WorldWideScience

Sample records for drug development demonstration

  1. Drug development in neuropsychopharmacology.

    Science.gov (United States)

    Fritze, Jürgen

    2008-03-01

    Personalized medicine is still in its infancy concerning drug development in neuropsychopharmacology. Adequate biomarkers with clinical relevance to drug response and/or tolerability and safety largely remain to be identified. Possibly, this kind of personalized medicine will first gain clinical relevance in the dementias. The clinical relevance of the genotyping of drug-metabolizing enzymes as suggested by drug licensing authorities for the pharmacokinetic evaluation of medicinal products needs to be proven in sound clinical trials.

  2. Metabonomics and drug development.

    Science.gov (United States)

    Ramana, Pranov; Adams, Erwin; Augustijns, Patrick; Van Schepdael, Ann

    2015-01-01

    Metabolites as an end product of metabolism possess a wealth of information about altered metabolic control and homeostasis that is dependent on numerous variables including age, sex, and environment. Studying significant changes in the metabolite patterns has been recognized as a tool to understand crucial aspects in drug development like drug efficacy and toxicity. The inclusion of metabonomics into the OMICS study platform brings us closer to define the phenotype and allows us to look at alternatives to improve the diagnosis of diseases. Advancements in the analytical strategies and statistical tools used to study metabonomics allow us to prevent drug failures at early stages of drug development and reduce financial losses during expensive phase II and III clinical trials. This chapter introduces metabonomics along with the instruments used in the study; in addition relevant examples of the usage of metabonomics in the drug development process are discussed along with an emphasis on future directions and the challenges it faces.

  3. Energy 2007. Research, development, demonstration; Energi 07. Forskning, udvikling, demonstration

    Energy Technology Data Exchange (ETDEWEB)

    Byriel, I.P.; Justesen, Helle; Beck, A.; Borup Jensen, J.; Rosenfeldt Jakobsen, Kl; Jacobsen, Steen Hartvig (eds.)

    2007-08-10

    Danish energy research is in an exciting and challenging situation. Rising oil prices, unstable energy supply, climate policy responsibilities and globalization have brought development of new environmentally friendly and more efficient energy technologies into focus. Promising international markets for newly developed energy technologies are emerging, and at the same time well established Danish positions of strength are challenged by new strong actors on the global market. The Danish government has set to work on its vision of an appreciable strengthening of public energy research funding through the recent law on the energy technological development and demonstration programme EUDP and the realization of globalization funds. The interaction between basic and applied research must be kept intact. In this report the various Danish energy research programmes administered by Energinet.dk, Danish Energy Authority, Danish Energy Association, Danish Council for Strategic Research's Programme Commission on Energy and Environment and Danish National Advanced Technology Foundation, coordinate their annual reports for the first time. The aim of Energy 2007 is to give the reader an idea of how the energy research programmes collaborate on solving the major energy technology challenges - also in an international context. (BA)

  4. Metallomics in drug development

    DEFF Research Database (Denmark)

    Nguyen, Trinh Thi Nhu Tam; Ostergaard, Jesper; Stürup, Stefan

    2013-01-01

    in plasma. A detection limit of 41 ng/mL of platinum and a precision of 2.1 % (for 10 µg/mL of cisplatin standard) were obtained. Simultaneous measurements of phosphorous and platinum allows the simultaneous monitoring of the liposomes, liposome-encapsulated cisplatin, free cisplatin and cisplatin bound...... to plasma constituents in plasma samples. It was demonstrated that this approach is suitable for studies of the stability of liposome formulations as leakage of active drug from the liposomes and subsequent binding to biomolecules in plasma can be monitored. This methodology has not been reported before...

  5. Melatonergic drugs in development

    Directory of Open Access Journals (Sweden)

    Carocci A

    2014-09-01

    Full Text Available Alessia Carocci,1 Alessia Catalano,1 Maria Stefania Sinicropi2 1Department of Pharmacy–Drug Sciences, University of Bari Aldo Moro, Bari, 2Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Cosenza, Italy Abstract: Melatonin (N-acetyl-5-methoxytryptamine is widely known as "the darkness hormone". It is a major chronobiological regulator involved in circadian phasing and sleep-wake cycle in humans. Numerous other functions, including cyto/neuroprotection, immune modulation, and energy metabolism have been ascribed to melatonin. A variety of studies have revealed a role for melatonin and its receptors in different pathophysiological conditions. However, the suitability of melatonin as a drug is limited because of its short half-life, poor oral bioavailability, and ubiquitous action. Due to the therapeutic potential of melatonin in a wide variety of clinical conditions, the development of new agents able to interact selectively with melatonin receptors has become an area of great interest during the last decade. Therefore, the field of melatonergic receptor agonists comprises a great number of structurally different chemical entities, which range from indolic to nonindolic compounds. Melatonergic agonists are suitable for sleep disturbances, neuropsychiatric disorders related to circadian dysphasing, and metabolic diseases associated with insulin resistance. The results of preclinical studies on animal models show that melatonin receptor agonists can be considered promising agents for the treatment of central nervous system-related pathologies. An overview of recent advances in the field of investigational melatonergic drugs will be presented in this review. Keywords: MT1/MT2 ligands, circadian rhythms, melatonin 

  6. Melatonergic drugs in development.

    Science.gov (United States)

    Carocci, Alessia; Catalano, Alessia; Sinicropi, Maria Stefania

    2014-01-01

    Melatonin (N-acetyl-5-methoxytryptamine) is widely known as "the darkness hormone". It is a major chronobiological regulator involved in circadian phasing and sleep-wake cycle in humans. Numerous other functions, including cyto/neuroprotection, immune modulation, and energy metabolism have been ascribed to melatonin. A variety of studies have revealed a role for melatonin and its receptors in different pathophysiological conditions. However, the suitability of melatonin as a drug is limited because of its short half-life, poor oral bioavailability, and ubiquitous action. Due to the therapeutic potential of melatonin in a wide variety of clinical conditions, the development of new agents able to interact selectively with melatonin receptors has become an area of great interest during the last decade. Therefore, the field of melatonergic receptor agonists comprises a great number of structurally different chemical entities, which range from indolic to nonindolic compounds. Melatonergic agonists are suitable for sleep disturbances, neuropsychiatric disorders related to circadian dysphasing, and metabolic diseases associated with insulin resistance. The results of preclinical studies on animal models show that melatonin receptor agonists can be considered promising agents for the treatment of central nervous system-related pathologies. An overview of recent advances in the field of investigational melatonergic drugs will be presented in this review.

  7. Drug Development Process

    Science.gov (United States)

    ... Preclinical Research Preclinical Research Drugs undergo laboratory and animal testing to answer basic questions about safety. More Information ... Medical Devices Radiation-Emitting Products Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products

  8. Quantitative decisions in drug development

    CERN Document Server

    Chuang-Stein, Christy

    2017-01-01

    This book offers a high-level treatise of evidence-based decisions in drug development. Because of the inseparable relationship between designs and decisions, a good portion of this book is devoted to the design of clinical trials. The book begins with an overview of product development and regulatory approval pathways. It then discusses how to incorporate prior knowledge into study design and decision making at different stages of drug development. The latter include selecting appropriate metrics to formulate decisions criteria, determining go/no-go decisions for progressing a drug candidate to the next stage and predicting the effectiveness of a product. Lastly, it points out common mistakes made by drug developers under the current drug-development paradigm. The book offers useful insights to statisticians, clinicians, regulatory affairs managers and decision-makers in the pharmaceutical industry who have a basic understanding of the drug-development process and the clinical trials conducted to support dru...

  9. Competence of medical students in communicating drug therapy: Value of role-play demonstrations.

    Science.gov (United States)

    Tayem, Yasin I; Altabtabaei, Abdulaziz S; Mohamed, Mohamed W; Arrfedi, Mansour M; Aljawder, Hasan S; Aldebous, Fahad A; James, Henry; Al Khaja, Khalid A J; Sequeira, Reginald P

    2016-01-01

    This study used role-play demonstrations to train medical students to communicate drug therapy and evaluated the perceptions on this instructional approach. The second-year medical students who attended a prescription writing session (n = 133), participated in this study. Prescription communication was introduced by using role-play demonstrations. Participant's perceptions were explored by a self-administered questionnaire and focus group discussion. The academic achievement of attendees and nonattendees was compared with an objective structured performance evaluation (OSPE) station that tested students' competence in this skill. Most attendees responded to the questionnaire (81.2%). Almost all respondents expressed their desire to have similar demonstrations in other units. A large proportion of participants reported that role-play demonstrations helped them develop their communication skills, in general, confidence to communicate drug-related information in a prescription, and the ability to explain the aim of drug therapy to patients. Most trainees thought also that they developed skills to communicate instructions on drug use including drug dose, frequency of administration, duration of therapy, adverse drug reactions, and warnings. During the focus group interviews, students thought that role-play was useful but would be more beneficial if conducted frequently in small group as part of the curriculum implementation. The majority of students also reported improved competence in writing a complete prescription. Analysis of attendees and nonattendees grades in the OSPE showed that the former scored higher than the latter group (P = 0.016). Role-play demonstrations were well accepted by medical students and led to the development of their competence in communicating drug therapy to patients.

  10. [Exploration and demonstration study on drug combination from clinical real world].

    Science.gov (United States)

    Xie, Yan-ming; Wang, Lian-xin; Wang, Yong-yan

    2014-09-01

    Drug combination is extensive in the clinical real world,which is an important part and the inherent requirements of the post-marketing evaluation of traditional Chinese medicine (TCM). The key issues and technology include multi-domain and multi-disciplinary such as the rationality, efficacy and safety evaluation of combination drug starting from clinical real world, study on component in vivo and mechanism of combination drug, the risk/benefit assessment and cost-benefit evaluation of combination drug and so on. The topic has been studied as clinical demonstration on combination therapy of variety of diseases such as coronary heart disease, stroke, insomnia, depression, hepatitis, herpes zoster, psoriasis and ectopic pregnancy. Meanwhile, multi-disciplinary dynamic innovation alliance of clinical drug combination has been presented, which can promote the academic development and improving service ability and level of TCM.

  11. Drug Development Pipeline

    Science.gov (United States)

    ... molecule that contains genetic instructions to make proteins. Delivery of CFTR-encoded mRNA would allow the lung cells to create normally functioning CFTR protein, regardless of an individual’s specific CFTR gene mutation. This drug is delivered via inhalation. Editas This program is ...

  12. Drug development and manufacturing

    Science.gov (United States)

    Warner, Benjamin P.; McCleskey, T. Mark; Burrell, Anthony K.

    2015-10-13

    X-ray fluorescence (XRF) spectrometry has been used for detecting binding events and measuring binding selectivities between chemicals and receptors. XRF may also be used for estimating the therapeutic index of a chemical, for estimating the binding selectivity of a chemical versus chemical analogs, for measuring post-translational modifications of proteins, and for drug manufacturing.

  13. Drug development for neurodevelopmental disorders

    DEFF Research Database (Denmark)

    Berry-Kravis, Elizabeth M; Lindemann, Lothar; Jønch, Aia E

    2018-01-01

    Neurodevelopmental disorders such as fragile X syndrome (FXS) result in lifelong cognitive and behavioural deficits and represent a major public health burden. FXS is the most frequent monogenic form of intellectual disability and autism, and the underlying pathophysiology linked to its causal ge......, FMR1, has been the focus of intense research. Key alterations in synaptic function thought to underlie this neurodevelopmental disorder have been characterized and rescued in animal models of FXS using genetic and pharmacological approaches. These robust preclinical findings have led...... to the implementation of the most comprehensive drug development programme undertaken thus far for a genetically defined neurodevelopmental disorder, including phase IIb trials of metabotropic glutamate receptor 5 (mGluR5) antagonists and a phase III trial of a GABAB receptor agonist. However, none of the trials has...... been able to unambiguously demonstrate efficacy, and they have also highlighted the extent of the knowledge gaps in drug development for FXS and other neurodevelopmental disorders. In this Review, we examine potential issues in the previous studies and future directions for preclinical and clinical...

  14. Development of demonstration advanced thermal reactor

    Energy Technology Data Exchange (ETDEWEB)

    Nishimura, Seiji; Oguchi, Isao; Touhei, Kazushige

    1982-08-01

    The design of the advanced thermal demonstration reactor with 600 MWe output was started in 1975. In order to make the compact core, 648 fuel assemblies, each comprising 36 fuel rods, were used, and the mean channel output was increased by 20% as compared with the prototype reactor. The heavy water dumping mechanism for the calandria was abolished. Advanced thermal reactors are suitable to burn plutonium, since the control rod worth does not change, the void reactivity coefficient of coolant shifts to the negative side, and the harmful influence of high order plutonium is small. The void reactivity coefficient is nearly zero, the fluctuation of output in relation to pressure disturbance is small, and the local output change of fuel by the operation of control rods is small, therefore, the operation following load change is relatively easy. The coolant recirculation system is of independent loop construction dividing the core into two, and steam and water are separated in respective steam drums. At present, the rationalizing design is in progress by the leadership of the Power Reactor and Nuclear Fuel Development Corp. The outline of the demonstration reactor, the reactor construction, the nuclear-thermal-hydraulic characteristics and the output control characteristics are reported.

  15. Development of demonstration advanced thermal reactor

    International Nuclear Information System (INIS)

    Nishimura, Seiji; Oguchi, Isao; Touhei, Kazushige.

    1982-01-01

    The design of the advanced thermal demonstration reactor with 600 MWe output was started in 1975. In order to make the compact core, 648 fuel assemblies, each comprising 36 fuel rods, were used, and the mean channel output was increased by 20% as compared with the prototype reactor. The heavy water dumping mechanism for the calandria was abolished. Advanced thermal reactors are suitable to burn plutonium, since the control rod worth does not change, the void reactivity coefficient of coolant shifts to the negative side, and the harmful influence of high order plutonium is small. The void reactivity coefficient is nearly zero, the fluctuation of output in relation to pressure disturbance is small, and the local output change of fuel by the operation of control rods is small, therefore, the operation following load change is relatively easy. The coolant recirculation system is of independent loop construction dividing the core into two, and steam and water are separated in respective steam drums. At present, the rationalizing design is in progress by the leadership of the Power Reactor and Nuclear Fuel Development Corp. The outline of the demonstration reactor, the reactor construction, the nuclear-thermal-hydraulic characteristics and the output control characteristics are reported. (Kako, I.)

  16. Nuclear imaging drug development tools

    International Nuclear Information System (INIS)

    Buchanan, L.; Jurek, P.; Redshaw, R.

    2007-01-01

    This article describes the development of nuclear imaging as an enabling technology in the pharmaceutical industry. Molecular imaging is maturing into an important tool with expanding applications from validating that a drug reaches the intended target through to market launch of a new drug. Molecular imaging includes anatomical imaging of organs or tissues, computerized tomography (CT), magnetic resonance imaging (MRI) and ultrasound.

  17. Obesity and Pediatric Drug Development.

    Science.gov (United States)

    Vaughns, Janelle D; Conklin, Laurie S; Long, Ying; Zheng, Panli; Faruque, Fahim; Green, Dionna J; van den Anker, John N; Burckart, Gilbert J

    2018-05-01

    There is a lack of dosing guidelines for use in obese children. Moreover, the impact of obesity on drug safety and clinical outcomes is poorly defined. The paucity of information needed for the safe and effective use of drugs in obese patients remains a problem, even after drug approval. To assess the current incorporation of obesity as a covariate in pediatric drug development, the pediatric medical and clinical pharmacology reviews under the Food and Drug Administration (FDA) Amendments Act of 2007 and the FDA Safety and Innovation Act (FDASIA) of 2012 were reviewed for obesity studies. FDA labels were also reviewed for statements addressing obesity in pediatric patients. Forty-five drugs studied in pediatric patients under the FDA Amendments Act were found to have statements and key words in the medical and clinical pharmacology reviews and labels related to obesity. Forty-four products were identified similarly with pediatric studies under FDASIA. Of the 89 product labels identified, none provided dosing information related to obesity. The effect of body mass index on drug pharmacokinetics was mentioned in only 4 labels. We conclude that there is little information presently available to provide guidance related to dosing in obese pediatric patients. Moving forward, regulators, clinicians, and the pharmaceutical industry should consider situations in drug development in which the inclusion of obese patients in pediatric trials is necessary to facilitate the safe and effective use of new drug products in the obese pediatric population. © 2018, The American College of Clinical Pharmacology.

  18. Drug discovery and developments in developing countries ...

    African Journals Online (AJOL)

    the major burden being in developing countries. Many of ... The driving force for drug discovery and development by pharmaceutical firms ... world and particularly in the third world countries ..... GFHR (2000) Global Forum for Health Research:.

  19. PV window - Development and demonstrations. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Haugaard, P.

    2011-05-15

    Using the results from the EU project RenewTransnet, which focused on the development of a pane with integrated solar cells, the goal of this project is to develop these principles into a window solution. This window solution is targeted to Danish building tradition and architecture. It is expected that an elegant PV-window solution for both new and retrofit buildings is developed during this project, and which appearance can be customized to each building. Based on results from a related projects carried out by Gaia Solar, the window solution will have the potential of being approximately 30% cheaper than similar products on the market. In this project this price reduction is the objective of the development of a window solution. The project team has succeeded in developing a 2-layer PV-window with glass / glass lamination with EVA as foil, which is 35% cheaper than similar products on the market. Since the price for the frame-profile does not differ significantly at market level, the price comparison is made on the basis of the developed PV-pane. The objective of 30 % price reduction in relation to similar products on the market is met. A special production process to the making glass/glass lamination with EVA as foil has been developed, in which a frame is put around the module which intends both to remove the unwanted tension along the edges, and to prevent the significant spillage of EVA from the module under pressure and prevent the invasive bubbles along the edge of module. Since the developed production method for making glass/glass modules with EVA is simple, a further cost reduction will primarily be in a reduction of the price of the cell. The project process has resulted in the development of a product, which due to continuous restrictions in the building regulations, will be very attractive in future buildings. (LN)

  20. Nursing Professional Development Organizational Value Demonstration Project.

    Science.gov (United States)

    Harper, Mary G; Aucoin, Julia; Warren, Joan I

    2016-01-01

    A common question nursing professional development (NPD) practitioners ask is, "How many NPD practitioners should my organization have?" This study examined correlations among facility size and structure, NPD practitioner characteristics and time in service, and organizational outcomes. Organizations with a higher rate of NPD full-time equivalents per bed had higher patient satisfaction with nurses' communication and provision of discharge instruction on their HCAHPS (Hospital Consumer Assessment of Healthcare Provider and Systems) scores.

  1. Superconducting coil development and motor demonstration: Overview

    Science.gov (United States)

    Gubser, D. U.

    1995-12-01

    Superconducting bismuth-cuprate wires, coils, and magnets are being produced by industry as part of a program to test the viability of using such magnets in Naval systems. Tests of prototype magnets, coils, and wires reveal progress in commercially produced products. The larger magnets will be installed in an existing superconducting homopolar motor and operated initially at 4.2K to test the performance. It is anticipated that approximately 400 Hp will be achieved by the motor. This article reports on the initial tests of the magnets, coils, and wires as well as the development program to improve their performance.

  2. Adolescent Brain Development and Drugs

    Science.gov (United States)

    Winters, Ken C.; Arria, Amelia

    2011-01-01

    Research now suggests that the human brain is still maturing during adolescence. The developing brain may help explain why adolescents sometimes make decisions that are risky and can lead to safety or health concerns, including unique vulnerabilities to drug abuse. This article explores how this new science may be put to use in our prevention and…

  3. Surrogacy in antiviral drug development

    Science.gov (United States)

    Shaunak, Sunil; Davies, Donald S

    2002-01-01

    The coming of age of molecular biology has resulted in an explosion in our understanding of the pathogenesis of virus related diseases. New pathogens have been identified and characterized as being responsible for old diseases. Empirical clinical evaluation of morbidity and mortality as outcome measures after a therapeutic intervention have started to give way to the use of an increasing number of surrogate markers. Using a combination of these markers, it is now possible to measure and monitor the pathogen as well as the host's response. Nowhere is this better exemplified in virology than in the field of AIDS. We have utilized the advances in pathogenesis and new antiretroviral drug development to: develop a new class of drugs which block the entry of HIV-1 into cells.develop a new approach for effectively delivering these drugs to those tissues in which most viral replication takes place. Over the last 10 years, our work has progressed from concept to clinical trial. Our laboratory based evaluation of the new molecules developed as well as our clinical evaluation of their safety and efficacy have had to respond and adapt to the rapid changes taking place in AIDS research. This paper discusses the problems encountered and the lessons learnt. PMID:12100230

  4. Drug development: from concept to marketing!

    Science.gov (United States)

    Tamimi, Nihad A M; Ellis, Peter

    2009-01-01

    Drug development is an expensive, long and high-risk business taking 10-15 years and is associated with a high attrition rate. It is driven by medical need, disease prevalence and the likelihood of success. Drug candidate selection is an iterative process between chemistry and biology, refining the molecular properties until a compound suitable for advancing to man is found. Typically, about one in a thousand synthesised compounds is ever selected for progression to the clinic. Prior to administration to humans, the pharmacology and biochemistry of the drug is established using an extensive range of in vitro and in vivo test procedures. It is also a regulatory requirement that the drug is administered to animals to assess its safety. Later-stage animal testing is also required to assess carcinogenicity and effects on the reproductive system. Clinical phases of drug development include phase I in healthy volunteers to assess primarily pharmacokinetics, safety and toleration, phase II in a cohort of patients with the target disease to establish efficacy and dose-response relationship and large-scale phase III studies to confirm safety and efficacy. Experience tells us that approximately only 1 in 10 drugs that start the clinical phase will make it to the market. Each drug must demonstrate safety and efficacy in the intended patient population and its benefits must outweigh its risks before it will be approved by the regulatory agencies. Strict regulatory standards govern the conduct of pre-clinical and clinical trials as well as the manufacturing of pharmaceutical products. The assessment of the new medicinal product's safety continues beyond the initial drug approval through post-marketing monitoring of adverse events. Copyright 2009 S. Karger AG, Basel.

  5. Drug Development for Metastasis Prevention.

    Science.gov (United States)

    Fontebasso, Yari; Dubinett, Steven M

    2015-01-01

    Metastatic disease is responsible for 90% of death from solid tumors. However, only a minority of metastasis-specific targets has been exploited therapeutically, and effective prevention and suppression of metastatic disease is still an elusive goal. In this review, we will first summarize the current state of knowledge about the molecular features of the disease, with particular focus on steps and targets potentially amenable to therapeutic intervention. We will then discuss the reasons underlying the paucity of metastatic drugs in the current oncological arsenal and potential ways to overcome this therapeutic gap. We reason that the discovery of novel promising targets, an increased understanding of the molecular features of the disease, the effect of disruptive technologies, and a shift in the current preclinical and clinical settings have the potential to create more successful drug development endeavors.

  6. Towards a sustainable system of drug development

    NARCIS (Netherlands)

    Moors, Ellen H.M.; Cohen, Adam F.; Schellekens, Huub

    2014-01-01

    Drug development has become the exclusive activity of large pharmaceutical companies. However, the output of new drugs has been decreasing for the past decade and the prices of new drugs have risen steadily, leading to access problems for many patients. By analyzing the history of drug development

  7. Prodrug Strategy in Drug Development

    Directory of Open Access Journals (Sweden)

    Hajnal Kelemen

    2016-09-01

    Full Text Available Prodrugs are chemically modified derivatives introduced in therapy due to their advantageous physico-chemical properties (greater stability, improved solubility, increased permeability, used in inactive form. Biological effect is exerted by the active derivatives formed in organism through chemical transformation (biotransformation. Currently, 10% of pharmaceutical products are used as prodrugs, nearly half of them being converted to active form by hydrolysis, mainly by ester hydrolysis. The use of prodrugs aims to improve the bioavailability of compounds in order to resolve some unfavorable characteristics and to reduce first-pass metabolism. Other objectives are to increase drug absorption, to extend duration of action or to achieve a better tissue/organ selective transport in case of non-oral drug delivery forms. Prodrugs can be characterized by chemical structure, activation mechanism or through the presence of certain functional groups suitable for their preparation. Currently we distinguish in therapy traditional prodrugs prepared by chemical derivatisation, bioprecursors and targeted delivery systems. The present article is a review regarding the introduction and applications of prodrug design in various areas of drug development.

  8. Developments in platinum anticancer drugs

    Science.gov (United States)

    Tylkowski, Bartosz; Jastrząb, Renata; Odani, Akira

    2018-01-01

    Platinum compounds represent one of the great success stories of metals in medicine. Following the unexpected discovery of the anticancer activity of cisplatin (Fig. 1) in 1965 by Prof. Rosenberg [1], a large number of its variants have been prepared and tested for their ability to kill cancer cells and inhibit tumor growth. Although cisplatin has been in use for over four decades, new and more effective platinum-based therapeutics are finally on the horizon. A wide introduction to anticancer studies is given by the authors of the previous chapter. This chapter aims at providing the readers with a comprehensive and in-depth understanding of recent developments of platinum anticancer drugs and to review the state of the art. The chapter is divided into two parts. In the first part we present a historical aspect of platinum and its complexes, while in the second part we give an overview of developments in the field of platinum anticancer agents.

  9. Development and Optimization of controlled drug release ...

    African Journals Online (AJOL)

    The aim of this study is to develop and optimize an osmotically controlled drug delivery system of diclofenac sodium. Osmotically controlled oral drug delivery systems utilize osmotic pressure for controlled delivery of active drugs. Drug delivery from these systems, to a large extent, is independent of the physiological factors ...

  10. Orphan drugs: trends and issues in drug development.

    Science.gov (United States)

    Rana, Proteesh; Chawla, Shalini

    2018-04-12

    Research in rare diseases has contributed substantially toward the current understanding in the pathophysiology of the common diseases. However, medical needs of patients with rare diseases have always been neglected by the society and pharmaceutical industries based on their small numbers and unprofitability. The Orphan Drug Act (1983) was the first serious attempt to address the unmet medical needs for patients with rare diseases and to provide impetus for the pharmaceutical industry to promote orphan drug development. The process of drug development for rare diseases is no different from common diseases but involves significant cost and infrastructure. Further, certain aspect of drug research may not be feasible for the rare diseases. The drug-approving authority must exercise their scientific judgment and ensure due flexibility while evaluating data at various stages of orphan drug development. The emergence of patent cliff combined with the government incentives led the pharmaceutical industry to realize the good commercial prospects in developing an orphan drug despite the small market size. Indeed, many drugs that were given orphan designation ended up being blockbusters. The orphan drug market is projected to reach $178 billion by 2020, and the prospects of research and development in rare diseases appears to be quite promising and rewarding.

  11. Alternative-fueled truck demonstration natural gas program: Caterpillar G3406LE development and demonstration

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-06-01

    In 1990, the California Energy Commission, the South Coast Air Quality Management District, and the Southern California Gas Company joined together to sponsor the development and demonstration of compressed natural gas engines for Class 8 heavy-duty line-haul trucking applications. This program became part of an overall Alternative-Fueled Truck Demonstration Program, with the goal of advancing the technological development of alternative-fueled engines. The demonstration showed natural gas to be a technically viable fuel for Class 8 truck engines.

  12. 40 CFR 270.65 - Research, development, and demonstration permits.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 26 2010-07-01 2010-07-01 false Research, development, and... Special Forms of Permits § 270.65 Research, development, and demonstration permits. (a) The Administrator may issue a research, development, and demonstration permit for any hazardous waste treatment facility...

  13. Orphan drug: Development trends and strategies

    Directory of Open Access Journals (Sweden)

    Aarti Sharma

    2010-01-01

    Full Text Available The growth of pharma industries has slowed in recent years because of various reasons such as patent expiries, generic competition, drying pipelines, and increasingly stringent regulatory guidelines. Many blockbuster drugs will loose their exclusivity in next 5 years. Therefore, the current economic situation plus the huge generic competition shifted the focus of pharmaceutical companies from the essential medicines to the new business model - niche busters, also called orphan drugs. Orphan drugs may help pharma companies to reduce the impact of revenue loss caused by patent expiries of blockbuster drugs. The new business model of orphan drugs could offer an integrated healthcare solution that enables pharma companies to develop newer areas of therapeutics, diagnosis, treatment, monitoring, and patient support. Incentives for drug development provided by governments, as well as support from the FDA and EU Commission in special protocols, are a further boost for the companies developing orphan drugs. Although there may still be challenges ahead for the pharmaceutical industry, orphan drugs seem to offer the key to recovery and stability within the market. In our study, we have compared the policies and orphan drug incentives worldwide alongwith the challenges faced by the pharmaceutical companies. Recent developments are seen in orphan drug approval, the various drugs in orphan drug pipeline, and the future prospectives for orphan drugs and diseases.

  14. NMR spectroscopy and drug development

    International Nuclear Information System (INIS)

    Craik, D.; Munro, S.

    1990-01-01

    The use of nuclear magnetic resonance (NMR) spectroscopy for structural and conformational studies on drug molecules, the three-dimensional investigation of proteins structure and their interactions with ligands are discussed. In-vivo NMR studies of the effects of drugs on metabolism in perfused organs and whole animals are also briefly presented. 5 refs., ills

  15. 10 CFR 1021.212 - Research, development, demonstration, and testing.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Research, development, demonstration, and testing. 1021... ACT IMPLEMENTING PROCEDURES DOE Decisionmaking § 1021.212 Research, development, demonstration, and testing. (a) This section applies to the adoption and application of programs that involve research...

  16. Pediatric Melanoma and Drug Development

    Directory of Open Access Journals (Sweden)

    Klaus Rose

    2018-03-01

    Full Text Available Importance—Pediatric melanoma occurs, albeit rarely. Should patients be treated by today’s medical standards, or be subjected to medically unnecessary clinical studies? Observations—We identified international, industry-sponsored pediatric melanoma studies triggered by regulatory demands in www.clinicaltrials.gov and further pediatric melanoma studies demanded by European Union pediatric investigation plans. We retrieved related regulatory documents from the internet. We analyzed these studies for rationale and medical beneficence on the basis of physiology, pediatric clinical pharmacology and rationale. Regulatory authorities define children by chronological age, not physiologically. Newborns’ organs are immature but they develop and mature rapidly. Separate proof of efficacy in underage patients is justified formally/regulatorily but lacks medical sense. Children—especially post-puberty—and adults vis-a-vis medications are physiologically very similar. Two adolescent melanoma studies were terminated in 2016 because of waning recruitment, while five studies in pediatric melanoma and other solid tumors, triggered by European Union pediatric investigation plans, continue recruiting worldwide. Conclusions and Relevance—Regulatory-demanded pediatric melanoma studies are medically superfluous. Melanoma patients of all ages should be treated with effective combination treatment. Babies need special attention. Children need dose-finding and pharmacokinetic studies but adolescents metabolize and respond to drugs similarly to adults. Institutional Review Boards/ethics committees should suspend ongoing questionable pediatric melanoma studies and reject newly submitted questionable studies.

  17. Use of SPring-8 in drug development

    International Nuclear Information System (INIS)

    Nishijima, Kazumi

    2006-01-01

    Protein structure analysis consortium was established by 21 drug companies and has analyzed protein structures using the beam line BL32B2 of SPring-8 since September in 2002. Outline of the protein structure analysis consortium, contribution of SPring-8 to drug development, and the present status and future of use of SPring-8 are stated. For examples of structure analysis, the human nuclear enzyme (PARP-1) fragment complex crystal structure, human ISG20, human dipeptidine peptidase IV, human cMDH, chromatin binding human nuclear enzyme complex, change of structure of each step of tyrosine activation of bacteria tyrosine tRNA synthetase are described. Contribution of analysis of protein structure and functions to drug development, development process of new drug, drug screening using compounds database on the basis of the three dimensional structure of receptor active site, genome drug development, and the effects of a target drug on the market are explained. (S.Y.)

  18. Pharmacometrics in early clinical drug development

    NARCIS (Netherlands)

    Keizer, R.J.

    2010-01-01

    Pharmacometrics, the science of quantitative clinical pharmacology, has been recognized as one of the main research fields able to improve efficiency in drug development, and to reduce attrition rates on the route from drug discovery to approval. This field of drug research, which builds heavily on

  19. Antimalarial Drug: From its Development to Deface.

    Science.gov (United States)

    Barik, Tapan Kumar

    2015-01-01

    Wiping out malaria is now the global concern as about three billion people are at risk of malaria infection globally. Despite of extensive research in the field of vaccine development for malaria, till now, no effective vaccine is available for use and hence only antimalarial drugs remain our best hope for both treatment and prevention of malaria. However, emergence and spread of drug resistance has been a major obstacle for the success of malaria elimination globally. This review will summarize the information related to antimalarial drugs, drug development strategies, drug delivery through nanoparticles, few current issues like adverse side effects of most antimalarial drugs, non availability of drugs in the market and use of fake/poor quality drugs that are hurdles to malaria control. As we don't have any other option in the present scenario, we have to take care of the existing tools and make them available to almost all malaria affected area.

  20. Biomarker-guided repurposing of chemotherapeutic drugs for cancer therapy: a novel strategy in drug development

    Directory of Open Access Journals (Sweden)

    Jan eStenvang

    2013-12-01

    Full Text Available Cancer is a leading cause of mortality worldwide and matters are only set to worsen as its incidence continues to rise. Traditional approaches to combat cancer include improved prevention, early diagnosis, optimized surgery, development of novel drugs and honing regimens of existing anti-cancer drugs. Although discovery and development of novel and effective anti-cancer drugs is a major research area, it is well known that oncology drug development is a lengthy process, extremely costly and with high attrition rates. Furthermore, those drugs that do make it through the drug development mill are often quite expensive, laden with severe side-effects and, unfortunately, to date, have only demonstrated minimal increases in overall survival. Therefore, a strong interest has emerged to identify approved non-cancer drugs that possess anti-cancer activity, thus shortcutting the development process. This research strategy is commonly known as drug repurposing or drug repositioning and provides a faster path to the clinics. We have developed and implemented a modification of the standard drug repurposing strategy that we review here; rather than investigating target-promiscuous non-cancer drugs for possible anti-cancer activity, we focus on the discovery of novel cancer indications for already approved chemotherapeutic anti-cancer drugs. Clinical implementation of this strategy is normally commenced at clinical phase II trials and includes pre-treated patients. As the response rates to any non-standard chemotherapeutic drug will be relatively low in such a patient cohort it is a pre-requisite that such testing is based on predictive biomarkers. This review describes our strategy of biomarker-guided repurposing of chemotherapeutic drugs for cancer therapy, taking the repurposing of topoisomerase I inhibitors and topoisomerase I as a potential predictive biomarker as case in point.

  1. Positron emission tomography in drug development

    International Nuclear Information System (INIS)

    Rubin, R. H.; Fischman, A. J.

    1997-01-01

    There are four kinds of measurements that can be carried out with positron emission tomography (PET) that can contribute significantly to the process of drug development: pharmacodynamic measurement of tissue metabolism influenced by a given drug; precise measurements of tissue blood flow; tissue pharmacokinetics of a given drug following administration of a particular dose; and the temporal course of ligand-receptor interaction. One or more of these measurements can greatly improve the decision making involved in determining the appropriate dose of a drug, the clinical situations in which a drug might be useful, and the linkage of pharmacokinetics with pharmacodynamics, which is at the heart of effective drug development. The greater the potential of a particular compound as a therapeutic agent, the greater the potential for PET to contribute to the drug development process

  2. 40 CFR 258.4 - Research, development, and demonstration permits.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Research, development, and...) SOLID WASTES CRITERIA FOR MUNICIPAL SOLID WASTE LANDFILLS General § 258.4 Research, development, and... State may issue a research, development, and demonstration permit for a new MSWLF unit, existing MSWLF...

  3. 17 CFR 256.188 - Research, development, or demonstration expenditures.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Research, development, or... COMPANIES, PUBLIC UTILITY HOLDING COMPANY ACT OF 1935 4. Deferred Debits § 256.188 Research, development, or... of all expenditures for research, development or demonstration undertaken by or sponsored through the...

  4. Human In Silico Drug Trials Demonstrate Higher Accuracy than Animal Models in Predicting Clinical Pro-Arrhythmic Cardiotoxicity

    Directory of Open Access Journals (Sweden)

    Elisa Passini

    2017-09-01

    Full Text Available Early prediction of cardiotoxicity is critical for drug development. Current animal models raise ethical and translational questions, and have limited accuracy in clinical risk prediction. Human-based computer models constitute a fast, cheap and potentially effective alternative to experimental assays, also facilitating translation to human. Key challenges include consideration of inter-cellular variability in drug responses and integration of computational and experimental methods in safety pharmacology. Our aim is to evaluate the ability of in silico drug trials in populations of human action potential (AP models to predict clinical risk of drug-induced arrhythmias based on ion channel information, and to compare simulation results against experimental assays commonly used for drug testing. A control population of 1,213 human ventricular AP models in agreement with experimental recordings was constructed. In silico drug trials were performed for 62 reference compounds at multiple concentrations, using pore-block drug models (IC50/Hill coefficient. Drug-induced changes in AP biomarkers were quantified, together with occurrence of repolarization/depolarization abnormalities. Simulation results were used to predict clinical risk based on reports of Torsade de Pointes arrhythmias, and further evaluated in a subset of compounds through comparison with electrocardiograms from rabbit wedge preparations and Ca2+-transient recordings in human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs. Drug-induced changes in silico vary in magnitude depending on the specific ionic profile of each model in the population, thus allowing to identify cell sub-populations at higher risk of developing abnormal AP phenotypes. Models with low repolarization reserve (increased Ca2+/late Na+ currents and Na+/Ca2+-exchanger, reduced Na+/K+-pump are highly vulnerable to drug-induced repolarization abnormalities, while those with reduced inward current density

  5. Human In Silico Drug Trials Demonstrate Higher Accuracy than Animal Models in Predicting Clinical Pro-Arrhythmic Cardiotoxicity.

    Science.gov (United States)

    Passini, Elisa; Britton, Oliver J; Lu, Hua Rong; Rohrbacher, Jutta; Hermans, An N; Gallacher, David J; Greig, Robert J H; Bueno-Orovio, Alfonso; Rodriguez, Blanca

    2017-01-01

    Early prediction of cardiotoxicity is critical for drug development. Current animal models raise ethical and translational questions, and have limited accuracy in clinical risk prediction. Human-based computer models constitute a fast, cheap and potentially effective alternative to experimental assays, also facilitating translation to human. Key challenges include consideration of inter-cellular variability in drug responses and integration of computational and experimental methods in safety pharmacology. Our aim is to evaluate the ability of in silico drug trials in populations of human action potential (AP) models to predict clinical risk of drug-induced arrhythmias based on ion channel information, and to compare simulation results against experimental assays commonly used for drug testing. A control population of 1,213 human ventricular AP models in agreement with experimental recordings was constructed. In silico drug trials were performed for 62 reference compounds at multiple concentrations, using pore-block drug models (IC 50 /Hill coefficient). Drug-induced changes in AP biomarkers were quantified, together with occurrence of repolarization/depolarization abnormalities. Simulation results were used to predict clinical risk based on reports of Torsade de Pointes arrhythmias, and further evaluated in a subset of compounds through comparison with electrocardiograms from rabbit wedge preparations and Ca 2+ -transient recordings in human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs). Drug-induced changes in silico vary in magnitude depending on the specific ionic profile of each model in the population, thus allowing to identify cell sub-populations at higher risk of developing abnormal AP phenotypes. Models with low repolarization reserve (increased Ca 2+ /late Na + currents and Na + /Ca 2+ -exchanger, reduced Na + /K + -pump) are highly vulnerable to drug-induced repolarization abnormalities, while those with reduced inward current density

  6. 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.

  7. New Zealand’s Drug Development Industry

    Directory of Open Access Journals (Sweden)

    Christopher Carswell

    2013-09-01

    Full Text Available The pharmaceutical industry’s profitability depends on identifying and successfully developing new drug candidates while trying to contain the increasing costs of drug development. It is actively searching for new sources of innovative compounds and for mechanisms to reduce the enormous costs of developing new drug candidates. There is an opportunity for academia to further develop as a source of drug discovery. The rising levels of industry outsourcing also provide prospects for organisations that can reduce the costs of drug development. We explored the potential returns to New Zealand (NZ from its drug discovery expertise by assuming a drug development candidate is out-licensed without clinical data and has anticipated peak global sales of $350 million. We also estimated the revenue from NZ’s clinical research industry based on a standard per participant payment to study sites and the number of industry-sponsored clinical trials approved each year. Our analyses found that NZ’s clinical research industry has generated increasing foreign revenue and appropriate policy support could ensure that this continues to grow. In addition the probability-based revenue from the out-licensing of a drug development candidate could be important for NZ if provided with appropriate policy and financial support.

  8. Drug development for airway diseases: looking forward

    NARCIS (Netherlands)

    Holgate, Stephen; Agusti, Alvar; Strieter, Robert M.; Anderson, Gary P.; Fogel, Robert; Bel, Elisabeth; Martin, Thomas R.; Reiss, Theodore F.

    2015-01-01

    Advancing drug development for airway diseases beyond the established mechanisms and symptomatic therapies requires redefining the classifications of airway diseases, considering systemic manifestations, developing new tools and encouraging collaborations

  9. Molecular science for drug development and biomedicine.

    Science.gov (United States)

    Zhong, Wei-Zhu; Zhou, Shu-Feng

    2014-11-04

    With the avalanche of biological sequences generated in the postgenomic age, molecular science is facing an unprecedented challenge, i.e., how to timely utilize the huge amount of data to benefit human beings. Stimulated by such a challenge, a rapid development has taken place in molecular science, particularly in the areas associated with drug development and biomedicine, both experimental and theoretical. The current thematic issue was launched with the focus on the topic of "Molecular Science for Drug Development and Biomedicine", in hopes to further stimulate more useful techniques and findings from various approaches of molecular science for drug development and biomedicine.[...].

  10. DEVELOPMENT AND REGISTRATION OF CHIRAL DRUGS

    NARCIS (Netherlands)

    WITTE, DT; ENSING, K; FRANKE, JP; DEZEEUW, RA

    1993-01-01

    In this review we describe the impact of chirality on drug development and registration in the United States, Japan and the European Community. Enantiomers may have differences in their pharmacological profiles, and, therefore, chiral drugs ask for special analytical and pharmacological attention

  11. Development and demonstration of atmospheric electricity hazards protection

    OpenAIRE

    Beavin , R.C.; Lippert , J.R.; La Voie , J.E.

    1986-01-01

    An Advanced Development Program (ADP) to develop and demonstrate effective Atmospheric Electricity Hazards Protection (AEHP) for the fighter, transport/bomber, helicopter and cruise missile classes of air vehicles is being conducted under an Air Force Wright Aeronautical Laboratories (AFWAL) contract with Boeing Military Airplane Company (BMAC). Other Government agencies are also supporting the ADP. The parameters characterizing the lightning threat have been defined for moderate and severe f...

  12. Laboratories and Demonstrations in Child Development with Unedited Videotapes.

    Science.gov (United States)

    Poole, Debra Ann

    1986-01-01

    Multipurpose demonstrations of child development are easy to produce by videotaping children while they interact with parents, siblings, or friends. Unlike commercial films, videotapes without narration allow students to formulate and test their own research questions. This article describes how to use unedited videotapes for laboratories in…

  13. New energy technologies. Research, development and demonstration; Denmark; Nye energiteknologier. Forskning, udvikling og demonstration

    Energy Technology Data Exchange (ETDEWEB)

    Holst Joergensen, B.; Muenster, M.

    2010-12-15

    This report was commissioned by the Danish Climate Commission in 2009 to analyse how research, development and demonstration (RD and D) on sustainable energy technologies can contribute to make Denmark independent on fossil energy by 2050. It focuses on the RD and D investments needed as well as adequate framework conditions for Danish knowledge production and diffusion within this field. First part focuses on the general aspects related to knowledge production and the challenges related to research. Energy technologies are categorized and recent attempt to optimize Danish efforts are addressed, including RD and D prioritisation, public-private partnerships and international RD and D cooperation. Part two describes the development and organisation of the Danish public RD and D activities, including benchmark with other countries. The national energy RD and D programmes and their contribution to the knowledge value chain are described as well as the coordination and alignment efforts. Part Three illustrates three national innovation systems for highly different technologies - wind, fuel cells and intelligent energy systems. Finally, six recommendations are put forward: to make a national strategic energy technology plan; to enforce the coordination and synergy between national RD and D programmes; to strengthen social science research related to the transition to a sustainable energy system; to increase public RD and D expenditure to at least 0.1% of GDP per year; to strengthen international RD and D cooperation; and to make a comprehensive analysis of the capacity and competence needs for the energy sector. (Author)

  14. Development and Evaluation of Chronotherapeutic Drug Delivery ...

    African Journals Online (AJOL)

    Conclusion: The developed system is capable of releasing the drug after a 4-h lag period. However ... concentration would be at its maximum level, ... spheronizer (Caleva MBS, UK)operating at .... capsules show that the color intensity of the.

  15. Advanced Simulation Capability for Environmental Management: Development and Demonstrations - 12532

    Energy Technology Data Exchange (ETDEWEB)

    Freshley, Mark D.; Freedman, Vicky; Gorton, Ian [Pacific Northwest National Laboratory, MSIN K9-33, P.O. Box 999, Richland, WA 99352 (United States); Hubbard, Susan S. [Lawrence Berkeley National Laboratory, 1 Cyclotron Road, MS 50B-4230, Berkeley, CA 94720 (United States); Moulton, J. David; Dixon, Paul [Los Alamos National Laboratory, MS B284, P.O. Box 1663, Los Alamos, NM 87544 (United States)

    2012-07-01

    The U.S. Department of Energy Office of Environmental Management (EM), Technology Innovation and Development is supporting development of the Advanced Simulation Capability for Environmental Management (ASCEM). ASCEM is a state-of-the-art scientific tool and approach for understanding and predicting contaminant fate and transport in natural and engineered systems. The modular and open source high-performance computing tool facilitates integrated approaches to modeling and site characterization that enable robust and standardized assessments of performance and risk for EM cleanup and closure activities. The ASCEM project continues to make significant progress in development of capabilities, which are organized into Platform and Integrated Tool-sets and a High-Performance Computing Multi-process Simulator. The Platform capabilities target a level of functionality to allow end-to-end model development, starting with definition of the conceptual model and management of data for model input. The High-Performance Computing capabilities target increased functionality of process model representations, tool-sets for interaction with Platform, and verification and model confidence testing. The new capabilities are demonstrated through working groups, including one focused on the Hanford Site Deep Vadose Zone. The ASCEM program focused on planning during the first year and executing a prototype tool-set for an early demonstration of individual components. Subsequently, ASCEM has focused on developing and demonstrating an integrated set of capabilities, making progress toward a version of the capabilities that can be used to engage end users. Demonstration of capabilities continues to be implemented through working groups. Three different working groups, one focused on EM problems in the deep vadose zone, another investigating attenuation mechanisms for metals and radionuclides, and a third focusing on waste tank performance assessment, continue to make progress. The project

  16. Technology Development and Demonstration Concepts for the Space Elevator

    Science.gov (United States)

    Smitherman, David V., Jr.

    2004-01-01

    During the 1990s several discoveries and advances in the development of carbon nano-tube (CNT) materials indicated that material strengths many times greater than common high-strength composite materials might be possible. Progress in the development of this material led to renewed interest in the space elevator concept for construction of a tether structure from the surface of the Earth through a geostationary orbit (GEO) and thus creating a new approach to Earth-to-orbit transportation infrastructures. To investigate this possibility the author, in 1999, managed for NASA a space elevator work:hop at the Marshall Space Flight Center to explore the potential feasibility of space elevators in the 21 century, and to identify the critical technologies and demonstration missions needed to make development of space elevators feasible. Since that time, a NASA Institute for Advanced Concepts (NIAC) funded study of the Space Elevator proposed a concept for a simpler first space elevator system using more near-term technologies. This paper will review some of the latest ideas for space elevator development, the critical technologies required, and some of the ideas proposed for demonstrating the feasibility for full-scale development of an Earth to GEO space elevator. Critical technologies include CNT composite materials, wireless power transmission, orbital object avoidance, and large-scale tether deployment and control systems. Numerous paths for technology demonstrations have been proposed utilizing ground experiments, air structures. LEO missions, the space shuttle, the international Space Station, GEO demonstration missions, demonstrations at the lunar L1 or L2 points, and other locations. In conclusion, this paper finds that the most critical technologies for an Earth to GEO space elevator include CNT composite materials development and object avoidance technologies; that lack of successful development of these technologies need not preclude continued development of

  17. 78 FR 72840 - Drug Products That Present Demonstrable Difficulties for Compounding Under Sections 503A and 503B...

    Science.gov (United States)

    2013-12-04

    ... reasonably demonstrate an adverse effect on the safety or effectiveness of that drug product'' (section 503A... because it included restrictions on the advertising or promotion of the compounding of any particular drug... effect on the safety or effectiveness of that drug product. In addition, the DQSA adds a new section 503B...

  18. INTERNATIONAL ENVIRONMENTAL TECHNOLOGY IDENTIFICATION, DEVELOPMENT, DEMONSTRATION, DEPLOYMENT AND EXCHANGE

    Energy Technology Data Exchange (ETDEWEB)

    Roy C. Herndon

    2001-02-28

    Cooperative Agreement (DE-FC21-95EW55101) between the U.S. Department of Energy (DOE) and the Florida State University's Institute for International Cooperative Environmental Research (IICER) was designed to facilitate a number of joint programmatic goals of both the DOE and the IICER related to international technology identification, development, demonstration and deployment using a variety of mechanisms to accomplish these goals. These mechanisms included: laboratory and field research; technology demonstrations; international training and technical exchanges; data collection, synthesis and evaluation; the conduct of conferences, symposia and high-level meetings; and other appropriate and effective approaches. The DOE utilized the expertise and facilities of the IICER at Florida State University to accomplish its goals related to this cooperative agreement. The IICER has unique and demonstrated capabilities that have been utilized to conduct the tasks for this cooperative agreement. The IICER conducted activities related to technology identification, development, evaluation, demonstration and deployment through its joint centers which link the capabilities at Florida State University with collaborating academic and leading research institutions in the major countries of Central and Eastern Europe (e.g., Czech Republic, Hungary, Poland) and Russia. The activities and accomplishments for this five-year cooperative agreement are summarized in this Final Technical Report.

  19. Clean coal technologies: Research, development, and demonstration program plan

    Energy Technology Data Exchange (ETDEWEB)

    1993-12-01

    The US Department of Energy, Office of Fossil Energy, has structured an integrated program for research, development, and demonstration of clean coal technologies that will enable the nation to use its plentiful domestic coal resources while meeting environmental quality requirements. The program provides the basis for making coal a low-cost, environmentally sound energy choice for electric power generation and fuels production. These programs are briefly described.

  20. Development of fresh fuel packaging for ATR demonstration reactor

    International Nuclear Information System (INIS)

    Kurakami, J.; Kurita, I.

    1993-01-01

    Related to development of the demonstration advanced thermal reactor, it is necessary and important to develop transport packaging which is used for transporting fresh fuel assemblies. Therefore, the packaging is now being developed in Power Reactor and Nuclear Fuel Development Corporation (PNC). Currently, PNC is fabricating two prototype packagings based on the final design, and land cruising and vibration tests, handling performance tests and prototype packaging tests will be executed with prototype packagings in order to experimentally confirm the soundness of packaging and its contents and the propriety of design technique. This paper describes the summary of general specifications and structures of this packaging and the summary of preliminary safety analysis of package. (J.P.N.)

  1. Demonstration of Decision Support Tools for Sustainable Development

    Energy Technology Data Exchange (ETDEWEB)

    Shropshire, David Earl; Jacobson, Jacob Jordan; Berrett, Sharon; Cobb, D. A.; Worhach, P.

    2000-11-01

    The Demonstration of Decision Support Tools for Sustainable Development project integrated the Bechtel/Nexant Industrial Materials Exchange Planner and the Idaho National Engineering and Environmental Laboratory System Dynamic models, demonstrating their capabilities on alternative fuel applications in the Greater Yellowstone-Teton Park system. The combined model, called the Dynamic Industrial Material Exchange, was used on selected test cases in the Greater Yellow Teton Parks region to evaluate economic, environmental, and social implications of alternative fuel applications, and identifying primary and secondary industries. The test cases included looking at compressed natural gas applications in Teton National Park and Jackson, Wyoming, and studying ethanol use in Yellowstone National Park and gateway cities in Montana. With further development, the system could be used to assist decision-makers (local government, planners, vehicle purchasers, and fuel suppliers) in selecting alternative fuels, vehicles, and developing AF infrastructures. The system could become a regional AF market assessment tool that could help decision-makers understand the behavior of the AF market and conditions in which the market would grow. Based on this high level market assessment, investors and decision-makers would become more knowledgeable of the AF market opportunity before developing detailed plans and preparing financial analysis.

  2. Phase 1 Development Testing of the Advanced Manufacturing Demonstrator Engine

    Science.gov (United States)

    Case, Nicholas L.; Eddleman, David E.; Calvert, Marty R.; Bullard, David B.; Martin, Michael A.; Wall, Thomas R.

    2016-01-01

    The Additive Manufacturing Development Breadboard Engine (BBE) is a pressure-fed liquid oxygen/pump-fed liquid hydrogen (LOX/LH2) expander cycle engine that was built and operated by NASA at Marshall Space Flight Center's East Test Area. The breadboard engine was conceived as a technology demonstrator for the additive manufacturing technologies for an advanced upper stage prototype engine. The components tested on the breadboard engine included an ablative chamber, injector, main fuel valve, turbine bypass valve, a main oxidizer valve, a mixer and the fuel turbopump. All parts minus the ablative chamber were additively manufactured. The BBE was successfully hot fire tested seven times. Data collected from the test series will be used for follow on demonstration tests with a liquid oxygen turbopump and a regeneratively cooled chamber and nozzle.

  3. TRPV3 in Drug Development

    Directory of Open Access Journals (Sweden)

    Lisa M. Broad

    2016-09-01

    Full Text Available Transient receptor potential vanilloid 3 (TRPV3 is a member of the TRP (Transient Receptor Potential super-family. It is a relatively underexplored member of the thermo-TRP sub-family (Figure 1, however, genetic mutations and use of gene knock-outs and selective pharmacological tools are helping to provide insights into its role and therapeutic potential. TRPV3 is highly expressed in skin, where it is implicated in skin physiology and pathophysiology, thermo-sensing and nociception. Gain of function TRPV3 mutations in rodent and man have enabled the role of TRPV3 in skin health and disease to be particularly well defined. Pre-clinical studies provide some rationale to support development of TRPV3 antagonists for therapeutic application for the treatment of inflammatory skin conditions, itch and pain. However, to date, only one compound directed towards block of the TRPV3 receptor (GRC15300 has progressed into clinical trials. Currently, there are no known clinical trials in progress employing a TRPV3 antagonist.

  4. Northwest Hazardous Waste Research, Development, and Demonstration Center: Program Plan

    International Nuclear Information System (INIS)

    1988-02-01

    The Northwest Hazardous Waste Research, Development, and Demonstration Center was created as part of an ongoing federal effort to provide technologies and methods that protect human health and welfare and environment from hazardous wastes. The Center was established by the Superfund Amendments and Reauthorization Act (SARA) to develop and adapt innovative technologies and methods for assessing the impacts of and remediating inactive hazardous and radioactive mixed-waste sites. The Superfund legislation authorized $10 million for Pacific Northwest Laboratory to establish and operate the Center over a 5-year period. Under this legislation, Congress authorized $10 million each to support research, development, and demonstration (RD and D) on hazardous and radioactive mixed-waste problems in Idaho, Montana, Oregon, and Washington, including the Hanford Site. In 1987, the Center initiated its RD and D activities and prepared this Program Plan that presents the framework within which the Center will carry out its mission. Section 1.0 describes the Center, its mission, objectives, organization, and relationship to other programs. Section 2.0 describes the Center's RD and D strategy and contains the RD and D objectives, priorities, and process to be used to select specific projects. Section 3.0 contains the Center's FY 1988 operating plan and describes the specific RD and D projects to be carried out and their budgets and schedules. 9 refs., 18 figs., 5 tabs

  5. Texas LPG fuel cell development and demonstration project

    Energy Technology Data Exchange (ETDEWEB)

    None, None

    2004-07-26

    The State Energy Conservation Office has executed its first Fuel Cell Project which was awarded under a Department of Energy competitive grant process. The Texas LPG Fuel Processor Development and Fuel Cell Demonstration Program is a broad-based public/private partnership led by the Texas State Energy Conservation Office (SECO). Partners include the Alternative Fuels Research and Education Division (AFRED) of the Railroad Commission of Texas; Plug Power, Inc., Latham, NY, UOP/HyRadix, Des Plaines, IL; Southwest Research Institute (SwRI), San Antonio, TX; the Texas Natural Resource Conservation Commission (TNRCC), and the Texas Department of Transportation (TxDOT). The team proposes to mount a development and demonstration program to field-test and evaluate markets for HyRadix's LPG fuel processor system integrated into Plug Power's residential-scale GenSys(TM) 5C (5 kW) PEM fuel cell system in a variety of building types and conditions of service. The program's primary goal is to develop, test, and install a prototype propane-fueled residential fuel cell power system supplied by Plug Power and HyRadix in Texas. The propane industry is currently funding development of an optimized propane fuel processor by project partner UOP/HyRadix through its national checkoff program, the Propane Education and Research Council (PERC). Following integration and independent verification of performance by Southwest Research Institute, Plug Power and HyRadix will produce a production-ready prototype unit for use in a field demonstration. The demonstration unit produced during this task will be delivered and installed at the Texas Department of Transportation's TransGuide headquarters in San Antonio, Texas. Simultaneously, the team will undertake a market study aimed at identifying and quantifying early-entry customers, technical and regulatory requirements, and other challenges and opportunities that need to be addressed in planning commercialization of the units

  6. Development Considerations for Nanocrystal Drug Products.

    Science.gov (United States)

    Chen, Mei-Ling; John, Mathew; Lee, Sau L; Tyner, Katherine M

    2017-05-01

    Nanocrystal technology has emerged as a valuable tool for facilitating the delivery of poorly water-soluble active pharmaceutical ingredients (APIs) and enhancing API bioavailability. To date, the US Food and Drug Administration (FDA) has received over 80 applications for drug products containing nanocrystals. These products can be delivered by different routes of administration and are used in a variety of therapeutic areas. To aid in identifying key developmental considerations for these products, a retrospective analysis was performed on the submissions received by the FDA to date. Over 60% of the submissions were for the oral route of administration. Based on the Biopharmaceutics Classification System (BCS), most nanocrystal drugs submitted to the FDA are class II compounds that possess low aqueous solubility and high intestinal permeability. Impact of food on drug bioavailability was reduced for most nanocrystal formulations as compared with their micronized counterparts. For all routes of administration, dose proportionality was observed for some, but not all, nanocrystal products. Particular emphasis in the development of nanocrystal products was placed on the in-process tests and controls at critical manufacturing steps (such as milling process), mitigation and control of process-related impurities, and the stability of APIs or polymorphic form (s) during manufacturing and upon storage. This emphasis resulted in identifying challenges to the development of these products including accurate determination of particle size (distribution) of drug substance and/or nanocrystal colloidal dispersion, identification of polymorphic form (s), and establishment of drug substance/product specifications.

  7. Drug Repurposing Is a New Opportunity for Developing Drugs against Neuropsychiatric Disorders

    Directory of Open Access Journals (Sweden)

    Hyeong-Min Lee

    2016-01-01

    Full Text Available Better the drugs you know than the drugs you do not know. Drug repurposing is a promising, fast, and cost effective method that can overcome traditional de novo drug discovery and development challenges of targeting neuropsychiatric and other disorders. Drug discovery and development targeting neuropsychiatric disorders are complicated because of the limitations in understanding pathophysiological phenomena. In addition, traditional de novo drug discovery and development are risky, expensive, and time-consuming processes. One alternative approach, drug repurposing, has emerged taking advantage of off-target effects of the existing drugs. In order to identify new opportunities for the existing drugs, it is essential for us to understand the mechanisms of action of drugs, both biologically and pharmacologically. By doing this, drug repurposing would be a more effective method to develop drugs against neuropsychiatric and other disorders. Here, we review the difficulties in drug discovery and development in neuropsychiatric disorders and the extent and perspectives of drug repurposing.

  8. Success rates for product development strategies in new drug development.

    Science.gov (United States)

    Dahlin, E; Nelson, G M; Haynes, M; Sargeant, F

    2016-04-01

    While research has examined the likelihood that drugs progress across phases of clinical trials, no research to date has examined the types of product development strategies that are the most likely to be successful in clinical trials. This research seeks to identify the strategies that are most likely to reach the market-those generated using a novel product development strategy or strategies that combine a company's expertise with both drugs and indications, which we call combined experience strategies. We evaluate the success of product development strategies in the drug development process for a sample of 2562 clinical trials completed by 406 US pharmaceutical companies. To identify product development strategies, we coded each clinical trial according to whether it consisted of an indication or a drug that was new to the firm. Accordingly, a clinical trial that consists of both an indication and a drug that were both new to the firm represents a novel product development strategy; indication experience is a product development strategy that consists of an indication that a firm had tested previously in a clinical trial, but with a drug that was new to the firm; drug experience is a product development strategy that consists of a drug that the firm had prior experience testing in clinical trials, but with an indication that was new to the firm; combined experience consists of both a drug and an indication that the firm had experience testing in clinical trials. Success rates for product development strategies across clinical phases were calculated for the clinical trials in our sample. Combined experience strategies had the highest success rate. More than three and a half percent (0·036) of the trials that combined experience with drugs and indications eventually reached the market. The next most successful strategy is drug experience (0·025) with novel strategies trailing closely (0·024). Indication experience strategies are the least successful (0·008

  9. Phase II clinical development of new drugs

    CERN Document Server

    Ting, Naitee; Ho, Shuyen; Cappelleri, Joseph C

    2017-01-01

    This book focuses on how to appropriately plan and develop a Phase II program, and how to design Phase II clinical trials and analyze their data. It provides a comprehensive overview of the entire drug development process and highlights key questions that need to be addressed for the successful execution of Phase II, so as to increase its success in Phase III and for drug approval. Lastly it warns project team members of the common potential pitfalls and offers tips on how to avoid them.

  10. Recent activities of SOFC research development and demonstration in Japan

    Energy Technology Data Exchange (ETDEWEB)

    Yokokawa, Harumi [National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki (Japan); Tokyo City Univ. (Japan). Advanced Research Labs.

    2010-07-01

    Currently Japanese efforts in developing the SOFC systems have two major targets; one is small SOFC cogeneration systems for residential houses or small business sites, the other being the SOFC-GT hybrid systems with an aim at larger stationary applications. The former activity exhibits impressively rapid progress in system development and demonstration in actual residential environment. On the other hand, the development of hybrid systems is not so rapid but successfully has continued to test the operation of the hybrid system in a 200 kW class. The common requirement for both applications is high durability such as 40,000-100,000 of life. To achieve a long life simultaneously with reasonably low price and high efficiency the NEDO project is going on to promote the cooperation among the stack developers, national institute and universities. To achieve well organized cooperation, it is highly required to create mutual reliance between industry and academic organizations. After several years' experience, progress has been made in maturing cooperation and in leading to many new insights into physicochemical understanding of degradation phenomena. Some of them will be reported. (orig.)

  11. Hazardous Waste Development, Demonstration, and Disposal (HAZWDDD) Program Plan

    International Nuclear Information System (INIS)

    McGinnis, C.P.; Eisenhower, B.M.; Reeves, M.E.; DePaoli, S.M.; Stinton, L.H.; Harrington, E.H.

    1989-02-01

    The objective of the Hazardous Waste Development, Demonstration and Disposal (HAZWDDD) Program Plan is to ensure that the needs for treatment and disposal of all its hazardous and mixed wastes have been identified and planned for. A multifaceted approach to developing and implementing this plan is given, including complete plans for each of the five installations, and an overall integrated plan is also described in this report. The HAZWDDD Plan accomplishes the following: (1) provides background and organizational information; (2) summarizes the 402 hazardous and mixed waste streams from the five installations by grouping them into 13 general waste categories; (3) presents current treatment, storage, and disposal capabilities within Energy Systems; (4) develops a management strategy by outlining critical issues, presents flow sheets describing management schemes for problem waste streams, and builds on the needs identified; (5) outlines specific activities needed to implement the strategy developed; and (6) presents schedule and budget requirements for the next decade. The HAZWDDD Program addresses current and future technical problems and regulatory issues and uncertainties. Because of the nature and magnitude of the problems in hazardous and mixed waste management, substantial funding will be required. 10 refs., 39 figs., 16 tabs

  12. Nevada Test Site-Directed Research, Development, and Demonstration

    International Nuclear Information System (INIS)

    Will Lewis, Compiler

    2006-01-01

    The Nevada Test Site-Directed Research, Development, and Demonstration (SDRD) program completed a very successful year of research and development activities in FY 2005. Fifty new projects were selected for funding this year, and five FY 2004 projects were brought to conclusion. The total funds expended by the SDRD program were $5.4 million, for an average per project cost of just under $100,000. Two external audits of SDRD accounting practices were conducted in FY 2005. Both audits found the program's accounting practices consistent with the requirements of DOE Order 413.2A, and one included the observation that the NTS contractor ''did an exceptional job in planning and executing year-start activities.'' Highlights for the year included: the filing of 18 invention disclosures for intellectual property generated by FY 2005 projects; programmatic adoption of 17 FY 2004 SDRD-developed technologies; participation in the tri-lab Laboratory Directed Research and Development (LDRD) and SDRD program review that was broadly attended by NTS, NNSA, LDRD, and U.S. Department of Homeland Security representatives; peer reviews of all FY 2005 projects; and the successful completion of 55 R and D projects, as presented in this report

  13. Mathematical modeling for novel cancer drug discovery and development.

    Science.gov (United States)

    Zhang, Ping; Brusic, Vladimir

    2014-10-01

    Mathematical modeling enables: the in silico classification of cancers, the prediction of disease outcomes, optimization of therapy, identification of promising drug targets and prediction of resistance to anticancer drugs. In silico pre-screened drug targets can be validated by a small number of carefully selected experiments. This review discusses the basics of mathematical modeling in cancer drug discovery and development. The topics include in silico discovery of novel molecular drug targets, optimization of immunotherapies, personalized medicine and guiding preclinical and clinical trials. Breast cancer has been used to demonstrate the applications of mathematical modeling in cancer diagnostics, the identification of high-risk population, cancer screening strategies, prediction of tumor growth and guiding cancer treatment. Mathematical models are the key components of the toolkit used in the fight against cancer. The combinatorial complexity of new drugs discovery is enormous, making systematic drug discovery, by experimentation, alone difficult if not impossible. The biggest challenges include seamless integration of growing data, information and knowledge, and making them available for a multiplicity of analyses. Mathematical models are essential for bringing cancer drug discovery into the era of Omics, Big Data and personalized medicine.

