WorldWideScience

Sample records for existing radioligands nida

  1. NIDA Notes

    Science.gov (United States)

    ... Treatment Basic Science Public Health Prevention More Categories Narrative of Discovery NIDA @ Work Director's ... used the statistical technique of latent class analysis to describe distinct patterns of marijuana use across ...

  2. NIDA for Teens

    Science.gov (United States)

    ... National Drug & Alcohol Facts Week® Enter Search Term(s): Teens: Drug Use and the Brain Get the latest on ... News About Drugs Activities, Games, and More National Drug & Alcohol Facts Week About ... Find NIDA for Teens on: Site last updated December 14, 2017 NOTE: ...

  3. Marihuana: A Conversation with NIDA's Robert L. DuPont.

    Science.gov (United States)

    Maugh, T H

    1976-05-14

    Robert L. DuPont, director of the National Institute on Drug Abuse (NIDA), made headlines recently when he became one of the first Administration officials publicly to recommend a liberalization of marihuana laws. The occasion was a press conference accompanying the release of Marihuana and Health, NIDA's fifth annual report to the Congress on marihuana research. Recently, Science talked with DuPont and asked him to elaborate on those views. DuPont, a 40-year-old Harvard M.D., served as Director of the District of Columbia's Narcotics Treatment Administration from 1970 to 1973, where he conducted a comprehensive program for treatment of heroin addiction. In June 1973, Richard Nixon appointed him director of the White House Special Action Office for Drug Abuse Prevention. He held that position until the office was terminated on 30 June 1975. He has been director of NIDA since September 1973.

  4. A Collection of NIDA Notes: Articles That Address Research on Marijuana.

    Science.gov (United States)

    National Inst. on Drug Abuse (DHHS/PHS), Bethesda, MD.

    Included in this document are selections of topic-specific articles on marijuana research reprinted from the National Institute on Drug Abuse's (NIDA) research newsletter, NIDA Notes. The collection features articles originally published from 1995 through 2002. Topics include long-term cognitive impairments in heavy marijuana users, evidence that…

  5. [Application of Nida's theory in English translation of traditional Chinese medicine].

    Science.gov (United States)

    Li, Yong-an; Li, Jing-yun

    2006-09-01

    The famous American translation theorist Eugene A. Nida has put forward lots of viewpoints and theories for translation work when he translated the Bible, which have important practical instructional meaning for translation of traditional Chinese medicine nowadays. The application of Nida's theories to translating practice of TCM is illustrated by specific examples in this paper.

  6. In what sense is the Louw/Nida dictionary authoritative? | Vorster ...

    African Journals Online (AJOL)

    This essay deals with four factors which make the Louw/Nida dictionary authoritative. These include the presentation of lexical meanings in semantic domains, the definition of meanings, the distinction that is made between meaning and reference, and the layout of the dictionary. All factors a re discussed critically and ...

  7. What Are Youth Asking about Drugs? A Report of NIDA Drug Facts Chat Day

    Science.gov (United States)

    Morton, Cory M.; Hoefinger, Heidi; Linn-Walton, Rebecca; Aikins, Ross; Falkin, Gregory P.

    2015-01-01

    The current study analyzes a sample of questions about drugs asked online by youth who participated in the National Institute on Drug Abuse's (NIDA) "Drug Facts Chat Day." The types of drugs youth asked about were coded into 17 substance categories, and the topics they raised were coded into seven thematic categories. The top five…

  8. Imaging tumors with peptide-based radioligands

    Energy Technology Data Exchange (ETDEWEB)

    Behr, T. M.; Gotthardt, M.; Barth, A.; Behe, M. [Philipps-University of Marburg, Dept. of Nuclear Medicine, Marburg (Germany)

    2001-06-01

    derivatives of gastrin showed excellent targeting of CCK-B receptor expressing tissues in animals and patients. A variety of further peptide-based radioligands, e.g. among many others, gastrin-releasing peptide/bombesin, neurotensin, substance-P, pan-somatostatin (somatostatin derivatives which bind to all five receptor subtypes) or glucagon-like peptide-1 (glp-1) analogs (the latter for the specific detection of insulinomas), is currently under development. Summarizing, radiolabeled regulatory peptides have opened new horizons in nuclear oncology for diagnosis (and potential internal radionuclide therapy). Future work will probably reveal a multitude of novel potentially clinically useful peptide-based radioligands.

