therapeutics, infectious disease still presents a significant threat to human health. Effective vaccines are frequently unavailable in developing countries, and successful vaccines have yet to be developed for major global maladies, such as tuberculosis. Furthermore, antibiotic resistance poses a growing threat to human health. The “Challenges and Future in Vaccines, Drug Development, and Immunomodulatory Therapy” session of the 2013 Pittsburgh International Lung Conference highlighted several recent and current studies related to treatment and prevention of antibiotic-resistant bacterial infections, highly pathogenic influenza, respiratory syncytial virus, and tuberculosis. Research presented here focused on novel antimicrobial therapies, new vaccines that are either in development or currently in clinical trials, and the potential for immunomodulatory therapies. These studies are making important contributions to the areas of microbiology, virology, and immunology related to pulmonary diseases and infections and are paving the way for improvements in the efficacy of vaccines and antimicrobials. PMID:25148426

  13. Challenges and future in vaccines, drug development, and immunomodulatory therapy.

    Science.gov (United States)

    Kling, Heather M; Nau, Gerard J; Ross, Ted M; Evans, Thomas G; Chakraborty, Krishnendu; Empey, Kerry M; Flynn, JoAnne L

    2014-08-01

    Pulmonary diseases and infections are among the top contributors to human morbidity and mortality worldwide, and despite the successful history of vaccines and antimicrobial therapeutics, infectious disease still presents a significant threat to human health. Effective vaccines are frequently unavailable in developing countries, and successful vaccines have yet to be developed for major global maladies, such as tuberculosis. Furthermore, antibiotic resistance poses a growing threat to human health. The "Challenges and Future in Vaccines, Drug Development, and Immunomodulatory Therapy" session of the 2013 Pittsburgh International Lung Conference highlighted several recent and current studies related to treatment and prevention of antibiotic-resistant bacterial infections, highly pathogenic influenza, respiratory syncytial virus, and tuberculosis. Research presented here focused on novel antimicrobial therapies, new vaccines that are either in development or currently in clinical trials, and the potential for immunomodulatory therapies. These studies are making important contributions to the areas of microbiology, virology, and immunology related to pulmonary diseases and infections and are paving the way for improvements in the efficacy of vaccines and antimicrobials.

  14. Design Anthropology, Emerging Technologies and Alternative Computational Futures

    DEFF Research Database (Denmark)

    Smith, Rachel Charlotte

    Emerging technologies are providing a new field for design anthropological inquiry that unite experiences, imaginaries and materialities in complex way and demands new approaches to developing sustainable computational futures.......Emerging technologies are providing a new field for design anthropological inquiry that unite experiences, imaginaries and materialities in complex way and demands new approaches to developing sustainable computational futures....

  15. ESRDC - Designing and Powering the Future Fleet

    Science.gov (United States)

    2018-02-22

    Carolina, as part of the Electric Ship Research and Development Consortium, has advanced technologies and methods applicable to electric ships in...We studied the application of advanced two-stage cooling technologies to the cooling of electronic power converters for ship electrical systems... technologies , • Used high speed generators for power generation, • Used an alternative electrical system topology. A master’s student used S3D to design a

  16. Future of color in the visual arts, architecture, and design

    Science.gov (United States)

    Green-Armytage, Paul

    2002-06-01

    My brief for this report was to reflect on the congress from the point of view of the visual arts, architecture and design, and to say something about how I see the future of color in these fields. I will say a bit about the congress itself, a bit about some of the topics that particularly struck me, and a bit about the future - the future that seems likely and the future that I hope for.

  17. Future directions in boiling water reactor design

    International Nuclear Information System (INIS)

    Wilkins, D.R.; Hucik, S.A.; Duncan, J.D.; Sweeney, J.I.

    1987-01-01

    The Advanced Boiling Water Reactor (ABWR) is being developed by an international team of BWR manufacturers to respond to worldwide utility needs in the 1990's. Major objectives of the ABWR program are design simplification; improved safety and reliability; reduced construction, fuel and operating costs; improved maneuver-ability; and reduced occupational exposure and radwaste. The ABWR incorporates the best proven features from BWR designs in Europe, Japan and the United States and application of leading edge technology. Key features of the ABWR are internal recirculation pumps; fine-motion, electrohydraulic control rod drives; digital control and instrumentation; multiplexed, fiber optic cabling netwoek; pressure suppression containment with horizontal vents; cylindrical reinforced concrete containment; structural integration of the containment and reactor building; severe accident capability; state-of-the-art fuel; advanced trubine/generator with 52'' last stage buckets; and advanced radwaste technology. The ABWR is ready for lead plant application in Japan, where it is being developed as the next generation Japan standard BWR under the guidance and leadership of The Tokyo Electric Power Company, Inc. and a group of Japanese BWR utilities. In the United States it is being adapted to the needs of US utilities through the Electric Power Research Institute's Advanced LWR Requirements Program, and is being reviewed by the US Nuclear Regulatory Commission for certification as a preapproved US standard BWR under the US Department of Energy's ALWR Design Verification Program. These cooperative Japanese and US programs are expected to establish the ABWR as a world class BWR for the 1990's...... (author)

  18. Abbreviated New Drug Applications (ANDAS): Future trend in radiopharmaceuticals

    International Nuclear Information System (INIS)

    Kishore, R.

    1990-01-01

    The Drug Price Competition and Patent Term Restoration Act (commonly called Waxman Hatch Amendment) of 1984, to the Federal Food, Drug, and Cosmetic Act provided for abbreviated new drug applications (ANDAs) if the conditions specified in the Code of Federal Regulations (CFR) Title 21, subsection 312.55 are met. Under this subsection, reports of nonclinical laboratory studies and clinical investigations can be omitted. New drugs approved under these regulations are so called generic drugs as opposed to listed or pioneer (innovator) drugs. As the patents on more and more radiopharmaceuticals reach their expiration, the radiopharmaceutical industry is likely to produce more of these generic versions of innovator drugs. The ANDAs are required to contain information specified under subsections 314.50(a), (b), (d)(1) and (3), (e), and (g)

  19. NMR in structure-based drug design.

    Science.gov (United States)

    Carneiro, Marta G; Ab, Eiso; Theisgen, Stephan; Siegal, Gregg

    2017-11-08

    NMR spectroscopy is a powerful technique that can provide valuable structural information for drug discovery endeavors. Here, we discuss the strengths (and limitations) of NMR applications to structure-based drug discovery, highlighting the different levels of resolution and throughput obtainable. Additionally, the emerging field of paramagnetic NMR in drug discovery and recent developments in approaches to speed up and automate protein-observed NMR data collection and analysis are discussed. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  20. Click chemistry, 3D-printing, and omics: the future of drug development.

    Science.gov (United States)

    Kurzrock, Razelle; Stewart, David J

    2016-01-19

    Genomics is a disruptive technology, having revealed that cancers are tremendously complex and differ from patient to patient. Therefore, conventional treatment approaches fit poorly with genomic reality. Furthermore, it is likely that this type of complexity will also be observed in other illnesses. Precision medicine has been posited as a way to better target disease-related aberrations, but developing drugs and tailoring therapy to each patient's complicated problem is a major challenge. One solution would be to match patients to existing compounds based on in silico modeling. However, optimization of complex therapy will eventually require designing compounds for patients using computer modeling and just-in-time production, perhaps achievable in the future by three-dimensional (3D) printing. Indeed, 3D printing is potentially transformative by virtue of its ability to rapidly generate almost limitless numbers of objects that previously required manufacturing facilities. Companies are already endeavoring to develop affordable 3D printers for home use. An attractive, but as yet scantily explored, application is to place chemical design and production under digital control. This could be accomplished by utilizing a 3D printer to initiate chemical reactions, and print the reagents and/or the final compounds directly. Of interest, the Food and Drug Administration (FDA) has recently approved a 3D printed drug-levetiracetam-indicated for seizures. Further, it is now increasingly clear that biologic materials-tissues, and eventually organs-can also be "printed." In the near future, it is plausible that high-throughput computing may be deployed to design customized drugs, which will reshape medicine.

  1. Future design of a Children's Hospice

    DEFF Research Database (Denmark)

    Poulsen, Mikkel; Knudstrup, Mary-Ann; Hoff, Peter

    2017-01-01

    and the promotion of wellbeing are key elements in a children’s hospice, and since the relatives are deeply affected by the pa- tient’s condition, there is a need for the relatives to stay at the hospice while also maintaining work and social life. By creating flexible environments where patients and relatives can......Children’s hospices are a recent concept within the Danish context. Current- ly, only the small experimental institution “Lukashuset” at ”Sankt Lukas Stiftelsen” exists. There has been both an increased demand for and a pub- lic and political interest in creating a dedicated children’s hospice......, similar to those in those in Britain, where the concept is more widespread. In Den- mark, the only choice is represented by children’s wards, which are ill-suited to palliative treatment. The objective of this paper is to describe and present a children’s hospice which has been designed using...

  2. 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.

  3. "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.

  4. 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.

  5. 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.

  6. 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

  7. New High: A Future-Oriented Study of American Drug Policy

    Science.gov (United States)

    2017-12-01

    physical health , leading to a decrease in morbidity and mortality from obesity. Nootropics on pharmacy shelves combat hunger, low energy, and...office of the future. 14. SUBJECT TERMS futures, megatrends, emerging technologies, drug policy, public health , war on drugs, forecasting, behavioral... health , scenarios, trends, innovation, regulation, policy, artificial intelligence, brain-computer interface, neural stimulation, nootropics

  8. Design and Synthesis of Epigenetic Drugs

    DEFF Research Database (Denmark)

    Leurs, Ulrike

    2014-01-01

    of histone- and DNA-modifying enzymes can lead to the development of diseases such as cancer. The histone demethylases of the KDM4 family have been implicated in a wide range of diseases, and are hence important drug targets. KDM4s belong to the bigger family of 2-OG oxygenases, an enzyme class sharing high...

  9. The future-essay as a design tool

    DEFF Research Database (Denmark)

    Thomsen, Bente Dahl; Kappel, Anne

    2007-01-01

    The aim of this paper is to present scenarios, photo-essays and future-essays as tools in communication, and as tools for clarifying the use of products in the future and the aesthetic qualities in the programme. In the design process, the programme is a description of the function, the condition...

  10. Developing DIVE, a design-led futures technique for SMEs

    NARCIS (Netherlands)

    Mejia Sarmiento, J.R.; Pasman, G.J.; Hultink, H.J.; Stappers, P.J.; Vogel, C.; Muratovski, G.

    2017-01-01

    Futures techniques have long been used in large enterprises as designerly means to explore the future and guide innovation. In the automotive industry, for instance, the development of concept cars is a technique which has repeatedly proven its value. However, while big companies have broadly

  11. Access to orphan drugs in Europe: current and future issues.

    Science.gov (United States)

    Michel, Morgane; Toumi, Mondher

    2012-02-01

    Orphan drugs target small populations of patients. In order to make the field more attractive to pharmaceutical companies and encourage R&D in rare diseases, incentives were put forward by the EU, which are discussed in this article. Because they often are the only available option to treat a disease, some orphan drugs are considered to have high value and as such benefit from high prices on national markets. This has made orphan drugs an attractive market for pharmaceutical companies, with approximately 40 approved orphan drugs generating over $200 million each in yearly sales. The resulting burden this puts on national health insurances may lead to a change in regulation and will certainly lead to new national pricing and reimbursement strategies. They will need to be coherent, fair, effective and sustainable so as to be predictable for companies. Reflection on the subject needs to be initiated.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. Ten Questions about the Future of Art and Design Education.

    Science.gov (United States)

    Steers, John

    1997-01-01

    Asks ten questions about the future of art, crafts, and design education. Focuses on why art, crafts, and design education should be included in the curriculum; how the curriculum should be defined; and how art educators should respond to conflicting calls for cultural relativism and for cultural nationalism. (DSK)

  17. Interventional procedures and future drug therapy for hypertension

    Science.gov (United States)

    Lobo, Melvin D.; Sobotka, Paul A.; Pathak, Atul

    2017-01-01

    Hypertension management poses a major challenge to clinicians globally once non-drug (lifestyle) measures have failed to control blood pressure (BP). Although drug treatment strategies to lower BP are well described, poor control rates of hypertension, even in the first world, suggest that more needs to be done to surmount the problem. A major issue is non-adherence to antihypertensive drugs, which is caused in part by drug intolerance due to side effects. More effective antihypertensive drugs are therefore required which have excellent tolerability and safety profiles in addition to being efficacious. For those patients who either do not tolerate or wish to take medication for hypertension or in whom BP control is not attained despite multiple antihypertensives, a novel class of interventional procedures to manage hypertension has emerged. While most of these target various aspects of the sympathetic nervous system regulation of BP, an additional procedure is now available, which addresses mechanical aspects of the circulation. Most of these new devices are supported by early and encouraging evidence for both safety and efficacy, although it is clear that more rigorous randomized controlled trial data will be essential before any of the technologies can be adopted as a standard of care. PMID:27406184

  18. Microcrystalline identification of selected designer drugs.

    Science.gov (United States)

    Elie, Leonie; Baron, Mark; Croxton, Ruth; Elie, Mathieu

    2012-01-10

    A microcrystalline test for the detection of 4-methylmethcathinone (mephedrone), benzylpiperazine (BZP) and 5,6-methylenedioxy-2-aminoindane (MDAI) using aqueous solutions of mercury chloride is described. Each of the compounds investigated formed specific drug-reagent crystals within minutes. The uniqueness of the test was confirmed by comparison of the microcrystalline response to that of other psychoactive stimulants and a common cutting agent. The limit of detection and cut-off levels for reference standards were established to 3 g/L and 5 g/L for mephedrone, 0.5 g/L for MDAI and 0.2 g/L and 0.3 g/L for BZP, respectively. Various mixtures of standards of either mephedrone, BZP or MDAI combined with caffeine were investigated for their microcrystalline response. Results showed that simultaneous detection of drug and cutting agent was possible with the concentrations tested but were dependant on the ratio of drug to cutting agent. BZP could be detected alongside caffeine from as low as 20% (v/v), MDAI from 40% (v/v) and mephedrone from 50% (v/v) and higher. Finally, seven samples of online purchased 'legal highs' were analysed using the developed test and the findings were compared to FTIR and GC-MS results. It was shown that 6 out of 7 samples did not contain the advertised active ingredient. Five samples consisted of BZP, caffeine and 1-[3-(trifluoromethyl)phenyl]piperazine (3-TFMPP). The microcrystalline tests carried out on these samples showed positive results for both BZP and caffeine without interference from other substances present. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  19. Emergency Physicians' Knowledge of Cannabinoid Designer Drugs

    Directory of Open Access Journals (Sweden)

    Patrick M Lank

    2013-09-01

    Full Text Available Introduction: The use of synthetic drugs of abuse in the United States has grown in the last few years, with little information available on how much physicians know about these drugs and how they are treating patients using them. The objective of this study was to assess emergency physician (EP knowledge of synthetic cannabinoids (SC.Methods: A self-administered internet-based survey of resident and attending EPs at a large urban emergency department (ED was administered to assess familiarity with the terms Spice or K2 and basic knowledge of SC, and to describe some practice patterns when managing SC intoxication in the ED.Results: Of the 83 physicians invited to participate, 73 (88% completed surveys. The terms “Spice” and “K2” for SC were known to 25/73 (34% and 36/73 (49% of respondents. Knowledge of SC came most commonly (72% from non-medical sources, with lay publications and the internet providing most respondents with information. Among those with previous knowledge of synthetic cannabinoids, 25% were not aware that SC are synthetic drugs, and 17% did not know they are chemically most similar to marijuana. Among all participants, 80% felt unprepared caring for a patient in the ED who had used synthetic cannabinoids.Conclusion: Clinically active EPs are unfamiliar with synthetic cannabinoids. Even those who stated they had heard of synthetic cannabinoids answered poorly on basic knowledge questions. More education is needed among EPs of all ages and levels of training on synthetic cannabinoids. [West J Emerg Med. 2013;14(5:467–470.

  20. Oral transmucosal drug delivery--current status and future prospects.

    Science.gov (United States)

    Sattar, Mohammed; Sayed, Ossama M; Lane, Majella E

    2014-08-25

    Oral transmucosal drug delivery (OTDD) dosage forms have been available since the 1980s. In contrast to the number of actives currently delivered locally to the oral cavity, the number delivered as buccal or sublingual formulations remains relatively low. This is surprising in view of the advantages associated with OTDD, compared with conventional oral drug delivery. This review examines a number of aspects related to OTDD including the anatomy of the oral cavity, models currently used to study OTDD, as well as commercially available formulations and emerging technologies. The limitations of current methodologies to study OTDD are considered as well as recent publications and new approaches which have advanced our understanding of this route of drug delivery. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. 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

  2. Design Rework Prediction in Concurrent Design Environment: Current Trends and Future Research Directions

    OpenAIRE

    Arundachawat, Panumas; Roy, Rajkumar; Al-Ashaab, Ahmed; Shehab, Essam

    2009-01-01

    Organised by: Cranfield University This paper aims to present state-of-the-art and formulate future research areas on design rework in concurrent design environment. Related literatures are analysed to extract the key factors which impact design rework. Design rework occurs due to changes from upstream design activities and/or by feedbacks from downstream design activities. Design rework is considered as negative iteration; therefore, value in design activities will be increase...

  3. Current and future drug targets in weight management

    NARCIS (Netherlands)

    Witkamp, R.F.

    2011-01-01

    Obesity will continue to be one of the leading causes of chronic disease unless the ongoing rise in the prevalence of this condition is reversed. Accumulating morbidity figures and a shortage of effective drugs have generated substantial research activity with several molecular targets being

  4. Plant derived antioxidants and antifibrotic drugs: past, present and future

    Directory of Open Access Journals (Sweden)

    Devaraj Ezhilarasan

    2014-09-01

    Full Text Available Hepatic fibrosis occurs as a wound-healing process after several forms of chronic hepatic injury. Activation and proliferation of hepatic stellate cells play pivotal role in the pathogenesis of hepatic fibrosis. Many researchers, from the therapeutic perspective, have focused their attention on searching for novel agents with inhibitory effects on hepatic stellate cells proliferation and activation to prevent hepatic fibrogenesis and a number of plant derived antioxidants have been tested as anti-fibrogenic agents, they generally suppress proliferation and collagen synthesis. Plants remain an imperative source of novel drugs, novel drug leads and new chemical entities. The plant based drug discovery resulted primarily in the development of antioxidant, anti-cancer and other anti-infectious agents and continues to contribute to the new leads in clinical trials. This review summarizes some of those most important plant derived anti-fibrotic drugs and their beneficial effects on experimentally induced hepatic fibrosis in vitro and in vivo. The plant derived antioxidant compounds described herein are curcumin, silymarin, silibinin, baicalein, resveratrol, salvianolic acids, tetrandine, quercetin and berberine. Studies from ours and as demonstrated by pervious workers much information has been accumulated over the past two decades through in vivo and in vitro. In light of those studies, it has been confirmed that plants derived antioxidants, particularly flavanoids, show a significant influence to block hepatic fibrosis regardless of any etiology. This review outlines recent progress in the use of plant derived drugs against experimentally induced liver fibrosis by in vitro and in vivo studies and summarizes the possible mechanisms anti-fibrotic effects of these compounds.

  5. 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.

  6. The future of drugs: recreational drug use and sexual health among gay and other men who have sex with men.

    Science.gov (United States)

    Race, Kane; Lea, Toby; Murphy, Dean; Pienaar, Kiran

    2017-02-01

    There are complex historical connections between sexual minoritisation and desires to chemically alter bodily experience. For gay men, drug and alcohol use can be a creative or experimental response to social marginalisation - and not necessarily a problematic one in every instance. Numerous studies have found that infection with HIV and other sexually transmissible infections (STIs) is more likely among gay and men who have sex with men (MSM) who use recreational drugs than those who do not, but the causal nature of these relations is uncertain. Sexualised drug use is associated with a range of other problems, including dependence, mental health issues, accident and overdose. A growing body of work in the Alcohol and Other Drugs (AOD) field demonstrates the action of drugs and their purported effects to be a product of their relations with various other actors, contexts and practices. Given these contingencies, it is impossible to predict the future of drugs or their effect on the sexual health of gay and MSM with any degree of certainty. This article outlines some of the conditions most likely to mediate such futures in the medium term. Public funding for lesbian, gay, bisexual, transgender and queer drug issues should not remain restricted to questions of HIV prevention and sexual health. It should be expanded to equip sexual health and AOD service providers with the cultural and sexual literacy to mitigate stigma and allow them to respond constructively to drug problems among sexual and gender minorities as a matter of priority.

  7. 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.

  8. Engineering design of TFTR and it's impact on future tokamaks

    International Nuclear Information System (INIS)

    Sabado, M.M.

    1981-01-01

    TFTR is a second generation tokamak whose key objective is scientific break-even. TFTR is expected to be the first machine to demonstrate proper combination of plasma confinement time, density, and temperature to obtain this objective. A summary of major TFTR design parameters, including TFM, is presented, and their potential impact on future tokamaks discussed. Details of the updated engineering design and analysis of components are described. Status of major hardware fabrication, assembly installation and test are reviewed. TFTR features, technology, predicted performance and their potential implication for future tokamaks are summarized

  9. Radiant coolers - Theory, flight histories, design comparisons and future applications

    Science.gov (United States)

    Donohoe, M. J.; Sherman, A.; Hickman, D. E.

    1975-01-01

    Radiant coolers have been developed for application to the cooling of infrared detectors aboard NASA earth observation systems and as part of the Defense Meteorological Satellite Program. The prime design constraints for these coolers are the location of the cooler aboard the satellite and the satellite orbit. Flight data from several coolers indicates that, in general, design temperatures are achieved. However, potential problems relative to the contamination of cold surfaces are also revealed by the data. A comparison among the various cooler designs and flight performances indicates design improvements that can minimize the contamination problem in the future.

  10. Cardiovascular effects of current and future anti-obesity drugs

    DEFF Research Database (Denmark)

    Comerma Steffensen, Simon Gabriel; Grann, Martin; Andersen, Charlotte U

    2014-01-01

    cardiovascular risk, while an inverse agonist at cannabinoid type 1 (CB1) receptors, rimonobant was withdrawn due to serious psychiatric problems. At present there are only few treatments available including orlistat and, phentermine alone or in combination with topiramate and lorcaserin, although cardiovascular...... side effects need to be clarified regarding phentermine and lorcaserin. Drugs approved for type 2 diabetes including glucagon like peptide (GLP-1) analogues and metformin also cause moderate weight losses and have a favourable cardiovascular profile, while the anti-obesity potential of nebivolol...

  11. 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.

  12. Commentary on ``Future directions: Building technologies and design tools``

    Energy Technology Data Exchange (ETDEWEB)

    Quadrel, R.W.

    1992-08-10

    This paper presents a number of interesting and thought-provoking scenarios about the future use of advanced technology in the design and operation of commercial buildings. I will express my reactions in the following series of short paragraphs. These thoughts will, I hope, raise some new questions and offer fruitful directions for further exploration.

  13. 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 .

  14. Status of core nuclear design technology for future fuel

    International Nuclear Information System (INIS)

    Joo, Hyung Kook; Jung, Hyung Guk; Noh, Jae Man; Kim, Yeong Il; Kim, Taek Kyum; Gil, Choong Sup; Kim, Jung Do; Kim, Young Jin; Sohn, Dong Seong

    1997-01-01

    The effective utilization of nuclear resource is more important factor to be considered in the design of next generation PWR in addition to the epochal consideration on economics and safety. Assuming that MOX fuel can be considered as one of the future fuel corresponding to the above request, the establishment of basic technology for the MOX core design has been performed : : the specification of the technical problem through the preliminary core design and nuclear characteristic analysis of MOX, the development and verification of the neutron library for lattice code, and the acquisition of data to be used for verification of lattice and core analysis codes. The following further studies will be done in future: detailed verification of library E63LIB/A, development of the spectral history effect treatment module, extension of decay chain, development of new homogenization for the MOX fuel assembly. (author). 6 refs., 7 tabs., 2 figs

  15. Design Disruption in Contested, Contingent and Contradictory Future-Making

    Directory of Open Access Journals (Sweden)

    Yoko Akama

    2015-10-01

    Full Text Available This paper aims to problematize how we step into situations that are often contested, contingent and contradictory. In this context, how can we sharpen our sensitivity of the role design plays in generating understanding and future-making possibilities? Here, we employ the term disruption as a way to question our own knowledge construction and research practices in Design Anthropology and Participatory Design. We pursue disruption as a political and necessary consciousness when Design Anthropology meets Participatory Design and discuss the generative, reflexive and analytical dimensions of disruption through three vignettes. These vignettes raises questions of how we interrogate disruptions of power to consider different ways in which this manifests when entering into and participating in ongoing changing process. They also highlight the need to displace existing knowledge, rather than pursuing ‘mutual learning’ that had been a defining commitment of Participatory Design. Lastly, the vignettes reveal the need to disrupt the designer-researcher in order to surrender to contradiction and contingency as part of future-making.

  16. Risk-informed design guidance for future reactor systems

    International Nuclear Information System (INIS)

    Delaney, Michael J.; Apostolakis, George E.; Driscoll, Michael J.

    2005-01-01

    Future reactor designs face an uncertain regulatory environment. It is anticipated that there will be some level of probabilistic insights in the regulations and supporting regulatory documents for Generation-IV nuclear reactors. Central to current regulations are design basis accidents (DBAs) and the general design criteria (GDC), which were established before probabilistic risk assessments (PRAs) were developed. These regulations implement a structuralist approach to safety through traditional defense in depth and large safety margins. In a rationalist approach to safety, accident frequencies are quantified and protective measures are introduced to make these frequencies acceptably low. Both approaches have advantages and disadvantages and future reactor design and licensing processes will have to implement a hybrid approach. This paper presents an iterative four-step risk-informed methodology to guide the design of future-reactor systems using a gas-cooled fast reactor emergency core cooling system as an example. This methodology helps designers to analyze alternative designs under potential risk-informed regulations and to anticipate design justifications the regulator may require during the licensing process. The analysis demonstrated the importance of common-cause failures and the need for guidance on how to change the quantitative impact of these potential failures on the frequency of accident sequences as the design changes. Deliberation is an important part of the four-step methodology because it supplements the quantitative results by allowing the inclusion in the design choice of elements such as best design practices and ease of online maintenance, which usually cannot be quantified. The case study showed that, in some instances, the structuralist and the rationalist approaches were inconsistent. In particular, GDC 35 treats the double-ended break of the largest pipe in the reactor coolant system with concurrent loss of offsite power and a single

  17. Safety design and evaluation policy for future FBRs in Japan

    International Nuclear Information System (INIS)

    Aizawa, Kiyoto

    1991-01-01

    The safety policy for fast breeder reactors (FBRs) has gradually matured in accordance with the development of FBRs. The safety assessment of the Japanese prototype FBR, Monju during the licensing process accelerated the maturity and the integration of knowledge and databases. Results are expected to be reflected in the establishment of the safety design and evaluation policy for FBRs. Although the methodologies and safety policies developed for LWRs are applicable in principle to future FBRs, it is neither rational nor realistic to treat safety only with these policies. It is recommended that one should develop the methodologies and safety policies starting from understanding of the inherent safety characteristics of FBR's through safety research, plant operating experience and design work. In the last few years, some technical committees were organized in Japan and have discussed key safety issues which are specific to FBRs in order to provide preparatory reports and to establish safety standards and guidelines for future commercial FBRs. (author)

  18. Rainwater catchment system design using simulated future climate data

    Science.gov (United States)

    Wallace, Corey D.; Bailey, Ryan T.; Arabi, Mazdak

    2015-10-01

    Rainwater harvesting techniques are used worldwide to augment potable water supply, provide water for small-scale irrigation practices, increase rainwater-use efficiency for sustained crop growth in arid and semi-arid regions, decrease urban stormwater flow volumes, and in general to relieve dependency on urban water resources cycles. A number of methods have been established in recent years to estimate reliability of rainwater catchment systems (RWCS) and thereby properly size the components (roof catchment area, storage tank size) of the system for a given climatic region. These methods typically use historical or stochastically-generated rainfall patterns to quantify system performance and optimally size the system, with the latter accounting for possible rainfall scenarios based on statistical relationships of historical rainfall patterns. To design RWCS systems that can sustainably meet water demand under future climate conditions, this paper introduces a method that employs climatic data from general circulation models (GCMs) to develop a suite of catchment area vs. storage size design curves that capture uncertainty in future climate scenarios. Monthly rainfall data for the 2010-2050 time period is statistically downscaled to daily values using a Markov chain algorithm, with results used only from GCMs that yield rainfall patterns that are statistically consistent with historical rainfall patterns. The process is demonstrated through application to two climatic regions of the Federated States of Micronesia (FSM) in the western Pacific, wherein the majority of the population relies on rainwater harvesting for potable water supply. Through the use of design curves, communities can provide household RWCS that achieve a certain degree of storage reliability. The method described herein can be applied generally to any geographic region. It can be used to first, assess the future performance of existing household systems; and second, to design or modify systems

  19. 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.

  20. 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.

  1. 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.

  2. 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.…

  3. 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)…

  4. 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.

  5. Current status and future prospects for enabling chemistry technology in the drug discovery process.

    Science.gov (United States)

    Djuric, Stevan W; Hutchins, Charles W; Talaty, Nari N

    2016-01-01

    This review covers recent advances in the implementation of enabling chemistry technologies into the drug discovery process. Areas covered include parallel synthesis chemistry, high-throughput experimentation, automated synthesis and purification methods, flow chemistry methodology including photochemistry, electrochemistry, and the handling of "dangerous" reagents. Also featured are advances in the "computer-assisted drug design" area and the expanding application of novel mass spectrometry-based techniques to a wide range of drug discovery activities.

  6. 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.

  7. 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.

  8. Fragment-based approaches to anti-HIV drug discovery: state of the art and future opportunities.

    Science.gov (United States)

    Huang, Boshi; Kang, Dongwei; Zhan, Peng; Liu, Xinyong

    2015-12-01

    The search for additional drugs to treat HIV infection is a continuing effort due to the emergence and spread of HIV strains resistant to nearly all current drugs. The recent literature reveals that fragment-based drug design/discovery (FBDD) has become an effective alternative to conventional high-throughput screening strategies for drug discovery. In this critical review, the authors describe the state of the art in FBDD strategies for the discovery of anti-HIV drug-like compounds. The article focuses on fragment screening techniques, direct fragment-based design and early hit-to-lead progress. Rapid progress in biophysical detection and in silico techniques has greatly aided the application of FBDD to discover candidate agents directed at a variety of anti-HIV targets. Growing evidence suggests that structural insights on key proteins in the HIV life cycle can be applied in the early phase of drug discovery campaigns, providing valuable information on the binding modes and efficiently prompting fragment hit-to-lead progression. The combination of structural insights with improved methodologies for FBDD, including the privileged fragment-based reconstruction approach, fragment hybridization based on crystallographic overlays, fragment growth exploiting dynamic combinatorial chemistry, and high-speed fragment assembly via diversity-oriented synthesis followed by in situ screening, offers the possibility of more efficient and rapid discovery of novel drugs for HIV-1 prevention or treatment. Though the use of FBDD in anti-HIV drug discovery is still in its infancy, it is anticipated that anti-HIV agents developed via fragment-based strategies will be introduced into the clinic in the future.

  9. 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.

  10. Design to learn: customizing services when the future matters

    Directory of Open Access Journals (Sweden)

    Dan Ariely

    2013-04-01

    Full Text Available Internet-based customization tools can be used to design service encounters that maximize customers' utility in the present or explore their tastes to provide more value in the future, where these two goals conflict with each other. Maximizing expected customer satisfaction in the present leads to slow rates of learning that may limit the ability to provide quality in the future. An emphasis on learning can lead to unsatisfied customers that will not only forego purchasing in the current period, but, more seriously, never return if they lose trust in the service provider's ability to meet their needs. This paper describes service design policies that balance the objectives of learning and selling by characterizing customer lifetime value as a function of knowledge. The analysis of the customization problem as a dynamic program yields three results. The first result is the characterization of customization policies that quantify the value of knowledge so as to adequately balance the expected revenue of present and future interactions. The second result is an analysis of the impact of operational decisions on loyalty, learning, and profitability over time. Finally, the quantification of the value of knowing the customer provides a connection between customer acquisition and retention policies, thus enhancing the current understanding of the mechanisms connecting service customization, value creation, and customer lifetime value.

  11. Willingness to treat drug dependence and depression: comparisons of future health professionals

    Directory of Open Access Journals (Sweden)

    Ríos-Bedoya CF

    2011-03-01

    treat nicotine and alcohol dependence-affected patients as compared to depression-affected patients. Personal history was not associated with the students' willingness to treat, but men were less willing to treat. Drawing strength from the randomized reinforcer experimental design nested within this survey approach, the study evidence suggests potential nonparticipation bias in standard surveys on this topic.Conclusion: These results indicate that future health professionals may prefer to treat depression as opposed to drug dependence conditions. For SBIRT success, curriculum change with educational interventions may be needed to increase willingness to treat patients with neuropsychiatric conditions such as drug dependence. Future research requires attention to a possible problem of nonparticipation bias in surveys of this type.Keywords: alcohol dependence, nicotine dependence, depression, health professionals, stigma 

  12. 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.

  13. Polymer-drug conjugates: origins, progress to date and future directions.

    Science.gov (United States)

    Kopeček, Jindřich

    2013-01-01

    This overview focuses on bioconjugates of water-soluble polymers with low molecular weight drugs and proteins. After a short discussion of the origins of the field, the state-of-the-art is reviewed. Then research directions needed for the acceleration of the translation of nanomedicines into the clinic are outlined. Two most important directions, synthesis of backbone degradable polymer carriers and drug-free macromolecular therapeutics, a new paradigm in drug delivery, are discussed in detail. Finally, the future perspectives of the field are briefly discussed. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. Nonthionamide Drugs for the Treatment of Hyperthyroidism: From Present to Future

    Directory of Open Access Journals (Sweden)

    Nattakarn Suwansaksri

    2018-01-01

    Full Text Available Hyperthyroidism is a common endocrine disease. Although thionamide antithyroid drugs are the cornerstone of hyperthyroidism treatment, some patients cannot tolerate this drug class because of its serious side effects including agranulocytosis, hepatotoxicity, and vasculitis. Therefore, nonthionamide antithyroid drugs (NTADs still have an important role in controlling hyperthyroidism in clinical practice. Furthermore, some situations such as thyroid storm or preoperative preparation require a rapid decrease in thyroid hormone by combination treatment with multiple classes of antithyroid drugs. NTADs include iodine-containing compounds, lithium carbonate, perchlorate, glucocorticoid, and cholestyramine. In this narrative review, we summarize the mechanisms of action, indications, dosages, and side effects of currently used NTADs for the treatment of hyperthyroidism. In addition, we also describe the state-of-the-art in future drugs under development including rituximab, small-molecule ligands (SMLs, and monoclonal antibodies with a thyroid-stimulating hormone receptor (TSHR antagonist effect.