  14. Challenges in developing drugs for primary headaches

    DEFF Research Database (Denmark)

    Schytz, Henrik Winther; Hargreaves, Richard; Ashina, Messoud

    2017-01-01

    This review considers the history of drug development in primary headaches and discusses challenges to the discovery of innovative headache therapeutics. Advances in headache genetics have yet to translate to new classes of therapeutics and there are currently no clear predictive human biomarkers...... for any of the primary headaches that can guide preventative drug discovery and development. Primary headache disorder subtypes despite common phenotypic presentation are undoubtedly heterogeneous in their pathophysiology as judged by the variability of response to headache medicines. Sub......, despite having promising effects in basic pain models, have not delivered efficacy in the clinic. Future efforts may triage novel physiological mediators using human experimental models of headache pain to support drug discovery strategies that target active pathways pharmacologically....

  15. Development and demonstration program for dynamic nuclear materials control

    International Nuclear Information System (INIS)

    Augustson, R.H.; Baron, N.; Ford, R.F.; Ford, W.; Hagen, J.; Li, T.K.; Marshall, R.S.; Reams, V.S.; Severe, W.R.; Shirk, D.G.

    1978-01-01

    A significant portion of the Los Alamos Scientific Laboratory Safeguards Program is directed toward the development and demonstration of dynamic nuclear materials control. The building chosen for the demonstration system is the new Plutonium Processing Facility in Los Alamos, which houses such operations as metal-to-oxide conversion, fuel pellet fabrication, and scrap recovery. A DYnamic MAterials Control (DYMAC) system is currently being installed in the facility as an integral part of the processing operation. DYMAC is structured around interlocking unit-process accounting areas. It relies heavily on nondestructive assay measurements made in the process line to draw dynamic material balances in near real time. In conjunction with the nondestructive assay instrumentation, process operators use interactive terminals to transmit additional accounting and process information to a dedicated computer. The computer verifies and organizes the incoming data, immediately updates the inventory records, monitors material in transit using elapsed time, and alerts the Nuclear Materials Officer in the event that material balances exceed the predetermined action limits. DYMAC is part of the United States safeguards system under control of the facility operator. Because of its advanced features, the system will present a new set of inspection conditions to the IAEA, whose response is the subject of a study being sponsored by the US-IAEA Technical Assistance Program. The central issue is how the IAEA can use the increased capabilities of such a system and still maintain independent verification

  16. Waste water pilot plant research, development, and demonstration permit application

    International Nuclear Information System (INIS)

    1993-03-01

    This permit application has been prepared to obtain a research, development, and demonstration permit to perform pilot-scale treatability testing on the 242-A Evaporator process condensate waste water effluent stream. It provides the management framework, and controls all the testing conducted in the waste water pilot plant using dangerous waste. It also provides a waste acceptance envelope (upper limits for selected constituents) and details the safety and environmental protection requirements for waste water pilot plant testing. This permit application describes the overall approach to testing and the various components or requirements that are common to all tests. This permit application has been prepared at a sufficient level of detail to establish permit conditions for all waste water pilot plant tests to be conducted

  17. The intersection of stress, drug abuse and development.

    Science.gov (United States)

    Thadani, Pushpa V

    2002-01-01

    Use or abuse of licit and illicit substances is often associated with environmental stress. Current clinical evidence clearly demonstrates neurobehavioral, somatic growth and developmental deficits in children born to drug-using mothers. However, the effects of environmental stress and its interaction with prenatal drug exposure on a child's development is unknown. Studies in pregnant animals under controlled conditions show drug-induced long-term alterations in brain structures and functions of the offspring. These cytoarchitecture alterations in the brain are often associated with perturbations in neurotransmitter systems that are intimately involved in the regulation of the stress responses. Similar abnormalities have been observed in the brains of animals exposed to other adverse exogenous (e.g., environmental stress) and/or endogenous (e.g., glucocorticoids) experiences during early life. The goal of this article is to: (1) provide evidence and a perspective that common neural systems are influenced during development both by perinatal drug exposure and early stress exposure; and (2) identify gaps and encourage new research examining the effects of early stress and perinatal drug exposure, in animal models, that would elucidate how stress- and drug-induced perturbations in neural systems influence later vulnerability to abused drugs in adult offspring.

  18. A Trojan horse in drug development

    DEFF Research Database (Denmark)

    Christensen, Søren Brøgger; Skytte, Dorthe Mondrup; Denmeade, Samuel R

    2009-01-01

    Available chemotherapeutics take advantage of the fast proliferation of cancer cells. Consequently slow growth makes androgen refractory prostate cancer resistant towards available drugs. No treatment is available at the present, when the cancer has developed metastases outside the prostate (T4 s...

  19. Has molecular imaging delivered to drug development?

    Science.gov (United States)

    Murphy, Philip S.; Patel, Neel; McCarthy, Timothy J.

    2017-10-01

    Pharmaceutical research and development requires a systematic interrogation of a candidate molecule through clinical studies. To ensure resources are spent on only the most promising molecules, early clinical studies must understand fundamental attributes of the drug candidate, including exposure at the target site, target binding and pharmacological response in disease. Molecular imaging has the potential to quantitatively characterize these properties in small, efficient clinical studies. Specific benefits of molecular imaging in this setting (compared to blood and tissue sampling) include non-invasiveness and the ability to survey the whole body temporally. These methods have been adopted primarily for neuroscience drug development, catalysed by the inability to access the brain compartment by other means. If we believe molecular imaging is a technology platform able to underpin clinical drug development, why is it not adopted further to enable earlier decisions? This article considers current drug development needs, progress towards integration of molecular imaging into studies, current impediments and proposed models to broaden use and increase impact. This article is part of the themed issue 'Challenges for chemistry in molecular imaging'.

  20. Challenges in the clinical development of new antiepileptic drugs.

    Science.gov (United States)

    Franco, Valentina; French, Jacqueline A; Perucca, Emilio

    2016-01-01

    Despite the current availability in the market of over two dozen antiepileptic drugs (AEDs), about one third of people with epilepsy fail to achieve complete freedom from seizures with existing medications. Moreover, currently available AEDs have significant limitations in terms of safety, tolerability and propensity to cause or be a target for clinically important adverse drug interactions. A review of the evidence shows that there are many misperceptions about the viability of investing into new therapies for epilepsy. In fact, there are clear incentives to develop newer and more efficacious medications. Developing truly innovative drugs requires a shift in the paradigms for drug discovery, which is already taking place by building on greatly expanded knowledge about the mechanisms involved in epileptogenesis, seizure generation, seizure spread and development of co-morbidities. AED development can also benefit by a review of the methodology currently applied in clinical AED development, in order to address a number of ethical and scientific concerns. As discussed in this article, many processes of clinical drug development, from proof-of-concept-studies to ambitious programs aimed at demonstrating antiepileptogenesis and disease-modification, can be facilitated by a greater integration of preclinical and clinical science, and by application of knowledge acquired during decades of controlled epilepsy trials. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Drugs and development: the global impact of drug use and trafficking on social and economic development.

    Science.gov (United States)

    Singer, Merrill

    2008-12-01

    Locating development efforts within the context of globalism and global drug capitalism, this article examines the significant health and social impact both legal and illegal drugs have on international development efforts. The paper takes on an issue that is generally overlooked in the development debate and is not much addressed in the current international development standard, the Millennium Development Goals, and yet is one that places serious constraints on the ability of underdeveloped nations to achieve improvement. The relationship between psychotropic or "mind/mood altering" drugs and sustainable development is rooted in the contribution that the legal and illegal drug trade makes to a set of barriers to development, including: (1) interpersonal crime and community violence; (2) the corruption of public servants and the disintegration of social institutions; (3) the emergence of new or enhanced health problems; (4) the lowering of worker productivity; (5) the ensnarement of youth in drug distribution and away from productive education or employment; (6) the skewing of economies to drug production and money laundering. The paper emphasizes the need for new approaches for diminishing the burden placed by drugs on development.

  2. Reactive Leadership: Divining, Developing, and Demonstrating Community Ontologies

    Science.gov (United States)

    Graybeal, J.

    2008-12-01

    The Marine Metadata Interoperability Project (known as MMI, on the web at http://marinemetadata.org) was formed to provide leadership in metadata practices to the marine science community. In 2004 this meant finding and writing about resources and best practices, which until then were all but invisible. In 2008 the scope is far wider, encompassing comprehensive guidance, collaborative community environments, and introduction and demonstration of advanced technologies to an increasingly interested scientific domain. MMI's technical leadership, based on experiences gained in the hydrologic community, emphasized the role ontologies could play in marine science. An early MMI workshop successfully incorporated a large number of community vocabularies, tools to harmonize them in a common ontological format, and the mapping of terms from vocabularies expressed in that format. That 2005 workshop demonstrated the connections to be made among different community vocabularies, and was well regarded by participants, but did not lead to widespread adoption of the tools, technologies, or even the vocabularies. Ontology development efforts for marine sensors and platforms showed intermittent progress, but again were not adopted or pushed toward completion. It is now 2008, and the marine community is increasingly attentive to a wide range of interoperability issues. A large part of the community has at least heard of "semantic interoperability", and many understand its critical role in finding and working with data. Demand for specific solutions, and for workable approaches, is becoming more vocal in the marine community. Yet there is still no encompassing model in place for achieving semantic interoperability, only simple operational registries have been set up for oceanographic community vocabularies, and only a few isolated applications demonstrate how semantic barriers can be overcome. Why has progress been so slow? Are good answers on the horizon? And if we build it, will the

  3. Secure, Mobile, Wireless Network Technology Designed, Developed, and Demonstrated

    Science.gov (United States)

    Ivancic, William D.; Paulsen, Phillip E.

    2004-01-01

    The inability to seamlessly disseminate data securely over a high-integrity, wireless broadband network has been identified as a primary technical barrier to providing an order-of-magnitude increase in aviation capacity and safety. Secure, autonomous communications to and from aircraft will enable advanced, automated, data-intensive air traffic management concepts, increase National Air Space (NAS) capacity, and potentially reduce the overall cost of air travel operations. For the first time ever, secure, mobile, network technology was designed, developed, and demonstrated with state-ofthe- art protocols and applications by a diverse, cooperative Government-industry team led by the NASA Glenn Research Center. This revolutionary technology solution will make fundamentally new airplane system capabilities possible by enabling secure, seamless network connections from platforms in motion (e.g., cars, ships, aircraft, and satellites) to existing terrestrial systems without the need for manual reconfiguration. Called Mobile Router, the new technology autonomously connects and configures networks as they traverse from one operating theater to another. The Mobile Router demonstration aboard the Neah Bay, a U.S. Coast Guard vessel stationed in Cleveland, Ohio, accomplished secure, seamless interoperability of mobile network systems across multiple domains without manual system reconfiguration. The Neah Bay was chosen because of its low cost and communications mission similarity to low-Earth-orbiting satellite platforms. This technology was successfully advanced from technology readiness level (TRL) 2 (concept and/or application formation) to TRL 6 (system model or prototype demonstration in a relevant environment). The secure, seamless interoperability offered by the Mobile Router and encryption device will enable several new, vehicle-specific and systemwide technologies to perform such things as remote, autonomous aircraft performance monitoring and early detection and

  4. Mixed WTO ruling on generic drug development.

    Science.gov (United States)

    Elliott, R

    2000-01-01

    On 17 March 2000, the World Trade Organization upheld the provision in Canada's patent laws that allows generic drug manufacturers to develop (but not sell) their cheaper versions of patented medicines before the 20-year patients expire. The decision prevents pharmaceutical companies from enjoying market monopolies beyond their patent terms, avoiding what would otherwise be even lengthier delays in the sale of cheaper, generic drugs in Canada. This decision is of significance not only to Canada, but also to other WTO member countries and to all individuals who use pharmaceutical products. However, the decision is not all positive: the WTO also ruled that Canada is violating international agreements by letting generic manufacturers stockpile their versions of patented drugs before patents expire. This article explains the issues, the arguments, and the decision.

  5. Heterocyclic Scaffolds: Centrality in Anticancer Drug Development.

    Science.gov (United States)

    Ali, Imran; Lone, Mohammad Nadeem; Al-Othman, Zeid A; Al-Warthan, Abdulrahman; Sanagi, Mohd Marsin

    2015-01-01

    Cancer has been cursed for human beings for long time. Millions people lost their lives due to cancer. Despite of the several anticancer drugs available, cancer cannot be cured; especially at the late stages without showing any side effect. Heterocyclic compounds exhibit exciting medicinal properties including anticancer. Some market selling heterocyclic anticancer drugs include 5-flourouracil, methortrexate, doxorubicin, daunorubicin, etc. Besides, some natural products such as vinblastine and vincristine are also used as anticancer drugs. Overall, heterocyclic moeities have always been core parts in the expansion of anticancer drugs. This article describes the importance of heterocyclic nuclei in the development of anticancer drugs. Besides, the attempts have been made to discuss both naturally occurring and synthetic heterocyclic compounds as anticancer agents. In addition, some market selling anticancer heterocyclic compounds have been described. Moreover, the efforts have been made to discuss the mechanisms of actions and recent advances in heterocyclic compounds as anticancer agents. The current challenges and future prospectives of heterocyclic compounds have also been discussed. Finally, the suggestions for syntheses of effective, selective, fast and human friendly anticancer agents are discussed into the different sections.

  6. [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

  7. Development of novel small molecules for imaging and drug release

    Science.gov (United States)

    Cao, Yanting

    Small organic molecules, including small molecule based fluorescent probes, small molecule based drugs or prodrugs, and smart multifunctional fluorescent drug delivery systems play important roles in biological research, drug discovery, and clinical practices. Despite the significant progress made in these fields, the development of novel and diverse small molecules is needed to meet various demands for research and clinical applications. My Ph.D study focuses on the development of novel functional molecules for recognition, imaging and drug release. In the first part, a turn-on fluorescent probe is developed for the detection of intracellular adenosine-5'-triphosphate (ATP) levels based on multiplexing recognitions. Considering the unique and complicated structure of ATP molecules, a fluorescent probe has been implemented with improved sensitivity and selectivity due to two synergistic binding recognitions by incorporating of 2, 2'-dipicolylamine (Dpa)-Zn(II) for targeting of phospho anions and phenylboronic acid group for cis-diol moiety. The novel probe is able to detect intracellular ATP levels in SH-SY5Y cells. Meanwhile, the advantages of multiplexing recognition design concept have been demonstrated using two control molecules. In the second part, a prodrug system is developed to deliver multiple drugs within one small molecule entity. The prodrug is designed by using 1-(2-nitrophenyl)ethyl (NPE) as phototrigger, and biphenol biquaternary ammonium as the prodrug. With controlled photo activation, both DNA cross-linking agents mechlorethamine and o-quinone methide are delivered and released at the preferred site, leading to efficient DNA cross-links formation and cell death. The prodrug shows negligible cytotoxicity towards normal skin cells (Hekn cells) with and without UV activation, but displays potent activity towards cancer cells (HeLa cells) upon UV activation. The multiple drug release system may hold a great potential for practical application. In the

  8. Possible futures for the development of a fusion demonstration plant

    International Nuclear Information System (INIS)

    Nichols, S.P.

    1976-01-01

    As indicated by the Fusion Planning Bulletins, the Division of Controlled Thermonuclear Research is becoming involved in planning with alternative scenarios. The Center for Energy Studies at the University of Texas at Austin has been involved with such planning for several years and has examined various scenarios for fusion power development using the Partitive Analytical Forecasting (PAF) technique. The most recent studies compare the long-term plan presented in WASH-1290, Fusion Power by Magnetic Confinement, with other plans that have been proposed, such as the plan proposed by Kulcinski and Conn of the University of Wisconsin. The study indicates that some of the alternative plans do have possibilities to shorten the required time for the completion of a demonstration fusion plant without increased costs or a decrease in the likelihood of success. The current efforts of the project are in the planning exercises recently completed by committees set up by the DCTR. Further comparisons of alternative scenarios will be performed as part of this effort

  9. Multi-target drugs: the trend of drug research and development.

    Science.gov (United States)

    Lu, Jin-Jian; Pan, Wei; Hu, Yuan-Jia; Wang, Yi-Tao

    2012-01-01

    Summarizing the status of drugs in the market and examining the trend of drug research and development is important in drug discovery. In this study, we compared the drug targets and the market sales of the new molecular entities approved by the U.S. Food and Drug Administration from January 2000 to December 2009. Two networks, namely, the target-target and drug-drug networks, have been set up using the network analysis tools. The multi-target drugs have much more potential, as shown by the network visualization and the market trends. We discussed the possible reasons and proposed the rational strategies for drug research and development in the future.

  10. Drug development against tuberculosis: Impact of alkaloids.

    Science.gov (United States)

    Mishra, Shardendu K; Tripathi, Garima; Kishore, Navneet; Singh, Rakesh K; Singh, Archana; Tiwari, Vinod K

    2017-09-08

    Despite of the advances made in the treatment and management, tuberculosis (TB) still remains one of main public health problem. The contrary effects of first and second-line anti-tuberculosis drugs have generated extended research interest in natural products in the hope of devising new antitubercular leads. Interestingly, plethoras of natural products have been discovered to exhibit activity towards various resistant strains of M. tuberculosis. Extensive applications of alkaloids in the field of therapeutics is well-established and nowday's researches being pursued to develop new potent drugs from natural sources for tuberculosis. Alkaloids are categorized in quite a few groups according to their structures and isolation from both terrestrial and marine sources. These new drugs might be a watershed in the battle against tuberculosis. This review summarizes alkaloids, which were found active against Mycobacteria since last ten years with special attention on the study of structure-activity relationship (SAR) and mode of action with their impact in drug discovery and development against tuberculosis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  11. 75 FR 32482 - Investigational New Drug Applications; Co-development of Investigational Drugs

    Science.gov (United States)

    2010-06-08

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0247] Investigational New Drug Applications; Co-development of Investigational Drugs AGENCY: Food and Drug Administration, HHS. ACTION: Notice; establishment of docket; request for comments. SUMMARY: The Food and Drug...

  12. Effects of Psychostimulant Drugs on Developing Brain

    Directory of Open Access Journals (Sweden)

    Ibrahim Durukan

    2013-08-01

    Full Text Available Although psychostimulants have been used for the treatment of attention deficit hyperactivity disorder for approximately 70 years, little is known about the long term effects of these drugs on developing brain. The observable effects of psychostimulants are influenced by the timing of exposure, the age of examination after drug exposure and sex. Preclinical studies point out that chronic psychostimulant exposure before adolescence cause reverse sensitization or tolerance and this leads to reduction in stimulant effectiveness in adolesecence and adulthood. Preclinical studies show the potential long term effects of psychostimulants. But it is necessary to investigate the relationship between preclinical effects and clinical practice. A developmental approach is needed to understand the impact of pediatric medications on the brain that includes assessment at multiple ages to completely characterize the long term effects of these medications. The aim of this paper is to review the effects of psychostimulants on developing brain.

  13. AMS in drug development at GSK

    International Nuclear Information System (INIS)

    Young, G.C.; Ellis, W.J.

    2007-01-01

    A history of the use of AMS in GSK studies spanning the last 8 years (1998-2005) is presented, including use in pilot studies through to clinical, animal and in vitro studies. A brief summary of the status of GSK's in-house AMS capability is outlined and views on the future of AMS in GSK are presented, including potential impact on drug development and potential advances in AMS technology

  14. Use of radiopharmaceuticals in the development of drug delivery systems

    International Nuclear Information System (INIS)

    Frier, M.

    1997-01-01

    Full text. Nuclear medicine imaging techniques have great potential in the study of the behaviour of drug formulations and drug delivery systems in human subjects. No other technique can locate so precisely the site of disintegration of a tablet in the Gl tract, the depth of penetration of a nebulized solution into the lung, or the residence time of a drug on the cornea. By using the gamma camera to image the in vivo distribution of pharmaceutical formulations radio labelled with a suitable gamma emitting radionuclide, images may be used to quantify the biodistribution, release and kinetics of drug formulations and delivery from novel carrier systems and devices. Radionuclide tracer techniques allow correlation between the observed pharmacological effects and the precise site of delivery. The strength of the technique lies in the quantitative nature of radionuclide images. Example will be shown of studies which examine the rate of transit of orally-administered formulations through the GI tract, as well as describing the development of devices for specific targeting of drugs to the colon. Data will also demonstrate the effectiveness of devices such as spacers in pulmonary drug delivery, in both normal volunteers, and in asthmatic subjects. Such studies not only provide data on the nature and characteristics of a product, such as reliability and reproducibility but, may also be used in submission to Regulatory Authorities in product registration dossiers

  15. Nonimaging detectors in drug development and approval.

    Science.gov (United States)

    Wagner, H N

    2001-07-01

    Regulatory applications for imaging biomarkers will expand in proportion to the validation of specific parameters as they apply to individual questions in the management of disease. This validation is likely to be applicable only to a particular class of drug or a single mechanism of action. Awareness among the world's regulatory authorities of the potential for these emerging technologies is high, but so is the cost to the sponsor (including the logistics of including images in a dossier), and therefore the pharmaceutical industry must evaluate carefully the potential benefit of each technology for its drug development programs, just as the authorities must consider carefully the extent to which the method is valid for the use to which the applicant has put it. For well-characterized tracer systems, it may be possible to design inexpensive cameras that make rapid assessments.

  16. Animal Migraine Models for Drug Development

    DEFF Research Database (Denmark)

    Jansen-Olesen, Inger; Tfelt-Hansen, Peer; Olesen, Jes

    2013-01-01

    Migraine is number seven in WHO's list of all diseases causing disability and the third most costly neurological disorder in Europe. Acute attacks are treatable by highly selective drugs such as the triptans but there is still a huge unmet therapeutic need. Unfortunately, drug development...... for headache has almost come to a standstill partly because of a lack of valid animal models. Here we review previous models with emphasis on optimal characteristics of a future model. In addition to selection of animal species, the method of induction of migraine-like changes and the method of recording...... responses elicited by such measures are crucial. The most naturalistic way of inducing attacks is by infusion of endogenous signaling molecules that are known to cause migraine in patients. The most valid response is recording of neural activity in the trigeminal system. The most useful headache related...

  17. Developing and Demonstrating an Augmented Reality Colorimetric Titration Tool

    Science.gov (United States)

    Tee, Nicholas Yee Kwang; Gan, Hong Seng; Li, Jonathan; Cheong, Brandon Huey-Ping; Tan, Han Yen; Liew, Oi Wah; Ng, Tuck Wah

    2018-01-01

    The handling of chemicals in the laboratory presents a challenge in instructing large class sizes and when students are relatively new to the laboratory environment. In this work, we describe and demonstrate an augmented reality colorimetric titration tool that operates out of the smartphone or tablet of students. It allows multiple students to…

  18. Live demonstration: Screen printed, microwave based level sensor for automated drug delivery

    KAUST Repository

    Karimi, Muhammad Akram; Arsalan, Muhammad; Shamim, Atif

    2018-01-01

    Level sensors find numerous applications in many industries to automate the processes involving chemicals. Recently, some commercial ultrasound based level sensors are also being used to automate the drug delivery process [1]. Some of the most

  19. The development and maintenance of drug addiction.

    Science.gov (United States)

    Wise, Roy A; Koob, George F

    2014-01-01

    What is the defining property of addiction? We dust off a several-decades-long debate about the relative importance of two forms of reinforcement—positive reinforcement, subjectively linked to drug-induced euphoria, and negative reinforcement, subjectively linked to the alleviation of pain—both of which figure importantly in addiction theory; each of these forms has dominated addiction theory in its time. We agree that addiction begins with the formation of habits through positive reinforcement and that drug-opposite physiological responses often establish the conditions for negative reinforcement to come into play at a time when tolerance, in the form of increasing reward thresholds, appears to develop into positive reinforcement. Wise’s work has tended to focus on positive-reinforcement mechanisms that are important for establishing drug-seeking habits and reinstating them quickly after periods of abstinence, whereas Koob’s work has tended to focus on the negative-reinforcement mechanisms that become most obvious in the late stages of sustained addiction. While we tend to agree with each other about the early and late stages of addiction, we hold different views as to (i) the point between early and late at which the diagnosis of ‘addiction’ should be invoked, (ii) the relative importance of positive and negative reinforcement leading up to this transition, and (iii) the degree to which the specifics of negative reinforcement can be generalized across the range of addictive agents.

  20. Computational fluid dynamics: a suitable assessment tool for demonstrating the antiobstructive effect of drugs in the therapy of allergic rhinitis.

    Science.gov (United States)

    Achilles, N; Pasch, N; Lintermann, A; Schröder, W; Mösges, R

    2013-02-01

    This systematic review aims first to summarize the previous areas of application of computational fluid dynamics (CFD) and then to demonstrate that CFD is also a suitable instrument for generating three-dimensional images that depict drug effects on nasal mucosa. Special emphasis is placed on the three-dimensional visualization of the antiobstructive effect of nasal steroids and antihistamines in the treatment of allergic rhinitis. In the beginning, CFD technology was only used to demonstrate physiological and pathophysiological airflow conditions in the nose and to aid in preoperative planning and postoperative monitoring of surgical outcome in the field of rhinosurgery. The first studies using CFD examined nasal respiratory physiology, important functions of the nose, such as conditioning and warming of inspired air, and the influence of pathophysiological changes on nasal breathing. Also, postoperative outcome of surgical procedures could be "predicted" using the nasal airflow model. Later studies focused on the three-dimensional visualization of the effect of nasal sprays in healthy subjects and postoperative patients. A completely new approach, however, was the use of CFD in the area of allergic rhinitis and the treatment of its cardinal symptom of nasal obstruction. In two clinical trials, a suitable patient with a positive history of allergic rhinitis was enrolled during a symptom-free period after the pollen season. The patient developed typical allergic rhinitis symptoms after provocation with birch pollen. The 3-D visualization showed that the antiallergic treatment successfully counteracted the effects of nasal allergen provocation on nasal airflow. These observations were attributed to the antiobstructive effect of a nasal steroid (mometasone furoate) and a systemic antihistamine (levocetirizine), respectively. CFD therefore constitutes a non-invasive, precise, reliable and objective examination procedure for generating three-dimensional images that

  1. Prototype development and demonstration for integrated dynamic transit operations.

    Science.gov (United States)

    2016-01-01

    This document serves as the Final Report specific to the Integrated Dynamic Transit Operations (IDTO) Prototype Development and Deployment Project, hereafter referred to as IDTO Prototype Deployment or IDTO PD project. This project was performed unde...

  2. Resin Infusion Rigidized Inflatable Concept Development and Demonstration

    Data.gov (United States)

    National Aeronautics and Space Administration — A novel concept utilizing resin infusion to rigidize inflatable structures was developed at JSC ES. This ICA project intends to complete manufacturing of a prototype...

  3. Development of Barnwell as a multinational demonstration facility

    International Nuclear Information System (INIS)

    Colby, L.J. Jr.

    1977-01-01

    The author takes an existing private business venture (Barnwell) with its assets of facilities, personnel, technology and domestic business commitments (past, present, and future) and develops a role for it which will be compatible with the advancement of multinational reprocessing facilities under international control

  4. [New drug developments of snake venom polypeptides and progress].

    Science.gov (United States)

    Fu, Sihai; Feng, Mei; Xiong, Yan

    2017-11-28

    The value of snake venom polypeptides in clinical application has drawn extensive attention, and the development of snake polypeptides into new drugs with anti-tumor, anti-inflammatory, antithrombotic, analgesic or antihypertensive properties has become the recent research hotspot. With the rapid development of molecular biology and biotechnology, the mechanisms of snake venom polypeptides are also gradually clarified. Numerous studies have demonstrated that snake venom polypeptides exert their pharmacological effects by regulating ion channels, cell proliferation, apoptosis, intracellular signaling pathway, and expression of cytokine as well as binding to relevant active sites or receptors.

  5. Pharmacogenomics to Revive Drug Development in Cardiovascular Disease.

    Science.gov (United States)

    Dubé, Marie-Pierre; de Denus, Simon; Tardif, Jean-Claude

    2016-02-01

    Investment in cardiovascular drug development is on the decline as large cardiovascular outcomes trials require considerable investments in time, efforts and financial resources. Pharmacogenomics has the potential to help revive the cardiovascular drug development pipeline by providing new and better drug targets at an earlier stage and by enabling more efficient outcomes trials. This article will review some of the recent developments highlighting the value of pharmacogenomics for drug development. We discuss how genetic biomarkers can enable the conduct of more efficient clinical outcomes trials by enriching patient populations for good responders to the medication. In addition, we assess past drug development programs which support the added value of selecting drug targets that have established genetic evidence supporting the targeted mechanism of disease. Finally, we discuss how pharmacogenomics can provide valuable evidence linking a drug target to clinically relevant outcomes, enabling novel drug discovery and drug repositioning opportunities.

  6. Mind the gap : predicting cardiovascular risk during drug development

    NARCIS (Netherlands)

    Chain, Anne S. Y.

    2012-01-01

    Cardiovascular safety issues, specifically drug-induced QT/QTc-interval prolongation, remain a major cause of drug attrition during clinical development and is one of the main causes for post-market drug withdrawals accounting for 15-34% of all drug discontinuation. Given the potentially fatal

  7. Development of a Thermoacoustic Stirling Engine Technology Demonstrator

    Science.gov (United States)

    Reissner, Alexander; Gerger, Joachim; Hummel, Stefan; Reißig, Jannis; Pawelke, Roland

    2014-08-01

    Waste heat is a primary source of energy loss in many aerospace and terrestrial applications. FOTEC, an Austrian Research Company located in Wiener Neustadt, is presently developing a micro power converter, promising high efficiencies even for small- scale applications. The converter is based on an innovative thermoacoustic stirling engine concept without any moving parts. Such a maintenance-free engine system would be particularly suitable for advanced space power systems (radioisotope, waste heat) or even within the scope of terrestrial energy harvesting. This paper will summarizes the status of our ongoing efforts on this micro power converter technology.

  8. Automotive Fuel Processor Development and Demonstration with Fuel Cell Systems

    Energy Technology Data Exchange (ETDEWEB)

    Nuvera Fuel Cells

    2005-04-15

    The potential for fuel cell systems to improve energy efficiency and reduce emissions over conventional power systems has generated significant interest in fuel cell technologies. While fuel cells are being investigated for use in many applications such as stationary power generation and small portable devices, transportation applications present some unique challenges for fuel cell technology. Due to their lower operating temperature and non-brittle materials, most transportation work is focusing on fuel cells using proton exchange membrane (PEM) technology. Since PEM fuel cells are fueled by hydrogen, major obstacles to their widespread use are the lack of an available hydrogen fueling infrastructure and hydrogen's relatively low energy storage density, which leads to a much lower driving range than conventional vehicles. One potential solution to the hydrogen infrastructure and storage density issues is to convert a conventional fuel such as gasoline into hydrogen onboard the vehicle using a fuel processor. Figure 2 shows that gasoline stores roughly 7 times more energy per volume than pressurized hydrogen gas at 700 bar and 4 times more than liquid hydrogen. If integrated properly, the fuel processor/fuel cell system would also be more efficient than traditional engines and would give a fuel economy benefit while hydrogen storage and distribution issues are being investigated. Widespread implementation of fuel processor/fuel cell systems requires improvements in several aspects of the technology, including size, startup time, transient response time, and cost. In addition, the ability to operate on a number of hydrocarbon fuels that are available through the existing infrastructure is a key enabler for commercializing these systems. In this program, Nuvera Fuel Cells collaborated with the Department of Energy (DOE) to develop efficient, low-emission, multi-fuel processors for transportation applications. Nuvera's focus was on (1) developing fuel

  9. The development and testing of pulsed detonation engine ground demonstrators

    Science.gov (United States)

    Panicker, Philip Koshy

    2008-10-01

    The successful implementation of a PDE running on fuel and air mixtures will require fast-acting fuel-air injection and mixing techniques, detonation initiation techniques such as DDT enhancing devices or a pre-detonator, an effective ignition system that can sustain repeated firing at high rates and a fast and capable, closed-loop control system. The control system requires high-speed transducers for real-time monitoring of the PDE and the detection of the detonation wave speed. It is widely accepted that the detonation properties predicted by C-J detonation relations are fairly accurate in comparison to experimental values. The post-detonation flow properties can also be expressed as a function of wave speed or Mach number. Therefore, the PDE control system can use C-J relations to predict the post-detonation flow properties based on measured initial conditions and compare the values with those obtained from using the wave speed. The controller can then vary the initial conditions within the combustor for the subsequent cycle, by modulating the frequency and duty cycle of the valves, to obtain optimum air and fuel flow rates, as well as modulate the energy and timing of the ignition to achieve the required detonation properties. Five different PDE ground demonstrators were designed, built and tested to study a number of the required sub-systems. This work presents a review of all the systems that were tested, along with suggestions for their improvement. The PDE setups, ranged from a compact PDE with a 19 mm (3/4 in.) i.d., to two 25 mm (1 in.) i.d. setups, to a 101 mm (4 in.) i.d. dual-stage PDE setup with a pre-detonator. Propane-oxygen mixtures were used in the smaller PDEs. In the dual-stage PDE, propane-oxygen was used in the pre-detonator, while propane-air mixtures were used in the main combustor. Both rotary valves and solenoid valve injectors were studied. The rotary valves setups were tested at 10 Hz, while the solenoid valves were tested at up to 30 Hz

  10. A Development of Hybrid Drug Information System Using Image Recognition

    Directory of Open Access Journals (Sweden)

    HwaMin Lee

    2015-04-01

    Full Text Available In order to prevent drug abuse or misuse cases and avoid over-prescriptions, it is necessary for medicine taker to be provided with detailed information about the medicine. In this paper, we propose a drug information system and develop an application to provide information through drug image recognition using a smartphone. We designed a contents-based drug image search algorithm using the color, shape and imprint of drug. Our convenient application can provide users with detailed information about drugs and prevent drug misuse.

  11. Tuberculosis related drug-lipid interactions demonstrated by evanescent field biosensor

    CSIR Research Space (South Africa)

    Lemmer, Yolandy

    2009-08-01

    Full Text Available stream_source_info Lemmer1_2009.pdf.txt stream_content_type text/plain stream_size 6475 Content-Encoding ISO-8859-1 stream_name Lemmer1_2009.pdf.txt Content-Type text/plain; charset=ISO-8859-1 Tuberculosis related drug... of Pretoria, Pretoria, South Africa bPolymers and Bioceramics, MSM, CSIR, Pretoria, South Africa Mycolic acids (MA), depicted in Fig.1, which are part of the cell envelope of Mycobacterium tuberculosis, play a major role in the pathogenesis of the bacteria...

  12. Open source biotechnology : A drug for developing countries' health problems?

    NARCIS (Netherlands)

    Schellekens, M.H.M.

    2008-01-01

    In developing countries, many people suffer from diseases for which there are no drugs or for which drugs exist that they cannot afford because they are too expensive. The advent of genomics has sparked the idea that new drugs can be more easily developed and that genomics thus could lessen the

  13. Solar heating - status and strategy. Research, development and demonstration; Solvarme - status og strategi. Forskning, udvikling og demonstration

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2007-05-15

    The Danish Energy Authority has prepared research and development strategies for a number of energy technologies, including solar heating. This report presents an inventory of solar heating and proposes a strategy for further development. The report has been prepared by a number of important stakeholders in the Danish solar heating area. The inventory part of the report includes most solar heating technologies, however, emphasis is on technologies which have had or are expected to become important for exploitation in Denmark. The strategy part of the report proposes prioritized areas in research, development and demonstration based on international trends and Danish strong and weak points, which are: 1) centralized solar heating supply, district heating, 2) individual solar heating supply in connection with development and construction of buildings, building integration, and finally 3) product development of solar collectors. (BA)

  14. Exosomes in development, metastasis and drug resistance of breast cancer.

    Science.gov (United States)

    Yu, Dan-dan; Wu, Ying; Shen, Hong-yu; Lv, Meng-meng; Chen, Wei-xian; Zhang, Xiao-hui; Zhong, Shan-liang; Tang, Jin-hai; Zhao, Jian-hua

    2015-08-01

    Transport through the cell membrane can be divided into active, passive and vesicular types (exosomes). Exosomes are nano-sized vesicles released by a variety of cells. Emerging evidence shows that exosomes play a critical role in cancers. Exosomes mediate communication between stroma and cancer cells through the transfer of nucleic acid and proteins. It is demonstrated that the contents and the quantity of exosomes will change after occurrence of cancers. Over the last decade, growing attention has been paid to the role of exosomes in the development of breast cancer, the most life-threatening cancer in women. Breast cancer could induce salivary glands to secret specific exosomes, which could be used as biomarkers in the diagnosis of early breast cancer. Exosome-delivered nucleic acid and proteins partly facilitate the tumorigenesis, metastasis and resistance of breast cancer. Exosomes could also transmit anti-cancer drugs outside breast cancer cells, therefore leading to drug resistance. However, exosomes are effective tools for transportation of anti-cancer drugs with lower immunogenicity and toxicity. This is a promising way to establish a drug delivery system. © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

  15. Personalized Medicine: Pharmacogenomics and Drug Development

    Directory of Open Access Journals (Sweden)

    Somayeh Mirsadeghi

    2017-03-01

    Full Text Available Personalized medicine aims is to supply the proper drug to the proper patient within the right dose. Pharmacogenomics (PGx is to recognize genetic variants that may influence drug efficacy and toxicity. All things considered, the fields cover a wide area, including basic drug discovery researches, the genetic origin of pharmacokinetics and pharmacodynamics, novel drug improvement, patient genetic assessment and clinical patient administration. At last, the objective of Pharmacogenomics is to anticipate a patient’s genetic response to a particular drug as a way of presenting the best possible medical treatment. By predicting the drug response of an individual, it will be possible to increase the success of therapies and decrease the incidence of adverse side effect.

  16. Drugs in development for Parkinson's disease: an update.

    Science.gov (United States)

    Johnston, Tom H; Brotchie, Jonathan M

    2006-01-01

    The current development of emerging pharmacological treatments for Parkinson's disease (PD), front preclinical to launch, is summarized. Advances over the past year are highlighted, including the significant progress of several drugs through various stages of development. Several agents have been discontinued from development, either because of adverse effects or lack of clinical efficacy. The methyl-esterified form of L-DOPA (melevodopa) and the monoamine oxidase type B inhibitor rasagiline have both been launched. With regard to the monoamine re-uptake inhibitors, many changes have been witnessed, with new agents reaching preclinical development and pre-existing ones being discontinued or having no development reported. Of the dopamine agonists, many continue to progress successfully through clinical trials. Others have struggled to demonstrate a significant advantage over currently available treatments and have been discontinued. The field of non-dopaminergic treatments remains dynamic. The alpha2 adrenergic receptor antagonists and the adenosine A2A receptor antagonists remain in clinical trials. Trials of the neuronal' synchronization modulator levetiracetam are at an advanced stage, and there has also been a new addition to the class (ie, seletracetam). There has been a change in the landscape of neuroprotective agents that modulate disease progression. Candidates from the classes of growth factors and glyceraldehyde-3-phosphate dehydrogenase inhibitors have been discontinued, or no development has been reported, and the mixed lineage kinase inhibitor CEP-1347 has been discontinued for PD treatment. Other drugs in this field, such as neuroimmunophilins, estrogens and alpha-synuclein oligomerization inhibitors, remain in development.

  17. The role of radiolabelled compounds in preclinical drug development

    International Nuclear Information System (INIS)

    Hawkins, D.R.

    1988-01-01

    The role of radiolabelled compounds in the development of new drugs is discussed, with particular reference to their use in toxicological, metabolic and pharmacokinetic studies for the pre-clinical safety evaluation of new drugs. (U.K.)

  18. Novel anti-Sialyl-Tn monoclonal antibodies and antibody-drug conjugates demonstrate tumor specificity and anti-tumor activity.

    Science.gov (United States)

    Prendergast, Jillian M; Galvao da Silva, Ana Paula; Eavarone, David A; Ghaderi, Darius; Zhang, Mai; Brady, Dane; Wicks, Joan; DeSander, Julie; Behrens, Jeff; Rueda, Bo R

    Targeted therapeutics that can differentiate between normal and malignant tumor cells represent the ideal standard for the development of a successful anti-cancer strategy. The Sialyl-Thomsen-nouveau antigen (STn or Sialyl-Tn, also known as CD175s) is rarely seen in normal adult tissues, but it is abundantly expressed in many types of human epithelial cancers. We have identified novel antibodies that specifically target with high affinity the STn glycan independent of its carrier protein, affording the potential to recognize a wider array of cancer-specific sialylated proteins. A panel of murine monoclonal anti-STn therapeutic antibodies were generated and their binding specificity and efficacy were characterized in vitro and in in vivo murine cancer models. A subset of these antibodies were conjugated to monomethyl auristatin E (MMAE) to generate antibody-drug conjugates (ADCs). These ADCs demonstrated in vitro efficacy in STn-expressing cell lines and significant tumor growth inhibition in STn-expressing tumor xenograft cancer models with no evidence of overt toxicity.

  19. Do national drug policies influence antiretroviral drug prices? Evidence from the Southern African Development community.

    Science.gov (United States)

    Liu, Yao; Galárraga, Omar

    2017-03-01

    The efficacy of low- and middle-income countries’ (LMIC) national drug policies in managing antiretroviral (ARV) pharmaceutical prices is not well understood. Though ARV drug prices have been declining in LMIC over the past decade, little research has been done on the role of their national drug policies. This study aims to (i) analyse global ARV prices from 2004 to 2013 and (ii) examine the relationship of national drug policies to ARV prices. Analysis of ARV drug prices utilized data from the Global Price Reporting Mechanism from the World Health Organization (WHO). Ten of the most common ARV drugs (first-line and second-line) were selected. National drug policies were also assessed for 12 countries in the South African Development Community (SADC), which self-reported their policies through WHO surveys. The best predictor of ARV drug price was generic status—the generic versions of 8 out of 10 ARV drugs were priced lower than branded versions. However, other factors such as transaction volume, HIV prevalence, national drug policies and PEPFAR/CHAI involvement were either not associated with ARV drug price or were not consistent predictors of price across different ARV drugs. In the context of emerging international trade agreements, which aim to strengthen patent protections internationally and potentially delay the sale of generic drugs in LMIC, this study shines a spotlight on the importance of generic drugs in controlling ARV prices. Further research is needed to understand the impact of national drug policies on ARV prices.

  20. Live demonstration: Screen printed, microwave based level sensor for automated drug delivery

    KAUST Repository

    Karimi, Muhammad Akram

    2018-01-02

    Level sensors find numerous applications in many industries to automate the processes involving chemicals. Recently, some commercial ultrasound based level sensors are also being used to automate the drug delivery process [1]. Some of the most desirable features of level sensors to be used for medical use are their non-intrusiveness, low cost and consistent performance. In this demo, we will present a completely new method of sensing the liquid level using microwaves. It is a common stereotype to consider microwaves sensing mechanism as being expensive. Unlike usual expensive, intrusive and bulky microwave methods of level sensing using guided radars, we will present an extremely low cost printed, non-intrusive microwave sensor to reliably sense the liquid level.

  1. 78 FR 57623 - TRICARE Over-the-Counter Drug Demonstration Project

    Science.gov (United States)

    2013-09-19

    ... B One-Step (levonorgestrel) emergency contraceptive as an over-the-counter product ``for all women...-Counter Plan B One-Step Emergency Contraceptive (levonorgestrel). (2) OTC availability of Plan B One-Step Emergency Contraceptive (levonorgestrel) through the demonstration project will be at retail dispensing...

  2. An Anesthetic Drug Demonstration and an Introductory Antioxidant Activity Experiment with "Eugene, the Sleepy Fish"

    Science.gov (United States)

    Barcena, Homar; Chen, Peishan

    2016-01-01

    Students are introduced to spectrophotometry in comparing the antioxidant activity of pure eugenol and oil of cloves from a commercial source using a modified ferric reducing antioxidant power (FRAP) assay. The extraction of the essential oil from dried cloves is demonstrated to facilitate discussions on green chemistry. The anesthetic properties…

  3. Prediction of resistance development against drug combinations by collateral responses to component drugs

    DEFF Research Database (Denmark)

    Munck, Christian; Gumpert, Heidi; Nilsson Wallin, Annika

    2014-01-01

    the genomes of all evolved E. coli lineages, we identified the mutational events that drive the differences in drug resistance levels and found that the degree of resistance development against drug combinations can be understood in terms of collateral sensitivity and resistance that occurred during...... adaptation to the component drugs. Then, using engineered E. coli strains, we confirmed that drug resistance mutations that imposed collateral sensitivity were suppressed in a drug pair growth environment. These results provide a framework for rationally selecting drug combinations that limit resistance......Resistance arises quickly during chemotherapeutic selection and is particularly problematic during long-term treatment regimens such as those for tuberculosis, HIV infections, or cancer. Although drug combination therapy reduces the evolution of drug resistance, drug pairs vary in their ability...

  4. Dabigatran – an exemplar case history demonstrating the need for comprehensive models to optimise the use of new drugs

    Directory of Open Access Journals (Sweden)

    Brian eGodman

    2014-06-01

    Full Text Available Background: There are potential conflicts between authorities and companies to fund new premium priced drugs especially where there are effectiveness, safety and/ or budget concerns. Dabigatran, a new oral anticoagulant for the prevention of stroke in patients with non-valvular atrial fibrillation (AF, exemplifies this issue. Whilst new effective treatments are needed, there are issues in the elderly with dabigatran due to variable drug concentrations, no known antidote and dependence on renal elimination. Published studies showed dabigatran to be cost-effective but there are budget concerns given the prevalence of AF. These concerns resulted in extensive activities pre- to post-launch to manage its introduction. Objective: To (i review authority activities across countries, (ii use the findings to develop new models to better manage the entry of new drugs, and (iii review the implications based on post-launch activities. Methodology: (i Descriptive review and appraisal of activities regarding dabigatran, (ii development of guidance for key stakeholder groups through an iterative process, (iii refining guidance following post launch studies. Results: Plethora of activities to manage dabigatran including extensive pre-launch activities, risk sharing arrangements, prescribing restrictions and monitoring of prescribing post launch. Reimbursement has been denied in some countries due to concerns with its budget impact and/or excessive bleeding. Development of a new model and future guidance is proposed to better manage the entry of new drugs, centring on three pillars of pre-, peri- and post-launch activities. Post-launch activities include increasing use of patient registries to monitor the safety and effectiveness of new drugs in clinical practice. Conclusion: Models for introducing new drugs are essential to optimise their prescribing especially where concerns. Without such models, new drugs may be withdrawn prematurely and/ or struggle for

  5. Developing a Molecular Roadmap of Drug-Food Interactions

    DEFF Research Database (Denmark)

    Jensen, Kasper; Ni, Yueqiong; Panagiotou, Gianni

    2015-01-01

    therapeutic interventions, a systematic approach for identifying, predicting and preventing potential interactions between food and marketed or novel drugs is not yet available. The overall objective of this work was to sketch a comprehensive picture of the interference of ∼ 4,000 dietary components present...... view of the associations between diet and dietary molecules with drug targets, metabolic enzymes, drug transporters and carriers currently deposited in Drug-Bank. Moreover, we identified disease areas and drug targets that are most prone to the negative effects of drug-food interactions, showcasing......Recent research has demonstrated that consumption of food -especially fruits and vegetables-can alter the effects of drugs by interfering either with their pharmacokinetic or pharmacodynamic processes. Despite the recognition of such drug-food associations as an important element for successful...

  6. Investigating Nature's Mysteries for Drug Development

    Science.gov (United States)

    More than half of the drugs approved to treat cancer come from a natural product or a natural product prototype. Scientists in NCI-Frederick's Natural Products Branch are exploring ways to harness chemicals produced by marine invertebrates, other animals, plants, and microbes for cancer drug discovery.

  7. Development, use and evaluation of drugs

    DEFF Research Database (Denmark)

    Hansen, E H; Launsø, Laila

    1987-01-01

    . Drugs offer a standard solution to health problems independent of the individuals' social life. Thus drugs become a tool which function in agreement with the disintegrated and achievement-orientated approach to disease as it is organized today. In general the statements in this article are not limited...

  8. Radiocarbon mass spectrometry for drug development

    International Nuclear Information System (INIS)

    Ulrich, Schulze-Konig Tim

    2011-01-01

    Full text: Radiocarbon has a huge potential as a tracer for metabolism studies in humans. By using Accelerator Mass Spectrometry (AMS) for its detection, a unique sensitivity is reached reducing required radiation doses to a negligible level. Until recently, a widespread use of AMS in biomedical research was impeded by the high complexity of the instrument, time-consuming sample preparation, and a limited availability of measurement capacity. Over the last few years, tremendous progress has been achieved in the reduction of size and complexity of AMS instruments. It allowed designing a compact AMS system, dubbed BioMICADAS to address the needs of biomedical users. For more than two years, this system is in successful operation at a commercial service provider for the pharmaceutical industry. A further drastic simplification of radiocarbon mass spectrometers seems possible and could establish a regular usage of this technology in drug development. However, to reach this goal a better integration of AMS into the workflow of bioanalytical laboratories will be necessary. For this purpose, CO 2 accepting ion sources may be a key, since they enable an almost automated sample preparation. The status of radiocarbon AMS in biomedical research and its perspective will be discussed

  9. The Development Impact of the Illegality of Drug Trade

    OpenAIRE

    Keefer, Philip; Loayza, Norman V.; Soares, Rodrigo R.

    2008-01-01

    This paper reviews the unintended consequences of the war on drugs, particularly for developing countries, and weighs them against the evidence regarding the efficacy of prohibition to curb drug use and trade. It reviews the available evidence and presents new results that indicate that prohibition has limited effects on drug prevalence and prices, most likely indicating a combination of i...

  10. Imaging biomarkers as surrogate endpoints for drug development

    International Nuclear Information System (INIS)

    Richter, Wolf S.

    2006-01-01

    The employment of biomarkers (including imaging biomarkers, especially PET) in drug development has gained increasing attention during recent years. This has been partly stimulated by the hope that the integration of biomarkers into drug development programmes may be a means to increase the efficiency and effectiveness of the drug development process by early identification of promising drug candidates - thereby counteracting the rising costs of drug development. More importantly, however, the interest in biomarkers for drug development is the logical consequence of recent advances in biosciences and medicine which are leading to target-specific treatments in the framework of ''personalised medicine''. A considerable proportion of target-specific drugs will show effects in subgroups of patients only. Biomarkers are a means to identify potential responders, or patient subgroups at risk for specific side-effects. Biomarkers are used in early drug development in the context of translational medicine to gain information about the drug's potential in different patient groups and disease states. The information obtained at this stage is mainly important for designing subsequent clinical trials and to identify promising drug candidates. Biomarkers in later phases of clinical development may - if properly validated - serve as surrogate endpoints for clinical outcomes. Regulatory agencies in the EU and the USA have facilitated the use of biomarkers early in the development process. The validation of biomarkers as surrogate endpoints is part of FDA's ''critical path initiative''. (orig.)

  11. Dabigatran – a case history demonstrating the need for comprehensive approaches to optimize the use of new drugs

    Science.gov (United States)

    Malmström, Rickard E.; Godman, Brian B.; Diogene, Eduard; Baumgärtel, Christoph; Bennie, Marion; Bishop, Iain; Brzezinska, Anna; Bucsics, Anna; Campbell, Stephen; Ferrario, Alessandra; Finlayson, Alexander E.; Fürst, Jurij; Garuoliene, Kristina; Gomes, Miguel; Gutiérrez-Ibarluzea, Iñaki; Haycox, Alan; Hviding, Krystyna; Herholz, Harald; Hoffmann, Mikael; Jan, Saira; Jones, Jan; Joppi, Roberta; Kalaba, Marija; Kvalheim, Christina; Laius, Ott; Langner, Irene; Lonsdale, Julie; Lööv, Sven-Äke; Malinowska, Kamila; McCullagh, Laura; Paterson, Ken; Markovic-Pekovic, Vanda; Martin, Andrew; Piessnegger, Jutta; Selke, Gisbert; Sermet, Catherine; Simoens, Steven; Tulunay, Cankat; Tomek, Dominik; Vončina, Luka; Vlahovic-Palcevski, Vera; Wale, Janet; Wilcock, Michael; Wladysiuk, Magdalena; van Woerkom, Menno; Zara, Corrine; Gustafsson, Lars L.

    2013-01-01

    Background: There are potential conflicts between authorities and companies to fund new premium priced drugs especially where there are safety and/or budget concerns. Dabigatran, a new oral anticoagulant for the prevention of stroke in patients with non-valvular atrial fibrillation (AF), exemplifies this issue. Whilst new effective treatments are needed, there are issues in the elderly with dabigatran due to variable drug concentrations, no known antidote and dependence on renal elimination. Published studies have shown dabigatran to be cost-effective but there are budget concerns given the prevalence of AF. There are also issues with potentially re-designing anticoagulant services. This has resulted in activities across countries to better manage its use. Objective: To (i) review authority activities in over 30 countries and regions, (ii) use the findings to develop new models to better manage the entry of new drugs, and (iii) review the implications for all major stakeholder groups. Methodology: Descriptive review and appraisal of activities regarding dabigatran and the development of guidance for groups through an iterative process. Results: There has been a plethora of activities among authorities to manage the prescribing of dabigatran including extensive pre-launch activities, risk sharing arrangements, prescribing restrictions, and monitoring of prescribing post-launch. Reimbursement has been denied in some countries due to concerns with its budget impact and/or excessive bleeding. Development of a new model and future guidance is proposed to better manage the entry of new drugs, centering on three pillars of pre-, peri-, and post-launch activities. Conclusion: Models for introducing new drugs are essential to optimize their prescribing especially where there are concerns. Without such models, new drugs may be withdrawn prematurely and/or struggle for funding. PMID:23717279

  12. Dabigatran - a case history demonstrating the need for comprehensive approaches to optimise the use of new drugs

    Directory of Open Access Journals (Sweden)

    Rickard eMalmstrom

    2013-05-01

    Full Text Available Background: There are potential conflicts between authorities and companies to fund new premium priced drugs especially where there are safety and/ or budget concerns. Dabigatran, a new oral anticoagulant for the prevention of stroke in patients with non-valvular AF, exemplifies this issue. Whilst new effective treatments are needed, there are issues in the elderly with dabigatran due to variable drug concentrations, no known antidote and dependence on renal elimination. Published studies have shown dabigatran to be cost-effective but there are budget concerns given the prevalence of atrial fibrillation. There are also issues with potentially re-designing anticoagulant services. This has resulted in activities across countries to better manage its use. Objective: To (i review authority activities in over 30 countries and regions, (ii use the findings to develop new models to better manage the entry of new drugs , and (iii review the implications for all major stakeholder groups. Methodology: Descriptive review and appraisal of activities regarding dabigatran and the development of guidance for groups through an iterative process. Results: There has been a plethora of activities to manage dabigatran including extensive pre-launch activities, risk sharing arrangements, prescribing restrictions and monitoring of prescribing post launch. Reimbursement has been denied in some countries due to concerns with its budget impact and/or excessive bleeding. Development of a new model and future guidance is proposed to better manage the entry of new drugs, centring on three pillars of pre-, peri- and post-launch activities. Conclusion: Models for introducing new drugs are essential to optimise their prescribing especially where there are concerns. Without such models, new drugs may be withdrawn prematurely and/ or struggle for funding.

  13. Investigation of toxic metabolites during drug development

    International Nuclear Information System (INIS)

    Park, Kevin; Williams, Dominic P.; Naisbitt, Dean J.; Kitteringham, Neil R.; Pirmohamed, Munir

    2005-01-01

    Adverse drug reactions (ADRs) are a significant human health problem. Any organ system can be affected, including the liver, skin and kidney. Drug-induced liver injury is the most frequent reason for the withdrawal of an approved drug from the market, and it also accounts for up to 50% of cases of acute liver failure. The clinical picture is often diverse, even for the same drug. Mild, asymptomatic effects occur at a relatively high frequency with a number of drugs. Idiosyncratic toxicity is rare but potentially life-threatening. Many serious ADRs that occur in man are unpredictable from routine pathology and clinical chemistry in laboratory animals and are therefore poorly understood. The drug metabolist can determine the propensity of a novel chemical entity to either accumulate in the hepatocyte or undergo bioactivation in numerous model systems, from expressed enzymes, genetically engineered cells to whole animals. Bioactivation can be measured using trapping experiments with model nucleophiles or by measurement of non-specific covalent binding. The chemistry of the process is defined and the medicinal chemist can address the issue by seeking a metabolically stable pharmacophore to replace the potential toxicophore. However, we require a more fundamental understanding of the role of drug chemistry and biochemistry in ADRs. This requires knowledge of the ultimate toxin, signalling in cell defense and the sequence of molecular events, which ultimately lead to cell and tissue damage. It is imperative that such studies have a clinical level, but then translated into laboratory-based molecular studies. This will provide a deeper understanding of potential toxicophores for drug design and define candidate genes for pharmacogenomic approaches to individualized medicines

  14. The worldwide trend of using botanical drugs and strategies for developing global drugs.

    Science.gov (United States)

    Ahn, Kyungseop

    2017-03-01

    Natural product drugs, or botanical drugs, are drugs composed of natural substances which have constituents with healthenhancing or medicinal activities. In Korea, government-led projects brought attention to botanical drugs invigorating domestic botanical drug industry. Foreign markets, as well, are growing bigger as the significance of botanical drugs stood out. To follow along with the tendency, Korea puts a lot of effort on developing botanical drugs suitable for global market. However, standards for approving drug sales vary by countries. And also, thorough standardization, certification, clinical studies and data of these will be required as well as data confirming safety and effectiveness. Meanwhile, as an international exchange in botanical drug market continues, the importance of plant resources was emphasized. Thus countries' ownership of domestic natural resources became vital. Not only establishing a systematic method to secure domestic plant resources, but also cooperation with other countries on sharing natural resources is essential to procure natural resources effectively. Korea started to show visible results with botanical drugs, and asthma/COPD treatment made out of speedwell is one example. Sufficient investment and government's active support for basic infrastructure for global botanical drugs will bring Korea to much higher level of botanical drug development. [BMB Reports 2017; 50(3): 111-116].

  15. In silico machine learning methods in drug development.

    Science.gov (United States)

    Dobchev, Dimitar A; Pillai, Girinath G; Karelson, Mati

    2014-01-01

    Machine learning (ML) computational methods for predicting compounds with pharmacological activity, specific pharmacodynamic and ADMET (absorption, distribution, metabolism, excretion and toxicity) properties are being increasingly applied in drug discovery and evaluation. Recently, machine learning techniques such as artificial neural networks, support vector machines and genetic programming have been explored for predicting inhibitors, antagonists, blockers, agonists, activators and substrates of proteins related to specific therapeutic targets. These methods are particularly useful for screening compound libraries of diverse chemical structures, "noisy" and high-dimensional data to complement QSAR methods, and in cases of unavailable receptor 3D structure to complement structure-based methods. A variety of studies have demonstrated the potential of machine-learning methods for predicting compounds as potential drug candidates. The present review is intended to give an overview of the strategies and current progress in using machine learning methods for drug design and the potential of the respective model development tools. We also regard a number of applications of the machine learning algorithms based on common classes of diseases.

  16. Developing artemisinin based drug combinations for the treatment of drug resistant falciparum malaria: A review

    Directory of Open Access Journals (Sweden)

    Olliaro P

    2004-01-01

    Full Text Available The emergence and spread of drug resistant malaria represents a considerable challenge to controlling malaria. To date, malaria control has relied heavily on a comparatively small number of chemically related drugs, belonging to either the quinoline or the antifolate groups. Only recently have the artemisinin derivatives been used but mostly in south east Asia. Experience has shown that resistance eventually curtails the life-span of antimalarial drugs. Controlling resistance is key to ensuring that the investment put into developing new antimalarial drugs is not wasted. Current efforts focus on research into new compounds with novel mechanisms of action, and on measures to prevent or delay resistance when drugs are introduced. Drug discovery and development are long, risky and costly ventures. Antimalarial drug development has traditionally been slow but now various private and public institutions are at work to discover and develop new compounds. Today, the antimalarial development pipeline is looking reasonably healthy. Most development relies on the quinoline, antifolate and artemisinin compounds. There is a pressing need to have effective, easy to use, affordable drugs that will last a long time. Drug combinations that have independent modes of action are seen as a way of enhancing efficacy while ensuring mutual protection against resistance. Most research work has focused on the use of artesunate combined with currently used standard drugs, namely, mefloquine, amodiaquine, sulfadoxine/pyrimethamine, and chloroquine. There is clear evidence that combinations improve efficacy without increasing toxicity. However, the absolute cure rates that are achieved by combinations vary widely and depend on the level of resistance of the standard drug. From these studies, further work is underway to produce fixed dose combinations that will be packaged in blister packs. This review will summarise current antimalarial drug developments and outline recent

  17. 18 CFR 367.1880 - Account 188, Research, development, or demonstration expenditures.

    Science.gov (United States)

    2010-04-01

    ... 188, Research, development, or demonstration expenditures. (a) This account must be charged with the cost of all expenditures coming within the meaning of research, development and demonstration (RD&D) of..., development, and demonstration expenditures that are nonrecurring and that would distort the annual research...

  18. A development perspective on adolescent drug abuse.

    Science.gov (United States)

    Baumrind, D; Moselle, K A

    1985-01-01

    Adolescent drug use is placed in an historical and developmental perspective. Existing evidence concerning causes and consequences of adolescent drug use is inconclusive. In the absence of conclusive empirical evidence and cogent theories, we present a prima facie case against early adolescent drug use by defending six propositions which posit specific cognitive, conative, and affective negative consequences including impairment of attention and memory; developmental lag imposing categorical limitations on the level of maximum functioning available to the user in cognitive, moral and psychosocial domains; amotivational syndrome; consolidation of diffuse or negative identity; and social alienation and estrangement. We call for a program of research which could provide credible evidence to support or rebut these propositions, and thus address the factual claims underlying the sociomoral concerns of social policy planners.

  19. Rethinking the Food and Drug Administration's 2013 guidance on developing drugs for early-stage Alzheimer's disease.

    Science.gov (United States)

    Schneider, Lon S

    2014-03-01

    The February 2013 Food and Drug Administration (FDA) draft guidance for developing drugs for early-stage Alzheimer's disease (AD) creates certain challenges as they guide toward the use of one cognitive outcome to gain accelerated marketing approval for preclinical AD drugs, and a composite clinical scale - the Clinical Dementia Rating Scale in particular - for the primary outcome for prodromal AD clinical trials. In light of the developing knowledge regarding early stage diagnoses and clinical trials outcomes, we recommend that FDA describe its requirements for validating preclinical AD diagnoses for drug development purposes, maintain the principle for requiring coprimary outcomes, and encourage the advancement of outcomes for early stage AD trials. The principles for drug development for early stage AD should not differ from those for clinical AD, especially as the diagnoses of prodromal and early AD impinge on each other. The FDA should not recommend that a composite scale be used as a sole primary efficacy outcome to support a marketing claim unless it requires that the cognitive and functional components of such a scale are demonstrated to be individually meaningful. The current draft guidelines may inadvertently constrain efforts to better assess the clinical effects of new drugs and inhibit innovation in an area where evidence-based clinical research practices are still evolving. Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  20. Open source drug discovery--a new paradigm of collaborative research in tuberculosis drug development.