  9. Imaging tumors with peptide-based radioligands.

    Science.gov (United States)

    Behr, T M; Gotthardt, M; Barth, A; Béhé, M

    2001-06-01

    gastrin showed excellent targeting of CCK-B receptor expressing tissues in animals and patients. A variety of further peptide-based radioligands, e.g. among many others, gastrin-releasing peptide/bombesin, neurotensin, substance-P, pan-somatostatin (somatostatin derivatives which bind to all five receptor subtypes) or glucagon-like peptide-1 (glp-1) analogs (the latter for the specific detection of insulinomas), is currently under development. Summarizing, radiolabeled regulatory peptides have opened new horizons in nuclear oncology for diagnosis (and potential internal radionuclide therapy). Future work will probably reveal a multitude of novel potentially clinically useful peptide-based radioligands.

  10. MaNIDA: Insight into the German Marine Network for Integrated Data Access

    Science.gov (United States)

    Schäfer, Angela; Scientific MaNIDA Team

    2013-04-01

    The Marine Network for Integrated Data Access (MaNIDA) builds a sustainable e-Infrastructure to support discovery and re-use of data from distinct marine and earth science data providers in Germany (see ESSI1.2 and ESSI2.2). Thereby we implement the "Data Portal of German Marine Research" for coherent discovery, view, download and dissemination of aggregated content. MaNIDA receives a unique momentum from the cooperation and financial partnership between main German marine research institutes (AWI, MARUM, HZG, GEOMAR, Uni Hamburg, Uni Kiel, Uni Bremen) and the Federal Maritime and Hydrographic Agency as well as active participation in international and major EU-initiatives (ICSU, GEOSS, SeaDataNet, EMODNET, ODIP). Together with a coherent management strategy coordinated by the Alfred Wegener Institute, Helmholtz Center for Polar and Marine Research, sustainability will be achieved via the long-term commitment of framework funding by the Helmholtz Association, Germany's largest scientific research organization for large-scale facilities and scientific infrastructure. Strategic Aims The installation of the "Data Portal of German Marine Research" will address the urgent demands of the German research community for reliable and easy access to marine research data at one single point of access and truth. Primary focus will be given to data derived from nationally operated research and monitoring facilities (vessels, observatories, alert systems, etc), whereby related contextual content and publications will become an integral part of the aggregation effort. For the scientific community we define responsibilities and commitments across partners while complementing existing data repositories and the new portal with well-articulated workflows from the instrument to the data product. Necessary level of quality assurance and user support will be implemented to achieve substantial enhancements in the whole lifecycle management of marine scientific data. The creation of a data

  11. Selected rare and protected macrofungi (Agaricomycetes as bioindicators of communities of xerothermic vegetation in the Nida Basin

    Directory of Open Access Journals (Sweden)

    Agnieszka Tomaszewska

    2015-08-01

    Full Text Available Results of mycological investigations conducted in xerothermic grasslands of the Nida Basin in the years 1984–2013 are presented. Our research brings up to date the current knowledge on ecological requirements of threatened species of macrofungi. Strong affiliations between macrofungi and specific phytocenoses of the alliances Festuco-Stipion and Seslerio-Festucion duriusculae were detected. A considerable influence of the occurrence of certain species of steppe fungi on the composition of the mycobiota in the Nida Basin was identified.

  12. PET radioligands for imaging of Tau pathology: Current status

    Energy Technology Data Exchange (ETDEWEB)

    Choe, Yearn Seong [Dept. of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Lee, Kyung Han [Dept. of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul (Korea, Republic of)

    2015-12-15

    The incidence of Alzheimer’s disease (AD), a progressive neurodegenerative disorder, continues to soar with the rapid growth of the elderly population, thus creating an enormous social and economic burden. Although disease-modifying drugs to treat AD are not yet available, several candidate drugs are in clinical trials. Most of these drugs are expected to be effective at the early stages of the disease, and therefore the early and accurate diagnosis of AD will be a critical factor in efforts to improve the prognosis of patients with AD. This review focuses on lead radioligands developed to date and their preclinical data in order to facilitate the development of tau-specific positron emission tomography radioligands that are of great interest to the scientific community.