  15. Swallowable smart pills for local drug delivery: present status and future perspectives.

    Science.gov (United States)

    Goffredo, Rosa; Accoto, Dino; Guglielmelli, Eugenio

    2015-01-01

    Smart pills were originally developed for diagnosis; however, they are increasingly being applied to therapy - more specifically drug delivery. In addition to smart drug delivery systems, current research is also looking into localization systems for reaching the target areas, novel locomotion mechanisms and positioning systems. Focusing on the major application fields of such devices, this article reviews smart pills developed for local drug delivery. The review begins with the analysis of the medical needs and socio-economic benefits associated with the use of such devices and moves onto the discussion of the main implemented technological solutions with special attention given to locomotion systems, drug delivery systems and power supply. Finally, desired technical features of a fully autonomous robotic capsule for local drug delivery are defined and future research trends are highlighted.

  16. Measurement of Drug Craving in Persian Speaking Subjects; a Review on Current Experiences and Future Perspectives

    Directory of Open Access Journals (Sweden)

    Masoomeh Maarefvand

    2012-09-01

    Full Text Available Background: Drug craving is considered as one of the main cores of drug dependency and addiction. Multidimensionality of drug craving, its cultural-bounded features and its intra individual rapidly changing nature makes it difficult to be measured. Nowadays, regarding different psychometric approaches, there are various instruments available for measurement of different aspects of drug craving but mainly for Latin-based languages in North America and European countries. High prevalence and special conditions, and unique subcultures in substance abuse and addiction in many countries, like Iran, make the design of culturally validated instruments for drug craving assessment priority. Materials and Methods: Comprehensive review on drug craving measurement instruments for Persian speaking subjects have been performed by searching in databases (ELSEVIER, Science Direct and Scientific Information Database (SID and investigating of related documents on regional experiences. Results: In this article seven main categories of drug craving instruments have been reviewed focusing on validated versions in Persian language including: self-reports, reinforcement “proxies”, drug self administration, psycho physiological responding, neurobiological responding, cognitive processing and expressive methods. Conclusion: Reviewing on weak and strength points of each instrument group and national and regional experiences shows that designing and validating a new series of ecologically-validated instruments for multidimensional measurement of drug craving in different addiction subcultures should be prioritized to cover current methodological gaps in substance abuse studies in Iran.

  17. 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

  18. Designing energy supply for the future. Gestaltung einer kuenftigen Energieversorgung

    Energy Technology Data Exchange (ETDEWEB)

    Roessle, G [Roessle Unternehmensberatung, Ludwigsburg (Germany)

    1991-12-01

    The government can design the energy future in two ways: Either by a defining energy plants and their organisation in a concrete manner and dictating the measures and regulations accordingly, or, by setting an abstract aim such as reduction of emissions without spelling out the necessary measures. The first model I should like to call the 'regulation model' the second as 'deregulation model'. The difference in method and performance of both models is comparable to the difference between a socialist planned economy and a social market economy. (orig.).

  19. 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...

  20. Detecting peptidic drugs, drug candidates and analogs in sports doping: current status and future directions.

    Science.gov (United States)

    Thevis, Mario; Thomas, Andreas; Schänzer, Wilhelm

    2014-12-01

    With the growing availability of mature systems and strategies in biotechnology and the continuously expanding knowledge of cellular processes and involved biomolecules, human sports drug testing has become a considerably complex field in the arena of analytical chemistry. Proving the exogenous origin of peptidic drugs and respective analogs at lowest concentration levels in biological specimens (commonly blood, serum and urine) of rather limited volume is required to pursue an action against cheating athletes. Therefore, approaches employing chromatographic-mass spectrometric, electrophoretic, immunological and combined test methods have been required and developed. These allow detecting the misuse of peptidic compounds of lower (such as growth hormone-releasing peptides, ARA-290, TB-500, AOD-9604, CJC-1295, desmopressin, luteinizing hormone-releasing hormones, synacthen, etc.), intermediate (e.g., insulins, IGF-1 and analogs, 'full-length' mechano growth factor, growth hormone, chorionic gonadotropin, erythropoietin, etc.) and higher (e.g., stamulumab) molecular mass with desired specificity and sensitivity. A gap between the technically possible detection and the day-to-day analytical practice, however, still needs to be closed.

  1. 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.

  2. 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.

  3. A future large-aperture UVOIR space observatory: reference designs

    Science.gov (United States)

    Rioux, Norman; Thronson, Harley; Feinberg, Lee; Stahl, H. Philip; Redding, Dave; Jones, Andrew; Sturm, James; Collins, Christine; Liu, Alice

    2015-09-01

    Our joint NASA GSFC/JPL/MSFC/STScI study team has used community-provided science goals to derive mission needs, requirements, and candidate mission architectures for a future large-aperture, non-cryogenic UVOIR space observatory. We describe the feasibility assessment of system thermal and dynamic stability for supporting coronagraphy. The observatory is in a Sun-Earth L2 orbit providing a stable thermal environment and excellent field of regard. Reference designs include a 36-segment 9.2 m aperture telescope that stows within a five meter diameter launch vehicle fairing. Performance needs developed under the study are traceable to a variety of reference designs including options for a monolithic primary mirror.

  4. 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.

  5. The future of the IMS Learning Design specification: a critical look

    NARCIS (Netherlands)

    Sloep, Peter

    2009-01-01

    P. B. Sloep (2009). The future of the IMS Learning Design specification: a critical look. Presentation at the IMS Learning Design seminar 'The future of IMS Learning Design'. December, 10, 2009, Wollongong, Australia: University of Wollongong.

  6. Designing future products: what difficulties do designers encounter and how can their creative process be supported?

    Science.gov (United States)

    Bonnardel, Nathalie

    2012-01-01

    To remain competitive, companies must regularly offer new products to consumers. A major challenge for designers is therefore to come up with design solutions and define products that are both new and adapted to future users and usages. Although classic methods and ergonomic recommendations are useful in most run-of-the-mill design contexts, they are of limited benefit when the design situation requires greater creativity. This paper therefore addresses issues related to product design by pursuing a triple objective: (1) highlight the difficulties encountered by designers in imagining and conceiving new products, (2) find out which conditions could help designers come up with creative ideas for innovative products, and (3) suggest methods and tools to support designers' creative process and help them take other stakeholders' needs and expectations into consideration.

  7. Dealing with sadness, madness and hostility. New psychotropic drug remedies for the future

    NARCIS (Netherlands)

    Loonen, A.J.M.

    1992-01-01

    The objective of this article is to present an overview of new forms of psychotropic drug therapy that may be expected to play a role in psychiatric practice in the 1990s. In predicting these future developments, three lines of approach have been followed. Firstly, progress in elucidating basic

  8. SMART drug delivery systems: Back to the future vs. clinical reality

    NARCIS (Netherlands)

    Lammers, Twan Gerardus Gertudis Maria

    2013-01-01

    Recent advances in nanotechnology and material science have re-ignited interest in drug delivery research. Arguably, however, hardly any of the systems developed and strategies proposed are really relevant for shaping the future (clinical) face of the nanomedicine field. Consequently, as outlined in

  9. 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...

  10. Transforming Future Teaching through ‘Carpe Diem’ Learning Design

    Directory of Open Access Journals (Sweden)

    Gilly Salmon

    2014-01-01

    Full Text Available Academic staff in Higher Education (HE need to transform their teaching practices to support more future-orientated, digital, student-centered learning. Promoting, enabling and implementing these changes urgently requires acceptable, meaningful and effective staff development for academics. We identify four key areas that are presenting as barriers to the implementation of successful staff development. We illuminate the Carpe Diem learning design workshop process and illustrate its impact on academic staff as a viable, constructive alternative to traditional staff development processes. The Carpe Diem model directly exposes and addresses the irony that educational institutions expect their academic staff to learn to design and deliver personalized, mobile and technology-enhanced learning to students, whilst wedded to ‘one size fits all’ face-to-face interventions…or worse, ‘page turning’ e-learning that masquerades as staff development. To avoid further frustrations and expensive, inappropriate initiatives, the spirit and practice of Carpe Diem could act as a ‘pathfinder beacon’, and be more widely adopted to enable fast, effective and fully embedded, learner-ready, future-proofed learning.

  11. Modelling and Designing Cryogenic Hydrogen Tanks for Future Aircraft Applications

    Directory of Open Access Journals (Sweden)

    Christopher Winnefeld

    2018-01-01

    Full Text Available In the near future, the challenges to reduce the economic and social dependency on fossil fuels must be faced increasingly. A sustainable and efficient energy supply based on renewable energies enables large-scale applications of electro-fuels for, e.g., the transport sector. The high gravimetric energy density makes liquefied hydrogen a reasonable candidate for energy storage in a light-weight application, such as aviation. Current aircraft structures are designed to accommodate jet fuel and gas turbines allowing a limited retrofitting only. New designs, such as the blended-wing-body, enable a more flexible integration of new storage technologies and energy converters, e.g., cryogenic hydrogen tanks and fuel cells. Against this background, a tank-design model is formulated, which considers geometrical, mechanical and thermal aspects, as well as specific mission profiles while considering a power supply by a fuel cell. This design approach enables the determination of required tank mass and storage density, respectively. A new evaluation value is defined including the vented hydrogen mass throughout the flight enabling more transparent insights on mass shares. Subsequently, a systematic approach in tank partitioning leads to associated compromises regarding the tank weight. The analysis shows that cryogenic hydrogen tanks are highly competitive with kerosene tanks in terms of overall mass, which is further improved by the use of a fuel cell.

  12. 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.

  13. Age and impulsive behavior in drug addiction: A review of past research and future directions.

    Science.gov (United States)

    Argyriou, Evangelia; Um, Miji; Carron, Claire; Cyders, Melissa A

    2018-01-01

    Impulsive behavior is implicated in the initiation, maintenance, and relapse of drug-seeking behaviors involved in drug addiction. Research shows that changes in impulsive behavior across the lifespan contribute to drug use and addiction. The goal of this review is to examine existing research on the relationship between impulsive behavior and drug use across the lifespan and to recommend directions for future research. Three domains of impulsive behavior are explored in this review: impulsive behavior-related personality traits, delay discounting, and prepotent response inhibition. First, we present previous research on these three domains of impulsive behavior and drug use across developmental stages. Then, we discuss how changes in impulsive behavior across the lifespan are implicated in the progression of drug use and addiction. Finally, we discuss the relatively limited attention given to middle-to-older adults in the current literature, consider the validity of the measures used to assess impulsive behavior in middle-to-older adulthood, and suggest recommendations for future research. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Low Power Design for Future Wearable and Implantable Devices

    Directory of Open Access Journals (Sweden)

    Katrine Lundager

    2016-10-01

    -less computing is drawn by looking at device circuit co-design for future system-on-chips (SoCs.

  15. Apodized Pupil Lyot Coronagraphs designs for future segmented space telescopes

    Science.gov (United States)

    St. Laurent, Kathryn; Fogarty, Kevin; Zimmerman, Neil; N’Diaye, Mamadou; Stark, Chris; Sivaramakrishnan, Anand; Pueyo, Laurent; Vanderbei, Robert; Soummer, Remi

    2018-01-01

    A coronagraphic starlight suppression system situated on a future flagship space observatory offers a promising avenue to image Earth-like exoplanets and search for biomarkers in their atmospheric spectra. One NASA mission concept that could serve as the platform to realize this scientific breakthrough is the Large UV/Optical/IR Surveyor (LUVOIR). Such a mission would also address a broad range of topics in astrophysics with a multi-wavelength suite of instruments.In support of the community’s assessment of the scientific capability of a LUVOIR mission, the Exoplanet Exploration Program (ExEP) has launched a multi-team technical study: Segmented Coronagraph Design and Analysis (SCDA). The goal of this study is to develop viable coronagraph instrument concepts for a LUVOIR-type mission. Results of the SCDA effort will directly inform the mission concept evaluation being carried out by the LUVOIR Science and Technology Definition Team. The apodized pupil Lyot coronagraph (APLC) is one of several coronagraph design families that the SCDA study is assessing. The APLC is a Lyot-style coronagraph that suppresses starlight through a series of amplitude operations on the on-axis field. Given a suite of seven plausible segmented telescope apertures, we have developed an object-oriented software toolkit to automate the exploration of thousands of APLC design parameter combinations. In the course of exploring this parameter space we have established relationships between APLC throughput and telescope aperture geometry, Lyot stop, inner working angle, bandwidth, and contrast level. In parallel with the parameter space exploration, we have investigated several strategies to improve the robustness of APLC designs to fabrication and alignment errors and integrated a Design Reference Mission framework to evaluate designs with scientific yield metrics.

  16. Beyond THC: the new generation of cannabinoid designer drugs

    Directory of Open Access Journals (Sweden)

    Liana eFattore

    2011-09-01

    Full Text Available Synthetic cannabinoids are functionally similar to delta9-tetrahydrocannabinol (THC, the psychoactive principle of cannabis, and bind to the same cannabinoid receptors in the brain and peripheral organs. From 2008, synthetic cannabinoids were detected in herbal smoking mixtures sold on websites and in head shops under the brand name of Spice Gold, Yucatan Fire, Aroma, and others. Although these products (also known as Spice drugs or legal highs do not contain tobacco or cannabis, when smoked they produce effects similar to THC. Intoxication, withdrawal, psychosis and death have been recently reported after consumption, posing difficult social, political and health challenges. More than 140 different Spice products have been identified to date. The ability to induce strong cannabis-like psychoactive effects, along with the fact that they are readily available on the Internet, still legal in many countries, marketed as natural safe substances, and undetectable by conventional drug screening tests, has rendered these drugs very popular and particularly appealing to young and drug-naïve individuals seeking new experiences. An escalating number of compounds with cannabinoid receptor activity are currently being found as ingredients of Spice, of which almost nothing is known in terms of pharmacology, toxicology and safety. Since legislation started to control the synthetic cannabinoids identified in these herbal mixtures, many new analogs have appeared on the market. New cannabimimetic compounds are likely to be synthesized in the near future to replace banned synthetic cannabinoids, leading to a dog chasing its tail situation. Spice smokers are exposed to drugs that are extremely variable in composition and potency, and are at risk of serious, if not lethal, outcomes. Social and health professionals should maintain a high degree of alertness for Spice use and its possible psychiatric effects in vulnerable people.

  17. 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.

  18. 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.

  19. 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.

  20. Reconfigurable manufacturing systems: Principles, design, and future trends

    Science.gov (United States)

    Koren, Yoram; Gu, Xi; Guo, Weihong

    2018-06-01

    Reconfigurable manufacturing systems (RMSs), which possess the advantages of both dedicated serial lines and flexible manufacturing systems, were introduced in the mid-1990s to address the challenges initiated by globalization. The principal goal of an RMS is to enhance the responsiveness of manufacturing systems to unforeseen changes in product demand. RMSs are costeffective because they boost productivity, and increase the lifetime of the manufacturing system. Because of the many streams in which a product may be produced on an RMS, maintaining product precision in an RMS is a challenge. But the experience with RMS in the last 20 years indicates that product quality can be definitely maintained by inserting in-line inspection stations. In this paper, we formulate the design and operational principles for RMSs, and provide a state-of-the-art review of the design and operations methodologies of RMSs according to these principles. Finally, we propose future research directions, and deliberate on how recent intelligent manufacturing technologies may advance the design and operations of RMSs.

  1. Temporal Shape Changes and Future Trends in European Automotive Design

    Directory of Open Access Journals (Sweden)

    Corrado Costa

    2015-09-01

    Full Text Available Evolution produces genuine novelty in morphology through the selection of competing designs as phenotypes. When applied to human creativity, the evolutionary paradigm can provide insight into the ways that our technology and its design are modified through time. The shape of European utilitarian cars in the past 60 years was analyzed in order to determine whether changes occur in a gradual fashion or through saltation, clarifying which are the more conserved and more variable parts of the designs. We also attempted to predict the future appearances of the cars within the next decade, discussing all results within the framework of relevant evolutionary-like equivalences. Here, we analyzed the modification in the shape of European utilitarian cars in the past 60 years by three-dimensional geometric morphometrics to test whether these changes occurred in a gradual or more saltatory fashion. The geometric morphometric shape analysis showed that even though car brands have always been preserving distinct shapes, all followed a gradual pattern of evolution which is now converging toward a more similar fusiform and compact asset. This process was described using Darwinian evolution as a metaphor to quantify and interpret changes over time and the societal pressures promoting them.

  2. [The role of biotechnology in pharmaceutical drug design].

    Science.gov (United States)

    Gaisser, Sibylle; Nusser, Michael

    2010-01-01

    Biotechnological methods have become an important tool in pharmaceutical drug research and development. Today approximately 15 % of drug revenues are derived from biopharmaceuticals. The most relevant indications are oncology, metabolic disorders and disorders of the musculoskeletal system. For the future it can be expected that the relevance of biopharmaceuticals will further increase. Currently, the share of substances in preclinical testing that rely on biotechnology is more than 25 % of all substances in preclinical testing. Products for the treatment of cancer, metabolic disorders and infectious diseases are most important. New therapeutic approaches such as RNA interference only play a minor role in current commercial drug research and development with 1.5 % of all biological preclinical substances. Investments in sustainable high technology such as biotechnology are of vital importance for a highly developed country like Germany because of its lack of raw materials. Biotechnology helps the pharmaceutical industry to develop new products, new processes, methods and services and to improve existing ones. Thus, international competitiveness can be strengthened, new jobs can be created and existing jobs preserved.

  3. Gifts to the Future: Design Reasoning, Design Research, and Critical Design Practitioners

    Directory of Open Access Journals (Sweden)

    Janet McDonnell

    Full Text Available Set in the context of a particular orthodoxy about the history of design research over the last 50 years, this opinion piece selectively surveys some of the significant findings from research into what expert design reasoning entails. Using the conceit of a pool of knowledge—which has come about from many different design research agendas, using multiple methods, and with differing foci of attention—it indicates some of what we know about design reasoning as a phenomenon by taking three “scoops” from the pool. These scoops, respectively characterize design reasoning as navigating the swamp; having negative capability; and being concerned with framing. This material is then used to contrast expert design reasoning with salient features of some popular characterizations of design thinking. The contribution concludes with some comments on designer formation, centered on the necessity of proficiency in reflection implied by any goal to nurture critical design practitioners.

  4. Design and fabrication stable LNF contact for future IC application

    International Nuclear Information System (INIS)

    Bhuiyan, M M I; Bhuiyan, M; Rashid, M M; Ahmed, Sayem; Kajihara, M

    2013-01-01

    Enable the design of a small contact spring for applications requiring high density, high speed and high durability. A low normal force (LNF) contact spring with high performance is fabricated using a unique combined MEMS photo resist lithography and electro fine forming (EFF) technology. Reducing a total contact material cost of a connector, a high-Hertz stress with LNF contact will be a key technology in the future. Only radius R 5μm tip with 0.1N force contact provides an excellent electrical performance which is much sharper than conventional contact. 0.30million cycle's durability test was passed at 300μm displacement and the contact resistance was ≤50mΩ

  5. Considerations in the Design of Future Planetary Laser Altimeters

    Science.gov (United States)

    Smith, D. E.; Neumann, G. A.; Mazarico, E.; Zuber, M. T.; Sun, X.

    2017-12-01

    Planetary laser altimeters have generally been designed to provide high accuracy measurements of the nadir range to an uncooperative surface for deriving the shape of the target body, and sometimes specifically for identifying and characterizing potential landing sites. However, experience has shown that in addition to the range measurement, other valuable observations can be acquired, including surface reflectance and surface roughness, despite not being given high priority in the original altimeter design or even anticipated. After nearly 2 decades of planetary laser altimeter design, the requirements are evolving and additional capabilities are becoming equally important. The target bodies, once the terrestrial planets, are now equally asteroids and moons that in many cases do not permit simple orbital operations due to their small mass, radiation issues, or spacecraft fuel limitations. In addition, for a number of reasons, it has become necessary to perform shape determination from a much greater range, even thousands of kilometers, and thus ranging is becoming as important as nadir altimetry. Reflectance measurements have also proved important for assessing the presence of ice, water or CO2, and laser pulse spreading informed knowledge of surface roughness; all indicating a need for improved instrument capability. Recently, the need to obtain accurate range measurement to laser reflectors on landers or on a planetary surface is presenting new science opportunities but for which current designs are far from optimal. These changes to classic laser altimetry have consequences for many instrument functions and capabilities, including beam divergence, laser power, number of beams and detectors, pixelation, energy measurements, pointing stability, polarization, laser wavelengths, and laser pulse rate dependent range. We will discuss how a new consideration of these trades will help make lidars key instruments to execute innovative science in future planetary

  6. Futures

    DEFF Research Database (Denmark)

    Pedersen, Michael Haldrup

    2017-01-01

    Currently both design thinking and critical social science experience an increased interest in speculating in alternative future scenarios. This interest is not least related to the challenges issues of global sustainability present for politics, ethics and design. This paper explores the potenti......Currently both design thinking and critical social science experience an increased interest in speculating in alternative future scenarios. This interest is not least related to the challenges issues of global sustainability present for politics, ethics and design. This paper explores...... the potentials of speculative thinking in relation to design and social and cultural studies, arguing that both offer valuable insights for creating a speculative space for new emergent criticalities challenging current assumptions of the relations between power and design. It does so by tracing out discussions...... of ‘futurity’ and ‘futuring’ in design as well as social and cultural studies. Firstly, by discussing futurist and speculative approaches in design thinking; secondly by engaging with ideas of scenario thinking and utopianism in current social and cultural studies; and thirdly by showing how the articulation...

  7. 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.

  8. 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.

  9. 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.

  10. Future CANDU nuclear power plant design requirements document executive summary

    International Nuclear Information System (INIS)

    Lee, Duk Su; Chang, Woo Hyun; Lee, Nam Young; S. A. Usmani

    1996-03-01

    The future CANDU Requirements Document (FCRED) describes a clear and complete statement of utility requirements for the next generation of CANDU nuclear power plants including those in Korea. The requirements are based on proven technology of PHWR experience and are intended to be consistent with those specified in the current international requirement documents. Furthermore, these integrated set of design requirements, incorporate utility input to the extent currently available and assure a simple, robust and more forgiving design that enhances the performance and safety. The FCRED addresses the entire plant, including the nuclear steam supply system and the balance of the plant, up to the interface with the utility grid at the distribution side of the circuit breakers which connect the switchyard to the transmission lines. Requirements for processing of low level radioactive waste at the plant site and spent fuel storage requirements are included in the FCRED. Off-site waste disposal is beyond the scope of the FCRED. 2 tabs., 1 fig. (Author) .new

  11. 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...

  12. 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...

  13. 3D printed drug delivery and testing systems - a passing fad or the future?

    Science.gov (United States)

    Lim, Seng Han; Kathuria, Himanshu; Tan, Justin Jia Yao; Kang, Lifeng

    2018-05-18

    The US Food and Drug Administration approval of the first 3D printed tablet in 2015 has ignited growing interest in 3D printing, or additive manufacturing (AM), for drug delivery and testing systems. Beyond just a novel method for rapid prototyping, AM provides key advantages over traditional manufacturing of drug delivery and testing systems. These includes the ability to fabricate complex geometries to achieve variable drug release kinetics; ease of personalising pharmacotherapy for patient and lowering the cost for fabricating personalised dosages. Furthermore, AM allows fabrication of complex and micron-sized tissue scaffolds and models for drug testing systems that closely resemble in vivo conditions. However, there are several limitations such as regulatory concerns that may impede the progression to market. Here, we provide an overview of the advantages of AM drug delivery and testing, as compared to traditional manufacturing techniques. Also, we discuss the key challenges and future directions for AM enabled pharmaceutical applications. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. 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.

  15. Electricity market design of the future; Strommarktdesign der Zukunft

    Energy Technology Data Exchange (ETDEWEB)

    Peek, Markus; Diels, Robert [r2b energy consulting GmbH, Koeln (Germany)

    2016-02-15

    The transformation of the power generation system, to one in which renewable energies will form a cornerstone, will change the requirements for all market actors. To achieve the goals of the German Energiewende ('energy transition'), greater flexibility in production and consumption is of particular importance. Flexibility enables the cost-effective integration of the fluctuating actual feed-in of renewable energies. On the one hand, the technical options for reducing existing technical inflexibilities are given to a considerable extent. On the other hand, analyses of the transnational compensation effects of load and renewable energy supply (RES) feed-in show that flexibility requirements can be reduced significantly in a common electricity market. Electricity markets in which there is open technological competition are an appropriate instrument for the flexibilization of the power supply system. In the short term, the mechanisms of competitive electricity markets ensure an efficient synchronization of supply and demand. Over the medium and long term, the market creates efficient incentives to adapt the generation system and the behavior of consumers to future needs, resulting from the changes in the residual load structure. But at the same time, in recent years the occurrence of negative electricity prices in situations with significantly positive residual loads show that flexibility restraints exist. The causes of these restraints are at least partly due to the market design or the regulatory framework. On the one hand, there are barriers to market entry and, on the other hand, price signals from the electricity markets do not reach all market actors or reach them distortedly. To enable the cost effective development of the different flexibility options in an open technology competition, restraints resulting from market design and the regulatory framework (e. g. in the framework of grid charges, the market and product design of control power markets

  16. Low energy nanoemulsification to design veterinary controlled drug delivery devices

    Directory of Open Access Journals (Sweden)

    Thierry F Vandamme

    2010-10-01

    Full Text Available Thierry F Vandamme, Nicolas Anton, University of Strasbourg, Faculty of Pharmacy, Illkirch Cedex, France; UMR CNRS 7199, Laboratoire de Conception et Application de Molécules Bioactives, équipe de Pharmacie Biogalénique, Illkirch Cedex, France,  This work is selected as Controlled Release Society Outstanding Veterinary Paper Award 2010Abstract: The unique properties of nanomaterials related to structural stability and quantum-scale reactive properties open up a world of possibilities that could be exploited to design and to target drug delivery or create truly microscale biological sensors for veterinary applications. We developed cost-saving and solvent-free nanoemulsions. Formulated with a low-energy method, these nanoemulsions can find application in the delivery of controlled amounts of drugs into the beverage of breeding animals (such as poultry, cattle, pigs or be used for the controlled release of injectable poorly water-soluble drugs.Keywords: nanoemulsion, nanomedicine, low-energy emulsification, veterinary, ketoprofen, sulfamethazine

  17. 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.

  18. The impact of pharmacophore modeling in drug design.

    Science.gov (United States)

    Guner, Osman F

    2005-07-01

    With the reliable use of computer simulations in scientific research, it is possible to achieve significant increases in productivity as well as a reduction in research costs compared with experimental approaches. For example, computer-simulation can substantially enchance productivity by focusing the scientist to better, more informed choices, while also driving the 'fail-early' concept to result in a significant reduction in cost. Pharmacophore modeling is a reliable computer-aided design tool used in the discovery of new classes of compounds for a given therapeutic category. This commentary will briefly review the benefits and applications of this technology in drug discovery and design, and will also highlight its historical evolution. The two most commonly used approaches for pharmacophore model development will be discussed, and several examples of how this technology was successfully applied to identify new potent leads will be provided. The article concludes with a brief outline of the controversial issue of patentability of pharmacophore models.

  19. Therapeutic drug monitoring in pediatric IBD: current application and future perspectives.

    Science.gov (United States)

    Lega, Sara; Bramuzzo, Matteo; Dubinsky, Marla

    2017-09-11

    As the paradigm for IBD management is evolving from symptom control to the more ambitious goal of complete deep remission, the concept of personalized medicine, as a mean to deliver individualized treatment with the best effectiveness and safety profile, is becoming paramount. Therapeutic drug monitoring (TDM) is an essential part of personalized medicine wherein serum drug concentrations are used to guide drug dosing on an individual basis. The concept of TDM has been introduced in the field of IBD along with thiopurines, over a decade ago, and evolved around anti-TNFs therapies. In the era of biologics, TDM entered the clinical field to assist clinicians managing anti-TNF failure and its role is now moving toward the concept of "proactive" TDM with the goal to optimize drug exposure and prevent loss of response. Research in TDM is rapidly expanding: while the role of TDM with new biologics is under investigation, preliminary data suggest that software-systems support tools could be an opportunity to guide dosing choices and maximize the cost-benefit profile of therapies in the near future. The review discusses the current knowledge that poses the rationale for the use of TDM and the present and future role of TDM-based approaches in the management of pediatric IBD. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  20. Review and future perspective of central receiver design and performance

    Science.gov (United States)

    Zhu, Guangdong; Libby, Cara

    2017-06-01

    overgeneration, spillage, and instability may occur. Energy storage may well become a necessity in some areas in order to maintain reliability. Next-generation central receiver technologies will have higher operating temperatures and additional features that allow higher-efficiency power generation and deliver other cost-performance advantages. The underlying innovations will come from areas such as multi-physics modeling, high-temperature materials, novel power cycles and heat exchanger designs, and collector field sensing and performance monitoring technologies. Technology innovation is expected to improve the cost and performance of central receiver designs. To deliver value as a generation and storage option, central receiver technology must also be supported by flexible and robust financial models and comprehensive energy and ancillary service markets justifying the capital-intensive investment. Progress in these areas will position CSP central receiver technology for future deployment.

  1. Review and Future Perspective of Central Receiver Design and Performance

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Guangdong; Libby, Cara

    2017-06-27

    accommodate, beyond which overgeneration, spillage, and instability may occur. Energy storage may well become a necessity in some areas in order to maintain reliability. Next-generation central receiver technologies will have higher operating temperatures and additional features that allow higher-efficiency power generation and deliver other cost-performance advantages. The underlying innovations will come from areas such as multi-physics modeling, high-temperature materials, novel power cycles and heat exchanger designs, and collector field sensing and performance monitoring technologies. Technology innovation is expected to improve the cost and performance of central receiver designs. To deliver value as a generation and storage option, central receiver technology must also be supported by flexible and robust financial models and comprehensive energy and ancillary service markets justifying the capital-intensive investment. Progress in these areas will position CSP central receiver technology for future deployment.

  2. 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.

  3. 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.

  4. 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

  5. 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

  6. 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.

  7. Biomedical data integration in computational drug design and bioinformatics.

    Science.gov (United States)

    Seoane, Jose A; Aguiar-Pulido, Vanessa; Munteanu, Cristian R; Rivero, Daniel; Rabunal, Juan R; Dorado, Julian; Pazos, Alejandro

    2013-03-01

    In recent years, in the post genomic era, more and more data is being generated by biological high throughput technologies, such as proteomics and transcriptomics. This omics data can be very useful, but the real challenge is to analyze all this data, as a whole, after integrating it. Biomedical data integration enables making queries to different, heterogeneous and distributed biomedical data sources. Data integration solutions can be very useful not only in the context of drug design, but also in biomedical information retrieval, clinical diagnosis, system biology, etc. In this review, we analyze the most common approaches to biomedical data integration, such as federated databases, data warehousing, multi-agent systems and semantic technology, as well as the solutions developed using these approaches in the past few years.

  8. CRITICAL ASSESSMENT OF CONTRIBUTION FROM INDIAN PUBLICATIONS: THE ROLE OF IN SILICO DESIGNING METHODS LEADING TO DRUGS OR DRUG-LIKE COMPOUNDS USING TEXT BASED MINING AND ASSOCIATION

    Directory of Open Access Journals (Sweden)

    Pawan Kumar

    2017-09-01

    Full Text Available Over the several decades, India is constantly challenged by communicable and non-communicable diseases which are originated either by poor lifestyle or by environmental factors. The pools of diseases are constantly posing serious threats to mankind especially among the poverty-stricken families. Scientific communities across the globe are working continuously to design drug molecules to overcome the burden of these life threaten diseases. In last three decades, many computational algorithms and tools have been developed to identify potential drug targets and their inhibitors. It is believed that computational techniques have reduced the time and money required to develop an inhibitor into drug. However, applicability and deliverability of these in silico techniques in rational drug designing are not fully evaluated. In the present study, PubMed/Medline extracted data driven analysis has been performed to highlight the influence and progress of the theoretical methods in the field of drug discovery across India and compared with the world. Drug discovery related keyword dictionary has been built and utilized to select only drug discovery related PubMed abstract. A second keyword set (related to bioinformatics tools is used for normalized pointwise mutual information (PMI based association analysis. Observations show that drug discovery has been an interdisciplinary research and used many tools starting with QSAR, docking, pharmacophore, Molecular Simulations etc. The publications contributed from India (2% are similar as compared to the contribution in total world publications, suggesting large scope in future. Data coverage as represented since 1990-2015 in PubMed as indicated by number of publications associated with drug discovery is almost same in world and India (~75%. Emerging institutes/Universities are contributing since last 10 years as observed from Indian publication list. However, this method has many limitations as discussed.

  9. 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…

  10. Spatial Patterns and Design Policies for Future American Cities

    Science.gov (United States)

    Dutt, Ashok K.; Costa, Frank J.

    1977-01-01

    Describes plans for future urban development which take into account energy needs, mass transportation, technological innovations, high density settlement along the rapid transit spine, and rational decision making. (Author/DB)

  11. Opportunities and Challenges for Drug Development: Public-Private Partnerships, Adaptive Designs and Big Data.

    Science.gov (United States)

    Yildirim, Oktay; Gottwald, Matthias; Schüler, Peter; Michel, Martin C

    2016-01-01

    Drug development faces the double challenge of increasing costs and increasing pressure on pricing. To avoid that lack of perceived commercial perspective will leave existing medical needs unmet, pharmaceutical companies and many other stakeholders are discussing ways to improve the efficiency of drug Research and Development. Based on an international symposium organized by the Medical School of the University of Duisburg-Essen (Germany) and held in January 2016, we discuss the opportunities and challenges of three specific areas, i.e., public-private partnerships, adaptive designs and big data. Public-private partnerships come in many different forms with regard to scope, duration and type and number of participants. They range from project-specific collaborations to strategic alliances to large multi-party consortia. Each of them offers specific opportunities and faces distinct challenges. Among types of collaboration, investigator-initiated studies are becoming increasingly popular but have legal, ethical, and financial implications. Adaptive trial designs are also increasingly discussed. However, adaptive should not be used as euphemism for the repurposing of a failed trial; rather it requires carefully planning and specification before a trial starts. Adaptive licensing can be a counter-part of adaptive trial design. The use of Big Data is another opportunity to leverage existing information into knowledge useable for drug discovery and development. Respecting limitations of informed consent and privacy is a key challenge in the use of Big Data. Speakers and participants at the symposium were convinced that appropriate use of the above new options may indeed help to increase the efficiency of future drug development.

  12. Opportunities and challenges for drug development: public-private partnerships, adaptive designs and big data

    Directory of Open Access Journals (Sweden)

    Oktay Yildirim

    2016-12-01

    Full Text Available Drug development faces the double challenge of increasing costs and increasing pressure on pricing. To avoid that lack of perceived commercial perspective will leave existing medical needs unmet, pharmaceutical companies and many other stakeholders are discussing ways to improve the efficiency of drug Research & Development. Based on an international symposium organized by the Medical School of the University of Duisburg-Essen (Germany and held in January 2016, we discuss the opportunities and challenges of three specific areas, i.e. public-private partnerships, adaptive designs and big data. Public-private partnerships come in many different forms with regard to scope, duration and type and number of participants. They range from project-specific collaborations to strategic alliances to large multi-party consortia. Each of them offers specific opportunities and faces distinct challenges. Among types of collaboration, investigator-initiated studies are becoming increasingly popular but have legal, ethical and financial implications. Adaptive trial designs are also increasingly discussed. However, adaptive should not be used as euphemism for the repurposing of a failed trial; rather it requires carefully planning and specification before a trial starts. Adaptive licensing can be a counter-part of adaptive trial design. The use of Big Data is another opportunity to leverage existing information into knowledge useable for drug discovery and development. Respecting limitations of informed consent and privacy is a key challenge in the use of Big Data. Speakers and participants at the symposium were convinced that appropriate use of the above new options may indeed help to increase the efficiency of future drug development.