    Science.gov (United States)

    Bhardwaj, Anshu; Scaria, Vinod; Raghava, Gajendra Pal Singh; Lynn, Andrew Michael; Chandra, Nagasuma; Banerjee, Sulagna; Raghunandanan, Muthukurussi V; Pandey, Vikas; Taneja, Bhupesh; Yadav, Jyoti; Dash, Debasis; Bhattacharya, Jaijit; Misra, Amit; Kumar, Anil; Ramachandran, Srinivasan; Thomas, Zakir; Brahmachari, Samir K

    2011-09-01

    It is being realized that the traditional closed-door and market driven approaches for drug discovery may not be the best suited model for the diseases of the developing world such as tuberculosis and malaria, because most patients suffering from these diseases have poor paying capacity. To ensure that new drugs are created for patients suffering from these diseases, it is necessary to formulate an alternate paradigm of drug discovery process. The current model constrained by limitations for collaboration and for sharing of resources with confidentiality hampers the opportunities for bringing expertise from diverse fields. These limitations hinder the possibilities of lowering the cost of drug discovery. The Open Source Drug Discovery project initiated by Council of Scientific and Industrial Research, India has adopted an open source model to power wide participation across geographical borders. Open Source Drug Discovery emphasizes integrative science through collaboration, open-sharing, taking up multi-faceted approaches and accruing benefits from advances on different fronts of new drug discovery. Because the open source model is based on community participation, it has the potential to self-sustain continuous development by generating a storehouse of alternatives towards continued pursuit for new drug discovery. Since the inventions are community generated, the new chemical entities developed by Open Source Drug Discovery will be taken up for clinical trial in a non-exclusive manner by participation of multiple companies with majority funding from Open Source Drug Discovery. This will ensure availability of drugs through a lower cost community driven drug discovery process for diseases afflicting people with poor paying capacity. Hopefully what LINUX the World Wide Web have done for the information technology, Open Source Drug Discovery will do for drug discovery. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. Developing a Dissociative Nanocontainer for Peptide Drug Delivery

    Directory of Open Access Journals (Sweden)

    Patrick Kelly

    2015-10-01

    Full Text Available The potency, selectivity, and decreased side effects of bioactive peptides have propelled these agents to the forefront of pharmacological research. Peptides are especially promising for the treatment of neurological disorders and pain. However, delivery of peptide therapeutics often requires invasive techniques, which is a major obstacle to their widespread application. We have developed a tailored peptide drug delivery system in which the viral capsid of P22 bacteriophage is modified to serve as a tunable nanocontainer for the packaging and controlled release of bioactive peptides. Recent efforts have demonstrated that P22 nanocontainers can effectively encapsulate analgesic peptides and translocate them across blood-brain-barrier (BBB models. However, release of encapsulated peptides at their target site remains a challenge. Here a Ring Opening Metathesis Polymerization (ROMP reaction is applied to trigger P22 nanocontainer disassembly under physiological conditions. Specifically, the ROMP substrate norbornene (5-Norbornene-2-carboxylic acid is conjugated to the exterior of a loaded P22 nanocontainer and Grubbs II Catalyst is used to trigger the polymerization reaction leading to nanocontainer disassembly. Our results demonstrate initial attempts to characterize the ROMP-triggered release of cargo peptides from P22 nanocontainers. This work provides proof-of-concept for the construction of a triggerable peptide drug delivery system using viral nanocontainers.

  2. Kinase-Centric Computational Drug Development

    NARCIS (Netherlands)

    Kooistra, Albert J.; Volkamer, Andrea

    2017-01-01

    Kinases are among the most studied drug targets in industry and academia, due to their involvement in a majority of cellular processes and, upon dysregulation, in a variety of diseases including cancer, inflammation, and autoimmune disorders. The high interest in this druggable protein family

  3. Preclinical experimental models of drug metabolism and disposition in drug discovery and development

    Directory of Open Access Journals (Sweden)

    Donglu Zhang

    2012-12-01

    Full Text Available Drug discovery and development involve the utilization of in vitro and in vivo experimental models. Different models, ranging from test tube experiments to cell cultures, animals, healthy human subjects, and even small numbers of patients that are involved in clinical trials, are used at different stages of drug discovery and development for determination of efficacy and safety. The proper selection and applications of correct models, as well as appropriate data interpretation, are critically important in decision making and successful advancement of drug candidates. In this review, we discuss strategies in the applications of both in vitro and in vivo experimental models of drug metabolism and disposition.

  4. A two-pronged approach in leishmaniasis drug development in ...

    African Journals Online (AJOL)

    Nancy Kamau

    Trouiller P; Olliaro P; Torreele E;. Orbinski J; Laing R and Ford N. Drug development for neglected diseases: a deficient market and a public-health policy failure. Lancet. 2002; 359: 2188–94. 9. Nwaka S and Ridley RG. Virtual drug discovery and development for neglected diseases through public-private partnerships.

  5. An active role for machine learning in drug development

    Science.gov (United States)

    Murphy, Robert F.

    2014-01-01

    Due to the complexity of biological systems, cutting-edge machine-learning methods will be critical for future drug development. In particular, machine-vision methods to extract detailed information from imaging assays and active-learning methods to guide experimentation will be required to overcome the dimensionality problem in drug development. PMID:21587249

  6. Delays in clinical development of neurological drugs in Japan.

    Science.gov (United States)

    Ikeda, Masayuki

    2017-06-28

    The delays in the approval and development of neurological drugs between Japan and other countries have been a major issue for patients with neurological diseases. The objective of this study was to analyze factors contributing to the delay in the launching of neurological drugs in Japan. We analyzed data from Japan and the US for the approval of 42 neurological drugs, all of which were approved earlier in the US than in Japan, and examined the potential factors that may cause the delay of their launch. Introductions of the 42 drugs in Japan occurred at a median of 87 months after introductions in the US. The mean review time of new drug applications for the 20 drugs introduced in Japan in January 2011 or later (15 months) was significantly shorter than that for the other 22 drugs introduced in Japan in December 2010 or earlier (24 months). The lag in the Japan's review time behind the US could not explain the approval delays. In the 31 of the 42 drugs, the application data package included overseas data. The mean review time of these 31 drugs (17 months) was significantly shorter than that of the other 11 drugs without overseas data (26 months). The mean approval lag behind the US of the 31 drugs (78 months) was also significantly shorter than that of the other 11 drugs (134 months). These results show that several important reforms in the Japanese drug development and approval system (e.g., inclusion of global clinical trial data) have reduced the delays in the clinical development of neurological drugs.

  7. [New drug development by innovative drug administration--"change" in pharmaceutical field].

    Science.gov (United States)

    Nagai, T

    1997-11-01

    New drug development can be made by providing products of higher "selectivity for the drug" for medical treatment. There are two ways for the approach to get higher "selectivity of drug": 1) discovery of new compounds with high selectivity of drug; 2) innovation of new drug administration, that is new formulation and/or method with high selectivity of drug by integration and harmonization of various hard/soft technologies. An extensive increase of biological information and advancement of surrounding science and technology may modify the situation as the latter overcomes the former in the 21 century. As the science and technology in the 21 century is said to be formed on "3H", that is, 1. hybrid; 2. hi-quality; 3. husbandry, the new drug development by innovative drug administration is exactly based on the science and technology of 3H. Its characteristic points are interdisciplinary/interfusion, international, of philosophy/ethics, and systems of hard/hard/heart. From these points of view, not only the advance of unit technology but also a revolution in thinking way should be "must" subjects. To organize this type of research well, a total research activity such as ROR (research on research) might take an important and efficient role. Here the key words are the "Optimization technology" and "Change in Pharmaceutical Fields." As some examples of new drug innovation, our trials on several topical mucosal adhesive dosage forms and parenteral administration of peptide drugs such as insulin and erythropoietin will be described.

  8. Developing a molecular roadmap of drug-food interactions.

    Directory of Open Access Journals (Sweden)

    Kasper Jensen

    2015-02-01

    Full Text Available Recent research has demonstrated that consumption of food -especially fruits and vegetables- can alter the effects of drugs by interfering either with their pharmacokinetic or pharmacodynamic processes. Despite the recognition of such drug-food associations as an important element for successful therapeutic interventions, a systematic approach for identifying, predicting and preventing potential interactions between food and marketed or novel drugs is not yet available. The overall objective of this work was to sketch a comprehensive picture of the interference of ∼ 4,000 dietary components present in ∼1800 plant-based foods with the pharmacokinetics and pharmacodynamics processes of medicine, with the purpose of elucidating the molecular mechanisms involved. By employing a systems chemical biology approach that integrates data from the scientific literature and online databases, we gained a global view of the associations between diet and dietary molecules with drug targets, metabolic enzymes, drug transporters and carriers currently deposited in DrugBank. Moreover, we identified disease areas and drug targets that are most prone to the negative effects of drug-food interactions, showcasing a platform for making recommendations in relation to foods that should be avoided under certain medications. Lastly, by investigating the correlation of gene expression signatures of foods and drugs we were able to generate a completely novel drug-diet interactome map.

  9. Reflection of successful anticancer drug development processes in the literature.

    Science.gov (United States)

    Heinemann, Fabian; Huber, Torsten; Meisel, Christian; Bundschus, Markus; Leser, Ulf

    2016-11-01

    The development of cancer drugs is time-consuming and expensive. In particular, failures in late-stage clinical trials are a major cost driver for pharmaceutical companies. This puts a high demand on methods that provide insights into the success chances of new potential medicines. In this study, we systematically analyze publication patterns emerging along the drug discovery process of targeted cancer therapies, starting from basic research to drug approval - or failure. We find clear differences in the patterns of approved drugs compared with those that failed in Phase II/III. Feeding these features into a machine learning classifier allows us to predict the approval or failure of a targeted cancer drug significantly better than educated guessing. We believe that these findings could lead to novel measures for supporting decision making in drug development. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Challenges in orphan drug development and regulatory policy in China.

    Science.gov (United States)

    Cheng, Alice; Xie, Zhi

    2017-01-18

    While regulatory policy is well defined for orphan drug development in the United States and Europe, rare disease policy in China is still evolving. Many Chinese patients currently pay out of pocket for international treatments that are not yet approved in China. The lack of a clear definition and therefore regulatory approval process for rare diseases has, until now, de-incentivized pharmaceutical companies to pursue rare disease drug development in China. In turn, many grassroots movements have begun to support rare disease patients and facilitate drug discovery through research. Recently, the Chinese FDA set new regulatory guidelines for drugs being developed in China, including an expedited review process for life-saving treatments. In this review, we discuss the effects of these new policy changes on and suggest potential solutions to innovate orphan drug development in China.

  11. Development and demonstration of energy saving technologies in agriculture; Udvikling og demonstration af energibesparende teknologi til landbruget

    Energy Technology Data Exchange (ETDEWEB)

    Pedersen, Joergen; Trenel, P.; Krogh Hansen, T.; Andersen, Mathias

    2010-07-01

    The energy consumption for agriculture is approx. 10% of the total corporate energy use in Denmark and is therefore a major source of total CO2 emission. This project aims to show that there is great potential for reducing energy use in agriculture. The project focused on saving energy in pig production, as this is the largest branch of production in farming and also the most energy consuming. The energy consumption in selected herds has been monitored with high accuracy making it possible to track down energy consumption, on system level, minute by minute. The energy consumption for light, ventilation and heating systems has been followed in various sections of different farms to compare the level of consumption. In the project 4 technologies were developed and tested. The results are: 1) Two new EC (electronically commuted) fans for livestock facilities makes it possible to reduce power consumption for ventilation with over 50% compared with frequency controlled fans; 2) An intelligent shelter for two climate stables was developed to regulate heat in the piglet pens. The system showed a 43% energy saving for heating compared to identical climate stables with normal floor heating; 3) An hour-based energy management system called Elspot was tested. The Elspot module can automatically activate and deactivate electrically powered equipment according to the energy price. The study found that farms can reduce their spending on electricity by 25% using the Elspot module on a feed mill; 4) A web interface for energy monitoring was designed specifically for farmers. This system makes it possible for farmers to monitor their energy consumption at and benchmark this against normative values or new technologies. The initial goal of the project was to develop and demonstrate solutions that could potentially reduce energy consumption in agriculture by 20%. Since the work was done only with energy saving technologies in livestock production, this corresponds to an energy

  12. Fragment-based drug discovery as alternative strategy to the drug development for neglected diseases.

    Science.gov (United States)

    Mello, Juliana da Fonseca Rezende E; Gomes, Renan Augusto; Vital-Fujii, Drielli Gomes; Ferreira, Glaucio Monteiro; Trossini, Gustavo Henrique Goulart

    2017-12-01

    Neglected diseases (NDs) affect large populations and almost whole continents, representing 12% of the global health burden. In contrast, the treatment available today is limited and sometimes ineffective. Under this scenery, the Fragment-Based Drug Discovery emerged as one of the most promising alternatives to the traditional methods of drug development. This method allows achieving new lead compounds with smaller size of fragment libraries. Even with the wide Fragment-Based Drug Discovery success resulting in new effective therapeutic agents against different diseases, until this moment few studies have been applied this approach for NDs area. In this article, we discuss the basic Fragment-Based Drug Discovery process, brief successful ideas of general applications and show a landscape of its use in NDs, encouraging the implementation of this strategy as an interesting way to optimize the development of new drugs to NDs. © 2017 John Wiley & Sons A/S.

  13. Accelerating Precision Drug Development and Drug Repurposing by Leveraging Human Genetics.

    Science.gov (United States)

    Pulley, Jill M; Shirey-Rice, Jana K; Lavieri, Robert R; Jerome, Rebecca N; Zaleski, Nicole M; Aronoff, David M; Bastarache, Lisa; Niu, Xinnan; Holroyd, Kenneth J; Roden, Dan M; Skaar, Eric P; Niswender, Colleen M; Marnett, Lawrence J; Lindsley, Craig W; Ekstrom, Leeland B; Bentley, Alan R; Bernard, Gordon R; Hong, Charles C; Denny, Joshua C

    2017-04-01

    The potential impact of using human genetic data linked to longitudinal electronic medical records on drug development is extraordinary; however, the practical application of these data necessitates some organizational innovations. Vanderbilt has created resources such as an easily queried database of >2.6 million de-identified electronic health records linked to BioVU, which is a DNA biobank with more than 230,000 unique samples. To ensure these data are used to maximally benefit and accelerate both de novo drug discovery and drug repurposing efforts, we created the Accelerating Drug Development and Repurposing Incubator, a multidisciplinary think tank of experts in various therapeutic areas within both basic and clinical science as well as experts in legal, business, and other operational domains. The Incubator supports a diverse pipeline of drug indication finding projects, leveraging the natural experiment of human genetics.

  14. Pharmacogenomics and its potential impact on drug and formulation development.

    Science.gov (United States)

    Regnstrom, Karin; Burgess, Diane J

    2005-01-01

    Recent advances in genomic research have provided the basis for new insights into the importance of genetic and genomic markers during the different stages of drug development. A new field of research, pharmacogenomics, which studies the relationship between drug effects and the genome, has emerged. Structural pharmacogenomics maps the complete DNA sequences of whole genomes (genotypes) including individual variations, and functional pharmacogenomics assesses the expression levels of thousands of genes in one single experiment. Together, these two areas of pharmacogenomics have generated massive databases, which have become a challenge for the research field of informatics and have fostered a new branch of research, bioinformatics. If skillfully used, the databases generated by pharmacogenomics together with data mining on the Web promise to improve the drug development process in a variety of areas: identification of drug targets, evaluation of toxicity, classification of diseases, evaluation of formulations, assessment of drug response and treatment, post-marketing applications, and development of personalized medicines.

  15. Otic drug delivery systems: formulation principles and recent developments.

    Science.gov (United States)

    Liu, Xu; Li, Mingshuang; Smyth, Hugh; Zhang, Feng

    2018-04-25

    Disorders of the ear severely impact the quality of life of millions of people, but the treatment of these disorders is an ongoing, but often overlooked challenge particularly in terms of formulation design and product development. The prevalence of ear disorders has spurred significant efforts to develop new therapeutic agents, but perhaps less innovation has been applied to new drug delivery systems to improve the efficacy of ear disease treatments. This review provides a brief overview of physiology, major diseases, and current therapies used via the otic route of administration. The primary focuses are on the various administration routes and their formulation principles. The article also presents recent advances in otic drug deliveries as well as potential limitations. Otic drug delivery technology will likely evolve in the next decade and more efficient or specific treatments for ear disease will arise from the development of less invasive drug delivery methods, safe and highly controlled drug delivery systems, and biotechnology targeting therapies.

  16. Recent developments in oral lipid-based drug delivery

    DEFF Research Database (Denmark)

    Thomas, N.; Rades, T.; Müllertz, A.

    2013-01-01

    The increasing number of poorly water-soluble drugs in development in the pharmaceutical industry has sparked interest in novel drug delivery options such as lipid-based drug delivery systems (LbDDS). Several LbDDS have been marketed successfully and have shown superior and more reliable...... bioavailability compared to conventional formulations. However, some reluctance in the broader application of LbDDS still appears, despite the growing commercial interest in lipids as a drug delivery platform. This reluctance might at least in part be related to the complexity associated with the development...... and characterization of LbDDS. In particular, the lack of standardized test protocols can be identified as the major obstacles for the broader application of LbDDS. This review seeks to summarize recent approaches in the field of lipid-based drug delivery that try to elucidate some critical steps in their development...

  17. Big Data: transforming drug development and health policy decision making.

    Science.gov (United States)

    Alemayehu, Demissie; Berger, Marc L

    The explosion of data sources, accompanied by the evolution of technology and analytical techniques, has created considerable challenges and opportunities for drug development and healthcare resource utilization. We present a systematic overview these phenomena, and suggest measures to be taken for effective integration of the new developments in the traditional medical research paradigm and health policy decision making. Special attention is paid to pertinent issues in emerging areas, including rare disease drug development, personalized medicine, Comparative Effectiveness Research, and privacy and confidentiality concerns.

  18. 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 ...

  19. Data-intensive drug development in the information age: applications of Systems Biology/Pharmacology/Toxicology.

    Science.gov (United States)

    Kiyosawa, Naoki; Manabe, Sunao

    2016-01-01

    Pharmaceutical companies continuously face challenges to deliver new drugs with true medical value. R&D productivity of drug development projects depends on 1) the value of the drug concept and 2) data and in-depth knowledge that are used rationally to evaluate the drug concept's validity. A model-based data-intensive drug development approach is a key competitive factor used by innovative pharmaceutical companies to reduce information bias and rationally demonstrate the value of drug concepts. Owing to the accumulation of publicly available biomedical information, our understanding of the pathophysiological mechanisms of diseases has developed considerably; it is the basis for identifying the right drug target and creating a drug concept with true medical value. Our understanding of the pathophysiological mechanisms of disease animal models can also be improved; it can thus support rational extrapolation of animal experiment results to clinical settings. The Systems Biology approach, which leverages publicly available transcriptome data, is useful for these purposes. Furthermore, applying Systems Pharmacology enables dynamic simulation of drug responses, from which key research questions to be addressed in the subsequent studies can be adequately informed. Application of Systems Biology/Pharmacology to toxicology research, namely Systems Toxicology, should considerably improve the predictability of drug-induced toxicities in clinical situations that are difficult to predict from conventional preclinical toxicology studies. Systems Biology/Pharmacology/Toxicology models can be continuously improved using iterative learn-confirm processes throughout preclinical and clinical drug discovery and development processes. Successful implementation of data-intensive drug development approaches requires cultivation of an adequate R&D culture to appreciate this approach.

  20. Inkjet Printing of Drug-Loaded Mesoporous Silica Nanoparticles-A Platform for Drug Development.

    Science.gov (United States)

    Wickström, Henrika; Hilgert, Ellen; Nyman, Johan O; Desai, Diti; Şen Karaman, Didem; de Beer, Thomas; Sandler, Niklas; Rosenholm, Jessica M

    2017-11-21

    Mesoporous silica nanoparticles (MSNs) have shown great potential in improving drug delivery of poorly water soluble (BCS class II, IV) and poorly permeable (BCS class III, IV) drugs, as well as facilitating successful delivery of unstable compounds. The nanoparticle technology would allow improved treatment by reducing adverse reactions of currently approved drugs and possibly reintroducing previously discarded compounds from the drug development pipeline. This study aims to highlight important aspects in mesoporous silica nanoparticle (MSN) ink formulation development for digital inkjet printing technology and to advice on choosing a method (2D/3D) for nanoparticle print deposit characterization. The results show that both unfunctionalized and polyethyeleneimine (PEI) surface functionalized MSNs, as well as drug-free and drug-loaded MSN-PEI suspensions, can be successfully inkjet-printed. Furthermore, the model BCS class IV drug remained incorporated in the MSNs and the suspension remained physically stable during the processing time and steps. This proof-of-concept study suggests that inkjet printing technology would be a flexible deposition method of pharmaceutical MSN suspensions to generate patterns according to predefined designs. The concept could be utilized as a versatile drug screening platform in the future due to the possibility of accurately depositing controlled volumes of MSN suspensions on various materials.

  1. Inkjet Printing of Drug-Loaded Mesoporous Silica Nanoparticles—A Platform for Drug Development

    Directory of Open Access Journals (Sweden)

    Henrika Wickström

    2017-11-01

    Full Text Available Mesoporous silica nanoparticles (MSNs have shown great potential in improving drug delivery of poorly water soluble (BCS class II, IV and poorly permeable (BCS class III, IV drugs, as well as facilitating successful delivery of unstable compounds. The nanoparticle technology would allow improved treatment by reducing adverse reactions of currently approved drugs and possibly reintroducing previously discarded compounds from the drug development pipeline. This study aims to highlight important aspects in mesoporous silica nanoparticle (MSN ink formulation development for digital inkjet printing technology and to advice on choosing a method (2D/3D for nanoparticle print deposit characterization. The results show that both unfunctionalized and polyethyeleneimine (PEI surface functionalized MSNs, as well as drug-free and drug-loaded MSN–PEI suspensions, can be successfully inkjet-printed. Furthermore, the model BCS class IV drug remained incorporated in the MSNs and the suspension remained physically stable during the processing time and steps. This proof-of-concept study suggests that inkjet printing technology would be a flexible deposition method of pharmaceutical MSN suspensions to generate patterns according to predefined designs. The concept could be utilized as a versatile drug screening platform in the future due to the possibility of accurately depositing controlled volumes of MSN suspensions on various materials.

  2. Ethnically diverse pluripotent stem cells for drug development.

    Science.gov (United States)

    Fakunle, Eyitayo S; Loring, Jeanne F

    2012-12-01

    Genetic variation is an identified factor underlying drug efficacy and toxicity, and adverse drug reactions, such as liver toxicity, are the primary reasons for post-marketing drug failure. Genetic predisposition to toxicity might be detected early in the drug development pipeline by introducing cell-based assays that reflect the genetic and ethnic variation of the expected treatment population. One challenge for this approach is obtaining a collection of suitable cell lines derived from ethnically diverse populations. Induced pluripotent stem cells (iPSCs) seem ideal for this purpose. They can be obtained from any individual, can be differentiated into multiple relevant cell types, and their self-renewal capability makes it possible to generate large quantities of quality-controlled cell types. Here, we discuss the benefits and challenges of using iPSCs to introduce genetic diversity into the drug development process. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. Benefit-Risk Assessment in Drug Development

    DEFF Research Database (Denmark)

    Sarac, Sinan

    developed, tested and used. Standardised diagrams for the visualisation of results from the assessment have been established, and different diagrams have been developed for different scenarios. For the visualisation of results from single and/or multiple similar trial assessments, tornado-like diagrams were...

  4. Research Ethics and Commercial Drug Development: When Integrity Threatens Profitability

    Directory of Open Access Journals (Sweden)

    Bélisle Pipon, Jean-Christophe

    2016-05-01

    Full Text Available This case, based on personal experiences and on those found in the literature, highlights the delicate tension faced by drug development companies having to balance research integrity and their profitability.

  5. Investigational drugs in early development for treating dengue infection.

    Science.gov (United States)

    Beesetti, Hemalatha; Khanna, Navin; Swaminathan, Sathyamangalam

    2016-09-01

    Dengue has emerged as the most significant arboviral disease of the current century. A drug for dengue is an urgent unmet need. As conventional drug discovery efforts have not produced any promising clinical candidates, there is a shift toward re-positioning pre-existing drugs for dengue to fast-track dengue drug development. This article provides an update on the current status of recently completed and ongoing dengue drug trials. All dengue drug trials described in this article were identified from a list of >230 trials that were returned upon searching the World Health Organization's International Clinical Trials Registry Platform web portal using the search term 'dengue' on December 31(st), 2015. None of the handful of drugs tested so far has yielded encouraging results. Early trial experience has served to emphasize the challenge of drug testing in the short therapeutic time window available, the need for tools to predict 'high-risk' patients early on and the limitations of the existing pre-clinical model systems. Significant investment of efforts and resources is a must before the availability of a safe, effective and inexpensive dengue drug becomes a reality. Currently, supportive fluid therapy remains the only option available for dengue treatment.

  6. A New Drug Release Method in Early Development of Transdermal Drug Delivery Systems

    Directory of Open Access Journals (Sweden)

    Bing Cai

    2012-01-01

    Full Text Available In vitro drug release tests are a widely used tool to measure the variance between transdermal product performances and required by many authorities. However, the result cannot provide a good estimation of the in vivo drug release. In the present work, a new method for measuring drug release from patches has been explored and compared with the conventional USP apparatus 2 and 5 methods. Durogesic patches, here used as a model patch, were placed on synthetic skin simulator and three moisture levels (29, 57, 198 μL cm−2 were evaluated. The synthetic skin simulators were collected after 1, 2, 3, 4, 6, and 24 hours and extracted with pH 1.0 hydrochloric acid solution. The drug concentrations in the extractions were measured by isocratic reverse phase high-pressure liquid chromatography. The results showed that, with the increasing moisture level on the synthetic skin simulator, the drug release rate increased. In comparison with the conventional USP method, the drug release results performed by the new method were in more correlation to the release rate claimed in the product label. This new method could help to differentiate the drug release rates among assorted formulations of transdermal drug delivery systems in the early stage of development.

  7. The Development of Drugs against Acanthamoeba Infections

    OpenAIRE

    Siddiqui, Ruqaiyyah; Aqeel, Yousuf; Khan, Naveed Ahmed

    2016-01-01

    For the past several decades, there has been little improvement in the morbidity and mortality associated with Acanthamoeba keratitis and Acanthamoeba encephalitis, respectively. The discovery of a plethora of antiacanthamoebic compounds has not yielded effective marketed chemotherapeutics. The rate of development of novel antiacanthamoebic chemotherapies of translational value and the lack of interest of the pharmaceutical industry in developing such chemotherapies have been disappointing. O...

  8. Modeling the development of drug addiction in male and female animals.

    Science.gov (United States)

    Lynch, Wendy J

    2018-01-01

    An increasing emphasis has been placed on the development and use of animal models of addiction that capture defining features of human drug addiction, including escalation/binge drug use, enhanced motivation for the drug, preference for the drug over other reward options, use despite negative consequences, and enhanced drug-seeking/relapse vulnerability. The need to examine behavior in both males and females has also become apparent given evidence demonstrating that the addiction process occurs differently in males and females. This review discusses the procedures that are used to model features of addiction in animals, as well as factors that influence their development. Individual differences are also discussed, with a particular focus on sex differences. While no one procedure consistently produces all characteristics, different models have been developed to focus on certain characteristics. A history of escalating/binge patterns of use appears to be critical for producing other features characteristic of addiction, including an enhanced motivation for the drug, enhanced drug seeking, and use despite negative consequences. These characteristics tend to emerge over abstinence, and appear to increase rather than decrease in magnitude over time. In females, these characteristics develop sooner during abstinence and/or following less drug exposure as compared to males, and for psychostimulant addiction, may require estradiol. Although preference for the drug over other reward options has been demonstrated in non-human primates, it has been more difficult to establish in rats. Future research is needed to define the parameters that optimally induce each of these features of addiction in the majority of animals. Such models are essential for advancing our understanding of human drug addiction and its treatment in men and women. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Demonstrating and implementing innovative technologies: Case studies from the USDOE Office of Technology Development

    International Nuclear Information System (INIS)

    Brouns, T.M.; Koegler, K.J.; Mamiya, L.S.

    1995-02-01

    This paper describes elements of success for demonstration, evaluation, and transfer for deployment of innovative technologies for environmental restoration. They have been compiled from lessons learned through the US Department of Energy (DOE) Office of Technology Development's Volatile Organic Compounds in Arid Soil Integrated Demonstration (VOC-Arid ID). The success of the VOC-Arid ID program was determined by the rapid development demonstration, and transfer for deployment of technologies to operational sites that improve on safety, cost, and/or schedule of performance over baseline technologies. The VOC-Arid ID successfully fielded more than 25 innovative technology field demonstrations; several of the technologies demonstrated have been successfully transferred for deployment Field demonstration is a critical element in the successful transfer of innovative technologies into environmental restoration operations. The measures of success for technology demonstrations include conducting the demonstration in a safe and controlled environment and generating the appropriate information by which to evaluate the technology. However, field demonstrations alone do not guarantee successful transfer for deployment There are many key elements throughout the development and demonstration process that have a significant impact on the success of a technology. This paper presents key elements for a successful technology demonstration and transfer for deployment identified through the experiences of the VOC-Arid ID. Also, several case studies are provided as examples

  10. Mathematical modeling of efficacy and safety for anticancer drugs clinical development.

    Science.gov (United States)

    Lavezzi, Silvia Maria; Borella, Elisa; Carrara, Letizia; De Nicolao, Giuseppe; Magni, Paolo; Poggesi, Italo

    2018-01-01

    Drug attrition in oncology clinical development is higher than in other therapeutic areas. In this context, pharmacometric modeling represents a useful tool to explore drug efficacy in earlier phases of clinical development, anticipating overall survival using quantitative model-based metrics. Furthermore, modeling approaches can be used to characterize earlier the safety and tolerability profile of drug candidates, and, thus, the risk-benefit ratio and the therapeutic index, supporting the design of optimal treatment regimens and accelerating the whole process of clinical drug development. Areas covered: Herein, the most relevant mathematical models used in clinical anticancer drug development during the last decade are described. Less recent models were considered in the review if they represent a standard for the analysis of certain types of efficacy or safety measures. Expert opinion: Several mathematical models have been proposed to predict overall survival from earlier endpoints and validate their surrogacy in demonstrating drug efficacy in place of overall survival. An increasing number of mathematical models have also been developed to describe the safety findings. Modeling has been extensively used in anticancer drug development to individualize dosing strategies based on patient characteristics, and design optimal dosing regimens balancing efficacy and safety.

  11. Breaking barriers to novel analgesic drug development.

    Science.gov (United States)

    Yekkirala, Ajay S; Roberson, David P; Bean, Bruce P; Woolf, Clifford J

    2017-08-01

    Acute and chronic pain complaints, although common, are generally poorly served by existing therapies. This unmet clinical need reflects a failure to develop novel classes of analgesics with superior efficacy, diminished adverse effects and a lower abuse liability than those currently available. Reasons for this include the heterogeneity of clinical pain conditions, the complexity and diversity of underlying pathophysiological mechanisms, and the unreliability of some preclinical pain models. However, recent advances in our understanding of the neurobiology of pain are beginning to offer opportunities for developing novel therapeutic strategies and revisiting existing targets, including modulating ion channels, enzymes and G-protein-coupled receptors.

  12. Counterfeit drugs and medical devices in developing countries

    Directory of Open Access Journals (Sweden)

    Glass BD

    2014-03-01

    Full Text Available Beverley D GlassSchool of Pharmacy and Molecular Sciences, James Cook University, Townsville, QLD, AustraliaAbstract: The World Health Organization has reported that counterfeit medicines potentially make up more than 50% of the global drug market, with a significant proportion of these fake products being encountered in developing countries. This occurrence is attributed to a lack of effective regulation and a weak enforcement capacity existing in these countries, with an increase in this trade resulting from the growing size and sophistication of drug counterfeiters. In addition, due to both cost and lack of availability of medicines, consumers in developing countries are more likely to seek out these inexpensive options. The World Health Organization is mindful of the impact of counterfeit drugs on consumer confidence in health care systems, health professionals, the supply chain, and genuine suppliers of medicines and medical devices. Antibiotics, antituberculosis drugs, and antimalarial and antiretroviral drugs are frequently targeted, with reports of 60% of the anti-infective drugs in Asia and Africa containing active pharmaceutical ingredients outside their pharmacopoeial limits. This has obvious public health implications of increasing drug resistance and negating all the efforts that have already gone into the provision of medicines to treat these life threatening conditions in the developing world. This review, while focusing on counterfeit medicines and medical devices in developing countries, will present information on their impact and how these issues can be addressed by regulation and control of the supply chain using technology appropriate to the developing world. The complexity of the problem will also be highlighted in terms of the definition of counterfeit and substandard medicines, including gray pharmaceuticals. Although this issue presents as a global public health problem, outcomes in developing countries where counterfeit

  13. Development of a gastroretentive pulsatile drug delivery platform.

    Science.gov (United States)

    Thitinan, Sumalee; McConville, Jason T

    2012-04-01

    To develop a novel gastroretentive pulsatile drug delivery platform by combining the advantages of floating dosage forms for the stomach and pulsatile drug delivery systems. A gastric fluid impermeable capsule body was used as a vessel to contain one or more drug layer(s) as well as one or more lag-time controlling layer(s). A controlled amount of air was sealed in the innermost portion of the capsule body to reduce the overall density of the drug delivery platform, enabling gastric floatation. An optimal mass fill inside the gastric fluid impermeable capsule body enabled buoyancy in a vertical orientation to provide a constant surface area for controlled erosion of the lag-time controlling layer. The lag-time controlling layer consisted of a swellable polymer, which rapidly formed a gel to seal the mouth of capsule body and act as a barrier to gastric fluid ingress. By varying the composition of the lag-time controlling layer, it was possible to selectively program the onset of the pulsatile delivery of a drug. This new delivery platform offers a new method of delivery for a variety of suitable drugs targeted in chronopharmaceutical therapy. This strategy could ultimately improve drug efficacy and patient compliance, and reduce harmful side effects by scaling back doses of drug administered. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.

  14. [Development of new drugs: opportunities and benefits for Peru].

    Science.gov (United States)

    Bayona, Andrés; Fajardo, Natalia

    2012-01-01

    The development of innovative drugs allows coming up with new medicines to prevent and better treat illnesses. This improves people's quality of life and makes it more productive. Therefore, the mission of pharmaceutical research is to develop safe and effective drugs. Clinical trials allow the evaluation of the safety and efficacy profiles of new medicines, medical devices and diagnostic tests. Research and development (R&D) of new drugs is a long and costly process, where out of every 5000 to 10000 new components that enter preclinical testing, only one is approved. Compared to 2011, drug development has increased by 7.6%. According to ClinicalTrials.gov, 5% of the trials take place in Latin America, and Peru is in the fifth position. On the other hand, according to the Global Competitiveness Report issued by the World Economic Forum, Peru ranks 61st, its biggest challenges being the functioning of its public institutions, investment in R&D and technological capacity. The complexity of drug R&D results in a search for competitive places to develop clinical trials. Clinical Research is a humanized industry due to its ethical platform, stated in the guidelines of good clinical practices. This industry demands our country to develop a differentiating value that contributes to the development of knowledge and its competitiveness.

  15. Wave energy technology. Strategy for research, development and demonstration 2012; Boelgekraftteknologi. Strategi for forskning, udvikling og demonstration 2012

    Energy Technology Data Exchange (ETDEWEB)

    Nielsen, K.; Krogh, J.; Kofoed, J.P. [Aalborg Univ., Aalborg (Denmark); Jensen, N.E.H. [Energinet.dk, Fredericia (Denmark); Friis-Madsen, E. [Boelgekraftforeningen, Hurup (Denmark); Mikkelsen, B.V. [Hanstholm Havneforum (Denmark); Jensen, A. [DanWEC, Thisted (Denmark)

    2012-06-15

    The vision for Danish development of wave energy technology is that Danish industrial and commercial firms gain skills for marketing of competitive wave energy technologies in both the Danish and the international market. Utilization of wave power is a prerequisite for that there in the future can be built offshore energy parks at greater sea depths. The development of wave energy technology should from 2030 at the latest provide the opportunity for cost-effective, sustainable electricity from offshore energy parks in Denmark. This strategy contains a detailed development plan and overview of the investment required to achieve the expected technological development. The objective to produce 1500 GWh / year at a reduced price of 0.10 DKK / kWh compared to pure offshore wind power will require a public investment of approx. 1.5 billion DKK over the next 20 years. This investment will, at the reduced electricity production cost alone, be paid back in 10 years. (LN)

  16. Development of a brazilian nanoencapsulated drug for schistosomiasis treatment

    Directory of Open Access Journals (Sweden)

    Laís Bastos da Fonseca

    2013-11-01

    Full Text Available Schistosomiasis is a parasitic disease that, according to the World Health Organization, constitutes a major public health problem associated with severe morbidity, mostly children in preschool age. The administration of drugs in children always constitutes a difficult task, especially when formulations are not developed specifically for pediatric use, when high doses of drug are required and the drug has a bitter taste, as in the case of praziquantel. Polymer nanoparticles are promising systems for development of encapsulated drugs with low water solubility and bitter taste, due to the good physical and chemical stability, adequate biocompatibility and simple manufacturing processes. Moreover, they can enhance the bioavailabili-ty and reduce variability of treatment among patients. Poly (methyl methacrylate doped with praziquantel was produced through a miniemulsion polymerization pro-cess to compose a pediatric pharmaceutical suspension. Nanoparticles were cha-racterized in terms of physico-chemical properties, toxicological properties and biological activity in mice, being concluded that obtained results were satisfactory. The results were encapsulation rate around 90%, absence of chemical interaction drug - polymer and the presence of biological activity. A collaborative approach was used for this development, involving national partnerships and independent funding mechanisms, a powerful pathway for development of drugs for neglected diseases.

  17. Use of biomarkers in ALS drug development and clinical trials.

    Science.gov (United States)

    Bakkar, Nadine; Boehringer, Ashley; Bowser, Robert

    2015-05-14

    The past decade has seen a dramatic increase in the discovery of candidate biomarkers for ALS. These biomarkers typically can either differentiate ALS from control subjects or predict disease course (slow versus fast progression). At the same time, late-stage clinical trials for ALS have failed to generate improved drug treatments for ALS patients. Incorporation of biomarkers into the ALS drug development pipeline and the use of biologic and/or imaging biomarkers in early- and late-stage ALS clinical trials have been absent and only recently pursued in early-phase clinical trials. Further clinical research studies are needed to validate biomarkers for disease progression and develop biomarkers that can help determine that a drug has reached its target within the central nervous system. In this review we summarize recent progress in biomarkers across ALS model systems and patient population, and highlight continued research directions for biomarkers that stratify the patient population to enrich for patients that may best respond to a drug candidate, monitor disease progression and track drug responses in clinical trials. It is crucial that we further develop and validate ALS biomarkers and incorporate these biomarkers into the ALS drug development process. This article is part of a Special Issue entitled ALS complex pathogenesis. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Integration of Antibody Array Technology into Drug Discovery and Development.

    Science.gov (United States)

    Huang, Wei; Whittaker, Kelly; Zhang, Huihua; Wu, Jian; Zhu, Si-Wei; Huang, Ruo-Pan

    Antibody arrays represent a high-throughput technique that enables the parallel detection of multiple proteins with minimal sample volume requirements. In recent years, antibody arrays have been widely used to identify new biomarkers for disease diagnosis or prognosis. Moreover, many academic research laboratories and commercial biotechnology companies are starting to apply antibody arrays in the field of drug discovery. In this review, some technical aspects of antibody array development and the various platforms currently available will be addressed; however, the main focus will be on the discussion of antibody array technologies and their applications in drug discovery. Aspects of the drug discovery process, including target identification, mechanisms of drug resistance, molecular mechanisms of drug action, drug side effects, and the application in clinical trials and in managing patient care, which have been investigated using antibody arrays in recent literature will be examined and the relevance of this technology in progressing this process will be discussed. Protein profiling with antibody array technology, in addition to other applications, has emerged as a successful, novel approach for drug discovery because of the well-known importance of proteins in cell events and disease development.

  19. Polymeric drugs: Advances in the development of pharmacologically active polymers

    Science.gov (United States)

    Li, Jing; Yu, Fei; Chen, Yi; Oupický, David

    2015-01-01

    Synthetic polymers play a critical role in pharmaceutical discovery and development. Current research and applications of pharmaceutical polymers are mainly focused on their functions as excipients and inert carriers of other pharmacologically active agents. This review article surveys recent advances in alternative pharmaceutical use of polymers as pharmacologically active agents known as polymeric drugs. Emphasis is placed on the benefits of polymeric drugs that are associated with their macromolecular character and their ability to explore biologically relevant multivalency processes. We discuss the main therapeutic uses of polymeric drugs as sequestrants, antimicrobials, antivirals, and anticancer and anti-inflammatory agents. PMID:26410809

  20. Impact of Drug Metabolism/Pharmacokinetics and Their Relevance upon Taxus-based Drug Development.

    Science.gov (United States)

    Hao, Da-Cheng; Ge, Guang-Bo; Wang, Ping; Yang, Ling

    2018-05-22

    Drug metabolism and pharmacokinetic (DMPK) studies of Taxus natural products, their semi-synthetic derivatives and analogs are indispensable in the optimization of lead compounds and clinical therapy. These studies can lead to development of new drug entities with improved absorption, distribution, metabolism, excretion and toxicity (ADME/T) profiles. To date, there have been no comprehensive reviews of the DMPK features of Taxus derived medicinal compounds.Natural and semi-synthetic taxanes may cause and could be affected by drug-drug interaction (DDI). Hence ADME/T studies of various taxane-containing formulations are important; to date these studies indicate that the role of cytochrome p450s and drug transporters is more prominent than phase II drug metabolizing enzymes. Mechanisms of taxane DMPK mediated by nuclear receptors, microRNAs, and single nucleotide polymorphisms are being revealed. Herein we review the latest knowledge on these topics, as well as the gaps in knowledge of the DMPK issues of Taxus compounds. DDIs significantly impact the PK/pharmacodynamics performance of taxanes and co-administered chemicals, which may inspire researchers to develop novel formula. While the ADME/T profiles of some taxanes are well defined, DMPK studies should be extended to more Taxus compounds, species, and Taxus -involved formulations, which would be streamlined by versatile omics platforms and computational analyses. Further biopharmaceutical investigations will be beneficial tothe translation of bench findings to the clinical applications. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  1. Development and demonstration of near-real-time accounting systems for reprocessing plants

    International Nuclear Information System (INIS)

    Cobb, D.D.; Hakkila, E.A.; Dayem, H.A.; Shipley, J.P.; Baker, A.L.

    1981-01-01

    A program to develop and demonstrate near-real-time accounting systems for reprocessing plants has been active at Los Alamos since 1976. The technology has been developed through modeling and simulation of process operation and measurement systems and evaluation of these data using decision analysis techniques. Aspects of near-real-time systems have been demonstrated successfully at the AGNS reprocessng plant as part of a joint study of near-real-time accounting

  2. Impact of biomarker development on drug safety assessment

    International Nuclear Information System (INIS)

    Marrer, Estelle; Dieterle, Frank

    2010-01-01

    Drug safety has always been a key aspect of drug development. Recently, the Vioxx case and several cases of serious adverse events being linked to high-profile products have increased the importance of drug safety, especially in the eyes of drug development companies and global regulatory agencies. Safety biomarkers are increasingly being seen as helping to provide the clarity, predictability, and certainty needed to gain confidence in decision making: early-stage projects can be stopped quicker, late-stage projects become less risky. Public and private organizations are investing heavily in terms of time, money and manpower on safety biomarker development. An illustrative and 'door opening' safety biomarker success story is the recent recognition of kidney safety biomarkers for pre-clinical and limited translational contexts by FDA and EMEA. This milestone achieved for kidney biomarkers and the 'know how' acquired is being transferred to other organ toxicities, namely liver, heart, vascular system. New technologies and molecular-based approaches, i.e., molecular pathology as a complement to the classical toolbox, allow promising discoveries in the safety biomarker field. This review will focus on the utility and use of safety biomarkers all along drug development, highlighting the present gaps and opportunities identified in organ toxicity monitoring. A last part will be dedicated to safety biomarker development in general, from identification to diagnostic tests, using the kidney safety biomarkers success as an illustrative example.

  3. Accessing external innovation in drug discovery and development.

    Science.gov (United States)

    Tufféry, Pierre

    2015-06-01

    A decline in the productivity of the pharmaceutical industry research and development (R&D) pipeline has highlighted the need to reconsider the classical strategies of drug discovery and development, which are based on internal resources, and to identify new means to improve the drug discovery process. Accepting that the combination of internal and external ideas can improve innovation, ways to access external innovation, that is, opening projects to external contributions, have recently been sought. In this review, the authors look at a number of external innovation opportunities. These include increased interactions with academia via academic centers of excellence/innovation centers, better communication on projects using crowdsourcing or social media and new models centered on external providers such as built-to-buy startups or virtual pharmaceutical companies. The buzz for accessing external innovation relies on the pharmaceutical industry's major challenge to improve R&D productivity, a conjuncture favorable to increase interactions with academia and new business models supporting access to external innovation. So far, access to external innovation has mostly been considered during early stages of drug development, and there is room for enhancement. First outcomes suggest that external innovation should become part of drug development in the long term. However, the balance between internal and external developments in drug discovery can vary largely depending on the company strategies.

  4. Actors of Columbian drug trade : development and transformation

    Directory of Open Access Journals (Sweden)

    Soňa Smolíková

    2011-06-01

    Full Text Available The aim of this article is to portray the main shifts which have been taking place in Colombian drug scene since the 70’s up to the present especially in relation to actors of this business and form of their activity. At first the development of Colombian drug trade till the 80’s when two big cartels centered in Medellín and Cali arose will be briefly outlined. These cartels were able to control a great part of domestic drug trade and due to their enormous power represented serious threat to Colombian state. Thus the cartels declared open warfare with the state in the 80’s. After the cartels’ elimination in the middle of 90’s new actors represented by small drug organizations arose in Colombian drug scene. These small groups were dependent upon cooperation with foreign partners, especially with Mexican cartels. Ever more important role in drug business is played by Colombian left-wing guerilla groups which will be described in the next part of the article. The problem of right-wing paramilitary groups and their participation in Colombian drug trade will be mentioned as well.

  5. Nano-formulations of drugs: Recent developments, impact and challenges.

    Science.gov (United States)

    Jeevanandam, Jaison; Chan, Yen San; Danquah, Michael K

    2016-01-01

    Nano-formulations of medicinal drugs have attracted the interest of many researchers for drug delivery applications. These nano-formulations enhance the properties of conventional drugs and are specific to the targeted delivery site. Dendrimers, polymeric nanoparticles, liposomes, nano-emulsions and micelles are some of the nano-formulations that are gaining prominence in pharmaceutical industry for enhanced drug formulation. Wide varieties of synthesis methods are available for the preparation of nano-formulations to deliver drugs in biological system. The choice of synthesis methods depend on the size and shape of particulate formulation, biochemical properties of drug, and the targeted site. This article discusses recent developments in nano-formulation and the progressive impact on pharmaceutical research and industries. Additionally, process challenges relating to consistent generation of nano-formulations for drug delivery are discussed. Copyright © 2016 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  6. 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.…

  7. The basics of preclinical drug development for neurodegenerative disease indications.

    Science.gov (United States)

    Steinmetz, Karen L; Spack, Edward G

    2009-06-12

    Preclinical development encompasses the activities that link drug discovery in the laboratory to initiation of human clinical trials. Preclinical studies can be designed to identify a lead candidate from several hits; develop the best procedure for new drug scale-up; select the best formulation; determine the route, frequency, and duration of exposure; and ultimately support the intended clinical trial design. The details of each preclinical development package can vary, but all have some common features. Rodent and nonrodent mammalian models are used to delineate the pharmacokinetic profile and general safety, as well as to identify toxicity patterns. One or more species may be used to determine the drug's mean residence time in the body, which depends on inherent absorption, distribution, metabolism, and excretion properties. For drugs intended to treat Alzheimer's disease or other brain-targeted diseases, the ability of a drug to cross the blood brain barrier may be a key issue. Toxicology and safety studies identify potential target organs for adverse effects and define the Therapeutic Index to set the initial starting doses in clinical trials. Pivotal preclinical safety studies generally require regulatory oversight as defined by US Food and Drug Administration (FDA) Good Laboratory Practices and international guidelines, including the International Conference on Harmonization. Concurrent preclinical development activities include developing the Clinical Plan and preparing the new drug product, including the associated documentation to meet stringent FDA Good Manufacturing Practices regulatory guidelines. A wide range of commercial and government contract options are available for investigators seeking to advance their candidate(s). Government programs such as the Small Business Innovative Research and Small Business Technology Transfer grants and the National Institutes of Health Rapid Access to Interventional Development Pilot Program provide funding and

  8. The basics of preclinical drug development for neurodegenerative disease indications

    Directory of Open Access Journals (Sweden)

    Spack Edward G

    2009-06-01

    Full Text Available Abstract Preclinical development encompasses the activities that link drug discovery in the laboratory to initiation of human clinical trials. Preclinical studies can be designed to identify a lead candidate from several hits; develop the best procedure for new drug scale-up; select the best formulation; determine the route, frequency, and duration of exposure; and ultimately support the intended clinical trial design. The details of each preclinical development package can vary, but all have some common features. Rodent and nonrodent mammalian models are used to delineate the pharmacokinetic profile and general safety, as well as to identify toxicity patterns. One or more species may be used to determine the drug's mean residence time in the body, which depends on inherent absorption, distribution, metabolism, and excretion properties. For drugs intended to treat Alzheimer's disease or other brain-targeted diseases, the ability of a drug to cross the blood brain barrier may be a key issue. Toxicology and safety studies identify potential target organs for adverse effects and define the Therapeutic Index to set the initial starting doses in clinical trials. Pivotal preclinical safety studies generally require regulatory oversight as defined by US Food and Drug Administration (FDA Good Laboratory Practices and international guidelines, including the International Conference on Harmonisation. Concurrent preclinical development activities include developing the Clinical Plan and preparing the new drug product, including the associated documentation to meet stringent FDA Good Manufacturing Practices regulatory guidelines. A wide range of commercial and government contract options are available for investigators seeking to advance their candidate(s. Government programs such as the Small Business Innovative Research and Small Business Technology Transfer grants and the National Institutes of Health Rapid Access to Interventional Development Pilot

  9. Improving clinical drug development regulatory procedures for anticonvulsants

    Directory of Open Access Journals (Sweden)

    Janković Slobodan

    2015-01-01

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

  10. [Alternatives to the drug research and development model].

    Science.gov (United States)

    Velásquez, Germán

    2015-03-01

    One-third of the global population lacks access to medications; the situation is worse in poor countries, where up to 50% of the population lacks access. The failure of current incentive systems based in intellectual property to offer the necessary pharmaceutical products, especially in the global south, is a call to action. Problems related to drug access cannot be solved solely through improvements or modifications in the existing incentive models. The intellectual property system model does not offer sufficient innovation for developing countries; new mechanisms that effectively promote innovation and drug access simultaneously are needed. A binding international agreement on research and development, negotiated under the auspices of the World Health Organization, could provide an adequate framework for guaranteeing priority-setting, coordination, and sustainable financing of drugs at reasonable prices for developing countries.

  11. The Use of Social Media in Orphan Drug Development.

    Science.gov (United States)

    Milne, Christopher-Paul; Ni, Wendi

    2017-11-01

    Social media has transformed how people interact with one another through the Internet, and it has the potential to do the same for orphan drug development. Currently, social media influences the orphan drug development process in the following three ways: assisting the study of orphan diseases, increasing the awareness of orphan disease, and playing a vital role in clinical trials. However, there are some caveats to the utilization of social media, such as the need to protect patient privacy by adequately de-identifying personal health information, assuring consistent quality and representativeness of the data, and preventing the unblinding of patient group assignments. Social media has both potential for improving orphan drug development and pitfalls, but with proper oversight on the part of companies, support and participation of patients and their advocacy groups, and timely guidance from regulatory authorities, the positives outweigh the negatives for this powerful and patient-centric tool. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

  12. Development and characterization of multifunctional nanoparticles for drug delivery to cancer cells

    Science.gov (United States)

    Nahire, Rahul Rajaram

    Lipid and polymeric nanoparticles, although proven to be effective drug delivery systems compared to free drugs, have shown considerable limitations pertaining to their uptake and release at tumor sites. Spatial and temporal control over the delivery of anticancer drugs has always been challenge to drug delivery scientists. Here, we have developed and characterized multifunctional nanoparticles (liposomes and polymersomes) which are targeted specifically to cancer cells, and release their contents with tumor specific internal triggers. To enable these nanoparticles to be tracked in blood circulation, we have imparted them with echogenic characteristic. Echogenicity of nanoparticles is evaluated using ultrasound scattering and imaging experiments. Nanoparticles demonstrated effective release with internal triggers such as elevated levels of MMP-9 enzyme found in the extracellular matrix of tumor cells, decreased pH of lysosome, and differential concentration of reducing agents in cytosol of cancer cells. We have also successfully demonstrated the sensitivity of these particles towards ultrasound to further enhance the release with internal triggers. To ensure the selective uptake by folate receptor- overexpressing cancer cells, we decorated these nanoparticles with folic acid on their surface. Fluorescence microscopic images showed significantly higher uptake of folate-targeted nanoparticles by MCF-7 (breast cancer) and PANC-1 (pancreatic cancer) cells compared to particles without any targeting ligand on their surface. To demonstrate the effectiveness of these nanoparticles to carry the drugs inside and kill cancer cells, we encapsulated doxorubicin and/or gemcitabine employing the pH gradient method. Drug loaded nanoparticles showed significantly higher killing of the cancer cells compared to their non-targeted counterparts and free drugs. With further development, these nanoparticles certainly have potential to be used as a multifunctional nanocarriers for image

  13. Low hanging fruit in infectious disease drug development.

    Science.gov (United States)

    Kraus, Carl N

    2008-10-01

    Cost estimates for developing new molecular entities (NME) are reaching non-sustainable levels and coupled with increasing regulatory requirements and oversight have led many pharmaceutical sponsors to divest their anti-microbial development portfolios [Projan SJ: Why is big Pharma getting out of anti-bacterial drug discovery?Curr Opin Microbiol 2003, 6:427-430] [Spellberg B, Powers JH, Brass EP, Miller LG, Edwards JE, Jr: Trends in antimicrobial drug development: implications for the future.Clin Infect Dis 2004, 38:1279-1286]. Operational issues such as study planning and execution are significant contributors to the overall cost of drug development that can benefit from the leveraging of pre-randomization data in an evidence-based approach to protocol development, site selection and patient recruitment. For non-NME products there is even greater benefit from available data resources since these data may permit smaller and shorter study programs. There are now many available open source intelligence (OSINT) resources that are being integrated into drug development programs, permitting an evidence-based or 'operational epidemiology' approach to study planning and execution.

  14. Diabetes mellitus: Exploring the challenges in the drug development process

    Directory of Open Access Journals (Sweden)

    Julius A Vaz

    2012-01-01

    Full Text Available Diabetes mellitus has reached epidemic proportions and continues to be a major burden on society globally. The International Diabetes Federation (IDF estimated the global burden of diabetes to be 366 million in 2011 and predicted that by 2030 this will have risen to 552 million. In spite of newer and effective treatment options, newer delivery and diagnostic devices, stricter glycaemic targets, better treatment guidelines and increased awareness of the disease, baseline glycosylated hemoglobin remains relatively high in subjects diagnosed and treated with type 2 diabetes. The search continues for an ideal anti diabetic drug that will not only normalize blood glucose but also provide beta cell rest and possibly restoration of beta cell function. The development of anti diabetic drugs is riddled with fundamental challenges. The concept of beta cell rest and restoration is yet to be completely understood and proven on a long term. The ideal therapeutic approach to treating type 2 diabetes is not yet determined. Our understanding of drug safety in early clinical development is primarily limited to "Type A" reactions. Until marketing authorization most drugs are approved based on the principle of confirming non-inferiority with an existing gold standard or determining superiority to a placebo. The need to obtain robust pharmaco-economic data prior to marketing authorization in order to determine appropriate pricing of a new drug remains a major challenge. The present review outlines some of the challenges in drug development of anti-diabetic drugs citing examples of pulmonary insulin, insulin analogues, thiazolidinediones and the GLP1 analogues.

  15. Diabetes mellitus: Exploring the challenges in the drug development process.

    Science.gov (United States)

    Vaz, Julius A; Patnaik, Ashis

    2012-07-01

    Diabetes mellitus has reached epidemic proportions and continues to be a major burden on society globally. The International Diabetes Federation (IDF) estimated the global burden of diabetes to be 366 million in 2011 and predicted that by 2030 this will have risen to 552 million. In spite of newer and effective treatment options, newer delivery and diagnostic devices, stricter glycaemic targets, better treatment guidelines and increased awareness of the disease, baseline glycosylated hemoglobin remains relatively high in subjects diagnosed and treated with type 2 diabetes. The search continues for an ideal anti diabetic drug that will not only normalize blood glucose but also provide beta cell rest and possibly restoration of beta cell function. The development of anti diabetic drugs is riddled with fundamental challenges. The concept of beta cell rest and restoration is yet to be completely understood and proven on a long term. The ideal therapeutic approach to treating type 2 diabetes is not yet determined. Our understanding of drug safety in early clinical development is primarily limited to "Type A" reactions. Until marketing authorization most drugs are approved based on the principle of confirming non-inferiority with an existing gold standard or determining superiority to a placebo. The need to obtain robust pharmaco-economic data prior to marketing authorization in order to determine appropriate pricing of a new drug remains a major challenge. The present review outlines some of the challenges in drug development of anti-diabetic drugs citing examples of pulmonary insulin, insulin analogues, thiazolidinediones and the GLP1 analogues.

  16. Quantitative PET Imaging in Drug Development: Estimation of Target Occupancy.

    Science.gov (United States)

    Naganawa, Mika; Gallezot, Jean-Dominique; Rossano, Samantha; Carson, Richard E

    2017-12-11

    Positron emission tomography, an imaging tool using radiolabeled tracers in humans and preclinical species, has been widely used in recent years in drug development, particularly in the central nervous system. One important goal of PET in drug development is assessing the occupancy of various molecular targets (e.g., receptors, transporters, enzymes) by exogenous drugs. The current linear mathematical approaches used to determine occupancy using PET imaging experiments are presented. These algorithms use results from multiple regions with different target content in two scans, a baseline (pre-drug) scan and a post-drug scan. New mathematical estimation approaches to determine target occupancy, using maximum likelihood, are presented. A major challenge in these methods is the proper definition of the covariance matrix of the regional binding measures, accounting for different variance of the individual regional measures and their nonzero covariance, factors that have been ignored by conventional methods. The novel methods are compared to standard methods using simulation and real human occupancy data. The simulation data showed the expected reduction in variance and bias using the proper maximum likelihood methods, when the assumptions of the estimation method matched those in simulation. Between-method differences for data from human occupancy studies were less obvious, in part due to small dataset sizes. These maximum likelihood methods form the basis for development of improved PET covariance models, in order to minimize bias and variance in PET occupancy studies.

  17. Potential drug development candidates for human soil-transmitted helminthiases.

    Directory of Open Access Journals (Sweden)

    Piero Olliaro

    2011-06-01

    Full Text Available Few drugs are available for soil-transmitted helminthiasis (STH; the benzimidazoles albendazole and mebendazole are the only drugs being used for preventive chemotherapy as they can be given in one single dose with no weight adjustment. While generally safe and effective in reducing intensity of infection, they are contra-indicated in first-trimester pregnancy and have suboptimal efficacy against Trichuris trichiura. In addition, drug resistance is a threat. It is therefore important to find alternatives.We searched the literature and the animal health marketed products and pipeline for potential drug development candidates. Recently registered veterinary products offer advantages in that they have undergone extensive and rigorous animal testing, thus reducing the risk, cost and time to approval for human trials. For selected compounds, we retrieved and summarised publicly available information (through US Freedom of Information (FoI statements, European Public Assessment Reports (EPAR and published literature. Concomitantly, we developed a target product profile (TPP against which the products were compared.The paper summarizes the general findings including various classes of compounds, and more specific information on two veterinary anthelmintics (monepantel, emodepside and nitazoxanide, an antiprotozoal drug, compiled from the EMA EPAR and FDA registration files.Few of the compounds already approved for use in human or animal medicine qualify for development track decision. Fast-tracking to approval for human studies may be possible for veterinary compounds like emodepside and monepantel, but additional information remains to be acquired before an informed decision can be made.

  18. Recent developments in drug eluting devices with tailored interfacial properties.

    Science.gov (United States)

    Sanchez-Rexach, Eva; Meaurio, Emilio; Sarasua, Jose-Ramon

    2017-11-01

    Drug eluting devices have greatly evolved during past years to become fundamental products of great marketing importance in the biomedical field. There is currently a large diversity of highly specialized devices for specific applications, making the development of these devices an exciting field of research. The replacement of the former bare metal devices by devices loaded with drugs allowed the sustained and controlled release of drugs, to achieve the desired local therapeutic concentration of drug. The newer devices have been "engineered" with surfaces containing micro- and nanoscale features in a well-controlled manner, that have shown to significantly affect cellular and subcellular function of various biological systems. For example, the topography can be structured to form an antifouling surface mimicking the defense mechanisms found in nature, like the skin of the shark. In the case of bone implants, well-controlled nanostructured interfaces can promote osteoblast differentiation and matrix production, and enhance short-term and long-term osteointegration. In any case, the goal of current research is to design implants that induce controlled, guided, and rapid healing. This article reviews recent trends in the development of drug eluting devices, as well as recent developments on the micro/nanotechnology scales, and their future challenges. For this purpose medical devices have been divided according to the different systems of the body they are focused to: orthopedic devices, breathing stents, gastrointestinal and urinary systems, devices for cardiovascular diseases, neuronal implants, and wound dressings. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Drugs' development in acute heart failure: what went wrong?

    Science.gov (United States)

    Teneggi, Vincenzo; Sivakumar, Nithy; Chen, Deborah; Matter, Alex

    2018-05-08

    Acute heart failure (AHF) is a major burden disease, with a complex physiopathology, unsatisfactory diagnosis, treatment and a very poor prognosis. In the last two decades, a number of drugs have progressed from preclinical to early and late clinical development, but only a few of them have been approved and added to a stagnant pharmacological armamentarium. We have reviewed the data published on drugs developed for AHF since early 2000s, trying to recognise factors that have worked for a successful approval or for the stoppage of the program, in an attempt to delineate future trajectories for AHF drug development. Our review has identified limitations at both preclinical and clinical levels. At the preclinical level, the major shortcoming is represented by animal models looking at short-term endpoints which do not recapitulate the complexity of the human disease. At the clinical level, the main weakness is given by the disconnect between short-term endpoints assessed in the early stage of drug development, and medium-long-term endpoints requested in Phase 3 for regulatory approval. This is further amplified by the lack of validation and standardisation of short- and long-term endpoints; absence of predictive biomarkers; conduct of studies on heterogeneous populations; and use of different eligibility criteria, time of assessments, drug schedules and background therapies. Key goals remain a better understanding of AHF and the construction of a successful drug development program. A reasonable way to move forward resides in a strong collaboration between main stakeholders of therapeutic innovation: scientific community, industry and regulatory agencies.

  20. Improvement of Pediatric Drug Development: Regulatory and Practical Frameworks.

    Science.gov (United States)

    Tsukamoto, Katusra; Carroll, Kelly A; Onishi, Taku; Matsumaru, Naoki; Brasseur, Daniel; Nakamura, Hidefumi

    2016-03-01

    A dearth in pediatric drug development often leaves pediatricians with no alternative but to prescribe unlicensed or off-label drugs with a resultant increased risk of adverse events. We present the current status of pediatric drug development and, based on our data analysis, clarify the problems in this area. Further action is proposed to improve the drug development that has pediatric therapeutic orphan status. We analyzed all Phase II/III and Phase III trials in ClinicalTrials.gov that only included pediatric participants (Performance index, an indicator of pediatric drug development, was calculated by dividing the annual number of pediatric clinical trials by million pediatric populations acquired from Census.gov. Effects of the 2 Japanese premiums introduced in 2010, for the enhancement of pediatric drug development, were analyzed by comparing mean performance index prepremiums (2006-2009) and postpremiums (2010-2014) among Japan, the European Union, and the United States. The European Union Clinical Trials Register and published reports from the European Medicines Agency were also surveyed to investigate the Paediatric Committee effect on pediatric clinical trials in the European Union. Mean difference of the performance index in prepremiums and postpremiums between Japan and the European Union were 0.296 (P 15% after 2008. Recruitment and ethical obstacles make conducting pediatric clinical trials challenging. An improved operational framework for conducting clinical trials should mirror the ever-improving regulatory framework that incentivizes investment in pediatric clinical trials. Technological approaches, enhancements in electronic medical record systems, and community approaches that actively incorporate input from physicians, researchers, and patients could offer a sustainable solution to recruitment of pediatric study participants. The key therefore is to improve pediatric pharmacotherapy collaboration among industry, government, academia, and

  1. Freihoelser Forst Local Training Area Demonstration Project: Prescription development and installation

    International Nuclear Information System (INIS)

    Hinchman, R.R.; Zellmer, S.D.; Brent, J.J.