  13. 5-HT Radioligands for Human Brain Imaging With PET and SPECT

    Science.gov (United States)

    Paterson, Louise M.; Kornum, Birgitte R.; Nutt, David J.; Pike, Victor W.; Knudsen, Gitte M.

    2014-01-01

    The serotonergic system plays a key modulatory role in the brain and is the target for many drug treatments for brain disorders either through reuptake blockade or via interactions at the 14 subtypes of 5-HT receptors. This review provides the history and current status of radioligands used for positron emission tomography (PET) and single photon emission computerized tomography (SPECT) imaging of human brain serotonin (5-HT) receptors, the 5-HT transporter (SERT), and 5-HT synthesis rate. Currently available radioligands for in vivo brain imaging of the 5-HT system in humans include antagonists for the 5-HT1A, 5-HT1B, 5-HT2A, and 5-HT4 receptors, and for SERT. Here we describe the evolution of these radioligands, along with the attempts made to develop radioligands for additional serotonergic targets. We describe the properties needed for a radioligand to become successful and the main caveats. The success of a PET or SPECT radioligand can ultimately be assessed by its frequency of use, its utility in humans, and the number of research sites using it relative to its invention date, and so these aspects are also covered. In conclusion, the development of PET and SPECT radioligands to image serotonergic targets is of high interest, and successful evaluation in humans is leading to invaluable insight into normal and abnormal brain function, emphasizing the need for continued development of both SPECT and PET radioligands for human brain imaging. PMID:21674551

  14. Interference of anaesthetics with radioligand binding in neuroreceptor studies

    Energy Technology Data Exchange (ETDEWEB)

    Elfving, Betina; Knudsen, Gitte Moos [Neurobiology Research Unit N9201, University hospital Rigshospitalet, 9 Blegdamsvej, 2100, Copenhagen (Denmark); Bjoernholm, Berith [Department of Computational Chemistry, H. Lundbeck A/S, Copenhagen-Valby (Denmark)

    2003-06-01

    Evaluations of new emission tomography ligands are usually carried out in animals. In order to keep the animals in a restricted position during the scan session, anaesthesia is almost inevitable. In ex vivo rat studies we investigated the interference of ketamine/xylazine, zoletile mixture, isoflurane and halothane with the serotonin re-uptake site, the serotonin{sub 2A} receptor and the dopamine re-uptake site by use of [{sup 3}H]-(S)-citalopram, [{sup 18}F]altanserin and [{sup 125}I]PE2I, respectively. Ketamine/xylazine decreased the target-to-background ratio (mean {+-} SD) of [{sup 3}H]-(S)-citalopram from 1.5{+-}0.19 to 0.81{+-}0.19 (P<0.05), whereas isoflurane and halothane increased the ratio from 1.5{+-}0.19 to 1.9{+-}0.24 and 2.1{+-}0.13 (P<0.05), respectively. Only with the zoletile mixture did the ratio remain unaltered. None of the tested anaesthetics affected the target-to-background ratio of [{sup 18}F]altanserin. The [{sup 125}I]PE2I target-to-background ratio decreased with both ketamine/xylazine (from 12.4{+-}0.81 to 10.1{+-}1.4, P<0.05) and isoflurane (from 12.4{+-}0.81 to 9.5{+-}1.1, P<0.05) treated rats, whereas treatment with zoletile mixture and halothane left the ratio unaltered. It is concluded that prior to performance of neuroreceptor radioligand studies, the possible interaction between radioligands and anaesthetics should be carefully evaluated. (orig.)

  15. NIDA-Drug Addiction Treatment Outcome Study (DATOS) Relapse as a Function of Spirituality/Religiosity.

    Science.gov (United States)

    Schoenthaler, Stephen J; Blum, Kenneth; Braverman, Eric R; Giordano, John; Thompson, Ben; Oscar-Berman, Marlene; Badgaiyan, Rajendra D; Madigan, Margaret A; Dushaj, Kristina; Li, Mona; Demotrovics, Zsolt; Waite, Roger L; Gold, Mark S