  13. Opportunities and Challenges for Drug Development: Public–Private Partnerships, Adaptive Designs and Big Data

    Science.gov (United States)

    Yildirim, Oktay; Gottwald, Matthias; Schüler, Peter; Michel, Martin C.

    2016-01-01

    Drug development faces the double challenge of increasing costs and increasing pressure on pricing. To avoid that lack of perceived commercial perspective will leave existing medical needs unmet, pharmaceutical companies and many other stakeholders are discussing ways to improve the efficiency of drug Research and Development. Based on an international symposium organized by the Medical School of the University of Duisburg-Essen (Germany) and held in January 2016, we discuss the opportunities and challenges of three specific areas, i.e., public–private partnerships, adaptive designs and big data. Public–private partnerships come in many different forms with regard to scope, duration and type and number of participants. They range from project-specific collaborations to strategic alliances to large multi-party consortia. Each of them offers specific opportunities and faces distinct challenges. Among types of collaboration, investigator-initiated studies are becoming increasingly popular but have legal, ethical, and financial implications. Adaptive trial designs are also increasingly discussed. However, adaptive should not be used as euphemism for the repurposing of a failed trial; rather it requires carefully planning and specification before a trial starts. Adaptive licensing can be a counter-part of adaptive trial design. The use of Big Data is another opportunity to leverage existing information into knowledge useable for drug discovery and development. Respecting limitations of informed consent and privacy is a key challenge in the use of Big Data. Speakers and participants at the symposium were convinced that appropriate use of the above new options may indeed help to increase the efficiency of future drug development. PMID:27999543

  14. 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.

  15. Design consideration on severe accident for future LWR

    International Nuclear Information System (INIS)

    Omoto, A.

    1998-01-01

    Utilities' Severe Accident Management strategies, selected based on Individual Plant Examination, are in the process of implementation for each operating plant. Activities for the next generation LWR design are going on by Utilities, NSSS vendors and Research Institutes. The proposed new designs vary from evolutionary design to revolutionary design such as the supercritical LWR. Discussion on the consideration of Severe Accident in the design of next generation LWR is being held to establish the industry's self-regulatory document on containment design and its performance, which ABWR-IER (Improved Evolutionary Reactor) on the part of BWR and Evolutionary APWR and New PWR21 on the part of PWR are expected to comply. Conceptual design study for ABWR-IER will illustrate an example of design approach for the prevention and mitigation of Severe Accident and its impact on capital cost

  16. Advanced drug delivery systems: Nanotechnology of health design A review

    Directory of Open Access Journals (Sweden)

    Javad Safari

    2014-04-01

    Full Text Available Nanotechnology has finally and firmly entered the realm of drug delivery. Performances of intelligent drug delivery systems are continuously improved with the purpose to maximize therapeutic activity and to minimize undesirable side-effects. This review describes the advanced drug delivery systems based on micelles, polymeric nanoparticles, and dendrimers. Polymeric carbon nanotubes and many others demonstrate a broad variety of useful properties. This review emphasizes the main requirements for developing new nanotech-nology-based drug delivery systems.

  17. Rube Goldbergineering: Lessons In Teaching Engineering Design To Future Engineers

    OpenAIRE

    Jordan, Shawn; Pereira, Nielsen

    2009-01-01

    Hands-on learning experiences and interactive learning environments can be effective in teaching K-12 students. Design, in essence, is an interactive, hands-on experience. Engineering design can be taught in the classroom using innovative hands-on projects, such as designing and building serve to teach design, promote creativity, and provide opportunities for hands-on problem solving, in addition to giving students experience working in cooperative teams. In turn, these experiences could enco...

  18. Models of Change: The Future of Design Education

    Science.gov (United States)

    Baynes, Ken; Baynes, Brochocka

    2010-01-01

    This paper discusses design and design education in the context of four major social and environmental concerns identified by Bruce Archer in 1973: overpopulation; pollution; depletion of natural resources; control. It argues for the social and economic importance of design education in primary and secondary schools. It identifies "designerly…

  19. Product Design: Research Trends and an Agenda for the Future

    NARCIS (Netherlands)

    Di Benedetto, A.C.

    2012-01-01

    Academic research in product design is growing in popular- ity, and new challenging research questions are emerging. This article explores several of these product design research issues. We first explore the role of design as a driver of innovation and as a strategic resource to senior managers for

  20. Product integrated PV: the future is design and styling

    NARCIS (Netherlands)

    Eggink, Wouter; Reinders, Angelina H.M.E.

    2016-01-01

    In this paper we explore how PV powered products have been designed in the past. For this purpose we have drawn a historical time line of the design features of PV powered products in the context of main stream design and styling. Our time frame is 1970 till 2016, focusing in first instance on

  1. Virtual fragment preparation for computational fragment-based drug design.

    Science.gov (United States)

    Ludington, Jennifer L

    2015-01-01

    Fragment-based drug design (FBDD) has become an important component of the drug discovery process. The use of fragments can accelerate both the search for a hit molecule and the development of that hit into a lead molecule for clinical testing. In addition to experimental methodologies for FBDD such as NMR and X-ray Crystallography screens, computational techniques are playing an increasingly important role. The success of the computational simulations is due in large part to how the database of virtual fragments is prepared. In order to prepare the fragments appropriately it is necessary to understand how FBDD differs from other approaches and the issues inherent in building up molecules from smaller fragment pieces. The ultimate goal of these calculations is to link two or more simulated fragments into a molecule that has an experimental binding affinity consistent with the additive predicted binding affinities of the virtual fragments. Computationally predicting binding affinities is a complex process, with many opportunities for introducing error. Therefore, care should be taken with the fragment preparation procedure to avoid introducing additional inaccuracies.This chapter is focused on the preparation process used to create a virtual fragment database. Several key issues of fragment preparation which affect the accuracy of binding affinity predictions are discussed. The first issue is the selection of the two-dimensional atomic structure of the virtual fragment. Although the particular usage of the fragment can affect this choice (i.e., whether the fragment will be used for calibration, binding site characterization, hit identification, or lead optimization), general factors such as synthetic accessibility, size, and flexibility are major considerations in selecting the 2D structure. Other aspects of preparing the virtual fragments for simulation are the generation of three-dimensional conformations and the assignment of the associated atomic point charges.

  2. 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

  3. 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.

  4. Bigger Data, Collaborative Tools and the Future of Predictive Drug Discovery

    Science.gov (United States)

    Clark, Alex M.; Swamidass, S. Joshua; Litterman, Nadia; Williams, Antony J.

    2014-01-01

    Over the past decade we have seen a growth in the provision of chemistry data and cheminformatics tools as either free websites or software as a service (SaaS) commercial offerings. These have transformed how we find molecule-related data and use such tools in our research. There have also been efforts to improve collaboration between researchers either openly or through secure transactions using commercial tools. A major challenge in the future will be how such databases and software approaches handle larger amounts of data as it accumulates from high throughput screening and enables the user to draw insights, enable predictions and move projects forward. We now discuss how information from some drug discovery datasets can be made more accessible and how privacy of data should not overwhelm the desire to share it at an appropriate time with collaborators. We also discuss additional software tools that could be made available and provide our thoughts on the future of predictive drug discovery in this age of big data. We use some examples from our own research on neglected diseases, collaborations, mobile apps and algorithm development to illustrate these ideas. PMID:24943138

  5. Monitoring the Future National Survey Results on Drug Use, 1975-2010. Volume I, Secondary School Students

    Science.gov (United States)

    Johnston, Lloyd D.; O'Malley, Patrick M.; Bachman, Jerald G.; Schulenberg, John E.

    2011-01-01

    The Monitoring the Future (MTF) study involves an ongoing series of national surveys of American adolescents and adults that has provided the nation with a vital window into the important, but largely hidden, problem behaviors of illegal drug use, alcohol use, tobacco use, anabolic steroid use, and psychotherapeutic drug use. For more than a third…

  6. A Novel Final Focus Design for Future Linear Colliders

    Energy Technology Data Exchange (ETDEWEB)

    Seryi, Andrei

    2000-05-30

    The length, complexity and cost of the present Final Focus designs for linear colliders grows very quickly with the beam energy. In this letter, a novel final focus system is presented and compared with the one proposed for NLC. This new design is simpler, shorter and cheaper, with comparable bandwidth, tolerances and tunability. Moreover, the length scales slower than linearly with energy allowing for a more flexible design which is applicable over a much larger energy range.

  7. A Practitioner’s View of the Future of Organization Design: Future Trends and Implications for Royal Dutch Shell

    Directory of Open Access Journals (Sweden)

    Jan Steinmetz

    2012-05-01

    Full Text Available Humanity is facing an increasingly challenging outlook for energy needs and the planet. Royal Dutch Shell is a global group of energy and petrochemicals companies with approximately 100,000 employees in more than 80 countries that is committed to help meet the challenges of the new energy environment in a sustainable and responsible manner. My statement will present some of the future trends and possible implications which can be seen for organization design within Royal Dutch Shell (Shell and which are applicable to other large, complex enterprises. It largely represents the personal views and reflections of a practitioner both inside and outside of Shell’s human resources (HR function in the United States. Using the lens of organization design, we will review the themes that emerged from the Shell Energy 2025 and Shell Energy 2050 global scenarios. Next, we will discuss Shell’s previous experience, challenges, and issues related to organization design, and how the recent redesign of the HR function has provided wider space and crisper focus to meet the challenges of the future. Finally, we will review the design challenges that the future trends impose upon the organization design practice. Although these challenges and implications are derived from experience working in Shell and its joint ventures, they are not confined solely to Shell. Because many of the challenges discussed below would benefit from scholarly research, the statement represents a practitioner’s view on how the future of organization design may play out.

  8. Predictors of Future Performance in Architectural Design Education

    Science.gov (United States)

    Roberts, A. S.

    2007-01-01

    The link between academic performance in secondary education and the subsequent performance of students studying architecture at university level is commonly questioned by educators and admissions tutors. This paper investigates the potential for using measures of cognitive style and spatial ability as predictors of future potential in…

  9. 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.

  10. Heuristic lipophilicity potential for computer-aided rational drug design

    Science.gov (United States)

    Du, Qishi; Arteca, Gustavo A.; Mezey, Paul G.

    1997-09-01

    In this contribution we suggest a heuristic molecular lipophilicitypotential (HMLP), which is a structure-based technique requiring noempirical indices of atomic lipophilicity. The input data used in thisapproach are molecular geometries and molecular surfaces. The HMLP is amodified electrostatic potential, combined with the averaged influences fromthe molecular environment. Quantum mechanics is used to calculate theelectron density function ρ(r) and the electrostatic potential V(r), andfrom this information a lipophilicity potential L(r) is generated. The HMLPis a unified lipophilicity and hydrophilicity potential. The interactions ofdipole and multipole moments, hydrogen bonds, and charged atoms in amolecule are included in the hydrophilic interactions in this model. TheHMLP is used to study hydrogen bonds and water-octanol partitioncoefficients in several examples. The calculated results show that the HMLPgives qualitatively and quantitatively correct, as well as chemicallyreasonable, results in cases where comparisons are available. Thesecomparisons indicate that the HMLP has advantages over the empiricallipophilicity potential in many aspects. The HMLP is a three-dimensional andeasily visualizable representation of molecular lipophilicity, suggested asa potential tool in computer-aided three-dimensional drug design.

  11. The ways and means of fragment-based drug design.

    Science.gov (United States)

    Doak, Bradley C; Norton, Raymond S; Scanlon, Martin J

    2016-11-01

    Fragment-based drug design (FBDD) has emerged as a mainstream approach for the rapid and efficient identification of building blocks that can be used to develop high-affinity ligands against protein targets. One of the strengths of FBDD is the relative ease and low cost of the primary screen to identify fragments that bind. However, the fragments that emerge from primary screens often have low affinities, with K D values in the high μM to mM range, and a significant challenge for FBDD is to develop the initial fragments into more potent ligands. Successful fragment elaboration often requires co-structures of the fragments bound to their target proteins, as well as a range of biophysical and biochemical assays to track potency and efficacy. These challenges have led to the development of specific chemical strategies for the elaboration of weakly-binding fragments into more potent "hits" and lead compounds. In this article we review different approaches that have been employed to meet these challenges and describe some of the strategies that have resulted in several fragment-derived compounds entering clinical trials. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Peptide-based proteasome inhibitors in anticancer drug design.

    Science.gov (United States)

    Micale, Nicola; Scarbaci, Kety; Troiano, Valeria; Ettari, Roberta; Grasso, Silvana; Zappalà, Maria

    2014-09-01

    The identification of the key role of the eukaryotic 26S proteasome in regulated intracellular proteolysis and its importance as a target in many pathological conditions wherein the proteasomal activity is defective (e.g., malignancies, autoimmune diseases, neurodegenerative diseases, etc.) prompted several research groups to the development of specific inhibitors of this multicatalytic complex with the aim of obtaining valid drug candidates. In regard to the anticancer therapy, the peptide boronate bortezomib (Velcade®) represents the first molecule approved by FDA for the treatment of multiple myeloma in 2003 and mantle cell lymphoma in 2006. Since then, a plethora of molecules targeting the proteasome have been identified as potential anticancer agents and a few of them reached clinical trials or are already in the market (i.e., carfilzomib; Kyprolis®). In most cases, the design of new proteasome inhibitors (PIs) takes into account a proven peptide or pseudopeptide motif as a base structure and places other chemical entities throughout the peptide skeleton in such a way to create an efficacious network of interactions within the catalytic sites. The purpose of this review is to provide an in-depth look at the current state of the research in the field of peptide-based PIs, specifically those ones that might find an application as anticancer agents. © 2014 Wiley Periodicals, Inc.

  13. Real options valuation in the design of Future surface combatants

    Science.gov (United States)

    2017-06-01

    design, different from the preceding FREMM multi-mission frigates, and features an unusual ‘ inverted bow’ intended to improve seakeeping in high sea...method of ship design is becoming cost-prohibitive when looking at the lifetime life-cycle cost for upgrades, overhauls, and drives inflexibility

  14. 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

  15. Status of LWR fuel design and future usage of JENDL

    International Nuclear Information System (INIS)

    Ito, Takuya

    2008-01-01

    For all conventional LWR fuel design codes of LWR fuel manufactures in Japan, the cross section library are based on the ENDF/B. Recently we can see several movements for the utilization of JENDL library for the LWR fuel design. The latest version of NEUPHYS cross section library is based on the JENDL-3.2. To accelerate this movement of JENDL utilization in LWR fuel design, it is necessary to prepare a high quality JENDL document, systematic validation of JENDL and to appeal them abroad effectively. (author)

  16. Three-dimensional structures in the design of therapeutics targeting parasitic protozoa: reflections on the past, present and future.

    Science.gov (United States)

    Hol, Wim G J

    2015-05-01

    Parasitic protozoa cause a range of diseases which threaten billions of human beings. They are responsible for tremendous mortality and morbidity in the least-developed areas of the world. Presented here is an overview of the evolution over the last three to four decades of structure-guided design of inhibitors, leads and drug candidates aiming at targets from parasitic protozoa. Target selection is a crucial and multi-faceted aspect of structure-guided drug design. The major impact of advances in molecular biology, genome sequencing and high-throughput screening is touched upon. The most advanced crystallographic techniques, including XFEL, have already been applied to structure determinations of drug targets from parasitic protozoa. Even cryo-electron microscopy is contributing to our understanding of the mode of binding of inhibitors to parasite ribosomes. A number of projects have been selected to illustrate how structural information has assisted in arriving at promising compounds that are currently being evaluated by pharmacological, pharmacodynamic and safety tests to assess their suitability as pharmaceutical agents. Structure-guided approaches are also applied to incorporate properties into compounds such that they are less likely to become the victim of resistance mechanisms. A great increase in the number of novel antiparasitic compounds will be needed in the future. These should then be combined into various multi-compound therapeutics to circumvent the diverse resistance mechanisms that render single-compound, or even multi-compound, drugs ineffective. The future should also see (i) an increase in the number of projects with a tight integration of structural biology, medicinal chemistry, parasitology and pharmaceutical sciences; (ii) the education of more `medicinal structural biologists' who are familiar with the properties that compounds need to have for a high probability of success in the later steps of the drug-development process; and (iii) the

  17. Integrated structure/control design - Present methodology and future opportunities

    Science.gov (United States)

    Weisshaar, T. A.; Newsom, J. R.; Zeiler, T. A.; Gilbert, M. G.

    1986-01-01

    Attention is given to current methodology applied to the integration of the optimal design process for structures and controls. Multilevel linear decomposition techniques proved to be most effective in organizing the computational efforts necessary for ISCD (integrated structures and control design) tasks. With the development of large orbiting space structures and actively controlled, high performance aircraft, there will be more situations in which this concept can be applied.

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

    NARCIS (Netherlands)

    Nales, D.A.; Kozarewicz, Piotr; Aylward, Brian; de Vries, Rutger; Egberts, Toine C G; Rademaker, Carin M A; Schobben, Alfred F A M

    The availability of licensed paediatric drugs is lagging behind those for adults, and there is a lack of safe formulations in suitable doses that children are able and willing to take. As a consequence, children are commonly treated with off-label or unlicensed drugs. As off-label and unlicensed

  19. Design and Development of a Proniosomal Transdermal Drug ...

    African Journals Online (AJOL)

    Purpose: The aim of the study was to develop a proniosomal carrier system for captopril for the treatment of hypertension that is capable of efficiently delivering entrapped drug over an extended period of time. Method: The potential of proniosomes as a transdermal drug delivery system for captopril was investigated by ...

  20. Containment design for Indian PHWRs - evolution and future trends

    International Nuclear Information System (INIS)

    Chatterjee, S.K.; Srinivasan, G.R.; Das, M.; Prakash, P.; Mulgund, S.

    1994-01-01

    The design of containment systems for PHWRs in India has undergone progressive improvements to enhance their reliability and effectiveness. The state-of-the-art containment design incorporates a double containment structure for minimizing radioactivity release to the environment, a completely passive vapour suppression system with huge suppression pool for limiting pressure build-up during postulated LOCA and various engineered systems for depressurizing the containment and cleaning the containment environment following an accident. The containment related Engineered Safety Features (ESFS) include Reactor Building (RB) coolers, Primary Containment Controlled Discharge (PCCD) system, Primary Containment Filtration and Pump-Back (PCFPB) system and Secondary Containment Filtered Recirculation and Purge (SCFRP) system. Studies indicate that the unique feature of double containment with huge suppression pool at basement and associated ESFs not only ensures near zero ground level release during Design Basis Accident (DBA) conditions, but also provides adequate assurance for containment integrity even in beyond DBA scenario. In this paper, an outline of the containment design evolution in Indian PHWRs is presented and salient features of standardized containment design are highlighted. Important containment related studies are discussed and outstanding safety issues viz. hydrogen generation and management, containment venting, containment over pressure capability, etc. are addressed. (author). 16 refs., 1 tab., 8 figs

  1. Embodied Cognition and the Magical Future of Interaction Design

    Directory of Open Access Journals (Sweden)

    David Kirsh

    2013-09-01

    Full Text Available The theory of embodied cognition can provide HCI practitioners and theorists with new ideas about interaction and new principles for better designs. I support this claim with four ideas about cognition: (1 interacting with tools changes the way we think and perceive – tools, when manipulated, are soon absorbed into the body schema, and this absorption leads to fundamental changes in the way we perceive and conceive of our environments; (2 we think with our bodies not just with our brains; (3 we know more by doing than 3by seeing – there are times when physically performing an activity is better than watching someone else perform the activity, even though our motor resonance system fires strongly during other person observa tion; (4 there are times when we literally think with things. These four ideas have major implications for interaction design, especially the design of tangible, physical, context aware, and telepresence systems.

  2. Using Free Computational Resources to Illustrate the Drug Design Process in an Undergraduate Medicinal Chemistry Course

    Science.gov (United States)

    Rodrigues, Ricardo P.; Andrade, Saulo F.; Mantoani, Susimaire P.; Eifler-Lima, Vera L.; Silva, Vinicius B.; Kawano, Daniel F.

    2015-01-01

    Advances in, and dissemination of, computer technologies in the field of drug research now enable the use of molecular modeling tools to teach important concepts of drug design to chemistry and pharmacy students. A series of computer laboratories is described to introduce undergraduate students to commonly adopted "in silico" drug design…

  3. 77 FR 74195 - Draft Guidance for Industry and Food and Drug Administration Staff; Design Considerations for...

    Science.gov (United States)

    2012-12-13

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-1161] Draft Guidance for Industry and Food and Drug Administration Staff; Design Considerations for Devices Intended for Home Use; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The...

  4. 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.

  5. 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...

  6. Wind diesel systems - design assessment and future potential

    DEFF Research Database (Denmark)

    Infield, D.G.; Scotney, A.; Lundsager, P.

    1992-01-01

    Diesels are the obvious form. of back-up electricity generation in small to medium sized wind systems. High wind penetrations pose significant technical problems for the system designer, ranging from component sizing to control specification and dynamic stability. A key role is seen for proven...... system models for assessing both dynamic characteristics and overall performance and economics. An introduction is provided to the Wind Diesel Engineering Design Toolkit currently under development (for implementation on PC) by a consortium of leading wind diesel experts, representing six European...

  7. Economic Evaluation of the Juvenile Drug Court/Reclaiming Futures (JDC/RF) Model.

    Science.gov (United States)

    McCollister, Kathryn; Baumer, Pamela; Davis, Monica; Greene, Alison; Stevens, Sally; Dennis, Michael

    2018-07-01

    Juvenile drug court (JDC) programs are an increasingly popular option for rehabilitating juvenile offenders with substance problems, but research has found inconsistent evidence regarding their effectiveness and economic impact. While assessing client outcomes such as reduced substance use and delinquency is necessary to gauge program effectiveness, a more comprehensive understanding of program success and sustainability can be attained by examining program costs and economic benefits. As part of the National Cross-Site Evaluation of JDC and Reclaiming Futures (RF), an economic analysis of five JDC/RF programs was conducted from a multisystem and multiagency perspective. The study highlights the direct and indirect costs of JDC/RF and the savings generated from reduced health problems, illegal activity, and missed school days. Results include the average (per participant) cost of JDC/RF, the total economic benefits per JDC/RF participant, and the net savings of JDC/RF relative to standard JDC.

  8. A Guide to Designing Future Ground-based CMB Experiments

    Energy Technology Data Exchange (ETDEWEB)

    Wu, W. L.K. [Stanford Univ., CA (United States); Kavli Inst. for Particle Astrophysics and Cosmology, Menlo, Park, CA (United States); Errard, J. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Univ. of California, Berkeley, CA (United States); Dvorkin, C. [Inst. for Advanced Study, Princeton, NJ (United States); Kuo, C. L. [Stanford Univ., CA (United States); Kavli Inst. for Particle Astrophysics and Cosmology, Menlo, Park, CA (United States); Lee, A. T. [Univ. of California, Berkeley, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); McDonald, P. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Slosar, A. [Brookhaven National Lab. (BNL), Upton, NY (United States); Zahn, O. [Univ. of California, Berkeley and Lawrence Berkeley National Lab. (LBNL), CA (United States)

    2014-02-18

    In this follow-up work to the High Energy Physics Community Summer Study 2013 (HEP CSS 2013, a.k.a. Snowmass), we explore the scientific capabilities of a future Stage-IV Cosmic Microwave Background polarization experiment (CMB-S4) under various assumptions on detector count, resolution, and sky coverage. We use the Fisher matrix technique to calculate the expected uncertainties in cosmological parameters in vΛCDM that are especially relevant to the physics of fundamental interactions, including neutrino masses, effective number of relativistic species, dark-energy equation of state, dark-matter annihilation, and inflationary parameters. To further chart the landscape of future cosmology probes, we include forecasted results from the Baryon Acoustic Oscillation (BAO) signal as measured by DESI to constrain parameters that would benefit from low redshift information. We find the following best 1-σ constraints: σ(Mv ) = 15 meV, σ(Neff ) = 0.0156, Dark energy Figure of Merit = 303, σ(pann) = 0.00588 x 3 x 10-26 cm3/s/GeV, σ( ΩK) = 0.00074, σ(ns) = 0.00110, σ( αs) = 0.00145, and σ(r) = 0.00009. We also detail the dependences of the parameter constraints on detector count, resolution, and sky coverage.

  9. A Guide to Designing Future Ground-based CMB Experiments

    International Nuclear Information System (INIS)

    Wu, W. L.K.; Errard, J.; Dvorkin, C.; Kuo, C. L.; Lee, A. T.; McDonald, P.; Slosar, A.; Zahn, O.

    2014-01-01

    In this follow-up work to the High Energy Physics Community Summer Study 2013 (HEP CSS 2013, a.k.a. Snowmass), we explore the scientific capabilities of a future Stage-IV Cosmic Microwave Background polarization experiment (CMB-S4) under various assumptions on detector count, resolution, and sky coverage. We use the Fisher matrix technique to calculate the expected uncertainties in cosmological parameters in vΛCDM that are especially relevant to the physics of fundamental interactions, including neutrino masses, effective number of relativistic species, dark-energy equation of state, dark-matter annihilation, and inflationary parameters. To further chart the landscape of future cosmology probes, we include forecasted results from the Baryon Acoustic Oscillation (BAO) signal as measured by DESI to constrain parameters that would benefit from low redshift information. We find the following best 1-δ constraints: δ(M_v ) = 15 meV, δ(N_e_f_f ) = 0.0156, Dark energy Figure of Merit = 303, δ(p_a_n_n) = 0.00588 x 3 x 10"-"2"6 cm"3/s/GeV, δ(Ω_K) = 0.00074, δ(n_s) = 0.00110, δ(α_s) = 0.00145, and δ(r) = 0.00009. We also detail the dependences of the parameter constraints on detector count, resolution, and sky coverage.

  10. Hypothesis driven drug design: improving quality and effectiveness of the design-make-test-analyse cycle.

    Science.gov (United States)

    Plowright, Alleyn T; Johnstone, Craig; Kihlberg, Jan; Pettersson, Jonas; Robb, Graeme; Thompson, Richard A

    2012-01-01

    In drug discovery, the central process of constructing and testing hypotheses, carefully conducting experiments and analysing the associated data for new findings and information is known as the design-make-test-analyse cycle. Each step relies heavily on the inputs and outputs of the other three components. In this article we report our efforts to improve and integrate all parts to enable smooth and rapid flow of high quality ideas. Key improvements include enhancing multi-disciplinary input into 'Design', increasing the use of knowledge and reducing cycle times in 'Make', providing parallel sets of relevant data within ten working days in 'Test' and maximising the learning in 'Analyse'. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. Instructional Design for the Future of Undergraduate Journalism Education

    Science.gov (United States)

    Farmer, Christopher J.

    2012-01-01

    In the face of communication changes brought on by technology, journalism curriculum needs restructuring while staying true to its core values. Using an instructional design framework, and a case study, this paper proposes a journalism education based on Esser's spheres of influence. Current practices and principles are discussed. A literature…

  12. Positron computed tomography. Present and future design alternatives

    International Nuclear Information System (INIS)

    Phelps, M.E.; Hoffman, E.J.; Sung-Cheng Huang; Kuhl, D.E.

    1981-01-01

    There are six commercial companies in the United States of America, Canada, Europe and Asia that have or are developing PCT programs. Although positron computed tomography (PCT) system designs are still evolving and all the complex issues of system optimization are still not completely defined, some design concepts have achieved general acceptance. Circumferential designs employing hexagonal, octagonal or circular geometries are preferred since they maximize the tomographic plane efficiency. Bismuth germanate has become the detector of choice because of its high efficiency (intrinsic photopeak and geometric through high packing densities) when the small detectors required for high spatial resolution are used. Caesium fluoride detectors are also being investigated because of their short coincidence time resolution and potential for time of flight measurements. Multiplane systems, consisting of stacked single plane geometries, have been developed to provide higher overall organ efficiency, with some compromise in image quality compared with a single plane system. The most poorly characterized aspect of multiplane systems is the slit and septa shielding design that has a large impact on random and scatter coincidences, count-rate capability, efficiency and uniformity of spatial resolution. Present PCT systems have spatial resolutions in the tomographic plane of about 8 to 17 mm and axial resolution of about 12 to 18 mm. PCT systems that have been or are now being developed are providing the means to demonstrate the unique capability of PCT to provide quantitative measurements of local biochemical and functional processes in man

  13. Designing future technologies for disabled people in a developing country

    CSIR Research Space (South Africa)

    Williams, Q

    2008-05-01

    Full Text Available Both the physical and virtual aspects of our current society are designed for able-bodied people. This means that very often people with disabilities are excluded from participation and faces barriers to living independently. This paper looks at how...

  14. Future Roles of Film Sound Design in VR-applications

    DEFF Research Database (Denmark)

    Nordahl, Rolf

    2005-01-01

    Virtual Environments offers new affordances for multimodal experiences. However, most research has been done on the visual modality and technologies supporting this sense In this paper new approaches to sound design for VE are proposed. Utilizing principles of film sound can prove beneficial in c...

  15. Powering the Future: A Wind Turbine Design Challenge

    Science.gov (United States)

    Pries, Caitlin Hicks; Hughes, Julie

    2011-01-01

    Nothing brings out the best in eighth-grade physical science students quite like an engineering challenge. The wind turbine design challenge described in this article has proved to be a favorite among students with its focus on teamwork and creativity and its (almost) sneaky reinforcement of numerous physics concepts. For this activity, pairs of…

  16. Fragment informatics and computational fragment-based drug design: an overview and update.

    Science.gov (United States)

    Sheng, Chunquan; Zhang, Wannian

    2013-05-01

    Fragment-based drug design (FBDD) is a promising approach for the discovery and optimization of lead compounds. Despite its successes, FBDD also faces some internal limitations and challenges. FBDD requires a high quality of target protein and good solubility of fragments. Biophysical techniques for fragment screening necessitate expensive detection equipment and the strategies for evolving fragment hits to leads remain to be improved. Regardless, FBDD is necessary for investigating larger chemical space and can be applied to challenging biological targets. In this scenario, cheminformatics and computational chemistry can be used as alternative approaches that can significantly improve the efficiency and success rate of lead discovery and optimization. Cheminformatics and computational tools assist FBDD in a very flexible manner. Computational FBDD can be used independently or in parallel with experimental FBDD for efficiently generating and optimizing leads. Computational FBDD can also be integrated into each step of experimental FBDD and help to play a synergistic role by maximizing its performance. This review will provide critical analysis of the complementarity between computational and experimental FBDD and highlight recent advances in new algorithms and successful examples of their applications. In particular, fragment-based cheminformatics tools, high-throughput fragment docking, and fragment-based de novo drug design will provide the focus of this review. We will also discuss the advantages and limitations of different methods and the trends in new developments that should inspire future research. © 2012 Wiley Periodicals, Inc.

  17. Design Pedagogy for an Unknown Future: A View from the Expanding Field of Design Scholarship and Professional Practice

    Science.gov (United States)

    Wilson, Stephanie Elizabeth; Zamberlan, Lisa

    2017-01-01

    This article draws on current research investigating the notion of design for an unknown future. It reflects on recent thinking about the role of creativity in design practice and discusses implications for the development and assessment of creativity in the design studio. It begins with a review of literature on the issues and challenges…

  18. Peripheral Applications of Drug-Coated Balloons: Past, Present and Future

    Energy Technology Data Exchange (ETDEWEB)

    Krokidis, Miltiadis, E-mail: mkrokidis@hotmail.com; Spiliopoulos, Stavros, E-mail: stavspiliop@upatras.gr; Katsanos, Konstantinos, E-mail: katsanos@med.upatras.gr; Sabharwal, Tarun, E-mail: tarun_sabharwal@yahoo.co.uk [Guy' s and St. Thomas' Hospitals, NHS Foundation Trust, Department of Radiology (United Kingdom)

    2013-04-15

    Drug-coated balloon (DCB) technologies represent the latest and hottest development in the field of endovascular treatment of peripheral arterial disease. Initial experience with paclitaxel-coated balloon use in the femoral artery has demonstrated lower mid-term restenosis and superior mid-term clinical outcomes in terms of improved wound healing and reduced repeat angioplasty rates compared with standard balloon angioplasty. Many companies are presently developing and/or improving DCB catheters and therefore ongoing, technical improvements of the already existing platforms, new drugs, and innovative carriers are expected. The ongoing basic research studies and various multicenter randomized, controlled trials that are currently in progress will offer valuable scientific insights regarding the long-term effectiveness and other crucial issues, such as efficacy in various vascular beds, optimal balloon dosage, and post angioplasty antiplatelet therapy. Future applications of these devices also could include in-stent restenosis, anastomotic stenosis of surgical bypass, and benign stenoses of the central venous system. The authors envision that DCB angioplasty will evolve to a major paradigm shift in the endovascular treatment of occlusive vascular diseases.

  19. Peripheral Applications of Drug-Coated Balloons: Past, Present and Future

    International Nuclear Information System (INIS)

    Krokidis, Miltiadis; Spiliopoulos, Stavros; Katsanos, Konstantinos; Sabharwal, Tarun

    2013-01-01

    Drug-coated balloon (DCB) technologies represent the latest and hottest development in the field of endovascular treatment of peripheral arterial disease. Initial experience with paclitaxel-coated balloon use in the femoral artery has demonstrated lower mid-term restenosis and superior mid-term clinical outcomes in terms of improved wound healing and reduced repeat angioplasty rates compared with standard balloon angioplasty. Many companies are presently developing and/or improving DCB catheters and therefore ongoing, technical improvements of the already existing platforms, new drugs, and innovative carriers are expected. The ongoing basic research studies and various multicenter randomized, controlled trials that are currently in progress will offer valuable scientific insights regarding the long-term effectiveness and other crucial issues, such as efficacy in various vascular beds, optimal balloon dosage, and post angioplasty antiplatelet therapy. Future applications of these devices also could include in-stent restenosis, anastomotic stenosis of surgical bypass, and benign stenoses of the central venous system. The authors envision that DCB angioplasty will evolve to a major paradigm shift in the endovascular treatment of occlusive vascular diseases.

  20. Designing a Methodology for Future Air Travel Scenarios

    Science.gov (United States)

    Wuebbles, Donald J.; Baughcum, Steven L.; Gerstle, John H.; Edmonds, Jae; Kinnison, Douglas E.; Krull, Nick; Metwally, Munir; Mortlock, Alan; Prather, Michael J.

    1992-01-01

    -subsonic future fleet. The methodology, procedures, and recommendations for the development of future HSCT and the subsonic fleet scenarios used for this evaluation are discussed.

  1. Identification of novel Mycobacterium tuberculosis dihydrofolate reductase inhibitors through rational drug design

    Directory of Open Access Journals (Sweden)

    Mymoona Akhter

    2016-01-01

    Conclusion: Structure based drug design can be used as an effective tool for the design of new cheiocal entity. Number of novel agents have been identified as antitubercular agents whose mechanism of action needs to be ascertained.