    1989-04-01

    The Freiholser Forst Local Training Area (LTA) Rehabilitation Demonstration Project is part of the Integrated Training Area Management program being developed by the US Army Corps of Engineers' Construction Engineering Research Laboratory for the Seventh Army Training Command of the US Army in Europe. The rehabilitation demonstration project was begun in 1987 to develop and demonstrate rapid, cost-effective methods to stabilize the LTA's barren, eroding maneuver areas and make training conditions more realistic. The sandy, infertile, and acidic soils at the LTA are considered the major factor limiting rehabilitation efforts there. The project involves the evaluation of three procedures to revegetate the soils, each incorporating identical methods for preparing the seedbed and a single seed mixture consisting of adapted, native species but using different soil amendments. All three treatments have satisfactorily reestablished vegetation and controlled erosion on the demonstration plots at the LTA, but their costs have varied widely

  2. Conceptual design study for the demonstration reactor of JSFR. (1) Current status of JSFR development

    International Nuclear Information System (INIS)

    Hayafune, Hiroki; Sakamoto, Yoshihiko; Kotake, Shoji; Aoto, Kazumi; Ohshima, Jun; Ito, Takaya

    2011-01-01

    JAEA is now conducting 'Fast Reactor Cycle Technology Development (FaCT)' project for the commercialization before 2050s. A demonstration reactor of Japan Sodium-cooled Fast Reactor (JSFR) is planned to start operation around 2025. In the FaCT project, conceptual design study on the demonstration reactor has been performed since 2007 to determine the referential reactor specifications for the next stage design work from 2011 for the licensing and construction. Plant performance as a demonstration reactor for the 1.5 GWe commercial reactor JSFR is being compared between 750 MWe and 500 MWe plant designs. By using the results of conceptual design study, output power will be determined during year of 2010. This paper describes development status of key technologies and comparison between 750 MWe and 500 MWe plants with the view points of demonstration ability for commercial JSFR plant. (author)

  3. Optimization and Simulation in Drug Development - Review and Analysis

    DEFF Research Database (Denmark)

    Schjødt-Eriksen, Jens; Clausen, Jens

    2003-01-01

    We give a review of pharmaceutical R&D and mathematical simulation and optimization methods used to support decision making within the pharmaceutical development process. The complex nature of drug development is pointed out through a description of the various phases of the pharmaceutical develo...... development process. A part of the paper is dedicated to the use of simulation techniques to support clinical trials. The paper ends with a section describing portfolio modelling methods in the context of the pharmaceutical industry....

  4. DEVELOPMENT OF DOMESTIC INFUSION DRUGS BASED ON PARACETAMOL

    Directory of Open Access Journals (Sweden)

    Almakaeva L.G.

    2016-06-01

    Full Text Available The intravenous form of paracetamol compared with oral more reliably supports effective drug concentration in blood plasma that promotes a higher therapeutic effect. Recent studies have confirmed that the use of the intravenous form of paracetamol to deal with postoperative pain multimodal analgesia modes results in reducing the frequency and quantity of opioids administered , and, as a consequence, its associated side effects. The drug Paracetamol , infusion solution 10 mg / ml to 100 ml glass bottles is a drug - generic . His qualitative and quantitative composition is developed from the study of literature data about the drug - similar to " Perfalhan , 10 mg / ml solution for infusion in 100 mL " company Bristol - Myers Squibb, France and experimental work. The aim of our study is development and support of the national composition of the infusion of the drug on the basis of paracetamol, selection of excipients that provide stability of the active substances. Materials and methods. The object of the study was the substance of paracetamol manufactured by Zhejiang Kangle Pharmaceutical Co. , Ltd, China. During the work conducted qualitative and quantitative monitoring sample preparation for indicators of stability: pH content of the active ingredient , transparency, color, impurities , contamination by the methods described in the SFU [and nor- ral documentation to the drug . One potential factor of instability is the effect of paracetamol oxygen, due to the presence in the molecule of paracetamol and -NH possibility of oxidation. Results and Discussion. Paracetamol is derived atsetamina . Substance acetylation are p - aminophenol with acetic anhydride . Saturated aqueous solution has a pH of paracetamol - ment about 6 . Paracetamol is a crystalline white powder , sparingly soluble in water, soluble in 96% alcohol, very slightly soluble in metilenhloride . . Active substance enters in comparison drug in the concentration of 10 mg/ml. Stable

  5. Recent Advances in Drug Development and Regulatory Science in China.

    Science.gov (United States)

    Chen, Jie; Zhao, Naiqing

    2018-01-01

    As the second largest pharmaceutical market with a great potential for future growth, China has drawn much attention from the global pharmaceutical community. With an increasing government investment in biomedical research, the domestic biopharmaceutical (biotechnological) companies in China are turning their attention to the development of innovative medicines and targeting the global market. To introduce innovative products to Chinese patients sooner, to improve the efficiency of its review and approval processes, and to harmonize its regulatory science with international standards, the China Food and Drug Administration (CFDA) has initiated a series of major changes to its policies and regulations. This paper presents a snapshot of China's pharmaceutical market, and research and development status, and introduces technical guidelines pertaining to clinical trials and new drug applications. The recent wave of ground-breaking reforms in CFDA's regulatory science is discussed. Examples of clinical trials and new drug applications are provided throughout the discussion.

  6. Technology development and demonstration for TRIGA research reactor decontamination, decommissioning and site restoration

    International Nuclear Information System (INIS)

    Oh, Won Zin; Jung, Ki Jung; Lee, Byung Jik

    1997-01-01

    This paper describes the introduction to research reactor decommissioning plan at KAERI, the background of technology development and demonstration, and the current status of the system decontamination technology for TRIGA reactors, concrete decontamination and dust treatment technologies, wall ranging robot and graphic simulation of dismantling processes, soil decontamination and restoration technology, recycling or reuse technologies for radioactive metallic wastes, and incineration technology demonstration for combustible wastes. 9 figs

  7. Integrated gasification combined-cycle research development and demonstration activities in the US

    Energy Technology Data Exchange (ETDEWEB)

    Ness, H.M.; Brdar, R.D.

    1996-09-01

    The United States Department of Energy (DOE)`s Office of Fossil Energy, Morgantown Energy Technology Center, is managing a research development and demonstration (RD&D) program that supports the commercialization of integrated gasification combined-cycle (IGCC) advanced power systems. This overview briefly describes the supporting RD&D activities and the IGCC projects selected for demonstration in the Clean Coal Technology (CCT) Program.

  8. Perestroika in pharma: evolution or revolution in drug development?

    Science.gov (United States)

    FitzGerald, Garret A

    2010-01-01

    New-drug approvals have remained roughly constant since 1950, while the cost of drug development has soared. It seems likely that a more modular approach to drug discovery and development will evolve, deriving some features from the not-for-profit sector. For this to occur, we must address the deficit in human capital with expertise in both translational medicine and therapeutics and also in regulatory science; utilize regulatory reform to incentivize innovation and the expansion of the precompetitive space; and develop an informatics infrastructure that permits the global, secure, and compliant sharing of heterogeneous data across academic and industry sectors. These developments, likely prompted by the perception of crisis rather than opportunity, will require linked initiatives among academia, the pharmaceutical industry, the US National Institutes of Health, and the US Food and Drug Administration, along with a more adventurous role for venture capital. A failure to respond threatens the United States' lead in biomedical science and in the development and regulation of novel therapeutics. 2010 Mount Sinai School of Medicine.

  9. Site-specific antibody-drug conjugates: the nexus of bioorthogonal chemistry, protein engineering, and drug development.

    Science.gov (United States)

    Agarwal, Paresh; Bertozzi, Carolyn R

    2015-02-18

    Antibody-drug conjugates (ADCs) combine the specificity of antibodies with the potency of small molecules to create targeted drugs. Despite the simplicity of this concept, generation of clinically successful ADCs has been very difficult. Over the past several decades, scientists have learned a great deal about the constraints on antibodies, linkers, and drugs as they relate to successful construction of ADCs. Once these components are in hand, most ADCs are prepared by nonspecific modification of antibody lysine or cysteine residues with drug-linker reagents, which results in heterogeneous product mixtures that cannot be further purified. With advances in the fields of bioorthogonal chemistry and protein engineering, there is growing interest in producing ADCs by site-specific conjugation to the antibody, yielding more homogeneous products that have demonstrated benefits over their heterogeneous counterparts in vivo. Here, we chronicle the development of a multitude of site-specific conjugation strategies for assembly of ADCs and provide a comprehensive account of key advances and their roots in the fields of bioorthogonal chemistry and protein engineering.

  10. [Does the public sector have an independent research role in the development of drugs?].

    Science.gov (United States)

    Poulsen, Henrik Enghusen; Grønlykke, Thor Buch

    2003-04-14

    Exclusively private companies do drug development. The State contributes with education of academics and basic research constituting the basis of half of the drugs developed by the private companies. The Danish private drug research amounts to six billion DKK per year, corresponding to the estimated price of the development of one new drug. The development shows a negative tendency. There are doubts about the scientific credibility, the number of new drugs is declining, drug development costs are rising, and the competitiveness in Europe is declining compared with the one of The United States. Continued improvement of Danish drug development can be achieved by stimulation of the public research related to drug development.

  11. Novel bacterial metabolite merochlorin A demonstrates in vitro activity against multi-drug resistant methicillin-resistant Staphylococcus aureus.

    Directory of Open Access Journals (Sweden)

    George Sakoulas

    Full Text Available We evaluated the in vitro activity of a merochlorin A, a novel compound with a unique carbon skeleton, against a spectrum of clinically relevant bacterial pathogens and against previously characterized clinical and laboratory Staphylococcus aureus isolates with resistance to numerous antibiotics.Merochlorin A was isolated and purified from a marine-derived actinomycete strain CNH189. Susceptibility testing for merochlorin A was performed against previously characterized human pathogens using broth microdilution and agar dilution methods. Cytotoxicity was assayed in tissue culture assays at 24 and 72 hours against human HeLa and mouse sarcoma L929 cell lines.The structure of as new antibiotic, merochlorin A, was assigned by comprehensive spectroscopic analysis. Merochlorin A demonstrated in vitro activity against Gram-positive bacteria, including Clostridium dificile, but not against Gram negative bacteria. In S. aureus, susceptibility was not affected by ribosomal mutations conferring linezolid resistance, mutations in dlt or mprF conferring resistance to daptomycin, accessory gene regulator knockout mutations, or the development of the vancomycin-intermediate resistant phenotype. Merochlorin A demonstrated rapid bactericidal activity against MRSA. Activity was lost in the presence of 20% serum.The unique meroterpenoid, merochlorin A demonstrated excellent in vitro activity against S. aureus and C. dificile and did not show cross-resistance to contemporary antibiotics against Gram positive organisms. The activity was, however, markedly reduced in 20% human serum. Future directions for this compound may include evaluation for topical use, coating biomedical devices, or the pursuit of chemically modified derivatives of this compound that retain activity in the presence of serum.

  12. From research on rare diseases to new orphan drug development

    NARCIS (Netherlands)

    Heemstra, H.E.

    2010-01-01

    Rare diseases have a prevalence of lower than 5 in 10,000 inhabitants and are life-threatening or chronically debilitating. It is estimated that worldwide more than 5000 rare diseases exist, which account for over 55 million patients in the EU and the US together. However, the development of drugs

  13. X-37 Flight Demonstrator: A Building Block in NASA's Future Access to Space; X-37 Flight Demonstrator: Orbital Vehicle Technology Development Approach

    Science.gov (United States)

    Jacobson, David

    2004-01-01

    Project management issues and subsystems development for the X-37 flight demonstrator are covered in this viewgraph presentation. Subsystems profiled include: thermal protection systems, hot structures, and lithium-ion batteries.

  14. Developing drug formularies for the "National Medical Holding" JSC.

    Science.gov (United States)

    Akhmadyar, N S; Khairulin, B E; Amangeldy-Kyzy, S; Ospanov, M A

    2015-01-01

    One of the main problems of drug provision of multidisciplinary hospitals is the necessity to improve the efficiency of budget spending. Despite the efforts undertaken in Kazakhstan for improving the mechanism of drug distribution (creation of the Kazakhstan National Formulary, Unified National Health System, the handbook of medicines (drugs) costs in the electronic register of inpatients (ERI), having a single distributor), the number of unresolved issues still remain."National Medical Holding" JSC (NMH) was established in 2008 and unites 6 innovational healthcare facilities with up to 1431 beds (700 children and 731 adults), located in the medical cluster - which are "National Research Center for Maternal and Child Health" JSC (NRCMC), "Republic Children's Rehabilitation Center" JSC (RCRC), "Republican Diagnostic Center" JSC (RDC), "National Centre for Neurosurgery" JSC (NCN), "National Research Center for Oncology and Transplantation" JSC (NRCOT) and "National Research Cardiac Surgery Center" JSC (NRCSC). The main purpose of NMH is to create an internationally competitive "Hospital of the Future", which will provide the citizens of Kazakhstan and others with a wide range of medical services based on advanced medical technology, modern hospital management, international quality and safety standards. These services include emergency care, outpatient diagnostic services, obstetrics and gynecology, neonatal care, internal medicine, neurosurgery, cardiac surgery, transplantation, cancer care for children and adults, as well as rehabilitation treatment. To create a program of development of a drug formulary of NMH and its subsidiaries. In order to create drug formularies of NMH, analytical, software and statistical methods were used.AII subsidiary organizations of NMH (5 out of 6) except for the NRCOT have been accredited by Joint Commission International (JCI) standards, which ensure the safety of patients and clinical staff, by improving the technological

  15. Development of novel drug delivery systems using phage display technology for clinical application of protein drugs.

    Science.gov (United States)

    Nagano, Kazuya; Tsutsumi, Yasuo

    2016-01-01

    Attempts are being made to develop therapeutic proteins for cancer, hepatitis, and autoimmune conditions, but their clinical applications are limited, except in the cases of drugs based on erythropoietin, granulocyte colony-stimulating factor, interferon-alpha, and antibodies, owing to problems with fundamental technologies for protein drug discovery. It is difficult to identify proteins useful as therapeutic seeds or targets. Another problem in using bioactive proteins is pleiotropic actions through receptors, making it hard to elicit desired effects without side effects. Additionally, bioactive proteins have poor therapeutic effects owing to degradation by proteases and rapid excretion from the circulatory system. Therefore, it is essential to establish a series of novel drug delivery systems (DDS) to overcome these problems. Here, we review original technologies in DDS. First, we introduce antibody proteomics technology for effective selection of proteins useful as therapeutic seeds or targets and identification of various kinds of proteins, such as cancer-specific proteins, cancer metastasis-related proteins, and a cisplatin resistance-related protein. Especially Ephrin receptor A10 is expressed in breast tumor tissues but not in normal tissues and is a promising drug target potentially useful for breast cancer treatment. Moreover, we have developed a system for rapidly creating functional mutant proteins to optimize the seeds for therapeutic applications and used this system to generate various kinds of functional cytokine muteins. Among them, R1antTNF is a TNFR1-selective antagonistic mutant of TNF and is the first mutein converted from agonist to antagonist. We also review a novel polymer-conjugation system to improve the in vivo stability of bioactive proteins. Site-specific PEGylated R1antTNF is uniform at the molecular level, and its bioactivity is similar to that of unmodified R1antTNF. In the future, we hope that many innovative protein drugs will be

  16. DEVELOPMENT AND DEMONSTRATION OF AN ULTRA LOW NOx COMBUSTOR FOR GAS TURBINES

    Energy Technology Data Exchange (ETDEWEB)

    NEIL K. MCDOUGALD

    2005-04-30

    Alzeta Corporation has developed surface-stabilized fuel injectors for use with lean premixed combustors which provide extended turndown and ultra-low NOX emission performance. These injectors use a patented technique to form interacting radiant and blue-flame zones immediately above a selectively-perforated porous metal surface. This allows stable operation at low reaction temperatures. This technology is being commercialized under the product name nanoSTAR. Initial tests demonstrated low NOX emissions but, were limited by flashback failure of the injectors. The weld seams required to form cylindrical injectors from flat sheet material were identified as the cause of the failures. The approach for this project was to first develop new fabrication methods to produce injectors without weld seams, verify similar emissions performance to the original flat sheet material and then develop products for microturbines and small gas turbines along parallel development paths. A 37 month project was completed to develop and test a surface stabilized combustion system for gas turbine applications. New fabrication techniques developed removed a technological barrier to the success of the product by elimination of conductive weld seams from the injector surface. The injectors demonstrated ultra low emissions in rig tests conducted under gas turbine operating conditions. The ability for injectors to share a common combustion chamber allowing for deployment in annular combustion liner was also demonstrated. Some further development is required to resolve integration issues related to specific engine constraints, but the nanoSTAR technology has clearly demonstrated its low emissions potential. The overall project conclusions can be summarized: (1) A wet-laid casting method successfully eliminated weld seams from the injector surface without degrading performance. (2) Gas turbine cycle analysis identified several injector designs and control schemes to start and load engines using

  17. Anti-influenza drugs: the development of sialidase inhibitors.

    Science.gov (United States)

    von Itzstein, Mark; Thomson, Robin

    2009-01-01

    Viruses, particularly those that are harmful to humans, are the 'silent terrorists' of the twenty-first century. Well over four million humans die per annum as a result of viral infections alone. The scourge of influenza virus has plagued mankind throughout the ages. The fact that new viral strains emerge on a regular basis, particularly out of Asia, establishes a continual socio-economic threat to mankind. The arrival of the highly pathogenic avian influenza H5N1 heightened the threat of a potential human pandemic to the point where many countries have put in place 'preparedness plans' to defend against such an outcome. The discovery of the first designer influenza virus sialidase inhibitor and anti-influenza drug Relenza, and subsequently Tamiflu, has now inspired a number of continuing efforts towards the discovery of next generation anti-influenza drugs. Such drugs may act as 'first-line-of-defence' against the spread of influenza infection and buy time for necessary vaccine development particularly in a human pandemic setting. Furthermore, the fact that influenza virus can develop resistance to therapeutics makes these continuing efforts extremely important. An overview of the role of the virus-associated glycoprotein sialidase (neuraminidase) and some of the most recent developments towards the discovery of anti-influenza drugs based on the inhibition of influenza virus sialidase is provided in this chapter.

  18. Drug development in Parkinson's disease: from emerging molecules to innovative drug delivery systems.

    Science.gov (United States)

    Garbayo, E; Ansorena, E; Blanco-Prieto, M J

    2013-11-01

    Current treatments for Parkinson's disease (PD) are aimed at addressing motor symptoms but there is no therapy focused on modifying the course of the disease. Successful treatment strategies have been so far limited and brain drug delivery remains a major challenge that restricts its treatment. This review provides an overview of the most promising emerging agents in the field of PD drug discovery, discussing improvements that have been made in brain drug delivery for PD. It will be shown that new approaches able to extend the length of the treatment, to release the drug in a continuous manner or to cross the blood-brain barrier and target a specific region are still needed. Overall, the results reviewed here show that there is an urgent need to develop both symptomatic and disease-modifying treatments, giving priority to neuroprotective treatments. Promising perspectives are being provided in this field by rasagiline and by neurotrophic factors like glial cell line-derived neurotrophic factor. The identification of disease-relevant genes has also encouraged the search for disease-modifying therapies that function by identifying molecularly targeted drugs. The advent of new molecular and cellular targets like α-synuclein, leucine-rich repeat serine/threonine protein kinase 2 or parkin, among others, will require innovative delivery therapies. In this regard, drug delivery systems (DDS) have shown great potential for improving the efficacy of conventional and new PD therapy and reducing its side effects. The new DDS discussed here, which include microparticles, nanoparticles and hydrogels among others, will probably open up possibilities that extend beyond symptomatic relief. However, further work needs to be done before DDS become a therapeutic option for PD patients. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  19. Managing Risk on a Technology Development Project/Advanced Mirror System Demonstrator

    Science.gov (United States)

    Byberg, Alicia; Russell, J. Kevin; Stahl, Phil (Technical Monitor)

    2002-01-01

    The risk management study applied to the Advanced Mirror System Demonstrator (AMSD), a precursor mirror technology development for the Next Generation Space Telescope (NGST) is documented. The AMSD will be developed as a segment of a lightweight primary mirror system that can be produced at a low cost and with a short manufacturing schedule. The technology gained from the program will support the risk mitigation strategy for the NGST, as well as other government agency space mirror programs.

  20. Development of Demonstrably Predictive Models for Emissions from Alternative Fuels Based Aircraft Engines

    Science.gov (United States)

    2017-05-01

    Engineering Chemistry Fundamentals, Vol. 5, No. 3, 1966, pp. 356–363. [14] Burns, R. A., Development of scalar and velocity imaging diagnostics...in an Aero- Engine Model Combustor at Elevated Pressure Using URANS and Finite- Rate Chemistry ,” 50th AIAA/ASME/SAE/ASEE Joint Propulsion Conference...FINAL REPORT Development of Demonstrably Predictive Models for Emissions from Alternative Fuels Based Aircraft Engines SERDP Project WP-2151

  1. 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

  2. Progress and promise for the MDMA drug development program.

    Science.gov (United States)

    Feduccia, Allison A; Holland, Julie; Mithoefer, Michael C

    2018-02-01

    Pharmacotherapy is often used to target symptoms of posttraumatic stress disorder (PTSD), but does not provide definitive treatment, and side effects of daily medication are often problematic. Trauma-focused psychotherapies are more likely than drug treatment to achieve PTSD remission, but have high dropout rates and ineffective for a large percentage of patients. Therefore, research into drugs that might increase the effectiveness of psychotherapy is a logical avenue of investigation. The most promising drug studied as a catalyst to psychotherapy for PTSD thus far is 3,4-methylenedioxymethamphetamine (MDMA), commonly known as the recreational drug "Ecstasy." MDMA stimulates the release of hormones and neurochemicals that affect key brain areas for emotion and memory processing. A series of recently completed phase 2 clinical trials of MDMA-assisted psychotherapy for treatment of PTSD show favorable safety outcomes and large effect sizes that warrant expansion into multi-site phase 3 trials, set to commence in 2018. The nonprofit sponsor of the MDMA drug development program, the Multidisciplinary Association for Psychedelic Studies (MAPS), is supporting these trials to explore whether MDMA, administered on only a few occasions, can increase the effectiveness of psychotherapy. Brain imaging techniques and animal models of fear extinction are elucidating neural mechanisms underlying the robust effects of MDMA on psychological processing; however, much remains to be learned about the complexities of MDMA effects as well as the complexities of PTSD itself.

  3. Drug repurposing based on drug-drug interaction.

    Science.gov (United States)

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

    2015-02-01

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

  4. Present state of development of demonstration FBR and prospect of practical use

    International Nuclear Information System (INIS)

    Inagaki, Tatsutoshi

    1996-01-01

    As for the FBR development in Japan, the Atomic Energy Commission revised the long term plan on the research, development and utilization of atomic energy in June, 1994, and under the basic policy that through the considerable period of using LWRs together, FBRs will be adopted as the main nuclear power plants in future, it was decided to establish FBR technology system so that the practical use of FBRs becomes feasible by about 2030 through two demonstration FBRs following the experimental FBR 'Joyo' and the prototype FBR 'Monju'. The Monju started power generation and transmission in August, 1995, but secondary sodium leak accident occurred in December, 1995, and at present it is stopped. The demonstration FBR No. 1 is a top entry type loop reactor, and the power output is about 660 MWe. The start of construction is scheduled at the beginning of 2000s. The research on the whole plant design is carried out as the research on the optimization of demonstration FBR plant for three years from fiscal year 1994. The design of the demonstration FBR No. 1, the research and development for it, the prospect of the practical use and the research and development for the practical use are reported. (K.I.)

  5. The National Long Term Care Demonstration: operational issues encountered in developing the research design.

    Science.gov (United States)

    Carcagno, G J; Kemper, P

    1983-01-01

    This paper describes the design of the National Long Term Care Demonstration and its evaluation and discusses a number of operational issues encountered in the design process: simultaneous design of research and operations, identification of the target population, randomization, collection of comparable data, development of an assessment instrument, potential changes in existing programs, and termination planning.

  6. How to calculate clearance of highly protein-bound drugs during continuous venovenous hemofiltration demonstrated with flucloxacillin.

    Science.gov (United States)

    Meyer, Brigitte; Ahmed el Gendy, Salwa; Delle Karth, Georg; Locker, Gottfried J; Heinz, Gottfried; Jaeger, Walter; Thalhammer, Florian

    2003-01-01

    Flucloxacillin is an important antimicrobial drug in the treatment of infections with Staphylococcus aureus and therefore is often used in staphylococcal infections. Furthermore, flucloxacillin has a high protein binding rate as for example ceftriaxone or teicoplanin--drugs which have formerly been characterized as not being dialyzable. The pharmacokinetic parameters of 4.0 g flucloxacillin every 8 h were examined in 10 intensive care patients during continuous venovenous hemofiltration (CVVH) using a polyamide capillary hemofilter. In addition, the difficulty of calculating the hemofiltration clearance of a highly protein-bound drug is described. Flucloxacillin serum levels were significantly lowered (56.9 +/- 24.0%) even though only 15% of the drug was detected in the ultrafiltrate. Elimination half-life, total body clearance and sieving coefficient were 4.9 +/- 0.7 h, 117.2 +/- 79.1 ml/min and 0.21 +/- 0.09, respectively. These discrepancies can be explained by the high protein binding of flucloxacillin, the adsorbing property of polyamide and the equation in order to calculate hemofiltration clearance. The unbound fraction of a 4.0 g flucloxacillin dosage facilitates time above the minimum inhibitory concentration (T > MIC) of 60% only for strains up to a minimum inhibitory concentration (MIC) of 0.5 mg/l. Based on the data of this study, we conclude that intensive care patients with staphylococcal infections on CVVH should be treated with 4.0 g flucloxacillin every 8 h which was safe and well tolerated. Moreover, further studies with highly protein-bound drugs are recommended to check the classical 'hemodialysis' equation as the standard equation in calculating the CVVH clearance of highly protein-bound drugs. Copyright 2003 S. Karger AG, Basel

  7. Mechanistic systems modeling to guide drug discovery and development.

    Science.gov (United States)

    Schmidt, Brian J; Papin, Jason A; Musante, Cynthia J

    2013-02-01

    A crucial question that must be addressed in the drug development process is whether the proposed therapeutic target will yield the desired effect in the clinical population. Pharmaceutical and biotechnology companies place a large investment on research and development, long before confirmatory data are available from human trials. Basic science has greatly expanded the computable knowledge of disease processes, both through the generation of large omics data sets and a compendium of studies assessing cellular and systemic responses to physiologic and pathophysiologic stimuli. Given inherent uncertainties in drug development, mechanistic systems models can better inform target selection and the decision process for advancing compounds through preclinical and clinical research. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. Core competencies for pharmaceutical physicians and drug development scientists

    Science.gov (United States)

    Silva, Honorio; Stonier, Peter; Buhler, Fritz; Deslypere, Jean-Paul; Criscuolo, Domenico; Nell, Gerfried; Massud, Joao; Geary, Stewart; Schenk, Johanna; Kerpel-Fronius, Sandor; Koski, Greg; Clemens, Norbert; Klingmann, Ingrid; Kesselring, Gustavo; van Olden, Rudolf; Dubois, Dominique

    2013-01-01

    Professional groups, such as IFAPP (International Federation of Pharmaceutical Physicians and Pharmaceutical Medicine), are expected to produce the defined core competencies to orient the discipline and the academic programs for the development of future competent professionals and to advance the profession. On the other hand, PharmaTrain, an Innovative Medicines Initiative project, has become the largest public-private partnership in biomedicine in the European Continent and aims to provide postgraduate courses that are designed to meet the needs of professionals working in medicines development. A working group was formed within IFAPP including representatives from PharmaTrain, academic institutions and national member associations, with special interest and experience on Quality Improvement through education. The objectives were: to define a set of core competencies for pharmaceutical physicians and drug development scientists, to be summarized in a Statement of Competence and to benchmark and align these identified core competencies with the Learning Outcomes (LO) of the PharmaTrain Base Course. The objectives were successfully achieved. Seven domains and 60 core competencies were identified and aligned accordingly. The effective implementation of training programs using the competencies or the PharmaTrain LO anywhere in the world may transform the drug development process to an efficient and integrated process for better and safer medicines. The PharmaTrain Base Course might provide the cognitive framework to achieve the desired Statement of Competence for Pharmaceutical Physicians and Drug Development Scientists worldwide. PMID:23986704

  9. Safe procedure development to manage hazardous drugs in the workplace

    Directory of Open Access Journals (Sweden)

    Marisa Gaspar Carreño

    2017-03-01

    Full Text Available Objective: To develop a safety working procedure for the employees in the Intermutual Hospital de Levante (HIL in those areas of activity that deal with the handling of hazardous drugs (MP. Methods: The procedure was developed in six phases: 1 hazard definition; 2 definition and identification of processes and development of general correct work practices about hazardous drugs’ selection and special handling; 3 detection, selection and set of specific recommendations to handle with hazardous drugs during the processes of preparation and administration included in the hospital GFT; 4 categorization of risk during the preparation/administration and development of an identification system; 5 information and training of professionals; 6 implementation of the identification measures and prevention guidelines. Results: Six processes were detected handling HD. During those processes, thirty HD were identified included in the hospital GFT and a safer alternative was found for 6 of them. The HD were classified into 4 risk categories based on those measures to be taken during the preparation and administration of each of them. Conclusions: The development and implementation of specific safety-work processes dealing with medication handling, allows hospital managers to accomplish effectively with their legal obligations about the area of prevention and provides healthcare professional staff with the adequate techniques and safety equipment to avoid possible dangers and risks of some drugs.

  10. Core Competencies for Pharmaceutical Physicians and Drug Development Scientists

    Directory of Open Access Journals (Sweden)

    Honorio eSilva

    2013-08-01

    Full Text Available Professional groups, such as IFAPP (International Federation of Pharmaceutical Physicians and Pharmaceutical Medicine, are expected to produce the defined core competencies to orient the discipline and the academic programs for the development of future competent professionals and to advance the profession. On the other hand, PharmaTrain, an Innovative Medicines Initiative project, has become the largest public-private partnership in biomedicine in the European Continent and aims to provide postgraduate courses that are designed to meet the needs of professionals working in medicines development. A working group was formed within IFAPP including representatives from PharmaTrain, academic institutions and national member associations, with special interest and experience on Quality Improvement through education. The objectives were: to define a set of core competencies for pharmaceutical physicians and drug development scientists, to be summarized in a Statement of Competence and to benchmark and align these identified core competencies with the Learning Outcomes of the PharmaTrain Base Course. The objectives were successfully achieved. Seven domains and 60 core competencies were identified and aligned accordingly. The effective implementation of training programs using the competencies or the PharmaTrain Learning Outcomes anywhere in the world may transform the drug development process to an efficient and integrated process for better and safer medicines. The PharmaTrain Base Course might provide the cognitive framework to achieve the desired Statement of Competence for Pharmaceutical Physicians and Drug Development Scientists worldwide.

  11. [Chapter 2. Transitions in drug-discovery technology and drug-development in Japan (1980-2010)].

    Science.gov (United States)

    Sakakibara, Noriko; Yoshioka, Ryuzo; Matsumoto, Kazuo

    2014-01-01

    In 1970s, the material patent system was introduced in Japan. Since then, many Japanese pharmaceutical companies have endeavored to create original in-house products. From 1980s, many of the innovative products were small molecular drugs and were developed using powerful medicinal-chemical technologies. Among them were antibiotics and effective remedies for the digestive organs and circulatory organs. During this period, Japanese companies were able to launch some blockbuster drugs. At the same time, the pharmaceutical market, which had grown rapidly for two decades, was beginning to level off. From the late 1990s, drug development was slowing down due to the lack of expertise in biotechnology such as genetic engineering. In response to the circumstances, the research and development on biotechnology-based drugs such as antibody drugs have become more dynamic and popular at companies than small molecule drugs. In this paper, the writers reviewed in detail the transitions in drug discovery and development between 1980 and 2010.

  12. TRL Assessment of Solar Sail Technology Development Following the 20-Meter System Ground Demonstrator Hardware Testing

    Science.gov (United States)

    Young, Roy M.; Adams, Charles L.

    2010-01-01

    The NASA In-Space Propulsion Technology (ISPT) Projects Office sponsored two separate, independent solar sail system design and development demonstration activities during 2002-2005. ATK Space Systems of Goleta, CA was the prime contractor for one development team and L' Garde, Inc. of Tustin, CA was the prime contractor for the other development team. The goal of these activities was to advance the technology readiness level (TRL) of solar sail propulsion from 3 towards 6 by the year 2006. Component and subsystem fabrication and testing were completed successfully, including the ground deployment of 10-meter and 20-meter demonstration hardware systems under vacuum conditions. The deployment and structural testing of the 20-meter solar sail systems was conducted in the 30 meter diameter Space Power Facility thermal-vacuum chamber at NASA Glenn Plum Brook in April though August, 2005. This paper will present the results of the TRL assessment following the solar sail technology development activities associated with the design, development, analysis and testing of the 20-meter system ground demonstrators.

  13. Imaging mass spectrometry in drug development and toxicology.

    Science.gov (United States)

    Karlsson, Oskar; Hanrieder, Jörg

    2017-06-01

    During the last decades, imaging mass spectrometry has gained significant relevance in biomedical research. Recent advances in imaging mass spectrometry have paved the way for in situ studies on drug development, metabolism and toxicology. In contrast to whole-body autoradiography that images the localization of radiolabeled compounds, imaging mass spectrometry provides the possibility to simultaneously determine the discrete tissue distribution of the parent compound and its metabolites. In addition, imaging mass spectrometry features high molecular specificity and allows comprehensive, multiplexed detection and localization of hundreds of proteins, peptides and lipids directly in tissues. Toxicologists traditionally screen for adverse findings by histopathological examination. However, studies of the molecular and cellular processes underpinning toxicological and pathologic findings induced by candidate drugs or toxins are important to reach a mechanistic understanding and an effective risk assessment strategy. One of IMS strengths is the ability to directly overlay the molecular information from the mass spectrometric analysis with the tissue section and allow correlative comparisons of molecular and histologic information. Imaging mass spectrometry could therefore be a powerful tool for omics profiling of pharmacological/toxicological effects of drug candidates and toxicants in discrete tissue regions. The aim of the present review is to provide an overview of imaging mass spectrometry, with particular focus on MALDI imaging mass spectrometry, and its use in drug development and toxicology in general.

  14. Privileged Electrophile Sensors: A Resource for Covalent Drug Development.

    Science.gov (United States)

    Long, Marcus John Curtis; Aye, Yimon

    2017-07-20

    This Perspective delineates how redox signaling affects the activity of specific enzyme isoforms and how this property may be harnessed for rational drug design. Covalent drugs have resurged in recent years and several reports have extolled the general virtues of developing irreversible inhibitors. Indeed, many modern pharmaceuticals contain electrophilic appendages. Several invoke a warhead that hijacks active-site nucleophiles whereas others take advantage of spectator nucleophilic side chains that do not participate in enzymatic chemistry, but are poised to bind/react with electrophiles. The latest data suggest that innate electrophile sensing-which enables rapid reaction with an endogenous signaling electrophile-is a quintessential resource for the development of covalent drugs. For instance, based on recent work documenting isoform-specific electrophile sensing, isozyme non-specific drugs may be converted to isozyme-specific analogs by hijacking privileged first-responder electrophile-sensing cysteines. Because this approach targets functionally relevant cysteines, we can simultaneously harness previously untapped moonlighting roles of enzymes linked to redox sensing. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Preliminary analysis of West Valley Waste Removal System equipment development and mock demonstration facilities

    International Nuclear Information System (INIS)

    Janicek, G.P.

    1981-06-01

    This report defines seven areas requiring further investigation to develop and demonstrate a safe and viable West Valley Waste Removal System. These areas of endeavor are discussed in terms of their minimum facility requirements. It is concluded that utilizing separated specific facilities at different points in time is of a greater advantage than an exact duplication of the West Valley tanks. Savannah River Plant's full-scale, full-circle and half-circle tanks, and their twelfth scale model tank would all be useful to varying degrees but would require modifications. Hanford's proposed full-size mock tank would be useful, but is not seriously considered because its construction may not coincide with West Valley needs. Costs of modifying existing facilities and/or constructing new facilities are assessed in terms of their benefit to the equipment development and mock demonstration. Six facilities were identified for further analysis which would benefit development of waste removal equipment

  16. Testing, development and demonstration of large scale solar district heating systems

    DEFF Research Database (Denmark)

    Furbo, Simon; Fan, Jianhua; Perers, Bengt

    2015-01-01

    In 2013-2014 the project “Testing, development and demonstration of large scale solar district heating systems” was carried out within the Sino-Danish Renewable Energy Development Programme, the so called RED programme jointly developed by the Chinese and Danish governments. In the project Danish...... know how on solar heating plants and solar heating test technology have been transferred from Denmark to China, large solar heating systems have been promoted in China, test capabilities on solar collectors and large scale solar heating systems have been improved in China and Danish-Chinese cooperation...

  17. JOYO modification program for demonstration tests of FBR innovative technology development

    International Nuclear Information System (INIS)

    Yoshimi, H.; Hachiya, Y.

    1990-01-01

    A plan is under way at PNC to modify the experimental fast reactor JOYO. The project is called MARK-III (MK-III) program. The purpose of MK-III is to expand the function of JOYO, and to make it possible to receive demonstration tests of new or high level technologies for FBR development. The MK-III program consists of two main modifications: conversion to a highly efficient irradiation facility; and a modification for demonstration testing of new technologies and concepts that have a high potential to reduce FBR plant construction cost, to evaluate plant reliability and to improve plant safety. These modifications are scheduled to start in 1991

  18. Integrating Substance Abuse Treatment and Child Welfare Services: Findings from the Illinois Alcohol and Other Drug Abuse Waiver Demonstration

    Science.gov (United States)

    Ryan, Joseph P.; Marsh, Jeanne C.; Testa, Mark F.; Louderman, Richard

    2006-01-01

    Alcohol and other drug abuse is a major problem for children and families involved with public child welfare. Substance abuse compromises appropriate parenting practices and increases the risk of child maltreatment. A substantial proportion of substantiated child abuse and neglect reports involve parental substance abuse. Once in the system,…

  19. MALDI imaging facilitates new topical drug development process by determining quantitative skin distribution profiles.

    Science.gov (United States)

    Bonnel, David; Legouffe, Raphaël; Eriksson, André H; Mortensen, Rasmus W; Pamelard, Fabien; Stauber, Jonathan; Nielsen, Kim T

    2018-04-01

    Generation of skin distribution profiles and reliable determination of drug molecule concentration in the target region are crucial during the development process of topical products for treatment of skin diseases like psoriasis and atopic dermatitis. Imaging techniques like mass spectrometric imaging (MSI) offer sufficient spatial resolution to generate meaningful distribution profiles of a drug molecule across a skin section. In this study, we use matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to generate quantitative skin distribution profiles based on tissue extinction coefficient (TEC) determinations of four different molecules in cross sections of human skin explants after topical administration. The four drug molecules: roflumilast, tofacitinib, ruxolitinib, and LEO 29102 have different physicochemical properties. In addition, tofacitinib was administrated in two different formulations. The study reveals that with MALDI-MSI, we were able to observe differences in penetration profiles for both the four drug molecules and the two formulations and thereby demonstrate its applicability as a screening tool when developing a topical drug product. Furthermore, the study reveals that the sensitivity of the MALDI-MSI techniques appears to be inversely correlated to the drug molecules' ability to bind to the surrounding tissues, which can be estimated by their Log D values. Graphical abstract.

  20. Safe procedure development to manage hazardous drugs in the workplace.

    Science.gov (United States)

    Gaspar Carreño, Marisa; Achau Muñoz, Rubén; Torrico Martín, Fátima; Agún Gonzalez, Juan José; Sanchez Santos, Jose Cristobal; Cercos Lletí, Ana Cristina; Ramos Orozco, Pedro

    2017-03-01

    To develop a safety working procedure for the employees in the Intermutual Hospital de Levante (HIL) in those areas of activity that deal with the handling of hazardous drugs (MP). The procedure was developed in six phases: 1) hazard definition; 2) definition and identification of processes and development of general correct work practices about hazardous drugs' selection and special handling; 3) detection, selection and set of specific recommendations to handle with hazardous drugs during the processes of preparation and administration included in the hospital GFT; 4) categorization of risk during the preparation/administration and development of an identification system; 5) information and training of professionals; 6) implementation of the identification measures and prevention guidelines. Six processes were detected handling HD. During those processes, thirty HD were identified included in the hospital GFT and a safer alternative was found for 6 of them. The HD were classified into 4 risk categories based on those measures to be taken during the preparation and administration of each of them. The development and implementation of specific safety-work processes dealing with medication handling, allows hospital managers to accomplish effectively with their legal obligations about the area of prevention and provides healthcare professional staff with the adequate techniques and safety equipment to avoid possible dangers and risks of some drugs. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  1. Influence networks based on coexpression improve drug target discovery for the development of novel cancer therapeutics

    Science.gov (United States)

    2014-01-01

    Background The demand for novel molecularly targeted drugs will continue to rise as we move forward toward the goal of personalizing cancer treatment to the molecular signature of individual tumors. However, the identification of targets and combinations of targets that can be safely and effectively modulated is one of the greatest challenges facing the drug discovery process. A promising approach is to use biological networks to prioritize targets based on their relative positions to one another, a property that affects their ability to maintain network integrity and propagate information-flow. Here, we introduce influence networks and demonstrate how they can be used to generate influence scores as a network-based metric to rank genes as potential drug targets. Results We use this approach to prioritize genes as drug target candidates in a set of ER + breast tumor samples collected during the course of neoadjuvant treatment with the aromatase inhibitor letrozole. We show that influential genes, those with high influence scores, tend to be essential and include a higher proportion of essential genes than those prioritized based on their position (i.e. hubs or bottlenecks) within the same network. Additionally, we show that influential genes represent novel biologically relevant drug targets for the treatment of ER + breast cancers. Moreover, we demonstrate that gene influence differs between untreated tumors and residual tumors that have adapted to drug treatment. In this way, influence scores capture the context-dependent functions of genes and present the opportunity to design combination treatment strategies that take advantage of the tumor adaptation process. Conclusions Influence networks efficiently find essential genes as promising drug targets and combinations of targets to inform the development of molecularly targeted drugs and their use. PMID:24495353

  2. Development of PEGylated PLGA nanoparticle for controlled and sustained drug delivery in cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Mazur Steven

    2010-09-01

    Full Text Available Abstract Background The mutation in the cystic fibrosis transmembrane conductance regulator (CFTR gene results in CF. The most common mutation, ΔF508-CFTR, is a temperature-sensitive, trafficking mutant with reduced chloride transport and exaggerated immune response. The ΔF508-CFTR is misfolded, ubiquitinated, and prematurely degraded by proteasome mediated- degradation. We recently demonstrated that selective inhibition of proteasomal pathway by the FDA approved drug PS-341 (pyrazylcarbonyl-Phe-Leuboronate, a.k.a. Velcade or bortezomib ameliorates the inflammatory pathophysiology of CF cells. This proteasomal drug is an extremely potent, stable, reversible and selective inhibitor of chymotryptic threonine protease-activity. The apprehension in considering the proteasome as a therapeutic target is that proteasome inhibitors may affect proteostasis and consecutive processes. The affect on multiple processes can be mitigated by nanoparticle mediated PS-341 lung-delivery resulting in favorable outcome observed in this study. Results To overcome this challenge, we developed a nano-based approach that uses drug loaded biodegradable nanoparticle (PLGA-PEGPS-341 to provide controlled and sustained drug delivery. The in vitro release kinetics of drug from nanoparticle was quantified by proteasomal activity assay from days 1-7 that showed slow drug release from day 2-7 with maximum inhibition at day 7. For in vivo release kinetics and biodistribution, these drug-loaded nanoparticles were fluorescently labeled, and administered to C57BL6 mice by intranasal route. Whole-body optical imaging of the treated live animals demonstrates efficient delivery of particles to murine lungs, 24 hrs post treatment, followed by biodegradation and release over time, day 1-11. The efficacy of drug release in CF mice (Cftr-/- lungs was determined by quantifying the changes in proteasomal activity (~2 fold decrease and ability to rescue the Pseudomonas aeruginosa LPS (Pa

  3. Research, development, demonstration, and early deployment policies for advanced-coal technology in China

    International Nuclear Information System (INIS)

    Zhao Lifeng; Gallagher, Kelly Sims

    2007-01-01

    Advanced-coal technologies will increasingly play a significant role in addressing China's multiple energy challenges. This paper introduces the current status of energy in China, evaluates the research, development, and demonstration policies for advanced-coal technologies during the Tenth Five-Year Plan, and gives policy prospects for advanced-coal technologies in the Eleventh Five-Year Plan. Early deployment policies for advanced-coal technologies are discussed and some recommendations are put forward. China has made great progress in the development of advanced-coal technologies. In terms of research, development, and demonstration of advanced-coal technologies, China has achieved breakthroughs in developing and demonstrating advanced-coal gasification, direct and indirect coal liquefaction, and key technologies of Integrated Gasification Combined Cycle (IGCC) and co-production systems. Progress on actual deployment of advanced-coal technologies has been more limited, in part due to insufficient supporting policies. Recently, industry chose Ultra Super Critical (USC) Pulverized Coal (PC) and Super Critical (SC) PC for new capacity coupled with pollution-control technology, and 300 MW Circulating Fluidized Bed (CFB) as a supplement

  4. Mixed Waste Focus Area alternative oxidation technologies development and demonstration program

    International Nuclear Information System (INIS)

    Borduin, L.C.; Fewell, T.; Gombert, D.; Priebe, S.

    1998-01-01

    The Mixed Waste Focus Area (MWFA) is currently supporting the development and demonstration of several alternative oxidation technology (AOT) processes for treatment of combustible mixed low-level wastes. The impetus for this support derives from regulatory and political hurdles frequently encountered by traditional thermal techniques, primarily incinerators. AOTs have been defined as technologies that destroy organic material without using open-flame reactions. Whether thermal or nonthermal, the processes have the potential advantages of relatively low-volume gaseous emissions, generation of few or no dioxin/furan compounds, and operation at low enough temperatures that metals (except mercury) and most radionuclides are not volatilized. Technology development and demonstration are needed to confirm and realize the potential of AOTs and to compare them on an equal basis with their fully demonstrated thermal counterparts. AOTs include both thermal and nonthermal processes that oxidize organic wastes but operate under significantly different physical and chemical conditions than incinerators. Nonthermal processes currently being studied include Delphi DETOX and acid digestion at the Savannah River Site, and direct chemical oxidation at Lawrence Livermore National Laboratory. All three technologies are at advanced stages of development or are entering the demonstration phase. Nonflame thermal processes include catalytic chemical oxidation, which is being developed and deployed at Lawrence Berkeley National Laboratory, and team reforming, a commercial process being supported by Department of Energy. Related technologies include two low-flow, secondary oxidation processes (Phoenix and Thermatrix units) that have been tested at MSE, Inc., in Butte, Montana. Although testing is complete on some AOT technologies, most require additional support to complete some or all of the identified development objectives. Brief descriptions, status, and planned paths forward for each

  5. Development of Drugs and Technology for Radiation Theragnosis

    Directory of Open Access Journals (Sweden)

    Hwan-Jeong Jeong

    2016-06-01

    Full Text Available Personalized medicine is tailored medical treatment that targets the individual characteristics of each patient. Theragnosis, combining diagnosis and therapy, plays an important role in selecting appropriate patients. Noninvasive in vivo imaging can trace small molecules, antibodies, peptides, nanoparticles, and cells in the body. Recently, imaging methods have been able to reveal molecular events in cells and tissues. Molecular imaging is useful not only for clinical studies but also for developing new drugs and new treatment modalities. Preclinical and early clinical molecular imaging shows biodistribution, pharmacokinetics, mechanisms of action, and efficacy. When therapeutic materials are labeled using radioisotopes, nuclear imaging with positron emission tomography or gamma camera can be used to treat diseases and monitor therapy simultaneously. Such nuclear medicine technology is defined as radiation theragnosis. We review the current development of drugs and technology for radiation theragnosis using peptides, albumin, nanoparticles, and cells.

  6. Development of drugs and technology for radiation theragnosis

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Hwan Jeong [Dept. of Nuclear Medicine, Biomedical Research Institute, Chonbuk National University Medical School and Hospital, Jeonju (Korea, Republic of); Lee, Byung Chul [Dept. of Nuclear Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Sungnam (Korea, Republic of); Ahn, Byeong Cheol [Dept. of Nuclear Medicine, Kyungpook National University School of Medicine and Hospital, Daegu (Korea, Republic of); Kang, Keon Wook [Dept. of Nuclear Medicine and Cancer Research Institute, Seoul National University, Seoul (Korea, Republic of)

    2016-06-15

    Personalized medicine is tailored medical treatment that targets the individual characteristics of each patient. Theragnosis, combining diagnosis and therapy, plays an important role in selecting appropriate patients. Noninvasive in vivo imaging can trace small molecules, antibodies, peptides, nanoparticles, and cells in the body. Recently, imaging methods have been able to reveal molecular events in cells and tissues. Molecular imaging is useful not only for clinical studies but also for developing new drugs and new treatment modalities. Preclinical and early clinical molecular imaging shows biodistribution, pharmacokinetics, mechanisms of action, and efficacy. When therapeutic materials are labeled using radioisotopes, nuclear imaging with positron emission tomography or gamma camera can be used to treat diseases and monitor therapy simultaneously. Such nuclear medicine technology is defined as radiation theragnosis. We review the current development of drugs and technology for radiation theragnosis using peptides, albumin, nanoparticles, and cells.

  7. Continued maturing of SOFC cell production technology and development and demonstration of SOFC stacks. Final report

    Energy Technology Data Exchange (ETDEWEB)

    2008-08-15

    The overall objective of the 6385 project was to develop stack materials, components and stack technology including industrial relevant manufacturing methods for cells components and stacks. Furthermore, the project should include testing and demonstration of the stacks under relevant operating conditions. A production of 6.829 cells, twenty 75-cell stacks and a number of small stacks was achieved. Major improvements were also made in the manufacturing methods and in stack design. Two test and demonstration activities were included in the project. The first test unit was established at H.C. OErsted power plant at the Copenhagen waterfront in order to perform test of SOFC stacks. The unit will be used for tests in other projects. The second demonstration unit is the alpha prototype demonstration in a system running on natural gas in Finland. The alpha prototype demonstration system with 24 TOFC (Topsoe Fuel Cell) stacks was established and started running in October 2007 and operational experience was gained in the period from October 2007 to February 2008. (auther)

  8. Didactic satellite based on Android platform for space operation demonstration and development

    Science.gov (United States)

    Ben Bahri, Omar; Besbes, Kamel

    2018-03-01

    Space technology plays a pivotal role in society development. It offers new methods for telemetry, monitoring and control. However, this sector requires training, research and skills development but the lack of instruments, materials and budgets affects the ambiguity to understand satellite technology. The objective of this paper is to describe a demonstration prototype of a smart phone device for space operations study. Therefore, the first task was carried out to give a demonstration for spatial imagery and attitude determination missions through a wireless communication. The smart phone's Bluetooth was used to achieve this goal inclusive of a new method to enable real time transmission. In addition, an algorithm around a quaternion based Kalman filter was included in order to detect the reliability of the prototype's orientation. The second task was carried out to provide a demonstration for the attitude control mission using the smart phone's orientation sensor, including a new method for an autonomous guided mode. As a result, the acquisition platform showed real time measurement with good accuracy for orientation detection and image transmission. In addition, the prototype kept the balance during the demonstration based on the attitude control method.

  9. An A BWR demonstration simulator for training and developing technical staff

    International Nuclear Information System (INIS)

    Powers, J.; Yonezawa, H.; Aoyagi, Y.; Kataoka, K.

    2015-09-01

    The US-Advanced Boiling Water Reactor (A BWR), certified by the US NRC, is a third generation, evolutionary boiling water reactor design which is the reference for the South Texas Project Units 3 and 4 (STP3-4) Combined License Application (Cola). Nuclear Innovation North America (Nina) is the License Applicant for this new build project, and Toshiba is the selected primary technology contractor. Toshiba has developed a Demonstration Simulator of the A BWR control room that provides a realistic experience for training and education on BWR principles and operations fundamentals. The Demonstration Simulator is located in the Toshiba America Nuclear Energy (Tane) office in Charlotte, North Carolina and is composed of standard office computer equipment set up in a specific arrangement that is representative of the layout of an A BWR control room. The Demonstration Simulator is not intended for licensed operator training, but can provide a framework for encouraging entry level technically oriented nuclear workers to enter the operations field; strengthening the linkage between university energy field curricula and real-life application of theory; and, improving understanding of integrated plant operations for developing station technical staff. This paper describes the A BWR Demonstration Simulator and its applications for training and educating future nuclear workers. (Author)

  10. An A BWR demonstration simulator for training and developing technical staff

    Energy Technology Data Exchange (ETDEWEB)

    Powers, J. [Toshiba America Nuclear Energy, Charlotte, North Carolina (United States); Yonezawa, H.; Aoyagi, Y.; Kataoka, K., E-mail: jim.powers@toshiba.com [Toshiba Corporation, Kawasaki, Kanagawa (Japan)

    2015-09-15

    The US-Advanced Boiling Water Reactor (A BWR), certified by the US NRC, is a third generation, evolutionary boiling water reactor design which is the reference for the South Texas Project Units 3 and 4 (STP3-4) Combined License Application (Cola). Nuclear Innovation North America (Nina) is the License Applicant for this new build project, and Toshiba is the selected primary technology contractor. Toshiba has developed a Demonstration Simulator of the A BWR control room that provides a realistic experience for training and education on BWR principles and operations fundamentals. The Demonstration Simulator is located in the Toshiba America Nuclear Energy (Tane) office in Charlotte, North Carolina and is composed of standard office computer equipment set up in a specific arrangement that is representative of the layout of an A BWR control room. The Demonstration Simulator is not intended for licensed operator training, but can provide a framework for encouraging entry level technically oriented nuclear workers to enter the operations field; strengthening the linkage between university energy field curricula and real-life application of theory; and, improving understanding of integrated plant operations for developing station technical staff. This paper describes the A BWR Demonstration Simulator and its applications for training and educating future nuclear workers. (Author)

  11. Ethical challenges in developing drugs for psychiatric disorders.

    Science.gov (United States)

    Carrier, Felix; Banayan, David; Boley, Randy; Karnik, Niranjan

    2017-05-01

    As the classification of mental disorders advances towards a disease model as promoted by the National Institute of Mental Health (NIMH) Research Domain Criteria (RDoC), there is hope that a more thorough neurobiological understanding of mental illness may allow clinicians and researchers to determine treatment efficacy with less diagnostic variability. This paradigm shift has presented a variety of ethical issues to be considered in the development of psychiatric drugs. These challenges are not limited to informed consent practices, industry funding, and placebo use. The consideration for alternative research models and quality of research design also present ethical challenges in the development of psychiatric drugs. The imperatives to create valid and sound research that justify the human time, cost, risk and use of limited resources must also be considered. Clinical innovation, and consideration for special populations are also important aspects to take into account. Based on the breadth of these ethical concerns, it is particularly important that scientific questions regarding the development of psychiatric drugs be answered collaboratively by a variety of stakeholders. As the field expands, new ethical considerations will be raised with increased focus on genetic markers, personalized medicine, patient-centered outcomes research, and tension over funding. We suggest that innovation in trial design is necessary to better reflect practices in clinical settings and that there must be an emphasized focus on expanding the transparency of consent processes, regard for suicidality, and care in working with special populations to support the goal of developing sound psychiatric drug therapies. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. The Iodine Satellite (iSAT) Hall Thruster Demonstration Mission Concept and Development

    Science.gov (United States)

    Dankanich, John W.; Polzin, Kurt A.; Calvert, Derek; Kamhawi, Hani

    2014-01-01

    The use of iodine propellant for Hall thrusters has been studied and proposed by multiple organizations due to the potential mission benefits over xenon. In 2013, NASA Marshall Space Flight Center competitively selected a project for the maturation of an iodine flight operational feed system through the Technology Investment Program. Multiple partnerships and collaborations have allowed the team to expand the scope to include additional mission concept development and risk reduction to support a flight system demonstration, the iodine Satellite (iSAT). The iSAT project was initiated and is progressing towards a technology demonstration mission preliminary design review. The current status of the mission concept development and risk reduction efforts in support of this project is presented.

  13. Non-profit Drug Research and Development at a Crossroads.

    Science.gov (United States)

    Jarosławski, Szymon; Toumi, Mondher; Auquier, Pascal; Dussart, Claude

    2018-02-07

    In wealthy nations, non-profit drug R&D has been proposed to reduce the prices of medicines. We sought to review the ethical and economic issues concerning non-profit drug R&D companies, and the possible impact that their pricing strategy may have on the innovation efforts from for-profit companies targeting the same segment of the pharmaceutical market. There are two possible approaches to pricing drugs developed by non-profit R&D programs: pricing that maximises profits and "affordable" pricing that reflects the cost of manufacturing and distribution, plus a margin that ensures sustainability of the drug supply. Overall, the non-profits face ethical challenges - due to the lack of resources, they are unable to independently commercialize their products on a large scale; however, the antitrust law does not permit them to impose prices on potential licensees. Also, reduced prices for the innovative products may result in drying the for-profit R&D in the area.

  14. Development of controlled drug release systems based on thiolated polymers.

    Science.gov (United States)

    Bernkop-Schnürch, A; Scholler, S; Biebel, R G

    2000-05-03

    The purpose of the present study was to generate mucoadhesive matrix-tablets based on thiolated polymers. Mediated by a carbodiimide, L-cysteine was thereby covalently linked to polycarbophil (PCP) and sodium carboxymethylcellulose (CMC). The resulting thiolated polymers displayed 100+/-8 and 1280+/-84 micromol thiol groups per gram, respectively (means+/-S.D.; n=6-8). In aqueous solutions these modified polymers were capable of forming inter- and/or intramolecular disulfide bonds. The velocity of this process augmented with increase of the polymer- and decrease of the proton-concentration. The oxidation proceeded more rapidly within thiolated PCP than within thiolated CMC. Due to the formation of disulfide bonds within thiol-containing polymers, the stability of matrix-tablets based on such polymers could be strongly improved. Whereas tablets based on the corresponding unmodified polymer disintegrated within 2 h, the swollen carrier matrix of thiolated CMC and PCP remained stable for 6.2 h (mean, n=4) and more than 48 h, respectively. Release studies of the model drug rifampicin demonstrated that a controlled release can be provided by thiolated polymer tablets. The combination of high stability, controlled drug release and mucoadhesive properties renders matrix-tablets based on thiolated polymers useful as novel drug delivery systems.

  15. Research, development, and demonstration of nickel-iron batteries for electric vehicle propulsion. Annual report, 1978

    Energy Technology Data Exchange (ETDEWEB)

    1979-10-01

    The objective of this program is to develop a nickel-iron battery suitable for use in electric vehicles. Ultimately, it is expected that a number of these batteries will be demonstrated under the Electric and Hybrid Vehicle Act of 1976. The report presents the technical approach and a summary of the progress that was achieved under the contract. Work began 1 May 1978. The report covers the period through September 1978. (TFD)

  16. Hazardous Waste Development, Demonstration, and Disposal (HAZWDDD) program plan: Executive summary

    International Nuclear Information System (INIS)

    McGinnis, C.P.; Eisenhower, B.M.; Reeves, M.E.; DePaoli, S.M.; Stinton, L.H.; Harrington, E.H.

    1989-02-01

    The Hazardous Waste Development, Demonstration, and Disposal (HAZWDDD) Program Plan provides a strategy for management of hazardous and mixed wastes generated by the five Department of Energy (DOE) installations managed by Martin Marietta Energy Systems, Inc. (Energy Systems). This integrated corporate plan is based on the individual installation plans, which identify waste streams, facility capabilities, problem wastes, future needs, and funding needs. Using this information, the corporate plan identifies common concerns and technology/facility needs over the next 10 years. The overall objective of this corporate plan is to ensure that treatment, storage, and disposal (TSD) needs for all hazardous and mixed wastes generated by Energy Systems installations have been identified and planned for. Specific objectives of the program plan are to (1) identify all hazardous and mixed waste streams; (2) identify hazardous and mixed waste TSD requirements; (3) identify any unresolved technical issues preventing implementation of the strategy; (4) develop schedules for studies, demonstrations, and facilities to resolve the issues; and (5) define the interfaces with the Low-Level Waste Disposal Development and Demonstration (LLWDDD) Program. 10 refs., 7 figs

  17. DEVELOPMENT AND DEMONSTRATION OF INTEGRATED CARBON RECOVERY SYSTEMS FROM FINE COAL PROCESSING WASTE

    Energy Technology Data Exchange (ETDEWEB)

    Y.P. Chugh; D. Patil; A. Patwardhan; R.Q. Honaker; B.K. Parekh; D. Tao; Latif Khan

    2000-07-01

    The project involves the development of an efficient, environmentally friendly system for the economical recovery of carbon from fine-coal refuse ponds. The project will be conducted in two phases. Phase I was involved in the development and evaluation of process equipment and techniques to be used in carbon recovery, product dewatering and reconstitution, and refuse management. Phase II will integrate the various units into a continuously operating circuit that will be demonstrated at a site selected based on the results presented in this study.

  18. The Development and Demonstration of a 360m/10 kA HTS DC Power Cable

    Science.gov (United States)

    Xiao, Liye

    With the quick development of renewable energy, it is expected that the electric power from renewable energy would be the dominant one for the future power grid. Due to the specialty of the renewable energy, the HVDC power transmission would be very useful for the transmission of electric power from renewable energy. DC power cable made of High Tc Superconductor (HTS) would be a possible alternative for the construction of HVDC power transmission system. In this chapter, we report the development and demonstration of a 360 m/10 kA HTS DC power cable and the test results.

  19. The drug-minded protein interaction database (DrumPID) for efficient target analysis and drug development.

    Science.gov (United States)

    Kunz, Meik; Liang, Chunguang; Nilla, Santosh; Cecil, Alexander; Dandekar, Thomas

    2016-01-01

    The drug-minded protein interaction database (DrumPID) has been designed to provide fast, tailored information on drugs and their protein networks including indications, protein targets and side-targets. Starting queries include compound, target and protein interactions and organism-specific protein families. Furthermore, drug name, chemical structures and their SMILES notation, affected proteins (potential drug targets), organisms as well as diseases can be queried including various combinations and refinement of searches. Drugs and protein interactions are analyzed in detail with reference to protein structures and catalytic domains, related compound structures as well as potential targets in other organisms. DrumPID considers drug functionality, compound similarity, target structure, interactome analysis and organismic range for a compound, useful for drug development, predicting drug side-effects and structure-activity relationships.Database URL:http://drumpid.bioapps.biozentrum.uni-wuerzburg.de. © The Author(s) 2016. Published by Oxford University Press.

  20. 1000kW on-site PAFC power plant development and demonstration

    Energy Technology Data Exchange (ETDEWEB)

    Satomi, Tomohide; Koike, Shunichi [Phosphoric Acid Fuel Cell Technology Research Association (PAFC-TRA), Osaka (Japan); Ishikawa, Ryou [New Energy and Industrial Technology Development Organization (NEDO), Tokyo (Japan)

    1996-12-31

    Phosphoric Acid Fuel Cell Technology Research Association (PAFC-TRA) and New Energy and Industrial Technology Development Organization (NEDO) have been conducting a joint project on development of a 5000kW urban energy center type PAFC power plant (pressurized) and a 1000kW on-site PAFC power plant (non-pressurized). The objective of the technical development of 1000kW on-site PAFC power plant is to realize a medium size power plant with an overall efficiency of over 70% and an electrical efficiency of over 36%, that could be installed in a large building as a cogeneration system. The components and system integration development work and the plant design were performed in 1991 and 1992. Manufacturing of the plant and installation at the test site were completed in 1994. PAC test was carried out in 1994, and generation test was started in January 1995. Demonstration test is scheduled for 1995 and 1996.

  1. Ion channels and transporters in the development of drug resistance in cancer cells

    DEFF Research Database (Denmark)

    Hoffmann, Else Kay; Lambert, Ian Henry

    2014-01-01

    Multi-drug resistance (MDR) to chemotherapy is the major challenge in the treatment of cancer. MDR can develop by numerous mechanisms including decreased drug uptake, increased drug efflux and the failure to undergo drug-induced apoptosis. Evasion of drug-induced apoptosis through modulation of i...

  2. 75 FR 65495 - Draft Guidance for Industry on Qualification Process for Drug Development Tools; Availability

    Science.gov (United States)

    2010-10-25

    ...] Draft Guidance for Industry on Qualification Process for Drug Development Tools; Availability AGENCY... Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, rm... Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 21, rm...

  3. Development and evaluation of 'Pure Rush': An online serious game for drug education.

    Science.gov (United States)

    Stapinski, Lexine A; Reda, Bill; Newton, Nicola C; Lawler, Siobhan; Rodriguez, Daniel; Chapman, Catherine; Teesson, Maree

    2018-04-01

    Learning is most effective when it is active, enjoyable and incorporates feedback. Past research demonstrates that serious games are prime candidates to utilise these principles, however the potential benefits of this approach for delivering drug education are yet to be examined in Australia, a country where drug education in schools is mandatory. The serious game 'Pure Rush' was developed across three stages. First, formative consultation was conducted with 115 students (67% male, aged 15-17 years), followed by feasibility and acceptability testing of a prototype of the game (n = 25, 68% male). In the final stage, 281 students (62% female, aged 13-16 years) were randomly allocated to receive a lesson involving Pure Rush or an active control lesson. The lessons were compared in terms of learning outcomes, lesson engagement and future intentions to use illicit drugs. Students enjoyed playing Pure Rush, found the game age-appropriate and the information useful to them. Both the Pure Rush and the active control were associated with significant knowledge increase from pre to post-test. Among females, multi-level mixed-effects regression showed knowledge gain was greater in the Pure Rush condition compared to control (β = 2.36, 95% confidence interval 0.36-4.38). There was no evidence of between condition differences in lesson engagement or future intentions to use illicit drugs. Pure Rush is an innovative online drug education game that is well received by students and feasible to implement in schools. [Stapinski LA, Reda B, Newton NC, Lawler S, Rodriguez D, Chapman C, Teesson M. Development and evaluation of 'Pure Rush': An online serious game for drug education. Drug Alcohol Rev 2017]. © 2017 Australasian Professional Society on Alcohol and other Drugs.

  4. FY94 Office of Technology Development Mixed Waste Operations Robotics Demonstration

    International Nuclear Information System (INIS)

    Kriikku, E.M.