    The connection between religion/spirituality and deviance, like substance abuse, was first made by Durkheim who defined socially expected behaviors as norms. He explained that deviance is due in large part to their absence (called anomie), and concluded that spirituality lowers deviance by preserving norms and social bonds. Impairments in brain reward circuitry, as observed in Reward Deficiency Syndrome (RDS), may also result in deviance and as such we wondered if stronger belief in spirituality practice and religious belief could lower relapse from drugs of abuse. The NIDA Drug Addiction Treatment Outcome Study data set was used to examine post hoc relapse rates among 2,947 clients who were interviewed at 12 months after intake broken down by five spirituality measures. Our main findings strongly indicate, that those with low spirituality have higher relapse rates and those with high spirituality have higher remission rates with crack use being the sole exception. We found significant differences in terms of cocaine, heroin, alcohol, and marijuana relapse as a function of strength of religious beliefs (x 2 = 15.18, p = 0.028; logistic regression = 10.65, p = 0.006); frequency of attending religious services (x 2 = 40.78, p Durkheim's social bond theory. Stronger spiritual/religious beliefs and practices are directly associated with remission from abused drugs except crack. Much like the value of having a sponsor, for clients who abuse drugs, regular spiritual practice, particularly weekly attendance at the religious services of their choice is associated with significantly higher remission. These results demonstrate the clinically significant role of spirituality and the social bonds it creates in drug treatment programs.

  16. Cerebellar heterogeneity and its impact on PET data quantification of 5-HT receptor radioligands

    DEFF Research Database (Denmark)

    Ganz, Melanie; Feng, Ling; Hansen, Hanne Demant

    2017-01-01

    standardized uptake values (SUV) and nondisplaceable neocortical binding potential (BPND). Statistical difference was assessed with paired nonparametric two-sided Wilcoxon signed-rank tests and multiple comparison corrected via false discovery rate. We demonstrate significant radioligand specific regional...

  17. Representaciones Sociales de mujeres amazônidas sobre el examen papanicolau: implicaciones para la salud de la mujer

    OpenAIRE

    SILVA, Sílvio Éder Dias da; VASCONCELOS, Esleane Vilela; SANTANA, Mary Elizabeth de; Lima, Vera Lúcia de Azevedo; CARVALHO, Francilene da Luz Carvalho; Mar,Dayse Farias

    2008-01-01

    Esta pesquisa tem como objetivos descrever as representações sociais de mulheres amazônidas sobre o exame Papanicolau e analisar as implicações desta para o cuidado de si mesmas. Trata-se de um estudo qualitativo-exploratório com o uso da Teoria das representações sociais. A coleta de dados foi realizada no período de janeiro a dezembro de 2007, com o emprego de duas técnicas: a entrevista semi-estruturada com perguntas abertas e a observação livre. Para a interpretação desses dados foi utili...

  18. MaNIDA: Integration of marine expedition information, data and publications: Data Portal of German Marine Research

    Science.gov (United States)

    Koppe, Roland; Scientific MaNIDA-Team

    2013-04-01

    The Marine Network for Integrated Data Access (MaNIDA) aims to build a sustainable e-infrastructure to support discovery and re-use of marine data from distinct data providers in Germany (see related abstracts in session ESSI 1.2). In order to provide users integrated access and retrieval of expedition or cruise metadata, data, services and publications as well as relationships among the various objects, we are developing (web) applications based on state of the art technologies: the Data Portal of German Marine Research. Since the German network of distributed content providers have distinct objectives and mandates for storing digital objects (e.g. long-term data preservation, near real time data, publication repositories), we have to cope with heterogeneous metadata in terms of syntax and semantic, data types and formats as well as access solutions. We have defined a set of core metadata elements which are common to our content providers and therefore useful for discovery and building relationships among objects. Existing catalogues for various types of vocabularies are being used to assure the mapping to community-wide used terms. We distinguish between expedition metadata and continuously harvestable metadata objects from distinct data providers. • Existing expedition metadata from distinct sources is integrated and validated in order to create an expedition metadata catalogue which is used as authoritative source for expedition-related content. The web application allows browsing by e.g. research vessel and date, exploring expeditions and research gaps by tracklines and viewing expedition details (begin/end, ports, platforms, chief scientists, events, etc.). Also expedition-related objects from harvesting are dynamically associated with expedition information and presented to the user. Hence we will provide web services to detailed expedition information. • Other harvestable content is separated into four categories: archived data and data products, near