  2. The Reflective Citizen : General Design Education for a Sustainable Future

    OpenAIRE

    Digranes, Ingvild; Fauske, Laila Belinda

    2010-01-01

    With the Norwegian 2006 curriculum, the thoughts of a global responsibility in terms of a wide understanding of sustainability was introduced in general education in Art and Design education from 1st grade through lower secondary school (6-15 years). The focus of individual expression that dominated the subject during the charismatic paradigm of self-expression has in the documents to some extent been replaced by the focus on citizenship and user participation. The introduction, o...

  3. Drug design: structure- and ligand-based approaches

    National Research Council Canada - National Science Library

    Merz, Kenneth M; Ringe, Dagmar; Reynolds, Charles H

    2010-01-01

    ..., computational ADME-Tox, and drug discovery case studies. A variety of authors from academic and commercial institutions all over the world have contributed to this book, which is illustrated with more than 200 images...

  4. Membrane Transporters: Structure, Function and Targets for Drug Design

    Science.gov (United States)

    Ravna, Aina W.; Sager, Georg; Dahl, Svein G.; Sylte, Ingebrigt

    Current therapeutic drugs act on four main types of molecular targets: enzymes, receptors, ion channels and transporters, among which a major part (60-70%) are membrane proteins. This review discusses the molecular structures and potential impact of membrane transporter proteins on new drug discovery. The three-dimensional (3D) molecular structure of a protein contains information about the active site and possible ligand binding, and about evolutionary relationships within the protein family. Transporters have a recognition site for a particular substrate, which may be used as a target for drugs inhibiting the transporter or acting as a false substrate. Three groups of transporters have particular interest as drug targets: the major facilitator superfamily, which includes almost 4000 different proteins transporting sugars, polyols, drugs, neurotransmitters, metabolites, amino acids, peptides, organic and inorganic anions and many other substrates; the ATP-binding cassette superfamily, which plays an important role in multidrug resistance in cancer chemotherapy; and the neurotransmitter:sodium symporter family, which includes the molecular targets for some of the most widely used psychotropic drugs. Recent technical advances have increased the number of known 3D structures of membrane transporters, and demonstrated that they form a divergent group of proteins with large conformational flexibility which facilitates transport of the substrate.

  5. 'Create the future': an environment for excellence in teaching future-oriented Industrial Design Engineering

    NARCIS (Netherlands)

    Eger, Arthur O.; Lutters, Diederick; van Houten, Frederikus J.A.M.

    2004-01-01

    In 2001, the University of Twente started a new course on Industrial Design Engineering. This paper describes the insights that have been employed in developing the curriculum, and in developing the environment in which the educational activities are facilitated. The University of Twente has a broad

  6. Design of a Dissolving Microneedle Platform for Transdermal Delivery of a Fixed-Dose Combination of Cardiovascular Drugs.

    Science.gov (United States)

    Quinn, Helen L; Bonham, Louise; Hughes, Carmel M; Donnelly, Ryan F

    2015-10-01

    Microneedles (MNs) are a minimally invasive drug delivery platform, designed to enhance transdermal drug delivery by breaching the stratum corneum. For the first time, this study describes the simultaneous delivery of a combination of three drugs using a dissolving polymeric MN system. In the present study, aspirin, lisinopril dihydrate, and atorvastatin calcium trihydrate were used as exemplar cardiovascular drugs and formulated into MN arrays using two biocompatible polymers, poly(vinylpyrrollidone) and poly(methylvinylether/maleic acid). Following fabrication, dissolution, mechanical testing, and determination of drug recovery from the MN arrays, in vitro drug delivery studies were undertaken, followed by HPLC analysis. All three drugs were successfully delivered in vitro across neonatal porcine skin, with similar permeation profiles achieved from both polymer formulations. An average of 126.3 ± 18.1 μg of atorvastatin calcium trihydrate was delivered, notably lower than the 687.9 ± 101.3 μg of lisinopril and 3924 ± 1011 μg of aspirin, because of the hydrophobic nature of the atorvastatin molecule and hence poor dissolution from the array. Polymer deposition into the skin may be an issue with repeat application of such a MN array, hence future work will consider more appropriate MN systems for continuous use, alongside tailoring delivery to less hydrophilic compounds. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  7. Design of Novel Ophthalmic Formulation Containing Drug Nanoparticles and Its Usefulness as Anti-glaucoma Drugs.

    Science.gov (United States)

    Nagai, Noriaki

    2016-01-01

    The ophthalmic application of drugs is the primary route of administration for the therapy of glaucoma; however, in traditional formulations, only small amounts of the administered drug penetrate the cornea to reach the desired intraocular tissue due to corneal barriers. Recently, nanoparticulate drug delivery is expected as a technology to overcome the difficulties in delivering drugs across biological barriers (improvement of bioavailability). In this study, we attempted to establish a new method for preparing solid drug nanoparticles by using a bead mill and various additives, and succeeded in preparing a high quality dispersion containing drug nanoparticles. For a more concrete example, a mean particle size of disulfiram (DSF) treated with bead mill is 183 nm. The corneal penetration and corneal residence time of DSF from the ophthalmic dispersion containing DSF nanoparticles were significantly higher than those from a 2-hydroxypropyl-β-cyclodextrin solution containing DSF (DSF solution). It is known that the administration of DSF has intraocular pressure (IOP)-reducing effects. The IOP-reducing effects of the ophthalmic dispersion containing DSF nanoparticles were significantly greater than those of the DSF solution in rabbits (the IOP was enhanced by placing the rabbits in a dark room for 5 h). In addition, the ophthalmic dispersion containing DSF nanoparticles is better tolerated by corneal epithelial cells than DSF solution. It is possible that dispersions containing DSF nanoparticles provide new possibilities for effectively treating glaucoma, and that ocular drug delivery systems using drug nanoparticles may expand their usage for therapy in the ophthalmologic field.

  8. Prediction of Human Drug Targets and Their Interactions Using Machine Learning Methods: Current and Future Perspectives.

    Science.gov (United States)

    Nath, Abhigyan; Kumari, Priyanka; Chaube, Radha

    2018-01-01

    Identification of drug targets and drug target interactions are important steps in the drug-discovery pipeline. Successful computational prediction methods can reduce the cost and time demanded by the experimental methods. Knowledge of putative drug targets and their interactions can be very useful for drug repurposing. Supervised machine learning methods have been very useful in drug target prediction and in prediction of drug target interactions. Here, we describe the details for developing prediction models using supervised learning techniques for human drug target prediction and their interactions.

  9. 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

  10. 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…

  11. Co-creation, Prevailing Streams and a Future Design Trajectory

    DEFF Research Database (Denmark)

    Degnegaard, Rex

    2014-01-01

    of the literature on co-creation to explore what the existing literature relates to and indeed to pinpoint if any patterns or streams can be identified. The paper illustrates how the use of the concept of co-creation suggests a necessity for focusing further on specific co-creation-related issues and challenges...... of significance to business and society. The paper highlights new co-creation-related issues and challenges. Further, the paper crystallises an emerging design trajectory in theory and practice....

  12. Designing the Climate Observing System of the Future

    Science.gov (United States)

    Weatherhead, Elizabeth C.; Wielicki, Bruce A.; Ramaswamy, V.; Abbott, Mark; Ackerman, Thomas P.; Atlas, Robert; Brasseur, Guy; Bruhwiler, Lori; Busalacchi, Antonio J.; Butler, James H.; Clack, Christopher T. M.; Cooke, Roger; Cucurull, Lidia; Davis, Sean M.; English, Jason M.; Fahey, David W.; Fine, Steven S.; Lazo, Jeffrey K.; Liang, Shunlin; Loeb, Norman G.; Rignot, Eric; Soden, Brian; Stanitski, Diane; Stephens, Graeme; Tapley, Byron D.; Thompson, Anne M.; Trenberth, Kevin E.; Wuebbles, Donald

    2018-01-01

    Climate observations are needed to address a large range of important societal issues including sea level rise, droughts, floods, extreme heat events, food security, and freshwater availability in the coming decades. Past, targeted investments in specific climate questions have resulted in tremendous improvements in issues important to human health, security, and infrastructure. However, the current climate observing system was not planned in a comprehensive, focused manner required to adequately address the full range of climate needs. A potential approach to planning the observing system of the future is presented in this article. First, this article proposes that priority be given to the most critical needs as identified within the World Climate Research Program as Grand Challenges. These currently include seven important topics: melting ice and global consequences; clouds, circulation and climate sensitivity; carbon feedbacks in the climate system; understanding and predicting weather and climate extremes; water for the food baskets of the world; regional sea-level change and coastal impacts; and near-term climate prediction. For each Grand Challenge, observations are needed for long-term monitoring, process studies and forecasting capabilities. Second, objective evaluations of proposed observing systems, including satellites, ground-based and in situ observations as well as potentially new, unidentified observational approaches, can quantify the ability to address these climate priorities. And third, investments in effective climate observations will be economically important as they will offer a magnified return on investment that justifies a far greater development of observations to serve society's needs.

  13. Carbon offset potentials and design: Anticipating future public policy

    International Nuclear Information System (INIS)

    Trexler, M.C.; Kosloff, L.H.; Gowen, M.

    1994-01-01

    Carbon offsets offer CO 2 emitters the opportunity to compensate for some proportion of their CO 2 emissions through the pursuit of emissions reduction or carbon sequestration projects beyond their own operational boundaries. The flexibility to pursue carbon offsets ''off-site'' can dramatically reduce the costs of achieving a given net emissions reduction. The future role of carbon offsets, however, continues to be a topic of considerable debate. Several processes are currently under way nationally and internationally that will help shape this role. This paper discusses how alternative policy outcomes could encourage or restrict the viability of carbon offsets as a component of corporate climate change mitigation portfolios and proposes criteria by which projects should be evaluated prior to the finalization of national or international policy frameworks. Based on these outcomes, the potential for offsets could be very large or very modest. It is vital that policy development in the offset arena account for the still voluntary nature of mitigation efforts and that the objective of climate change mitigation not be forgotten in the push for offset rules and regulations. At the same time, carbon offsets are far from a panacea for climate change mitigation and should be evaluated in the context of a larger global mitigation portfolio

  14. Towards a lumped reaction model for future designer fuels

    Energy Technology Data Exchange (ETDEWEB)

    Vandersickel, A.; Wright, Y.M.; Boulouchos, K. [ETH Zurich, Aerothermochemistry and Combustion Systems Laboratory, Zurich (Switzerland). Inst. of Energy Technology

    2009-07-01

    The homogeneous charge compression ignition (HCCI) is one of the most promising engine processes to simultaneously reduce nitrogen oxide and soot emissions. However, its applicability is hindered by its relatively limited operating range. Designer fuels offer unique possibilities for tailoring evaporation and auto-ignition properties, offering a means to control and expand the HCCI operation range. The identification of HCCI relevant fuel properties as well as the definition of a new fuel index able to describe a fuels suitability for HCCI was required in order to develop such designer fuels. This paper discussed a numerical and experimental investigation of a large set of technical fuels covering a wide range of properties. The paper discussed mechanism development approaches, optimization of the lumped mechanism, and and results. Zheng's 7-step reaction mechanism was successfully coupled with a genetic optimization algorithm and fitted to n-heptane ignition delay data. It was concluded that the presented coupled approach could improve the predictive quality of the model and demonstrate that the Zheng model was sufficiently elaborate to emulate the influence of temperature, pressure, exhaust gas recirculation and lambda on ignition. 8 refs., 1 tab., 3 figs.

  15. Towards a lumped reaction model for future designer fuels

    International Nuclear Information System (INIS)

    Vandersickel, A.; Wright, Y.M.; Boulouchos, K.

    2009-01-01

    The homogeneous charge compression ignition (HCCI) is one of the most promising engine processes to simultaneously reduce nitrogen oxide and soot emissions. However, its applicability is hindered by its relatively limited operating range. Designer fuels offer unique possibilities for tailoring evaporation and auto-ignition properties, offering a means to control and expand the HCCI operation range. The identification of HCCI relevant fuel properties as well as the definition of a new fuel index able to describe a fuels suitability for HCCI was required in order to develop such designer fuels. This paper discussed a numerical and experimental investigation of a large set of technical fuels covering a wide range of properties. The paper discussed mechanism development approaches, optimization of the lumped mechanism, and and results. Zheng's 7-step reaction mechanism was successfully coupled with a genetic optimization algorithm and fitted to n-heptane ignition delay data. It was concluded that the presented coupled approach could improve the predictive quality of the model and demonstrate that the Zheng model was sufficiently elaborate to emulate the influence of temperature, pressure, exhaust gas recirculation and lambda on ignition. 8 refs., 1 tab., 3 figs.

  16. Future control room design (modernization of control room systems)

    International Nuclear Information System (INIS)

    Reischl, Ludwig; Freitag, Timo; Dergel, Rene

    2009-01-01

    In the frame of lifetime extension for nuclear power plants the modernization of the complete safety and operational control technology will be digitalized. It is also recommended to modernize the operator facilities, monitoring systems in the control room, the back-up shut-down center and the local control stations. The authors summarize the reasons for the modernization recommendations and discuss possible solutions for display-oriented control rooms. A concept for control room backfitting includes generic requirements, requirements of the local authorities, ergonomic principles information content and information density, and the design process. The backfitting strategy should include a cooperation with the operational personnel, The quality assurance and training via simulator needs sufficient timing during the implementation of the backfitting.

  17. Sustainable winter cities: Future directions for planning, policy and design

    Science.gov (United States)

    Pressman, Norman E. P.

    Attempts to generate a "climate-responsive" northern urban form are part of a relatively recent phenomenon and field of investigation. In conjunction with the international "winter cities" movement, the need has been established for explicit, systematic inquiry directed toward national and local action to improve the comfort and lifestyles of all northern inhabitants. It is important to recognize that winter-induced discomforts exist and that they must be acknowledged in planning theory and practice. For northern cities to function more satisfactorily, the negative impacts of winter must be reduced while its beneficial characteristics are enhanced. While not all summer activities can or should be abandoned during winter, proper micro-climatic control is essential if human life is to be retained outside. The outdoor season should be extended since so much indoor isolation occurs. The main principles to be incorporated in exemplary "winter city" design should be contact with nature, year-round usability, user participation, cultural continuity, and the creation of comfortable micro-climatic conditions throughout much of the city's open spaces. All valuable sources of inspiration must be harnessed in the attempt to mediate between organic regionalism and internationalism, on the one hand, and romanticism and pragmatic realism, on the other. Creating optimum conditions for human well-being, habitation, work and intellectual development in each of the four seasons is vital under harsh environments. Adopting a climate-sensitive approach to planning policy and urban design can render everyday life less stressful, especially during the lengthy winter periods found in many northern latitude and high altitude settings.

  18. Developmental framework to validate future designs of ballistic neck protection.

    Science.gov (United States)

    Breeze, J; Midwinter, M J; Pope, D; Porter, K; Hepper, A E; Clasper, J

    2013-01-01

    The number of neck injuries has increased during the war in Afghanistan, and they have become an appreciable source of mortality and long-term morbidity for UK servicemen. A three-dimensional numerical model of the neck is necessary to allow simulation of penetrating injury from explosive fragments so that the design of body armour can be optimal, and a framework is required to validate and describe the individual components of this program. An interdisciplinary consensus group consisting of military maxillofacial surgeons, and biomedical, physical, and material scientists was convened to generate the components of the framework, and as a result it incorporates the following components: analysis of deaths and long-term morbidity, assessment of critical cervical structures for incorporation into the model, characterisation of explosive fragments, evaluation of the material of which the body armour is made, and mapping of the entry sites of fragments. The resulting numerical model will simulate the wound tract produced by fragments of differing masses and velocities, and illustrate the effects of temporary cavities on cervical neurovascular structures. Using this framework, a new shirt to be worn under body armour that incorporates ballistic cervical protection has been developed for use in Afghanistan. New designs of the collar validated by human factors and assessment of coverage are currently being incorporated into early versions of the numerical model. The aim of this paper is to describe this developmental framework and provide an update on the current progress of its individual components. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

  19. Quantitative modeling of selective lysosomal targeting for drug design

    DEFF Research Database (Denmark)

    Trapp, Stefan; Rosania, G.; Horobin, R.W.

    2008-01-01

    log K ow. These findings were validated with experimental results and by a comparison to the properties of antimalarial drugs in clinical use. For ten active compounds, nine were predicted to accumulate to a greater extent in lysosomes than in other organelles, six of these were in the optimum range...... predicted by the model and three were close. Five of the antimalarial drugs were lipophilic weak dibasic compounds. The predicted optimum properties for a selective accumulation of weak bivalent bases in lysosomes are consistent with experimental values and are more accurate than any prior calculation...

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

    Directory of Open Access Journals (Sweden)

    Lucianna Helene Santos

    2015-11-01

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

  1. Embodiment and enculturation: the future of architectural design.

    Science.gov (United States)

    Mallgrave, Harry F

    2015-01-01

    A half-century ago the Dutch architect Aldo van Eyck encouraged designers to think about "space and time" not as abstractions in themselves but rather as cultural events better approached through the medium of "place and occasion." Van Eyck made this point on the basis of his own travels and through his extensive readings in cultural anthropology, and his prescience is only now acquiring the credibility that it deserves through the work of a multitude of interdisciplinary researchers. Phenomenologists argue that we are embodied organisms-acting-within-environments, and these inhabiting abodes are constructed of both material and cultural dimensions. We are thus preeminently social in our range of self-consciousness, and intensely ceremonial in every facet of our being. Evolutionary psychologists and anthropologists are currently locating the origin and development of our most basic social behaviors far in our pre-human past; neuroscientists are today modeling our social circuits in the deepest reaches of our brains. Architecture would gain much from an updated cultural theory grounded in these new models of human existence.

  2. Service design as an approach to new service development : reflections and futures studies

    OpenAIRE

    Yu, Eun; Sangiorgi, Daniela

    2014-01-01

    This paper illustrates how, although Service Design has been described as evolving from a narrow description of a phase in New Service Development (NSD) to an approach to Service Innovation, the current Service Design research is still focused on the initial stages of NSD. Comparing existing Service Design research with foundational knowledge on NSD, the authors have proposed two complementary directions for future Service Design studies: 1) the expansion of ‘service design as a phase’ to inv...

  3. Targeting the dopamine D3 receptor: an overview of drug design strategies.

    Science.gov (United States)

    Cortés, Antoni; Moreno, Estefanía; Rodríguez-Ruiz, Mar; Canela, Enric I; Casadó, Vicent

    2016-07-01

    Dopamine is a neurotransmitter widely distributed in both the periphery and the central nervous system (CNS). Its physiological effects are mediated by five closely related G protein-coupled receptors (GPCRs) that are divided into two major subclasses: the D1-like (D1, D5) and the D2-like (D2, D3, D4) receptors. D3 receptors (D3Rs) have the highest density in the limbic areas of the brain, which are associated with cognitive and emotional functions. These receptors are therefore attractive targets for therapeutic management. This review summarizes the functional and pharmacological characteristics of D3Rs, including the design and clinical relevance of full agonists, partial agonists and antagonists, as well as the capacity of these receptors to form active homodimers, heterodimers or higher order receptor complexes as pharmacological targets in several neurological and neurodegenerative disorders. The high sequence homology between D3R and the D2-type challenges the development of D3R-selective compounds. The design of new D3R-preferential ligands with improved physicochemical properties should provide a better pharmacokinetic/bioavailability profile and lesser toxicity than is found with existing D3R ligands. It is also essential to optimize D3R affinity and, especially, D3R vs. D2-type binding and functional selectivity ratios. Developing allosteric and bitopic ligands should help to improve the D3R selectivity of these drugs. As most evidence points to the ability of GPCRs to form homomers and heteromers, the most promising therapeutic strategy in the future is likely to involve the application of heteromer-selective drugs. These selective ligands would display different affinities for a given receptor depending on the receptor partners within the heteromer. Therefore, designing novel compounds that specifically target and modulate D1R-D3R heteromers would be an interesting approach for the treatment of levodopa (L-DOPA)-induced dyskinesias.

  4. Design, testing and modifications of the Pelletron accelerator and future uses

    International Nuclear Information System (INIS)

    Lopez V, H.; Valdovinos A, M.; Hernandez M, V.; Alba P, U.; Garcia R, R.; Rodriguez, R.; Alba P, R.; Ruiz M, J.

    1989-01-01

    Solutions to various problems in the design of high voltage generator and acceleration units of the Pelletron electron accelerator designed and constructed at ININ are presented. Information on the design of the control system of the electron beams, activities proposed for utilization of sulfur hexafluoride as an accelerator isolating gas as well as some future uses of the Pelletron. (Author). 7 refs, 3 figs

  5. Current therapeutic molecules and targets in neurodegenerative diseases based on in silico drug design.

    Science.gov (United States)

    Sehgal, Sheikh Arslan; Hammad, Mirza A; Tahir, Rana Adnan; Akram, Hafiza Nisha; Ahmad, Faheem

    2018-03-15

    As the number of elderly persons increases, neurodegenerative diseases are becoming ubiquitous. There is currently a great need for knowledge concerning management of old-age neurodegenerative diseases; the most important of which are: Alzheimer's disease, Parkinson's disease, Amyotrophic Lateral Sclerosis, and Huntington's disease. To summarize the potential of computationally predicted molecules and targets against neurodegenerative diseases. Review of literature published since 1997 against neurodegenerative diseases, utilizing as keywords: in silico, Alzheimer's disease, Parkinson's disease, Amyotrophic Lateral Sclerosis ALS, and Huntington's disease. Due to the costs associated with experimentation and current ethical law, performing experiments directly on living organisms has become much more difficult. In this scenario, in silico techniques have been successful and have become powerful tools in the search to cure disease. Researchers use the Computer Aided Drug Design pipeline which: 1) generates 3-dimensional structures of target proteins through homology modeling 2) achieves stabilization through molecular dynamics simulation, and 3) exploits molecular docking through large compound libraries. Next generation sequencing is continually producing enormous amounts of raw sequence data while neuroimaging is producing a multitude of raw image data. To solve such pressing problems, these new tools and algorithms are required. This review elaborates precise in silico tools and techniques for drug targets, active molecules, and molecular docking studies, together with future prospects and challenges concerning possible breakthroughs in Alzheimer's, Parkinson's, Amyotrophic Lateral Sclerosis, and Huntington's disease. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  6. Computational drug designing of fungal pigments as potential aromatase inhibitors

    Directory of Open Access Journals (Sweden)

    Nighat Fatima

    2014-12-01

    Full Text Available The existing aromatase inhibitors produced unwelcome effects impose the discovery of novel drugs with privileged selectivity, a reduced amount of toxicity and humanizing potency. In this study, we illuminate the binding mode of polyketide azaphilanoid pigments monascin, ankaflavin, monascorubrin and monascorubramine isolated from Monascus fungus to the aromatase by molecular docking. The 3-dimensional structure of aromatase enzyme (PDB: 4KQ8 was obtained from the Protein Data Bank. PatchDock docking software was used to analyze structural complexes of the aromatase with monascus pigments. Comparatively, the AutoGrid model presented the most briskly constructive binding mode of monascin to aromatase. Docked energies in kcal/mol are: monascin;-13.2; monascorubramine:-12.8, monascorubrin:-12.3; ankaflavin: -10.5. These outcomes exposed these ligands could be potential drugs to treat hormone dependent breast cancer.

  7. Design of Drug Delivery Systems Containing Artemisinin and Its Derivatives

    Directory of Open Access Journals (Sweden)

    Blessing Atim Aderibigbe

    2017-02-01

    Full Text Available Artemisinin and its derivatives have been reported to be experimentally effective for the treatment of highly aggressive cancers without developing drug resistance, they are useful for the treatment of malaria, other protozoal infections and they exhibit antiviral activity. However, they are limited pharmacologically by their poor bioavailability, short half-life in vivo, poor water solubility and long term usage results in toxicity. They are also expensive for the treatment of malaria when compared to other antimalarials. In order to enhance their therapeutic efficacy, they are incorporated onto different drug delivery systems, thus yielding improved biological outcomes. This review article is focused on the currently synthesized derivatives of artemisinin and different delivery systems used for the incorporation of artemisinin and its derivatives.

  8. Design of vision concepts to explore the future : Nature, context and design techniques

    NARCIS (Netherlands)

    Mejia Sarmiento, J.R.; Simonse, W.L.

    2015-01-01

    Industrial firms are facing a constant dilemma, to be ready for the future, have a vision, and at the same time act within the current situation, exploit current products efficiently. This research examines visions that embody future opportunities and ideas, “vision concepts” such as concept cars

  9. Fragment-based drug discovery using rational design.

    Science.gov (United States)

    Jhoti, H

    2007-01-01

    Fragment-based drug discovery (FBDD) is established as an alternative approach to high-throughput screening for generating novel small molecule drug candidates. In FBDD, relatively small libraries of low molecular weight compounds (or fragments) are screened using sensitive biophysical techniques to detect their binding to the target protein. A lower absolute affinity of binding is expected from fragments, compared to much higher molecular weight hits detected by high-throughput screening, due to their reduced size and complexity. Through the use of iterative cycles of medicinal chemistry, ideally guided by three-dimensional structural data, it is often then relatively straightforward to optimize these weak binding fragment hits into potent and selective lead compounds. As with most other lead discovery methods there are two key components of FBDD; the detection technology and the compound library. In this review I outline the two main approaches used for detecting the binding of low affinity fragments and also some of the key principles that are used to generate a fragment library. In addition, I describe an example of how FBDD has led to the generation of a drug candidate that is now being tested in clinical trials for the treatment of cancer.

  10. Liposheres as a Novel Carrier for Lipid Based Drug Delivery: Current and Future Directions.

    Science.gov (United States)

    Swain, Suryakanta; Beg, Sarwar; Babu, Sitty M

    2016-01-01

    Researchers are facing challenges to develop robust formulation and to enhance the bioavailability of poorly water-soluble drugs towards clinical applications. The development of new drug molecule alone is not adequate to assure ample pharmacotherapy of various diseases. Considerable results obtained from in vitro studies are not supported by in vivo data due to inadequate plasma drug concentrations. This may occur due to limited drug solubility and absorption. To resolve these problems, development of new drug delivery systems will be a promising approach. One of the promising pharmaceutical strategies is the use of lipospheres drug delivery system to deliver the poorly water-soluble drugs. Therefore, the present review described the methodology for manufacturing of lipospheres and factors influencing the formulation to deliver the drugs to the targeted site. Apart from that, this review also enlisted briefly the various applications of liposphers in medical and biomedical fields and critically discussed the recent patent system.

  11. submitter Can you afford to wait? Designing the collider of the future

    CERN Document Server

    Benedikt, Michael

    2017-01-01

    Designing a future circular collider is a next step in humanity’s quest to explain the world. This effort is not only about striving for a profound understanding of nature, but also about creating an exciting perspective for future generations.

  12. Future Technology Workshop: A Collaborative Method for the Design of New Learning Technologies and Activities

    Science.gov (United States)

    Vavoula, Giasemi N.; Sharples, Mike

    2007-01-01

    We describe the future technology workshop (FTW), a method whereby people with everyday knowledge or experience in a specific area of technology use (such as using digital cameras) envision and design the interactions between current and future technology and activity. Through a series of structured workshop sessions, participants collaborate to…

  13. Teens in Action. Creating a Drug-Free Future for America's Youth.

    Science.gov (United States)

    Adams, Tom; Resnik, Hank

    This book on drug abuse prevention is addressed to teenagers and covers five main areas where drug use can be prevented: schools, communities, media, the social scene, and the family. The first chapter on school programs briefly discusses peer-led alcohol and drug education, peer counseling, creating a positive school climate, and developing…

  14. 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.

  15. French Health Technology Assessment of Antineoplastic Drugs Indicated in the Treatment of Solid Tumours: Perspective for Future Trends.

    Science.gov (United States)

    Chouaid, Christos; Borget, Isabelle; Braun, Eric; Bazil, Marie-Laure; Schaetz, Dominique; Rémuzat, Cécile; Toumi, Mondher

    2016-08-01

    France is one of the European countries that spend the most on oncology drugs. To keep pharmaceutical expenditure under control, Health Authorities highly scrutinize market access of costly medicines. To assess current and future trends in French health technology assessment (HTA) of antineoplastic drugs indicated in the treatment of solid tumours. A review of the SMR and ASMR drivers of the Transparency Committee (CT) opinions issued for antineoplastic drugs indicated in the treatment of solid tumours and approved between 2009 and 2014 was performed to assess current trends in French health technology assessment (HTA), complemented by an expert board consultation to capture the critical issues on the future of antineoplastic drugs HTA. Thirty-one drugs indicated for the treatment of solid tumours were identified (77 % targeted therapies). Initial CT assessments were available for 26 drugs. Four key items in the CT assessment were identified: 1) Clinical trial methodology; 2) Acceptance of progression-free survival (PFS) as a valuable endpoint; 3) Transferability of clinical trials in clinical practice; 4) Unpredictability of CT decisions. Experts raised the important development of personalised medicines in oncology and key challenges for oncology products to generate information expected from HTA perspective. The French system remains committed to its values and philosophy (access of all innovations for everybody) which are threatened by the increasing launch of innovative therapies and budget constraint. Both HTA decision framework evolution and revision of the current pricing process should be considered in France to cope with these new challenges.

  16. Application of in situ polymerization for design and development of oral drug delivery systems.

    Science.gov (United States)

    Ngwuluka, Ndidi

    2010-12-01

    Although preformed polymers are commercially available for use in the design and development of drug delivery systems, in situ polymerization has also been employed. In situ polymerization affords the platform to tailor and optimize the drug delivery properties of polymers. This review brings to light the benefits of in situ polymerization for oral drug delivery and the possibilities it provides to overcome the challenges of oral route of administration.

  17. Application of In Situ Polymerization for Design and Development of Oral Drug Delivery Systems

    OpenAIRE

    Ngwuluka, Ndidi

    2010-01-01

    Although preformed polymers are commercially available for use in the design and development of drug delivery systems, in situ polymerization has also been employed. In situ polymerization affords the platform to tailor and optimize the drug delivery properties of polymers. This review brings to light the benefits of in situ polymerization for oral drug delivery and the possibilities it provides to overcome the challenges of oral route of administration.

  18. TRPV1: A Target for Rational Drug Design

    Directory of Open Access Journals (Sweden)

    Vincenzo Carnevale

    2016-08-01

    Full Text Available Transient Receptor Potential Vanilloid 1 (TRPV1 is a non-selective, Ca2+ permeable cation channel activated by noxious heat, and chemical ligands, such as capsaicin and resiniferatoxin (RTX. Many compounds have been developed that either activate or inhibit TRPV1, but none of them are in routine clinical practice. This review will discuss the rationale for antagonists and agonists of TRPV1 for pain relief and other conditions, and strategies to develop new, better drugs to target this ion channel, using the newly available high-resolution structures.

  19. Designing clinical trials to assess antiepileptic drugs as monotherapy : difficulties and solutions.

    Science.gov (United States)

    Perucca, Emilio

    2008-01-01

    Designing monotherapy trials in epilepsy is fraught with many hurdles, including diagnostic and classification difficulties, sparse information regarding the natural history of the disorder, and ethical objections to the use of placebo or a suboptimal comparator in a condition where the consequences of therapeutic failure can be serious. These issues are further complicated by regulatory differences between the US and the EU.In the US, the FDA considers that evidence of efficacy requires demonstration of superiority to a comparator. Because available antiepileptic drugs possess relatively high efficacy, in most settings it is unrealistic to expect that a new treatment will be superior to a standard treatment used at optimized dosages. To circumvent this problem, trial designs have been developed whereby patients in the control group are assigned to receive a suboptimal comparator and are required to exit from the trial if seizure deterioration occurs. This allows demonstration of a between-group difference in efficacy endpoints, such as time to exit or time to first seizure. Although these trials have come under increasing criticism because of ethical concerns, extensive information is now available on the outcome of patients with chronic epilepsy randomized to suboptimal treatment in similarly designed conversion to monotherapy trials. This has allowed the construction of a dataset of historical controls against which response to a fully active treatment can be compared. A number of studies using this novel approach are now in progress.In the EU, in addition to requiring data on conversion to monotherapy in refractory patients, the European Medicines Agency stipulates that a monotherapy indication in newly diagnosed epilepsy can only be granted if a candidate drug has shown at least a similar benefit/risk balance compared with an acknowledged standard at its optimal use during an assessment period of no less than 1 year. This has led to the implementation of

  20. 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...

  1. In silico ADME in drug design – enhancing the impact

    Directory of Open Access Journals (Sweden)

    Susanne Winiwarter

    2018-03-01

    Full Text Available Each year the pharmaceutical industry makes thousands of compounds, many of which do not meet the desired efficacy or pharmacokinetic properties, describing the absorption, distribution, metabolism and excretion (ADME behavior. Parameters such as lipophilicity, solubility and metabolic stability can be measured in high throughput in vitro assays. However, a compound needs to be synthesized in order to be tested. In silico models for these endpoints exist, although with varying quality. Such models can be used before synthesis and, together with a potency estimation, influence the decision to make a compound. In practice, it appears that often only one or two predicted properties are considered prior to synthesis, usually including a prediction of lipophilicity. While it is important to use all information when deciding which compound to make, it is somewhat challenging to combine multiple predictions unambiguously. This work investigates the possibility of combining in silico ADME predictions to define the minimum required potency for a specified human dose with sufficient confidence. Using a set of drug discovery compounds,in silico predictions were utilized to compare the relative ranking based on minimum potency calculation with the outcomes from the selection of lead compounds. The approach was also tested on a set of marketed drugs and the influence of the input parameters investigated.

  2. Some thoughts on the future of probabilistic structural design of nuclear components

    International Nuclear Information System (INIS)

    Stancampiano, P.A.

    1978-01-01

    This paper presents some views on the future role of probabilistic methods in the structural design of nuclear components. The existing deterministic design approach is discussed and compared to the probabilistic approach. Some of the objections to both deterministic and probabilistic design are listed. Extensive research and development activities are required to mature the probabilistic approach suficiently to make it cost-effective and competitive with current deterministic design practices. The required research activities deal with probabilistic methods development, more realistic casual failure mode models development, and statistical data models development. A quasi-probabilistic structural design approach is recommended which accounts for the random error in the design models. (Auth.)

  3. Marijuana-based Drugs: Innovative Therapeutics or Designer Drugs of Abuse?

    OpenAIRE

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

    2011-01-01

    Marijuana has been used recreationally and medicinally for centuries. The principle psychoactive component, Δ9-tetrahydrocannabinol (Δ9-THC), activates CB1 cannabinoid receptors (CB1Rs). CB1R agonists and antagonists could potentially treat a wide variety of diseases; unfortunately, therapeutic doses produce unacceptable psychiatric effects. “K2” or “Spice” (K2/Spice), an emerging drug of abuse, exhibits psychotropic actions via CB1R activation. Because of structural dissimilarity to Δ9-THC, ...

  4. Design of a modular digital computer system, DRL 4. [for meeting future requirements of spaceborne computers

    Science.gov (United States)

    1972-01-01

    The design is reported of an advanced modular computer system designated the Automatically Reconfigurable Modular Multiprocessor System, which anticipates requirements for higher computing capacity and reliability for future spaceborne computers. Subjects discussed include: an overview of the architecture, mission analysis, synchronous and nonsynchronous scheduling control, reliability, and data transmission.