    1994-01-01

    The Department of Energy (DOE) Office of Technology Development (OTD) develops technologies to help solve waste management and environmental problems at DOE sites. The OTD includes the Robotics Technology Development Program (RTDP) and the Mixed Waste Integrated Program (MWIP). Together these programs will provide technologies for DOE mixed waste cleanup projects. Mixed waste contains both radioactive and hazardous constituents. DOE sites currently store over 240,000 cubic meters of low level mixed waste and cleanup activities will generate several hundred thousand more cubic meters. Federal and state regulations require that this waste must be processed before final disposal. The OTD RTDP Mixed Waste Operations (MWO) team held several robotic demonstrations at the Savannah River Site (SRS) during November of 1993. Over 330 representatives from DOE, Government Contractors, industry, and universities attended. The MWO team includes: Fernald Environmental Management Project (FEMP), Idaho National Engineering Laboratory (INEL), Lawrence Livermore National Laboratory (LLNL), Oak Ridge National Engineering Laboratory (ORNL), Sandia National Laboratory (SNL), and Savannah River Technology Center (SRTC). SRTC is the lead site for MWO and provides the technical coordinator. The primary demonstration objective was to show that robotic technologies can make DOE waste facilities run better, faster, more cost effective, and safer. To meet the primary objective, the demonstrations successfully showed the following remote waste drum processing activities: non-destructive drum examination, drum transportation, drum opening, removing waste from a drum, characterize and sort waste items, scarify metal waste, and inspect stored drums. To further meet the primary objective, the demonstrations successfully showed the following remote waste box processing activities: swing free crane control, workcell modeling, and torch standoff control

  5. 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.

  6. Discovery and development of new antibacterial drugs: learning from experience?

    Science.gov (United States)

    Jackson, Nicole; Czaplewski, Lloyd; Piddock, Laura J V

    2018-06-01

    Antibiotic (antibacterial) resistance is a serious global problem and the need for new treatments is urgent. The current antibiotic discovery model is not delivering new agents at a rate that is sufficient to combat present levels of antibiotic resistance. This has led to fears of the arrival of a 'post-antibiotic era'. Scientific difficulties, an unfavourable regulatory climate, multiple company mergers and the low financial returns associated with antibiotic drug development have led to the withdrawal of many pharmaceutical companies from the field. The regulatory climate has now begun to improve, but major scientific hurdles still impede the discovery and development of novel antibacterial agents. To facilitate discovery activities there must be increased understanding of the scientific problems experienced by pharmaceutical companies. This must be coupled with addressing the current antibiotic resistance crisis so that compounds and ultimately drugs are delivered to treat the most urgent clinical challenges. By understanding the causes of the failures and successes of the pharmaceutical industry's research history, duplication of discovery programmes will be reduced, increasing the productivity of the antibiotic drug discovery pipeline by academia and small companies. The most important scientific issues to address are getting molecules into the Gram-negative bacterial cell and avoiding their efflux. Hence screening programmes should focus their efforts on whole bacterial cells rather than cell-free systems. Despite falling out of favour with pharmaceutical companies, natural product research still holds promise for providing new molecules as a basis for discovery.

  7. Bridging Adult Experience to Pediatrics in Oncology Drug Development.

    Science.gov (United States)

    Leong, Ruby; Zhao, Hong; Reaman, Gregory; Liu, Qi; Wang, Yaning; Stewart, Clinton F; Burckart, Gilbert

    2017-10-01

    Pediatric drug development in the United States has grown under the current regulations made permanent by the Food and Drug Administration Safety and Innovation Act of 2012. Over 1200 pediatric studies have now been submitted to the US FDA, but there is still a high rate of failure to obtain pediatric labeling for the indication pursued. Pediatric oncology represents special problems in that the disease is most often dissimilar to any cancer found in the adult population. Therefore, the development of drug dosing in pediatric oncology patients represents a special challenge. Potential approaches to pediatric dosing in oncology patients include extrapolation of efficacy from adult studies in those few cases where the disease is similar, inclusion of adolescent patients in adult trials when possible, and bridging the adult dose to the pediatric dose. An analysis of the recommended phase 2 dose for 40 molecularly targeted agents in pediatric patients provides some insight into current practices. Increased knowledge of tumor biology and efforts to identify and validate molecular targets and genetic abnormalities that drive childhood cancers can lead to increased opportunities for precision medicine in the treatment of pediatric cancers. © 2017, The American College of Clinical Pharmacology.

  8. Assessment of energy research, development, and demonstration priorities for New York State. Interim report. Volume I

    Energy Technology Data Exchange (ETDEWEB)

    Allentuck, J; Appleman, J; Carroll, T O; Palmedo, P F; Nathans, R

    1977-11-01

    In compliance with its mandate to accelerate the development and use of energy technologies in furtherance of the state's economic growth and the best interests of its population, the New York State Energy Research and Development Authority (NYSERDA) initiated, in March 1977, an assessment of energy research and development priorities. This report presents a view of the energy supply-demand future of the state, and the ways in which this future can be affected by external contingencies and concerted policies. That view takes into consideration energy supplies that may be available to the state as well as energy demands as they are affected by demographic and economic changes within the state. Also included are the effects of national energy policies and technological developments as they modify both supplies and demands in New York State. Finally, this report proceeds to identify those general technological areas in which the Authority's program can be of greatest potential benefit to the state's social and economic well being. This effort aims at a cost/benefit analysis determination of RD and D priorities. The preliminary analysis thus far indicates these areas as being of highest priority: energy conservation in buildings (promotion and execution of RD and D) and industry; district heating; fuel cell demonstration;solar heating and cooling (analysis, demonstration, and information dissemination); energy-environment interaction (analysis); energy information services; and, in general, the attraction of Federal RD and D programs to the state.

  9. Development and Demonstration of Sustainable Surface Infrastructure for Moon/Mars Exploration

    Science.gov (United States)

    Sanders, Gerald B.; Larson, William E.; Picard, Martin

    2011-01-01

    For long-term human exploration of the Moon and Mars to be practical, affordable, and sustainable, future missions must be able to identify and utilize resources at the site of exploration. The ability to characterize, extract, processes, and separate products from local material, known as In-Situ Resource Utilization (ISRU), can provide significant reductions in launch mass, logistics, and development costs while reducing risk through increased mission flexibility and protection as well as increased mission capabilities in the areas of power and transportation. Making mission critical consumables like propellants, fuel cell reagents and life support gases, as well as in-situ crew/hardware protection and energy storage capabilities can significantly enhance robotic and human science and exploration missions, however other mission systems need to be designed to interface with and utilize these in-situ developed products and services from the start or the benefits will be minimized or eliminated. This requires a level of surface and transportation system development coordination not typically utilized during early technology and system development activities. An approach being utilized by the US National Aeronautics and Space Administration and the Canadian Space Agency has been to utilize joint analogue field demonstrations to focus technology development activities to demonstrate and integrate new and potentially game changing. mission critical capabilities that would enable an affordable and sustainable surface infrastructure for lunar and Mars robotic and human exploration. Two analogue field tests performed in November 2008 and February 2010 demonstrated first generation capabilities for lunar resource prospecting, exploration site preparation, and oxygen extraction from regolith while initiating integration with mobility, science, fuel cell power, and propulsion disciplines. A third analogue field test currently planned for June 2012 will continue and expand

  10. Technical support to the Solvent Refined Coal (SRC) demonstration projects: assessment of current research and development

    Energy Technology Data Exchange (ETDEWEB)

    Edwards, M.S.; Rodgers, B.R.; Brown, C.H.; Carlson, P.K.; Gambill, W.R.; Gilliam, T.M.; Holmes, J.M.; Krishnan, R.P.; Parsly, L.F.

    1980-12-01

    A program to demonstrate Solvent Refined Coal (SRC) technology has been initiated by the US Department of Energy (DOE) in partnership with two industrial groups. Project management responsibility has been assigned to the Oak Ridge Operations Office (ORO) of DOE. ORO requested that the Oak Ridge National Laboratory assess current research and development (R and D) activities and develop recommendations for those activities that might contribute to successful completion of the SRC demonstration plant projects. The objectives of this final report are to discuss in detail the problem areas in SRC; to discuss the current and planned R and D investigations relevant to the problems identified; and to suggest appropriate R and D activities in support of designs for the SRC demonstration plants. Four types of R and D activities are suggested: continuation of present and planned activities; coordination of activities and results, present and proposed; extension/redirection of activities not involving major equipment purchase or modifications; and new activities. Important examples of the first type of activity include continuation of fired heater, slurry rheology, and slurry mixing studies at Ft. Lewis. Among the second type of activity, coordination of data acquisition and interpretation is recommended in the areas of heat transfer, vapor/liquid equilibria, and physical properties. Principal examples of recommendations for extension/redirection include screening studies at laboratory scale on the use of carbonaceous precoat (e.g., anthracite) infiltration, and 15- to 30-day continuous tests of the Texaco gasifier at the Texaco Montebello facility (using SRC residues).

  11. Challenges and opportunities for the development of new antipsychotic drugs.

    Science.gov (United States)

    Forray, Carlos; Buller, Raimund

    2017-11-01

    In spite of the significant impact that the serendipitous discovery of drugs with antipsychotic properties had on the care of patients with psychotic disorders, there are significant challenges when aiming at therapeutic goals such as remission, recovery, improved health-related quality of life and functioning. The efficacy and effectiveness of existing antipsychotic drugs fail to address the full spectrum of symptoms and functional deficits that currently prevent patients with psychotic disorders from achieving fulfilling lives. The study of the pharmacological mechanism of action has increased our knowledge on molecular targets and brain circuits related to the antipsychotic properties of this drug class. However, our understanding of how these molecular targets and brain circuits relate to other aspects of disease pathophysiology like cognitive impairment and negative symptoms is incomplete although these are significant clinical unmet needs. Currently, there is still an important knowledge gap between psychopathology and pathophysiology in schizophrenia research. This may have contributed to some recent costly failures of large clinical development programs for drugs targeted at glutamatergic function and nicotinic receptors. The lack of success of these pharmacological approaches to achieve clinical validation raises important questions concerning the underlying hypothesis that guided the choice of molecular targets, and about the predictive validity of translational models that supported the rationale for testing these drugs in clinical studies. From a clinical perspective there is a need to more strongly consider the disease heterogeneity linked to the use of the current diagnostic classification of subjects and to the validity of the psychopathological constructs and assessments that are used to assess clinical outcomes. A paradigm shift in the development of drugs for schizophrenia is needed. This will require among other addressing: the shortcomings of a

  12. Which Benefits Are Mentioned Most Often in Drug Development Publications?

    Directory of Open Access Journals (Sweden)

    Vanessa Strüver, MSc

    2017-01-01

    Conclusions: Both theoretically expected and actually reported benefits in the majority of the included publications emphasized the importance of individual patient benefits from drug development rather than the collective benefits to society in general. The authors of these publications emphasized the right of each individual patient or subject to look for and expect some personal benefit from participating in a clinical trial rather than considering societal benefit as a top priority. From an ethical point of view, the benefits each individual patient receives from his or her participation in a clinical trial might also be seen as a societal benefit, especially when the drug or device tested, if approved for marketing, would eventually be made available for other similar patients from the country in which the clinical trial was conducted.

  13. Drug-diagnostics co-development in oncology

    Directory of Open Access Journals (Sweden)

    Richard eSimon

    2013-12-01

    Full Text Available Developments in genomics are providing a biological basis for the heterogeneity of clinical course and response to treatment that have long been apparent to clinicians The ability to molecularly characterize of human diseases presents new opportunities to develop more effective treatments and new challenges for the design and analysis of clinical trials.In oncology, treatment of broad populations with regimens that benefit a minority of patients is less economically sustainable with expensive molecularly targeted therapeutics. The established molecular heterogeneity of human diseases requires the development of new paradigms for the design and analysis of randomized clinical trials as a reliable basis for predictive medicine. We review prospective designs for the development of new therapeutics and predictive biomarkers to inform their use. We cover designs for a wide range of settings. At one extreme is the development of a new drug with a single candidate biomarker and strong biological evidence that marker negative patients are unlikely to benefit from the new drug. At the other extreme are phase III clinical trials involving both genome-wide discovery of a predictive classifier and internal validation of that classifier. We have outlined a prediction based approach to the analysis of randomized clinical trials that both preserves the type I error and provides a reliable internally validated basis for predicting which patients are most likely or unlikely to benefit from a new regimen.

  14. Biomarkers as drug development tools: discovery, validation, qualification and use.

    Science.gov (United States)

    Kraus, Virginia B

    2018-06-01

    The 21st Century Cures Act, approved in the USA in December 2016, has encouraged the establishment of the national Precision Medicine Initiative and the augmentation of efforts to address disease prevention, diagnosis and treatment on the basis of a molecular understanding of disease. The Act adopts into law the formal process, developed by the FDA, of qualification of drug development tools, including biomarkers and clinical outcome assessments, to increase the efficiency of clinical trials and encourage an era of molecular medicine. The FDA and European Medicines Agency (EMA) have developed similar processes for the qualification of biomarkers intended for use as companion diagnostics or for development and regulatory approval of a drug or therapeutic. Biomarkers that are used exclusively for the diagnosis, monitoring or stratification of patients in clinical trials are not subject to regulatory approval, although their qualification can facilitate the conduct of a trial. In this Review, the salient features of biomarker discovery, analytical validation, clinical qualification and utilization are described in order to provide an understanding of the process of biomarker development and, through this understanding, convey an appreciation of their potential advantages and limitations.

  15. Sex, gender, and pharmaceutical politics: From drug development to marketing.

    Science.gov (United States)

    Fisher, Jill A; Ronald, Lorna M

    2010-08-01

    Biological sex differences and sociocultural gender norms affect the provision of health care products and services, but there has been little explicit analysis of the impact of sex differences and gender norms on the regulation of pharmaceutical development and marketing. This article provides an overview of the regulation of pharmaceuticals and examines the ways that regulatory agencies account for sex and gender in their review of scientific data and marketing materials. The primary focus is on the US context, but information is also included about regulatory models in Europe, Canada, and Japan for comparative purposes. Specific examples show how sex differences and gender norms influence scientific and policy decisions about pharmaceuticals. The United States and Canada were found to be the only countries that have explicit requirements to include women in clinical trials and to perform sex-based subgroup analysis on study results. The potential influence of politics on regulatory decisions may have led to an uneven application of standards, as seen through the examples of mifepristone (for abortion) and sildenafil citrate (for erectile dysfunction). Three detailed case studies illustrate the importance of considering sex and gender in pharmaceutical development and marketing: Phase I clinical trials; human papillomavirus quadrivalent vaccine; and tegaserod, a drug for irritable bowel syndrome. Sex and gender play important roles in pharmaceutical regulation, from the design of clinical trials and the approval of new drugs to advertising and postmarketing surveillance. However, regulatory agencies pay insufficient attention to both biological sex differences and sociocultural gender norms. This disregard perpetuates inequalities by ignoring drug safety problems that predominate in women and by allowing misleading drug marketing that reinforces gender stereotypes. Recommendations have been made to improve the regulation of pharmaceuticals in regard to sex and

  16. A study on development of Pyro process integrated inactive demonstration facility

    International Nuclear Information System (INIS)

    Cho, I.; Lee, E.; Choung, W.; You, G.; Kim, H.

    2010-10-01

    Since 2007, the Pride (Pyro process integrated inactive demonstration facility) has been developed to demonstrate the integrated engineering-scale pyro processing using natural uranium with surrogate materials. In this paper, safety evaluation on hypothetical accident case is carried out to ensure the release of radioactivity being negligible to the environment and the performance of indoor argon flow for the argon cell has been investigated by means of CFD analysis. The worst accident case, even in the firing of the all uranium metal in argon cell, cause dose rate are negligible comparing to 0.25 Sv of effective dose rate to whole body or 3 Sv of equivalent dose rate to the thyroid preliminary CFD analyses show the temperature and velocity distribution of argon cell, and give the information to change the argon exchange rate and displace the argon supply or exhaust duct. CFD will allow design change and improvements in ventilation systems at lower cost. (Author)

  17. Development of Demonstration Facility Design Technology for Advanced Nuclear Fuel Cycle Process

    International Nuclear Information System (INIS)

    Cho, Il Je; You, G. S.; Choung, W. M.

    2010-04-01

    The main objective of this R and D is to develop the PRIDE (PyRoprocess Integrated inactive DEmonstration) facility for engineering-scale inactive test using fresh uranium, and to establish the design requirements of the ESPF (Engineering Scale Pyroprocess Facility) for active demonstration of the pyroprocess. Pyroprocess technology, which is applicable to GEN-IV systems as one of the fuel cycle options, is a solution of the spent fuel accumulation problems. PRIDE Facility, pyroprocess mock-up facility, is the first facility that is operated in inert atmosphere in the country. By using the facility, the functional requirements and validity of pyroprocess technology and facility related to the advanced fuel cycle can be verified with a low cost. Then, PRIDE will contribute to evaluate the technology viability, proliferation resistance and possibility of commercialization of the pyroprocess technology. The PRIDE evaluation data, such as performance evaluation data of equipment and operation experiences, will be directly utilized for the design of ESPF

  18. NASA Systems Autonomy Demonstration Project - Development of Space Station automation technology

    Science.gov (United States)

    Bull, John S.; Brown, Richard; Friedland, Peter; Wong, Carla M.; Bates, William

    1987-01-01

    A 1984 Congressional expansion of the 1958 National Aeronautics and Space Act mandated that NASA conduct programs, as part of the Space Station program, which will yield the U.S. material benefits, particularly in the areas of advanced automation and robotics systems. Demonstration programs are scheduled for automated systems such as the thermal control, expert system coordination of Station subsystems, and automation of multiple subsystems. The programs focus the R&D efforts and provide a gateway for transfer of technology to industry. The NASA Office of Aeronautics and Space Technology is responsible for directing, funding and evaluating the Systems Autonomy Demonstration Project, which will include simulated interactions between novice personnel and astronauts and several automated, expert subsystems to explore the effectiveness of the man-machine interface being developed. Features and progress on the TEXSYS prototype thermal control system expert system are outlined.

  19. Water Use Optimization Toolset Project: Development and Demonstration Phase Draft Report

    Energy Technology Data Exchange (ETDEWEB)

    Gasper, John R. [Argonne National Laboratory; Veselka, Thomas D. [Argonne National Laboratory; Mahalik, Matthew R. [Argonne National Laboratory; Hayse, John W. [Argonne National Laboratory; Saha, Samrat [Argonne National Laboratory; Wigmosta, Mark S. [PNNL; Voisin, Nathalie [PNNL; Rakowski, Cynthia [PNNL; Coleman, Andre [PNNL; Lowry, Thomas S. [SNL

    2014-05-19

    This report summarizes the results of the development and demonstration phase of the Water Use Optimization Toolset (WUOT) project. It identifies the objective and goals that guided the project, as well as demonstrating potential benefits that could be obtained by applying the WUOT in different geo-hydrologic systems across the United States. A major challenge facing conventional hydropower plants is to operate more efficiently while dealing with an increasingly uncertain water-constrained environment and complex electricity markets. The goal of this 3-year WUOT project, which is funded by the U.S. Department of Energy (DOE), is to improve water management, resulting in more energy, revenues, and grid services from available water, and to enhance environmental benefits from improved hydropower operations and planning while maintaining institutional water delivery requirements. The long-term goal is for the WUOT to be used by environmental analysts and deployed by hydropower schedulers and operators to assist in market, dispatch, and operational decisions.

  20. Recent trends for drug lag in clinical development of oncology drugs in Japan: does the oncology drug lag still exist in Japan?

    Science.gov (United States)

    Maeda, Hideki; Kurokawa, Tatsuo

    2015-12-01

    This study exhaustively and historically investigated the status of drug lag for oncology drugs approved in Japan. We comprehensively investigated oncology drugs approved in Japan between April 2001 and July 2014, using publicly available information. We also examined changes in the status of drug lag between Japan and the United States, as well as factors influencing drug lag. This study included 120 applications for approval of oncology drugs in Japan. The median difference over a 13-year period in the approval date between the United States and Japan was 875 days (29.2 months). This figure peaked in 2002, and showed a tendency to decline gradually each year thereafter. In 2014, the median approval lag was 281 days (9.4 months). Multiple regression analysis identified the following potential factors that reduce drug lag: "Japan's participation in global clinical trials"; "bridging strategies"; "designation of priority review in Japan"; and "molecularly targeted drugs". From 2001 to 2014, molecularly targeted drugs emerged as the predominant oncology drug, and the method of development has changed from full development in Japan or bridging strategy to global simultaneous development by Japan's taking part in global clinical trials. In line with these changes, the drug lag between the United States and Japan has significantly reduced to less than 1 year.

  1. Cancer Drug Development: New Targets for Cancer Treatment.

    Science.gov (United States)

    Curt

    1996-01-01

    cancer drug screening and cancer drug development. At the NCI, for example, the old in vivo mouse screen using mouse lymphomas has been shelved; it discovered compounds with some activity in lymphomas, but not the common solid tumors of adulthood. It has been replaced with an initial in vitro screen of some sixty cell lines, representing the common solid tumors-ovary, G.I., lung, breast, CNS, melanoma and others. The idea was to not only discover new drugs with specific anti-tumor activity but also to use the small volumes required for in vitro screening as a medium to screen for new natural product compounds, one of the richest sources of effective chemotherapy. The cell line project had an unexpected dividend. The pattern of sensitivity in the panel predicted the mechanism of action of unknown compounds. An antifolate suppressed cell growth of the different lines like other antifolates, anti-tubulin compounds suppressed like other anti-tubulins, and so on. It now became possible, at a very early stage of cancer drug screening, to select for drugs with unknown-and potentially novel-mechanisms of action. The idea was taken to the next logical step, and that was to characterize the entire panel for important molecular properties of human malignancy: mutations in the tumor suppressor gene p53, expression of important oncogenes like ras or myc, the gp170 gene which confers multiple drug resistance, protein-specific kinases, and others. It now became possible to use the cell line panel as a tool to detect new drugs which targeted a specific genetic property of the tumor cell. Researchers can now ask whether a given drug is likely to inhibit multiple drug resistance or kill cells which over-express specific oncogenes at the earliest phase of drug discovery. In this issue of The Oncologist, Tom Connors celebrates the fiftieth anniversary of cancer chemotherapy. His focus is on the importance of international collaboration in clinical trials and the negative impact of

  2. Microgrid Design, Development and Demonstration - Final Report for Phase I and Phase II

    Energy Technology Data Exchange (ETDEWEB)

    Bose, Sumit [GE Global Research Center, Niskayuna, NY (United States); Krok, Michael [GE Global Research Center, Niskayuna, NY (United States)

    2011-02-08

    This document constitutes GE’s final report for the Microgrid Design, Development and Demonstration program for DOE’s Office of Electricity Delivery and Energy Reliability, Award DE-FC02-05CH11349. It contains the final report for Phase I in Appendix I, and the results the work performed in Phase II. The program goal was to develop and demonstrate a Microgrid Energy Management (MEM) framework for a broad set of Microgrid applications that provides unified controls, protection, and energy management. This project contributed to the achievement of the U.S. Department of Energy’s Renewable and Distributed Systems Integration Program goals by developing a fully automated power delivery microgrid network that: - Reduces carbon emissions and emissions of other air pollutants through increased use of optimally dispatched renewable energy, - Increases asset use through integration of distributed systems, - Enhances reliability, security, and resiliency from microgrid applications in critical infrastructure protection, constrained areas of the electric grid, etc. - Improves system efficiency with on-site, distributed generation and improved economic efficiency through demand-side management.

  3. Development and demonstration of treatment technologies for the processing of US Department of Energy mixed waste

    International Nuclear Information System (INIS)

    Berry, J.B.; Bloom, G.A.; Kuchynka, D.J.

    1994-01-01

    Mixed waste is defined as waste contaminated with chemically hazardous (governed by the Resource Conservation and Recovery Act) and radioactive species [governed by US Department of Energy (DOE) orders]. The Mixed Waste Integrated Program (MWIP) is responding to the need for DOE mixed waste treatment technologies that meet these dual regulatory requirements. MWIP is developing emerging and innovative treatment technologies to determine process feasibility. Technology demonstrations will be used to determine whether processes are superior to existing technologies in reducing risk, minimizing life-cycle cost, and improving process performance. The Program also provides a forum for stakeholder and customer involvement in the technology development process. MWIP is composed of six technical areas that support a mixed-waste treatment system: (1) systems analysis, (2) materials handling, (3) chemical/physical separation, (4) waste destruction and stabilization, (5) off-gas treatment, and (6) final waste form stabilization. The status of the technical initiatives and the current research, development, and demonstration in each of these areas is described in this paper

  4. Controlling type I error rate for fast track drug development programmes.

    Science.gov (United States)

    Shih, Weichung J; Ouyang, Peter; Quan, Hui; Lin, Yong; Michiels, Bart; Bijnens, Luc

    2003-03-15

    The U.S. Food and Drug Administration (FDA) Modernization Act of 1997 has a Section (No. 112) entitled 'Expediting Study and Approval of Fast Track Drugs' (the Act). In 1998, the FDA issued a 'Guidance for Industry: the Fast Track Drug Development Programs' (the FTDD programmes) to meet the requirement of the Act. The purpose of FTDD programmes is to 'facilitate the development and expedite the review of new drugs that are intended to treat serious or life-threatening conditions and that demonstrate the potential to address unmet medical needs'. Since then many health products have reached patients who suffered from AIDS, cancer, osteoporosis, and many other diseases, sooner by utilizing the Fast Track Act and the FTDD programmes. In the meantime several scientific issues have also surfaced when following the FTDD programmes. In this paper we will discuss the concept of two kinds of type I errors, namely, the 'conditional approval' and the 'final approval' type I errors, and propose statistical methods for controlling them in a new drug submission process. Copyright 2003 John Wiley & Sons, Ltd.

  5. Federal research, development, and demonstration priorities for carbon dioxide removal in the United States

    Science.gov (United States)

    Sanchez, Daniel L.; Amador, Giana; Funk, Jason; Mach, Katharine J.

    2018-01-01

    Atmospheric carbon dioxide removal (CDR) technologies may be critical to achieving deep decarbonization. Yet a lack of technical and commercial maturity of CDR technologies hinders potential deployment. Needs for commercialization span research, development, and demonstration (RD&D) activities, including development of new materials, reactors, and processes, and rigorous monitoring of a portfolio of demonstration projects. As a world leader in supporting science and engineering, the United States (US) can play an important role in reducing costs and clarifying the sustainable scale of CDR. To date, federal agencies have focused on voluntary or piecemeal CDR programs. Here, we present a synthesis of research and developement needs, relevant agency authority, barriers to coordination, and interventions to enhance RD&D across the federal government of the US. On the basis of agency authority and expertise, the Department of Energy, Department of Agriculture, Department of the Interior, National Oceanic and Atmospheric Administration, and National Science Foundation are most central to conducting research, funding projects, monitoring effects, and promulgating regulations. Key enablers for successful programs include embracing technological diversity and administrative efficiency, fostering agency buy-in, and achieving commercial deployment. Based on these criteria, the executive branch could effectively coordinate RD&D strategy through two complementary pathways: (1) renewing intra-agency commitment to CDR in five primary agencies, including both research and demonstration, and (2) coordinating research prioritization and outcomes across agencies, led by the Office of Science and Technology Policy and loosely based on the National Nanotechnology Initiative. Both pathways can be stimulated by executive order or Congressional mandate. Executive branch implementation can begin at any time; future Farm and Energy Bills provide legislative vehicles for enhancing programs.

  6. Synthesis and applications of radiolabelled drugs in pharmaceutical development

    International Nuclear Information System (INIS)

    Landvatter, S.W.; Heys, J.R.; Garner, K.T.; Mack, J.F.; Senderoff, S.G.; Shu, A.Y.; Villani, A.J.; Saunders, D.

    1994-01-01

    Radiolabelled drugs play a vital role in the development of new pharmaceuticals including application in drug discovery, pre-clinical development and clinical development. The synthesis of these pharmaceuticals in tritium or carbon-14 labelled form poses many challenges for the synthetic organic chemist. The actual choice of synthetic route must take into account the small scale, limited choice and high cost of labelled precursors, and the positioning of the label into a metabolically stable position. There are, however, a number of synthetic strategies available for overcoming these constraints. Although in some C-14 syntheses the requisite labelled raw material can be purchased and the existing synthesis adapted for labelling, frequently the synthetic challenge is the synthesis of a structurally simple, yet commercially unavailable, labelled precursor (e.g., γ-butyrolactone-[2- 14 C], cyclohexanone-[ 3 H], CuCN-[ 14 C], 2-furancarboxaldehyde-[ 14 C]). Another useful strategy in C-14 synthesis is the conversion of an advanced intermediate, or perhaps the unlabelled product itself, into a precursor which can then be reconverted into the labelled version of the intermediate. Occasionally, a new total synthesis must be developed. In addition to these strategies, tritium labelling can uniquely take advantage of exchange labelling techniques, synthesis and reduction of unsaturated precursors, or tritium-halogen replacement reactions. Examples of these strategies and use of the labelled products are discussed

  7. Energy Savings Potential and Research, Development, & Demonstration Opportunities for Commercial Building Appliances

    Energy Technology Data Exchange (ETDEWEB)

    Zogg, Robert [Navigant Consulting, Inc., Burlington, MA (United States); Goetzler, William [Navigant Consulting, Inc., Burlington, MA (United States); Ahlfeldt, Christopher [Navigant Consulting, Inc., Burlington, MA (United States); Hiraiwa, Hirokazu [Navigant Consulting, Inc., Burlington, MA (United States); Sathe, Amul [Navigant Consulting, Inc., Burlington, MA (United States); Sutherland, Timothy [Navigant Consulting, Inc., Burlington, MA (United States)

    2009-12-01

    This study characterizes and assesses the appliances used in commercial buildings. The primary objectives of this study were to document the energy consumed by commercial appliances and identify research, development and demonstration (RD&D) opportunities for efficiency improvements, excluding product categories such as HVAC, building lighting, refrigeration equipment, and distributed generation systems. The study included equipment descriptions, characteristics of the equipment’s market, national energy consumption, estimates of technical potential for energy-saving technologies, and recommendations for U.S. Department of Energy programs that can promote energy savings in commercial appliances.

  8. 76 FR 35214 - Notice of Determination of Adequacy of Ohio's Research, Development and Demonstration (RD&D...

    Science.gov (United States)

    2011-06-16

    ... Research, Development and Demonstration (RD&D) Permit Provisions for Municipal Solid Waste Landfills AGENCY... regulations allowing research, development and demonstration (RD&D) permits to be issued to certain municipal... landfill criteria in 40 CFR Part 258 to allow for research, development and demonstration permits (69 FR...

  9. Novel approaches in anti-arenaviral drug development

    International Nuclear Information System (INIS)

    Lee, Andrew M.; Pasquato, Antonella; Kunz, Stefan

    2011-01-01

    Hemorrhagic fevers caused by arenaviruses are among the most devastating emerging human diseases. Considering the number of individuals affected, the current lack of a licensed vaccine, and the limited therapeutic options, arenaviruses are arguably among the most neglected tropical pathogens and the development of efficacious anti-arenaviral drugs is of high priority. Over the past years significant efforts have been undertaken to identify novel potent inhibitors of arenavirus infection. High throughput screening of small molecule libraries employing pseudotype platforms led to the discovery of several potent and broadly active inhibitors of arenavirus cell entry that are effective against the major hemorrhagic arenaviruses. Mechanistic studies revealed that these novel entry inhibitors block arenavirus membrane fusion and provided novel insights into the unusual mechanism of this process. The success of these approaches highlights the power of small molecule screens in antiviral drug discovery and establishes arenavirus membrane fusion as a robust drug target. These broad screenings have been complemented by strategies targeting cellular factors involved in productive arenavirus infection. Approaches targeting the cellular protease implicated in maturation of the fusion-active viral envelope glycoprotein identified the proteolytic processing of the arenavirus glycoprotein precursor as a novel and promising target for anti-arenaviral strategies.

  10. Development of immunotoxicity testing strategies for immunomodulatory drugs.

    Science.gov (United States)

    Kawabata, Thomas T; Evans, Ellen W

    2012-01-01

    The ICH S8 immunotoxicity testing guideline for human pharmaceuticals was published in 2006 and was intended to provide guidance for assessing the immunotoxicity potential of low-molecular-weight drugs that are not intended to alter the immune system. For drugs intended to modulate the immune system, immunotoxicity testing strategies are generally developed on a case-by-case approach since the targets, intended patient population, and mechanisms of action of the test compound will determine the type of testing needed. Some of the general principles of ICH S8, however, may be applied to immunotoxicity testing strategies for immunomodulatory drugs. A weight-of-evidence approach using factors discussed in ICH S8 in concert with an assessment of the potential value of additional immunotoxicity testing should be considered. For most situations, immunotoxicity studies with immunomodulatory compounds evaluate off-target effects on the immune system and exaggerated pharmacology. The potential use of data from these studies and considerations such as translatability to humans are discussed.

  11. Engineering development and demonstration of DETOXSM wet oxidation for mixed waste treatment

    International Nuclear Information System (INIS)

    Dhooge, P.M.; Goldblatt, S.D.; Moslander, J.E.; Robertson, D.T.; Rogers, T.W.; Zigmond, J.A.

    1997-12-01

    DETOX SM , a catalyzed chemical oxidation process, is under development for treatment of hazardous and mixed wastes at Department of Energy sites. To support this effort, developmental engineering studies have been formed for aspects of the process to help ensure safe and effective operation. Subscale agitation studies have been preformed to identify a suitable mixing head and speed for the primary reaction vessel agitator. Mechanisms for feeding solid waste materials to the primary reaction vessel have been investigated. Filtration to remove solid field process residue, and the use of various filtration aids, has been studied. Extended compatibility studies on the materials of construction have been performed. Due to a change to Rocky Flats Environmental Technology Site (RFETS) for the mixed waste portion of the demonstration, types of wastes suitable and appropriate for treatment at RFETS had to be chosen. A Prototype unit has been fabricated and will be demonstrated on hazardous and mixed wastes at Savannah River Site (SRS) and RFETS during 1997 and 1998. The unit is in shakedown testing at present. Data validation and an engineering evaluation will be performed during the demonstration

  12. Development and functional demonstration of a wireless intraoral inductive tongue computer interface for severely disabled persons.

    Science.gov (United States)

    N S Andreasen Struijk, Lotte; Lontis, Eugen R; Gaihede, Michael; Caltenco, Hector A; Lund, Morten Enemark; Schioeler, Henrik; Bentsen, Bo

    2017-08-01

    Individuals with tetraplegia depend on alternative interfaces in order to control computers and other electronic equipment. Current interfaces are often limited in the number of available control commands, and may compromise the social identity of an individual due to their undesirable appearance. The purpose of this study was to implement an alternative computer interface, which was fully embedded into the oral cavity and which provided multiple control commands. The development of a wireless, intraoral, inductive tongue computer was described. The interface encompassed a 10-key keypad area and a mouse pad area. This system was embedded wirelessly into the oral cavity of the user. The functionality of the system was demonstrated in two tetraplegic individuals and two able-bodied individuals Results: The system was invisible during use and allowed the user to type on a computer using either the keypad area or the mouse pad. The maximal typing rate was 1.8 s for repetitively typing a correct character with the keypad area and 1.4 s for repetitively typing a correct character with the mouse pad area. The results suggest that this inductive tongue computer interface provides an esthetically acceptable and functionally efficient environmental control for a severely disabled user. Implications for Rehabilitation New Design, Implementation and detection methods for intra oral assistive devices. Demonstration of wireless, powering and encapsulation techniques suitable for intra oral embedment of assistive devices. Demonstration of the functionality of a rechargeable and fully embedded intra oral tongue controlled computer input device.

  13. Direct anti-atherosclerotic therapy; development of natural anti-atherosclerotic drugs preventing cellular cholesterol retention.

    Science.gov (United States)

    Orekhov, Alexander N

    2013-01-01

    The results of numerous clinical trials with statins and other drugs have demonstrated the principal possibility of the prevention and regression of atherosclerosis by pharmacotherapy. This review describes the use of cultured human arterial cells for the mass screening of anti-atherosclerotic substances, the investigation of the mechanisms responsible for their atherosclerosis-related effects, and the optimization of anti-atherosclerotic and anti-atherogenic drug and dietary therapies. Natural products can be considered promising drugs for anti-atherosclerotic therapy. Our basic studies have shown that cellular lipidosis is the principal event in the genesis of atherosclerotic lesions. Using cellular models and natural products, we have developed an approach to prevent lipid accumulation in arterial cells. Based on our knowledge of atherosclerosis, we developed drugs that possess direct anti-atherosclerotic activity. Two-year treatment with allicor (garlic powder) has a direct anti-atherosclerotic effect on carotid atherosclerosis in asymptomatic men. Inflaminat (calendula, elder, and violet), which possesses anti-cytokine activity, has been shown to cause the regression of carotid atherosclerosis following the treatment of asymptomatic men for one year. The phytoestrogen-rich drug karinat (garlic powder, extract of grape seeds, green tea leaves, hop cones, β-carotene, α-tocopherol, and ascorbic acid) prevents the development of carotid atherosclerosis in postmenopausal women. Thus, our basic findings were successfully translated into clinical practice. Because of this translation, a novel approach to antiatherosclerotic therapy was developed. Our clinical trial confirmed the efficacy of both the novel approach and the novel drugs.

  14. U.S. Department of Energy, Office of Technology Development, mixed-waste treatment research, development, demonstration, testing, and evaluation

    International Nuclear Information System (INIS)

    Berry, J.B.

    1993-01-01

    Both chemically hazardous and radioactive species contaminate mixed waste. Historically, technology has been developed to treat either hazardous or radioactive waste. Technology specifically designed to produce a low-risk final waste form for mixed low-level waste has not been developed, demonstrated, or tested. Site-specific solutions to management of mixed waste have been initiated; however, site-specific programs result in duplication of technology development effort between various sites. There is a clear need for technology designed to meet the unique requirements for mixed-waste processing and a system-wide integrated strategy for developing technology and managing mixed waste. This paper discusses the US Department of Energy (DOE) approach to addressing these unique requirements through a national technology development effort

  15. Development and demonstration of treatment technologies for the processing of US Department of Energy Mixed Waste

    International Nuclear Information System (INIS)

    Bloom, G.A.; Berry, J.B.

    1994-01-01

    Mixed waste is defined as ''waste contaminated with chemically hazardous and radioactive species.'' The Mixed Waste Integrated Program (MWIP) was established in response to the need for a unified, DOE complexwide solution to issues of mixed waste treatment that meets regulatory requirements. MWIP is developing treatment technologies that reduce risk, minimize life-cycle cost, and improve process performance as compared to existing technologies. Treatment for waste streams for which no current technology exists, and suitable waste forms for disposal, will be provided to improve operations of the DOE Office of Waste Management. MWIP is composed of six technical areas within a mixed-waste treatment system: (1) systems analysis, (2) materials handling, (3) chemical/physical separation, (4) waste destruction and stabilization, (5) off-gas treatment, and (6) final waste form stabilization. The status of the technical initiatives and the current research, development, and demonstration in each of these areas are described in this paper

  16. Waste management technology development and demonstration programs at Brookhaven National Laboratory

    Science.gov (United States)

    Kalb, Paul D.; Colombo, Peter

    1991-01-01

    Two thermoplastic processes for improved treatment of radioactive, hazardous, and mixed wastes were developed from bench scale through technology demonstration: polyethylene encapsulation and modified sulfur cement encapsulation. The steps required to bring technologies from the research and development stage through full scale implementation are described. Both systems result in durable waste forms that meet current Nuclear Regulatory Commission and Environmental Protection Agency regulatory criteria and provide significant improvements over conventional solidification systems such as hydraulic cement. For example, the polyethylene process can encapsulate up to 70 wt pct. nitrate salt, compared with a maximum of about 20 wt pct. for the best hydraulic cement formulation. Modified sulfur cement waste forms containing as much as 43 wt pct. incinerator fly ash were formulated, whereas the maximum quantity of this waste in hydraulic cement is 16 wt pct.

  17. Pit disassembly and conversion demonstration environmental assessment and research and development activities

    International Nuclear Information System (INIS)

    1998-08-01

    A significant portion of the surplus plutonium is in the form of pits, a nuclear weapons component. Pits are composed of plutonium which is sealed in a metallic shell. These pits would need to be safely disassembled and permanently converted to an unclassified form that would be suitable for long-term disposition and international inspection. To determine the feasibility of an integrated pit disassembly and conversion system, a Pit Disassembly and Conversion Demonstration is proposed to take place at the Los Alamos National Laboratory (LANL). This demonstration would be done in existing buildings and facilities, and would involve the disassembly of up to 250 pits and conversion of the recovered plutonium to plutonium metal ingots and plutonium dioxide. This demonstration also includes the conversion of up to 80 kilograms of clean plutonium metal to plutonium dioxide because, as part of the disposition process, some surplus plutonium metal may be converted to plutonium dioxide in the same facility as the surplus pits. The equipment to be used for the proposed demonstration addressed in this EA would use some parts of the Advanced Recovery and Integrated Extraction System (ARIES) capability, other existing equipment/capacities, plus new equipment that was developed at other sites. In addition, small-scale R and D activities are currently underway as part of the overall surplus plutonium disposition program. These R and D activities are related to pit disassembly and conversion, MOX fuel fabrication, and immobilization (in glass and ceramic forms). They are described in Section 7.0. On May 16, 1997, the Office of Fissile Materials Disposition (MD) notified potentially affected states and tribes that this EA would be prepared in accordance with NEPA. This EA has been prepared to provide sufficient information for DOE to determine whether a Finding of No Significant Impact (FONSI) is warranted or whether an EIS must be prepared

  18. Development of anti-inflammatory drugs - the research and development process.

    Science.gov (United States)

    Knowles, Richard Graham

    2014-01-01

    The research and development process for novel drugs to treat inflammatory diseases is described, and several current issues and debates relevant to this are raised: the decline in productivity, attrition, challenges and trends in developing anti-inflammatory drugs, the poor clinical predictivity of experimental models of inflammatory diseases, heterogeneity within inflammatory diseases, 'improving on the Beatles' in treating inflammation, and the relationships between big pharma and biotechs. The pharmaceutical research and development community is responding to these challenges in multiple ways which it is hoped will lead to the discovery and development of a new generation of anti-inflammatory medicines. © 2013 Nordic Pharmacological Society. Published by John Wiley & Sons Ltd.

  19. Developing a research and practice tool to measure walkability: a demonstration project.

    Science.gov (United States)

    Giles-Corti, Billie; Macaulay, Gus; Middleton, Nick; Boruff, Bryan; Bull, Fiona; Butterworth, Iain; Badland, Hannah; Mavoa, Suzanne; Roberts, Rebecca; Christian, Hayley

    2014-12-01

    Growing evidence shows that higher-density, mixed-use, pedestrian-friendly neighbourhoods encourage active transport, including transport-related walking. Despite widespread recognition of the benefits of creating more walkable neighbourhoods, there remains a gap between the rhetoric of the need for walkability and the creation of walkable neighbourhoods. Moreover, there is little objective data to benchmark the walkability of neighbourhoods within and between Australian cities in order to monitor planning and design intervention progress and to assess built environment and urban policy interventions required to achieve increased walkability. This paper describes a demonstration project that aimed to develop, trial and validate a 'Walkability Index Tool' that could be used by policy makers and practitioners to assess the walkability of local areas; or by researchers to access geospatial data assessing walkability. The overall aim of the project was to develop an automated geospatial tool capable of creating walkability indices for neighbourhoods at user-specified scales. The tool is based on open-source software architecture, within the Australian Urban Research Infrastructure Network (AURIN) framework, and incorporates key sub-component spatial measures of walkability (street connectivity, density and land use mix). Using state-based data, we demonstrated it was possible to create an automated walkability index. However, due to the lack of availability of consistent of national data measuring land use mix, at this stage it has not been possible to create a national walkability measure. The next stage of the project is to increase useability of the tool within the AURIN portal and to explore options for alternative spatial data sources that will enable the development of a valid national walkability index. AURIN's open-source Walkability Index Tool is a first step in demonstrating the potential benefit of a tool that could measure walkability across Australia. It

  20. Development and demonstration of a validation methodology for vehicle lateral dynamics simulation models

    Energy Technology Data Exchange (ETDEWEB)

    Kutluay, Emir

    2013-02-01

    In this thesis a validation methodology to be used in the assessment of the vehicle dynamics simulation models is presented. Simulation of vehicle dynamics is used to estimate the dynamic responses of existing or proposed vehicles and has a wide array of applications in the development of vehicle technologies. Although simulation environments, measurement tools and mathematical theories on vehicle dynamics are well established, the methodical link between the experimental test data and validity analysis of the simulation model is still lacking. The developed validation paradigm has a top-down approach to the problem. It is ascertained that vehicle dynamics simulation models can only be validated using test maneuvers although they are aimed for real world maneuvers. Test maneuvers are determined according to the requirements of the real event at the start of the model development project and data handling techniques, validation metrics and criteria are declared for each of the selected maneuvers. If the simulation results satisfy these criteria, then the simulation is deemed ''not invalid''. If the simulation model fails to meet the criteria, the model is deemed invalid, and model iteration should be performed. The results are analyzed to determine if the results indicate a modeling error or a modeling inadequacy; and if a conditional validity in terms of system variables can be defined. Three test cases are used to demonstrate the application of the methodology. The developed methodology successfully identified the shortcomings of the tested simulation model, and defined the limits of application. The tested simulation model is found to be acceptable but valid only in a certain dynamical range. Several insights for the deficiencies of the model are reported in the analysis but the iteration step of the methodology is not demonstrated. Utilizing the proposed methodology will help to achieve more time and cost efficient simulation projects with

  1. Initial Development and Pilot Study Design of Interactive Lecture Demonstrations for ASTRO 101

    Science.gov (United States)

    Schwortz, Andria C.; French, D. A; Gutierrez, Joseph V; Sanchez, Richard L; Slater, Timothy F.; Tatge, Coty

    2014-06-01

    Interactive lecture demonstrations (ILDs) have repeatedly shown to be effective tools for improving student achievement in the context of learning physics. As a first step toward systematic development of interactive lecture demonstrations in ASTRO 101, the introductory astronomy survey course, a systematic review of education research, describing educational computer simulations (ECSs) reveals that initial development requires a targeted study of how ASTRO 101 students respond to ECSs in the non-science majoring undergraduate lecture setting. In this project we have adopted the process by which ILDs were designed, pilot-tested, and successfully implemented in the context of physics teaching (Sokoloff & Thornton, 1997; Sokoloff & Thornton, 2004). We have designed the initial pilot-test set of ASTRO 101 ILD instructional materials relying heavily on ECSs. Both an instructor’s manual and a preliminary classroom-ready student workbook have been developed, and we are implementing a pilot study to explore their effectiveness in communicating scientific content, and the extent to which they might enhance students’ knowledge of and perception about astronomy and science in general. The study design uses a pre-/post-test quasi-experimental study design measuring students’ normalized gain scores, calculated as per Hake (1998) and Prather (2009), using a slightly modified version of S. Slater’s (2011) Test Of Astronomy STandards TOAST combined with other instruments. The results of this initial study will guide the iterative development of ASTRO 101 ILDs that are intended to both be effective at enhancing student achievement and easy for instructors to successfully implement.

  2. Drugs in development for toxoplasmosis: advances, challenges, and current status.

    Science.gov (United States)

    Alday, P Holland; Doggett, Joseph Stone

    2017-01-01

    Toxoplasma gondii causes fatal and debilitating brain and eye diseases. Medicines that are currently used to treat toxoplasmosis commonly have toxic side effects and require prolonged courses that range from weeks to more than a year. The need for long treatment durations and the risk of relapsing disease are in part due to the lack of efficacy against T. gondii tissue cysts. The challenges for developing a more effective treatment for toxoplasmosis include decreasing toxicity, achieving therapeutic concentrations in the brain and eye, shortening duration, eliminating tissue cysts from the host, safety in pregnancy, and creating a formulation that is inexpensive and practical for use in resource-poor areas of the world. Over the last decade, significant progress has been made in identifying and developing new compounds for the treatment of toxoplasmosis. Unlike clinically used medicines that were repurposed for toxoplasmosis, these compounds have been optimized for efficacy against toxoplasmosis during preclinical development. Medicines with enhanced efficacy as well as features that address the unique aspects of toxoplasmosis have the potential to greatly improve toxoplasmosis therapy. This review discusses the facets of toxoplasmosis that are pertinent to drug design and the advances, challenges, and current status of preclinical drug research for toxoplasmosis.

  3. Office of Technology Development`s Research, Development, Demonstration, Testing and Evaluation Mid-Year Program Review. Volume 1

    Energy Technology Data Exchange (ETDEWEB)

    1994-08-01

    This document presents brief summaries of waste management, remedial action, decommissioning/decontamination, and waste processing programs and issues currently being developed at Department of Energy Facilities.

  4. Manufacturing of cells and stacks for SOFC development, test and demonstration projects and SOFC hotbox design development

    Energy Technology Data Exchange (ETDEWEB)

    2008-09-15

    The purpose of this project is to support the continued SOFC development through manufacturing process optimization and manufacturing of SOFC cells and stacks. These cells and stacks will serve as a necessary base for the development activities and for the establishment of a number of test and demonstration activities. The manufacture will also help provide operating experience and reduce manufacturing cost. Another main focus of the manufacturing is to assure technical improvements and reliability. It is imperative to the eventual success of the technology that test and demonstration is carried out in the pre-market conditions that will exist for the next years in the three market segments targeted by TOFC (Distributed generation, micro CHP and APU incl. marine APU). Finally, the project also includes development activities focusing on the stack-system interface (hotbox design development) and on dealing with transients and start up and shut down times, which is of particular importance for APU and micro CHP applications. Three topics are addressed:1) Cell manufacture, including production development, capacity lift and manuf. of cells for test and demonstration; 2) Stack manufacture and test, including a test facility, stack manuf. and test of stacks in a system at HCV; 3) Hotbox design development, including design, prototype construction and testing. The progress of this project is documented. Major achievements are successful manufacture of adequate amounts of cells and stacks according to the application. Furthermore significant over-performance in design, construction and test of a methanol based hotbox prototype as well as publication of this. (au)

  5. Preclinical demonstration of synergistic Active Nutrients/Drug (AND combination as a potential treatment for malignant pleural mesothelioma.

    Directory of Open Access Journals (Sweden)

    Viviana Volta

    Full Text Available Malignant pleural mesothelioma (MPM is a poor prognosis disease lacking adequate therapy. We have previously shown that ascorbic acid administration is toxic to MPM cells. Here we evaluated a new combined therapy consisting of ascorbate/epigallocatechin-3-gallate/gemcitabine mixture (called AND, for Active Nutrients/Drug. In vitro effects of AND therapy on various MPM cell lines revealed a synergistic cytotoxic mechanism. In vivo experiments on a xenograft mouse model for MPM, obtained by REN cells injection in immunocompromised mice, showed that AND strongly reduced the size of primary tumor as well as the number and size of metastases, and prevented abdominal hemorrhage. Kaplan Meier curves and the log-rank test indicated a marked increase in the survival of AND-treated animals. Histochemical analysis of dissected tumors showed that AND induced a shift from cell proliferation to apoptosis in cancer cells. Lysates of tumors from AND-treated mice, analyzed with an antibody array, revealed decreased TIMP-1 and -2 expressions and no effects on angiogenesis regulating factors. Multiplex analysis for signaling protein phosphorylation exhibited inactivation of cell proliferation pathways. The complex of data showed that the AND treatment is synergistic in vitro on MPM cells, and blocks in vivo tumor progression and metastasization in REN-based xenografts. Hence, the AND combination is proposed as a new treatment for MPM.

  6. Two-Phase Flow Technology Developed and Demonstrated for the Vision for Exploration

    Science.gov (United States)

    Sankovic, John M.; McQuillen, John B.; Lekan, Jack F.

    2005-01-01

    NASA s vision for exploration will once again expand the bounds of human presence in the universe with planned missions to the Moon and Mars. To attain the numerous goals of this vision, NASA will need to develop technologies in several areas, including advanced power-generation and thermal-control systems for spacecraft and life support. The development of these systems will have to be demonstrated prior to implementation to ensure safe and reliable operation in reduced-gravity environments. The Two-Phase Flow Facility (T(PHI) FFy) Project will provide the path to these enabling technologies for critical multiphase fluid products. The safety and reliability of future systems will be enhanced by addressing focused microgravity fluid physics issues associated with flow boiling, condensation, phase separation, and system stability, all of which are essential to exploration technology. The project--a multiyear effort initiated in 2004--will include concept development, normal-gravity testing (laboratories), reduced gravity aircraft flight campaigns (NASA s KC-135 and C-9 aircraft), space-flight experimentation (International Space Station), and model development. This project will be implemented by a team from the NASA Glenn Research Center, QSS Group, Inc., ZIN Technologies, Inc., and the Extramural Strategic Research Team composed of experts from academia.

  7. Nevada Test Site-Directed Research, Development, and Demonstration. FY2005 report

    Energy Technology Data Exchange (ETDEWEB)

    Lewis, Will [comp.

    2006-09-01

    The Nevada Test Site-Directed Research, Development, and Demonstration (SDRD) program completed a very successful year of research and development activities in FY 2005. Fifty new projects were selected for funding this year, and five FY 2004 projects were brought to conclusion. The total funds expended by the SDRD program were $5.4 million, for an average per project cost of just under $100,000. Two external audits of SDRD accounting practices were conducted in FY 2005. Both audits found the program's accounting practices consistent with the requirements of DOE Order 413.2A, and one included the observation that the NTS contractor ''did an exceptional job in planning and executing year-start activities.'' Highlights for the year included: the filing of 18 invention disclosures for intellectual property generated by FY 2005 projects; programmatic adoption of 17 FY 2004 SDRD-developed technologies; participation in the tri-lab Laboratory Directed Research and Development (LDRD) and SDRD program review that was broadly attended by NTS, NNSA, LDRD, and U.S. Department of Homeland Security representatives; peer reviews of all FY 2005 projects; and the successful completion of 55 R&D projects, as presented in this report.

  8. Development and evaluation of an electronic drug and therapeutics bulletin.

    Science.gov (United States)

    Alderman, Christopher P

    2002-10-01

    To describe the development, implementation, and initial evaluation of a paperless drug and therapeutics bulletin that is distributed by electronic mail from the pharmacy department of an Australian teaching hospital. A standardized format for the bulletin was designed and approved in February 2001. The aim of the bulletin is to facilitate the timely dissemination of concise, factual information about issues of current interest in therapeutics, drug safety, and the cost-effective use of medicines. A simple and attractive graphic design was chosen, and the hospital's clinical pharmacists and drug information staff developed an initial bank of content during the period immediately preceding the launch. The bulletin is presented as a 1-page, read-only file in Word for Windows format and was initially distributed by electronic mail to all users of the hospital's computerized communication network. As the popularity of the bulletin increased, healthcare practitioners from outside of the hospital began to request permission for inclusion on the circulation list, and the content was frequently forwarded by E-mail to workers in other hospitals and community-based settings. The bulletin is now distributed to pharmacists around Australia via 2 separate moderated discussion lists, one of which provides an archive site for previous editions. Healthcare workers in Singapore, the US, Canada, and New Zealand also receive the bulletin, which is now also abstracted by a major Australian pharmacy journal. A readership survey (also electronically distributed) was used to seek feedback after the publication of the first 12 editions. Readers indicated a high level of satisfaction with the content, format, and frequency of distribution of the materials. Although the concept and execution of this project was relatively simple, an extensive literature review did not reveal any previously published reports describing this type of approach to the distribution of a pharmacy bulletin. The

  9. Research, Development and Demonstration of Micro-CHP System for Residential Applications

    Energy Technology Data Exchange (ETDEWEB)

    Karl Mayer

    2010-03-31

    ECR International and its joint venture company, Climate Energy, are at the forefront of the effort to deliver residential-scale combined heat and power (Micro-CHP) products to the USA market. Part of this substantial program is focused on the development of a new class of steam expanders that offers the potential for significantly lower costs for small-scale power generation technology. The heart of this technology is the scroll expander, a machine that has revolutionized the HVAC refrigerant compressor industry in the last 15 years. The liquid injected cogeneration (LIC) technology is at the core of the efforts described in this report, and remains an excellent option for low cost Micro-CHP systems. ECR has demonstrated in several prototype appliances that the concept for LIC can be made into a practical product. The continuing challenge is to identify economical scroll machine designs that will meet the performance and endurance requirements needed for a long life appliance application. This report describes the numerous advances made in this endeavor by ECR International. Several important advances are described in this report. Section 4 describes a marketing and economics study that integrates the technical performance of the LIC system with real-world climatic data and economic analysis to assess the practical impact that different factors have on the economic application of Micro-CHP in residential applications. Advances in the development of a working scroll steam expander are discussed in Section 5. A rigorous analytical assessment of the performance of scroll expanders, including the difficult to characterize impact of pocket to pocket flank leakage, is presented in Section 5.1. This is followed with an FEA study of the thermal and pressure induced deflections that would result from the normal operation of an advanced scroll expander. Section 6 describes the different scroll expanders and test fixtures developed during this effort. Another key technical

  10. Medication Development of Ibogaine as a Pharmacotherapy for Drug Dependencea.

    Science.gov (United States)

    Mash, Deborah C; Kovera, Craig A; Buck, Billy E; Norenberg, Michael D; Shapshak, Paul; Hearn, W Lee; Sanchez-Ramos, Juan

    1998-05-01

    The potential for deriving new psychotherapeutic medications from natural sources has led to renewed interest in rain forest plants as a source of lead compounds for the development of antiaddiction medications. Ibogaine is an indole alkaloid found in the roots of Tabernanthe iboga (Apocynaceae family), a rain forest shrub that is native to equatorial Africa. Ibogaine is used by indigenous peoples in low doses to combat fatigue, hunger and in higher doses as a sacrament in religious rituals. Members of American and European addict self-help groups have claimed that ibogaine promotes long-term drug abstinence from addictive substances, including psychostimulants and cocaine. Anecdotal reports attest that a single dose of ibogaine eliminates withdrawal symptoms and reduces drug cravings for extended periods of time. The purported antiaddictive properties of ibogaine require rigorous validation in humans. We have initiated a rising tolerance study using single administration to assess the safety of ibogaine for the treatment of cocaine dependency. The primary objectives of the study are to determine safety, pharmacokinetics and dose effects, and to identify relevant parameters of efficacy in cocaine-dependent patients. Pharmacokinetic and pharmacodynamic characteristics of ibogaine in humans are assessed by analyzing the concentration-time data of ibogaine and its desmethyl metabolite (noribogaine) from the Phase I trial, and by conducting in vitro experiments to elucidate the specific disposition processes involved in the metabolism of both parent drug and metabolite. The development of clinical safety studies of ibogaine in humans will help to determine whether there is a rationale for conducting efficacy trials in the future.

  11. Medication development of ibogaine as a pharmacotherapy for drug dependence.

    Science.gov (United States)

    Mash, D C; Kovera, C A; Buck, B E; Norenberg, M D; Shapshak, P; Hearn, W L; Sanchez-Ramos, J

    1998-05-30

    The potential for deriving new psychotherapeutic medications from natural sources has led to renewal interest in rain forest plants as a source of lead compounds for the development of antiaddiction medications. Ibogaine is an indole alkaloid found in the roots of Tabernanthe iboga (Apocynaceae family), a rain forest shrub that is native to equatorial Africa. Ibogaine is used by indigenous peoples in low doses to combat fatigue, hunger and in higher doses as a sacrament in religious rituals. Members of American and European addict self-help groups have claimed that ibogaine promotes long-term drug abstinence from addictive substances, including psychostimulants and cocaine. Anecdotal reports attest that a single dose of ibogaine eliminates withdrawal symptoms and reduces drug cravings for extended periods of time. The purported antiaddictive properties of ibogaine require rigorous validation in humans. We have initiated a rising tolerance study using single administration to assess the safety of ibogaine for treatment of cocaine dependency. The primary objectives of the study are to determine safety, pharmacokinetics and dose effects, and to identify relevant parameters of efficacy in cocaine-dependent patients. Pharmacokinetic and pharmacodynamic characteristics of ibogaine in humans are assessed by analyzing the concentration-time data of ibogaine and its desmethyl metabolite (noribogaine) from the Phase I trial, and by conducting in vitro experiments to elucidate the specific disposition processes involved in the metabolism of both parent drug and metabolite. The development of clinical safety studies of ibogaine in humans will help to determine whether there is a rationale for conducting efficacy trials in the future.

  12. The road to commercialization in Africa: lessons from developing the sickle-cell drug Niprisan.

    Science.gov (United States)

    Perampaladas, Kumar; Masum, Hassan; Kapoor, Andrew; Shah, Ronak; Daar, Abdallah S; Singer, Peter A

    2010-12-13

    Developing novel drugs from traditional medicinal knowledge can serve as a means to improve public health. Yet countries in sub-Saharan Africa face barriers in translating traditional medicinal knowledge into commercially viable health products. Barriers in moving along the road towards making a new drug available include insufficient manufacturing capacity; knowledge sharing between scientists and medical healers; regulatory hurdles; quality control issues; pricing and distribution; and lack of financing. The case study method was used to illustrate efforts to overcome these barriers during the development in Nigeria of Niprisan - a novel drug for the treatment of sickle cell anemia, a chronic blood disorder with few effective therapies. Building on the knowledge of a traditional medicine practitioner, Nigeria's National Institute for Pharmaceutical Research and Development (NIPRD) developed the traditional herbal medicine Niprisan. The commercialization of Niprisan reached a number of commercial milestones, including regulatory approval in Nigeria; securing US-based commercial partner XeChem; demonstrating clinical efficacy and safety; being awarded orphan drug status by the US Food and Drug Administration; and striking important relationships with domestic and international groups. Despite these successes, however, XeChem did not achieve mainstream success for Niprisan in Nigeria or in the United States. A number of reasons, including inconsistent funding and manufacturing and management challenges, have been put forth to explain Niprisan's commercial demise. As of this writing, NIPRD is considering options for another commercial partner to take the drug forward. Evidence from the Niprisan experience suggests that establishing benefit-sharing agreements, fostering partnerships with established research institutions, improving standardization and quality control, ensuring financial and managerial due diligence, and recruiting entrepreneurial leaders capable of

  13. The road to commercialization in Africa: lessons from developing the sickle-cell drug Niprisan

    Directory of Open Access Journals (Sweden)

    Daar Abdallah S

    2010-12-01

    Full Text Available Abstract Background Developing novel drugs from traditional medicinal knowledge can serve as a means to improve public health. Yet countries in sub-Saharan Africa face barriers in translating traditional medicinal knowledge into commercially viable health products. Barriers in moving along the road towards making a new drug available include insufficient manufacturing capacity; knowledge sharing between scientists and medical healers; regulatory hurdles; quality control issues; pricing and distribution; and lack of financing. The case study method was used to illustrate efforts to overcome these barriers during the development in Nigeria of Niprisan – a novel drug for the treatment of sickle cell anemia, a chronic blood disorder with few effective therapies. Discussion Building on the knowledge of a traditional medicine practitioner, Nigeria’s National Institute for Pharmaceutical Research and Development (NIPRD developed the traditional herbal medicine Niprisan. The commercialization of Niprisan reached a number of commercial milestones, including regulatory approval in Nigeria; securing US-based commercial partner XeChem; demonstrating clinical efficacy and safety; being awarded orphan drug status by the US Food and Drug Administration; and striking important relationships with domestic and international groups. Despite these successes, however, XeChem did not achieve mainstream success for Niprisan in Nigeria or in the United States. A number of reasons, including inconsistent funding and manufacturing and management challenges, have been put forth to explain Niprisan’s commercial demise. As of this writing, NIPRD is considering options for another commercial partner to take the drug forward. Summary Evidence from the Niprisan experience suggests that establishing benefit-sharing agreements, fostering partnerships with established research institutions, improving standardization and quality control, ensuring financial and managerial due

  14. What does systems biology mean for drug development?

    Science.gov (United States)

    Schrattenholz, André; Soskić, Vukić

    2008-01-01

    regard to a new focus on agents that modulate multiple targets simultaneously. Targeting cellular function as a system rather than on the level of the single protein molecule significantly increases the size of the drugable proteome and is expected to introduce novel classes of multi-target drugs with fewer adverse effects and toxicity. Multiple target approaches have recently been used to design medications against atherosclerosis, cancer, depression, psychosis and neurodegenerative diseases. A focussed approach towards "systemic" drugs will certainly require the development of novel computational and mathematical concepts for appropriate modelling of complex data and extraction of "screenable" information from biological systems essentially ruled by deterministic chaotic processes on a background of individual stochasticity.

  15. US Department of Energy, Office of Technology Development, mixed-waste treatment research, development, demonstration, testing, and evaluation

    International Nuclear Information System (INIS)

    Berry, J.B.; Backus, P.M.; Conley, T.B.; Coyle, G.J.; Lurk, P.W.; Wolf, S.M.

    1993-01-01

    Department of Energy (DOE) mixed waste is contaminated with both chemically hazardous and radioactive species. The DOE is responsible for regulating radioactive species while the Environmental Protection Agency (EPA) is responsible for regulating hazardous species. Dual regulations establish treatment standards and therefore affect the treatment technologies used to process mixed waste. This duality is reflected in technology development initiatives. Significant technology development has been conducted for either radioactive or hazardous waste, but limited technology development, specifically addressing mixed waste treatment issues, has been completed. Technology has not been designed, developed, demonstrated, or tested to produce a low-risk final waste form that increases the probability that the final waste form will be disposed

  16. Development and Characterization of Nanoembedded Microparticles for Pulmonary Delivery of Antitubercular Drugs against Experimental Tuberculosis.