  19. Representações sociais de mulheres amazônidas sobre o exame papanicolau: implicações para a saúde da mulher Representaciones Sociales de mujeres amazônidas sobre el examen papanicolau: implicaciones para la salud de la mujer Social Representations of women amazônidas on examination papanicolau: implications for the health of the woman

    OpenAIRE

    Sílvio Éder Dias da Silva; Esleane Vilela Vasconcelos; Mary Elizabeth de Santana; Vera Lúcia de Azevedo Lima; Francileni da Luz Carvalho; Dayse Farias Mar

    2008-01-01

    Esta pesquisa tem como objetivos descrever as representações sociais de mulheres amazônidas sobre o exame Papanicolau e analisar as implicações desta para o cuidado de si mesmas. Trata-se de um estudo qualitativo-exploratório com o uso da Teoria das representações sociais. A coleta de dados foi realizada no período de janeiro a dezembro de 2007, com o emprego de duas técnicas: a entrevista semi-estruturada com perguntas abertas e a observação livre. Para a interpretação desses dados foi utili...

  20. 5-HT radioligands for human brain imaging with PET and SPECT

    DEFF Research Database (Denmark)

    Paterson, Louise M; Kornum, Birgitte R; Nutt, David J

    2013-01-01

    The serotonergic system plays a key modulatory role in the brain and is the target for many drug treatments for brain disorders either through reuptake blockade or via interactions at the 14 subtypes of 5-HT receptors. This review provides the history and current status of radioligands used...... for positron emission tomography (PET) and single photon emission computerized tomography (SPECT) imaging of human brain serotonin (5-HT) receptors, the 5-HT transporter (SERT), and 5-HT synthesis rate. Currently available radioligands for in vivo brain imaging of the 5-HT system in humans include antagonists...... to image serotonergic targets is of high interest, and successful evaluation in humans is leading to invaluable insight into normal and abnormal brain function, emphasizing the need for continued development of both SPECT and PET radioligands for human brain imaging....

  1. Radioligands for PET studies of central benzodiazepine receptors and PK (peripheral benzodiazepine) binding sites -current status

    Energy Technology Data Exchange (ETDEWEB)

    Pike, V.W.; Osman, S.; Shah, F.; Turton, D.R.; Waters, S.L. (Hammersmith Hospital, London (United Kingdom). M.R.C. Cyclotron Unit); Halldin, C. (Karolinska Sjukhuset, Stockholm (Sweden)); Crouzel, C. (CEA, 91 - Orsay (France). Service Hospitalier Frederic Joliot); Barre, L. (CEA, CYCERON, Caen (France)); Nutt, D.J. (Bristol Univ. (United Kingdom). School of Medical Sciences)

    1993-05-01

    The status of the radiochemical development and biological evaluation of radioligands for PET studies of central benzodiazepine (BZ) receptors and the so-called peripheral benzodiazepine binding sites, here discriminated and referred to as PK binding sites, is reviewed against current pharmacological knowledge, indicating those agents with present value and those with future potential. Practical recommendations are given for the preparation of two useful radioligands for PET studies, (N-methyl-[sup 11]C)flumazenil for central BZ receptors, and (N-methyl)-[sup 11]CPK 11195 for PK binding sites. Quality assurance and plasma metabolite analysis are also reviewed for these radioligands and practical recommendations are given on methodology for their performance. (author).

  2. Comparative quantitative prevalence of mycobacteria and functionally abundant nidA, nahAc, and nagAc Dioxygenase genes in coal tar contaminated sediments

    Energy Technology Data Exchange (ETDEWEB)

    Jennifer M. DeBruyn; Christopher S. Chewning; Gary S. Sayler [University of Tennessee, Knoxville, TN (United States). Department of Ecology and Evolutionary Biology