  5. Design Innovations and Implementation Challenges - A Case of Smart Textiles in Future Hospital Interiors

    DEFF Research Database (Denmark)

    Mogensen, Jeppe; Jørgensen, Poul-Erik; Poulsen, Søren Bolvig

    2014-01-01

    Concerned with the overall challenges of implementing design innovations, this paper relates to the specific case of applying smart textiles in future hospital interiors. The methodological approach is inspired by design thinking and implementation processes, and through the scope of a developed ...

  6. Hard X-ray/soft gamma-ray telescope designs for future astrophysics missions

    DEFF Research Database (Denmark)

    Ferreira, Desiree Della Monica; Christensen, Finn Erland; Pivovaroff, Michael J.

    2013-01-01

    We present several concept designs of hard X-ray/soft λ-ray focusing telescopes for future astrophysics missions. The designs are based on depth graded multilayer coatings. These have been successfully employed on the NuSTAR mission for energies up to 80 keV. Recent advances in demonstrating...

  7. 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.

  8. Attributions, future time perspective and career maturity in nursing undergraduates: correlational study design.

    Science.gov (United States)

    Cheng, Cheng; Yang, Liu; Chen, Yuxia; Zou, Huijing; Su, Yonggang; Fan, Xiuzhen

    2016-01-25

    Career maturity is an important parameter as nursing undergraduates prepare for their future careers. However, little is known regarding the relationships between attributions, future time perspective and career maturity among nursing undergraduates. The purpose of this study was to investigate the degree of career maturity and its relationship with attributions and future time perspective. A cross-sectional survey was designed. This survey was administered to 431 Chinese nursing undergraduates. Independent-sample t-tests and one-way ANOVA were performed to examine the mean differences between categories of binary and categorical demographic characteristics, respectively. Pearson correlations and multiple linear regressions were used to test the relationships between attributions, future time perspective and career maturity. The degree of career maturity was moderate among nursing undergraduates and that internal attributions of academic achievement, future efficacy and future purpose consciousness were positively associated with career maturity (all p time perspective and to facilitate their transition from school to clinical practice.

  9. Current status and future prospects for enabling chemistry technology in the drug discovery process

    Science.gov (United States)

    Djuric, Stevan W.; Hutchins, Charles W.; Talaty, Nari N.

    2016-01-01

    This review covers recent advances in the implementation of enabling chemistry technologies into the drug discovery process. Areas covered include parallel synthesis chemistry, high-throughput experimentation, automated synthesis and purification methods, flow chemistry methodology including photochemistry, electrochemistry, and the handling of “dangerous” reagents. Also featured are advances in the “computer-assisted drug design” area and the expanding application of novel mass spectrometry-based techniques to a wide range of drug discovery activities. PMID:27781094

  10. Introducing rapid diagnostic tests for malaria into drug shops in Uganda: design and implementation of a cluster randomized trial.

    Science.gov (United States)

    Mbonye, Anthony K; Magnussen, Pascal; Chandler, Clare I R; Hansen, Kristian S; Lal, Sham; Cundill, Bonnie; Lynch, Caroline A; Clarke, Siân E

    2014-07-29

    An intervention was designed to introduce rapid diagnostics tests for malaria (mRDTs) into registered drug shops in Uganda to encourage rational and appropriate treatment of malaria with artemisinin-based combination therapy (ACT). We conducted participatory training of drug shop vendors and implemented supporting interventions to orientate local communities (patients) and the public sector (health facility staff and district officials) to the behavioral changes in diagnosis, treatment and referral being introduced in drug shops. The intervention was designed to be evaluated through a cluster randomized trial. In this paper, we present detailed design, implementation and evaluation experiences in order to help inform future studies of a complex nature. Three preparatory studies (formative, baseline and willingness-to-pay) were conducted to explore perceptions on diagnosis and treatment of malaria at drug shops, and affordable prices for mRDTs and ACTs in order to inform the design of the intervention and implementation modalities. The intervention required careful design with the intention to be acceptable, sustainable and effective. Critical components of intervention were: community sensitization and creating awareness, training of drug shop vendors to diagnose malaria with mRDTs, treat and refer customers to formal health facilities, giving pre-referral rectal artesunate and improved record-keeping. The primary outcome was the proportion of patients receiving appropriately-targeted treatment with ACT, evaluated against microscopy on a research blood slide. Introducing mRDTs in drug shops may seem simple, but our experience of intervention design, conduct and evaluation showed this to be a complex process requiring multiple interventions and evaluation components drawing from a combination of epidemiological, social science and health economics methodologies. The trial was conducted in phases sequenced such that each benefited from the other. The main challenges

  11. The next generation of CANDU: reactor design to meet future energy markets

    International Nuclear Information System (INIS)

    Hopwood, J.M.; Love, J.W.; Wren, D.J.

    2001-01-01

    Nuclear power plant designs for the future must respond to increasingly demanding market requirements. This means that value can be gained from substantial product development directed at these requirements. For the CANDU system, AECL has adopted the revolutionary approach, accommodating significant changes to design while retaining traditional CANDU strengths. The focus of the new design is to achieve a 40% reduction in capital cost, quicken construction time and higher efficiency. Key aspects of the new design include: light water coolant, smaller core, slightly enriched fuel, higher temperature and pressure coolant. Work is well advanced on the preliminary design

  12. 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...

  13. Disease-modifying antirheumatic drugs in pregnancy - Current status and implications for the future

    NARCIS (Netherlands)

    Vroom, Fokaline; de Walle, Hermien E. K.; van de Laar, Mart A. J. F.; Brouwers, Jacobus R. B. J.; de Jong-van den Berg, Lolkje T. W.

    2006-01-01

    Drug use during pregnancy is sometimes unavoidable, especially in chronic inflammatory diseases such as rheumatoid arthritis (RA). The use of disease-modifying antirheumatic drugs (DMARDs) often starts in the early stage of RA; therefore, women of reproductive age are at risk for exposure to a DMARD

  14. Forfeiture of the profits and proceeds derived from drug trafficking: thoughts on future action in Malaysia.

    Science.gov (United States)

    Vohrah, K C

    1984-01-01

    While the Dangerous Drugs Act 1952 of Malaysia has been amended to take into account changing patterns of drug abuse and trafficking, it lacks provisions for the mandatory forfeiture of proceeds derived from drug trafficking. Nor do the general powers of forfeiture in the Criminal Procedure Code of the country extend to such proceeds. To meet further changing patterns of drug trafficking involving criminal syndicate leaders, who rarely incriminate themselves through overt and detectable acts, Malaysia has a bill in Parliament the purpose of which, when it becomes law, is to detain without trial, upon cogent evidence, persons who have been associated with any activity relating to or involving drug trafficking, and to prevent them from further committing drug crimes. In addition, serious thinking has been given to the possibility of adopting, within the constraints of the Malaysian Constitution, a law on forfeiture of the proceeds derived from drug trafficking. There are, in this respect, several problems to be resolved, such as the secrecy of bank accounts and taxpayers' returns, which might make it difficult to trace proceeds and to keep track of tainted money being remitted abroad, although it is believed that such problems could be overcome by domestic measures. A more serious problem is the lack of international co-operation for investigations to be carried out outside national borders to trace, seize, freeze and secure the forfeiture of the proceeds of drug crimes located abroad.

  15. From the past to the future: Integrating work experience into the design process.

    Science.gov (United States)

    Bittencourt, João Marcos; Duarte, Francisco; Béguin, Pascal

    2017-01-01

    Integrating work activity issues into design process is a broadly discussed theme in ergonomics. Participation is presented as the main means for such integration. However, a late participation can limit the development of both project solutions and future work activity. This article presents the concept of construction of experience aiming at the articulated development of future activities and project solutions. It is a non-teleological approach where the initial concepts will be transformed by the experience built up throughout the design process. The method applied was a case study of an ergonomic participation during the design of a new laboratory complex for biotechnology research. Data was obtained through analysis of records in a simulation process using a Lego scale model and interviews with project participants. The simulation process allowed for developing new ways of working and generating changes in the initial design solutions, which enable workers to adopt their own developed strategies for conducting work more safely and efficiently in the future work system. Each project decision either opens or closes a window of opportunities for developing a future activity. Construction of experience in a non-teleological design process allows for understanding the consequences of project solutions for future work.

  16. 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.

  17. Turning theory into practice: the development of modern transdermal drug delivery systems and future trends.

    Science.gov (United States)

    Perumal, O; Murthy, S N; Kalia, Y N

    2013-01-01

    Despite its remarkable barrier function, the skin remains an attractive site for systemic drug delivery given its easy accessibility, large surface area and the possibility to bypass the gastrointestinal tract and the liver and so modify drug absorption kinetics. The pioneering work of Scheuplein, Higuchi and others in the 1960s helped to explain the processes involved in passive percutaneous absorption and led to the development of mathematical models to describe transdermal drug delivery. The intervening years have seen these theories turned to practice and a significant number of transdermal systems are now available including some that employ active drug delivery. This review briefly discusses the evolution of transdermal therapeutic systems over the years and the potential of newer transdermal technologies to deliver hydrophilic drugs and macromolecules through the skin. © 2013 S. Karger AG, Basel.

  18. Drugs for Neglected Diseases initiative model of drug development for neglected diseases: current status and future challenges.

    Science.gov (United States)

    Ioset, Jean-Robert; Chang, Shing

    2011-09-01

    The Drugs for Neglected Diseases initiative (DNDi) is a patients' needs-driven organization committed to the development of new treatments for neglected diseases. Created in 2003, DNDi has delivered four improved treatments for malaria, sleeping sickness and visceral leishmaniasis. A main DNDi challenge is to build a solid R&D portfolio for neglected diseases and to deliver preclinical candidates in a timely manner using an original model based on partnership. To address this challenge DNDi has remodeled its discovery activities from a project-based academic-bound network to a fully integrated process-oriented platform in close collaboration with pharmaceutical companies. This discovery platform relies on dedicated screening capacity and lead-optimization consortia supported by a pragmatic, structured and pharmaceutical-focused compound sourcing strategy.

  19. What is past is prologue: future directions in Tokamak Power Reactor Design Research

    International Nuclear Information System (INIS)

    Conn, R.W.

    1976-01-01

    After reviewing the first generation of studies and the primary conclusions they produced, four current designs are discussed that are representative of present trends in this area of research. In particular, the trends towards reduced reactor size and higher neutron wall loadings are discussed. Moving in this direction requires new approaches to many subsystem designs. New approaches and future directions in first wall and blanket designs that can achieve reliable operation and reasonable lifetime, the use of cryogenic but normal aluminum magnets for the pulsed coils in a tokamak, blanket designs that allow elimination of the intermediate loop, and low activity shields and toroidal field magnets are described. A discussion is given of the future role of conceptual reactor design research and the need for close interactions with ongoing experiments in fusion technology

  20. Troubling Futures: Can Participatory Design Research provide a Constitutive Anthropology for the 21st Century?

    Directory of Open Access Journals (Sweden)

    Ann Light

    2015-10-01

    Full Text Available This paper argues there is value in considering participatory design as a form of anthropology at a time when we recognise that we need not only to understand cultures but to change them towards sustainable living. Holding up the democratically-oriented practices of some participatory design research to definitions of anthropology allows the essay to explore the role of intervention in social process. And, challenging definitional boundaries, it examines design as a participatory tool for cultural change, creating and interrogating futures (and the idea of futures. In analysing how designing moves towards change in the world, the paper brings together design research and anthropological concepts to help us better understand and operationalise our interventions and pursue them in a fair and sustainable manner.

  1. Safety aspects of designs for future light water reactors (evolutionary reactors)

    International Nuclear Information System (INIS)

    1993-07-01

    The main purpose of this document is to describe the major innovations of proposed designs of future light water reactors, to describe specific safety characteristics and safety analysis methodologies, and to give a general overview of the most important safety aspects related to future reactors. The reactors considered in this report are limited to those intended for fixed station electrical power production, excluding most revolutionary concepts. More in depth discussion is devoted to those designs that are in a more advanced state of completion and have been more extensively described and analysed in the open literature. Other designs will be briefly described, as evidence of the large spectrum of new proposals. Some designs are similar; others implement unique features and require specific discussion (not all aspects of designs with unique features are fully discussed in this document). 131 refs, 22 figs

  2. Lethal drugs in capital punishment in USA: History, present, and future perspectives.

    Science.gov (United States)

    Kas, Kristen; Yim, Richard; Traore, Salematou; ElFadaly, Marwa; Lang, Lynn; Freeman, Robert A; Parmar, Jayesh R; Kharel, Madan K

    Lethal injection is the preferred method for the execution of condemned prisoners in the United States. A recent decision of The European Union to prohibit the export of drugs used in capital punishment to the USA along with domestic firms ceasing to manufacture these drugs has resulted in a drug shortage and a search for alternative drugs and new drug combinations that have not been previously validated for inducing death. As a consequence, some of the executions did not proceed as expected and sparked public debate regarding whether recent executions by lethal injection serve the purpose of avoiding "cruel and unusual punishment" in executions. Moreover, a cottage industry comprised of compounding pharmacies as emerged as a source of drug combinations used in capital punishment. Although there is a growing trend toward the abolishment of capital punishment in United States, the controversy concerning the efficacy of drug and involvement of health care professionals in the execution procedure is far from over. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Molecular dynamics in drug design: new generations of compstatin analogs.

    Science.gov (United States)

    Tamamis, Phanourios; López de Victoria, Aliana; Gorham, Ronald D; Bellows-Peterson, Meghan L; Pierou, Panayiota; Floudas, Christodoulos A; Morikis, Dimitrios; Archontis, Georgios

    2012-05-01

    We report the computational and rational design of new generations of potential peptide-based inhibitors of the complement protein C3 from the compstatin family. The binding efficacy of the peptides is tested by extensive molecular dynamics-based structural and physicochemical analysis, using 32 atomic detail trajectories in explicit water for 22 peptides bound to human, rat or mouse target protein C3, with a total of 257 ns. The criteria for the new design are: (i) optimization for C3 affinity and for the balance between hydrophobicity and polarity to improve solubility compared to known compstatin analogs; and (ii) development of dual specificity, human-rat/mouse C3 inhibitors, which could be used in animal disease models. Three of the new analogs are analyzed in more detail as they possess strong and novel binding characteristics and are promising candidates for further optimization. This work paves the way for the development of an improved therapeutic for age-related macular degeneration, and other complement system-mediated diseases, compared to known compstatin variants. © 2012 John Wiley & Sons A/S.

  4. 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.

  5. Mechatronic futures challenges and solutions for mechatronic systems and their designers

    CERN Document Server

    Bradley, David

    2016-01-01

    Offering a comprehensive overview of the challenges, risks and options facing the future of mechatronics, this book provides insights into how these issues are currently assessed and managed. Building on the previously published book ‘Mechatronics in Action,’ it identifies and discusses the key issues likely to impact on future mechatronic systems. It supports mechatronics practitioners in identifying key areas in design, modeling and technology and places these in the wider context of concepts such as cyber-physical systems and the Internet of Things. For educators it considers the potential effects of developments in these areas on mechatronic course design, and ways of integrating these. Written by experts in the field, it explores topics including systems integration, design, modeling, privacy, ethics and future application domains. Highlighting novel innovation directions, it is intended for academics, engineers and students working in the field of mechatronics, particularly those developing new conc...

  6. A New Framework to Evaluate Urban Design Using Urban Microclimatic Modeling in Future Climatic Conditions

    Directory of Open Access Journals (Sweden)

    Dasaraden Mauree

    2018-04-01

    Full Text Available Building more energy-efficient and sustainable urban areas that will both mitigate the effects of climate change and anticipate living conditions in future climate scenarios requires the development of new tools and methods that can help urban planners, architects and communities achieve this goal. In the current study, we designed a workflow that links different methodologies developed separately, to derive the energy consumption of a university school campus for the future. Three different scenarios for typical future years (2039, 2069, 2099 were run, as well as a renovation scenario (Minergie-P. We analyzed the impact of climate change on the heating and cooling demand of buildings and determined the relevance of taking into account the local climate in this particular context. The results from the simulations confirmed that in the future, there will be a constant decrease in the heating demand, while the cooling demand will substantially increase. Significantly, it was further demonstrated that when the local urban climate was taken into account, there was an even higher rise in the cooling demand, but also that a set of proposed Minergie-P renovations were not sufficient to achieve resilient buildings. We discuss the implication of this work for the simulation of building energy consumption at the neighborhood scale and the impact of future local climate on energy system design. We finally give a few perspectives regarding improved urban design and possible pathways for future urban areas.

  7. Evolution of the physicochemical properties of marketed drugs: can history foretell the future?

    Science.gov (United States)

    Faller, Bernard; Ottaviani, Giorgio; Ertl, Peter; Berellini, Giuliano; Collis, Alan

    2011-11-01

    A set of diverse bioactive molecules, relevant from a medicinal chemistry viewpoint, was assembled and used to navigate the physicochemical property space of new and old, or traditional drugs against a larger set of 12,000 diverse bioactive small molecules. Most drugs on the market only occupy a fraction of the property space of the bioactive molecules, whereas new molecular entities (NMEs) approved since 2002 are moving away from this traditional drug space. In this new territory, semi-empirical rules derived from knowledge accumulated from historic, older molecules are not necessarily valid and different liabilities become more prominent. Copyright © 2011 Elsevier Ltd. All rights reserved.

  8. TERATOGENIC EFFECTS OF DRUGS ON THE ORGANISM OF A FUTURE CHILD DURING FETAL STAGE OF DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    S.A. Sher

    2011-01-01

    Full Text Available Article assesses the impact of adverse factors on intrauterine development of the child, first of all, drugs. The author stresses that the importance of drug safety (D is due to the large number of unintended pregnancies worldwide. A list of the D, providing proven teratogenic effects on a child organism is presenting. It is shown that the D teratogenic effect in humans can not be assessed on the basis of experimental data obtained in animals due to the difference between metabolic and detoxification processes in a different mammals and individuals. Key words: drugs, safety, teratogenic effects, fetal development, the unborn child. (Pediatric pharmacology. — 2011; 8 (6: 57–60.

  9. 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.

  10. Protein-Protein Docking in Drug Design and Discovery.

    Science.gov (United States)

    Kaczor, Agnieszka A; Bartuzi, Damian; Stępniewski, Tomasz Maciej; Matosiuk, Dariusz; Selent, Jana

    2018-01-01

    Protein-protein interactions (PPIs) are responsible for a number of key physiological processes in the living cells and underlie the pathomechanism of many diseases. Nowadays, along with the concept of so-called "hot spots" in protein-protein interactions, which are well-defined interface regions responsible for most of the binding energy, these interfaces can be targeted with modulators. In order to apply structure-based design techniques to design PPIs modulators, a three-dimensional structure of protein complex has to be available. In this context in silico approaches, in particular protein-protein docking, are a valuable complement to experimental methods for elucidating 3D structure of protein complexes. Protein-protein docking is easy to use and does not require significant computer resources and time (in contrast to molecular dynamics) and it results in 3D structure of a protein complex (in contrast to sequence-based methods of predicting binding interfaces). However, protein-protein docking cannot address all the aspects of protein dynamics, in particular the global conformational changes during protein complex formation. In spite of this fact, protein-protein docking is widely used to model complexes of water-soluble proteins and less commonly to predict structures of transmembrane protein assemblies, including dimers and oligomers of G protein-coupled receptors (GPCRs). In this chapter we review the principles of protein-protein docking, available algorithms and software and discuss the recent examples, benefits, and drawbacks of protein-protein docking application to water-soluble proteins, membrane anchoring and transmembrane proteins, including GPCRs.

  11. A proposed approach for enhancing design safety assurance of future plants

    International Nuclear Information System (INIS)

    Oh, Kyu Myeng; Ahn, Sang Kyu; Lee, Chang Ju; Kim, Inn Seock

    2010-01-01

    This paper provides various insights from a detailed review of deterministic approaches typically applied to ensure design safety of nuclear power plants (NPPs) and risk-informed approaches proposed to evaluate safety of advanced reactors such as Generation IV reactors. Also considered herein are the risk-informed safety analysis (RISA) methodology suggested by Westinghouse as a means to improve the conventional accident analysis, together with the Technology Neutral Framework recently suggested by the U.S. NRC for safety evaluation of future plants. These insights from the comparative review of deterministic and risk-informed approaches could be used in further enhancing the methodology for design safety assurance of future plants

  12. An emerging integration between ionic liquids and nanotechnology: general uses and future prospects in drug delivery.

    Science.gov (United States)

    de Almeida, Tânia Santos; Júlio, Ana; Mota, Joana Portugal; Rijo, Patrícia; Reis, Catarina Pinto

    2017-06-01

    There is a growing need to develop drug-delivery systems that overcome drawbacks such as poor drug solubility/loading/release, systemic side effects and limited stability. Ionic liquids (ILs) offer many advantages and their tailoring represents a valuable tuning tool. Nano-based systems are also prized materials that prevent drug degradation, enhance their transport/distribution and extend their release. Consequently, structures containing ILs and nanoparticles (NPs) have been developed to attain synergistic effects. This overview on the properties of ILs, NPs and of their combined structures, reveals the recent advances in these areas through a review of pertinent literature. The IL-NP structures present enhanced properties and the subsequent performance upgrade proves to be useful in drug delivery, although much is yet to be done.

  13. Modulating sensitivity to drug-induced apoptosis: the future for chemotherapy?

    International Nuclear Information System (INIS)

    Makin, Guy; Dive, Caroline

    2001-01-01

    Drug resistance is a fundamental problem in the treatment of most common human cancers. Our understanding of the cellular mechanisms underlying death and survival has allowed the development of rational approaches to overcoming drug resistance. The mitogen activated protein kinase family of protein serine/threonine kinases has been implicated in this complex web of signalling, with some members acting to enhance death and other members to prevent it. A recent publication by MacKeigan et al is the first to demonstrate an enhancement of drug-induced cell death by simultaneous blockade of MEK-mediated survival signalling, and offers the potential for targeted adjuvant therapy as a means of overcoming drug resistance

  14. A basic design of alarm system for the future nuclear power plants in Korea

    International Nuclear Information System (INIS)

    Lee, Cheol-Kwon; Hur, Seop; Shin, Jae-Hwal; Koo, In-Soo; Park, Jong-Kyun

    1997-01-01

    The design of an advanced alarm system is under way to apply to the new MMIS for the future nuclear power plants in Korea. Based on the alarm system design bases we established the design requirements and are now refining them with the results of evaluation through the prototype. To realize the advanced system new algorithms for alarm processing and display are implemented and various new devices are examined. The evaluation for the design is performed in accordance with the verification and validation plans and through the prototype. (author). 7 refs, 2 figs

  15. Drugs of abuse in pregnancy, poor neonatal development, and future neurodegeneration. Is oxidative stress the culprit?

    Science.gov (United States)

    Neri, Margherita; Bello, Stefania; Turillazzi, Emanuela; Riezzo, Irene

    2015-01-01

    The abuse of licit and illicit drugs is a worldwide issue that is a cause for concern in pregnant women. It may lead to complications in pregnancy that may affect the mother, fetus, and /or neonate. The effects of any substance on the developing embryo and fetus are dependent upon dosing, timing, duration of drug exposure, and the extent of drug distribution. Teratogenic effects have been described when exposure takes place during the embryonic stage; however drugs have subtle effects, including abnormal growth and/or maturation, alterations in neurotransmitters and their receptors, and brain organization. The mechanisms by which intrauterine exposure to many substances may result in neuronal injury have not been completely elucidated. Oxidative stress and epigenetic changes have been recently implicated in the pathogenesis of long - term adverse health sequelae, and neuro-developmental impairment in the offspring of addicted mothers. Transgenerational epigenetics may also explain the alarming datum that developmental abnormalities, impairment in learning and memory, and attention deficit can occur even in the absence of direct fetal exposure, when drugs are consumed prior to conception. There is a growing body of evidence demonstrating a link between redox state unbalance, epigenetic markers, developmental anomalies, and neurodegeneration. The reviewed literature data uphold redox homeostasis disruption as an important factor in the pathogenesis of drug of abuse- induced neurodegeneration, and highlight the potential for new therapies that could prevent neurodegeneration through antioxidant and epigenetic modulatory mechanisms. This therefore reveals important targets for novel neuroprotective strategies.

  16. New drugs for the treatment of tuberculosis: needs, challenges, promise, and prospects for the future.

    Science.gov (United States)

    Lienhardt, Christian; Raviglione, Mario; Spigelman, Mel; Hafner, Richard; Jaramillo, Ernesto; Hoelscher, Michael; Zumla, Alimuddin; Gheuens, Jan

    2012-05-15

    For the first time in 40 years, a portfolio of promising new compounds for the treatment of tuberculosis is on the horizon. The introduction of new drugs in combination treatment for all forms of tuberculosis raises several issues related to patients' access to novel treatments, programmatic feasibility, cost effectiveness, and implications for monitoring and surveillance, particularly with regard to the development of drug resistance. Particular attention should be given to the identification of optimal drug combination(s) for the treatment of all forms of tuberculosis, particularly in high-risk and vulnerable groups, such as human immunodeficiency virus-coinfected persons and children, and to the rational use of new drugs. Addressing these issues adequately requires the establishment of clear guidelines to assist countries in the development of policies for the proper use of tuberculosis drugs in a way that guarantees access to best treatments for all those in need and avoids inappropriate use of new drugs. After a description of these various challenges, we present activities that will be carried out by the World Health Organization in collaboration with key stakeholders for the development of policy guidelines for optimal treatment of tuberculosis.

  17. Understanding the Design Context for Australian University Teachers: Implications for the Future of Learning Design

    Science.gov (United States)

    Bennett, Sue; Thomas, Lisa; Agostinho, Shirley; Lockyer, Lori; Jones, Jennifer; Harper, Barry

    2011-01-01

    Based on the premise that providing support for university teachers in designing for their teaching will ultimately improve the quality of student learning outcomes, recent interest in the development of support tools and strategies has gained momentum. This article reports on a study that examined the context in which Australian university…

  18. Designing domestic buildings for future summers: Attitudes and opinions of building professionals

    International Nuclear Information System (INIS)

    Gul, Mehreen S.; Menzies, Gillian F.

    2012-01-01

    A changing climate will produce summertime overheating where conventional domestic building design approaches do not adequately address future warming risk. This risk cannot be fully identified and avoided unless future climate information and building related adaptation measures are considered. The Low Carbon Futures project is developing a tool that uses UKCP09 climate projections input to predict dwelling overheating risks. To enhance the usefulness of this tool for the building industry, and to better understand current building design processes, interviews were conducted with building professionals, allowing industry preferences for the tool to be sought and to provide clearer indications of proposed outcomes. This paper examines results from a questionnaire, focus groups and semi-structured interviews with building industry professionals. The research shows that the housing industry maintains adherence to traditional designing methods where overheating, whether current or future, is not considered a serious concern. No design stage detailed overheating assessments are currently undertaken to reduce the UK's increased room air-conditioner sales, despite drives for low energy/zero carbon homes. The collated feedback will help tailor the tool and its eventual outputs, with this paper attempting to converge on a set of recommendations for low carbon dwelling design with reduced overheating risk. - Highlights: ► Interviews to gauge attitudes of building professionals towards future warming. ► Client requirements, capital costs and regulations take priority in typical practice. ► No actions are currently taken to prevent overheating risks in the housing sector. ► Overheating risks in housing can be tackled by the use of dynamic modelling. ► The LCF tool further helps to adapt a dwelling to reduce future overheating risks.

  19. PWR design for low doses in the United Kingdom: The present and the future

    Energy Technology Data Exchange (ETDEWEB)

    Zodiates, A.M.; Willcock, A. [PWR Project Group, Knutsford, England (United Kingdom)

    1995-03-01

    The Pressurizer Water Reactor (PWR) design chosen for adoption by Nuclear Electric plc was based on the Westinghouse Standard Nuclear Unit Power Plant System (SNUPPS). This design was developed to meet the United Kingdom (UK) requirements and those improvements are embodied in the Sizewell B plant. Nuclear Electric plc is now looking to the design of the future PWRs to be built in the UK. These PWRs will be based as replicas of the Sizewell B design, but attention will be given to reducing operator doses further. This paper details the approach in operator protection improvements incorporated at Sizewall B, presents the estimated annual collective dose, and identifies the approach being adopted to reduce further operator doses in future plants.

  20. 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 ...

  1. Design status of the NLC beam-delivery system and possible future studies

    International Nuclear Information System (INIS)

    Zimmermann, F.; Bowden, G.; Burke, D.

    1996-10-01

    The authors outline some highlights in the present design of the beam-delivery and removal system for the Next Linear Collider (NLC), and present a long list of possible or desirable future studies. On several of the listed items work has already been started since the Snowmass workshop. Other studies could be conducted, for example, in the framework of a conceptual design report (CDR)

  2. 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.

  3. Quantum mechanics implementation in drug-design workflows: does it really help?

    Science.gov (United States)

    Arodola, Olayide A; Soliman, Mahmoud Es

    2017-01-01

    The pharmaceutical industry is progressively operating in an era where development costs are constantly under pressure, higher percentages of drugs are demanded, and the drug-discovery process is a trial-and-error run. The profit that flows in with the discovery of new drugs has always been the motivation for the industry to keep up the pace and keep abreast with the endless demand for medicines. The process of finding a molecule that binds to the target protein using in silico tools has made computational chemistry a valuable tool in drug discovery in both academic research and pharmaceutical industry. However, the complexity of many protein-ligand interactions challenges the accuracy and efficiency of the commonly used empirical methods. The usefulness of quantum mechanics (QM) in drug-protein interaction cannot be overemphasized; however, this approach has little significance in some empirical methods. In this review, we discuss recent developments in, and application of, QM to medically relevant biomolecules. We critically discuss the different types of QM-based methods and their proposed application to incorporating them into drug-design and -discovery workflows while trying to answer a critical question: are QM-based methods of real help in drug-design and -discovery research and industry?

  4. Energy drink consumption and the perceived risk and disapproval of drugs: Monitoring the Future, 2010-2016.

    Science.gov (United States)

    Jackson, Dylan B; Leal, Wanda E

    2018-07-01

    Energy drinks have become quite popular in recent years among adolescents, prompting a wealth of recent research examining the potential deleterious consequences of energy drink consumption among youth. The present study adds to this body of work by exploring perceptions of risk and disapproval of soft and hard drugs among adolescents and whether such attitudes are predicted by patterns of energy drink/shot consumption. Data were derived from the seven most recent cohorts (2010-2016) of the Monitoring the Future (MTF) study, a nationally representative survey of U.S. youth. The significance of associations between energy drink/shot consumption and drug perceptions/attitudes was tested using logistic regression techniques employing adjustments for covariates and cohort-specific fixed effects. Energy drink/shot consumption was largely associated with significant increases in the odds of failing to perceive any risk of drug use and failing to disapprove of drug use among youths, regardless of whether attitudes concerning soft or hard drugs were examined. These associations were particularly robust in the case of habitual energy drink/shot consumers (relative to occasional consumers or abstainers). Additional efforts should be made to heighten awareness and education concerning the potential dangers of energy drink consumption among youth, particularly as it pertains to drug attitudes and diminished perceptions of substance use risk. Policies that minimize energy drink consumption among youth as well as programs that educate parents and teachers about the drug attitudes of youths who regularly consume energy drinks and promote active monitoring of these adolescents may be worthwhile. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. Future of the transdermal drug delivery market--have we barely touched the surface?

    Science.gov (United States)

    Watkinson, Adam C; Kearney, Mary-Carmel; Quinn, Helen L; Courtenay, Aaron J; Donnelly, Ryan F

    2016-01-01

    Transdermal drug delivery is the movement of drugs across the skin for absorption into the systemic circulation. Transfer of the drug can occur via passive or active means; passive transdermal products do not disrupt the stratum corneum to facilitate delivery whereas active technologies do. Due to the very specific physicochemical properties necessary for successful passive transdermal drug delivery, this sector of the pharmaceutical industry is relatively small. There are many well-documented benefits of this delivery route however, and as a result there is great interest in increasing the number of therapeutic substances that can be delivered transdermally. This review discusses the various transdermal products that are currently/have been marketed, and the paths that led to their success, or lack of. Both passive and active transdermal technologies are considered with the advantages and limitations of each highlighted. In addition to marketed products, technologies that are in the investigative stages by various pharmaceutical companies are reviewed. Passive transdermal drug delivery has made limited progress in recent years, however with the ongoing intense research into active technologies, there is great potential for growth within the transdermal delivery market. A number of active technologies have already been translated into marketed products, with other platforms including microneedles, rapidly progressing towards commercialisation.

  6. 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.

  7. Designing Online Instruction for Success: Future Oriented Motivation and Self-Regulation

    Science.gov (United States)

    Schmidt, Joel T.; Werner, Christian H.

    2007-01-01

    Given the high rate of student drop-out and withdrawal from courses and programs using an online learning format, it is important to consider innovative ways to foster and encourage student success in online environments. One such way is to incorporate aspects of student future orientation into the design of online instruction. This paper presents…

  8. Commentary on Future directions: Building technologies and design tools''

    Energy Technology Data Exchange (ETDEWEB)

    Quadrel, R.W.

    1992-08-10

    This paper presents a number of interesting and thought-provoking scenarios about the future use of advanced technology in the design and operation of commercial buildings. I will express my reactions in the following series of short paragraphs. These thoughts will, I hope, raise some new questions and offer fruitful directions for further exploration.

  9. Technical Meeting on Impact of Fukushima Event on Current and Future Fast Reactor Designs. Working Material

    International Nuclear Information System (INIS)

    2012-01-01

    The overall purpose of the Technical Meeting was to recognize and analyse the implications of the accident occurred at the Fukushima Dai-ichi Nuclear Power Station on current and future fast neutron systems design and operation. The aim was to provide a global forum for discussing the principal lessons learned from this event, and thus to review safety principles and characteristics of existing and future fast neutron concepts, especially in relation with extreme natural events which potentially may lead to severe accident scenarios. The participants also presented and discussed innovative technical solutions, design features and countermeasures for design extension conditions - including earthquakes, tsunami and other extreme natural hazards - which can enhance the safety level of existing and future fast neutron systems. Furthermore, the meeting gave the opportunity to present advanced methods for the evaluation of the robustness of plants against design extension conditions. Another important goal of this TM was to discuss how to harmonize safety approaches and goals for next generation’s fast reactors. Finally, the meeting was intended to identify areas where further research and development in nuclear safety, technology and engineering in the light of the Fukushima accident are needed. In the frame of the implementation of its Nuclear Safety Action Plan endorsed by all Member States, the IAEA will consider these areas as potential technical topics for new Coordinated Research Projects, to be launched in the near future

  10. Imagining future places : How designs co-constitute what is, and thus influence what will be

    NARCIS (Netherlands)

    van Dijk, Terry

    Despite attempts to connect planning with design disciplines, some opportunities to do so still await further inquiry, particularly the conception promoted by Throgmorton of planning as persuasive storytelling. According to this perspective, we persuade one another about what the future should and

  11. Technical Meeting on Impact of Fukushima Event on Current and Future Fast Reactor Designs. Presentations

    International Nuclear Information System (INIS)

    2012-01-01

    The overall purpose of the Technical Meeting was to recognize and analyse the implications of the accident occurred at the Fukushima Dai-ichi Nuclear Power Station on current and future fast neutron systems design and operation. The aim was to provide a global forum for discussing the principal lessons learned from this event, and thus to review safety principles and characteristics of existing and future fast neutron concepts, especially in relation with extreme natural events which potentially may lead to severe accident scenarios. The participants also presented and discussed innovative technical solutions, design features and countermeasures for design extension conditions - including earthquakes, tsunami and other extreme natural hazards - which can enhance the safety level of existing and future fast neutron systems. Furthermore, the meeting gave the opportunity to present advanced methods for the evaluation of the robustness of plants against design extension conditions. Another important goal of this TM was to discuss how to harmonize safety approaches and goals for next generation’s fast reactors. Finally, the meeting was intended to identify areas where further research and development in nuclear safety, technology and engineering in the light of the Fukushima accident are needed. In the frame of the implementation of its Nuclear Safety Action Plan endorsed by all Member States, the IAEA will consider these areas as potential technical topics for new Coordinated Research Projects, to be launched in the near future

  12. Design of a Push-Broom Multi-Beam Radiometer for Future Ocean Observations

    DEFF Research Database (Denmark)

    Cappellin, C.; Pontoppidan, K.; Nielsen, P. H.