    Science.gov (United States)

    Goyal, Amit Kumar; Garg, Tarun; Rath, Goutam; Gupta, Umesh Datta; Gupta, Pushpa

    2015-11-02

    The foremost objective of the present research study was to develop and evaluate the potential of rifampicin (RIF) and isoniazid (INH) loaded spray dried nanoembedded microparticles against experimental tuberculosis (TB). In this study, RIF-INH loaded various formulations (chitosan, guar gum, mannan, and guar gum coated chitosan) were prepared by spray drying and characterized on the basis of in vitro as well as in vivo studies. Results showed that guar gum spray dried particles showed uniform size distribution with smooth surface as compare to mannan formulations. Guar gum batches exhibited excellent flow ability attributed to their optimum moisture content and uniform size distribution. The drug release showed the biphasic pattern of release, i.e., initial burst followed by a sustained release pattern. The preferential uptake of guar gum coated formulations suggested the presence and selective uptake capability of mannose moiety to the specific cell surface of macrophages. In vivo lung distribution study showed that guar gum coated chitosan (GCNP) batches demonstrated prolonged residence at the target site and thereby improve the therapeutic utility of drug with a significant reduction in systemic toxicity. Optimized drug loaded GCNP formulation has resulted in almost 5-fold reduction of the number of bacilli as compared to control group. Histopathology study also demonstrated that none of the treated groups show any evidence of lung tissue abnormality. Hence, GCNPs could be a promising carrier for selective delivery of antitubercular drugs to alveolar macrophages with the interception of minimal side effects, for efficient management of TB.

  17. Interdisciplinary researches for potential developments of drugs and natural products

    Directory of Open Access Journals (Sweden)

    Arunrat Chaveerach

    2017-04-01

    Full Text Available Developments of drugs or natural products from plants are possibly made, simple to use and lower cost than modern drugs. The development processes can be started with studying local wisdom and literature reviews to choose the plants which have long been used in diverse areas, such as foods, traditional medicine, fragrances and seasonings. Then those data will be associated with scientific researches, namely plant collection and identification, phytochemical screening by gas chromatography-mass spectrometry, pharmacological study/review for their functions, and finally safety and efficiency tests in human. For safety testing, in vitro cell toxicity by cell viability assessment and in vitro testing of DNA breaks by the comet assay in human peripheral blood mononuclear cells can be performed. When active chemicals and functions containing plants were chosen with safety and efficacy for human uses, then, the potential medicinal natural products will be produced. Based on these procedures, the producing cost will be cheaper and the products can be evaluated for their clinical properties. Thus, the best and lowest-priced medicines and natural products can be distributed worldwide.

  18. Drug discovery and development tomorrow -- changing the mindset.

    Science.gov (United States)

    Coleman, Robert A

    2009-09-01

    Today's drug discovery and development paradigm is not working, and something needs to be done about it. There is good reason to believe that a move away from reliance on animal surrogates for human subjects in the Pharma Industry's R&D programmes could provide an important step forward. However, no serious move will be made in that direction until there is some hard evidence that it will be rewarded with improved productivity outcomes. The Safer Medicines Trust are proposing that a study be undertaken, involving a range of drugs that have been approved for human use, but have subsequently proved to have limitations in terms of safety and/or efficacy. The aim is to determine the efficiency of a battery of human-based test methods to identify a compound's safety and efficacy profiles, and to compare this with that of the more traditional, largely animal-based methods that were employed in their original development. Should such an approach prove more reliable, the authorities will be faced with important decisions relating to the role of human biological test data in regulatory submissions, while the Pharma Industry will be faced with the key logistical issue of how to acquire the human biomaterials necessary to make possible the routine application of such test methods. 2009 FRAME.

  19. Interdisciplinary researches for potential developments of drugs and natural products

    Institute of Scientific and Technical Information of China (English)

    Arunrat Chaveerach; Runglawan Sudmoon; Tawatchai Tanee

    2017-01-01

    Developments of drugs or natural products from plants are possibly made,simple to use and lower cost than modern drugs.The development processes can be started with studying local wisdom and literature reviews to choose the plants which have long been used in diverse areas,such as foods,traditional medicine,fragrances and seasonings.Then those data will be associated with scientific researches,namely plant collection and identification,phytochemical screening by gas chromatography-mass spectrometry,pharmacological study/review for their functions,and finally safety and efficiency tests in human.For safety testing,in vitro cell toxicity by cell viability assessment and in vitro testing of DNA breaks by the comet assay in human peripheral blood mononuclear cells can be performed.When active chemicals and functions containing plants were chosen with safety and efficacy for human uses,then,the potential medicinal natural products will be produced.Based on these procedures,the producing cost will be cheaper and the products can be evaluated for their clinical properties.Thus,the best and lowest-priced medicines and natural products can be distributed worldwide.

  20. HAXWDDD (Hazardous Waste Development, Demonstration, and Disposal) - An exercise in corporate planning

    International Nuclear Information System (INIS)

    McGinnis, C.P.; Pechin, W.H.

    1988-01-01

    The Hazardous Waste Development, Demonstration, and Disposal (HAZWDDD) program is a corporate initiative that is coordinated between Martin Marietta Energy Systems, Inc. (Energy Systems), and the US Department of Energy's Oak Ridge Operations Office (DOE-ORO). The major objective of HAZWDDD is to develop a comprehensive management strategy for the hazardous and mixed wastes generated by the five Energy Systems installations. This program is of prime importance because federal and state regulations for handling hazardous wastes are becoming increasingly stringent and the generator of such wastes retains legally mandated liability for their disposal indefinitely. In addition, no acceptable method is currently available for handling mixed (hazardous and radioactive) wastes. Both Energy Systems corporate management and DOE-ORO management have recognized the seriousness of these problems and have established several programs to determine acceptable courses of action. A plan has been developed for low-level radioactive waste (LLW), and an active dialogue pertaining to LLW is maintained with the state and federal regulators. During 1986, DOE-ORO and Energy Systems identified the need for a plan to address hazardous and mixed wastes. Each installation supports the concept of HAZWDDD through funding and the development of individual HAZWDDD implementation plans. A corporate plan is being developed to integrate the issues discussed in the five installation plans. This paper describes: (1) the approach taken in collecting the necessary information for the plan; (2) some of the techniques used in analyzing the information provided; (3) preliminary data that have been collected in preparation of this plan, (4) the identification of common concerns and issues, and (5) the integration of this information into a corporate approach to mixed and hazardous waste management

  1. Industrial advanced turbine systems: Development and demonstration. Quarterly report, October 1--December 31, 1997

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-06-01

    The US DOE has initiated a program for advanced turbine systems (ATS) that will serve industrial power generation markets. The ATS will provide ultra-high efficiency, environmental superiority, and cost competitiveness. The Industrial ATS Development and Demonstration program is a multi-phased effort. Solar Turbines Incorporated (Solar) has participated in Phases 1 and 2 of the program. On September 14, 1995 Solar was awarded a Cooperative Agreement for Phases 3 and 4 of the program. Phase 3 of the work is separated into two subphases: Phase 3A entails Component Design and Development; Phase 3B will involve Integrated Subsystem Testing. Phase 4 will cover Host Site Testing. Forecasts call for completion of the program within budget as originally estimated. Scheduled completion is forecasted to be approximately 3 years late to original plan. This delay has been intentionally planned in order to better match program tasks to the anticipated availability of DOE funds. To ensure the timely realization of DOE/Solar program goals, the development schedule for the smaller system (Mercury 50) and enabling technologies has been maintained, and commissioning of the field test unit is scheduled for May of 2000. As of the end of the reporting period work on the program is 24.7% complete (22.8% last quarter). Work on the Mercury 50 development and ATS technology development portions of the program (WBS 10000 et seq) is 41.6% complete. Although a great amount of work occurred in the quarter, a significant amount of this work entailed the revision and rerelease of several Mercury 50 drawings. Estimates of percent compete are based upon milestones completed. In order to maintain objectivity in assessing schedule progress, Solar uses a 0/100 percent complete assumption for milestones rather than subjectively estimating progress toward completion of milestones. Cost and schedule variation information is provided in Section 4.0 Program Management.

  2. Development and pilot demonstration program of a waste minimization plan at Argonne National Laboratory

    International Nuclear Information System (INIS)

    Peters, R.W.; Wentz, C.A.; Thuot, J.R.

    1991-01-01

    In response to US Department of Energy directives, Argonne National Laboratory (ANL) has developed a waste minimization plan aimed at reducing the amount of wastes at this national research and development laboratory. Activities at ANL are primarily research- oriented and as such affect the amount and type of source reduction that can be achieved at this facility. The objective of ANL's waste minimization program is to cost-effectively reduce all types of wastes, including hazardous, mixed, radioactive, and nonhazardous wastes. The ANL Waste Minimization Plan uses a waste minimization audit as a systematic procedure to determine opportunities to reduce or eliminate waste. To facilitate these audits, a computerized bar-coding procedure is being implemented at ANL to track hazardous wastes from where they are generated to their ultimate disposal. This paper describes the development of the ANL Waste Minimization Plan and a pilot demonstration of the how the ANL Plan audited the hazardous waste generated within a selected divisions of ANL. It includes quantitative data on the generation and disposal of hazardous waste at ANL and describes potential ways to minimize hazardous wastes. 2 refs., 5 figs., 8 tabs

  3. Development of demonstration facility design technology for advanced nuclear fuel cycle process

    International Nuclear Information System (INIS)

    Cho, Il Je; You, G. S.; Choung, W. M.; Lee, E. P.; Hong, D. H.; Lee, W. K.; Ku, J. H.; Moon, S. I.; Kwon, K. C.; Lee, K. I. and other

    2012-04-01

    PRIDE Facility, pyroprocess mock-up facility, is the first facility that is operated in inert atmosphere in the country. By using the facility, the functional requirements and validity of pyroprocess technology and facility related to the advanced fuel cycle can be verified with a low cost. Then, PRIDE will contribute to evaluate the technology viability, proliferation resistance and possibility of commercialization of the pyroprocess technology. It is essential to develop design technologies for the advanced nuclear fuel cycle demonstration facilities and complete the detailed design of PRIDE facility with capabilities of the stringent inert atmosphere control, fully remote operation which are necessary to develop the high-temperature molten salts technology. For these, it is necessary to design the essential equipment of large scale inert cell structure and the control system to maintain the inert atmosphere, and evaluate the safety. To construct the hot cell system which is appropriate for pyroprocess, some design technologies should be developed, which include safety evaluation for effective operation and maintenance, radiation safety analysis for hot cell, structural analysis, environmental evaluation, HVAC systems and electric equipment

  4. Industrial Advanced Turbine Systems: Development and Demonstration. Annual report, September 14, 1995--September 30, 1996

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-12-31

    The U.S. Department of Energy (DOE) has initiated a program for advanced turbine systems (ATS) that will serve industrial power generation markets. The objective of the cooperative agreements granted under the program is to join the DOE with industry in research and development that will lead to commercial offerings in the private sector. The ATS will provide ultra-high efficiency, environmental superiority, and cost competitiveness. The ATS will foster (1) early market penetration that enhances the global competitiveness of U.S. industry, (2) public health benefits resulting from reduced exhaust gas emissions of target pollutants, (3) reduced cost of power used in the energy-intensive industrial marketplace and (4) the retention and expansion of the skilled U.S. technology base required for the design, development and maintenance of state-of-the-art advanced turbine products. The Industrial ATS Development and Demonstration program is a multi-phased effort. Solar Turbines Incorporated (Solar) has participated in Phases 1 and 2 of the program. On September 14, 1995 Solar was awarded a Cooperative Agreement for Phases 3 and 4 of the program (DE-FC21-95MC31173) by the DOE`s Office of Energy Efficiency and Renewable Energy (EE). Technical administration of the Cooperative Agreement will be provided from EE`s Chicago Operations Office. Contract administration of the Cooperative Agreement will be provided from DOE`s Office of Fossil Energy, Morgantown Energy Technology Center (METC).

  5. UTX and UTY demonstrate histone demethylase-independent function in mouse embryonic development.

    Directory of Open Access Journals (Sweden)

    Karl B Shpargel

    2012-09-01

    Full Text Available UTX (KDM6A and UTY are homologous X and Y chromosome members of the Histone H3 Lysine 27 (H3K27 demethylase gene family. UTX can demethylate H3K27; however, in vitro assays suggest that human UTY has lost enzymatic activity due to sequence divergence. We produced mouse mutations in both Utx and Uty. Homozygous Utx mutant female embryos are mid-gestational lethal with defects in neural tube, yolk sac, and cardiac development. We demonstrate that mouse UTY is devoid of in vivo demethylase activity, so hemizygous X(Utx- Y(+ mutant male embryos should phenocopy homozygous X(Utx- X(Utx- females. However, X(Utx- Y(+ mutant male embryos develop to term; although runted, approximately 25% survive postnatally reaching adulthood. Hemizygous X(+ Y(Uty- mutant males are viable. In contrast, compound hemizygous X(Utx- Y(Uty- males phenocopy homozygous X(Utx- X(Utx- females. Therefore, despite divergence of UTX and UTY in catalyzing H3K27 demethylation, they maintain functional redundancy during embryonic development. Our data suggest that UTX and UTY are able to regulate gene activity through demethylase independent mechanisms. We conclude that UTX H3K27 demethylation is non-essential for embryonic viability.

  6. Development of active CFRP/metal laminates and their demonstrations in complicated forms

    Science.gov (United States)

    Asanuma, H.; Nakata, T.; Tanaka, T.; Imori, M.; Haga, O.

    2006-03-01

    This paper describes development of high performance CFRP/metal active laminates and demonstrations of them in complicated forms. Various types of the laminates were made by hot-pressing of an aluminum, aluminum alloys, a stainless steel and a titanium for the metal layer as a high CTE material, a unidirectional CFRP prepreg as a low CTE/electric resistance heating material, a unidirectional KFRP prepreg as a low CTE/insulating material. The aluminum and its alloy type laminates have almost the same and the highest room temperature curvatures and they linearly change with increasing temperature up to their fabrication temperature. The curvature of the stainless steel type jumps from one to another around its fabrication temperature, whereas the titanium type causes a double curvature and its change becomes complicated. The output force of the stainless steel type attains the highest of the three under the same thickness. The aluminum type successfully increased its output force by increasing its thickness and using its alloys. The electric resistance of the CFRP layer can be used to monitor the temperature, that is, the curvature of the active laminate because the curvature is a function of temperature. The aluminum type active laminate was made into complicated forms, that is, a hatch, a stack, a coil and a lift types, and their actuation performances were successfully demonstrated.

  7. Experimental Development and Demonstration of Ultrasonic Measurement Diagnostics for Sodium Fast Reactor Thermal-hydraulics

    Energy Technology Data Exchange (ETDEWEB)

    Tokuhiro, Akira; Jones, Byron

    2013-09-13

    This research project will address some of the principal technology issues related to sodium-cooled fast reactors (SFR), primarily the development and demonstration of ultrasonic measurement diagnostics linked to effective thermal convective sensing under normatl and off-normal conditions. Sodium is well-suited as a heat transfer medium for the SFR. However, because it is chemically reactive and optically opaque, it presents engineering accessibility constraints relative to operations and maintenance (O&M) and in-service inspection (ISI) technologies that are currently used for light water reactors. Thus, there are limited sensing options for conducting thermohydraulic measurements under normal conditions and off-normal events (maintenance, unanticipated events). Acoustic methods, primarily ultrasonics, are a key measurement technology with applications in non-destructive testing, component imaging, thermometry, and velocimetry. THis project would have yielded a better quantitative and qualitative understanding of the thermohydraulic condition of solium under varied flow conditions. THe scope of work will evaluate and demonstrate ultrasonic technologies and define instrumentation options for the SFR.

  8. Antibody-drug conjugates for cancer therapy: The technological and regulatory challenges of developing drug-biologic hybrids.

    Science.gov (United States)

    Hamilton, Gregory S

    2015-09-01

    Antibody-drug conjugates (ADCs) are a new class of therapeutic agents that combine the targeting ability of monoclonal antibodies (mAbs) with small molecule drugs. The combination of a mAb targeting a cancer-specific antigen with a cytotoxin has tremendous promise as a new type of targeted cancer therapy. Two ADCs have been approved and many more are in clinical development, suggesting that this new class of drugs is coming to the forefront. Because of their unique nature as biologic-small drug hybrids, ADCs are challenging to develop, from both the scientific and regulatory perspectives. This review discusses both these aspects in current practice, and surveys the current state of the art of ADC drug development. Copyright © 2015 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

  9. Research, development, and demonstration of nickel-iron batteries for electric vehicle propulsion. Annual report, 1980

    Energy Technology Data Exchange (ETDEWEB)

    1981-03-01

    The objective of the Eagle-Picher nickel-iron battery program is to develop a nickel-iron battery for use in the propulsion of electric and electric-hybrid vehicles. To date, the program has concentrated on the characterization, fabrication and testing of the required electrodes, the fabrication and testing of full-scale cells, and finally, the fabrication and testing of full-scale (270 AH) six (6) volt modules. Electrodes of the final configuration have now exceeded 1880 cycles and are showing minimal capacity decline. Full-scale cells have presently exceeded 600 cycles and are tracking the individual electrode tests almost identically. Six volt module tests have exceeded 500 cycles, with a specific energy of 48 Wh/kg. Results to date indicate the nickel-iron battery is beginning to demonstrate the performance required for electric vehicle propulsion.

  10. Development of a Terrestrial Modeling System: The China-wide Demonstration

    Science.gov (United States)

    Duan, Q.; Dai, Y.; Zheng, X.; Ye, A.; Chen, Z.; Shangguang, W.

    2010-12-01

    A terrestrial modeling system (TMS) is being developed at Beijing Normal University. The purposes of TMS are (1) to provide a land surface parameterization scheme fully capable of being coupled with and climate and Earth system models of different scales; (2) to provide a standalone platform for simulation and prediction of land surface processes; and (3) to provide a platform for studying human-Earth system interactions. This system will build on and extend existing capabilities at BNU, including the Common Land Model (CoLM) system, high-resolution atmospheric forcing data sets, high-resolution soil and vegetation data sets, and high-performance computing facilities and software. This presentation describes the system design and demonstrates the initial capabilities of TMS in simulating water and energy fluxes over the continental China for a multi-year period.

  11. Denmark - supplier of competitive offshore wind solutions. Megavind's strategy for offshore wind research, development and demonstration

    Energy Technology Data Exchange (ETDEWEB)

    2010-12-15

    In May 2006, the Danish Government presented a report on promoting environmentally effective technology and established a number of innovative partnerships. The partnerships intend to strengthen public-private cooperation between the state, industry, universities and venture capital to accelerate innovation for a number of green technologies. The partnership for wind energy is called Megavind. Megavind's strategy for offshore wind describes the offshore challenges and suggests research, development and demonstration (RD and D) priorities to enable offshore wind power become to competitive with other energy technologies. The strategy lists key recommendations as well as key thematic priorities and for each of these a number of RD and D priorities. Under each thematic priority references are made to the European Strategic Energy Technology plan (SET-plan), which prioritises offshore wind RD and D in Europe. (LN)

  12. Identification of sites for the low-level waste disposal development and demonstration program

    International Nuclear Information System (INIS)

    Ketelle, R.H.; Lee, D.W.

    1988-04-01

    This report presents the results of site selection studies for potential low-level radioactive waste disposal sites on the Oak Ridge Reservation (ORR). Summaries of the site selection procedures used and results of previous site selection studies on the ORR are included. This report includes recommendations of sites for demonstration of shallow land burial using engineered trench designs and demonstration of above-grade disposal using design concepts similar to those used in tumulus disposal. The site selection study, like its predecessor (ORNL/TM-9717, Use of DOE Site Selection Criteria for Screening Low-Level Waste Disposal Sites on the Oak Ridge Reservation), involved application of exclusionary site screening criteria to the region of interest to eliminate unacceptable areas from consideration. Also like the previous study, the region of interest for this study was limited to the Oak Ridge Department of Energy Reservation. Reconnaissance-level environmental data were used in the study, and field inspections of candidate sites were made to verify the available reconnaissance data. Five candidate sites, all underlain by Knox dolomite residuum and bedrock, were identified for possible development of shallow land burial facilities. Of the five candidate sites, the West Chestnut site was judged to be best suited for deployment of the shallow land burial technology. Three candidate sites, all underlain by the Conasauga Group in Bear Creek Valley, were identified for possible development of above-grade disposal technologies. Of the three sites identified, the Central Bear Creek Valley site lying between State Route 95 and Gum Hollow Road was ranked most favorable for deployment of the above-grade disposal technology

  13. Affordable Development and Demonstration of a Small NTR Engine and Stage: How Small is Big Enough?

    Science.gov (United States)

    Borowski, Stanley K.; Sefcik, Robert J.; Fittje, James E.; McCurdy, David R.; Qualls, Arthur L.; Schnitzler, Bruce G.; Werner, James E.; Weitzberg (Abraham); Joyner, Claude R.

    2015-01-01

    The Nuclear Thermal Rocket (NTR) derives its energy from fission of uranium-235 atoms contained within fuel elements that comprise the engine's reactor core. It generates high thrust and has a specific impulse potential of approximately 900 seconds - a 100% increase over today's best chemical rockets. The Nuclear Thermal Propulsion (NTP) project, funded by NASA's AES program, includes five key task activities: (1) Recapture, demonstration, and validation of heritage graphite composite (GC) fuel (selected as the "Lead Fuel" option); (2) Engine Conceptual Design; (3) Operating Requirements Definition; (4) Identification of Affordable Options for Ground Testing; and (5) Formulation of an Affordable Development Strategy. During FY'14, a preliminary DDT&E plan and schedule for NTP development was outlined by GRC, DOE and industry that involved significant system-level demonstration projects that included GTD tests at the NNSS, followed by a FTD mission. To reduce cost for the GTD tests and FTD mission, small NTR engines, in either the 7.5 or 16.5 klbf thrust class, were considered. Both engine options used GC fuel and a "common" fuel element (FE) design. The small approximately 7.5 klbf "criticality-limited" engine produces approximately 157 megawatts of thermal power (MWt) and its core is configured with parallel rows of hexagonal-shaped FEs and tie tubes (TTs) with a FE to TT ratio of approximately 1:1. The larger approximately 16.5 klbf Small Nuclear Rocket Engine (SNRE), developed by LANL at the end of the Rover program, produces approximately 367 MWt and has a FE to TT ratio of approximately 2:1. Although both engines use a common 35 inch (approximately 89 cm) long FE, the SNRE's larger diameter core contains approximately 300 more FEs needed to produce an additional 210 MWt of power. To reduce the cost of the FTD mission, a simple "1-burn" lunar flyby mission was considered to reduce the LH2 propellant loading, the stage size and complexity. Use of existing and

  14. Developing and implementing a positive behavioral reinforcement intervention in prison-based drug treatment: Project BRITE.

    Science.gov (United States)

    Burdon, William M; St De Lore, Jef; Prendergast, Michael L

    2011-09-01

    Within prison settings, the reliance on punishment for controlling inappropriate or noncompliant behavior is self-evident. What is not so evident is the similarity between this reliance on punishment and the use of positive reinforcements to increase desired behaviors. However, seldom do inmates receive positive reinforcement for engaging in prosocial behaviors or, for inmates receiving drug treatment, behaviors that are consistent with or support their recovery. This study provides an overview of the development and implementation of a positive behavioral reinforcement intervention in male and female prison-based drug treatment programs. The active involvement of institutional staff, treatment staff, and inmates enrolled in the treatment programs in the development of the intervention along with the successful branding of the intervention were effective at promoting support and participation. However, these factors may also have ultimately impacted the ability of the randomized design to reliably demonstrate the effectiveness of the intervention.

  15. Liposomal Drug Product Development and Quality: Current US Experience and Perspective.

    Science.gov (United States)

    Kapoor, Mamta; Lee, Sau L; Tyner, Katherine M

    2017-05-01

    Research in the area of liposomes has grown substantially in the past few decades. Liposomes are lipid bilayer structures that can incorporate drug substances to modify the drug's pharmacokinetic profile thereby improving drug delivery. The agency has received over 400 liposomal drug product submissions (excluding combination therapies), and there are currently eight approved liposomal drug products on the US market. In order to identify the pain points in development and manufacturing of liposomal drug products, a retrospective analysis was performed from a quality perspective on submissions for new and generic liposomal drug products. General analysis on liposomal drug product submissions was also performed. Results indicated that 96% of the submissions were Investigational New Drug (IND) applications, 3% were New Drug Applications (NDAs), and the remaining 1% was Abbreviated New Drug Applications (ANDAs). Doxorubicin hydrochloride was the most commonly used drug substance incorporated into the liposomes (31%). The majority of the liposomal products were administered via intravenous route (84%) with cancer (various types) being the most common indication (63%). From a quality perspective, major challenges during the development of liposomal drug products included identification and (appropriate) characterization of critical quality attributes of liposomal drug products and suitable control strategies during product development. By focusing on these areas, a faster and more efficient development of liposomal drug products may be achieved. Additionally, in this way, the drug review process for such products can be streamlined.

  16. Industrial advanced turbine systems: Development and demonstration. Annual report, October 1, 1996--September 30, 1997

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-12-31

    The US DOE has initiated a program for advanced turbine systems (ATS) that will serve industrial power generation markets. The ATS will provide ultra-high efficiency, environmental superiority, and cost competitiveness. The ATS will foster (1) early market penetration that enhances the global competitiveness of US industry, (2) public health benefits resulting from reduced exhaust gas emissions of target pollutants, (3) reduced cost of power used in the energy-intensive industrial marketplace and (4) the retention and expansion of the skilled US technology base required for the design, development and maintenance of state-of-the-art advanced turbine products. The Industrial ATS Development and Demonstration program is a multi-phased effort. Solar Turbines Incorporated (Solar) has participated in Phases 1 and 2 of the program. On September 14, 1995 Solar was awarded a Cooperative Agreement for Phases 3 and 4 of the program. Phase 3 of the work is separated into two subphases: Phase 3A entails Component Design and Development Phase 3B will involve Integrated Subsystem Testing. Phase 4 will cover Host Site Testing. Forecasts call for completion of the program within budget as originally estimated. Scheduled completion is forecasted to be approximately 3 years late to original plan. This delay has been intentionally planned in order to better match program tasks to the anticipated availability of DOE funds. To ensure the timely realization of DOE/Solar program goals, the development schedule for the smaller system (Mercury 50) and enabling technologies has been maintained, and commissioning of the field test unit is scheduled for May of 2000. As of the end of the reporting period work on the program is 22.80% complete based upon milestones completed. This measurement is considered quite conservative as numerous drawings on the Mercury 50 are near release. Variance information is provided in Section 4.0-Program Management.

  17. 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.

  18. The role of globalization in drug development and access to orphan drugs: orphan drug legislation in the US/EU and in Latin America.

    Science.gov (United States)

    Arnold, Renée J G; Bighash, Lida; Bryón Nieto, Alejandro; Tannus Branco de Araújo, Gabriela; Gay-Molina, Juan Gabriel; Augustovski, Federico

    2015-01-01

    Compared to a decade ago, nearly three times as many drugs for rare diseases are slated for development. This article addresses the market access issues associated with orphan drug status in Europe and the United States in contrast to the legislation in five Latin American (LA) countries that have made strides in this regard--Mexico, Brazil, Colombia, Chile and Argentina. Based on the success of orphan drug legislation in the EU and US, LA countries should strive to adopt similar strategies with regard to rare diseases and drug development. With the implementation of new targeted regulations, reimbursement strategies, and drug approvals, accessibility to treatment will be improved for people afflicted with rare diseases in these developing countries.

  19. 77 FR 11133 - Draft Guidance for Industry on Complicated Urinary Tract Infections: Developing Drugs for...

    Science.gov (United States)

    2012-02-24

    ...] Draft Guidance for Industry on Complicated Urinary Tract Infections: Developing Drugs for Treatment... Urinary Tract Infections: Developing Drugs for Treatment.'' The purpose of this guidance is to assist sponsors in the clinical development of drugs for the treatment of complicated urinary tract infections (c...

  20. Development of a hardware-in-the-loop testbed to demonstrate multiple spacecraft operations in proximity

    Science.gov (United States)

    Eun, Youngho; Park, Sang-Young; Kim, Geuk-Nam

    2018-06-01

    This paper presents a new state-of-the-art ground-based hardware-in-the-loop test facility, which was developed to verify and demonstrate autonomous guidance, navigation, and control algorithms for space proximity operations and formation flying maneuvers. The test facility consists of two complete spaceflight simulators, an aluminum-based operational arena, and a set of infrared motion tracking cameras; thus, the testbed is capable of representing space activities under circumstances prevailing on the ground. The spaceflight simulators have a maximum of five-degree-of-freedom in a quasi-momentum-free environment, which is produced by a set of linear/hemispherical air-bearings and a horizontally leveled operational arena. The tracking system measures the real-time three-dimensional position and attitude to provide state variables to the agents. The design of the testbed is illustrated in detail for every element throughout the paper. The practical hardware characteristics of the active/passive measurement units and internal actuators are identified in detail from various perspectives. These experimental results support the successful development of the entire facility and enable us to implement and verify the spacecraft proximity operation strategy in the near future.

  1. Good Practice Policy Framework for Energy Technology Research Development and Demonstration (RD and D)

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2011-07-01

    The transition to a low carbon economy clearly requires accelerating energy innovation and technology adoption. Governments have an important role in this context. They can help by establishing the enabling environment in which innovation can thrive, and within which effective and efficient policies can be identified, with the specific goal of advancing research, development, demonstration and, ultimately, deployment (RDD&D) of clean energy technologies. At the front end of the innovation process, significant increases in, and restructuring of, global RD&D efforts will be required, combined with well-targeted government RD&D policies. The development of a clear policy framework for energy technology RD&D, based on good practices, should include six elements: Coherent energy RD&D strategy and priorities; Adequate government RD&D funding and policy support; Co-ordinated energy RD&D governance; Strong collaborative approach, engaging industry through public private partnerships (PPPs); Effective RD&D monitoring and evaluation; and Strategic international collaboration. While countries have been favouring certain technologies over others, based on decisions on which areas are to receive funding, clear priorities are not always determined through structured analysis and documented processes. A review of stated energy RD&D priorities, based on announced technology programmes and strategies, and recent spending trends reveals some important deviations from stated priorities and actual RD&D funding.

  2. A National Plan for Energy Research, Development and Demonstration: Creating Energy Choices for the Future (1976)

    Energy Technology Data Exchange (ETDEWEB)

    Seamans, Jr., Robert C. [Energy Research and Development Administration (ERDA), Washington, DC (United States)

    1976-04-15

    This is the first annual update of the initial report submitted to you in June 1975 (ERDA-48), and complies with the requirements of Section 15 of the Federal Nonnuclear Energy Research and Development Act of 1974. This report represents an evolution in approach over the previous document. ERDA's proposed National Plan has been expanded in scope and depth of coverage and the basic goals and strategy are refined, but remain essentially intact. The Plan summarizes ERDA's current views on the energy technologies the Nation will need to achieve longer-term energy independence, specifically: The paramount role of the private sector in the development and commercialization of new energy technologies is addressed; Conservation (energy efficiency) technologies are singled out for increased attention and are now ranked with several supply technologies as being of the highest priority for national action; The President's 1977 budget requests a large increase - 30% over 1976 - in funding for energy RD&D with particular emphasis on accelerating energy RD&D programs directed at achieving greater long-term energy independence, encouraging cost-sharing with private industry and avoiding the undertaking of RD&D more appropriately the responsibility of the private sector, and supporting the commercial demonstration of synthetic fuel production by providing loan guarantees beginning in FY 76; Federal programs to assist industry in accelerating the market penetration of energy technologies with near-term potential are a key element of the Plan.

  3. Strategy for research, development and demonstration of thermal biomass gasification in Denmark

    Energy Technology Data Exchange (ETDEWEB)

    Hansen, Morten Tony

    2011-12-15

    Technology for thermal gasification of biomass is one of the key elements to make the vision of an energy system without fossil fuels a reality. Gasification technology can enhance the flexibility needed to maintain a future energy system with a large share of wind power. Furthermore, gasification has advantages in terms of ash recycling and utilisation of vast but challenging biomass residues. Danish companies are globally well advanced with this technology and the market for gasification technology is great in both Denmark and abroad. There is a clear need for targeted technology RD and D in order to reach the last stretch to a commercial breakthrough. The project ''Strategy for research, development and demonstration of thermal biomass gasification in Denmark'' is the Danish industrys contribution to the development of biomass gasification and goes into detail with the RD and D needs. The project has been conducted by FORCE Technology for DI Bioenergy with funding from EUDP, Energinet.dk, DI Bioenergy and FORCE Technology and five stakeholder companies. (LN)

  4. Power-up of Fugen reactor and development of demonstration plant

    International Nuclear Information System (INIS)

    Sawai, Sadamu; Akebi, Michio; Yazaki, Akira.

    1979-06-01

    The Fugen Nuclear Power Station is the 165 MWe prototype plant characterized by heavy water-moderated, boiling light water-cooled, pressure tube type, and was developed by the Power Reactor and Nuclear Fuel Development Corporation, Japan. The plant went into commercial operation on March 20, 1979, in Tsuruga, Fukui Prefecture. Some delay in the overall schedule occurred due to the shortage of cement caused by the oil crisis, more stringent regulations as the result of stress corrosion cracking experienced in BWRs, and design modifications. All functional tests, the final check-up of the whole plant, and remaining modifying works had been completed by March 10, 1978. The minimum criticality was achieved with 22 mixed oxide fuel assemblies on March 20, 1978. Thereafter, the tests on reactor physics, plant dynamics, the performances of components and systems, and radiation and water chemistry have been carried out. 5 MWe was sent to grid system for the first time on July 29, 1978. The commercial operation of the plant was licenced by the Government on March 30, 1979. The conceptual design of the 600 MWe demonstration plant was finished in early 1979, and the detailed design is to be carried out in 1979 and 1980. The main design principle was incorporated in the conceptual design, but some modifications are to be made to reduce the power cost and to facilitate the easy maintenance. (Kako, I.)

  5. Real options valuation of US federal renewable energy research, development, demonstration, and deployment

    International Nuclear Information System (INIS)

    Siddiqui, Afzal S.; Marnay, Chris; Wiser, Ryan H.

    2007-01-01

    Benefits analysis of US Federal government research, development, demonstration, and deployment (RD 3 ) programmes for renewable energy (RE) technology improvement typically employs a deterministic forecast of the cost and performance of renewable and non-renewable fuels. The benefits estimate for the programme derives from the difference between two forecasts, with and without the RD 3 programme in place. Three deficiencies of this approach are that it ignores: (1) uncertainty in the cost of non-renewable energy (NRE); (2) the possibility of adjustment to the RD 3 effort commensurate with the evolving state of the world; and (3) the underlying technical risk associated with RD 3 . In this paper, an intuitive approach to determining the option value of RE RD 3 is developed. This approach seeks to tackle the first two deficiencies noted above by providing an estimate via a compound real option of an RE RD 3 programme in a future with uncertain NRE costs. A binomial lattice reveals the economic intuition underlying the decision-making process, while a numerical example illustrates the option components embedded in a simplified representation of current US Federal RE RD 3

  6. Analysis of Drug Development Paradigms for Immune Checkpoint Inhibitors.

    Science.gov (United States)

    Jardim, Denis L; de Melo Gagliato, Débora; Giles, Francis J; Kurzrock, Razelle

    2018-04-15

    Immune checkpoint inhibitors have unique toxicities and response kinetics compared with cytotoxic and gene-targeted anticancer agents. We investigated the impact of innovative/accelerated immunotherapy drug development/approval models on the accuracy of safety and efficacy assessments by searching the FDA website. Initial phase I trials for each agent were reviewed and safety and efficacy data compared with that found in later trials leading to regulatory approvals of the same agents. As of June 2017, the FDA approved six checkpoint inhibitors for a variety of cancer types. All checkpoint inhibitors received a priority review status and access to at least two additional FDA special access programs, more often breakthrough therapy designation and accelerated approval. Median clinical development time (investigational new drug application to approval) was 60.77 months [avelumab had the shortest timeline (52.33 months)]. Response rates during early phase I trials (median = 16%) are higher than for phase I trials of other agents (with the exception of gene-targeted agents tested with a biomarker). Doses approved were usually not identical to doses recommended on phase I trials. Approximately 50% of types of immune-related and 43% of types of clinically relevant toxicities from later trials were identified in early-phase trials. Even so, treatment-related mortality remains exceedingly low in later studies (0.33% of patients). In conclusion, efficacy and safety of immune checkpoint inhibitors appear to be reasonably predicted from the dose-finding portion of phase I trials, indicating that the fast-track development of these agents is safe and justified. Clin Cancer Res; 24(8); 1785-94. ©2017 AACR . ©2017 American Association for Cancer Research.

  7. Targeting DNA repair systems in antitubercular drug development.

    Science.gov (United States)

    Minias, Alina; Brzostek, Anna; Dziadek, Jaroslaw

    2018-01-28

    Infections with Mycobacterium tuberculosis, the causative agent of tuberculosis, are difficult to treat using currently available chemotherapeutics. Clinicians agree on the urgent need for novel drugs to treat tuberculosis. In this mini review, we summarize data that prompts the consideration of DNA repair-associated proteins as targets for the development of new antitubercular compounds. We discuss data, including gene expression data, that highlight the importance of DNA repair genes during the pathogenic cycle as well as after exposure to antimicrobials currently in use. Specifically, we report experiments on determining the essentiality of DNA repair-related genes. We report the availability of protein crystal structures and summarize discovered protein inhibitors. Further, we describe phenotypes of available gene mutants of M. tuberculosis and model organisms Mycobacterium bovis and Mycobacterium smegmatis. We summarize experiments regarding the role of DNA repair-related proteins in pathogenesis and virulence performed both in vitro and in vivo during the infection of macrophages and animals. We detail the role of DNA repair genes in acquiring mutations, which influence the rate of drug resistance acquisition. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Approaches to modernize the combination drug development paradigm

    Directory of Open Access Journals (Sweden)

    Daphne Day

    2016-10-01

    Full Text Available Abstract Recent advances in genomic sequencing and omics-based capabilities are uncovering tremendous therapeutic opportunities and rapidly transforming the field of cancer medicine. Molecularly targeted agents aim to exploit key tumor-specific vulnerabilities such as oncogenic or non-oncogenic addiction and synthetic lethality. Additionally, immunotherapies targeting the host immune system are proving to be another promising and complementary approach. Owing to substantial tumor genomic and immunologic complexities, combination strategies are likely to be required to adequately disrupt intricate molecular interactions and provide meaningful long-term benefit to patients. To optimize the therapeutic success and application of combination therapies, systematic scientific discovery will need to be coupled with novel and efficient clinical trial approaches. Indeed, a paradigm shift is required to drive precision medicine forward, from the traditional “drug-centric” model of clinical development in pursuit of small incremental benefits in large heterogeneous groups of patients, to a “strategy-centric” model to provide customized transformative treatments in molecularly stratified subsets of patients or even in individual patients. Crucially, to combat the numerous challenges facing combination drug development—including our growing but incomplete understanding of tumor biology, technical and informatics limitations, and escalating financial costs—aligned goals and multidisciplinary collaboration are imperative to collectively harness knowledge and fuel continual innovation.

  9. Stabilized Polymer Micelles for the Development of IT-147, an Epothilone D Drug-Loaded Formulation

    Directory of Open Access Journals (Sweden)

    Adam Carie

    2016-01-01

    Full Text Available Epothilones have demonstrated promising potential for oncology applications but suffer from a narrow therapeutic window. Epothilone D stabilizes microtubules leading to apoptosis, is active against multidrug-resistant cells, and is efficacious in animal tumor models despite lack of stability in rodent plasma. Clinical development was terminated in phase II due to dose limiting toxicities near the efficacious dose. Taken together, this made epothilone D attractive for encapsulation in a stabilized polymer micelle for improved safety and efficacy. We have designed a library of triblock copolymers to develop IT-147, a lead formulation of epothilone D that extends plasma circulation for accumulation in the tumor environment, and potentially decrease systemic exposure to reduce dose limiting toxicities. The drug loading efficiency for IT-147 exceeds 90%, is 75 nm in diameter, and demonstrates pH-dependent release of epothilone D without chemical conjugation or enzymatic activation. Administration of IT-147 at 20 mg/kg increases exposure of epothilone D to the plasma compartment over 6-fold compared to free drug. At the same dose, 20 mg/kg epothilone D from IT-147 is considered the no observed adverse effect level (NOAEL but is the maximum tolerated dose for free drug. Consequently, IT-147 is positioned to be a safer, more effective means to deliver epothilone D.

  10. An Advanced Multi-Sensor Acousto-Ultrasonic Structural Health Monitoring System: Development and Aerospace Demonstration.

    Science.gov (United States)

    Smithard, Joel; Rajic, Nik; van der Velden, Stephen; Norman, Patrick; Rosalie, Cedric; Galea, Steve; Mei, Hanfei; Lin, Bin; Giurgiutiu, Victor

    2017-07-20

    A key longstanding objective of the Structural Health Monitoring (SHM) research community is to enable the embedment of SHM systems in high value assets like aircraft to provide on-demand damage detection and evaluation. As against traditional non-destructive inspection hardware, embedded SHM systems must be compact, lightweight, low-power and sufficiently robust to survive exposure to severe in-flight operating conditions. Typical Commercial-Off-The-Shelf (COTS) systems can be bulky, costly and are often inflexible in their configuration and/or scalability, which militates against in-service deployment. Advances in electronics have resulted in ever smaller, cheaper and more reliable components that facilitate the development of compact and robust embedded SHM systems, including for Acousto-Ultrasonics (AU), a guided plate-wave inspection modality that has attracted strong interest due mainly to its capacity to furnish wide-area diagnostic coverage with a relatively low sensor density. This article provides a detailed description of the development, testing and demonstration of a new AU interrogation system called the Acousto Ultrasonic Structural health monitoring Array Module⁺ (AUSAM⁺). This system provides independent actuation and sensing on four Piezoelectric Wafer Active Sensor (PWAS) elements with further sensing on four Positive Intrinsic Negative (PIN) photodiodes for intensity-based interrogation of Fiber Bragg Gratings (FBG). The paper details the development of a novel piezoelectric excitation amplifier, which, in conjunction with flexible acquisition-system architecture, seamlessly provides electromechanical impedance spectroscopy for PWAS diagnostics over the full instrument bandwidth of 50 KHz-5 MHz. The AUSAM⁺ functionality is accessed via a simple hardware object providing a myriad of custom software interfaces that can be adapted to suit the specific requirements of each individual application.

  11. Industrial advanced turbine systems: Development and demonstration. Quarterly report, July 1--September 30, 1997

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-12-31

    The US DOE has initiated a program for advanced turbine systems (ATS) that will serve industrial power generation markets. The ATS will foster (1) early market penetration that enhances the global competitiveness of US industry, (2) public health benefits resulting from reduced exhaust gas emissions of target pollutants, (3) reduced cost of power used in the energy-intensive industrial marketplace and (4) the retention and expansion of the skilled US technology base required for the design, development and maintenance of state-of-the-art advanced turbine products. The Industrial ATS Development and Demonstration program is a multi-phased effort. Solar Turbines Incorporated (Solar) has participated in Phases 1 and 2 of the program. On September 14, 1995 Solar was awarded a Cooperative Agreement for Phases 3 and 4 of the program. Phase 3 of the work is separated into two subphases: Phase 3A entails Component Design and Development; Phase 3B will involve Integrated Subsystem Testing. Phase 4 will cover Host Site Testing. Forecasts call for completion of the program within budget as originally estimated. Scheduled completion is forecasted to be approximately 3 years late to original plan. Significant efforts were spent this quarter to reforecast and control expenditures due to Solar`s and DOE`s current funding and resource constraints. Selective reductions and delays in program activities were identified and implemented. Although these actions will increase technical risk and the attainment of stretch goals, it is not anticipated that the schedule for initial test units or the attainment of basic program performance requirements will be impacted. As of the end of the reporting period work on the program is 22.80% complete based upon milestones completed. This measurement is considered quite conservative as numerous drawings on the Mercury 50 are near release. Variance information is provided in Section 4.0-Program Management.

  12. Developing drugs for the developing world: an economic, legal, moral, and political dilemma.

    Science.gov (United States)

    Resnik, D B

    2001-05-01

    This paper discusses the economic, legal, moral, and political difficulties in developing drugs for the developing world. It argues that large, global pharmaceutical companies have social responsibilities to the developing world, and that they may exercise these responsibilities by investing in research and development related to diseases that affect developing nations, offering discounts on drug prices, and initiating drug giveaways. However, these social responsibilities are not absolute requirements and may be balanced against other obligations and commitments in light of economic, social, legal, political, and other conditions. How a company decides to exercise its social responsibilities to the developing world depends on (1) the prospects for a reasonable profit and (2) the prospects for a productive business environment. Developing nations can either help or hinder the pharmaceutical industry's efforts to exercise social responsibility through various policies and practices. To insure that companies can make a reasonable profit, developing nations should honor pharmaceutical product patents and adhere to international intellectual property treaties, such as the Trade-Related Aspects of Intellectual Property Rights (TRIPS) agreement. To insure the companies have a good business environment, developing nations should try to promote the rule of law, ethical business practices, stable currencies, reliable banking systems, free and open markets, democracy, and other conditions conducive to business. Overall, this paper advocates for reciprocity and cooperation between pharmaceutical companies and developing nations to address the problem of developing drugs for the developing world. In pursuing this cooperative approach, developing nations may use a variety of other techniques to encourage pharmaceutical companies to act responsibly, such as subsidizing pharmaceutical research, helping to design and implement research protocols, providing a guaranteed market, and

  13. 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

  14. 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.

  15. Pitfalls in new artemisinin-containing antimalarial drug development.

    Science.gov (United States)

    Jambou, Ronan; Le Bras, Jacques; Randrianarivelojosia, Milijaona

    2011-02-01

    Artemisinin combination therapy (ACT) paves the way for new opportunities to eliminate malaria in the tropics. However, the huge increase of ACT consumption raises major concerns about their availability over the next few years. At the same time a decrease in their efficacy has already been reported. Alongside the deployment of multifocal control programs, the process ranging from artemisia crop production to accreditation of new ACT combinations urgently needs to be strengthened to supply sufficient quantities of high-quality drugs. New suppliers will have the opportunity to enter this market to develop new formulations, and bioequivalence studies are required to validate these new formulations. It is thus crucial for national malaria control teams to be able to better scrutinize the dossier of these new formulations. Copyright © 2010 Elsevier Ltd. All rights reserved.

  16. Multi-regional clinical trials and global drug development

    Directory of Open Access Journals (Sweden)

    Premnath Shenoy

    2016-01-01

    Full Text Available Drug development has been globalized, and multi-regional clinical trial (MRCT for regulatory submission has widely been conducted by many discovery based global pharmaceutical companies with the objective of reducing the time lag of launch in key markets and improve patient access to new and innovative treatments. Sponsors are facing several challenges while conducting multiregional clinical trials. Challenges under the heads statistics, clinical, regulatory operational, and ethics have been discussed. Regulators in different countries such as USA, EU-Japan, and China have issued guidance documents in respect of MRCT's. Lack of harmonization in the design and planning of MRCT is perceived to create a difficult situation to sponsors adversely affecting progressing MRCT in more and more discoveries. International conference on hormonisation (ICH has initiated the process for having a harmonized guidance document on MRCT. This document is likely to be issued in early 2017.

  17. Nonstructural Proteins of Alphavirus—Potential Targets for Drug Development

    Directory of Open Access Journals (Sweden)

    Farhana Abu Bakar

    2018-02-01

    Full Text Available Alphaviruses are enveloped, positive single-stranded RNA viruses, typically transmitted by arthropods. They often cause arthralgia or encephalitic diseases in infected humans and there is currently no targeted antiviral treatment available. The re-emergence of alphaviruses in Asia, Europe, and the Americas over the last decade, including chikungunya and o’nyong’nyong viruses, have intensified the search for selective inhibitors. In this review, we highlight key molecular determinants within the alphavirus replication complex that have been identified as viral targets, focusing on their structure and functionality in viral dissemination. We also summarize recent structural data of these viral targets and discuss how these could serve as templates to facilitate structure-based drug design and development of small molecule inhibitors.

  18. Developing a coordinated response to drug abuse in Pakistan.

    LENUS (Irish Health Repository)

    Khalily, Muhammad Tahir

    2010-03-01

    This paper describes moves towards the coordination of efforts to respond to the worsening drug abuse situation in Pakistan which affects all segments of society. The efforts reported seek to rectify inconsistencies in treatment policy resulting in unsatisfactory outcomes. Examples of collaborative strategies with encouraging results need further underpinning and expansion. There is, however, a lack of realization at the policy level of the need to effect changes in treatment formulated on a consistent and evidence-based approach. Policy has therefore been reviewed and proposals made for a comprehensive treatment strategy in line with international best practices to deal with this problem effectively and efficiently. Establishment of an addiction study centre at university level to continue professional and academic development is suggested.

  19. Development, Characterization and Evaluation of Solid Lipid Nanoparticles as a potential Anticancer Drug Delivery System

    Science.gov (United States)

    Patel, Meghavi

    Solid lipid nanoparticles (SLNs) consist of spherical solid lipid particles in the nanometer size range, which are dispersed in water or in an aqueous surfactant solution. SLN technology represents a promising new approach to deliver hydrophilic as well as lipophilic drugs. The commercialization of SLN technology remains limited despite numerous efforts from researchers. The purpose of this research was to advance SLN preparation methodology by investigating the feasibility of preparing glyceryl monostearate (GMS) nanoparticles by using three preparation methods namely microemulsion technique, magnetic stirring technique and temperature modulated solidification technique of which the latter two were developed in our laboratory. An anticancer drug 5-fluorouracil was incorporated in the SLNs prepared via the temperature modulated solidification process. Optimization of the magnetic stirring process was performed to evaluate how the physicochemical properties of the SLN was influenced by systematically varying process parameters including concentration of the lipid, concentration of the surfactant, type of surfactant, time of stirring and temperature of storage. The results demonstrated 1:2 GMS to tween 80 ratio, 150 ml dispersion medium and 45 min stirring at 4000 RPM speed provided an optimum formulation via the temperature modulated solidification process. SLN dispersions were lyophilized to stabilize the solid lipid nanoparticles and the lyophilizates exhibited good redispersibility. The SLNs were characterized by particle size analysis via dynamic light scattering (DLS), zeta potential, transmission electron microscopy (TEM), differential scanning calorimetry (DSC), drug encapsulation efficiency and in vitro drug release studies. Particle size of SLN dispersion prepared via the three preparation techniques was approximately 66 nm and that of redispersed lyophilizates was below 500 nm. TEM images showed spherical to oval particles that were less dense in the core

  20. 78 FR 68459 - Medical Device Development Tools; Draft Guidance for Industry, Tool Developers, and Food and Drug...

    Science.gov (United States)

    2013-11-14

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-D-1279] Medical Device Development Tools; Draft Guidance for Industry, Tool Developers, and Food and Drug Administration Staff; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food...

  1. Research, development and demonstration. Issue paper - working group 3; Denmark. Smart Grid Network; Forskning, udvikling og demonstration. Issue paper, arbejdsgruppe 3

    Energy Technology Data Exchange (ETDEWEB)

    Balasiu, A [Siemens A/S, Ballerup (Denmark); Troi, A [Danmarks Tekniske Univ. Risoe Nationallaboratoriet for Baeredygtig Energi, Roskilde (Denmark); Andersen, Casper [DI Energibranchen, Copenhagen (Denmark); and others

    2011-07-01

    The Smart Grid Network was established in 2010 by the Danish climate and energy minister tasked with developing recommendations for future actions and initiatives that make it possible to handle up to 50% electricity from wind energy in the power system in 2020. The task of working group 3 was defined as: - An overview of the Danish research and development of smart grids and related areas; - Conducting an analysis of the research and development needs required for the introduction of a smart grid in Denmark. Based on this analysis, provide suggestions for new large research and development projects; - Provide recommendations on how the activities are best carried out taking into account innovation, economic growth and jobs. In the analysis it is explained that Denmark so far has a strong position in several elements of RD and D activities. This position will soon be threatened as several European countries have launched ambitious initiatives to strengthen the national position. The working group recommends that Denmark gives priority to Smart Grids as a national action in order to solve the challenge of technically and economically efficient integration of renewable energy. Smart Grid is a catalyst that strengthens a new green growth industry (cleantech) in Denmark. Research and development has an important role to play in this development. A common vision and roadmap must be established for research institutions, energy companies and industries related to research, development and demonstration of Smart Grid, which can maintain and expand Denmark's global leadership position. As part of this, there is a need to strengthen and market research infrastructures, which can turn Denmark into a global hub for smart grid development. There is a current need to strengthen the advanced technical and scientific research in the complexities of the power system, research on market design, user behavior and smart grid interoperability. (LN)

  2. Research, development and demonstration. Issue paper - working group 3; Denmark. Smart Grid Network; Forskning, udvikling og demonstration. Issue paper, arbejdsgruppe 3

    Energy Technology Data Exchange (ETDEWEB)

    Balasiu, A. (Siemens A/S, Ballerup (Denmark)); Troi, A. (Danmarks Tekniske Univ.. Risoe Nationallaboratoriet for Baeredygtig Energi, Roskilde (Denmark)); Andersen, Casper (DI Energibranchen, Copenhagen (Denmark)) (and others)

    2011-07-01

    The Smart Grid Network was established in 2010 by the Danish climate and energy minister tasked with developing recommendations for future actions and initiatives that make it possible to handle up to 50% electricity from wind energy in the power system in 2020. The task of working group 3 was defined as: - An overview of the Danish research and development of smart grids and related areas; - Conducting an analysis of the research and development needs required for the introduction of a smart grid in Denmark. Based on this analysis, provide suggestions for new large research and development projects; - Provide recommendations on how the activities are best carried out taking into account innovation, economic growth and jobs. In the analysis it is explained that Denmark so far has a strong position in several elements of RD and D activities. This position will soon be threatened as several European countries have launched ambitious initiatives to strengthen the national position. The working group recommends that Denmark gives priority to Smart Grids as a national action in order to solve the challenge of technically and economically efficient integration of renewable energy. Smart Grid is a catalyst that strengthens a new green growth industry (cleantech) in Denmark. Research and development has an important role to play in this development. A common vision and roadmap must be established for research institutions, energy companies and industries related to research, development and demonstration of Smart Grid, which can maintain and expand Denmark's global leadership position. As part of this, there is a need to strengthen and market research infrastructures, which can turn Denmark into a global hub for smart grid development. There is a current need to strengthen the advanced technical and scientific research in the complexities of the power system, research on market design, user behavior and smart grid interoperability. (LN)

  3. A primer of drug safety surveillance: an industry perspective. Part I: Information flow, new drug development, and federal regulations.

    Science.gov (United States)

    Allan, M C

    1992-01-01

    To place the fundamentals of clinical drug safety surveillance in a conceptual framework that will facilitate understanding and application of adverse drug event data to protect the health of the public and support a market for pharmaceutical manufacturers' products. Part I of this series provides a background for the discussion of drug safety by defining the basic terms and showing the flow of safety information through a pharmaceutical company. The customers for adverse drug event data are identified to provide a basis for providing quality service. The development of a drug product is briefly reviewed to show the evolution of safety data. Drug development and safety are defined by federal regulations. These regulations are developed by the FDA with information from pharmaceutical manufacturers. The intent of the regulations and the accompanying guidelines is described. An illustration from the news media is cited to show an alternative, positive approach to handling an adverse event report. This review uses primary sources from the federal laws (regulations), commentaries, and summaries. Very complex topics are briefly summarized in the text and additional readings are presented in an appendix. Secondary sources, ranging from newspaper articles to judicial summaries, illustrate the interpretation of adverse drug events and opportunities for drug safety surveillance intervention. The reference materials used were articles theoretically or practically applicable in the day-to-day practice of drug safety surveillance. The role of clinical drug safety surveillance in product monitoring and drug development is described. The process of drug safety surveillance is defined by the Food and Drug Administration regulations, product labeling, product knowledge, and database management. Database management is subdivided into the functions of receipt, retention, retrieval, and review of adverse event reports. Emphasis is placed on the dynamic interaction ;of the components

  4. Solar cells. Proposal for a national strategy for research, development and demonstration; Solceller. Oplaeg til en national strategi for forskning, udvikling og demonstration

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2004-07-01

    The Danish Energy Authority, Elkraft System and Eltra have initiated collaboration on the development of national R and D strategies for a number of energy technologies including solar cells. The aim is to ensure a coordinated national effort as regards research, development and demonstration within societal and energy political frames, and, furthermore, to ensure coordination with similar international initiatives, especially within the European Union. The overall aim is for the Danish solar cell strategy to contribute to support Danish national energy policy and to ensure and improve Danish competence, which can manifest itself internationally. The efforts within solar cell technology must aim at increasing solar cell systems' efficiency and service life, and furthermore, aim at reducing production costs. Hereby the efforts can contribute to an improvement of solar cell systems' competitive power in relation to other power production technologies with a view to make installation of solar cell systems attractive, both in Denmark and internationally. (BA)

  5. Development of analytical cell support for vitrification at the West Valley Demonstration Project. Topical report

    Energy Technology Data Exchange (ETDEWEB)

    Barber, F.H.; Borek, T.T.; Christopher, J.Z. [and others

    1997-12-01

    Analytical and Process Chemistry (A&PC) support is essential to the high-level waste vitrification campaign at the West Valley Demonstration Project (WVDP). A&PC characterizes the waste, providing information necessary to formulate the recipe for the target radioactive glass product. High-level waste (HLW) samples are prepared and analyzed in the analytical cells (ACs) and Sample Storage Cell (SSC) on the third floor of the main plant. The high levels of radioactivity in the samples require handling them in the shielded cells with remote manipulators. The analytical hot cells and third floor laboratories were refurbished to ensure optimal uninterrupted operation during the vitrification campaign. New and modified instrumentation, tools, sample preparation and analysis techniques, and equipment and training were required for A&PC to support vitrification. Analytical Cell Mockup Units (ACMUs) were designed to facilitate method development, scientist and technician training, and planning for analytical process flow. The ACMUs were fabricated and installed to simulate the analytical cell environment and dimensions. New techniques, equipment, and tools could be evaluated m in the ACMUs without the consequences of generating or handling radioactive waste. Tools were fabricated, handling and disposal of wastes was addressed, and spatial arrangements for equipment were refined. As a result of the work at the ACMUs the remote preparation and analysis methods and the equipment and tools were ready for installation into the ACs and SSC m in July 1995. Before use m in the hot cells, all remote methods had been validated and four to eight technicians were trained on each. Fine tuning of the procedures has been ongoing at the ACs based on input from A&PC technicians. Working at the ACs presents greater challenges than had development at the ACMUs. The ACMU work and further refinements m in the ACs have resulted m in a reduction m in analysis turnaround time (TAT).

  6. Development of analytical cell support for vitrification at the West Valley Demonstration Project. Topical report

    International Nuclear Information System (INIS)

    Barber, F.H.; Borek, T.T.; Christopher, J.Z.

    1997-12-01

    Analytical and Process Chemistry (A ampersand PC) support is essential to the high-level waste vitrification campaign at the West Valley Demonstration Project (WVDP). A ampersand PC characterizes the waste, providing information necessary to formulate the recipe for the target radioactive glass product. High-level waste (HLW) samples are prepared and analyzed in the analytical cells (ACs) and Sample Storage Cell (SSC) on the third floor of the main plant. The high levels of radioactivity in the samples require handling them in the shielded cells with remote manipulators. The analytical hot cells and third floor laboratories were refurbished to ensure optimal uninterrupted operation during the vitrification campaign. New and modified instrumentation, tools, sample preparation and analysis techniques, and equipment and training were required for A ampersand PC to support vitrification. Analytical Cell Mockup Units (ACMUs) were designed to facilitate method development, scientist and technician training, and planning for analytical process flow. The ACMUs were fabricated and installed to simulate the analytical cell environment and dimensions. New techniques, equipment, and tools could be evaluated m in the ACMUs without the consequences of generating or handling radioactive waste. Tools were fabricated, handling and disposal of wastes was addressed, and spatial arrangements for equipment were refined. As a result of the work at the ACMUs the remote preparation and analysis methods and the equipment and tools were ready for installation into the ACs and SSC m in July 1995. Before use m in the hot cells, all remote methods had been validated and four to eight technicians were trained on each. Fine tuning of the procedures has been ongoing at the ACs based on input from A ampersand PC technicians. Working at the ACs presents greater challenges than had development at the ACMUs. The ACMU work and further refinements m in the ACs have resulted m in a reduction m in

  7. Real Options Valuation of U.S. Federal Renewable Energy Research,Development, Demonstration, and Deployment

    Energy Technology Data Exchange (ETDEWEB)

    Siddiqui, Afzal S.; Marnay, Chris; Wiser, Ryan H.

    2005-03-01

    Benefits analysis of US Federal government funded research, development, demonstration, and deployment (RD3) programs for renewable energy (RE) technology improvement typically employs a deterministic forecast of the cost and performance of renewable and nonrenewable fuels. The benefits estimate for a program derives from the difference between two forecasts, with and without the RD3 in place. The deficiencies of the current approach are threefold: (1) it does not consider uncertainty in the cost of non-renewable energy (NRE), and the option or insurance value of deploying RE if and when NRE costs rise; (2) it does not consider the ability of the RD3 manager to adjust the RD3 effort to suit the evolving state of the world, and the option value of this flexibility; and (3) it does not consider the underlying technical risk associated with RD3, and the impact of that risk on the programs optimal level of RD3 effort. In this paper, a rudimentary approach to determining the option value of publicly funded RE RD3 is developed. The approach seeks to tackle the first deficiency noted above by providing an estimate of the options benefit of an RE RD3 program in a future with uncertain NRE costs.While limited by severe assumptions, a computable lattice of options values reveals the economic intuition underlying the decision-making process. An illustrative example indicates how options expose both the insurance and timing values inherent in a simplified RE RD3 program that coarsely approximates the aggregation of current Federal RE RD3.This paper also discusses the severe limitations of this initial approach, and identifies needed model improvements before the approach can adequately respond to the RE RD3 analysis challenge.

  8. Development and Demonstration (RD and D) Plan for the disposal of radioactive waste in Switzerland

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2016-12-15

    This comprehensive brochure published by the Swiss National Cooperative for the Disposal of Radioactive Waste (NAGRA) discusses NAGRA’s Research, Development and Demonstration (RD and D) Plan together with its Waste Management Program. The present RD and D Plan is in line with the Swiss Federal Council’s decision and in accordance with the regulatory framework in Switzerland. The two types of repository foreseen, one for low- and intermediate-level waste (L/ILW) and one for vitrified high-level waste are discussed. The overall objectives of this report are stated and the planning premises for implementation of the repositories are discussed, as are the strategic requirements involved and the stages of their implementation. The methodology and the resources available for implementing the RD and D programme are described. The status of the RD and D program is noted and an overview of the technical program for the next 10 years is presented. The report includes many diagrams, illustrations and tables and describes activities at various research installations in Switzerland.

  9. Development of simulated tank wastes for the US Department of Energy's Underground Storage Tank Integrated Demonstration

    International Nuclear Information System (INIS)

    Elmore, M.R.; Colton, N.G.; Jones, E.O.

    1992-08-01

    The purpose of the Underground Storage Tank Integrated Demonstration (USTID) is to identify and evaluate technologies that may be used to characterize, retrieve, treat, and dispose of hazardous and radioactive wastes contained in tanks on US Department of Energy sites. Simulated wastes are an essential component of the evaluation process because they provide controlled samples for technology assessment, and minimize costs and risks involved when working with radioactive wastes. Pacific Northwest Laboratory has developed a recipe to simulate Hanford single-shell tank, (SST) waste. The recipe is derived from existing process recipes, and elemental concentrations are based on characterization data from 18 SSTs. In this procedure, salt cake and metal oxide/hydroxide sludge are prepared individually, and mixed together at varying ratios depending on the specific tank, waste to be simulated or the test being conducted. Elemental and physical properties of the stimulant are comparable with analyzed tank samples, and chemical speciation in the simulant is being improved as speciation data for actual wastes become available. The nonradioactive chemical waste simulant described here is useful for testing technologies on a small scale

  10. Accelerator production of tritium plant design and supporting engineering development and demonstration work

    International Nuclear Information System (INIS)

    Lisowski, P.W.

    1997-11-01

    Tritium is an isotope of hydrogen with a half life of 12.3 years. Because it is essential for US thermonuclear weapons to function, tritium must be periodically replenished. Since K reactor at Savannah River Site stopped operating in 1988, tritium has been recycled from dismantled nuclear weapons. This process is possible only as long as many weapons are being retired. Maintaining the stockpile at the level called for in the present Strategic Arms Reduction Treaty (START-I) will require the Department of Energy to have an operational tritium production capability in the 2005--2007 time frame. To make the required amount of tritium using an accelerator based system (APT), neutrons will be produced through high energy proton reactions with tungsten and lead. Those neutrons will be moderated and captured in 3 He to make tritium. The APT plant design will use a 1,700 MeV linear accelerator operated at 100 mA. In preparation for engineering design, starting in October 1997 and subsequent construction, a program of engineering development and demonstration is underway. That work includes assembly and testing of the first 20 MeV of the low energy plant linac at 100 mA, high-energy linac accelerating structure prototyping, radiofrequency power system improvements, neutronic efficiency measurements, and materials qualifications

  11. Demonstrating Starshade Performance as Part of NASA's Technology Development for Exoplanet Missions

    Science.gov (United States)

    Kasdin, N. Jeremy; Spergel, D. N.; Vanderbei, R. J.; Lisman, D.; Shaklan, S.; Thomson, M. W.; Walkemeyer, P. E.; Bach, V. M.; Oakes, E.; Cady, E. J.; Martin, S. R.; Marchen, L. F.; Macintosh, B.; Rudd, R.; Mikula, J. A.; Lynch, D. H.