    2015-01-01

    The design of a push-broom multi-beam radiometer for future ocean observations is described. The radiometer provides a sensitivity one order of magnitude higher than a traditional conical scanning radiometer, and has the big advantage of being fully stationary relative to the satellite platform...

  13. The challenges and future of oral drug delivery: An interview with David Brayden.

    Science.gov (United States)

    Brayden, David J

    2016-12-01

    David Brayden speaks to Hannah Makin, Commissioning Editor: David Brayden is a Full Professor (Advanced Drug Delivery) at the School of Veterinary Medicine, University College Dublin (UCD) and also a Fellow of the UCD Conway Institute. Following a PhD in Pharmacology at the University of Cambridge, UK (1989), and a postdoctoral research fellowship at Stanford University, CA, USA, he set up Elan Biotechnology Research's in vitro pharmacology laboratory in Dublin (1991). At Elan, he became a senior scientist and project manager of several of Elan's joint-venture drug delivery research collaborations with US biotech companies. In 2001, he joined UCD as a lecturer in veterinary pharmacology and was appointed Associate Professor in 2006 and Full Professor in 2014. He was a Director of the Science Foundation Ireland Research Cluster (The Irish Drug Delivery Research Network) from 2007 to 2013, is a Deputy Coordinator of an FP7 Consortium on oral peptides in nanoparticles ('TRANS-INT', 2012-2017), and is a Co-Principal Investigator in 'CURAM', Science Foundation Ireland's new Centre for Medical Devices (2014-2020 [ 1 ]). He was made a Fellow of the Controlled Release Society in 2012. He is the author or co-author of >200 research publications and patents. D Brayden serves on the Editorial Advisory Boards of Drug Discovery Today, European Journal of Pharmaceutical Sciences, Advanced Drug Delivery Reviews and the Journal of Veterinary Pharmacology and Therapeutics, and is an Associate Editor of Therapeutic Delivery. D Brayden works as an independent consultant for drug delivery companies.

  14. 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.

  15. Durable past - sustainable future; Heritage-based design; Designing from Heritage. Strategies for Conservation and Conversion

    Directory of Open Access Journals (Sweden)

    Irmgard van Koningsbruggen

    2018-06-01

    elkaar. De opleidingsnaam vanaf 2004, ‘rMIT ’, weerspiegelde deze koers van versmelten. De ontwerpopgave werd verbonden met onderzoek van de cultuurhistorische waarde van gebouw en omgeving en met dat van technologiespecialisten die zich concentreren op materialen (en hun schade, duurzaamheid en energietransitie. Dit leidde tot de drie leerstoelgebieden Design, Cultural Value en Technology en de huidige naam voor deze masteropleiding: Heritage & Architecture. In een gelijkbenige ‘leerstoeldriehoek’ werd de versmelting verbeeld.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. First Considerations on Beam Optics and Lattice Design for the Future Hadron-Hadron Collider FCC

    CERN Document Server

    Alemany Fernandez, R

    2014-01-01

    The present document explains the steps carried out in order to make the first design of the Future Hadron-Hadron Collider (FCC-hh) following the base line parameters that can be found in [1]. Two lattice layouts are presented, a ring collider with 12 arcs and 12 straight sections, four of them designed as interaction points, and a racetrack like collider with two arcs and two straight sections, each of them equipped with two interaction points. The lattice design presented in the paper is modular allowing the same modules be used for both layouts. The present document addresses as well the beta star reach at the interaction points.

  1. Current status and future prospects of Korean standardized nuclear power plant design

    International Nuclear Information System (INIS)

    Rieh, C.-H.; Park, S.-K.; Lee, B.-R.

    1992-01-01

    The authors reviewed a brief history of Korean nuclear industry since the first Kori-1 plant operation in 1978 with special emphasis on the NSSS and BOP design and engineering, and the design approaches for nuclear power plants in the future. Continued effort to enhance plant economy and operational safety has been made by increasing plant size, and improving safety features, systems and component reliability in various design aspects. Korean nuclear industry is now trying to be one of the major contributors to the world nuclear field in sharing nuclear technology gained from past experience and developed through internation technical cooperation programs

  2. A Compact Design of Planar Array Antenna with Fractal Elements for Future Generation Applications

    DEFF Research Database (Denmark)

    Ojaroudiparchin, Naser; Shen, Ming; Pedersen, Gert F.

    2016-01-01

    In this paper, a planar phased array fractal antenna for the future fifth generation (5G) applications is presented. The proposed array antenna is designed to operate at 22 GHz. 64 patch antenna elements with coaxial-probe feeds have been used for the proposed design. The antenna elements are based...... on Vicsek fractal geometry where the third iteration patches operate over a wide bandwidth and contribute to improve the efficiency and realized gain performance. The designed planar array has more than 22 dB realized gain and -0.3 dB total efficiency when its beam is tilted to 0 degrees elevation...

  3. Projecting the Future for Design Science Research: An Action‐Case Based Analysis

    DEFF Research Database (Denmark)

    Baskerville, Richard; Pries-Heje, Jan

    2015-01-01

    and theories appears to be a key challenge. In this paper we commence with a DESRIST paper from 2012 that instantiated design principles in an artifact for a bank. That paper included plans and techniques for future use of its principles (propagation), including prescriptions for a five-phase adoption process...... or theories have stimulated many actual projections. We demonstrate these concepts in a case study of propagation: a chemical manufacturer and service provider that adopted the design principles arising from that 2012 DESRIST banking-based design science research. We conclude that generalizability is too well...

  4. The future of drug discovery: enabling technologies for enhancing lead characterization and profiling therapeutic potential.

    Science.gov (United States)

    Janero, David R

    2014-08-01

    Technology often serves as a handmaiden and catalyst of invention. The discovery of safe, effective medications depends critically upon experimental approaches capable of providing high-impact information on the biological effects of drug candidates early in the discovery pipeline. This information can enable reliable lead identification, pharmacological compound differentiation and successful translation of research output into clinically useful therapeutics. The shallow preclinical profiling of candidate compounds promulgates a minimalistic understanding of their biological effects and undermines the level of value creation necessary for finding quality leads worth moving forward within the development pipeline with efficiency and prognostic reliability sufficient to help remediate the current pharma-industry productivity drought. Three specific technologies discussed herein, in addition to experimental areas intimately associated with contemporary drug discovery, appear to hold particular promise for strengthening the preclinical valuation of drug candidates by deepening lead characterization. These are: i) hydrogen-deuterium exchange mass spectrometry for characterizing structural and ligand-interaction dynamics of disease-relevant proteins; ii) activity-based chemoproteomics for profiling the functional diversity of mammalian proteomes; and iii) nuclease-mediated precision gene editing for developing more translatable cellular and in vivo models of human diseases. When applied in an informed manner congruent with the clinical understanding of disease processes, technologies such as these that span levels of biological organization can serve as valuable enablers of drug discovery and potentially contribute to reducing the current, unacceptably high rates of compound clinical failure.

  5. 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...

  6. Spatio-temporal model based optimization framework to design future hydrogen infrastructure networks

    International Nuclear Information System (INIS)

    Konda, N.V.S.; Shah, N.; Brandon, N.P.

    2009-01-01

    A mixed integer programming (MIP) spatio-temporal model was used to design hydrogen infrastructure networks for the Netherlands. The detailed economic analysis was conducted using a multi-echelon model of the entire hydrogen supply chain, including feed, production, storage, and transmission-distribution systems. The study considered various near-future and commercially available technologies. A multi-period model was used to design evolutionary hydrogen supply networks in coherence with growing demand. A scenario-based analysis was conducted in order to account for uncertainties in future demand. The study showed that competitive hydrogen networks can be designed for any conceivable scenario. It was concluded that the multi-period model presented significant advantages in relation to decision-making over long time-horizons

  7. Animal Models of Seizures and Epilepsy: Past, Present, and Future Role for the Discovery of Antiseizure Drugs.

    Science.gov (United States)

    Löscher, Wolfgang

    2017-07-01

    The identification of potential therapeutic agents for the treatment of epilepsy requires the use of seizure models. Except for some early treatments, including bromides and phenobarbital, the antiseizure activity of all clinically used drugs was, for the most part, defined by acute seizure models in rodents using the maximal electroshock and subcutaneous pentylenetetrazole seizure tests and the electrically kindled rat. Unfortunately, the clinical evidence to date would suggest that none of these models, albeit useful, are likely to identify those therapeutics that will effectively manage patients with drug resistant seizures. Over the last 30 years, a number of animal models have been developed that display varying degrees of pharmacoresistance, such as the phenytoin- or lamotrigine-resistant kindled rat, the 6-Hz mouse model of partial seizures, the intrahippocampal kainate model in mice, or rats in which spontaneous recurrent seizures develops after inducing status epilepticus by chemical or electrical stimulation. As such, these models can be used to study mechanisms of drug resistance and may provide a unique opportunity for identifying a truly novel antiseizure drug (ASD), but thus far clinical evidence for this hope is lacking. Although animal models of drug resistant seizures are now included in ASD discovery approaches such as the ETSP (epilepsy therapy screening program), it is important to note that no single model has been validated for use to identify potential compounds for as yet drug resistant seizures, but rather a battery of such models should be employed, thus enhancing the sensitivity to discover novel, highly effective ASDs. The present review describes the previous and current approaches used in the search for new ASDs and offers some insight into future directions incorporating new and emerging animal models of therapy resistance.

  8. What is past is prologue: future directions in tokamak power reactor design research

    International Nuclear Information System (INIS)

    Conn, R.W.

    1976-01-01

    Conceptual tokamak power reactor designs over the last five years have provided us with many fundamental insights regarding tokamaks as fusion reactors. This first generation of studies has helped lay the groundwork upon which to build improvements in reactor design and begin a process of optimization. After reviewing the first generation of studies and the primary conclusions they produced, we discuss four current designs that are representative of present trends in this area of research. In particular, we discuss the trends towards reduced reactor size and higher neutron wall loadings. Moving in this direction requires new approaches to many subsystem designs. We describe new approaches and future directions in first wall and blanket designs that can achieve reliable operation and reasonable lifetime, the use of cryogenic but normal aluminum magnets for the pulsed coils in a tokamak, blanket designs that allow elimination of the intermediate loop, and low activity shields and toroidal field magnets. We close with a discussion of the future role of conceptual reactor design research and the need for close interaction with ongoing experiments in fusion technology

  9. 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

  10. 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

  11. Design and fabrication of a magnetically actuated non-invasive reusable drug delivery device.

    Science.gov (United States)

    Dsa, Joyline; Goswami, Manish; Singh, B R; Bhatt, Nidhi; Sharma, Pankaj; Chauhan, Meenakshi K

    2018-07-01

    We present a novel approach of designing and fabricating a noninvasive drug delivery device which is capable of delivering the drug to the target site in a controlled manner. The device utilizes a reservoir which can be reused once the drug has completely diffused from it. This micro-reservoir based fabricated device has been successfully tested using niosomes of insulin drug filled in, which was then sealed with a magnetic membrane of 20 µm thick and was actuated by applying magnetic field. The deflection of the membrane on application of magnetic field results in the drug release from the reservoir. The discharge of the drug solution and the release rates was controlled by external magnetic field. The simulation of the membrane deflection using COMSOL software was carried out to optimize the concentration of the ferrous nanopowder in PDMS matrix. The characterization of the devices was implemented in-vitro on water and in-vivo on Wistar rats. It was also validated using high-performance liquid chromatography (HPLC) by observing characteristic peak of insulin. The blood samples showed the retention time of 2.79 min at λ max of 280 nm which further authenticated the effectiveness of the proposed work. This noninvasive fabricated device provides reusability, precise control and can enable the patient or a physician to actively administrate the drug when required.

  12. Price Sensitivity of Demand for Prescription Drugs: Exploiting a Regression Kink Design

    DEFF Research Database (Denmark)

    Simonsen, Marianne; Skipper, Lars; Skipper, Niels

    This paper investigates price sensitivity of demand for prescription drugs using drug purchase records for at 20% random sample of the Danish population. We identify price responsiveness by exploiting exogenous variation in prices caused by kinked reimbursement schemes and implement a regression ...... education and income are, however, more responsive to the price. Also, essential drugs that prevent deterioration in health and prolong life have lower associated average price sensitivity....... kink design. Thus, within a unifying framework we uncover price sensitivity for different subpopulations and types of drugs. The results suggest low average price responsiveness with corresponding price elasticities ranging from -0.08 to -0.25, implying that demand is inelastic. Individuals with lower...

  13. Possibilities of 50 years experience application of design activity of 'Energoprojekt-Warsaw' for nuclear energetics in future

    International Nuclear Information System (INIS)

    Roguska, M.; Grzebula, K.; Patrycy, A.

    2000-01-01

    The 50 year experience in design activity for energetics can be profitable for Polish nuclear energetics in the future. Especially previous works on nuclear power plant localization, design of nuclear technique objects and system of quality assurance certified (ISO 9001-1994) can give the solid base for design of future nuclear power plant in Poland when needed

  14. Medicines by Design

    Science.gov (United States)

    ... Home > Science Education > Medicines By Design Medicines By Design Spotlight Nature's Medicine Cabinet A Medicine's Life Inside ... hunt for drugs of the future. Medicines By Design in PDF | E-PUB Tell Us What You ...

  15. Microencapsulation for the Therapeutic Delivery of Drugs, Live Mammalian and Bacterial Cells, and Other Biopharmaceutics: Current Status and Future Directions

    Directory of Open Access Journals (Sweden)

    Catherine Tomaro-Duchesneau

    2013-01-01

    Full Text Available Microencapsulation is a technology that has shown significant promise in biotherapeutics, and other applications. It has been proven useful in the immobilization of drugs, live mammalian and bacterial cells and other cells, and other biopharmaceutics molecules, as it can provide material structuration, protection of the enclosed product, and controlled release of the encapsulated contents, all of which can ensure efficient and safe therapeutic effects. This paper is a comprehensive review of microencapsulation and its latest developments in the field. It provides a comprehensive overview of the technology and primary goals of microencapsulation and discusses various processes and techniques involved in microencapsulation including physical, chemical, physicochemical, and other methods involved. It also summarizes the state-of-the-art successes of microencapsulation, specifically with regard to the encapsulation of microorganisms, mammalian cells, drugs, and other biopharmaceutics in various diseases. The limitations and future directions of microencapsulation technologies are also discussed.

  16. Microencapsulation for the Therapeutic Delivery of Drugs, Live Mammalian and Bacterial Cells, and Other Biopharmaceutics: Current Status and Future Directions

    Science.gov (United States)

    Saha, Shyamali; Malhotra, Meenakshi; Kahouli, Imen; Prakash, Satya

    2013-01-01

    Microencapsulation is a technology that has shown significant promise in biotherapeutics, and other applications. It has been proven useful in the immobilization of drugs, live mammalian and bacterial cells and other cells, and other biopharmaceutics molecules, as it can provide material structuration, protection of the enclosed product, and controlled release of the encapsulated contents, all of which can ensure efficient and safe therapeutic effects. This paper is a comprehensive review of microencapsulation and its latest developments in the field. It provides a comprehensive overview of the technology and primary goals of microencapsulation and discusses various processes and techniques involved in microencapsulation including physical, chemical, physicochemical, and other methods involved. It also summarizes the state-of-the-art successes of microencapsulation, specifically with regard to the encapsulation of microorganisms, mammalian cells, drugs, and other biopharmaceutics in various diseases. The limitations and future directions of microencapsulation technologies are also discussed. PMID:26555963

  17. 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.

  18. 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....

  19. Recent and future advances in anticancer drug delivery: an interview with Khaled Greish.

    Science.gov (United States)

    Greish, Khaled

    2018-05-01

    Khaled Greish speaks to Hannah Makin, Commissioning Editor: Khaled Greish is Associate Professor of Molecular Medicine, and head of the Nano-research unit, at Princes Al-Jawhara Center, Arabian Gulf University, Kingdom of Bahrain. His previous appointments included Senior lecturer of Pharmacology at the University of Otago, New Zealand, and Assistant Professor of Pharmaceutical Chemistry at University of Utah (UT, USA). He has published >70 peer reviewed papers, and ten book chapters in the field of targeted anticancer drug delivery. Controlled Release Society (CRS) awarded him the CRS Postdoctoral Achievement Award in 2008 and in 2010; he was elected as member of the CRS College of Fellows. In recognition of his research, University of Otago awarded him "Early Career Awards for Distinction in Research" in 2014. His research focuses on nanomedicine, tumor vascular biology and anticancer drug discovery/development.

  20. Neuromarketing techniques in pharmaceutical drugs advertising. A discussion and agenda for future research.

    Science.gov (United States)

    Orzan, G; Zara, I A; Purcarea, V L

    2012-12-15

    Recent years have seen an "explosion" in the abilities of scientists to use neuroscience in new domains. Unfortunately, it is little known and reported on how advertising companies make more effective pharmaceutical drugs commercials. The purpose of this paper is to analyze how neuromarketing techniques may impact the consumer response to pharmaceutical advertising campaigns. The result shows that using neuromarketing methods a pharmaceutical company can better understand the conscious and unconscious consumer's thoughts and tailor specific marketing messages.

  1. Monitoring the Future National Survey Results on Drug Use, 1975-2016. Volume I, Secondary School Students

    Science.gov (United States)

    Miech, Richard A.; Johnston, Lloyd D.; O'Malley, Patrick M.; Bachman, Jerald G.; Schulenberg, John E.; Patrick, Megan E.

    2017-01-01

    Monitoring the Future (MTF) is designed to give sustained attention to substance use among the nation's youth and adults. It is an investigator-initiated study that originated with and is conducted by a team of research professors at the University of Michigan's Institute for Social Research. Since its onset in 1975, MTF has been continuously…

  2. 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.

  3. Biosampling strategies for emerging drugs of abuse: towards the future of toxicological and forensic analysis.

    Science.gov (United States)

    Mercolini, Laura; Protti, Michele

    2016-10-25

    The term "new psychoactive substances" refers to emerging drugs of abuse whose chemical structure and psychoactive effects are similar to other already known compounds, often providing a "legal" alternative to internationally regulated drugs and mostly available via on-line retail sites. There are several categories of new psychoactive substances, such as synthetic cannabinoids, cathinone analogues, phenethylamines, tryptamines, and the need to identify and quantify an unprecedented and growing number of new compounds represents a unique challenge for toxicological and forensic analysis. The purpose of this review is to highlight biosampling, sample preparation and analysis of the most important classes of emerging drugs of abuse in biological matrices, focusing on alternatives to classical blood and urine "in tube" approach, still representing the standard routine for bioanalysis, despite inherent flaws regarding handling, stability and process feasibility. Chromatographic techniques coupled to mass spectrometry are usually exploited to identify and quantify new psychoactive substances; due to their high sensitivity and selectivity, it is possible to determine low concentrations not only in plasma and urine, but also in alternative matrices like dried blood spots, oral fluid, hair, other body fluids and tissues. Current literature on analytical methodologies applied to these samples is still limited and a more thorough validation is often required, including a comparison among the results obtained from conventional approaches and from innovative strategies, in order to determine their actual suitability. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Design measures to facilitate implementation of safeguards at future water cooled nuclear power plants

    International Nuclear Information System (INIS)

    1999-01-01

    The report is intended to present guidelines to the State authorities, designers and prospective purchasers of future water cooled power reactors which, if taken into account, will minimize the impact of IAEA safeguards on plant operation and ensure efficient and effective acquisition of safeguards data to the mutual benefit of the Member State, the plant operator and the IAEA. These guidelines incorporate the IAEA's experience in establishing and carrying out safeguards at currently operating nuclear power plants, the ongoing development of safeguards techniques and feedback of experience from plant operators and designers on the impact of IAEA safeguards on plant operation. The following main subjects are included: The IAEA's safeguards function for current and future nuclear power plants; summary of the political and legal foundations of the IAEA's safeguards system; the technical objective of safeguards and the supply and use of required design information; safeguards approaches for nuclear power plants; design implications of experience in safeguarding nuclear power plants and guidelines for future water cooled reactors to facilitate the implementation of safeguards

  5. Development of safety principles for the design of future nuclear power plants

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-06-01

    The main purpose of this TECDOC is to propose updates to existing safety principles which could be used as a basis for developing safety principles for the design of future NPPs. Accordingly, this document is intended to be useful to reactor designers, owners, operators, researchers and regulators. It is also expected that this document can contribute to international harmonization of safety approaches, and that it will help ensure that future reactors will be designed worldwide to a high standard of safety. As such, these proposed updates are intended to provide general guidance which, if carefully and properly implemented, will result in reactor designs with enhanced safety characteristics beyond those currently in operation. This enhancement results from the fact that the proposals are derived from the lessons learned from more recent operational experience, R and D, design, testing, and analysis developed over the past decade or so, as well as from attempts to reflect the current trends in reactor design, such as the introduction of new technologies. 8 refs, 3 figs.

  6. Development of safety principles for the design of future nuclear power plants

    International Nuclear Information System (INIS)

    1995-06-01

    The main purpose of this TECDOC is to propose updates to existing safety principles which could be used as a basis for developing safety principles for the design of future NPPs. Accordingly, this document is intended to be useful to reactor designers, owners, operators, researchers and regulators. It is also expected that this document can contribute to international harmonization of safety approaches, and that it will help ensure that future reactors will be designed worldwide to a high standard of safety. As such, these proposed updates are intended to provide general guidance which, if carefully and properly implemented, will result in reactor designs with enhanced safety characteristics beyond those currently in operation. This enhancement results from the fact that the proposals are derived from the lessons learned from more recent operational experience, R and D, design, testing, and analysis developed over the past decade or so, as well as from attempts to reflect the current trends in reactor design, such as the introduction of new technologies. 8 refs, 3 figs

  7. 10 CFR 707.7 - Random drug testing requirements and identification of testing designated positions.

    Science.gov (United States)

    2010-01-01

    ... contractor, to have the potential to significantly affect the environment, public health and safety, or... evidence of the use of illegal drugs of employees in testing designated positions identified in this... section shall provide for random tests at a rate equal to 30 percent of the total number of employees in...

  8. Elucidating Concepts in Drug Design through Taste with Natural and Artificial Sweeteners

    Science.gov (United States)

    Lipchock, James M.; Lipchock, Sarah V.

    2016-01-01

    Fundamental concepts in biochemistry important for drug design often lack connection to the macroscopic world and can be difficult for students to grasp, particularly those in introductory science courses at the high school and college level. Educational research has shown that multisensory teaching facilitates learning, but teaching at the high…

  9. 21 CFR 516.30 - Annual reports for a MUMS-designated drug.

    Science.gov (United States)

    2010-04-01

    ... status or results of such studies; (b) A description of the investigational plan for the coming year, as well as any anticipated difficulties in development, testing, and marketing; and (c) A brief discussion of any changes that may affect the MUMS-designated drug status of the product. For example...

  10. The semiempirical quantum mechanical scoring function for in-silico drug design

    Czech Academy of Sciences Publication Activity Database

    Fanfrlík, Jindřich; Lepšík, Martin; Řezáč, Jan; Kolář, Michal; Pecina, Adam; Nachtigallová, Dana; Hobza, Pavel

    2015-01-01

    Roč. 22, č. 1 (2015), s. 34 ISSN 1211-5894. [Discussions in Structural Molecular Biology. Annual Meeting of the Czech Society for Structural Biology /13./. 19.03.2015-21.03.2015, Nové Hrady] Institutional support: RVO:61388963 Keywords : drug design * SQM methods * binding Subject RIV: CF - Physical ; Theoretical Chemistry

  11. 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

  12. Future Challenges and Opportunities in Online Prescription Drug Promotion Research; Comment on “Trouble Spots in Online Direct-to-Consumer Prescription Drug Promotion: A Content Analysis of FDA Warning Letters”

    Directory of Open Access Journals (Sweden)

    Brian G. Southwell

    2016-03-01

    Full Text Available Despite increased availability of online promotional tools for prescription drug marketers, evidence on online prescription drug promotion is far from settled or conclusive. We highlight ways in which online prescription drug promotion is similar to conventional broadcast and print advertising and ways in which it differs. We also highlight five key areas for future research: branded drug website influence on consumer knowledge and behavior, interactive features on branded drug websites, mobile viewing of branded websites and mobile advertisements, online promotion and non-US audiences, and social media and medication decisions.

  13. Future Challenges and Opportunities in Online Prescription Drug Promotion Research Comment on "Trouble Spots in Online Direct-to-Consumer Prescription Drug Promotion: A Content Analysis of FDA Warning Letters".

    Science.gov (United States)

    Southwell, Brian G; Rupert, Douglas J

    2016-01-16

    Despite increased availability of online promotional tools for prescription drug marketers, evidence on online prescription drug promotion is far from settled or conclusive. We highlight ways in which online prescription drug promotion is similar to conventional broadcast and print advertising and ways in which it differs. We also highlight five key areas for future research: branded drug website influence on consumer knowledge and behavior, interactive features on branded drug websites, mobile viewing of branded websites and mobile advertisements, online promotion and non-US audiences, and social media and medication decisions. © 2016 by Kerman University of Medical Sciences.

  14. PROJECT AND ACTON STAGE OD DESIGNING FUTURE MUSIC TEACHERS’ ETHNOCULTURAL TRAINING

    Directory of Open Access Journals (Sweden)

    Xu Jiayu

    2017-04-01

    Full Text Available In the article the issue of developing future music teachers’ ethnocultural training in the process of their professional training is revealed. The author emphasizes on the relevance of the issue as future music teachers’ ethnocultural training contributes to, on the one hand, completing mastering the national system of cultural values of native people by students of higher musical educational institutions and, on the other hand, involving perception and understanding of other nations’ cultural values, allowing future music teachers to transmit values expressed by the young generation to their professional activity. It is reported that the main feature of future music teachers’ ethnocultural training is a system of ethnic and cultural values which is the background of musical and psychological-pedagogical and art training; it is actively engaged as value tools musical folk art and national art. Value methods that are involved in the process of training are methods of traditional pedagogy, as well as the basis of pedagogical communication – people’s ethics. It is noted that developing future music teachers’ ethnocultural training requires designing the special methodology. The constant items of this methodology are thought to be the forms, methods, techniques and means of pedagogical and ethnopedagogical impacts as tools for developing students’ ethnopedagogical thinking in the process of musical and pedagogical activities; the system of controlling future music teachers’ ethnopedagogical, ethnological, ethnomusical knowledge and skills as a combination of methods that enables an opportunity to compare the level of mastering the knowledge and skills at different stages of educational process; to organize tuition using innovative technologies. The special attention is paid to professional and active component of this methodology. The diagnostic tests according to the criterion of “a degree of professional effectiveness in

  15. 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...

  16. 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.

  17. Consumer Intervention Mapping—A Tool for Designing Future Product Strategies within Circular Product Service Systems

    Directory of Open Access Journals (Sweden)

    Matt Sinclair

    2018-06-01

    Full Text Available Re-distributed manufacturing presents a number of opportunities and challenges for New Product Development in a future Circular Economy. It has been argued that small-scale, flexible and localised production systems will reduce resource consumption, lower transport emissions and extend product lifetimes. At the same time smart products within the Internet of Things will gather and report data on user behaviour and product status. Many sustainable design tools have previously been developed but few are able to imagine and develop visions of how future sustainable product service systems might be manifested. This paper introduces the concept of Consumer Intervention Mapping as a tool for creating future product strategies. The tool visualises the points within a product’s lifecycle where stakeholders are able to intervene in the product’s expected journey. This perspective enables the rapid construction of scenarios that explore and describe future circular product service systems. Validation of the tool in three workshops is described and the outcomes are presented. Consumer Intervention Mapping is successful in creating scenarios that describe existing product service systems and new product concepts adapted to a Circular Economy paradigm. Further work is required to refine the tool’s performance in more focused and reflective design exercises.

  18. Neuromarketing techniques in pharmaceutical drugs advertising. A discussion and agenda for future research

    Science.gov (United States)

    Orzan, G; Zara, IA; Purcarea, VL

    2012-01-01

    Recent years have seen an “explosion" in the abilities of scientists to use neuroscience in new domains. Unfortunately, it is little known and reported on how advertising companies make more effective pharmaceutical drugs commercials. The purpose of this paper is to analyze how neuromarketing techniques may impact the consumer response to pharmaceutical advertising campaigns. The result shows that using neuromarketing methods a pharmaceutical company can better understand the conscious and unconscious consumer’s thoughts and tailor specific marketing messages. PMID:23346245

  19. Instrumentation and control of future sodium cooled fast reactors - Design improvements

    International Nuclear Information System (INIS)

    Madhusoodanan, K.; Sakthivel, M.; Chellapandi, P.

    2013-06-01

    India's fast reactor program started with the 40 MWt Fast Breeder Test Reactor. 500 MWe Prototype Fast Breeder Reactor (PFBR) is currently under construction at Kalpakkam. Safety of PFBR is enhanced by improved design features of I and C system. Since the design of Instrumentation and control (I and C) of PFBR, considerable improvements in terms of advancement in technology and indigenization has taken place. Further improvements in I and C is proposed for solving many of the difficulties faced during the design and construction phases of PFBR. Design improvements proposed are covered in this paper which will make the implementation and maintenance of I and C of future SFRs easier. (authors)

  20. Inherent safe design of advanced high temperature reactors - concepts for future nuclear power plants

    International Nuclear Information System (INIS)

    Hodzic, A.; Kugeler, K.

    1997-01-01

    This paper discusses the applicable solutions for a commercial size High Temperature Reactor (HTR) with inherent safety features. It describes the possible realization using an advanced concept which combines newly proposed design characteristics with some well known and proven HTR inherent safety features. The use of the HTR technology offers the conceivably best solution to meet the legal criteria, recently stated in Germany, for the future reactor generation. Both systems, block and pebble bed ,reactor, could be under certain design conditions self regulating in terms of core nuclear heat, mechanical stability and the environmental transfer. 23 refs., 7 figs

  1. Past, present, and future design of urban drainage systems with focus on Danish experiences

    DEFF Research Database (Denmark)

    Arnbjerg-Nielsen, Karsten

    2011-01-01

    over time? Based on an analysis of the underlying key drivers of changes that are expected to affect urban drainage systems the current problems and their predicted development over time are presented. One key issue is management of risk and uncertainties and therefore a framework for design......Climate change will influence the water cycle substantially, and extreme precipitation will become more frequent in many regions in the years to come. How should this fact be incorporated into design of urban drainage systems, if at all? And how important is climate change compared to other changes...... and analysis of urban structures in light of present and future uncertainties is presented....

  2. Rational design of new materials using recombinant structural proteins: Current state and future challenges.

    Science.gov (United States)

    Sutherland, Tara D; Huson, Mickey G; Rapson, Trevor D

    2018-01-01

    Sequence-definable polymers are seen as a prerequisite for design of future materials, with many polymer scientists regarding such polymers as the holy grail of polymer science. Recombinant proteins are sequence-defined polymers. Proteins are dictated by DNA templates and therefore the sequence of amino acids in a protein is defined, and molecular biology provides tools that allow redesign of the DNA as required. Despite this advantage, proteins are underrepresented in materials science. In this publication we investigate the advantages and limitations of using proteins as templates for rational design of new materials. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  3. The Swedish Utilities joint approach to form common basis for design requirements for the future

    International Nuclear Information System (INIS)

    Hansson, B.

    1998-01-01

    The Owners of the Swedish Nuclear Power Plants have decided to form a document that should state the design principals and requirement for cost-effective and continuous development of the reactor safety in the future. The development of this document will be a part of the modernization and development of the Swedish Nuclear Power Plants. The basis for this document is an evaluation of Swedish and International standards and regulations as IAEA/INSAG, US-regulations, EUR etc. (author)

  4. 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.

  5. A new roadmap for biopharmaceutical drug product development: Integrating development, validation, and quality by design.

    Science.gov (United States)

    Martin-Moe, Sheryl; Lim, Fredric J; Wong, Rita L; Sreedhara, Alavattam; Sundaram, Jagannathan; Sane, Samir U

    2011-08-01

    Quality by design (QbD) is a science- and risk-based approach to drug product development. Although pharmaceutical companies have historically used many of the same principles during development, this knowledge was not always formally captured or proactively submitted to regulators. In recent years, the US Food and Drug Administration has also recognized the need for more controls in the drug manufacturing processes, especially for biological therapeutics, and it has recently launched an initiative for Pharmaceutical Quality for the 21st Century to modernize pharmaceutical manufacturing and improve product quality. In the biopharmaceutical world, the QbD efforts have been mainly focused on active pharmaceutical ingredient processes with little emphasis on drug product development. We present a systematic approach to biopharmaceutical drug product development using a monoclonal antibody as an example. The approach presented herein leverages scientific understanding of products and processes, risk assessments, and rational experimental design to deliver processes that are consistent with QbD philosophy without excessive incremental effort. Data generated using these approaches will not only strengthen data packages to support specifications and manufacturing ranges but hopefully simplify implementation of postapproval changes. We anticipate that this approach will positively impact cost for companies, regulatory agencies, and patients, alike. Copyright © 2011 Wiley-Liss, Inc.

  6. Present and future etiological treatment of bacterial pneumonia 3. The antibacterial drugs under development

    Directory of Open Access Journals (Sweden)

    A.A. Abaturov

    2017-08-01

    Full Text Available The rapid spread of antibiotic-resistant bacterial strains necessitates the development of new antibacterial agents and a review of the guidelines for etiological treatment of bacterial infections, including pneumonia. Currently, new antibacterial agents are being developed that disrupt the biosynthesis of peptidoglycan, teichoic and lipoteichoic acids, and also block the attachment of virulent factors to the bacterial wall. New molecules of old classes of antibiotics and representatives of new classes of antibiotics with their targets (lipid II and III, teichoic and lipoteichoic acids, alanine racemase, and sortase A will become practical tools in clinical practice in the very near future. The goals and mechanisms of action of new antibacterial compounds predetermine their clinical prospects in future strategies for the treatment of infectious bacterial diseases.