    2012-01-01

    In this poster we describe the results of our project to design, manufacture, and measure a prototype starshade petal as part of the Technology Development for Exoplanet Missions program. An external occult is a satellite employing a large screen, or starshade,that flies in formation with a spaceborne telescope to provide the starlight suppression needed for detecting and characterizing exoplanets. Among the advantages of using an occulter are the broadband allowed for characterization and the removal of light for the observatory, greatly relaxing the requirements on the telescope and instrument. In this first two-year phase we focused on the key requirement of manufacturing a precision petal with the precise tolerances needed to meet the overall error budget. These tolerances are established by modeling the effect that various mechanical and thermal errors have on scatter in the telescope image plane and by suballocating the allowable contrast degradation between these error sources. We show the results of this analysis and a representative error budget. We also present the final manufactured occulter petal and the metrology on its shape that demonstrates it meets requirements. We show that a space occulter built of petals with the same measured shape would achieve better than 1e-9 contrast. We also show our progress in building and testing sample edges with the sharp radius of curvature needed for limiting solar glint. Finally, we describe our plans for the second TDEM phase.

  12. Development and Demonstration (RD and D) Plan for the disposal of radioactive waste in Switzerland

    International Nuclear Information System (INIS)

    2016-12-01

    This comprehensive brochure published by the Swiss National Cooperative for the Disposal of Radioactive Waste (NAGRA) discusses NAGRA’s Research, Development and Demonstration (RD and D) Plan together with its Waste Management Program. The present RD and D Plan is in line with the Swiss Federal Council’s decision and in accordance with the regulatory framework in Switzerland. The two types of repository foreseen, one for low- and intermediate-level waste (L/ILW) and one for vitrified high-level waste are discussed. The overall objectives of this report are stated and the planning premises for implementation of the repositories are discussed, as are the strategic requirements involved and the stages of their implementation. The methodology and the resources available for implementing the RD and D programme are described. The status of the RD and D program is noted and an overview of the technical program for the next 10 years is presented. The report includes many diagrams, illustrations and tables and describes activities at various research installations in Switzerland

  13. Research, development and demonstration in the energy area in Switzerland - List of projects 2000/2001

    International Nuclear Information System (INIS)

    2002-01-01

    This report prepared by the Swiss Federal Office of Energy (SFOE) reviews research, development and demonstration projects in the energy area that were partly or wholly supported by the Swiss Federation in the years 2000/2001. A list of over 1,000 projects is presented, whereby many projects supported by the Swiss Cantons and local authorities are not included in the statistics. The report also contains figures on the efforts made by the private economy in these areas. The classification of the projects in the four main areas 'efficient use of energy', 'renewable energy sources', 'nuclear energy' and 'energy economics' is presented. This allows comparison with other publications such as the Federal Energy-Research Concept or the Overviews of the Energy-Research Programme Managers. The classification system is also compared with that used by the International Energy Agency (IEA). The Network for Information and Technology Transfer (ENET) is also presented, which has a comprehensive data base at its disposal and which maintains a systematic collection of energy-relevant publications. Details on these projects can be obtained from the appropriate heads of programmes and SFOE departmental heads, whose addresses are given in the report

  14. Characterization and demonstration results of a SQUID magnetometer system developed for geomagnetic field measurements

    Science.gov (United States)

    Kawai, J.; Miyamoto, M.; Kawabata, M.; Nosé, M.; Haruta, Y.; Uehara, G.

    2017-08-01

    We characterized a low temperature superconducting quantum interference device (SQUID) magnetometer system developed for high-sensitivity geomagnetic field measurement, and demonstrated the detection of weak geomagnetic signals. The SQUID magnetometer system is comprised of three-axis SQUID magnetometers housed in a glass fiber reinforced plastic cryostat, readout electronics with flux locked loop (FLL), a 24-bit data logger with a global positioning system and batteries. The system noise was approximately 0.2 pT √Hz- 1/2 in the 1-50 Hz frequency range. This performance was determined by including the thermal noise and the shielding effect of the copper shield, which covered the SQUID magnetometers to eliminate high-frequency interference. The temperature drift of the system was ˜0.8 pT °C- 1 in an FLL operation. The system operated for a month using 33 l liquid helium. Using this system, we performed the measurements of geomagnetic field in the open-air, far away from the city. The system could detect weak geomagnetic signals such as the Schumann resonance with sixth harmonics, and the ionospheric Alfvén resonance appearing at night, for the north-south and east-west components of the geomagnetic field. We confirm that the system was capable of high-sensitivity measurement of the weak geomagnetic activities.

  15. Development of polymer-polysaccharide hydrogels for controlling drug delivery

    Science.gov (United States)

    Baldwin, Aaron David

    The use of polymers as biomaterials has evolved over the past several decades, encompassing an expanding synthetic toolbox and many bio-mimetic approaches. Both synthetic and natural polymers have been used as components for biomaterials as their unique chemical structures can provide specific functions for desired applications. Of these materials, heparin, a highly sulfated naturally occurring polysaccharide, has been investigated extensively as a core component in drug delivery platforms and tissue engineering. The goal of this work was to further explore the use of heparin via conjugation with synthetic polymers for applications in drug delivery. We begin by investigating low molecular weight heparin (LMWH), a depolymerized heparin that is used medicinally in the prevention of thrombosis by subcutaneous injection or intravenous drip. Certain disease states or disorders require frequent administration with invasive delivery modalities leading to compliance issues for individuals on prolonged therapeutic courses. To address these issues, a long-term delivery method was developed for LMWH via subcutaneous injection of in situ hydrogelators. This therapy was accomplished by chemical modification of LMWH with maleimide functionality so that it may be crosslinked into continuous hydrogel networks with four-arm thiolated polyethylene glycol (PEG-SH). These hydrogels degrade via hydrolysis over a period of weeks and release bioactive LMWH with first-order kinetics as determined by in vitro and in vivo models, thus indicating the possibility of an alternative means of heparin delivery over current accepted methodologies. Evaluation of the maleimide-thiol chemistries applied in the LMWH hydrogels revealed reversibility for some conjugates under reducing conditions. Addition chemistries, such as maleimide-thiol reactions, are widely employed in biological conjugates and are generally accepted as stable. Here we show that the resulting succinimide thioether formed by the

  16. Evaluation of transporters in drug development: Current status and contemporary issues.

    Science.gov (United States)

    Lee, Sue-Chih; Arya, Vikram; Yang, Xinning; Volpe, Donna A; Zhang, Lei

    2017-07-01

    Transporters govern the access of molecules to cells or their exit from cells, thereby controlling the overall distribution of drugs to their intracellular site of action. Clinically relevant drug-drug interactions mediated by transporters are of increasing interest in drug development. Drug transporters, acting alone or in concert with drug metabolizing enzymes, can play an important role in modulating drug absorption, distribution, metabolism and excretion, thus affecting the pharmacokinetics and/or pharmacodynamics of a drug. The drug interaction guidance documents from regulatory agencies include various decision criteria that may be used to predict the need for in vivo assessment of transporter-mediated drug-drug interactions. Regulatory science research continues to assess the prediction performances of various criteria as well as to examine the strength and limitations of each prediction criterion to foster discussions related to harmonized decision criteria that may be used to facilitate global drug development. This review discusses the role of transporters in drug development with a focus on methodologies in assessing transporter-mediated drug-drug interactions, challenges in both in vitro and in vivo assessments of transporters, and emerging transporter research areas including biomarkers, assessment of tissue concentrations, and effect of diseases on transporters. Published by Elsevier B.V.

  17. Integrating scientific data for drug discovery and development using the Life Sciences Grid.

    Science.gov (United States)

    Dow, Ernst R; Hughes, James B; Stephens, Susie M; Narayan, Vaibhav A; Bishop, Richard W

    2009-06-01

    There are many daunting challenges for companies who wish to bring novel drugs to market. The information complexity around potential drug targets has increased greatly with the introduction of microarrays, high-throughput screening and other technological advances over the past decade, but has not yet fundamentally increased our understanding of how to modify a disease with pharmaceuticals. Further, the bar has been raised in getting a successful drug to market as just being new is no longer enough: the drug must demonstrate improved performance compared with the ever increasing generic pharmacopeia to gain support from payers and government authorities. In addition, partly as a consequence of a climate of concern regarding the safety of drugs, regulatory authorities have approved fewer new molecular entities compared to historical norms over the past few years. To overcome these challenges, the pharmaceutical industry must fully embrace information technology to bring better understood compounds to market. An important first step in addressing an unmet medical need is in understanding the disease and identifying the physiological target(s) to be modulated by the drug. Deciding which targets to pursue for a given disease requires a multidisciplinary effort that integrates heterogeneous data from many sources, including genetic variations of populations, changes in gene expression and biochemical assays. The Life Science Grid was developed to provide a flexible framework to integrate such diverse biological, chemical and disease information to help scientists make better-informed decisions. The Life Science Grid has been used to rapidly and effectively integrate scientific information in the pharmaceutical industry and has been placed in the open source community to foster collaboration in the life sciences community.

  18. Analysis of combination drug therapy to develop regimens with shortened duration of treatment for tuberculosis.

    Directory of Open Access Journals (Sweden)

    George L Drusano

    Full Text Available Tuberculosis remains a worldwide problem, particularly with the advent of multi-drug resistance. Shortening therapy duration for Mycobacterium tuberculosis is a major goal, requiring generation of optimal kill rate and resistance-suppression. Combination therapy is required to attain the goal of shorter therapy.Our objective was to identify a method for identifying optimal combination chemotherapy. We developed a mathematical model for attaining this end. This is accomplished by identifying drug effect interaction (synergy, additivity, antagonism for susceptible organisms and subpopulations resistant to each drug in the combination.We studied the combination of linezolid plus rifampin in our hollow fiber infection model. We generated a fully parametric drug effect interaction mathematical model. The results were subjected to Monte Carlo simulation to extend the findings to a population of patients by accounting for between-patient variability in drug pharmacokinetics.All monotherapy allowed emergence of resistance over the first two weeks of the experiment. In combination, the interaction was additive for each population (susceptible and resistant. For a 600 mg/600 mg daily regimen of linezolid plus rifampin, we demonstrated that >50% of simulated subjects had eradicated the susceptible population by day 27 with the remaining organisms resistant to one or the other drug. Only 4% of patients had complete organism eradication by experiment end.These data strongly suggest that in order to achieve the goal of shortening therapy, the original regimen may need to be changed at one month to a regimen of two completely new agents with resistance mechanisms independent of the initial regimen. This hypothesis which arose from the analysis is immediately testable in a clinical trial.

  19. Development of gellan gum containing formulations for transdermal drug delivery: Component evaluation and controlled drug release using temperature responsive nanogels.

    Science.gov (United States)

    Carmona-Moran, Carlos A; Zavgorodnya, Oleksandra; Penman, Andrew D; Kharlampieva, Eugenia; Bridges, S Louis; Hergenrother, Robert W; Singh, Jasvinder A; Wick, Timothy M

    2016-07-25

    Enhancing skin permeation is important for development of new transdermal drug delivery formulations. This is particularly relevant for non-steroidal anti-inflammatory drugs (NSAIDs). To address this, semisolid gel and solid hydrogel film formulations containing gellan gum as a gelling agent were developed and the effects of penetration enhancers (dimethyl sulfoxide, isopropyl alcohol and propylene glycol) on transport of the NSAID diclofenac sodium was quantified. A transwell diffusion system was used to accelerate formulation development. After 4h, diclofenac flux from a superior formulation of the semisolid gel or the solid hydrogel film was 130±11μg/cm(2)h and 108±7μg/cm(2)h, respectively, and significantly greater than that measured for a currently available diclofenac sodium topical gel (30±4μg/cm(2)h, ptransdermal drug formulations with adjustable drug transport kinetics. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. The development and demonstration of integrated models for the evaluation of severe accident management strategies - SAMEM

    International Nuclear Information System (INIS)

    Ang, M.L.; Peers, K.; Kersting, E.; Fassmann, W.; Tuomisto, H.; Lundstroem, P.; Helle, M.; Gustavsson, V.; Jacobsson, P.

    2001-01-01

    This study is concerned with the further development of integrated models for the assessment of existing and potential severe accident management (SAM) measures. This paper provides a brief summary of these models, based on Probabilistic Safety Assessment (PSA) methods and the Risk Oriented Accident Analysis Methodology (ROAAM) approach, and their application to a number of case studies spanning both preventive and mitigative accident management regimes. In the course of this study it became evident that the starting point to guide the selection of methodology and any further improvement is the intended application. Accordingly, such features as the type and area of application and the confidence requirement are addressed in this project. The application of an integrated ROAAM approach led to the implementation, at the Loviisa NPP, of a hydrogen mitigation strategy, which requires substantial plant modifications. A revised level 2 PSA model was applied to the Sizewell B NPP to assess the feasibility of the in-vessel retention strategy. Similarly the application of PSA based models was extended to the Barseback and Ringhals 2 NPPs to improve the emergency operating procedures, notably actions related to manual operations. A human reliability analysis based on the Human Cognitive Reliability (HCR) and Technique For Human Error Rate (THERP) models was applied to a case study addressing secondary and primary bleed and feed procedures. Some aspects pertinent to the quantification of severe accident phenomena were further examined in this project. A comparison of the applications of PSA based approach and ROAAM to two severe accident issues, viz hydrogen combustion and in-vessel retention, was made. A general conclusion is that there is no requirement for further major development of the PSA and ROAAM methodologies in the modelling of SAM strategies for a variety of applications as far as the technical aspects are concerned. As is demonstrated in this project, the

  1. Stable isotope-resolved metabolomics and applications for drug development

    Science.gov (United States)

    Fan, Teresa W-M.; Lorkiewicz, Pawel; Sellers, Katherine; Moseley, Hunter N.B.; Higashi, Richard M.; Lane, Andrew N.

    2012-01-01

    Advances in analytical methodologies, principally nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS), during the last decade have made large-scale analysis of the human metabolome a reality. This is leading to the reawakening of the importance of metabolism in human diseases, particularly cancer. The metabolome is the functional readout of the genome, functional genome, and proteome; it is also an integral partner in molecular regulations for homeostasis. The interrogation of the metabolome, or metabolomics, is now being applied to numerous diseases, largely by metabolite profiling for biomarker discovery, but also in pharmacology and therapeutics. Recent advances in stable isotope tracer-based metabolomic approaches enable unambiguous tracking of individual atoms through compartmentalized metabolic networks directly in human subjects, which promises to decipher the complexity of the human metabolome at an unprecedented pace. This knowledge will revolutionize our understanding of complex human diseases, clinical diagnostics, as well as individualized therapeutics and drug response. In this review, we focus on the use of stable isotope tracers with metabolomics technologies for understanding metabolic network dynamics in both model systems and in clinical applications. Atom-resolved isotope tracing via the two major analytical platforms, NMR and MS, has the power to determine novel metabolic reprogramming in diseases, discover new drug targets, and facilitates ADME studies. We also illustrate new metabolic tracer-based imaging technologies, which enable direct visualization of metabolic processes in vivo. We further outline current practices and future requirements for biochemoinformatics development, which is an integral part of translating stable isotope-resolved metabolomics into clinical reality. PMID:22212615

  2. Old and new therapeutics for Rheumatoid Arthritis: in vivo models and drug development

    DEFF Research Database (Denmark)

    Sardar, Samra; Andersson, Åsa

    2016-01-01

    Development of novel drugs for treatment of chronic inflammatory diseases is to a large extent dependent on the availability of good experimental in vivo models in order to perform preclinical tests of new drugs and for the identification of novel drug targets. Here, we review a number of existing...... of in vivo models during development of anti-rheumatic drugs; from Methotrexate to various antibody treatments, to novel drugs that are, or have recently been, in clinical trials. For novel drugs, we have explored websites for clinical trials. Although one Rheumatoid Arthritis in vivo model cannot mirror...

  3. FY 1994 program summary: Office of Technology Development, Office of Research and Development, Office of Demonstration, Testing, and Evaluation

    Energy Technology Data Exchange (ETDEWEB)

    1994-10-01

    The US Department of Energy (DOE) Office of Environmental Management, formerly the Office of Environmental Restoration and Waste Management (EM), was established in November 1989 as the first step toward correcting contamination problems resulting from nearly 50 years of nuclear weapons production and fuel processing activities. EM consolidates several DOE organizations previously responsible for the handling, treatment, and disposition of radioactive and hazardous waste. Within EM, the Office of Technology Development (OTD/EM-50) is responsible for developing technologies to meet DOE`s goal for environmental restoration. OTD manages an aggressive national program of applied research, development, demonstration, testing, and evaluation (RDDT and E) for environmental cleanup, waste management, and related technologies. The program is designed to resolve major technical issues, to rapidly advanced beyond current technologies for environmental restoration and waste management operations, and to expedite compliance with applicable environmental laws and regulations. This report summarizes Fiscal Year 1994 (FY94) programmatic information, accomplishments, and planned activities relevant to the individual activities within OTD`s RDDT and E.

  4. FY 1994 program summary: Office of Technology Development, Office of Research and Development, Office of Demonstration, Testing, and Evaluation

    International Nuclear Information System (INIS)

    1994-10-01

    The US Department of Energy (DOE) Office of Environmental Management, formerly the Office of Environmental Restoration and Waste Management (EM), was established in November 1989 as the first step toward correcting contamination problems resulting from nearly 50 years of nuclear weapons production and fuel processing activities. EM consolidates several DOE organizations previously responsible for the handling, treatment, and disposition of radioactive and hazardous waste. Within EM, the Office of Technology Development (OTD/EM-50) is responsible for developing technologies to meet DOE's goal for environmental restoration. OTD manages an aggressive national program of applied research, development, demonstration, testing, and evaluation (RDDT and E) for environmental cleanup, waste management, and related technologies. The program is designed to resolve major technical issues, to rapidly advanced beyond current technologies for environmental restoration and waste management operations, and to expedite compliance with applicable environmental laws and regulations. This report summarizes Fiscal Year 1994 (FY94) programmatic information, accomplishments, and planned activities relevant to the individual activities within OTD's RDDT and E

  5. Tailored approaches in drug development and diagnostics : from molecular design to biological model systems

    NARCIS (Netherlands)

    Sahlgren, C.M.; Meinander, A.; Zhang, H.; Cheng, F.; Preis, Maren; Xu, C.; Salminen, T.A.; Toivola, D.M.; Abankwa, D.; Rosling, A.; Karaman, D.Ş.; Salo-Ahen, O.M.H.; Österbacka, R.; Eriksson, J.E.; Willför, S.; Petre, I.; Peltonen, J.; Leino, R.; Johnson, M.; Rosenholm, J.; Sandler, N.

    2017-01-01

    Approaches to increase the efficiency in developing drugs and diagnostics tools, including new drug delivery and diagnostic technologies, are needed for improved diagnosis and treatment of major diseases and health problems such as cancer, inflammatory diseases, chronic wounds, and antibiotic

  6. 78 FR 66744 - Draft Guidance for Industry on Pulmonary Tuberculosis: Developing Drugs for Treatment; Availability

    Science.gov (United States)

    2013-11-06

    ...] Draft Guidance for Industry on Pulmonary Tuberculosis: Developing Drugs for Treatment; Availability...) is announcing the availability of a draft guidance for industry entitled ``Pulmonary Tuberculosis... of antimycobacterial drugs for the treatment of pulmonary tuberculosis. This guidance applies to the...

  7. Projecting ADME Behavior and Drug-Drug Interactions in Early Discovery and Development: Application of the Extended Clearance Classification System.

    Science.gov (United States)

    El-Kattan, Ayman F; Varma, Manthena V; Steyn, Stefan J; Scott, Dennis O; Maurer, Tristan S; Bergman, Arthur

    2016-12-01

    To assess the utility of Extended Clearance Classification System (ECCS) in understanding absorption, distribution, metabolism, and elimination (ADME) attributes and enabling victim drug-drug interaction (DDI) predictions. A database of 368 drugs with relevant ADME parameters, main metabolizing enzymes, uptake transporters, efflux transporters, and highest change in exposure (%AUC) in presence of inhibitors was developed using published literature. Drugs were characterized according to ECCS using ionization, molecular weight and estimated permeability. Analyses suggested that ECCS class 1A drugs are well absorbed and systemic clearance is determined by metabolism mediated by CYP2C, esterases, and UGTs. For class 1B drugs, oral absorption is high and the predominant clearance mechanism is hepatic uptake mediated by OATP transporters. High permeability neutral/basic drugs (class 2) showed high oral absorption, with metabolism mediated generally by CYP3A, CYP2D6 and UGTs as the predominant clearance mechanism. Class 3A/4 drugs showed moderate absorption with dominant renal clearance involving OAT/OCT2 transporters. Class 3B drugs showed low to moderate absorption with hepatic uptake (OATPs) and/or renal clearance as primary clearance mechanisms. The highest DDI risk is typically seen with class 2/1B/3B compounds manifested by inhibition of either CYP metabolism or active hepatic uptake. Class 2 showed a wider range in AUC change likely due to a variety of enzymes involved. DDI risk for class 3A/4 is small and associated with inhibition of renal transporters. ECCS provides a framework to project ADME profiles and further enables prediction of victim DDI liabilities in drug discovery and development.

  8. Thirty Years of Orphan Drug Legislation and the Development of Drugs to Treat Rare Seizure Conditions: A Cross Sectional Analysis.

    Science.gov (United States)

    Döring, Jan Henje; Lampert, Anette; Hoffmann, Georg F; Ries, Markus

    2016-01-01

    Epilepsy is a serious chronic health condition with a high morbidity impairing the life of patients and afflicted families. Many epileptic conditions, especially those affecting children, are rare disorders generating an urgent medical need for more efficacious therapy options. Therefore, we assessed the output of the US and European orphan drug legislations. Quantitative analysis of the FDA and EMA databases for orphan drug designations according to STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) criteria. Within the US Orphan Drug Act 40 designations were granted delivering nine approvals, i.e. clobazam, diazepam viscous solution for rectal administration, felbamate, fosphenytoin, lamotrigine, repository corticotropin, rufinamide, topiramate, and vigabatrin. Since 2000 the EMA granted six orphan drug designations whereof two compounds were approved, i.e. rufinamide and stiripentol. In the US, two orphan drug designations were withdrawn. Orphan drugs were approved for conditions including Lennox-Gastaut syndrome, infantile spasms, Dravet syndrome, and status epilepticus. Comparing time to approval for rufinamide, which was approved in the US and the EU to treat rare seizure conditions, the process seems faster in the EU (2.2 years) than in the US (4.3 years). Orphan drug development in the US and in the EU delivered only few molecular entities to treat rare seizure disorders. The development programs focused on already approved antiepileptic drugs or alternative pharmaceutical formulations. Most orphan drugs approved in the US are not approved in the EU to treat rare seizures although some were introduced after 2000 when the EU adopted the Orphan Drug Regulation.

  9. VISDTA: A video imaging system for detection, tracking, and assessment: Prototype development and concept demonstration

    Energy Technology Data Exchange (ETDEWEB)

    Pritchard, D.A.

    1987-05-01

    It has been demonstrated that thermal imagers are an effective surveillance and assessment tool for security applications because: (1) they work day or night due to their sensitivity to thermal signatures; (2) penetrability through fog, rain, dust, etc., is better than human eyes; (3) short or long range operation is possible with various optics; and (4) they are strictly passive devices providing visible imagery which is readily interpreted by the operator with little training. Unfortunately, most thermal imagers also require the setup of a tripod, connection of batteries, cables, display, etc. When this is accomplished, the operator must manually move the camera back and forth searching for signs of aggressor activity. VISDTA is designed to provide automatic panning, and in a sense, ''watch'' the imagery in place of the operator. The idea behind the development of VISDTA is to provide a small, portable, rugged system to automatically scan areas and detect targets by computer processing of images. It would use a thermal imager and possibly an intensified day/night TV camera, a pan/ tilt mount, and a computer for system control. If mounted on a dedicated vehicle or on a tower, VISDTA will perform video motion detection functions on incoming video imagery, and automatically scan predefined patterns in search of abnormal conditions which may indicate attempted intrusions into the field-of-regard. In that respect, VISDTA is capable of improving the ability of security forces to maintain security of a given area of interest by augmenting present techniques and reducing operator fatigue.

  10. Genetic Interactions of STAT3 and Anticancer Drug Development

    International Nuclear Information System (INIS)

    Fang, Bingliang

    2014-01-01

    Signal transducer and activator of transcription 3 (STAT3) plays critical roles in tumorigenesis and malignant evolution and has been intensively studied as a therapeutic target for cancer. A number of STAT3 inhibitors have been evaluated for their antitumor activity in vitro and in vivo in experimental tumor models and several approved therapeutic agents have been reported to function as STAT3 inhibitors. Nevertheless, most STAT3 inhibitors have yet to be translated to clinical evaluation for cancer treatment, presumably because of pharmacokinetic, efficacy, and safety issues. In fact, a major cause of failure of anticancer drug development is lack of efficacy. Genetic interactions among various cancer-related pathways often provide redundant input from parallel and/or cooperative pathways that drives and maintains survival environments for cancer cells, leading to low efficacy of single-target agents. Exploiting genetic interactions of STAT3 with other cancer-related pathways may provide molecular insight into mechanisms of cancer resistance to pathway-targeted therapies and strategies for development of more effective anticancer agents and treatment regimens. This review focuses on functional regulation of STAT3 activity; possible interactions of the STAT3, RAS, epidermal growth factor receptor, and reduction-oxidation pathways; and molecular mechanisms that modulate therapeutic efficacies of STAT3 inhibitors

  11. Physiologically Based Pharmacokinetic Modeling: Methodology, Applications, and Limitations with a Focus on Its Role in Pediatric Drug Development

    Directory of Open Access Journals (Sweden)

    Feras Khalil

    2011-01-01

    Full Text Available The concept of physiologically based pharmacokinetic (PBPK modeling was introduced years ago, but it has not been practiced significantly. However, interest in and implementation of this modeling technique have grown, as evidenced by the increased number of publications in this field. This paper demonstrates briefly the methodology, applications, and limitations of PBPK modeling with special attention given to discuss the use of PBPK models in pediatric drug development and some examples described in detail. Although PBPK models do have some limitations, the potential benefit from PBPK modeling technique is huge. PBPK models can be applied to investigate drug pharmacokinetics under different physiological and pathological conditions or in different age groups, to support decision-making during drug discovery, to provide, perhaps most important, data that can save time and resources, especially in early drug development phases and in pediatric clinical trials, and potentially to help clinical trials become more “confirmatory” rather than “exploratory”.

  12. Waste management system functional requirements for Interim Waste Management Facilities (IWMFs) and technology demonstrations, LLWDDD [Low-Level Disposal Development and Demonstration] Program

    International Nuclear Information System (INIS)

    1988-03-01

    The purpose of this report is to build upon the preceding decisions and body of information to prepare draft system functional requirements for each classification of waste disposal currently proposed for Low-Level Waste Disposal Development Demonstration (LLWDDD) projects. Functional requirements identify specific information and data needs necessary to satisfy engineering design criteria/objectives for Interim Waste Management Facilities. This draft will suppor the alternatives evaluation process and will continue to evolve as strategy is implemented, regulatory limits are established, technical and economic uncertainties are resolved, and waste management plans are being implemented. This document will become the planning basis for the new generation of solid LLW management facilities on new sites on the Reservation. Eighteen (18) general system requirements are identified which are applicable to all four Low-Level Waste (LLW) disposal classifications. Each classification of LLW disposal is individually addressed with respect ot waste characteristics, site considerations, facility operations, facility closure/post-closure, intruder barriers, institutional control, and performance monitoring requirements. Three initial LLW disposal sites have been proposed as locations on the ORR for the first demonstrations

  13. Survey of public green energy research, development and demonstration in Denmark; Kortlaegning af offentlig groen energiforskning, -udvikling og -demonstration i Danmark

    Energy Technology Data Exchange (ETDEWEB)

    2012-07-01

    The Danish energy research has a leading position in the world - both in terms of volume and quality. This is the result of a survey of the public green energy research, development and demonstration. The Danish Ministry of Climate, Energy and Building and the Ministry of Science, Innovation and Higher Education have prepared the survey, which provides a factual status with a number of key figures for the public green energy-related RD and D. The survey shows the basic fact that Denmark has a good foundation for RD and D in green energy. Moreover, the survey shows that prioritisation of energy research can be a major driving force behind increased growth and employment. (LN)

  14. Two X-38 Ship Demonstrators in Development at NASA Johnson Space Flight Center

    Science.gov (United States)

    1999-01-01

    This photo shows two X-38 Crew Return Vehicle technology demonstrators under development at NASA's Johnson Space Flight Center, Houston, Texas. The X-38 Crew Return Vehicle (CRV) research project is designed to develop the technology for a prototype emergency crew return vehicle, or lifeboat, for the International Space Station. The project is also intended to develop a crew return vehicle design that could be modified for other uses, such as a joint U.S. and international human spacecraft that could be launched on the French Ariane-5 Booster. The X-38 project is using available technology and off-the-shelf equipment to significantly decrease development costs. Original estimates to develop a capsule-type crew return vehicle were estimated at more than $2 billion. X-38 project officials have estimated that development costs for the X-38 concept will be approximately one quarter of the original estimate. Off-the-shelf technology is not necessarily 'old' technology. Many of the technologies being used in the X-38 project have never before been applied to a human-flight spacecraft. For example, the X-38 flight computer is commercial equipment currently used in aircraft and the flight software operating system is a commercial system already in use in many aerospace applications. The video equipment for the X-38 is existing equipment, some of which has already flown on the space shuttle for previous NASA experiments. The X-38's primary navigational equipment, the Inertial Navigation System/Global Positioning System, is a unit already in use on Navy fighters. The X-38 electromechanical actuators come from previous joint NASA, U.S. Air Force, and U.S. Navy research and development projects. Finally, an existing special coating developed by NASA will be used on the X-38 thermal tiles to make them more durable than those used on the space shuttles. The X-38 itself was an unpiloted lifting body designed at 80 percent of the size of a projected emergency crew return vehicle

  15. Use of PET and the radioligand [carbonyl-11C]WAY-100635 in psychotropic drug development

    International Nuclear Information System (INIS)

    Andree, Bengt; Halldin, Christer; Thorberg, Seth-Olov; Sandell, Johan; Farde, Lars

    2000-01-01

    Positron-emission tomography (PET) provides potential in neuropsychiatric drug development by expanding knowledge of drug action in the living human brain and reducing time consumption and costs. The 5-hydroxytryptamine 1A (5-HT 1A ) receptor is of central interest as a target for the treatment of anxiety, depression, and schizophrenia. Research on the clinical significance of the 5-HT 1A receptor now benefits from the highly selective radioligand [carbonyl- 11 C]WAY-100635 (WAY) for quantitative determination of 5-HT 1A receptors in the primate and human brain in vivo using PET. In this paper, three studies are reviewed to demonstrate the suitability of WAY as radioligand for quantification of central 5-HT 1A receptors in brain and as an applicable tool for drug development. In the first study a monkey model was used to characterize WAY binding. It was confirmed that the reference ligand 8-OH-DPAT and psychoactive drugs such as buspirone and pindolol occupies 5-HT 1A receptors in the primate brain. Pindolol is an β-adrenoreceptor antagonist with a high affinity to 5-HT 1A receptors. This drug has been suggested in combination with selective serotonin reuptake inhibitors for the treatment of depression and was given to healthy males in the second study. Pindolol induced a marked inhibition of central 5-HT 1A receptors as calculated by the ratio-analysis method and simplified reference tissue model, 2 h after administration of 10 mg as a single oral dose. This observation suggests that pindolol may have a role for the suggested potentiation of selective serotonin reuptake inhibitor treatment of depression. The third study was on robalzotan (NAD-299), a recently developed 5-HT 1A receptor antagonist and putative drug with implications for the treatment of depression. In the cynomolgus monkey brain, robalzotan in the dose range 2-100 μg/kg IV occupied 5-HT 1A receptors in a dose-dependent and saturable manner with a maximal calculated occupancy of 70-80%. The

  16. 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

  17. Paediatric Drug Development and Formulation Design—a European Perspective

    NARCIS (Netherlands)

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

    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

  18. Drug-Induced Apoptosis: Mechanism by which Alcohol and Many Other Drugs Can Disrupt Brain Development

    Directory of Open Access Journals (Sweden)

    John W. Olney

    2013-07-01

    Full Text Available Maternal ingestion of alcohol during pregnancy can cause a disability syndrome termed Fetal Alcohol Spectrum Disorder (FASD, which may include craniofacial malformations, structural pathology in the brain, and a variety of long-term neuropsychiatric disturbances. There is compelling evidence that exposure to alcohol during early embryogenesis (4th week of gestation can cause excessive death of cell populations that are essential for normal development of the face and brain. While this can explain craniofacial malformations and certain structural brain anomalies that sometimes accompany FASD, in many cases these features are absent, and the FASD syndrome manifests primarily as neurobehavioral disorders. It is not clear from the literature how alcohol causes these latter manifestations. In this review we will describe a growing body of evidence documenting that alcohol triggers widespread apoptotic death of neurons and oligodendroglia (OLs in the developing brain when administered to animals, including non-human primates, during a period equivalent to the human third trimester of gestation. This cell death reaction is associated with brain changes, including overall or regional reductions in brain mass, and long-term neurobehavioral disturbances. We will also review evidence that many drugs used in pediatric and obstetric medicine, including general anesthetics (GAs and anti-epileptics (AEDs, mimic alcohol in triggering widespread apoptotic death of neurons and OLs in the third trimester-equivalent animal brain, and that human children exposed to GAs during early infancy, or to AEDs during the third trimester of gestation, have a significantly increased incidence of FASD-like neurobehavioral disturbances. These findings provide evidence that exposure of the developing human brain to GAs in early infancy, or to alcohol or AEDs in late gestation, can cause FASD-like neurodevelopmental disability syndromes. We propose that the mechanism by which

  19. Homelessness and drug misuse in developing countries: A mathematical approach

    Science.gov (United States)

    Bhunu, C. P.

    2014-06-01

    Homelessness and drug-misuse are known to exist like siamese twins. We present a model to capture the dynamics in the growth in the number of homeless (street kids and street adults) and drug misusers. The reproduction numbers of the model are determined and analyzed. Results from this study suggests that adult peer pressure plays a more significant role in the growth of drug-misuse and the number of street kids. This result suggests that in resource constrained settings intervention strategies should be tailor made to target adults whose behaviour influence others to misuse drugs and abuse children. Furthermore, numerical simulations show that homelessness and drug-misuse positively enhances, the growth of each other. Thus, to effectively control these two social problems require strategies targeting both of them.

  20. HIV and AIDS among adolescents who use drugs: opportunities for drug policy reform within the sustainable development agenda.

    Science.gov (United States)

    Tinasti, Khalid

    2018-02-01

    The international community's commitment to halve by 2015 the HIV transmission among people who inject drugs has not only been largely missed, instead new HIV infections have increased by 30%. Moreover, drug injection remains one of the drivers of new HIV infections due to punitive responses and lack of harm reduction resourcing. In the midst of this situation, adolescents are a forgotten component of the global response to illegal drugs and their link with HIV infection. The Sustainable Development Goals (SDGs) present an opportunity to achieve the global objective of ending AIDS among adolescents who use drugs, by addressing the structural vulnerabilities they face be they economic, social, criminal, health-related or environmental. The implementation of the SDGs presents an opportunity to address the horizontal nature of drug policy and to efficiently address the drugs-adolescents-HIV risk nexus. Adolescent-focused drug policies are linked to goals 1, 3, 4, 10, 16 and 17. Goals 3 and 16 are the most relevant; the targets of the latter link to the criminalization of drug use and punitive policy environments and their impact on adolescents' health and HIV transmission risks. Moreover, it presents an opportunity to include adolescent needs that are missing in the three drug control conventions (1961, 1971 and 1988), and link them with the provisions of the Convention on the Rights of the Child (1989). Finally, the six principles to deliver on sustainable development are also an opportunity to divert adolescents who use drugs away from criminalization and punitive environments in which their vulnerability to HIV is greater. Addressing HIV among adolescents who use drugs is an extremely complex policy issue depending on different sets of binding and non-binding commitments, interventions and stakeholders. The complexity requires a horizontal response provided by the SDGs framework, starting with the collection of disaggregated data on this specific subgroup. Ending

  1. Development and demonstration of calculation tool for industrial drying processes ''DryPack''; Udvikling og demonstration af beregningsvaerktoej til industrielle toerreprocesser ''DryPack''

    Energy Technology Data Exchange (ETDEWEB)

    Schneider, P.; Weinkauff Kristoffersen, J.; Blazniak Andreasen, M. [Teknologisk Institut, Aarhus (Denmark); Elmegaard, B.; Kaern, M. [Danmarks Tekniske Univ.. DTU Mekanik, Kgs. Lyngby (Denmark); Monrad Andersen, C. [Lokal Energi, Viby J. (Denmark); Grony, K. [SE Big Blue, Kolding (Denmark); Stihoej, A. [Enervision, Kolding (Denmark)

    2013-03-15

    In this project we have developed a calculation tool for calculating energy consumption in different drying processes - primarily drying processes with air. The program can be used to determine the energy consumption of a current drying process, after which it can be calculated how much energy can be saved by various measures. There is also developed a tool for the simulation of a batch drier, which calculates the drying of a batch depending on the time. The programs have demonstrated their usefulness in connection with three cases that are reviewed in the report. In the project measurements on four different dryers have been carried out, and energy consumption is calculated using ''DryPack''. With ''DryPack'' it is possible to find potential savings by optimizing the drying processes. The program package includes utilities for the calculation of moist air: 1) Calculation of the thermodynamic properties of moist air; 2) Device operation with moist air (mixing, heating, cooling and humidification); 3) Calculation of the relative change of the drying time by changing the process parameters; 4) IX-diagram at a temperature above 100 deg. C. (LN)

  2. The impact of the written request process on drug development in childhood cancer.

    Science.gov (United States)

    Snyder, Kristen M; Reaman, Gregory; Avant, Debbie; Pazdur, Richard

    2013-04-01

    The Food and Drug Administration (FDA) Modernization Act, enacted in 1997, created a pediatric exclusivity incentive allowing sponsors to qualify for an additional 6 months of marketing exclusivity after satisfying the requirements outlined in the Written Request (WR). This review evaluates the impact of the WR mechanism on the development of oncology drugs in children. A search of the FDA document archiving, reporting, and regulatory tracking system was performed for January 1, 2000 to December 31, 2010. Drugs were identified and pediatric-specific labeling information was obtained from Drugs@fda.gov and FDA Pediatric Labeling Changes Table. Fifty WRs have been issued for oncology drugs. Pediatric studies have been submitted for 14 drugs. Thirteen received pediatric exclusivity. As of December 31, 2010, labeling changes have been made for 11 drugs. Three drugs were approved for pediatric use. WRs have provided a mechanism to promote the study of drugs in pediatric malignancies. Information from studies resulting from the WRs regarding safety, pharmacokinetics, and tolerability of oncology drugs has been incorporated into pediatric labeling for 11/14 of the drugs. Earlier communication and collaboration between the FDA, National Cancer Institute, clinical investigators, and commercial sponsors are envisioned to facilitate the identification and prioritization of emerging new drugs of interest for WR consideration. Since this is the only regulatory mechanism, resulting from specific legislative initiatives relevant to cancer drug development for children, efforts to enhance its impact on increasing drug approval for pediatric cancer indications are warranted. Copyright © 2013 Wiley Periodicals, Inc.

  3. Cdc7 kinase - a new target for drug development.

    Science.gov (United States)

    Swords, Ronan; Mahalingam, Devalingam; O'Dwyer, Michael; Santocanale, Corrado; Kelly, Kevin; Carew, Jennifer; Giles, Francis

    2010-01-01

    The cell division cycle 7 (Cdc7) is a serine threonine kinase that is of critical importance in the regulation of normal cell cycle progression. Cdc7 kinase is highly conserved during evolution and much has been learned about its biological roles in humans through the study of lower eukaryotes, particularly yeasts. Two important regulator proteins, Dbf4 and Drf1, bind to and modulate the kinase activity of human Cdc7 which phosphorylates several sites on Mcm2 (minichromosome maintenance protein 2), one of the six subunits of the replicative DNA helicase needed for duplication of the genome. Through regulation of both DNA synthesis and DNA damage response, both key functions in the survival of tumour cells, Cdc7 becomes an attractive target for pharmacological inhibition. There are much data available on the pre-clinical anti-cancer effects of Cdc7 depletion and although there are no available Cdc7 inhibitors in clinical trials as yet, several lead compounds are being optimised for this purpose. In this review, we will address the current status of Cdc7 as an important target for new drug development.

  4. Development of Novel Drugs from Marine Surface Associated Microorganisms

    Directory of Open Access Journals (Sweden)

    Suhelen Egan

    2010-03-01

    Full Text Available While the oceans cover more than 70% of the Earth’s surface, marine derived microbial natural products have been largely unexplored. The marine environment is a habitat for many unique microorganisms, which produce biologically active compounds (“bioactives” to adapt to particular environmental conditions. For example, marine surface associated microorganisms have proven to be a rich source for novel bioactives because of the necessity to evolve allelochemicals capable of protecting the producer from the fierce competition that exists between microorganisms on the surfaces of marine eukaryotes. Chemically driven interactions are also important for the establishment of cross-relationships between microbes and their eukaryotic hosts, in which organisms producing antimicrobial compounds (“antimicrobials”, may protect the host surface against over colonisation in return for a nutrient rich environment. As is the case for bioactive discovery in general, progress in the detection and characterization of marine microbial bioactives has been limited by a number of obstacles, such as unsuitable culture conditions, laborious purification processes, and a lack of de-replication. However many of these limitations are now being overcome due to improved microbial cultivation techniques, microbial (meta- genomic analysis and novel sensitive analytical tools for structural elucidation. Here we discuss how these technical advances, together with a better understanding of microbial and chemical ecology, will inevitably translate into an increase in the discovery and development of novel drugs from marine microbial sources in the future.

  5. Overview of Biomarkers and Surrogate Endpoints in Drug Development

    Directory of Open Access Journals (Sweden)

    John A. Wagner

    2002-01-01

    Full Text Available There are numerous factors that recommend the use of biomarkers in drug development including the ability to provide a rational basis for selection of lead compounds, as an aid in determining or refining mechanism of action or pathophysiology, and the ability to work towards qualification and use of a biomarker as a surrogate endpoint. Examples of biomarkers come from many different means of clinical and laboratory measurement. Total cholesterol is an example of a clinically useful biomarker that was successfully qualified for use as a surrogate endpoint. Biomarkers require validation in most circumstances. Validation of biomarker assays is a necessary component to delivery of high-quality research data necessary for effective use of biomarkers. Qualification is necessary for use of a biomarker as a surrogate endpoint. Putative biomarkers are typically identified because of a relationship to known or hypothetical steps in a pathophysiologic cascade. Biomarker discovery can also be effected by expression profiling experiment using a variety of array technologies and related methods. For example, expression profiling experiments enabled the discovery of adipocyte related complement protein of 30 kD (Acrp30 or adiponectin as a biomarker for in vivo activation of peroxisome proliferator-activated receptors (PPAR γ activity.

  6. PCSK9: Regulation and Target for Drug Development for Dyslipidemia.

    Science.gov (United States)

    Burke, Amy C; Dron, Jacqueline S; Hegele, Robert A; Huff, Murray W

    2017-01-06

    Proprotein convertase subtilisin/kexin type-9 (PCSK9) is a secreted zymogen expressed primarily in the liver. PCSK9 circulates in plasma, binds to cell surface low-density lipoprotein (LDL) receptors, is internalized, and then targets the receptors to lysosomal degradation. Studies of naturally occurring PCSK9 gene variants that caused extreme plasma LDL cholesterol (LDL-C) deviations and altered atherosclerosis risk unleashed a torrent of biological and pharmacological research. Rapid progress in understanding the physiological regulation of PCSK9 was soon translated into commercially available biological inhibitors of PCSK9 that reduced LDL-C levels and likely also cardiovascular outcomes. Here we review the swift evolution of PCSK9 from novel gene to drug target, to animal and human testing, and finally to outcome trials and clinical applications. In addition, we explore how the genetics-guided path to PCSK9 inhibitor development exemplifies a new paradigm in pharmacology. Finally, we consider some potential challenges as PCSK9 inhibition becomes established in the clinic.

  7. Evaluation of waste treatment technologies by LLWDDD [Low-Level Waste Disposal Development and Demonstration] Programs

    International Nuclear Information System (INIS)

    Kennerly, J.M.; Williams, L.C.; Dole, L.R.; Genung, R.K.

    1987-01-01

    Waste treatments are divided into four categories: (1) volume reduction; (2) conditioning to improve waste form performance; (3) segregation to achieve waste reduction; and (4) separation to remove radioactive (or hazardous) constituents. Two waste treatment demonstrations are described. In the first, volume reduction by mechanical means was achieved during the supercompaction of 300 55-gal drums of solid waste at ORNL. In the second demonstration, conditioning of waste through immobilization and packaging to improve the performance of the waste form is being evaluated. The final section of this paper describes potential scenarios for the management of uranium-contaminated wastes at the Y-12 Plant in Oak Ridge and emphasizes where demonstrations of treatment technology will be needed to implement the scenarios. Separation and thermal treatment are identified as the principal means for treating these wastes. 15 figs

  8. Development of a demonstration reactor using thoria as a Fischer-Tropsch catalyst

    International Nuclear Information System (INIS)

    Colmenares, C.A.; McLean, W.

    1981-12-01

    We have demonstrated experimentally that thorium oxide may be used as a catalyst with CO + H 2 mixtures to produce either methanol or a mixture of hydrocarbons from C 1 to C 5 (saturated and unsaturated). The immunity of ThO 2 to poisoning by sulfur compounds makes its use very attractive for industrial applications. We are proposing to optimize the experimental conditions of the catalytic process using a one-inch reactor and to scope and define the experimental conditions for a pilot plant demonstration

  9. Intraarterial Microdosing, a Novel Drug Development Approach, Proof-of-Concept PET Study in Rats

    Science.gov (United States)

    Burt, Tal; Rouse, Douglas C.; Lee, Kihak; Wu, Huali; Layton, Anita T.; Hawk, Thomas C.; Weitzel, Douglas H.; Chin, Bennett B.; Cohen-Wolkowiez, Michael; Chow, Shein-Chung; Noveck, Robert J.

    2016-01-01

    Intraarterial microdosing (IAM) is a novel drug development approach combining intraarterial drug delivery and microdosing. We aimed to demonstrate that IAM leads to target exposure similar to that of systemic full-dose administration but with minimal systemic exposure. IAM could enable the safe, inexpensive, and early study of novel drugs at the first-in-human stage and the study of established drugs in vulnerable populations. Methods Insulin was administered intraarterially (ipsilateral femoral artery) or systemically to 8 CD IGS rats just before blood sampling or 60-min 18F-FDG uptake PET imaging of ipsilateral and contralateral leg muscles (lateral gastrocnemius) and systemic muscles (spinotrapezius). The 18F-FDG uptake slope analysis was used to compare the interventions. Plasma levels of insulin and glucose were compared using area under the curve calculated by the linear trapezoidal method. A physiologically based computational pharmacokinetics/pharmacodynamics model was constructed to simulate the relationship between the administered dose and response over time. Results 18F-FDG slope analysis found no difference between IAM and systemic full-dose slopes (0.0066 and 0.0061, respectively; 95% confidence interval [CI], −0.024 to 0.029; P = 0.7895), but IAM slope was statistically significantly greater than systemic microdose (0.0018; 95% CI, −0.045 to −0.007; P = 0.0147) and sham intervention (−0.0015; 95% CI, 0.023–0.058; P = 0.0052). The pharmacokinetics/pharmacodynamics data were used to identify model parameters that describe membrane insulin binding and glucose–insulin dynamics. Conclusion Target exposure after IAM was similar to systemic full dose administration but with minimal systemic effects. The computational pharmacokinetics/pharmacodynamics model can be generalized to predict whole-body response. Findings should be validated in larger, controlled studies in animals and humans using a range of targets and classes of drugs. PMID

  10. Research synergy and drug development: Bright stars in neighboring constellations.

    Science.gov (United States)

    Keserci, Samet; Livingston, Eric; Wan, Lingtian; Pico, Alexander R; Chacko, George

    2017-11-01

    Drug discovery and subsequent availability of a new breakthrough therapeutic or 'cure' is a compelling example of societal benefit from research advances. These advances are invariably collaborative, involving the contributions of many scientists to a discovery network in which theory and experiment are built upon. To document and understand such scientific advances, data mining of public and commercial data sources coupled with network analysis can be used as a digital methodology to assemble and analyze component events in the history of a therapeutic. This methodology is extensible beyond the history of therapeutics and its use more generally supports (i) efficiency in exploring the scientific history of a research advance (ii) documenting and understanding collaboration (iii) portfolio analysis, planning and optimization (iv) communication of the societal value of research. Building upon prior art, we have conducted a case study of five anti-cancer therapeutics to identify the collaborations that resulted in the successful development of these therapeutics both within and across their respective networks. We have linked the work of over 235,000 authors in roughly 106,000 scientific publications that capture the research crucial for the development of these five therapeutics. Applying retrospective citation discovery, we have identified a core set of publications cited in the networks of all five therapeutics and additional intersections in combinations of networks. We have enriched the content of these networks by annotating them with information on research awards from the US National Institutes of Health (NIH). Lastly, we have mapped these awards to their cognate peer review panels, identifying another layer of collaborative scientific activity that influenced the research represented in these networks.

  11. Research synergy and drug development: Bright stars in neighboring constellations

    Directory of Open Access Journals (Sweden)

    Samet Keserci

    2017-11-01

    Full Text Available Drug discovery and subsequent availability of a new breakthrough therapeutic or ‘cure’ is a compelling example of societal benefit from research advances. These advances are invariably collaborative, involving the contributions of many scientists to a discovery network in which theory and experiment are built upon. To document and understand such scientific advances, data mining of public and commercial data sources coupled with network analysis can be used as a digital methodology to assemble and analyze component events in the history of a therapeutic. This methodology is extensible beyond the history of therapeutics and its use more generally supports (i efficiency in exploring the scientific history of a research advance (ii documenting and understanding collaboration (iii portfolio analysis, planning and optimization (iv communication of the societal value of research. Building upon prior art, we have conducted a case study of five anti-cancer therapeutics to identify the collaborations that resulted in the successful development of these therapeutics both within and across their respective networks. We have linked the work of over 235,000 authors in roughly 106,000 scientific publications that capture the research crucial for the development of these five therapeutics. Applying retrospective citation discovery, we have identified a core set of publications cited in the networks of all five therapeutics and additional intersections in combinations of networks. We have enriched the content of these networks by annotating them with information on research awards from the US National Institutes of Health (NIH. Lastly, we have mapped these awards to their cognate peer review panels, identifying another layer of collaborative scientific activity that influenced the research represented in these networks. Keywords: Information science, Cancer research

  12. Development of novel alkylating drugs as anticancer agents.

    Science.gov (United States)

    Izbicka, Elzbieta; Tolcher, Anthony W

    2004-06-01

    Although conventional alkylating drugs have proven efficacy in the treatment of malignancies, the agents themselves are not selective. Therefore, non-specific alkylation of cellular nucleophilic targets may contribute to many of the observed toxic effects. Novel approaches to drug discovery have resulted in candidate agents that are focused on 'soft alkylation'--alkylators with greater target selectivity. This review highlights the discovery of small molecule drugs that bind to DNA with higher selectivity, act in a unique hypoxic tumor environment, or covalently bind specific protein targets overexpressed in cancer, such as topoisomerase II, glutathione transferase pi1, beta-tubulin and histone deacetylase.

  13. Demonstration of genetic exchange during cyclical development of Leishmania in the sand fly vector.

    Science.gov (United States)

    Akopyants, Natalia S; Kimblin, Nicola; Secundino, Nagila; Patrick, Rachel; Peters, Nathan; Lawyer, Phillip; Dobson, Deborah E; Beverley, Stephen M; Sacks, David L

    2009-04-10

    Genetic exchange has not been shown to be a mechanism underlying the extensive diversity of Leishmania parasites. We report here evidence that the invertebrate stages of Leishmania are capable of having a sexual cycle consistent with a meiotic process like that described for African trypanosomes. Hybrid progeny were generated that bore full genomic complements from both parents, but kinetoplast DNA maxicircles from one parent. Mating occurred only in the sand fly vector, and hybrids were transmitted to the mammalian host by sand fly bite. Genetic exchange likely contributes to phenotypic diversity in natural populations, and analysis of hybrid progeny will be useful for positional cloning of the genes controlling traits such as virulence, tissue tropism, and drug resistance.

  14. 78 FR 29755 - Human Immunodeficiency Virus Patient-Focused Drug Development and Human Immunodeficiency Virus...

    Science.gov (United States)

    2013-05-21

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0473] Human Immunodeficiency Virus Patient-Focused Drug Development and Human Immunodeficiency Virus Cure... an opportunity for public comment on human immunodeficiency virus (HIV) Patient-Focused Drug...

  15. 78 FR 46969 - Human Immunodeficiency Virus Patient-Focused Drug Development and Human Immunodeficiency Virus...

    Science.gov (United States)

    2013-08-02

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0473] Human Immunodeficiency Virus Patient-Focused Drug Development and Human Immunodeficiency Virus Cure... for the notice of public meeting entitled ``Human Immunodeficiency Virus (HIV) Patient-Focused Drug...

  16. 78 FR 63223 - Fibromyalgia Public Meeting on Patient-Focused Drug Development; Correction

    Science.gov (United States)

    2013-10-23

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-N-2013-1041] Fibromyalgia Public Meeting on Patient-Focused Drug Development; Correction AGENCY: Food and Drug... 23, 2013 (78 FR 58313). The document announced a public meeting entitled ``Fibromyalgia Public...

  17. 78 FR 32667 - Draft Guidance for Industry on Rheumatoid Arthritis: Developing Drug Products for Treatment...

    Science.gov (United States)

    2013-05-31

    ... products. This guidance revises the guidance for industry entitled ``Clinical Development Programs for... Information, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave... (HFM-40), Center for Biologics Evaluation and Research, Food and Drug Administration, 1401 Rockville...

  18. 78 FR 32669 - New Approaches to Antibacterial Drug Development; Request for Comments

    Science.gov (United States)

    2013-05-31

    ... Management (HFA- 305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. FOR... concern, we are seeking to explore new clinical development paradigms for antibacterial drugs. Areas of ongoing need are numerous and include new drugs for treatment of hospital-acquired bacterial pneumonia...

  19. Development and Demonstration of the Open Automated Demand Response Standard for the Residential Sector

    Energy Technology Data Exchange (ETDEWEB)

    Herter, Karen; Rasin, Josh; Perry, Tim

    2009-11-30

    The goal of this study was to demonstrate a demand response system that can signal nearly every customer in all sectors through the integration of two widely available and non- proprietary communications technologies--Open Automated Demand Response (OpenADR) over lnternet protocol and Utility Messaging Channel (UMC) over FM radio. The outcomes of this project were as follows: (1) a software bridge to allow translation of pricing signals from OpenADR to UMC; and (2) a portable demonstration unit with an lnternet-connected notebook computer, a portfolio of DR-enabling technologies, and a model home. The demonstration unit provides visitors the opportunity to send electricity-pricing information over the lnternet (through OpenADR and UMC) and then watch as the model appliances and lighting respond to the signals. The integration of OpenADR and UMC completed and demonstrated in this study enables utilities to send hourly or sub-hourly electricity pricing information simultaneously to the residential, commercial and industrial sectors.

  20. Development of large aperture telescope technology (LATT): test results on a demonstrator bread-board

    Science.gov (United States)

    Briguglio, R.; Xompero, M.; Riccardi, A.; Lisi, F.; Duò, F.; Vettore, C.; Gallieni, D.; Tintori, M.; Lazzarini, P.; Patauner, C.; Biasi, R.; D'Amato, F.; Pucci, M.; Pereira do Carmo, João.

    2017-11-01

    The concept of a low areal density primary mirror, actively controlled by actuators, has been investigated through a demonstration prototype. A spherical mirror (400 mm diameter, 2.7 Kg mass) has been manufactured and tested in laboratory and on the optical bench, to verify performance, controllability and optical quality. In the present paper we will describe the prototype and the test results.

  1. From demonstration projects to volume market : Market development for advanced housing renovation

    NARCIS (Netherlands)

    Mlecnik, E.; Prendergast, E.; Rodsjo, A.; Haavik, T.; Parker, P.

    2010-01-01

    How do we get from demonstration projects to a volume market for very low energy demand in advanced housing renovation? The contributors to this report have been working with this issue for many years. Some worked in both IEA SHC Task 28 Sustainable Housing (2000-2005) and in SHC Task 37 Advanced

  2. Development of a Pharmacoeconomic Model to Demonstrate the Effect of Clinical Pharmacist Involvement in Diabetes Management.

    Science.gov (United States)

    Ourth, Heather; Nelson, Jordan; Spoutz, Patrick; Morreale, Anthony P

    2018-05-01

    A data collection tool was developed and nationally deployed to clinical pharmacists (CPs) working in advanced practice provider roles within the Department of Veterans Affairs to document interventions and associated clinical outcomes. Intervention and short-term clinical outcome data derived from the tool were used to populate a validated clinical outcomes modeling program to predict long-term clinical and economic effects. To predict the long-term effect of CP-provided pharmacotherapy management on outcomes and costs for patients with type 2 diabetes. Baseline patient demographics and biomarkers were extracted for type 2 diabetic patients having > 1 encounter with a CP using the tool between January 5, 2013, and November 20, 2014. Treatment biomarker values were extracted 12 months after the patient's initial visit with the CP. The number of visits with the CP was extracted from the electronic medical record, and duration of visit time was quantified by Current Procedural Terminology codes. Simulation modeling was performed on 3 patient cohorts-those with a baseline hemoglobin A1c of 8% to < 9%, 9% to < 10%, and ≥ 10%-to estimate long-term cost and clinical outcomes using modeling based on pivotal trial data (the Archimedes Model). A sensitivity analysis was conducted to assess the extent to which our results were dependent on assumptions related to program effectiveness and costs. A total of 7,310 patients were included in the analysis. Analysis of costs and events on 2-, 3-, 5-, and 10-year time horizons demonstrated significant reductions in major adverse cardiovascular events (MACEs), myocardial infarctions (MIs), episodes of acute heart failure, foot ulcers, and foot amputations in comparison with a control group receiving usual guideline-directed medical care. In the cohort with a baseline A1c of ≥ 10%, the absolute risk reduction was 1.82% for MACE, 1.73% for MI, 2.43% for acute heart failure, 5.38% for foot ulcers, and 2.03% for foot amputations. The

  3. Scenarios for Benefits Analysis of Energy Research, Development,Demonstration and Deployment

    Energy Technology Data Exchange (ETDEWEB)

    Gumerman, Etan; Marnay, Chris

    2005-09-07

    For at least the last decade, evaluation of the benefits of research, development, demonstration, and deployment (RD3) by the U.S. Department of Energy has been conducted using deterministic forecasts that unrealistically presume we can precisely foresee our future 10, 25,or even 50 years hence. This effort tries, in a modest way, to begin a process of recognition that the reality of our energy future is rather one rife with uncertainty. The National Energy Modeling System (NEMS) is used by the Department of Energy's Office of Energy Efficiency and Renewable Energy (EE) and Fossil Energy (FE) for their RD3 benefits evaluation. In order to begin scoping out the uncertainty in these deterministic forecasts, EE and FE designed two futures that differ significantly from the basic NEMS forecast. A High Fuel Price Scenario and a Carbon Cap Scenario were envisioned to forecast alternative futures and the associated benefits. Ernest Orlando Lawrence Berkeley National Laboratory (LBNL) implemented these scenarios into its version of NEMS,NEMS-LBNL, in late 2004, and the Energy Information Agency created six scenarios for FE in early 2005. The creation and implementation of the EE-FE scenarios are explained in this report. Both a Carbon Cap Scenario and a High Fuel Price Scenarios were implemented into the NEMS-LBNL. EIA subsequently modeled similar scenarios using NEMS. While the EIA and LBNL implementations were in some ways rather different, their forecasts do not significantly diverge. Compared to the Reference Scenario, the High Fuel Price Scenario reduces energy consumption by 4 percent in 2025, while in the EIA fuel price scenario (known as Scenario 4) reduction from its corresponding reference scenario (known as Scenario 0) in 2025 is marginal. Nonetheless, the 4 percent demand reduction does not lead to other cascading effects that would significantly differentiate the two scenarios. The LBNL and EIA carbon scenarios were mostly identical. The only major

  4. A Development-Oriented IS Evaluation Approach: Case Demonstration for DSS

    Directory of Open Access Journals (Sweden)

    Shah J Miah

    2012-04-01

    Full Text Available Information systems (IS development research needs a broader conceptual lens for evaluating IS design qualities. Most conventional IS evaluation approaches are focused on narrow objectives, such as the process and content rather than the development process as a whole. This paper describes a qualitative evaluation of a new approach that extends evaluation strategies to incorporate development phases, specifically within decision support systems (DSS development. The conceptual approach is based on a mental model from the design science research paradigm and evaluates DSS development at various design checkpoints. This paper also describes qualitative findings on the applicability of the conceptual approach in a socio-technical design context.

  5. Applying insights from biofilm biology to drug development - can a new approach be developed?

    DEFF Research Database (Denmark)

    Bjarnsholt, Thomas; Ciofu, Oana; Molin, Søren

    2013-01-01

    Most of the research on bacterial pathogenesis has focused on acute infections, but much less is known about the pathogenesis of infections caused by bacteria that grow as aggregates in biofilms. These infections tend to be chronic as they resist innate and adaptive immune defence mechanisms...... and pathology, and discuss how a deep insight into the physical and biological characteristics of biofilms can inform therapeutic strategies and molecular targets for the development of anti-biofilm drugs....

  6. The development of the human exploration demonstration project (HEDP), a planetary systems testbed

    Science.gov (United States)

    Chevers, Edward S.; Korsmeyer, David J.

    1993-01-01

    The Human Exploration Demonstration Project (HEDP) is an ongoing task at the National Aeronautics and Space Administration's Ames Research Center to address the advanced technology requirements necessary to implement an integrated working and living environment for a planetary surface habitat. The integrated environment will consist of life support systems, physiological monitoring of project crew, a virtual environment workstation, and centralized data acquisition and habitat systems health monitoring. There will be several robotic systems on a simulated planetary landscape external to the habitat environment to provide representative work loads for the crew. This paper describes the status of the HEDP after one year, the major facilities composing the HEDP, the project's role as an Ames Research Center testbed, and the types of demonstration scenarios that will be run to showcase the technologies.

  7. A small scale accelerator driven subcritical assembly development and demonstration experiment at LAMPF

    International Nuclear Information System (INIS)

    Wender, S.A.; Venneri, F.; Bowman, C.D.; Arthur, E.D.; Heighway, E.A.; Beard, C.A.; Bracht, R.R.; Buksa, J.J.; Chavez, W.; DeVolder, B.G.

    1994-01-01

    A small scale experiment is described that will demonstrate many of the aspects of accelerator-driven transmutation technology. This experiment uses the high-power proton beam from the Los Alamos Meson Physics Facility accelerator and will be located in the Area-A experimental hall. Beam currents of up to 1 mA will be used to produce neutrons with a molten lead target. The target is surrounded by a molten salt and graphite moderator blanket. Fissionable material can be added to the molten salt to demonstrate plutonium burning or transmutation of commercial spent fuel or energy production from thorium. The experiment will be operated at power levels up to 5 MW t

  8. Graphite Isotope Ratio Method Development Report: Irradiation Test Demonstration of Uranium as a Low Fluence Indicator

    International Nuclear Information System (INIS)

    Reid, B.D.; Gerlach, D.C.; Love, E.F.; McNeece, J.P.; Livingston, J.V.; Greenwood, L.R.; Petersen, S.L.; Morgan, W.C.

    1999-01-01

    This report describes an irradiation test designed to investigate the suitability of uranium as a graphite isotope ratio method (GIRM) low fluence indicator. GIRM is a demonstrated concept that gives a graphite-moderated reactor's lifetime production based on measuring changes in the isotopic ratio of elements known to exist in trace quantities within reactor-grade graphite. Appendix I of this report provides a tutorial on the GIRM concept

  9. The current status of orphan drug development in Europe and the US

    OpenAIRE

    Hall, Anthony K; Carlson, Marilyn R

    2014-01-01

    Orphan drug legislation has been introduced in a number of countries in order to stimulate the development of treatments for rare diseases by introducing commercial incentives for companies wishing to undertake that development. In order to navigate the maze of regulatory regulations and procedures so that companies can make proper use of the orphan drug incentives, specialist knowledge is required. This article will review the current status of orphan drug development in the EU and the US, e...

  10. Demonstration technology development of new hydrogen energy; Shinsuiso energy jissho gijutsu kaihatsu

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-03-01

    A phenomenon of excess heat generation through the electrolysis of heavy water using palladium metals as electrode can be recognized as new hydrogen energy. Its mechanism has been investigated for four years since FY 1993. In FY 1993, the New Hydrogen Energy Demonstration Research Center and the New Hydrogen Energy Demonstration Laboratory were organized, and the research was initiated. For the excess heat generation demonstration model tests, two types of electrolysis experimental units were constructed, and the Pd/D-based electrolysis experiments were initiated. For the measurements of excess heat using an open type electrolysis cell, there were rather large errors ranging from -13% to +7%. It is necessary to improve the accuracy. For the measurements using a fuel cell type electrolysis cell, generation of the excess heat ranging from 0% to 6% was observed. For the validity of this, it is required to confirm the long-term stability of calibration and cell components. For the correlation between the increase in absorbing rate and the generation of excess heat, results of 2 to 3% lower were obtained. 28 refs., 89 figs., 26 tabs.

  11. Development and feasibility of the misuse, abuse, and diversion drug event reporting system (MADDERS®).

    Science.gov (United States)

    Treister, Roi; Trudeau, Jeremiah J; Van Inwegen, Richard; Jones, Judith K; Katz, Nathaniel P

    2016-12-01

    Inappropriate use of analgesic drugs has become increasingly pervasive over the past decade. Currently, drug abuse potential is primarily assessed post-marketing; no validated tools are available to assess this potential in phase II and III clinical trials. This paper describes the development and feasibility testing of a Misuse, Abuse, and Diversion Drug Event Reporting System (MADDERS), which aims to identify potentially abuse-related events and classify them according to a recently developed classification scheme, allowing the quantification of these events in clinical trials. The system was initially conceived and designed with input from experts and patients, followed by field-testing to assess its feasibility and content validity in both completed and ongoing clinical trials. The results suggest that MADDERS is a feasible system with initial validity. It showed higher rates of the triggering events in subjects taking medications with known abuse potential than in patients taking medications without abuse potential. Additionally, experts agreed on the classification of most abuse-related events in MADDERS. MADDERS is a new systematic approach to collect information on potentially abuse-related events in clinical trials and classify them. The system has demonstrated feasibility for implementation. Additional research is ongoing to further evaluate its validity. Currently, there are no validated tools to assess drug abuse potential during clinical trials. Because of its ease of implementation, its systematic approach, and its preliminary validation results, MADDERS could provide such a tool for clinical trials. (Am J Addict 2016;25:641-651). © 2016 American Academy of Addiction Psychiatry.

  12. An empirical review of major legislation affecting drug development: past experiences, effects, and unintended consequences.

    Science.gov (United States)

    Kesselheim, Aaron S

    2011-09-01

    With the development of transformative drugs at a low point, numerous commentators have recommended new legislation that uses supplementary market exclusivity as an incentive to promote innovation in the pharmaceutical market. This report provides an historical perspective on proposals for encouraging drug research. Four legislative programs have been primarily designed to offer market exclusivity to promote public health goals in the pharmaceutical or biomedical sciences: the Bayh-Dole Act of 1980, the Orphan Drug Act of 1983, the Hatch-Waxman Act of 1984, and the pediatric exclusivity provisions of the FDA Modernization Act of 1997. I reviewed quantitative and qualitative studies that reported on the outcomes from these programs and evaluated the quality of evidence generated. All four legislative programs generally have been regarded as successful, although such conclusions are largely based on straightforward descriptive reports rather than on more rigorous comparative data or analyses that sufficiently account for confounding. Overall, solid data demonstrate that market exclusivity incentives can attract interest from parties involved in drug development. However, using market exclusivity to promote innovation in the pharmaceutical market can be prone to misuse, leading to improper gains. In addition, important collateral effects have emerged with substantial negative public health implications. Using market exclusivity to promote pharmaceutical innovation can lead to positive outcomes, but the practice is also characterized by waste and collateral effects. Certain practices, such as mechanisms for reevaluation and closer ties of incentives programs to public health outcomes, can help address these problems. © 2011 Milbank Memorial Fund. Published by Wiley Periodicals Inc.

  13. Platelet-activating factor podoplanin: from discovery to drug development.

    Science.gov (United States)

    Takemoto, Ai; Miyata, Kenichi; Fujita, Naoya

    2017-06-01

    Tumor cell-induced platelet aggregation facilitates hematogenous metastasis by promoting tumor embolization, preventing immunological assaults and shear stress, and the platelet-releasing growth factors support tumor growth and invasion. Podoplanin, also known as Aggrus, is a type I transmembrane mucin-like glycoprotein and is expressed on wide range of tumor cells. Podoplanin has a role in platelet aggregation and metastasis formation through the binding to its platelet receptor, C-type lectin-like receptor 2 (CLEC-2). The podoplanin research was originally started from the cloning of highly metastatic NL-17 subclone from mouse colon 26 cancer cell line and from the establishment of 8F11 monoclonal antibody (mAb) that could neutralize NL-17-induced platelet aggregation and hematogenous metastasis. Later on, podoplanin was identified as the antigen of 8F11 mAb, and its ectopic expression brought to cells the platelet-aggregating abilities and hematogenous metastasis phenotypes. From the 8F11 mAb recognition epitopes, podoplanin is found to contain tandemly repeated, highly conserved motifs, designated platelet aggregation-stimulating (PLAG) domains. Series of analyses using the cells expressing the mutants and the established neutralizing anti-podoplanin mAbs uncovered that both PLAG3 and PLAG4 domains are associated with the CLEC-2 binding. The neutralizing mAbs targeting PLAG3 or PLAG4 could suppress podoplanin-induced platelet aggregation and hematogenous metastasis through inhibiting the podoplanin-CLEC-2 binding. Therefore, these domains are certainly functional in podoplanin-mediated metastasis through its platelet-aggregating activity. This review summarizes the platelet functions in metastasis formation, the role of platelet aggregation-inducing factor podoplanin in pathological and physiological situations, and the possibility to develop podoplanin-targeting drugs in the future.

  14. A strategy for developing representative germplasm sets for systematic QTL validation, demonstrated for apple, peach, and sweet cherry

    NARCIS (Netherlands)

    Peace, C.P.; Luby, J.; Weg, van de W.E.; Bink, M.C.A.M.; Iezzoni, A.F.

    2014-01-01

    Horticultural crop improvement would benefit from a standardized, systematic, and statistically robust procedure for validating quantitative trait loci (QTLs) in germplasm relevant to breeding programs. Here, we describe and demonstrate a strategy for developing reference germplasm sets of

  15. Affordable Development and Demonstration of a Small NTR engine and Stage: A Preliminary NASA, DOE, and Industry Assessment

    Science.gov (United States)

    Borowski, S. K.; Sefcik, R. J.; Fittje, J. E.; McCurdy, D. R.; Qualls, A. L.; Schnitzler, B. G; Werner, J.; Weitzberg, A.; Joyner, C. R.

    2015-01-01

    In FY'11, Nuclear Thermal Propulsion (NTP) was identified as a key propulsion option under the Advanced In-Space Propulsion (AISP) component of NASA's Exploration Technology Development and Demonstration (ETDD) program A strategy was outlined by GRC and NASA HQ that included 2 key elements -"Foundational Technology Development" followed by specific "Technology Demonstration" projects. The "Technology Demonstration "element proposed ground technology demonstration (GTD) testing in the early 2020's, followed by a flight technology demonstration (FTD) mission by approx. 2025. In order to reduce development costs, the demonstration projects would focus on developing a small, low thrust (approx. 7.5 -16.5 klb(f)) engine that utilizes a "common" fuel element design scalable to the higher thrust (approx. 25 klb(f)) engines used in NASA's Mars DRA 5.0 study(NASA-SP-2009-566). Besides reducing development costs and allowing utilization of existing, flight proven engine hard-ware (e.g., hydrogen pumps and nozzles), small, lower thrust ground and flight demonstration engines can validate the technology and offer improved capability -increased payloads and decreased transit times -valued for robotic science missions identified in NASA's Decadal Study.

  16. Research, development and demonstration of nickel-zinc batteries for electric vehicle propulsion. Annual report, 1979

    Energy Technology Data Exchange (ETDEWEB)

    1980-06-01

    Activities in a program to develop a Ni/Zn battery for electric vehicle propulsion are reported. Aspects discussed include battery design and development, nickel cathode study, and basic electrochemistry. A number of engineering drawings are supplied. 61 figures, 11 tables. (RWR)

  17. Books and Becoming Good: Demonstrating Aristotle's Theory of Moral Development in the Act of Reading

    Science.gov (United States)

    Cain, Amanda

    2005-01-01

    In the Nicomachean ethics, Aristotle sets down a scattered and fractional account of the development of moral virtue within young people. Philosopher Martha Nussbaum defends Aristotle's neglect of a systematic account of moral development and argues that more complex expressions of character-building, such as learning to expose oneself to proper…

  18. Microdialysis Monitoring in Clinical Traumatic Brain Injury and Its Role in Neuroprotective Drug Development.

    Science.gov (United States)

    Thelin, Eric Peter; Carpenter, Keri L H; Hutchinson, Peter J; Helmy, Adel

    2017-03-01

    Injuries to the central nervous system continue to be vast contributors to morbidity and mortality; specifically, traumatic brain injury (TBI) is the most common cause of death during the first four decades of life. Several modalities are used to monitor patients suffering from TBI in order to prevent detrimental secondary injuries. The microdialysis (MD) technique, introduced during the 1990s, presents the treating physician with a robust monitoring tool for brain chemistry in addition to conventional intracranial pressure monitoring. Nevertheless, some limitations remain, such as limited spatial resolution. Moreover, while there have been several attempts to develop new potential pharmacological therapies in TBI, there are currently no available drugs which have shown clinical efficacy that targets the underlying pathophysiology, despite various trials investigating a plethora of pharmaceuticals. Specifically in the brain, MD is able to demonstrate penetration of the drug through the blood-brain barrier into the brain extracellular space at potential site of action. In addition, the downstream effects of drug action can be monitored directly. In the future, clinical MD, together with other monitoring modalities, can identify specific pathological substrates which require tailored treatment strategies for patients suffering from TBI.

  19. Research, development and demonstration of nickel-zinc batteries for electric vehicle propulsion. Annual report, 1979

    Energy Technology Data Exchange (ETDEWEB)

    1980-06-01

    Progress achieved under ANL Contract No. 31-109-38-4248 from 16 August 1978 to 16 August 1979 is reported. The first segment of the overall program, component development, consists of four basic tasks proceeding in parallel: nickel electrode development, zinc electrode development, separator development, and sealed cell development. Each of these tasks is reported herein on a self-contained basis. System engineering is the second major subdivision of the effort. It includes the design and testing of all cells, the investigation of charge control devices and techniques, and the complete analysis of all cells for failure modes. It also encompasses the accelerated testing of 20-Ah cells. To date, large numbers of these cells (incorporating separator variations, active material additives and internal design variations) have been subjected to this type of testing. 48 figures, 47 tables. (RWR)

  20. Research, development and demonstration of nickel-zinc batteries for electric vehicle propulsion

    Science.gov (United States)

    1980-06-01

    The feasibility of the nickel zinc battery for electric vehicle propulsion is discussed. The program is divided into seven distinct but highly interactive tasks collectively aimed at the development and commercialization of nickel zinc technology. These basic technical tasks are separator development, electrode development, product design and analysis, cell/module battery testing, process development, pilot manufacturing, and thermal manufacturing, and thermal management. Significant progress has been made in the understanding of separator failure mechanisms, and a generic category of materials has been specified for the 300+ deep discharge applications. Shape change has been reduced significantly. Progress in the area of thermal management was significant, with the development of a model that accurately represents heat generation and rejection rates during battery operation.

  1. The link between research, development and demonstration and stakeholder confidence: the perspective of an academic

    International Nuclear Information System (INIS)

    Marsily, Ghislain de

    2006-01-01

    The author contributed to the discussion by providing a presentation from the perspective of an academic. In reviewing the role of science, the author focused on the important roles of science and R and D following a siting process. Science and R and D is essential for understanding the physical systems, displaying and demonstrating processes involved, measuring key parameters, and assessing areas of residual uncertainty. He outlined a number of factors that are key to making a strong case to stakeholders, to demonstrate that the system is well understood: - explaining the past history of the site; - explaining unexpected features or occurrences (such as seismic anomalies); - ensuring the capacity to observe and note unexpected features; - having the capacity to introduce new measurements that can inform the system; - deriving scientific validation of theory (noting the example of WIPP); - maintaining the capacity to be at the frontier of science; and - having the ability to answer unexpected questions from any party. It was suggested that credibility and stakeholder confidence is linked, in part, to credibility of the research in the eyes of the scientific community. The scientific community must be engaged to address questions of interest to the public. The role of peer review is essential in establishing the credibility of researchers, and within academic circles, publications in the scientific literature is highly valued. It is important for both implementers and regulators to retain their own capabilities and competence to be credible in the eyes of stakeholders. The experience of Andra was noted, in underscoring the importance of having high-level scientists internal to the implementing organization to ensure momentum and institutional knowledge. Thesis students also offer ways of promoting science in areas of interest concerning radioactive waste management. Demonstration plays an essential and distinct role from R and D. It offers tangible insight to

  2. Tetraphenylborate Catalyst Development for the Oak Ridge National Laboratory 20-L Continuously Stirred Tank Reactor Demonstration

    International Nuclear Information System (INIS)

    Barnes, M.J.

    2001-01-01

    The Salt Disposition Systems Engineering Team identified Small Tank Tetraphenylborate Precipitation as one of the three alternatives to replace the In-Tank Precipitation Facility at the Savannah River Site. The proposed design incorporates two continuous stirred tank reactors (CSTR) a concentrate tank and a sintered metal crossflow filter. Previous use of tetraphenylborate in batch operation and testing demonstrated the ability of the feed material to catalyze the decomposition of tetraphenylborate. The Small Tank Tetraphenylborate Precipitation design seeks to overcome the processing limitation of the unwanted reaction by rapid throughput and temperature control. Nitrogen inerting of the vapor space helps mitigate any safety (i.e., flammable) concerns of the reaction

  3. Liposomes and nanotechnology in drug development: focus on oncotargets

    Directory of Open Access Journals (Sweden)

    Kozako T

    2012-09-01

    Full Text Available Tomohiro Kozako,1 Naomichi Arima,2 Makoto Yoshimitsu,3 Shin-Ichro Honda,1 Shinji Soeda11Department of Biochemistry, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan; 2Division of Hematology and Immunology, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan; 3Department of Hematology and Immunology, Kagoshima University Hospital, Kagoshima, JapanAbstract: Nanotechnology is the development of an engineered device at the atomic, molecular, and macromolecular level in the nanometer range. Advances in nanotechnology have proven beneficial in therapeutic fields such as drug-delivery and gene/protein delivery. Antigen delivery systems are important for inducing and modifying immune responses. In cellular immunity, cytotoxic T lymphocytes (CTLs are important in the host defense against tumors. Key to the development of CTL-inducible vaccines is the ability to deliver antigens to antigen-presenting cells efficiently and to induce the subsequent activation of T cell-mediated immunity without adjuvants, as they can induce excessive inflammation leading to systemic febrile disease. Since expression and cloning methods for tumor-associated antigens have been reported, cancer vaccines that induce effective cell immunity may be promising therapeutic candidates, but Th2 cells are undesirable for use in cancer immunotherapy. Peptide vaccines have immunological and economic advantages as cancer vaccines because CTL epitope peptides from tumor-associated antigens have high antigen-specificity. However, cancer vaccines have had limited effectiveness in clinical responses due to the ability of cancer cells to “escape” from cancer immunity and a low efficiency of antigen-specific CTL induction due to immunogenic-free synthetic peptides. In contrast, carbohydrate-decorated particles such as carbohydrate-coated liposomes with encapsulated antigens might be more suitable as

  4. Drug development for breast, colorectal, and non-small cell lung cancers from 1979 to 2014.

    Science.gov (United States)

    Nixon, Nancy A; Khan, Omar F; Imam, Hasiba; Tang, Patricia A; Monzon, Jose; Li, Haocheng; Sun, Gavin; Ezeife, Doreen; Parimi, Sunil; Dowden, Scot; Tam, Vincent C

    2017-12-01

    Understanding the drug development pathway is critical for streamlining the development of effective cancer treatments. The objective of the current study was to delineate the drug development timeline and attrition rate of different drug classes for common cancer disease sites. Drugs entering clinical trials for breast, colorectal, and non-small cell lung cancer were identified using a pharmaceutical business intelligence database. Data regarding drug characteristics, clinical trials, and approval dates were obtained from the database, clinical trial registries, PubMed, and regulatory Web sites. A total of 411 drugs met the inclusion criteria for breast cancer, 246 drugs met the inclusion criteria for colorectal cancer, and 315 drugs met the inclusion criteria for non-small cell lung cancer. Attrition rates were 83.9% for breast cancer, 87.0% for colorectal cancer, and 92.0% for non-small cell lung cancer drugs. In the case of non-small cell lung cancer, there was a trend toward higher attrition rates for targeted monoclonal antibodies compared with other agents. No tumor site-specific differences were noted with regard to cytotoxic chemotherapy, immunomodulatory, or small molecule kinase inhibitor drugs. Drugs classified as "others" in breast cancer had lower attrition rates, primarily due to the higher success of hormonal medications. Mean drug development times were 8.9 years for breast cancer, 6.7 years for colorectal cancer, and 6.6 years for non-small cell lung cancer. Overall oncologic drug attrition rates remain high, and drugs are more likely to fail in later-stage clinical trials. The refinement of early-phase trial design may permit the selection of drugs that are more likely to succeed in the phase 3 setting. Cancer 2017;123:4672-4679. © 2017 American Cancer Society. © 2017 American Cancer Society.

  5. Guidelines for integrated catchments monitoring: ICM mind map development and demonstration

    CSIR Research Space (South Africa)

    Jovanovic, Nebojsa

    2011-09-01

    Full Text Available Advances have been made in recent years in developing networks and databases for monitoring water systems in South Africa. However, these monitoring systems need to be consolidated and integrated amongst various components of catchment systems...

  6. Development and Demonstration of Carbon Fuel Cell Final Report CRADA No. TC02091.0

    Energy Technology Data Exchange (ETDEWEB)

    Cooper, J. F. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Berner, J. K. [Contained Energy, Inc., Shaker Heights, OH (United States)

    2017-09-08

    This was a collaborative effort between The Regents of the University of California, Lawrence Livermore National Laboratory (LLNL) and Contained Energy, Inc. (CEI), to conduct necessary research and to develop, fabricate and test a multi-cell carbon fuel cell.

  7. Development of magnetic drug delivery system using HTS bulk magnet

    International Nuclear Information System (INIS)

    Terada, T.; Fukui, S.; Mishima, F.; Akiyama, Y.; Izumi, Y.; Nishijima, S.

    2008-01-01

    Magnetic drug delivery system (MDDS) is the method which the magnetic seeded drug is injected into a blood vessel and then controlled and accumulated by a magnet located outside of the human body. A high accumulation efficiency of the drug to a local diseased part and reduction in side-effects to normal organs are expected by using MDDS. The most important element in MDDS is a magnetic field generator. The high temperature superconducting (HTS) bulk magnet which can generate high magnetic field and magnetic field gradient extending to a point distant from the magnet in several ten millimeters is necessary to achieve the MDDS. In this study, the computer simulation and model experiment were conducted in order to confirm the applicability of MDDS to ovary of the cow body

  8. Drugs of abuse and increased risk of psychosis development.

    Science.gov (United States)

    Gururajan, Anand; Manning, Elizabeth E; Klug, Maren; van den Buuse, Maarten

    2012-12-01

    There is considerable evidence to suggest that the abuse of illicit drugs, particularly cannabis and methamphetamine, has aetiological roles in the pathogenesis of psychosis and schizophrenia. Factors that may increase susceptibility to the propsychotic effects of these drugs include the age at which the abuse starts as well as family history of genetic polymorphisms relevant to the pathophysiology of this disorder. However, the neurobiological mechanisms involved in drug abuse-associated psychosis remain largely unclear. This paper presents an overview of the available evidence, including clinical, animal model, and molecular studies, with a focus on brain regions and neurotransmitters systems, such as dopamine and glutamate, previously implicated in psychosis. It is clear that further studies are urgently needed to provide a greater insight into the mechanisms that mediate the long-term and neurodevelopmental effects of cannabis and methamphetamine. A dialogue between basic science and clinical research may help to identify at-risk individuals and novel pathways for treatment and prevention.

  9. Modeling of pharmacokinetics of cocaine in human reveals the feasibility for development of enzyme therapies for drugs of abuse.

    Directory of Open Access Journals (Sweden)

    Fang Zheng

    Full Text Available A promising strategy for drug abuse treatment is to accelerate the drug metabolism by administration of a drug-metabolizing enzyme. The question is how effectively an enzyme can actually prevent the drug from entering brain and producing physiological effects. In the present study, we have developed a pharmacokinetic model through a combined use of in vitro kinetic parameters and positron emission tomography data in human to examine the effects of a cocaine-metabolizing enzyme in plasma on the time course of cocaine in plasma and brain of human. Without an exogenous enzyme, cocaine half-lives in both brain and plasma are almost linearly dependent on the initial cocaine concentration in plasma. The threshold concentration of cocaine in brain required to produce physiological effects has been estimated to be 0.22±0.07 µM, and the threshold area under the cocaine concentration versus time curve (AUC value in brain (denoted by AUC2(∞ required to produce physiological effects has been estimated to be 7.9±2.7 µM·min. It has been demonstrated that administration of a cocaine hydrolase/esterase (CocH/CocE can considerably decrease the cocaine half-lives in both brain and plasma, the peak cocaine concentration in brain, and the AUC2(∞. The estimated maximum cocaine plasma concentration which a given concentration of drug-metabolizing enzyme can effectively prevent from entering brain and producing physiological effects can be used to guide future preclinical/clinical studies on cocaine-metabolizing enzymes. Understanding of drug-metabolizing enzymes is key to the science of pharmacokinetics. The general insights into the effects of a drug-metabolizing enzyme on drug kinetics in human should be valuable also in future development of enzyme therapies for other drugs of abuse.

  10. Modeling of pharmacokinetics of cocaine in human reveals the feasibility for development of enzyme therapies for drugs of abuse.

    Science.gov (United States)

    Zheng, Fang; Zhan, Chang-Guo

    2012-01-01

    A promising strategy for drug abuse treatment is to accelerate the drug metabolism by administration of a drug-metabolizing enzyme. The question is how effectively an enzyme can actually prevent the drug from entering brain and producing physiological effects. In the present study, we have developed a pharmacokinetic model through a combined use of in vitro kinetic parameters and positron emission tomography data in human to examine the effects of a cocaine-metabolizing enzyme in plasma on the time course of cocaine in plasma and brain of human. Without an exogenous enzyme, cocaine half-lives in both brain and plasma are almost linearly dependent on the initial cocaine concentration in plasma. The threshold concentration of cocaine in brain required to produce physiological effects has been estimated to be 0.22±0.07 µM, and the threshold area under the cocaine concentration versus time curve (AUC) value in brain (denoted by AUC2(∞)) required to produce physiological effects has been estimated to be 7.9±2.7 µM·min. It has been demonstrated that administration of a cocaine hydrolase/esterase (CocH/CocE) can considerably decrease the cocaine half-lives in both brain and plasma, the peak cocaine concentration in brain, and the AUC2(∞). The estimated maximum cocaine plasma concentration which a given concentration of drug-metabolizing enzyme can effectively prevent from entering brain and producing physiological effects can be used to guide future preclinical/clinical studies on cocaine-metabolizing enzymes. Understanding of drug-metabolizing enzymes is key to the science of pharmacokinetics. The general insights into the effects of a drug-metabolizing enzyme on drug kinetics in human should be valuable also in future development of enzyme therapies for other drugs of abuse.

  11. Development, testing, and demonstration of an optimal fine coal cleaning circuit

    Energy Technology Data Exchange (ETDEWEB)

    Mishra, M.; Placha, M.; Bethell, P. [and others

    1995-11-01

    The overall objective of this project is to improve the efficiency of fine coal cleaning. The project will be completed in two phases: bench-scale testing and demonstration of four advanced flotation cells and; in-plant proof-of-concept (POC) pilot plant testing of two flotation cells individually and in two-stage combinations. The goal is to ascertain if a two-stage circuit can result in reduced capital and operating costs while achieving improved separation efficiency. The plant selected for this project, Cyprus Emerald Coal Preparation plant, cleans 1200 tph of raw coal. The plant produces approximately 4 million tonnes of clean coal per year at an average as received energy content of 30.2 MJ/Kg (13,000 Btu/lb).

  12. Development, testing, and demonstration of an optimal fine coal cleaning circuit

    International Nuclear Information System (INIS)

    Mishra, M.; Placha, M.; Bethell, P.

    1995-01-01

    The overall objective of this project is to improve the efficiency of fine coal cleaning. The project will be completed in two phases: bench-scale testing and demonstration of four advanced flotation cells and; in-plant proof-of-concept (POC) pilot plant testing of two flotation cells individually and in two-stage combinations. The goal is to ascertain if a two-stage circuit can result in reduced capital and operating costs while achieving improved separation efficiency. The plant selected for this project, Cyprus Emerald Coal Preparation plant, cleans 1200 tph of raw coal. The plant produces approximately 4 million tonnes of clean coal per year at an average as received energy content of 30.2 MJ/Kg (13,000 Btu/lb)

  13. Multi-Lab EV Smart Grid Integration Requirements Study. Providing Guidance on Technology Development and Demonstration

    Energy Technology Data Exchange (ETDEWEB)

    Markel, T. [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Meintz, A. [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Hardy, K. [Argonne National Lab. (ANL), Argonne, IL (United States); Chen, B. [Argonne National Lab. (ANL), Argonne, IL (United States); Bohn, T. [Argonne National Lab. (ANL), Argonne, IL (United States); Smart, J. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Scoffield, D. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Hovsapian, R. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Saxena, S. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); MacDonald, J. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Kiliccote, S. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Kahl, K. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Pratt, R. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2015-05-28

    The report begins with a discussion of the current state of the energy and transportation systems, followed by a summary of some VGI scenarios and opportunities. The current efforts to create foundational interface standards are detailed, and the requirements for enabling PEVs as a grid resource are presented. Existing technology demonstrations that include vehicle to grid functions are summarized. The report also includes a data-based discussion on the magnitude and variability of PEVs as a grid resource, followed by an overview of existing simulation tools that vi This report is available at no cost from the National Renewable Energy Laboratory (NREL) at www.nrel.gov/publications. can be used to explore the expansion of VGI to larger grid functions that might offer system and customer value. The document concludes with a summary of the requirements and potential action items that would support greater adoption of VGI.

  14. Fluoride Salt-Cooled High-Temperature Reactor Technology Development and Demonstration Roadmap

    Energy Technology Data Exchange (ETDEWEB)

    Holcomb, David Eugene [ORNL; Flanagan, George F [ORNL; Mays, Gary T [ORNL; Pointer, William David [ORNL; Robb, Kevin R [ORNL; Yoder Jr, Graydon L [ORNL

    2013-11-01

    Fluoride salt-cooled High-temperature Reactors (FHRs) are an emerging reactor class with potentially advantageous performance characteristics, and fully passive safety. This roadmap describes the principal remaining FHR technology challenges and the development path needed to address the challenges. This roadmap also provides an integrated overview of the current status of the broad set of technologies necessary to design, evaluate, license, construct, operate, and maintain FHRs. First-generation FHRs will not require any technology breakthroughs, but do require significant concept development, system integration, and technology maturation. FHRs are currently entering early phase engineering development. As such, this roadmap is not as technically detailed or specific as would be the case for a more mature reactor class. The higher cost of fuel and coolant, the lack of an approved licensing framework, the lack of qualified, salt-compatible structural materials, and the potential for tritium release into the environment are the most obvious issues that remain to be resolved.

  15. [Significance of re-evaluation and development of Chinese herbal drugs].

    Science.gov (United States)

    Gao, Yue; Ma, Zengchun; Zhang, Boli

    2012-01-01

    The research of new herbal drugs involves in new herbal drugs development and renew the old drugs. It is necessary to research new herbal drugs based on the theory of traditional Chinese medicine (TCM). The current development of famous TCM focuses on the manufacture process, quality control standards, material basis and clinical research. But system management of security evaluation is deficient, the relevant system for the safety assessment TCM has not been established. The causes of security problems, security risks, target organ of toxicity, weak link of safety evaluation, and ideas of safety evaluation are discussed in this paper. The toxicology research of chinese herbal drugs is necessary based on standard of good laboratory practices (GLP), the characteristic of Chinese herbal drugs is necessary to be fully integrated into safety evaluation. The safety of new drug research is necessary to be integrated throughout the entire process. Famous Chinese medicine safety research must be paid more attention in the future.

  16. Preparative Scale Resolution of Enantiomers Enables Accelerated Drug Discovery and Development

    Directory of Open Access Journals (Sweden)

    Hanna Leek

    2017-01-01

    Full Text Available The provision of pure enantiomers is of increasing importance not only for the pharmaceutical industry but also for agro-chemistry and biotechnology. In drug discovery and development, the enantiomers of a chiral drug depict unique chemical and pharmacological behaviors in a chiral environment, such as the human body, in which the stereochemistry of the chiral drugs determines their pharmacokinetic, pharmacodynamic and toxicological properties. We present a number of challenging case studies of up-to-kilogram separations of racemic or enriched isomer mixtures using preparative liquid chromatography and super critical fluid chromatography to generate individual enantiomers that have enabled the development of new candidate drugs within AstraZeneca. The combination of chromatography and racemization as well as strategies on when to apply preparative chiral chromatography of enantiomers in a multi-step synthesis of a drug compound can further facilitate accelerated drug discovery and the early clinical evaluation of the drug candidates.

  17. [A novel dipeptidyl peptidase IV inhibitors developed through scaffold hopping and drug splicing strategy].

    Science.gov (United States)

    Wang, Shan-Chun; Zeng, Li-Li; Ding, Yu-Yang; Zeng, Shao-Gao; Song, Hong-Rui; Hu, Wen-Hui; Xie, Hui

    2014-01-01

    Though all the marketed drugs of dipeptidyl peptidase IV inhibitors are structurally different, their inherent correlation is worthy of further investigation. Herein we rapidly discovered a novel DPP-IV inhibitor 8g (IC50 = 4.9 nmol.L-1) which exhibits as good activity and selectivity as the market drugs through scaffold hopping and drug splicing strategies based on alogliptin and linagliptin. This study demonstrated that the employment of classic medicinal chemistry strategy to the marketed drugs with specific target is an efficient approach to discover novel bioactive molecules.

  18. 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.

  19. DEVELOPMENT AND DEMONSTRATION OF A BIDIRECTIONAL ADVECTIVE FLUX METER FOR SEDIMENT-WATER INTERFACE

    Science.gov (United States)

    A bidirectional advective flux meter for measuring water transport across the sediment-water interface has been successfully developed and field tested. The flow sensor employs a heat-pulse technique combined with a flow collection funnel for the flow measurement. Because the dir...

  20. Research, development, and demonstration of lead-acid batteries for electric vehicle propulsion. Annual report, 1980

    Energy Technology Data Exchange (ETDEWEB)

    1981-03-01

    The progress and status of Eltra's Electric Vehicle Battery Program during FY-80 are presented under five divisional headings: Research on Components and Processes; Development of Cells and Modules for Electric Vehicle Propulsion; Sub-Systems; Pilot Line Production of Electric Vehicle Battery Prototypes; and Program Management.

  1. The Development and Demonstration of Multiple Regression Models for Operant Conditioning Questions.

    Science.gov (United States)

    Fanning, Fred; Newman, Isadore

    Based on the assumption that inferential statistics can make the operant conditioner more sensitive to possible significant relationships, regressions models were developed to test the statistical significance between slopes and Y intercepts of the experimental and control group subjects. These results were then compared to the traditional operant…

  2. Mixing Interviews and Rasch Modeling: Demonstrating a Procedure Used to Develop an Instrument That Measures Trust

    Science.gov (United States)

    David, Shannon L.; Hitchcock, John H.; Ragan, Brian; Brooks, Gordon; Starkey, Chad

    2018-01-01

    Developing psychometrically sound instruments can be difficult, especially if little is known about the constructs of interest. When constructs of interest are unclear, a mixed methods approach can be useful. Qualitative inquiry can be used to explore a construct's meaning in a way that informs item writing and allows the strengths of one analysis…

  3. 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.

  4. Therapeutic Targets for Influenza - Perspectives in Drug Development

    Czech Academy of Sciences Publication Activity Database

    Majerová, Taťána; Hoffman, H.; Majer, F.

    2010-01-01

    Roč. 75, č. 1 (2010), s. 81-103 ISSN 0010-0765 R&D Projects: GA MŠk 1M0508 Institutional research plan: CEZ:AV0Z40550506 Keywords : influenza * drug research * protein structure * oligonucleotides Subject RIV: CE - Biochemistry Impact factor: 0.853, year: 2010

  5. Drugs in development and dietary approach for Duchenne muscular dystrophy

    Directory of Open Access Journals (Sweden)

    Angelini C

    2015-08-01

    Full Text Available Corrado Angelini, Elisabetta Tasca Neuromuscular Laboratory, Fondazione San Camillo Hospital IRCCS, Venice, Italy Abstract: Therapeutic trials studying Duchenne muscular dystrophy (DMD in Europe and the USA have been done using a protocol that includes manual muscle testing and functional testing, and have shown the efficacy of steroid drugs in various doses and regimens. Further, drisapersen and eteplirsen (exon skipping drugs and ataluren (a drug to overcome stop codon mutations have achieved some clinical improvement. Cardioprotective drugs are efficacious in DMD, and eplerenone, an aldosterone inhibitor and diuretic, is now being used to treat the disease. The dietary approach should be used in wheelchair-bound DMD children in combination with respiratory assistance. The importance of some of the treatments proposed is that they might also be useful in other genetic disorders where stop codon mutations are present; moreover, it is possible that these new treatments will improve quality of life for many patients. Keywords: Duchenne muscular dystrophy, steroids, ataluren, drisapersen, eplerenone, eteplirsen

  6. Development of a Gastroretentive Drug Delivery System based on ...

    African Journals Online (AJOL)

    Erah

    Purpose: The aim of this work was to synthesize superporous hydrogels of rosiglitazone using chitosan and to study its swelling behaviour for application as a gastroretentive drug delivery system. Methods: Chitosan superporous hydrogels were synthesized using glyoxal as a crosslinking agent by gas blowing method.

  7. Challenges in the clinical development of orphan drugs

    NARCIS (Netherlands)

    Kreeftmeijer-Vegter, A.R.

    2015-01-01

    Rare diseases are characterised by a low prevalence. There are so many different rare diseases, that millions of people are affected.The vast majority of these diseases suffer from a lack of approved treatment options and orphan drugs (ODs) therefore represent a huge unmet medical need. ODs face

  8. Research, Development and Demonstration of Micro-CHP Systems for Residential Applications - Phase I

    Energy Technology Data Exchange (ETDEWEB)

    Robert A. Zogg

    2011-03-14

    The objective of the Micro-CHP Phase I effort was to develop a conceptual design for a Micro-CHP system including: Defining market potential; Assessing proposed technology; Developing a proof-of-principle design; and Developing a commercialization strategy. TIAX LLC assembled a team to develop a Micro-CHP system that will provide electricity and heating. TIAX, the contractor and major cost-share provider, provided proven expertise in project management, prime-mover design and development, appliance development and commercialization, analysis of residential energy loads, technology assessment, and market analysis. Kohler Company, the manufacturing partner, is a highly regarded manufacturer of standby power systems and other residential products. Kohler provides a compellingly strong brand, along with the capabilities in product development, design, manufacture, distribution, sales, support, service, and marketing that only a manufacturer of Kohler's status can provide. GAMA, an association of appliance and equipment manufacturers, provided a critical understanding of appliance commercialization issues, including regulatory requirements, large-scale market acceptance issues, and commercialization strategies. The Propane Education & Research Council, a cost-share partner, provided cost share and aided in ensuring the fuel flexibility of the conceptual design. Micro-CHP systems being commercialized in Europe and Japan are generally designed to follow the household thermal load, and generate electricity opportunistically. In many cases, any excess electricity can be sold back to the grid (net metering). These products, however, are unlikely to meet the demands of the U.S. market. First, these products generally cannot provide emergency power when grid power is lost--a critical feature to market success in the U.S. Even those that can may have insufficient electric generation capacities to meet emergency needs for many U.S. homes. Second, the extent to which net

  9. Runway exit designs for capacity improvement demonstrations. Phase 2: Computer model development

    Science.gov (United States)

    Trani, A. A.; Hobeika, A. G.; Kim, B. J.; Nunna, V.; Zhong, C.

    1992-01-01

    The development is described of a computer simulation/optimization model to: (1) estimate the optimal locations of existing and proposed runway turnoffs; and (2) estimate the geometric design requirements associated with newly developed high speed turnoffs. The model described, named REDIM 2.0, represents a stand alone application to be used by airport planners, designers, and researchers alike to estimate optimal turnoff locations. The main procedures are described in detail which are implemented in the software package and possible applications are illustrated when using 6 major runway scenarios. The main output of the computer program is the estimation of the weighted average runway occupancy time for a user defined aircraft population. Also, the location and geometric characteristics of each turnoff are provided to the user.

  10. Development and demonstration of optical polarization controller; Hikari henpa seigyo sochi no kaihatsu to jissho

    Energy Technology Data Exchange (ETDEWEB)

    Kurono, M. [Central Research Institute of Electric Power Industry, Tokyo (Japan)

    1997-04-01

    If fiber transmission light can be controlled in a stabilized polarization state, realization of coherent optical communication is anticipated. In the case of adopting it to OPGW, however, it is necessary to compensate high speed polarization variation caused by lightning strike. But this was difficult in the conventional method. Accordingly, a high speed polarization control method was proposed which uses an electric effect of lithium niobate (LN) crystals. In the study, a polarization control unit was manufactured based on the method proposed and the performance was demonstrated. As a result of measuring output light with input light changed in every state of polarization, the object horizontal polarization component obtained a stabilized light intensity at {+-}0.1dB, and a light intensity of the component slipped out of the horizontal polarization was suppressed under -20dB. To cope with the polarization variation by lightning strike, it is necessary to make the control delay 10{mu}sec or below, and improvement in processing unit, etc. may make it possible since LN crystals respond below 1{mu}sec. High speed control of the infinitely continuing arbitrary polarization variation became possible. 14 refs., 19 figs.

  11. Development of derived investigation levels for use in internal dosimetry at the West Valley Demonstration Project

    International Nuclear Information System (INIS)

    Johnson, P.

    1991-01-01

    The objective was to determine if the routine intemal dosimetry program at the West Valley Demonstration Project is capable of meeting the performance objective of 1 mSv annual effective dose equivalent due to internal contamination. With the use of the computer code REMedy the annual effective dose equivalent is calculated. Some of the radionuclides of concern result in an annual effective dose equivalent that exceeds the performance objective. Although the results exceed the performance objective, in all but two cases they do not exceed the US DOE regulatory limits. In these instances the Th-232 and Am-241 were determined to exceed the committed dose equivalent limit to their limiting tissue. In order to document the potential missed dose for regulatory compliance, Sr-90 is used as an indicator for Th-232. For Am-241 an investigation as to whether or not the minimum detectable amount can be lowered is performed. The derived investigation levels as a result of this project are 4.9E3 Bq/lung count for Co-60, 2.2E4 Bq/lung count for Cs-137, 1.9 Bq/1 for Sr-90 and for radionuclides other than Sr-90 any value greater than or equal to three standard deviations above their net count is considered to require further investigation

  12. Development, Demonstration and Validation of the Deep Space Orbit Determination Software Using Lunar Prospector Tracking Data

    Directory of Open Access Journals (Sweden)

    Eunji Lee

    2017-09-01

    Full Text Available The deep space orbit determination software (DSODS is a part of a flight dynamic subsystem (FDS for the Korean Pathfinder Lunar Orbiter (KPLO, a lunar exploration mission expected to launch after 2018. The DSODS consists of several sub modules, of which the orbit determination (OD module employs a weighted least squares algorithm for estimating the parameters related to the motion and the tracking system of the spacecraft, and subroutines for performance improvement and detailed analysis of the orbit solution. In this research, DSODS is demonstrated and validated at lunar orbit at an altitude of 100 km using actual Lunar Prospector tracking data. A set of a priori states are generated, and the robustness of DSODS to the a priori error is confirmed by the NASA planetary data system (PDS orbit solutions. Furthermore, the accuracy of the orbit solutions is determined by solution comparison and overlap analysis as about tens of meters. Through these analyses, the ability of the DSODS to provide proper orbit solutions for the KPLO are proved.

  13. Demonstration technology development of new hydrogen energy; Shinsuiso energy jissho gijutsu kaihatsu

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-03-01

    This report describes results of the study on the excess heat generation phenomenon during the electrolysis of heavy water using palladium metals as electrode in FY 1995. For the measurements of excess heat using an open type electrolysis cell during the excess heat generation demonstration model tests, significant excess heat beyond the range of input was not measured both for ICARUS-1 and for ICARUS-2. For the measurements using a fuel cell, high absorbing rate more than 0.85 was stably achieved for highly pure Pd electrode material by heat treatment and surface treatment. The excess heat could be reproduced for plural tests. The heat recovery rate more than 98% was obtained using the NHE type flow calorimetric system. The excess heat measurements using this are examined. For the reactive palladium materials, various materials ranging from single crystal to cold working polycrystal materials were systematically used for the absorbing experiments. Benchmark tests were also conducted through the cooperation with related researchers. 18 refs., 135 figs., 28 tabs.

  14. Cummins Engine Company B5.9 Propane Engine Development, Certification, and Demonstration Project

    Energy Technology Data Exchange (ETDEWEB)

    The ADEPT Group, Inc. (Los Angeles, California)

    1998-12-18

    The objective of this project was to successfuly develop and certify an LPG-dedicated medium-duty original equipment manufacturer (OEM) engine that could be put into production. The engine was launched into production in 1994, and more than 800 B5.9G engines are now in service in the United States and abroad. This engine is now offered by more than 30 bus and truck OEMs.

  15. Normal and abnormal fetal brain development during the third trimester as demonstrated by neurosonography

    International Nuclear Information System (INIS)

    Malinger, G.; Lev, D.; Lerman-Sagie, T.

    2006-01-01

    The multiplanar neurosonographic examination of the fetus enables superb visualization of brain anatomy during pregnancy. The examination may be performed using a transvaginal or a transfundal approach and it is indicated in patients at high risk for CNS anomalies or in those with a suspicious finding during a routine examination. The purpose of this paper is to present a description of the normal brain and of abnormal findings usually diagnosed late in pregnancy, including malformations of cortical development, infratentorial anomalies, and prenatal insults

  16. Research, development and demonstration of lead-acid batteries for electric vehicle propulsion. Annual report, 1979

    Energy Technology Data Exchange (ETDEWEB)

    1980-06-01

    This report describes work performed from October 1, 1978 to September 30, 1979. The approach for development of both the Improved State-of-the-Art (ISOA) and Advanced lead-acid batteries is three pronged. This approach concentrates on simultaneous optimization of battery design, materials, and manufacturing processing. The 1979 fiscal year saw the achievement of significant progress in the program. Some of the major accomplishments of the year are outlined. 33 figures, 13 tables. (RWR)

  17. Development and demonstration of sodium fire mitigation system in the SAPFIRE facility

    International Nuclear Information System (INIS)

    Himeno, Y.; Miyahara, S.; Morii, T.; Sasaki, K.

    1989-01-01

    Flow pattern of a realistic sodium leak from the sodium piping equipped with jackets and thermal insulator was experimentally investigated. Then, based on this result, the fire mitigation system consisting of an inclined liner, a drain piping, and a smothering tank has been developed. The performance of the system was, in final, validated in the large-scale sodium leak and fire test in the SAPFIRE facility. (author)

  18. NextGen UAS Research, Development and Demonstration Roadmap. Version 1.0

    Science.gov (United States)

    2012-03-15

    18. NUMBER OF PAGES 80 19a. NAME OF RESPONSIBLE PERSON a. REPORT unclassified b. ABSTRACT unclassified c. THIS PAGE unclassified Standard ...individual COA, UAS may operate under both Visual Flight Rules (VFR) and Instrument Flight Rules ( IFR ), in both special use airspace and non- segregated...National Aeronautics Research and Development Plan,” February 2010 , which cites the importance of integrating UAS into the NextGen NAS and establishes

  19. HAZWDDD [Hazardous Waste Development, Demonstration, and Disposal]: An exercise in corporate planning

    International Nuclear Information System (INIS)

    McGinnis, C.P.; Pechin, W.H.

    1988-01-01

    Both Energy Systems corporate management and US Department of Energy's Oak Ridge Operations Office (DOE-ORO) management have recognized the seriousness of these problems and have established several programs to determine acceptable courses of action. A plan has been developed for low-level radioactive waste (LLW), and an active dialogue pertaining to LLW is maintained with the state and federal regulators. During 1986, DOE-ORO and Energy Systems identified the need for a plan to address hazardous and mixed wastes. Each installation supports the concept of HAZWDDD through funding and the development of individual HAZWDDD implementation plans. A corporate plan is being developed to integrate the issues discussed in the five installation plans. This paper describes the approach taken in collecting the necessary information for the plan, some of the techniques used in analyzing the information provided, preliminary data that have been collected in preparation of this plan, the identification of common concerns and issues, and the integration of this information into a corporate approach to mixed and hazardous waste management. 1 fig., 5 tabs

  20. Global gene expression profiling of individual human oocytes and embryos demonstrates heterogeneity in early development.

    Directory of Open Access Journals (Sweden)

    Lisa Shaw

    Full Text Available Early development in humans is characterised by low and variable embryonic viability, reflected in low fecundity and high rates of miscarriage, relative to other mammals. Data from assisted reproduction programmes provides additional evidence that this is largely mediated at the level of embryonic competence and is highly heterogeneous among embryos. Understanding the basis of this heterogeneity has important implications in a number of areas including: the regulation of early human development, disorders of pregnancy, assisted reproduction programmes, the long term health of children which may be programmed in early development, and the molecular basis of pluripotency in human stem cell populations. We have therefore investigated global gene expression profiles using polyAPCR amplification and microarray technology applied to individual human oocytes and 4-cell and blastocyst stage embryos. In order to explore the basis of any variability in detail, each developmental stage is replicated in triplicate. Our data show that although transcript profiles are highly stage-specific, within each stage they are relatively variable. We describe expression of a number of gene families and pathways including apoptosis, cell cycle and amino acid metabolism, which are variably expressed and may be reflective of embryonic developmental competence. Overall, our data suggest that heterogeneity in human embryo developmental competence is reflected in global transcript profiles, and that the vast majority of existing human embryo gene expression data based on pooled oocytes and embryos need to be reinterpreted.

  1. Drug-induced trafficking of p-glycoprotein in human brain capillary endothelial cells as demonstrated by exposure to mitomycin C.

    Science.gov (United States)

    Noack, Andreas; Noack, Sandra; Hoffmann, Andrea; Maalouf, Katia; Buettner, Manuela; Couraud, Pierre-Olivier; Romero, Ignacio A; Weksler, Babette; Alms, Dana; Römermann, Kerstin; Naim, Hassan Y; Löscher, Wolfgang

    2014-01-01

    P-glycoprotein (Pgp; ABCB1/MDR1) is a major efflux transporter at the blood-brain barrier (BBB), restricting the penetration of various compounds. In other tissues, trafficking of Pgp from subcellular stores to the cell surface has been demonstrated and may constitute a rapid way of the cell to respond to toxic compounds by functional membrane insertion of the transporter. It is not known whether drug-induced Pgp trafficking also occurs in brain capillary endothelial cells that form the BBB. In this study, trafficking of Pgp was investigated in human brain capillary endothelial cells (hCMEC/D3) that were stably transfected with a doxycycline-inducible MDR1-EGFP fusion plasmid. In the presence of doxycycline, these cells exhibited a 15-fold increase in Pgp-EGFP fusion protein expression, which was associated with an increased efflux of the Pgp substrate rhodamine 123 (Rho123). The chemotherapeutic agent mitomycin C (MMC) was used to study drug-induced trafficking of Pgp. Confocal fluorescence microscopy of single hCMEC/D3-MDR1-EGFP cells revealed that Pgp redistribution from intracellular pools to the cell surface occurred within 2 h of MMC exposure. Pgp-EGFP exhibited a punctuate pattern at the cell surface compatible with concentrated regions of the fusion protein in membrane microdomains, i.e., lipid rafts, which was confirmed by Western blot analysis of biotinylated cell surface proteins in Lubrol-resistant membranes. MMC exposure also increased the functionality of Pgp as assessed in three functional assays with Pgp substrates (Rho123, eFluxx-ID Gold, calcein-AM). However, this increase occurred with some delay after the increased Pgp expression and coincided with the release of Pgp from the Lubrol-resistant membrane complexes. Disrupting rafts by depleting the membrane of cholesterol increased the functionality of Pgp. Our data present the first direct evidence of drug-induced Pgp trafficking at the human BBB and indicate that Pgp has to be released from lipid

  2. Drug-Induced Trafficking of P-Glycoprotein in Human Brain Capillary Endothelial Cells as Demonstrated by Exposure to Mitomycin C

    Science.gov (United States)

    Noack, Andreas; Noack, Sandra; Hoffmann, Andrea; Maalouf, Katia; Buettner, Manuela; Couraud, Pierre-Olivier; Romero, Ignacio A.; Weksler, Babette; Alms, Dana; Römermann, Kerstin; Naim, Hassan Y.; Löscher, Wolfgang

    2014-01-01

    P-glycoprotein (Pgp; ABCB1/MDR1) is a major efflux transporter at the blood-brain barrier (BBB), restricting the penetration of various compounds. In other tissues, trafficking of Pgp from subcellular stores to the cell surface has been demonstrated and may constitute a rapid way of the cell to respond to toxic compounds by functional membrane insertion of the transporter. It is not known whether drug-induced Pgp trafficking also occurs in brain capillary endothelial cells that form the BBB. In this study, trafficking of Pgp was investigated in human brain capillary endothelial cells (hCMEC/D3) that were stably transfected with a doxycycline-inducible MDR1-EGFP fusion plasmid. In the presence of doxycycline, these cells exhibited a 15-fold increase in Pgp-EGFP fusion protein expression, which was associated with an increased efflux of the Pgp substrate rhodamine 123 (Rho123). The chemotherapeutic agent mitomycin C (MMC) was used to study drug-induced trafficking of Pgp. Confocal fluorescence microscopy of single hCMEC/D3-MDR1-EGFP cells revealed that Pgp redistribution from intracellular pools to the cell surface occurred within 2 h of MMC exposure. Pgp-EGFP exhibited a punctuate pattern at the cell surface compatible with concentrated regions of the fusion protein in membrane microdomains, i.e., lipid rafts, which was confirmed by Western blot analysis of biotinylated cell surface proteins in Lubrol-resistant membranes. MMC exposure also increased the functionality of Pgp as assessed in three functional assays with Pgp substrates (Rho123, eFluxx-ID Gold, calcein-AM). However, this increase occurred with some delay after the increased Pgp expression and coincided with the release of Pgp from the Lubrol-resistant membrane complexes. Disrupting rafts by depleting the membrane of cholesterol increased the functionality of Pgp. Our data present the first direct evidence of drug-induced Pgp trafficking at the human BBB and indicate that Pgp has to be released from lipid

  3. Utilization of the Bridging Strategy for the Development of New Drugs in Oncology to Avoid Drug Lag.

    Science.gov (United States)

    Kogure, Seiji; Koyama, Nobuyuki; Hidaka, Shinji

    2017-11-01

    Global trial (GT) strategy and bridging (BG) strategy are currently the main clinical development strategies of oncology drugs in Japan, but the relationship between development style and drug lag and how the bridging strategy has contributed to the solution of drug lag have not been clear. We investigated the potential factors that influenced submission lag (SL), and also compared the differences in SL among early-initiation BG strategy, late-initiation BG strategy, and GT strategy. A stepwise linear regression analysis identified the potential factors that shorten SL: development start lag and development style. Comparison of the differences in SL among the strategies also indicated that the SL in the GT strategy and that in the early-initiation BG strategy were significantly shorter than that in the late-initiation BG strategy. The findings in our study suggest that the late-initiation BG strategy may not contribute to shortening drug lag. Because the number of late-initiation BG studies has not decreased, we propose first that pharmaceutical companies should initiate clinical development as early as possible in Japan so that they can choose the GT strategy as a first option at the next step, and second when they cannot choose the GT strategy after investigating differences in exposure between Japanese and non-Japanese in a phase 1 study, they should select the early BG strategy to avoid future drug lag. It is also important for the regulatory authorities to provide reasonable guidance to have a positive impact on strategic decisions, even for foreign-capital companies. © 2017, The American College of Clinical Pharmacology.

  4. Development and demonstration of low-energy district heating for low-energy buildings. Main report and appendices; Udvikling og demonstration af lavenergifjernvarme til lavenergibyggeri. Hovedrapport + bilag

    Energy Technology Data Exchange (ETDEWEB)

    Christiansen, C.H.; Paulsen, O.; Boehm, B. (Teknologisk Institut, Taastrup (Denmark)); Thorsen, J.E. (Danfoss A/S, (Denmark)); Ting Larsen, C.; Jepsen, B.K. (LOGSTOR A/S, (Denmark)); Kaarup Olsen, P.; Lambertsen, H.; Hummelshoej, R. (COWI A/S, (Denmark)); Svendsen, Svend; Fan, J.; Furbo, S. (DTU-BYG, Kgs. Lyngby (Denmark)); Worm, J.; Didriksen, J. (Energitjenesten, Copenhagen (Denmark))

    2009-03-15

    The project describes a design concept for district heating supply of low energy houses based on 24 hour equalizing of load and very low district heating flow temperatures. District heating is a very flexible system in terms of utilizing waste heat from CHPplants, refuse incineration and industrial processes as well as renewable energy sources in an energy efficient manner. However, in relation to district heating for low energy houses there are some challenges according to investment costs and costs related to heat loss from distribution network. The objective of the project is to develop a design concept that will reduce these costs and be a 'de facto' standard of district heating to low energy houses. The design concept is based on a new type of consumer station with a domestic hot water plate heat exchanger connected to a tank on the district heating primary side. To specify design and operating parameters a simulation model of the consumer station was developed in TRNSYS. Different parameters were investigated e.g. tank size (60-200 liter) and charge flow (120-14 kg/h). An area of 92 single family houses classified as 'class 1' (42.6 kWh/m2) according to the Danish Building Regulation was chosen as reference area. Hydraulic and thermal analysis in the calculation tool TERMIS were used to lay out the distribution network based on pre-insulated twinpipes (supply and return in same casing pipe) with low-lambda PUR insulation and diffusion barrier. The design concept is compared with 3 other types of district heating systems. For a traditional system with single pipes and high district heating temperatures, the heat loss of the distribution network is calculated to 36%. In comparison, the distribution loss of the design concept can be as low as 12%. The total investment costs are almost equal for the 4 systems. In the new design concept, the cost of distribution network is reduced due to the use of smaller dimensions and twin-pipes. Though, the

  5. Research, development, and demonstration of nickel-iron batteries for electric vehicle propulsion. Annual report, 1979

    Energy Technology Data Exchange (ETDEWEB)

    1980-06-01

    The program has progressed to the stage of evaluating full-sized (220 Ah) cells, multicell modules, and 22 kWh batteries. Nickel electrodes that display stable capacities of up to 24 Ah/plate (at C/3 drain rate) at design thickness (2.5 mm) in tests at 200/sup +/ test cycles. Iron electrodes of the composite-type are also delivering 24 Ah/plate (at C/3) at target thickness (1.0 mm). Iron plates are displaying capacity stability for 300/sup +/ test cycles in continuing 3 plate cell tests. Best finished cells are delivering 57 to 63 Wh/kg at C/3, based on cell weights of the finished cells, and in the actual designed cell volume. 6-cell module (6-1) performance has demonstrated 239 Ah, 1735 Wh, 53 WH/kg at the C/3 drain rate. This module is now being evaluated at the National Battery Test Laboratory. The 2 x 4 battery has been constructed, tested, and delivered for engineering test and evaluation. The battery delivered 22.5 kWh, as required (199 Ah discharge at 113 V-bar) at the C/3 drain rate. The battery has performed satisfactorily under dynamometer and constant current drain tests. Some cell problems, related to construction, necessitated changing 3 modules, but the battery is now ready for further testing. Reduction in nickel plate swelling (and concurrent stack electrolyte starvation), to improve cycling, is one area of major effort to reach the final battery objectives. Pasted nickel electrodes are showing promise in initial full-size cell tests and will continue to be evaluated in finished cells, along with other technology advancements. 30 figures, 14 tables.

  6. Research, development and demonstration of nickel-zinc batteries for electric vehicle propulsion. Annual report, 1978

    Energy Technology Data Exchange (ETDEWEB)

    1979-10-01

    This is the first annual report of progress achieved under ANL Contract 31-109-38-4248. It covers the report period from 15 March 1978 to 15 August 1978. The nickel electrode development program is directed at the optimization of the electrical performance, specifically, in terms of increased cycle life. The work concentrated upon both the development of pilot plant facilities to produce nickel hydroxide and upon optimizing the manufacturing processes to produce nickel hydroxide which has high electrochemical utilization. The primary goal of the zinc electrode studies is to increase the cycle life of this electrode. This effort is primarily concentrating on the effect of additives upon shape change and cycle performance and on the mechanistic processes involved in the shape change. The separator effort has as its major goal the development of a low-cost separator which exhibits stability in the electrolyte, has uniform pores which are of a sufficiently small size to impede the growth of zinc dendrites, and exhibits low electrical resistance and good flexibility. The process itself is now optimized for pilot plant manufacture; hundreds of formulations have been produced and subsequently screened in both the laboratory and in actual cells. Promising formulations are presently being subjected to additional characterization tests and life cycles. The goal of the sealed cell studies is to determine the feasibility of sealed-cell operation. Large numbers of 20-Ah cells have been subjected to accelerated testing. These cells incorporated separator variations, active material additives, and internal design variations. Cycle lives up to 150 deep cycles were achieved. Cell failure modes are analyzed. 51 figures, 20 tables.

  7. Development, Demonstration, and Field Testing of Enterprise-Wide Distributed Generation Energy Management System: Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Greenberg, S.; Cooley, C.

    2005-01-01

    This report details progress on subcontract NAD-1-30605-1 between the National Renewable Energy Laboratory and RealEnergy (RE), the purpose of which is to describe RE's approach to the challenges it faces in the implementation of a nationwide fleet of clean cogeneration systems to serve contemporary energy markets. The Phase 2 report covers: utility tariff risk and its impact on market development; the effect on incentives on distributed energy markets; the regulatory effectiveness of interconnection in California; a survey of practical field interconnection issues; trend analysis for on-site generation; performance of dispatch systems; and information design hierarchy for combined heat and power.

  8. Biomarkers in early phase development of central nervous system drugs : a conceptual framework

    NARCIS (Netherlands)

    Post, Jeroen-Paul van der

    2006-01-01

    The main objective of this thesis is to provide a conceptual framework for the use of Central Nervous System (CNS) biomarkers in early phase clinical drug development. In the Introduction the current use of biomarkers in early CNS drug development is discussed. A conceptual framework for the

  9. 77 FR 69634 - International Conference on Harmonisation; Guidance on Q11 Development and Manufacture of Drug...

    Science.gov (United States)

    2012-11-20

    ...] International Conference on Harmonisation; Guidance on Q11 Development and Manufacture of Drug Substances... Administration (FDA) is announcing the availability of a guidance entitled ``Q11 Development and Manufacture of... guidance is intended to apply only to the manufacture of drug substance, not the manufacture of finished...

  10. A Cloud-Based Global Flood Disaster Community Cyber-Infrastructure: Development and Demonstration

    Science.gov (United States)

    Wan, Zhanming; Hong, Yang; Khan, Sadiq; Gourley, Jonathan; Flamig, Zachary; Kirschbaum, Dalia; Tang, Guoqiang

    2014-01-01

    Flood disasters have significant impacts on the development of communities globally. This study describes a public cloud-based flood cyber-infrastructure (CyberFlood) that collects, organizes, visualizes, and manages several global flood databases for authorities and the public in real-time, providing location-based eventful visualization as well as statistical analysis and graphing capabilities. In order to expand and update the existing flood inventory, a crowdsourcing data collection methodology is employed for the public with smartphones or Internet to report new flood events, which is also intended to engage citizen-scientists so that they may become motivated and educated about the latest developments in satellite remote sensing and hydrologic modeling technologies. Our shared vision is to better serve the global water community with comprehensive flood information, aided by the state-of-the- art cloud computing and crowdsourcing technology. The CyberFlood presents an opportunity to eventually modernize the existing paradigm used to collect, manage, analyze, and visualize water-related disasters.

  11. Engineering Model Propellant Feed System Development for an Iodine Hall Thruster Demonstration Mission

    Science.gov (United States)

    Polzin, Kurt A.

    2016-01-01

    CUBESATS are relatively new spacecraft platforms that are typically deployed from a launch vehicle as a secondary payload, providing low-cost access to space for a wide range of end-users. These satellites are comprised of building blocks having dimensions of 10x10x10 cu cm and a mass of 1.33 kg (a 1-U size). While providing low-cost access to space, a major operational limitation is the lack of a propulsion system that can fit within a CubeSat and is capable of executing high (Delta)v maneuvers. This makes it difficult to use CubeSats on missions requiring certain types of maneuvers (i.e. formation flying, spacecraft rendezvous). Recently, work has been performed investigating the use of iodine as a propellant for Hall-effect thrusters (HETs) 2 that could subsequently be used to provide a high specific impulse path to CubeSat propulsion. 3, 4 Iodine stores as a dense solid at very low pressures, making it acceptable as a propellant on a secondary payload. It has exceptionally high ?Isp (density times specific impulse), making it an enabling technology for small satellite near-term applications and providing the potential for systems-level advantages over mid-term high power electric propulsion options. Iodine flow can also be thermally regulated, subliming at relatively low temperature (engineering model propellant feed system for iSAT (see Fig. 1). The feed system is based around an iodine propellant reservoir and two proportional control valves (PFCVs) that meter the iodine flow to the cathode and anode. The flow is split upstream of the PFCVs to both components can be fed from a common reservoir. Testing of the reservoir is reported to demonstrate that the design is capable of delivering the required propellant flow rates to operate the thruster. The tubing and reservoir are fabricated from hastelloy to resist corrosion by the heated gaseous iodine propellant. The reservoir, tubing, and PFCVs are heated to ensure the sublimed propellant will not re

  12. Combined Heat and Power Systems Technology Development and Demonstration 370 kW High Efficiency Microturbine

    Energy Technology Data Exchange (ETDEWEB)

    none,

    2015-10-14

    The C370 Program was awarded in October 2010 with the ambitious goal of designing and testing the most electrically efficient recuperated microturbine engine at a rated power of less than 500 kW. The aggressive targets for electrical efficiency, emission regulatory compliance, and the estimated price point make the system state-of-the-art for microturbine engine systems. These goals will be met by designing a two stage microturbine engine identified as the low pressure spool and high pressure spool that are based on derivative hardware of Capstone’s current commercially available engines. The development and testing of the engine occurred in two phases. Phase I focused on developing a higher power and more efficient engine, that would become the low pressure spool which is based on Capstone’s C200 (200kW) engine architecture. Phase II integrated the low pressure spool created in Phase I with the high pressure spool, which is based on Capstone’s C65 (65 kW) commercially available engine. Integration of the engines, based on preliminary research, would allow the dual spool engine to provide electrical power in excess of 370 kW, with electrical efficiency approaching 42%. If both of these targets were met coupled with the overall CHP target of 85% total combined heating and electrical efficiency California Air Resources Board (CARB) level emissions, and a price target of $600 per kW, the system would represent a step change in the currently available commercial generation technology. Phase I of the C370 program required the development of the C370 low pressure spool. The goal was to increase the C200 engine power by a minimum of 25% — 250 kW — and efficiency from 32% to 37%. These increases in the C200 engine output were imperative to meet the power requirements of the engine when both spools were integrated. An additional benefit of designing and testing the C370 low pressure spool was the possibility of developing a stand-alone product for possible

  13. Justicia pectoralis, a coumarin medicinal plant have potential for the development of antiasthmatic drugs?

    Directory of Open Access Journals (Sweden)

    Luzia Kalyne Almeida Moreira Leal

    Full Text Available ABSTRACT Justicia pectoralis Jacq., Acanthaceae, is a medicinal plant found Central America. In the Northeast of Brazil, it is popularly known as “chambá” being extensively used in homemade preparations for the treatment of cough, bronchitis and asthma. The species is part of a public phytotherapy program in Brazil entitled “Farmácias Vivas”, National Record of Plants of Interest to the National Health System and the National Formulary of Herbal medicines. This paper aims to critically review the available scientific literature regarding the health promoting effects of J. pectoralis var. stenophylla. The traditional uses, phytochemistry, pharmacological activities, toxicology, quality control and potential interactions with conventional drugs were included in the present review. Botanical, chemical and pharmacognostical studies stablished several parameters useful for quality control of plant drug, extracts and phytomedicine from aerial parts of J. pectoralis using as markers two bioactive coumarins. A wide range of evidence have demonstrated the anti-inflammatory, anti-nociceptive, anti-spasmodic, smooth muscle relaxant and anxiolytic effects of J. pectoralis and its chemical constituents. Pilot clinical studies showed the efficacy of a syrup preparation of J. pectoralis in the treatment of mild and moderate asthma. The pharmacological potential make these medicinal plants good candidates for the development of new phytomedicine for the treatment of asthma. However, a strong collaboration to bridge the gap between preclinical and clinical study is still necessary for the development of an effective medicine from J. pectoralis.