  7. Colon-targeted oral drug delivery systems: design trends and approaches.

    Science.gov (United States)

    Amidon, Seth; Brown, Jack E; Dave, Vivek S

    2015-08-01

    Colon-specific drug delivery systems (CDDS) are desirable for the treatment of a range of local diseases such as ulcerative colitis, Crohn's disease, irritable bowel syndrome, chronic pancreatitis, and colonic cancer. In addition, the colon can be a potential site for the systemic absorption of several drugs to treat non-colonic conditions. Drugs such as proteins and peptides that are known to degrade in the extreme gastric pH, if delivered to the colon intact, can be systemically absorbed by colonic mucosa. In order to achieve effective therapeutic outcomes, it is imperative that the designed delivery system specifically targets the drugs into the colon. Several formulation approaches have been explored in the development colon-targeted drug delivery systems. These approaches involve the use of formulation components that interact with one or more aspects of gastrointestinal (GI) physiology, such as the difference in the pH along the GI tract, the presence of colonic microflora, and enzymes, to achieve colon targeting. This article highlights the factors influencing colon-specific drug delivery and colonic bioavailability, and the limitations associated with CDDS. Further, the review provides a systematic discussion of various conventional, as well as relatively newer formulation approaches/technologies currently being utilized for the development of CDDS.

  8. Rational design of dendrimer/lipid nanoassemblies in drug delivery for cancer chemotherapy

    Science.gov (United States)

    Sun, Qihang

    Nanocarriers can minimize the side effects and improve therapeutic efficacy of anticancer drugs. Although some success has been achieved via active or passive drug delivery to tumor cells, the known nanocarriers are far from satisfying therapeutic efficacy expectations. This is because they usually fail in one of the four crucial requirements, that is, to retain drug in blood circulation but release it reliably in tumor cells and to be stealthy in transport in circulation and tumor tissue but sticky upon arrival at the tumor cell. Therefore, the goal of this work is to fabricate nanoassemblies of dendrimers and lipids to address all these challenges. Particularly, nanoassemblies designed and prepared in this work are illustrated to improve the tumor tissue penetration. Examples of dendrimers synthesized in this work are water-insoluble, pH-dependent water-insoluble and water-soluble biodegradable polyester dendrimers. These dendrimers are shown to be encapsulated by commonly used fusogenic and long-circulating lipids to form reliable nanoassemblies. The dendrimer/lipid nanocarriers are used to demonstrate a cascade drug delivery. They are expected to be stable in circulation, due to their appropriately large size, but to release the drug-loaded dendrimers in tumor tissue. The released dendrimers carrying drugs are much smaller and hence expected to have a much deeper penetration throughout the tumor tissue.

  9. A Narrative Review of Potential Future Antidiabetic Drugs: Should We Expect More?

    Science.gov (United States)

    Chikara, Gaurav; Sharma, Pramod Kumar; Dwivedi, Pradeep; Charan, Jaykaran; Ambwani, Sneha; Singh, Surjit

    2018-04-01

    Prevalence of diabetes mellitus, a chronic metabolic disease characterized by hyperglycemia, is growing worldwide. The majority of the cases belong to type 2 diabetes mellitus (T2DM). Globally, India ranks second in terms of diabetes prevalence among adults. Currently available classes of therapeutic agents are used alone or in combinations but seldom achieve treatment targets. Diverse pathophysiology and the need of therapeutic agents with more favourable pharmacokinetic-pharmacodynamics profile make newer drug discoveries in the field of T2DM essential. A large number of molecules, some with novel mechanisms, are in pipeline. The essence of this review is to track and discuss these potential agents, based on their developmental stages, especially those in phase 3 or phase 2. Unique molecules are being developed for existing drug classes like insulins, DPP-4 inhibitors, GLP-1 analogues; and under newer classes like dual/pan PPAR agonists, dual SGLT1/SGLT2 inhibitors, glimins, anti-inflammatory agents, glucokinase activators, G-protein coupled receptor agonists, hybrid peptide agonists, apical sodium-dependent bile acid transporter (ASBT) inhibitors, glucagon receptor antagonists etc. The heterogeneous clinical presentation and therapeutic outcomes in phenotypically similar patients is a clue to think beyond the standard treatment strategy.

  10. Nonclinical safety biomarkers of drug-induced vascular injury: current status and blueprint for the future.

    Science.gov (United States)

    Mikaelian, Igor; Cameron, Mark; Dalmas, Deidre A; Enerson, Bradley E; Gonzalez, Raymond J; Guionaud, Silvia; Hoffmann, Peter K; King, Nicholas M P; Lawton, Michael P; Scicchitano, Marshall S; Smith, Holly W; Thomas, Roberta A; Weaver, James L; Zabka, Tanja S

    2014-06-01

    Better biomarkers are needed to identify, characterize, and/or monitor drug-induced vascular injury (DIVI) in nonclinical species and patients. The Predictive Safety Testing Consortium (PSTC), a precompetitive collaboration of pharmaceutical companies and the U.S. Food and Drug Administration (FDA), formed the Vascular Injury Working Group (VIWG) to develop and qualify translatable biomarkers of DIVI. The VIWG focused its research on acute DIVI because early detection for clinical and nonclinical safety monitoring is desirable. The VIWG developed a strategy based on the premise that biomarkers of DIVI in rat would be translatable to humans due to the morphologic similarity of vascular injury between species regardless of mechanism. The histomorphologic lexicon for DIVI in rat defines degenerative and adaptive findings of the vascular endothelium and smooth muscles, and characterizes inflammatory components. We describe the mechanisms of these changes and their associations with candidate biomarkers for which advanced analytical method validation was completed. Further development is recommended for circulating microRNAs, endothelial microparticles, and imaging techniques. Recommendations for sample collection and processing, analytical methods, and confirmation of target localization using immunohistochemistry and in situ hybridization are described. The methods described are anticipated to aid in the identification and qualification of translational biomarkers for DIVI. © 2014 by The Author(s).

  11. Demographic Subgroup Trends among Adolescents in the Use of Various Licit and Illicit Drugs, 1975-2016. Monitoring the Future Occasional Paper Series. Paper 88

    Science.gov (United States)

    Johnston, Lloyd D.; O'Malley, Patrick M.; Miech, Richard A.; Bachman, Jerald G.; Schulenberg, John E.

    2017-01-01

    This occasional paper presents national demographic subgroup data for the 1975-2016 Monitoring the Future (MTF) national survey results on 8th , 10th, and 12th graders' use of drugs, alcohol, and tobacco. MTF is funded by the National Institute on Drug Abuse at the National Institutes of Health under a series of investigator-initiated, competitive…

  12. Demographic Subgroup Trends among Adolescents in the Use of Various Licit and Illicit Drugs, 1975-2015. Monitoring the Future Occasional Paper Series. Paper 86

    Science.gov (United States)

    Johnston, Lloyd D.; O'Malley, Patrick M.; Miech, Richard A.; Bachman, Jerald G.; Schulenberg, John E.

    2016-01-01

    This occasional paper presents national demographic subgroup data for the 1975-2015 Monitoring the Future (MTF) national survey results on 8th, 10th, and 12th graders' use of drugs, alcohol, and tobacco. MTF is funded by the National Institute on Drug Abuse at the National Institutes of Health under a series of investigator-initiated, competitive…

  13. Demographic Subgroup Trends among Adolescents in the Use of Various Licit and Illicit Drugs, 1975-2014. Monitoring the Future Occasional Paper Series. Paper 83

    Science.gov (United States)

    Johnston, Lloyd D.; O'Malley, Patrick M.; Miech, Richard A.; Bachman, Jerald G.; Schulenberg, John E.

    2015-01-01

    This occasional paper presents national demographic subgroup data for the 1975-2014 Monitoring the Future (MTF) national survey results on 8th, 10th, and 12th graders' use of drugs, alcohol, and tobacco. MTF is funded by the National Institute on Drug Abuse at the National Institutes of Health under a series of investigator-initiated, competitive…

  14. 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.

  15. 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.

  16. Recent insights in nanotechnology-based drugs and formulations designed for effective anti-cancer therapy.

    Science.gov (United States)

    Piktel, Ewelina; Niemirowicz, Katarzyna; Wątek, Marzena; Wollny, Tomasz; Deptuła, Piotr; Bucki, Robert

    2016-05-26

    The rapid development of nanotechnology provides alternative approaches to overcome several limitations of conventional anti-cancer therapy. Drug targeting using functionalized nanoparticles to advance their transport to the dedicated site, became a new standard in novel anti-cancer methods. In effect, the employment of nanoparticles during design of antineoplastic drugs helps to improve pharmacokinetic properties, with subsequent development of high specific, non-toxic and biocompatible anti-cancer agents. However, the physicochemical and biological diversity of nanomaterials and a broad spectrum of unique features influencing their biological action requires continuous research to assess their activity. Among numerous nanosystems designed to eradicate cancer cells, only a limited number of them entered the clinical trials. It is anticipated that progress in development of nanotechnology-based anti-cancer materials will provide modern, individualized anti-cancer therapies assuring decrease in morbidity and mortality from cancer diseases. In this review we discussed the implication of nanomaterials in design of new drugs for effective antineoplastic therapy and describe a variety of mechanisms and challenges for selective tumor targeting. We emphasized the recent advantages in the field of nanotechnology-based strategies to fight cancer and discussed their part in effective anti-cancer therapy and successful drug delivery.

  17. Design and Synthesis of Self-Assembled Polymeric Nanoparticles for Cancer Drug Delivery

    Science.gov (United States)

    Logie, Jennifer

    Current chemotherapeutics are plagued by poor solubility and selectivity, requiring toxic excipients in formulations and causing a number of dose limiting side effects. Nanoparticle delivery has emerged as a strategy to more effectively deliver chemotherapeutics to the tumour site. Specifically, polymeric micelles enable the solubilization of hydrophobic small molecule drugs within the core and mitigate the necessity of excipients. Notwithstanding the significant progress made in polymeric micelle delivery, translation is limited by poor stability and low drug loading. In this work, a rational design approach is used to chemically modify poly(D,L-lactide-co-2-methyl-2-carboxytrimethylene carbonate)-graft-poly(ethylene glycol) (P(LA-co-TMCC)-g-PEG) in order to overcome these limitations and effectively deliver drug to tumours. The PEG density of the polymer system was optimized to enhance the stability of our polymeric micelles. Higher PEG densities permitted the lyophilization of micelles and enhanced the serum stability of the system. To increase the drug loading of our system, we facilitated specific intermolecular interactions within the micelle core. For drugs that form colloidal aggregates, such as pentyl-PABC doxazolidine, polymers were used to stabilize the colloidal core against aggregation and protein adsorption. For more challenging molecules, where self-assembly cannot be controlled, such as docetaxel, we modified the polymeric backbone with a peptide from the binding site of the drug to achieve loadings five times higher than those achieved in conventional micelle systems. This novel docetaxel nanoparticle was assessed in vivo in an orthotopic mouse model of breast cancer, where it showed a wider therapeutic index than the conventional ethanolic polysorbate 80 formulation. The improved tolerability of this formulation enabled higher dosing regimens and led to heightened efficacy and survival in this mouse model. Combined, these studies validated P

  18. Crystals of Human Serum Albumin for Use in Genetic Engineering and Rational Drug Design

    Science.gov (United States)

    Carter, Daniel C. (Inventor)

    1994-01-01

    This invention pertains to crystals of serum albumin and processes for growing them. The purpose of the invention is to provide crystals of serum albumin which can be studied to determine binding sites for drugs. Form 2 crystals grow in the monoclinic space P2(sub 1), and possesses the following unit cell constraints: a = 58.9 +/- 7, b = 88.3 +/- 7, c = 60.7 +/- 7, Beta = 101.0 +/- 2 degrees. One advantage of the invention is that it will allow rational drug design

  19. Consequences for designer and manufacturer of mechanical components due to future requirements in Europe

    International Nuclear Information System (INIS)

    Hans-Joachim, Frank

    2001-01-01

    In the frame of European harmonization, a lot of changes on requirements for designer and manufacturer of mechanical components have been performed. Differed organizations are involved in preparing future requirements for nuclear application. On one side the French German cooperation on the development of EPR. At the origin of this project was the common decision in 1989 of Framatome and Siemens to cooperate through NPI, to design the Nuclear Island, which meets the future needs of utilities. EDF and a group of the main German Utilities joined this cooperation in 1991 and since then they have been totally involved to the progress of the work. In addition, all the process was backed up to the end by the strong cooperation between the French and the German. Safety Authorities, which have a long lasting cooperation to define common requirements, which have to be applied to future Nuclear Power Plants. Furthermore an organization has been set up to elaborate common codes related to the EPR design, at the level of the French design and construction rules (RCC) or the German KTA safety standards, the so-called EPR technical codes (ETC). On the other side, the European utilities co-operate on a much broader basis for the establishment of European Utilities Requirements (EUR). These requirements are prepared by a group of European utilities that represent the major European electricity generating companies that are determined to keep the nuclear option open. The technical requirements specified in the EUR document define the boundaries in which future plants need to be designed in order to be acceptable for the needs of the utilities and in order to fulfill the basic requirements of competitive power generation costs and licensability in all countries represented in the EUR group. All the new requirements have to be applied by designer and manufacturer. Siemens /SNP act as a designer of a lot of various vessels and tanks, heat exchangers and other items of process

  20. Risk-informed assessment of regulatory and design requirements for future nuclear power plants. Annual report

    International Nuclear Information System (INIS)

    2000-01-01

    OAK B188 Risk-informed assessment of regulatory and design requirements for future nuclear power plants. Annual report. The overall goal of this research project is to support innovation in new nuclear power plant designs. This project is examining the implications, for future reactors and future safety regulation, of utilizing a new risk-informed regulatory system as a replacement for the current system. This innovation will be made possible through development of a scientific, highly risk-formed approach for the design and regulation of nuclear power plants. This approach will include the development and/or confirmation of corresponding regulatory requirements and industry standards. The major impediment to long term competitiveness of new nuclear plants in the U.S. is the capital cost component--which may need to be reduced on the order of 35% to 40% for Advanced Light Water Reactors (ALWRS) such as System 80+ and Advanced Boiling Water Reactor (ABWR). The required cost reduction for an ALWR such as AP600 or AP1000 would be expected to be less. Such reductions in capital cost will require a fundamental reevaluation of the industry standards and regulatory bases under which nuclear plants are designed and licensed. Fortunately, there is now an increasing awareness that many of the existing regulatory requirements and industry standards are not significantly contributing to safety and reliability and, therefore, are unnecessarily adding to nuclear plant costs. Not only does this degrade the economic competitiveness of nuclear energy, it results in unnecessary costs to the American electricity consumer. While addressing these concerns, this research project will be coordinated with current efforts of industry and NRC to develop risk-informed, performance-based regulations that affect the operation of the existing nuclear plants; however, this project will go further by focusing on the design of new plants

  1. A Generic Approach to Analyze the Impact of a Future Aircraft Design on the Boarding Process

    Directory of Open Access Journals (Sweden)

    Bekir Yildiz

    2018-01-01

    Full Text Available The turnaround process constitutes an important part of the air transportation system. Airports often represent bottlenecks in air traffic management (ATM, thus operations related to the preparation of the aircraft for the next flight leg have to be executed smoothly and in a timely manner. The ATM significantly depends on a reliable turnaround process. Future paradigm changes with respect to airplane energy sources, aircraft design or propulsion concepts will also influence the airport layout. As a consequence, operational processes associated with the turnaround will be affected. Airlines aim for efficient and timely turnaround operations that are correlated with higher profits. This case study discusses an approach to investigate a new aircraft design with respect to the implications on the turnaround. The boarding process, as part of the turnaround, serves as an example to evaluate the consequences of new design concepts. This study is part of an interdisciplinary research to investigate future energy, propulsion and designs concepts and their implications on the whole ATM system. Due to these new concepts, several processes of the turnaround will be affected. For example, new energy storage concepts will influence the fueling process on the aircraft itself or might lead to a new infrastructure at the airport. This paper aims to evaluate the applied methodology in the case of a new boarding process, due to a new aircraft design, by means of a generic example. An agent-based boarding simulation is applied to assess passenger behavior during boarding, particularly with regard to cabin layout and seat configuration. The results of the generic boarding simulation are integrated into a simplified, deterministic and generic simulation of the turnaround process. This was done to assess the proposed framework for future investigations which on the one hand address the ATM system holistically and on the other, incorporate additional or adapted

  2. Risk-informed assessment of regulatory and design requirements for future nuclear power plants. Annual report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-08-01

    OAK B188 Risk-informed assessment of regulatory and design requirements for future nuclear power plants. Annual report. The overall goal of this research project is to support innovation in new nuclear power plant designs. This project is examining the implications, for future reactors and future safety regulation, of utilizing a new risk-informed regulatory system as a replacement for the current system. This innovation will be made possible through development of a scientific, highly risk-formed approach for the design and regulation of nuclear power plants. This approach will include the development and/or confirmation of corresponding regulatory requirements and industry standards. The major impediment to long term competitiveness of new nuclear plants in the U.S. is the capital cost component--which may need to be reduced on the order of 35% to 40% for Advanced Light Water Reactors (ALWRS) such as System 80+ and Advanced Boiling Water Reactor (ABWR). The required cost reduction for an ALWR such as AP600 or AP1000 would be expected to be less. Such reductions in capital cost will require a fundamental reevaluation of the industry standards and regulatory bases under which nuclear plants are designed and licensed. Fortunately, there is now an increasing awareness that many of the existing regulatory requirements and industry standards are not significantly contributing to safety and reliability and, therefore, are unnecessarily adding to nuclear plant costs. Not only does this degrade the economic competitiveness of nuclear energy, it results in unnecessary costs to the American electricity consumer. While addressing these concerns, this research project will be coordinated with current efforts of industry and NRC to develop risk-informed, performance-based regulations that affect the operation of the existing nuclear plants; however, this project will go further by focusing on the design of new plants.

  3. Oxcarbazepine: Drug of the future in the treatment of trigeminal neuralgia

    Directory of Open Access Journals (Sweden)

    Revant H Chole

    2011-01-01

    Full Text Available Background: The aim of the study was to estimate the efficacy of oxcarbazepine in trigeminal neuralgia. Oxcarbazepine is a novel antiepilepfic drug, and its effect on trigeminal neuralgia has not been studied extensively previously. Materials and methods: Fifty-three patients with trigeminal neuralgia (34 men and 19 women took a mean dose of 600 mg of oxcarbazepine for a period of three weeks. Pain intensity was measured by using visual analog scale. Results: Of the 53 patients, 42 (79% were completely or well controlled by OXC, and nine (17% partially but acceptably controlled. Treatment with OXC was therefore satisfactory initially in 51 (96% of the patients. In seven of these patients, mild transient side effects occurred but did not necessitate cessation of treatment Conclusion: OXC appears to be an effective substitute for carbamazepine in those patients intolerant of this agent, or experiencing significant side effects.

  4. The Future of Organization Design: An Interpretative Synthesis in Three Themes

    Directory of Open Access Journals (Sweden)

    Richard M. Burton

    2013-04-01

    Full Text Available In the inaugural issue of the Journal of Organization Design (Vol. 1, #1, 2012, noted scholars and experienced practitioners presented their views on the future of organization design. The seven wise and provocative statements were subsequently discussed by members of the Organizational Design Community at a conference held at Harvard University on August 3, 2012. I was asked by JOD to monitor the discussion and identify the broad organization design themes that emerged. Although the discussion was wide ranging, three themes were noticeable. The first theme is that there are fundamentals of organization design, and all agreed that design involves creating a cohesive socio-technical system from a number of constituent elements. The second theme is that the boundaries of many newer organizational forms extend beyond that of the single firm, so the scope of organization design needs to expand to include ecosystems, collaborative communities, industries, and other supra-firm architectures. The third theme involves time and change, requiring a shift in focus from how organizations become stable and predictable to how they can become more agile.

  5. Design and characterisation of matrix tablets of highly water soluble drug

    Directory of Open Access Journals (Sweden)

    Vijayalakshmi Prakya

    2012-04-01

    Full Text Available Tramadol HCL is a centrally acting opioid analgesic. Although the drug has a higher plasma half life, the steady state plasma concentration is not achieved with frequent dosing of q.i.d at 6 hour intervals. Therefore, the objective of the present work was to formulate a 100mg strength Tramadol matrix tablets to extend the drug release and thus decrease the dosing frequency and achieve steady state plasma concentration. Initially, preformulation studies were carried out to rule out any incompatibility between the drug and the chosen polymer(s after exposing physical mixtures of the drug and the polymer(s to 40 and deg;C/75% RH for three months. A suitable method was developed for drug estimation at 271nm by a UV double beam spectrophotometer. Next, various batches of tablets were designed using different polymers such as Ethylcellulose, Carnauba wax, HPMC-K100M, Carbopol-974P and Kollidon-SR. Direct compression technique was used except for the formulation containing carnauba wax for which melt granulation was done followed by compression. Formulations F-1 to F-15 contained single polymers in increasing concentrations in drug:polymer ratios of 1:1, 1:2 and 1:3 where it was observed that the drug release extended with increasing polymer concentrations. Carbopol-974P extended drug release better followed by HPMC-K100M and Carnauba wax compared to other polymers. A combination of these polymers was also used at various ratios to get formulations F-16 to F-20 and observed that the polymer combinations controlled drug release better. The type of fillers like lactose and microcrystalline cellulose had no effect on the physiochemical characters as well as on the drug release profiles. The in vitro release data from the best formulation fitted well in Higuchi as well as Peppas model, the and #8216;n and #8217; value, which confirmed that the release mechanism shifted from initial dissolution to later extended diffusion in which both diffusion and erosion

  6. Future aircraft cabins and design thinking: optimisation vs. win-win scenarios

    Directory of Open Access Journals (Sweden)

    A. Hall

    2013-06-01

    Full Text Available With projections indicating an increase in mobility over the next few decades and annual flight departures expected to rise to over 16 billion by 2050, there is a demand for the aviation industry and associated stakeholders to consider new forms of aircraft and technology. Customer requirements are recognized as a key driver in business. The airline is the principal customer for the aircraft manufacture. The passenger is, in turn, the airline's principal customer but they are just one of several stakeholders that include aviation authorities, airport operators, air-traffic control and security agencies. The passenger experience is a key differentiator used by airlines to attract and retain custom and the fuselage that defines the cabin envelope for the in-flight passenger experience and cabin design therefore receives significant attention for new aircraft, service updates and refurbishments. Decision making in design is crucial to arriving at viable and worthwhile cabin formats. Too little innovation will result in an aircraft manufacturer and airlines using its products falling behind its competitors. Too much may result in an over-extension with, for example, use of immature technologies that do not have the necessary reliability for a safety critical industry or sufficient value to justify the development effort. The multiple requirements associated with cabin design, can be viewed as an area for optimisation, accepting trade-offs between the various parameters. Good design, however, is often defined as developing a concept that resolves the contradictions and takes the solution towards a win-win scenario. Indeed our understanding and practice of design allows for behaviors that enhance design thinking through divergence and convergence, the use of abductive reasoning, experimentation and systems thinking. This paper explores and defines the challenges of designing the aircraft cabin of the future that will deliver on the multiple

  7. Metabolism-Activated Multitargeting (MAMUT): An Innovative Multitargeting Approach to Drug Design and Development.

    Science.gov (United States)

    Mátyus, Péter; Chai, Christina L L

    2016-06-20

    Multitargeting is a valuable concept in drug design for the development of effective drugs for the treatment of multifactorial diseases. This concept has most frequently been realized by incorporating two or more pharmacophores into a single hybrid molecule. Many such hybrids, due to the increased molecular size, exhibit unfavorable physicochemical properties leading to adverse effects and/or an inappropriate ADME (absorption, distribution, metabolism, and excretion) profile. To avoid this limitation and achieve additional therapeutic benefits, here we describe a novel multitargeting strategy based on the synergistic effects of a parent drug and its active metabolite(s). The concept of metabolism-activated multitargeting (MAMUT) is illustrated using a number of examples. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Design of shared unit-dose drug distribution network using multi-level particle swarm optimization.

    Science.gov (United States)

    Chen, Linjie; Monteiro, Thibaud; Wang, Tao; Marcon, Eric

    2018-03-01

    Unit-dose drug distribution systems provide optimal choices in terms of medication security and efficiency for organizing the drug-use process in large hospitals. As small hospitals have to share such automatic systems for economic reasons, the structure of their logistic organization becomes a very sensitive issue. In the research reported here, we develop a generalized multi-level optimization method - multi-level particle swarm optimization (MLPSO) - to design a shared unit-dose drug distribution network. Structurally, the problem studied can be considered as a type of capacitated location-routing problem (CLRP) with new constraints related to specific production planning. This kind of problem implies that a multi-level optimization should be performed in order to minimize logistic operating costs. Our results show that with the proposed algorithm, a more suitable modeling framework, as well as computational time savings and better optimization performance are obtained than that reported in the literature on this subject.

  9. 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.

  10. 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.

  11. Licensing process for future applications of advanced-design nuclear reactors

    International Nuclear Information System (INIS)

    Miller, C.L.

    1990-01-01

    The existing 10CFR50 two-step licensing process in the Code of Federal Regulations can continue to be a viable licensing vehicle for future applications, at least for the near future. The US Nuclear Regulatory Commission (NRC) Commissioners and staff, the public, and the utilities (along with supporting architect/engineers and nuclear steam supply system vendors) have a vast body of experience and knowledge of the existing part 50 licensing process. All these participants are familiar with their respective roles in this process, and history shows this process to be a workable licensing vehicle. Nevertheless, the use of 10CFR52 should be encouraged for future applications. This proposed new rule is intended to achieve the early resolution of licensing issues, to reduce the complexity and uncertainty of the licensing process, and enhance the safety and reliability of nuclear power plants. Part 52's overall purpose is to improve reactor safety and streamline the licensing process by encouraging the use of standard reactor designs and by allowing the early resolution of site environmental and reactor safety issues. The public should be afforded an earlier entry into the licensing process as a result of design certification rulemaking process and combined construction permit/operating license hearings

  12. Physiological and biochemical response of plants to engineered NMs: Implications on future design.

    Science.gov (United States)

    de la Rosa, Guadalupe; García-Castañeda, Concepción; Vázquez-Núñez, Edgar; Alonso-Castro, Ángel Josabad; Basurto-Islas, Gustavo; Mendoza, Ángeles; Cruz-Jiménez, Gustavo; Molina, Carlos

    2017-01-01

    Engineered nanomaterials (ENMs) form the basis of a great number of commodities that are used in several areas including energy, coatings, electronics, medicine, chemicals and catalysts, among others. In addition, these materials are being explored for agricultural purposes. For this reason, the amount of ENMs present as nanowaste has significantly increased in the last few years, and it is expected that ENMs levels in the environment will increase even more in the future. Because plants form the basis of the food chain, they may also function as a point-of-entry of ENMs for other living systems. Understanding the interactions of ENMs with the plant system and their role in their potential accumulation in the food chain will provide knowledge that may serve as a decision-making framework for the future design of ENMs. The purpose of this paper was to provide an overview of the current knowledge on the transport and uptake of selected ENMs, including Carbon Based Nanomaterials (CBNMs) in plants, and the implication on plant exposure in terms of the effects at the macro, micro, and molecular level. We also discuss the interaction of ENMs with soil microorganisms. With this information, we suggest some directions on future design and areas where research needs to be strengthened. We also discuss the need for finding models that can predict the behavior of ENMs based on their chemical and thermodynamic nature, in that few efforts have been made within this context. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  13. 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.

  14. Natural extracellular nanovesicles and photodynamic molecules: is there a future for drug delivery?

    Science.gov (United States)

    Kusuzaki, Katsuyuki; Matsubara, Takao; Murata, Hiroaki; Logozzi, Mariantonia; Iessi, Elisabetta; Di Raimo, Rossella; Carta, Fabrizio; Supuran, Claudiu T; Fais, Stefano

    2017-12-01

    Photodynamic molecules represent an alternative approach for cancer therapy for their property (i) to be photo-reactive; (ii) to be not-toxic for target cells in absence of light; (iii) to accumulate specifically into tumour tissues; (iv) to be activable by a light beam only at the tumour site and (v) to exert cytotoxic activity against tumour cells. However, to date their clinical use is limited by the side effects elicited by systemic administration. Extracellular vesicles are endogenous nanosized-carriers that have been recently introduced as a natural delivery system for therapeutic molecules. We have recently shown the ability of human exosomes to deliver photodynamic molecules. Therefore, this review focussed on extracellular vesicles as a novel strategy for the delivery of photodynamic molecules at cancer sites. This completely new approach may enhance the delivery and decrease the toxicity of photodynamic molecules, therefore, represent the future for photodynamic therapy for cancer treatment.

  15. Resolution V fractional factorial Design for Screening of factors affecting weakly basic drugs liposomal systems.

    Science.gov (United States)

    El-Helaly, Sara Nageeb; Habib, Basant A; Abd El-Rahman, Mohamed K

    2018-04-21

    This study aims to investigate factors affecting weakly basic drugs liposomal systems. Resolution V fractional factorial design (2 V 5-1 ) is used as an example of screening designs that would better be used as a wise step before proceeding with detailed factors effects or optimization studies. Five factors probable to affect liposomal systems of weakly basic drugs were investigated using Amisulpride as a model drug. Factors studied were; A: Preparation technique B: Phosphatidyl choline (PhC) amount (mg) C: Cholesterol: PhC molar ratio, D: Hydration volume (ml) and E: Sonication type. Levels investigated were; Ammonium sulphate-pH gradient technique or Transmembrane zinc chelation-pH gradient technique, 200 or 400 mg, 0 or 0.5, 10 or 20 ml and bath or probe sonication for A, B, C, D and E respectively. Responses measured were Particle size (PS) (nm), Zeta potential (ZP) (mV) and Entrapment efficiency percent (EE%). Ion selective electrode was used as a novel method for measuring unentrapped drug concentration and calculating entrapment efficiency without the need for liposomal separation. Factors mainly affecting the studied responses were Cholesterol: PhC ratio and hydration volume for PS, preparation technique for ZP and preparation technique and hydration volume for EE%. The applied 2 V 5-1 design enabled the use of only 16 trial combinations for screening the influence of five factors on weakly basic drugs liposomal systems. This clarifies the value of the use of screening experiments before extensive investigation of certain factors in detailed optimization studies. Copyright © 2017. Published by Elsevier B.V.

  16. 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...

  17. 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...

  18. Synthesis of mesoporous silica nanoparticles by sol–gel as nanocontainer for future drug delivery applications

    Energy Technology Data Exchange (ETDEWEB)

    Vazquez, N.I.; Gonzalez, Z.; Ferrari, B.; Castro, Y.

    2017-07-01

    Development of mesoporous silica nanoparticles as carriers for drug delivery systems has increased exponentially during the last decade. The present work is focused on the synthesis of silica carriers by sol–gel from tetraethyl orthosilicate (TEOS) as precursor of silica and cetyltrimethylammonium bromide (CTAB) as pore generating agent. The synthesis conditions were modified varying the molar ratio of water/TEOS, NH3/TEOS and amount of CTAB. The silica particles were characterized by scan electron microscopy techniques (FESEM), high resolution transmission electron microscopy (HR-TEM), N2 adsorption–desorption isotherms, Zeta-potential and Dynamic Light Scattering (DLS). The results show that the specific surface area and the porosity of silica particles were strongly affected by the addition of CTAB and the amount of H2O. The dispersion and stability of silica mesoporous particles is achieved in spite of the high surface reactivity. The synthesis formulation affects considerably to the particle morphology, which changes from spheres to rods when the molar ratio of H2O increases. A maximum specific surface area of 1480m2/g was obtained with pore sizes ranging 2.5–2.8nm. (Author)

  19. 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.

  20. Self nano-emulsifying drug delivery system for Embelin: Design, characterization and in-vitro studies

    Directory of Open Access Journals (Sweden)

    Komal Parmar

    2015-10-01

    Full Text Available CThe objective of the present study was to prepare solid self-nanoemulsifying drug delivery system (S-SNEDDS containing Capryol-90 as oil phase for the delivery of Embelin, a poorly water soluble herbal active ingredient. Box-Behnken experimental design was employed to optimise the formulation variables, X1 (amount of oil; Capryol 90, X2 (amount of surfactant; Acrysol EL 135 and X3 (amount of co-surfactant; PEG 400. Systems were appraised for visual characteristics for self emulsifying time, globule size and drug release. Optimised liquid formulations were formulated into free flowing granules (S-SNEDDS by adsorption on the porous materials like Aerosil 200 and Neusilin and thereby compressed into tablet. In vitro dissolution studies of SNEDDS revealed increased in the dissolution rate of the drug. FT-IR data revealed no physicochemical interaction between drug and excipients. Solid state characterization of S-SNEDDS by DSC and Powder XRD confirmed reduction in drug crystallinity which further supports the results of dissolution studies. TEM analysis exhibited spherical globules. Further, the accelerated stability studies for 6 months revealed that S-SNEDDS of Embelin are found to be stable without any significant change in physicochemical properties. Thus, the present studies demonstrated dissolution enhancement potential of porous carrier based S-SNEDDS for poorly water soluble herbal active ingredient, Embelin.

  1. The solubility-permeability interplay and oral drug formulation design: Two heads are better than one.

    Science.gov (United States)

    Dahan, Arik; Beig, Avital; Lindley, David; Miller, Jonathan M

    2016-06-01

    Poor aqueous solubility is a major challenge in today's biopharmaceutics. While solubility-enabling formulations can significantly increase the apparent solubility of the drug, the concomitant effect on the drug's apparent permeability has been largely overlooked. The mathematical equation to describe the membrane permeability of a drug comprises the membrane/aqueous partition coefficient, which in turn is dependent on the drug's apparent solubility in the GI milieu, suggesting that the solubility and the permeability are closely related, exhibit a certain interplay between them, and treating the one irrespectively of the other may be insufficient. In this article, an overview of this solubility-permeability interplay is provided, and the available data is analyzed in the context of the effort to maximize the overall drug exposure. Overall, depending on the type of solubility-permeability interplay, the permeability may decrease, remain unchanged, and even increase, in a way that may critically affect the formulation capability to improve the overall absorption. Therefore, an intelligent design of solubility-enabling formulation needs to consider both the solubility afforded by the formulation and the permeability in the new luminal environment resulting from the formulation. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. [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.

  3. Analysis and Design of the Cryogenic System of the Future Circular Collider

    CERN Document Server

    Kotnig, Claudio; Brenn, Günter

    Particle colliders are today's most advanced tools to perform particle physics experiments and penetrate the mysteries of matter. The largest existing particle collider, the LHC, is about to reach its technical limits and the particle physics society has to decide which future machine will enable the successful research to gain new knowledge. One option is the superconducting Future Circular Collider (FCC), which would exceed the LHC's size and generated particle energies by far. The enormous particle energies call for high magnetic fields, which only can be created reliably and economically by special superconducting materials at cryogenic temperature level. The intelligent design of the cryogenic distribution and discharge system to sustain the thermodynamic state of the superconducting electromagnets is the basis for an efficient and functional refrigeration and consequently for the physics experiments themselves. Several requirements and constraints limit the technical possibilities and the cryogenic syst...

  4. Design of inhibitors of thymidylate kinase from Variola virus as new selective drugs against smallpox.

    Science.gov (United States)

    Guimarães, Ana P; de Souza, Felipe R; Oliveira, Aline A; Gonçalves, Arlan S; de Alencastro, Ricardo B; Ramalho, Teodorico C; França, Tanos C C

    2015-02-16

    Recently we constructed a homology model of the enzyme thymidylate kinase from Variola virus (VarTMPK) and proposed it as a new target to the drug design against smallpox. In the present work, we used the antivirals cidofovir and acyclovir as reference compounds to choose eleven compounds as leads to the drug design of inhibitors for VarTMPK. Docking and molecular dynamics (MD) studies of the interactions of these compounds inside VarTMPK and human TMPK (HssTMPK) suggest that they compete for the binding region of the substrate and were used to propose the structures of ten new inhibitors for VarTMPK. Further docking and MD simulations of these compounds, inside VarTMPK and HssTMPK, suggest that nine among ten are potential selective inhibitors of VarTMPK. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  5. 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.

  6. LEGO-inspired drug design: Discovery of novel fungal Plasma membrane H+-ATPase (Pma1) inhibitors from small molecule libraries: An introduction of HFSA-SBS_DOS-RD strategy in drug discovery

    DEFF Research Database (Denmark)

    Tung, Truong Thanh; Dao, Trong Tuan; Palmgren, Michael B.

    to extracellular, this enzyme generates a transmembrane electrochem. gradient, as a consequence, fungi can uptake nutrients by secondary transport systems. Until now, only low resoln. of protein structure has been reported, and notably there a no report of co-crystal structure of Pma1 with inhibitors. Therefore......-oriented synthesis (SBS_DOS) and rational design (RD), so called HFSA-SBS_DOS-RD strategy in drug discovery and development process. Using HFSA-SBS_DOS-RD, our group successfully designed, synthesized, and performed SAR studies of novel compds. potent Pma1 inhibitors. An expeditious, high yield and scalable...... microwave-assisted synthesis was developed and applied for synthesis of library compds. To our delight, ours compd. libraries were able to inhibit Pma1 activity and growth inhibitory activity of C. albican and S. cerevisiae revealed the most promising example for future development of antifungal drugs...

  7. Studies on novel drug development using developing chick embryo and its future aspect

    International Nuclear Information System (INIS)

    Abe, Chiaki; Uto, Yoshihiro; Hori, Hitoshi; Endo, Yoshio

    2011-01-01

    Described is the use of developing chick embryo (DCE), an advantageous alternative experimental animal, in studies on development of novel drugs like radio-sensitizer and on toxicological evaluation. Authors have established DCE transplanted with mouse mammary gland tumor EMT6/KU cells and have found that etanidazole, a radio-sensitizing nitroimidazole derivative, exerts the significant tumor shrinking activity in this tumor-bearing DCE when irradiated by 8 Gy X-ray. They are to test the sensitizing activity of their synthetic nitroimidazole derivatives and other structure-related sensitizers like clinically used (in Denmark) nimorazole. In addition, as the antioxidant activity in vivo can be hardly tested, authors are trying to make DCE system for it since they have studied the activity of derivatives of artepillin C, an active principle of propolis. They are also using DCE chorioallantoic membrane (CAM) for testing the anti-angiogenic activity aiming to develop an antitumor agent from compounds related to fingolimod (FTY-720). For the test of anti-tumor activity in various cell types, their observation is that some of tumor cell types cannot take in DCE. Recently DCE has been used in toxicology for prediction of cardiovascular system like bradycardia and QT elongation, and for lethality test. Hen's egg test-CAM (HET-CAM) and cultured cell system to test irritation are reported to be more valid than other standard methods. DCE system is simple, inexpensive, and unnecessary for particular equipment and facility and desirably becomes an alternative experimental animal next to those like zebra-fish, rat and mouse. (author)

  8. The Semiempirical Quantum Mechanical Scoring Function for In Silico Drug Design

    Czech Academy of Sciences Publication Activity Database

    Lepšík, Martin; Řezáč, Jan; Kolář, Michal; Pecina, Adam; Hobza, Pavel; Fanfrlík, Jindřich

    2013-01-01

    Roč. 78, č. 9 (2013), s. 921-931 ISSN 2192-6506 R&D Projects: GA ČR GBP208/12/G016 Grant - others:Operational Program Research and Development for Innovations(XE) CZ 1.05/2.1.00/03/0058 Institutional support: RVO:61388963 Keywords : computational chemistry * drug design * noncovalent interactions * quantum chemistry * semiempirical calculations Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.242, year: 2013

  9. 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.

  10. 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

  11. New design of cable-in-conduit conductor for application in future fusion reactors

    Science.gov (United States)

    Qin, Jinggang; Wu, Yu; Li, Jiangang; Liu, Fang; Dai, Chao; Shi, Yi; Liu, Huajun; Mao, Zhehua; Nijhuis, Arend; Zhou, Chao; Yagotintsev, Konstantin A.; Lubkemann, Ruben; Anvar, V. A.; Devred, Arnaud

    2017-11-01

    The China Fusion Engineering Test Reactor (CFETR) is a new tokamak device whose magnet system includes toroidal field, central solenoid (CS) and poloidal field coils. The main goal is to build a fusion engineering tokamak reactor with about 1 GW fusion power and self-sufficiency by blanket. In order to reach this high performance, the magnet field target is 15 T. However, the huge electromagnetic load caused by high field and current is a threat for conductor degradation under cycling. The conductor with a short-twist-pitch (STP) design has large stiffness, which enables a significant performance improvement in view of load and thermal cycling. But the conductor with STP design has a remarkable disadvantage: it can easily cause severe strand indentation during cabling. The indentation can reduce the strand performance, especially under high load cycling. In order to overcome this disadvantage, a new design is proposed. The main characteristic of this new design is an updated layout in the triplet. The triplet is made of two Nb3Sn strands and one soft copper strand. The twist pitch of the two Nb3Sn strands is large and cabled first. The copper strand is then wound around the two superconducting strands (CWS) with a shorter twist pitch. The following cable stages layout and twist pitches are similar to the ITER CS conductor with STP design. One short conductor sample with a similar scale to the ITER CS was manufactured and tested with the Twente Cable Press to investigate the mechanical properties, AC loss and internal inspection by destructive examination. The results are compared to the STP conductor (ITER CS and CFETR CSMC) tests. The results show that the new conductor design has similar stiffness, but much lower strand indentation than the STP design. The new design shows potential for application in future fusion reactors.

  12. Ayurveda and botanical drugs for epilepsy: Current evidence and future prospects.

    Science.gov (United States)

    Sriranjini, Sitaram Jaideep; Sandhya, Kumar; Mamta, Vernekar Sanjeeva

    2015-11-01

    The understanding of epilepsy has progressed since its earliest impression as a disease associated with paranormal and superstitious beliefs. Landmark advances have been made in deciphering the pathophysiological substrates involved in the disease process, and treatment advances have contributed significantly to ameliorating the seizures. However, disease-modifying agents are yet to be discovered. Ayurveda is a system of medicine that stresses a holistic approach to disease, and treatment is focused on disease modification and symptom management. Herbs form the core of Ayurveda medicine; though many of them have been studied for their anticonvulsant activity, very few actually mention the reference of these herbs in Ayurveda literature. Other therapeutic interventions used in Ayurveda are relatively unexplored, and future research will need to focus on this. The current manuscript briefly discusses the understanding of epilepsy as per Ayurveda and reviews herbs that have been studied for their anticonvulsant activity mentioned in Ayurveda literature. This article is part of a Special Issue entitled "Botanicals for Epilepsy". Copyright © 2015 Elsevier Inc. All rights reserved.

  13. [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.

  14. Protein folding and non-conventional drug design: a primer for nuclear structure physicists

    International Nuclear Information System (INIS)

    Broglia, R.A.; Tiana, G.; Provasi, D.

    2004-01-01

    Some of the paradigms emerging from the study of the phenomena of phase transitions in finite many-body systems, like e.g. the atomic nucleus can be used at profit to solve the protein folding problem within the framework of simple (although not oversimplified) models. From this solution a paradigm emerges for the design of non-conventional drugs, which inhibit enzymatic action without inducing resistance (mutations). The application of these concepts to the design of an inhibitor to the HIV-protease central in the life cycle of the HIV virus is discussed

  15. Experimental Design for CMIP6: Aerosol, Land Use, and Future Scenarios Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Arnott, James [AGCI

    2015-10-30

    The Aspen Global Change Institute hosted a technical science workshop entitled, “Experimental design for CMIP6: Aerosol, Land Use, and Future Scenarios,” on August 3-8, 2014 in Aspen, CO. Claudia Tebaldi (NCAR) and Brian O’Neill (NCAR) served as co-chairs for the workshop. The Organizing committee also included Dave Lawrence (NCAR), Jean-Francois Lamarque (NCAR), George Hurtt (University of Maryland), & Detlef van Vuuren (PBL Netherlands Environmental Change). The meeting included the participation of 22 scientists representing many of the major climate modeling centers for a total of 110 participant days.

  16. Prescription drug advertising, disease knowledge, and older adults' optimistic bias about the future risk of Alzheimer's disease.

    Science.gov (United States)

    Park, Jin Seong; Ju, Ilwoo

    2016-01-01

    This study aims to broaden the scope of knowledge on the role of direct-to-consumer prescription drug advertising (DTCA) in the construction of consumers' optimistic bias regarding health issues and their intentions for coping actions. Based on an online survey of U.S. adults aged 65 years or older (N = 622), this study revealed that (a) respondents were optimistically biased in estimating their future risk of Alzheimer's disease (AD); (b) exposure to DTCA for AD medicine related negatively to optimistic bias when respondents had a low level of knowledge about AD, while the relationship disappeared when knowledge was high; (c) optimistic bias was negatively associated with intentions to seek information about AD and professional help to discuss it; and (d) optimistic bias mediated the relationship between the DTCA exposure × AD knowledge interaction and information- and help-seeking intentions. Implications for the theory and practice of DTCA are discussed.

  17. Quality by design case study: an integrated multivariate approach to drug product and process development.

    Science.gov (United States)

    Huang, Jun; Kaul, Goldi; Cai, Chunsheng; Chatlapalli, Ramarao; Hernandez-Abad, Pedro; Ghosh, Krishnendu; Nagi, Arwinder

    2009-12-01

    To facilitate an in-depth process understanding, and offer opportunities for developing control strategies to ensure product quality, a combination of experimental design, optimization and multivariate techniques was integrated into the process development of a drug product. A process DOE was used to evaluate effects of the design factors on manufacturability and final product CQAs, and establish design space to ensure desired CQAs. Two types of analyses were performed to extract maximal information, DOE effect & response surface analysis and multivariate analysis (PCA and PLS). The DOE effect analysis was used to evaluate the interactions and effects of three design factors (water amount, wet massing time and lubrication time), on response variables (blend flow, compressibility and tablet dissolution). The design space was established by the combined use of DOE, optimization and multivariate analysis to ensure desired CQAs. Multivariate analysis of all variables from the DOE batches was conducted to study relationships between the variables and to evaluate the impact of material attributes/process parameters on manufacturability and final product CQAs. The integrated multivariate approach exemplifies application of QbD principles and tools to drug product and process development.

  18. Media milling process optimization for manufacture of drug nanoparticles using design of experiments (DOE).

    Science.gov (United States)

    Nekkanti, Vijaykumar; Marwah, Ashwani; Pillai, Raviraj

    2015-01-01

    Design of experiments (DOE), a component of Quality by Design (QbD), is systematic and simultaneous evaluation of process variables to develop a product with predetermined quality attributes. This article presents a case study to understand the effects of process variables in a bead milling process used for manufacture of drug nanoparticles. Experiments were designed and results were computed according to a 3-factor, 3-level face-centered central composite design (CCD). The factors investigated were motor speed, pump speed and bead volume. Responses analyzed for evaluating these effects and interactions were milling time, particle size and process yield. Process validation batches were executed using the optimum process conditions obtained from software Design-Expert® to evaluate both the repeatability and reproducibility of bead milling technique. Milling time was optimized to process variables by applying DOE resulted in considerable decrease in milling time to achieve the desired particle size. The study indicates the applicability of DOE approach to optimize critical process parameters in the manufacture of drug nanoparticles.

  19. Radiology department design to accommodate the future introduction of global PACS

    International Nuclear Information System (INIS)

    Naylor, A.F.

    1992-01-01

    In the light of the continuing development of pictorial archiving and communication systems (PACS) and image management and communications (MACS) systems it is appropriate to consider the provision that should be made in the design of a new or renovated department of radiology to accommodate these new technologies at either an earlier or later date. This paper considers 3 particular aspects of the influence of PACS on future department design: 1) the requirement for either more or less total department gross square feet, 2) the provision for the specific allocation of spaces at certain locations for PACS equipment and functions, and 3) the provision for dedicated pathways for fiber optic communications among the many locations in the department where PACS components would be located. (author). 1 fig

  20. New computing systems, future computing environment, and their implications on structural analysis and design

    Science.gov (United States)

    Noor, Ahmed K.; Housner, Jerrold M.

    1993-01-01

    Recent advances in computer technology that are likely to impact structural analysis and design of flight vehicles are reviewed. A brief summary is given of the advances in microelectronics, networking technologies, and in the user-interface hardware and software. The major features of new and projected computing systems, including high performance computers, parallel processing machines, and small systems, are described. Advances in programming environments, numerical algorithms, and computational strategies for new computing systems are reviewed. The impact of the advances in computer technology on structural analysis and the design of flight vehicles is described. A scenario for future computing paradigms is presented, and the near-term needs in the computational structures area are outlined.

  1. Preliminary design of the beam screen cooling for the Future Circular Collider of hadron beams

    Science.gov (United States)

    Kotnig, C.; Tavian, L.

    2015-12-01

    Following recommendations of the recent update of the European strategy in particle physics, CERN has undertaken an international study of possible future circular colliders beyond the LHC. This study considers an option for a very high energy (100 TeV) hadron-hadron collider located in a quasi-circular underground tunnel having a circumference of 80 to 100 km. The synchrotron radiation emitted by the high-energy hadron beam increases by more than two orders of magnitude compared to the LHC. To reduce the entropic load on the superconducting magnets’ refrigeration system, beam screens are indispensable to extract the heat load at a higher temperature level. After illustrating the decisive constraints of the beam screen's refrigeration design, this paper presents a preliminary design of the length of a continuous cooling loop comparing helium and neon, for different cooling channel geometries with emphasis on the cooling length limitations and the exergetic efficiency.

  2. Preliminary design of the beam screen cooling for the Future Circular Collider of hadron beams

    CERN Document Server

    Kotnig, C

    2015-01-01

    Following recommendations of the recent update of the European strategy in particle physics, CERN has undertaken an international study of possible future circular colliders beyond the LHC. This study considers an option for a very high energy (100 TeV) hadron-hadron collider located in a quasi-circular underground tunnel having a circumference of 80 to 100 km. The synchrotron radiation emitted by the high-energy hadron beam increases by more than two orders of magnitude compared to the LHC. To reduce the entropic load on the superconducting magnets' refrigeration system, beam screens are indispensable to extract the heat load at a higher temperature level. After illustrating the decisive constraints of the beam screen's refrigeration design, this paper presents a preliminary design of the length of a continuous cooling loop comparing helium and neon, for different cooling channel geometries with emphasis on the cooling length limitations and the exergetic efficiency.

  3. Estimation of Cyclic Interstory Drift Capacity of Steel Framed Structures and Future Applications for Seismic Design

    Directory of Open Access Journals (Sweden)

    Edén Bojórquez

    2014-01-01

    Full Text Available Several studies have been devoted to calibrate damage indices for steel and reinforced concrete members with the purpose of overcoming some of the shortcomings of the parameters currently used during seismic design. Nevertheless, there is a challenge to study and calibrate the use of such indices for the practical structural evaluation of complex structures. In this paper, an energy-based damage model for multidegree-of-freedom (MDOF steel framed structures that accounts explicitly for the effects of cumulative plastic deformation demands is used to estimate the cyclic drift capacity of steel structures. To achieve this, seismic hazard curves are used to discuss the limitations of the maximum interstory drift demand as a performance parameter to achieve adequate damage control. Then the concept of cyclic drift capacity, which incorporates information of the influence of cumulative plastic deformation demands, is introduced as an alternative for future applications of seismic design of structures subjected to long duration ground motions.

  4. The duality of health technology in chronic illness: how designers envision our future.

    Science.gov (United States)

    Lehoux, Pascale

    2008-06-01

    This essay critically explores the role of technological innovation in the constitution of chronic states and illness. Drawing on the co-construction of technology and society perspective, it focuses more specifically on the way in which innovation designers envisage the enhancement of the chronically ill and build certain kinds of socio-technical configuration to deal with chronic illness. Using the case of ;intelligent distance patient monitoring' as an illustration, the paper argues that technology creates as much as it solves the problem of chronic illness. Technology is recursively embedded in chronic illness and it generates dual effects: it constrains and sustains users' daily practices. Only by recognizing technology's duality and eventually transcending it will research and policy initiatives be able to deal creatively and responsibly with the design of our future health experiences.

  5. Designing Decision Support System to Detect Drug Interactions Type 2 Diabetes.

    Science.gov (United States)

    Rasoolimoghadam, Mehdi; Safdari, Reza; Ghazisaeidi, Marjan; Maharanitehrani, MohammadReza; Tahmasebiyan, Shahram

    2015-12-01

    Type II Diabetes is the most common diseases of metabolic disorders and the treatment of oral anti-diabetic drug use takes place But The problem of using multi-drug and interactions at the same time is an issue that has always been a major challenge And diagnosis of drug interactions, particularly in Diabetic patients due to the problem with the disease is very important. The purpose of this studying is, to design a clinical assistant decided to use this approach to determine the type II diabetes drug interactions this makes it easy for those who are active in the field. Study is Developmental that to determine the content of the system a self-made checklist was used. Checklist Validity and reliability has been confirmed by four professors. The Research community to determine the content of the system was country endocrine that are 124 people. The sample size was calculated using Cochran that was 57 people. The Score of checklist was calculated in SPSS version 20 .finally, the checklist was approved by at least 70% points. The system by using Microsoft SQL server 2008 and visual Studio 2012 development environment was designed in C#.net. In the end, In order to evaluate the software to determine the level of satisfaction, usability and ease of use, designed systems sharing with all Medical Informatics students of Tehran University of Medical Sciences. For this purpose a self-made questionnaire was used. Questionnaire Validity has been confirmed by four professors and reliability was assessed by Cronbach method. The results of the survey are showing that the majority of students found out and believed the software is useful and easy to use and generally expressed their satisfaction software. The methodology provides a suitable approach for analysis and modeling of data in the medical field and the performance is good.

  6. Design of nanocarriers for nanoscale drug delivery to enhance cancer treatment using hybrid polymer and lipid building blocks.

    Science.gov (United States)

    Zhang, Rui Xue; Ahmed, Taksim; Li, Lily Yi; Li, Jason; Abbasi, Azhar Z; Wu, Xiao Yu

    2017-01-26

    Polymer-lipid hybrid nanoparticles (PLN) are an emerging nanocarrier platform made from building blocks of polymers and lipids. PLN integrate the advantages of biomimetic lipid-based nanoparticles (i.e. solid lipid nanoparticles and liposomes) and biocompatible polymeric nanoparticles. PLN are constructed from diverse polymers and lipids and their numerous combinations, which imparts PLN with great versatility for delivering drugs of various properties to their nanoscale targets. PLN can be classified into two types based on their hybrid nanoscopic structure and assembly methods: Type-I monolithic matrix and Type-II core-shell systems. This article reviews the history of PLN development, types of PLN, lipid and polymer candidates, fabrication methods, and unique properties of PLN. The applications of PLN in delivery of therapeutic or imaging agents alone or in combination for cancer treatment are summarized and illustrated with examples. Important considerations for the rational design of PLN for advanced nanoscale drug delivery are discussed, including selection of excipients, synthesis processes governing formulation parameters, optimization of nanoparticle properties, improvement of particle surface functionality to overcome macroscopic, microscopic and cellular biological barriers. Future directions and potential clinical translation of PLN are also suggested.

  7. Gas fired boilers: Perspective for near future fuel composition and impact on burner design process

    Science.gov (United States)

    Schiro, Fabio; Stoppato, Anna; Benato, Alberto

    2017-11-01

    The advancements on gas boiler technology run in parallel with the growth of renewable energy production. The renewable production will impact on the fuel gas quality, since the gas grid will face an increasing injection of alternative fuels (biogas, biomethane, hydrogen). Biogas allows producing energy with a lower CO2 impact; hydrogen production by electrolysis can mitigate the issues related to the mismatch between energy production by renewable and energy request. These technologies will contribute to achieve the renewable production targets, but the impact on whole fuel gas production-to-consumption chain must be evaluated. In the first part of this study, the Authors present the future scenario of the grid gas composition and the implications on gas fed appliances. Given that the widely used premixed burners are currently designed mainly by trial and error, a broader fuel gas quality range means an additional hitch on this design process. A better understanding and structuring of this process is helpful for future appliance-oriented developments. The Authors present an experimental activity on a premixed condensing boiler setup. A test protocol highlighting the burners' flexibility in terms of mixture composition is adopted and the system fuel flexibility is characterized around multiple reference conditions.

  8. Gas fired boilers: Perspective for near future fuel composition and impact on burner design process

    Directory of Open Access Journals (Sweden)

    Schiro Fabio

    2017-01-01

    Full Text Available The advancements on gas boiler technology run in parallel with the growth of renewable energy production. The renewable production will impact on the fuel gas quality, since the gas grid will face an increasing injection of alternative fuels (biogas, biomethane, hydrogen. Biogas allows producing energy with a lower CO2 impact; hydrogen production by electrolysis can mitigate the issues related to the mismatch between energy production by renewable and energy request. These technologies will contribute to achieve the renewable production targets, but the impact on whole fuel gas production-to-consumption chain must be evaluated. In the first part of this study, the Authors present the future scenario of the grid gas composition and the implications on gas fed appliances. Given that the widely used premixed burners are currently designed mainly by trial and error, a broader fuel gas quality range means an additional hitch on this design process. A better understanding and structuring of this process is helpful for future appliance-oriented developments. The Authors present an experimental activity on a premixed condensing boiler setup. A test protocol highlighting the burners' flexibility in terms of mixture composition is adopted and the system fuel flexibility is characterized around multiple reference conditions.

  9. Design and optimization of self-nanoemulsifying drug delivery systems for improved bioavailability of cyclovirobuxine D.

    Science.gov (United States)

    Ke, Zhongcheng; Hou, Xuefeng; Jia, Xiao-Bin

    2016-01-01

    The main purpose of this research was to design a self-nanoemulsifying drug delivery system (SNEDDS) for improving the bioavailability of cyclovirobuxine D as a poorly water-soluble drug. Solubility trials, emulsifying studies, and pseudo-ternary phase diagrams were used to screen the SNEDDS formulations. The optimized drug-loaded SNEDDS was prepared at a mass ratio of 3:24:38:38 for cyclovirobuxine D, oleic acid, Solutol SH15, and propylene glycol, respectively. The optimized formulation was characterized in terms of physicochemical and pharmacokinetic parameters compared with marketed cyclovirobuxine D tablets. The optimized cyclovirobuxine-D-loaded SNEDDS was spontaneously dispersed to form a nanoemulsion with a globule size of 64.80±3.58 nm, which exhibited significant improvement of drug solubility, rapid absorption rate, and enhanced area under the curve, together with increased permeation and decreased efflux. Fortunately, there was a nonsignificant cytotoxic effect toward Caco-2 cells. The relative bioavailability of SNEDDS was 200.22% in comparison with market tablets, in rabbits. SNEDDS could be a potential candidate for an oral dosage form of cyclovirobuxine D with improved bioavailability.

  10. [Benzimidazole and its derivatives--from fungicides to designer drugs. A new occupational and environmental hazards].

    Science.gov (United States)

    Lutz, Piotr

    2012-01-01

    Benzimidazole and benzimidazole derivatives play an important role in controlling various fungal pathogens. The benzimidazoles are also used to treat nematode and trematode infections in humans and animals. It acts by binding to the microtubules and stopping hyphal growth. It also binds to the spindle microtubules and blocks nuclear division. The most popular fungicide is carbendazim. The fungicide is used to control plant diseases in cereals and fruits. Laboratory studies have shown that carbendazim cause infertility and destroy the testicles of laboratory animals. Other benzimidazole derivatives are used as a preservative in paint, textile, papermaking, leather industry, and warehousing practices, as well as a preservative of fruits. Occupational exposure to benzimidazole may occur through inhalation and dermal contact with those compounds at workplaces where benzimidazole is used or produced. Some of the benzimidazoles are common environmental pollutants. They are often found in food and fruit products. Some of the benzimidazoles, like a astemizole or esomeprazole have found applications in diverse therapeutical areas. Despite of the clear advantages afforded by the use of benzimidazole derivatives, they share a danger potential. The most hazardous, however, are new illegally synthesed psychoactive drugs known as designer drugs. Some of them, like nitazene, etonitazene or clonitazene belong to benzimidazole derivatives. Laboratory animal studies revealed that etonitazene produced very similar effects in central nervous system as those observed after morphine administration. Considering etonitazene's properties, it seems reasonable to expected that long-term exposure to other benzimidazole derivatives may result in drug abuse and development of drug dependence.

  11. Optimization of primaquine diphosphate tablet formulation for controlled drug release using the mixture experimental design.

    Science.gov (United States)

    Duque, Marcelo Dutra; Kreidel, Rogério Nepomuceno; Taqueda, Maria Elena Santos; Baby, André Rolim; Kaneko, Telma Mary; Velasco, Maria Valéria Robles; Consiglieri, Vladi Olga

    2013-01-01

    A tablet formulation based on hydrophilic matrix with a controlled drug release was developed, and the effect of polymer concentrations on the release of primaquine diphosphate was evaluated. To achieve this purpose, a 20-run, four-factor with multiple constraints on the proportions of the components was employed to obtain tablet compositions. Drug release was determined by an in vitro dissolution study in phosphate buffer solution at pH 6.8. The polynomial fitted functions described the behavior of the mixture on simplex coordinate systems to study the effects of each factor (polymer) on tablet characteristics. Based on the response surface methodology, a tablet composition was optimized with the purpose of obtaining a primaquine diphosphate release closer to a zero order kinetic. This formulation released 85.22% of the drug for 8 h and its kinetic was studied regarding to Korsmeyer-Peppas model, (Adj-R(2) = 0.99295) which has confirmed that both diffusion and erosion were related to the mechanism of the drug release. The data from the optimized formulation were very close to the predictions from statistical analysis, demonstrating that mixture experimental design could be used to optimize primaquine diphosphate dissolution from hidroxypropylmethyl cellulose and polyethylene glycol matrix tablets.

  12. Does the Drug Facts Label for nonprescription drugs meet its design objectives? A new procedure for assessing label effectiveness

    Directory of Open Access Journals (Sweden)

    Michael P Ryan

    2017-07-01

    Full Text Available We demonstrate an expanded procedure for assessing drug-label comprehension. Innovations include a pretest of drug preconceptions, verbal ability and label attentiveness measures, a label-scanning task, a free-recall test, category-clustering measures, and preconception-change scores. In total, 55 female and 39 male undergraduates read a facsimile Drug Facts Label for aspirin, a Cohesive-Prose Label, or a Scrambled-Prose Label. The Drug Facts Label outperformed the Scrambled-Prose Label, but not the Cohesive-Prose Label, in scanning effectiveness. The Drug Facts Label was no better than the Cohesive-Prose Label or the Scrambled-Prose Label in promoting attentiveness, recall and organization of drug facts, or misconception refutation. Discussion focuses on the need for refutational labels based on a sequence-of-events text schema.

  13. Sustainable Skyscrapers: Designing the Net Zero Energy Building of the Future

    Science.gov (United States)

    Kothari, S.; Bartsch, A.

    2016-12-01

    Cities of the future will need to increase population density in order to keep up with the rising populations in the limited available land area. In order to provide sufficient power as the population grows, cities must become more energy efficient. Fossil fuels and grid energy will continue to become more expensive as nonrenewable resources deplete. The obvious solution to increase population density while decreasing the reliance on fossil fuels is to build taller skyscrapers that are energy neutral, i.e. self-sustaining. However, current skyscrapers are not energy efficient, and therefore cannot provide a sustainable solution to the problem of increasing population density in the face of depleting energy resources. The design of a net zero energy building that includes both residential and commercial space is presented. Alternative energy systems such as wind turbines, photovoltaic cells, and a waste-to-fuel conversion plant have been incorporated into the design of a 50 story skyscraper that is not reliant on fossil fuels and has a payback time of about six years. Although the current building was designed to be located in San Francisco, simple modifications to the design would allow this building to fit the needs of any city around the world.

  14. Design of shipping packages to transport varying radioisotopic source materials for future space and terrestrial missions

    International Nuclear Information System (INIS)

    Barklay, C.D.

    1995-01-01

    The exploration of space will begin with manned missions to the moon and to Mars, first for scientific discoveries, then for mining and manufacturing. Because of the great financial costs of this type of exploration, it can only be accomplished through an international team effort. This unified effort must include the design, planning and, execution phases of future space missions, extending down to such activities as isotope processing, and shipping package design, fabrication, and certification. All aspects of this effort potentially involve the use of radioisotopes in some capacity, and the transportation of these radioisotopes will be impossible without a shipping package that is certified by the Nuclear Regulatory Commission or the U.S. Department of Energy for domestic shipments, and the U.S. Department of Transportation or the International Atomic Energy Agency for international shipments. To remain without the international regulatory constraints, and still support the needs of new and challenging space missions conducted within ever-shrinking budgets, shipping package concepts must be innovative. A shipping package must also be versatile enough to be reconfigured to transport the varying radioisotopic source materials that may be required to support future space and terrestrial missions. One such package is the Mound USA/9516/B(U)F. Taking into consideration the potential need to transport specific types of radioisotopes, approximations of dose rates at specific distances were determined taking into account the attenuation of dose rate with distance for varying radioisotopic source materials. As a result, it has been determined that the shipping package requirements that will be demanded by future space (and terrestrial) missions can be met by making minor modifications to the USA/9516/B(U)F. copyright 1995 American Institute of Physics

  15. 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.

  16. An Engineering Design Reference Mission for a Future Large-Aperture UVOIR Space Observatory

    Science.gov (United States)

    Thronson, Harley A.; Bolcar, Matthew R.; Clampin, Mark; Crooke, Julie A.; Redding, David; Rioux, Norman; Stahl, H. Philip

    2016-01-01

    From the 2010 NRC Decadal Survey and the NASA Thirty-Year Roadmap, Enduring Quests, Daring Visions, to the recent AURA report, From Cosmic Birth to Living Earths, multiple community assessments have recommended development of a large-aperture UVOIR space observatory capable of achieving a broad range of compelling scientific goals. Of these priority science goals, the most technically challenging is the search for spectroscopic biomarkers in the atmospheres of exoplanets in the solar neighborhood. Here we present an engineering design reference mission (EDRM) for the Advanced Technology Large-Aperture Space Telescope (ATLAST), which was conceived from the start as capable of breakthrough science paired with an emphasis on cost control and cost effectiveness. An EDRM allows the engineering design trade space to be explored in depth to determine what are the most demanding requirements and where there are opportunities for margin against requirements. Our joint NASA GSFC/JPL/MSFC/STScI study team has used community-provided science goals to derive mission needs, requirements, and candidate mission architectures for a future large-aperture, non-cryogenic UVOIR space observatory. The ATLAST observatory is designed to operate at a Sun-Earth L2 orbit, which provides a stable thermal environment and excellent field of regard. Our reference designs have emphasized a serviceable 36-segment 9.2 m aperture telescope that stows within a five-meter diameter launch vehicle fairing. As part of our cost-management effort, this particular reference mission builds upon the engineering design for JWST. Moreover, it is scalable to a variety of launch vehicle fairings. Performance needs developed under the study are traceable to a variety of additional reference designs, including options for a monolithic primary mirror.

  17. Modern drug design: the implication of using artificial neuronal networks and multiple molecular dynamic simulations

    Science.gov (United States)

    Yakovenko, Oleksandr; Jones, Steven J. M.

    2018-01-01

    We report the implementation of molecular modeling approaches developed as a part of the 2016 Grand Challenge 2, the blinded competition of computer aided drug design technologies held by the D3R Drug Design Data Resource (https://drugdesigndata.org/). The challenge was focused on the ligands of the farnesoid X receptor (FXR), a highly flexible nuclear receptor of the cholesterol derivative chenodeoxycholic acid. FXR is considered an important therapeutic target for metabolic, inflammatory, bowel and obesity related diseases (Expert Opin Drug Metab Toxicol 4:523-532, 2015), but in the context of this competition it is also interesting due to the significant ligand-induced conformational changes displayed by the protein. To deal with these conformational changes we employed multiple simulations of molecular dynamics (MD). Our MD-based protocols were top-ranked in estimating the free energy of binding of the ligands and FXR protein. Our approach was ranked second in the prediction of the binding poses where we also combined MD with molecular docking and artificial neural networks. Our approach showed mediocre results for high-throughput scoring of interactions.

  18. Community pharmacy services for people with drug problems over two decades in Scotland: Implications for future development.

    Science.gov (United States)

    Matheson, Catriona; Thiruvothiyur, Manimekalai; Robertson, Helen; Bond, Christine

    2016-01-01

    In Scotland community pharmacies are heavily involved in service delivery for people with drug problems (PWDP) as documented through surveys of all community pharmacies in 1995, 2000 and 2006. A further survey in 2014 enabled trends in service demand/provision to be analysed and provides insight into future development. The lead pharmacist in every Scottish pharmacy (n=1246) was invited to complete a postal questionnaire covering attitudes towards PWDP and service provision and level of involvement in services (needle exchange, dispensing for PWDP and methadone supervision). Additional questions covered new services of take-home naloxone (THN) and pharmacist prescribing for opioid dependence. Telephone follow-up of non-responders covered key variables. A comparative analysis of four cross-sectional population surveys of the community pharmacy workforce (1995, 2000, 2006 and 2014) was undertaken. Completed questionnaires were returned by 709 (57%) pharmacists in 2014. Key variables (questionnaire or telephone follow-up) were available from 873 (70%). The proportion of pharmacies providing needle exchange significantly increased from 1995 to 2014 (8.6%, 9.5%, 12.2%, 17.8%, p<0.001) as did the proportion of pharmacies dispensing for the treatment of drug misuse (58.9%, 73.4%, 82.6% and 88%, p<0.001). Methadone was dispensed to 16,406 individuals and buprenorphine to 1777 individuals (increased from 12,400 and 192 respectively in 2006). Attitudes improved significantly from 1995 to 2014 (p<0.001). Being male and past training in drug misuse significantly predicted higher attitude scores (p<0.05) in all four years. Attitude score was a consistently significant predictor in all four years for dispensing for the treatment of drug misuse [OR=1.1 (1995 and 2006, CI 1.1-1.3, and 2014 CI 1.1-1.4) and 1.2 (2000), CI 1.3-1.5] and providing needle exchange [OR=1.1 (1995 and 2006), CI 1.1-1.2, 1.1-1.3 and 1.2 (2000 and 2014), CI 1.1-1.3 and 1.1-1.5]. In 2014, 53% of pharmacists

  19. 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.

  20. 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