    2007-08-01

    The Chattanooga Creek Superfund site is heavily contaminated with metals, pesticides, and coal tar with sediments exhibiting high concentrations of polycyclic aromatic hydrocarbons (PAHs). High molecular weight PAHs are of concern because of their toxicity and recalcitrance in the environment; as such, there is great interest in microbes, such as fast-growing Mycobacterium spp., capable of degradation of these compounds. Real-time quantitative PCR assays were developed targeting multiple dioxygenase genes to assess the ecology and functional diversity of PAH-degrading communities. These assays target the Mycobacterium nidA, {beta}-proteobacteria nagAc, and {gamma}-proteobacteria nahAc with the specific goal of testing the hypothesis that Mycobacteria catabolic genes are enriched and may be functionally associated with high molecular weight PAH biodegradation in Chattanooga Creek. Dioxygenase gene abundances were quantitatively compared to naphthalene and pyrene mineralization, and temporal and spatial PAH concentrations. nidA abundances ranged from 5.69 x 10{sup 4} to 4.92 x 10{sup 6} copies per gram sediment; nagAc from 2.42 x 10{sup 3} to 1.21 x 10{sup 7}, and nahAc from below detection to 4.01 x 10{sup 6} copies per gram sediment. There was a significantly greater abundance of nidA and nagAc at sites with the greatest concentrations of PAHs. In addition, nidA and nagAc were significantly positively correlated, indicating a coexistence of organisms carrying these genes. A positive relationship was also observed between nidA and nagAc and pyrene mineralization indicating that these genes serve as biomarkers for pyrene degradation. A 16S rDNA clone library of fast-growing Mycobacteria indicated that the population is very diverse and likely plays an important role in attenuation of high molecular weight PAHs from Chattanooga Creek. 35 refs., 5 figs., 1 tab.

  3. Evaluation of potential agonist radioligands for imaging dopamine D2/3 receptors

    NARCIS (Netherlands)

    van Wieringen, J.P.

    2015-01-01

    Imaging dopamine receptors with PET and SPECT can shed light on the nature of neuropsychiatric disorders which are characterized by disturbances in dopamine D2/3 receptor functioning. Agonist radioligands are considered superior to antagonists because they are more sensitive to detect dopamine

  4. Chemical development of radioligands for PET studies of central neurotransmitters in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Shah, F

    1999-07-01

    The aims of this research were to identify potential receptor or binding site radioligands for imaging in vivo with PET (positron emission tomography) and to develop methods for their labelling with cyclotron-produced radioisotopes (carbon-11, t{sub 1/2} = 20.4 min; bromine-76, t{sub 1/2} = 966 min) at high specific radioactivity. PK 11195 (N-methyl-N-(1-methylpropyl)-1-(2-chlorophenyl)-isoquinoline-3-carboxamide) is a selective ligand for the 'so-called' peripheral benzodiazepine receptor (PK binding site). [N-methyl-{sup 11}C]PK 11195 is widely used as a radioligand with PET for the detection of PK binding sites in vivo (e.g. in stroke). However, this radioligand is racemic and gives a low signal. Two alternatives were identified based on their potency and lower lipophilicity, namely PK 11211 (the 2'-fluoro analogue of PK 11195) and PK 14105 (the 2'-fluoro-5'-nitro analogue of PK 11195). Homochiral nor analogues of PK 11195, PK 11211 and PK 14105 were synthesised, via the reaction of homochiral sec-butylamines with activated carboxylic acids, prepared via acylation, azlactone synthesis and Freidel-Crafts reactions. Conditions were found for the efficient N-methylation of these precursors with [{sup 11}C]iodomethane to provide the labelled R- and S-enantiomers of each radioligand. The enantiomers of [N-methyl-{sup 11}C]PK 11195 were produced for comparison in rats. The R-enantiomer was found to be the superior radioligand. Effective radioligands are required for imaging the serotonin (5-HT) re-uptake site in neuropsychiatric disorders. The potent 5-HT reuptake site ligand, WY 27587 (N[[[1-[(6-fluoro-2-naphthalenyl)methyl]-4-piperdinyl]aminolcarbonyl] -3-pyridine carboxamide) was identified as a candidate radioligand for the 5-HT reuptake site, and many possibilities for labelling with different positron-emitters (e.g. {sup 11}C and {sup 76}Br) were explored. ({gamma}-Emitting bromine-77 was used as a surrogate for bromine-76). [{sup 77}Br

  5. Representações sociais de mulheres amazônidas sobre o exame papanicolau: implicações para a saúde da mulher Representaciones Sociales de mujeres amazônidas sobre el examen papanicolau: implicaciones para la salud de la mujer Social Representations of women amazônidas on examination papanicolau: implications for the health of the woman

    Directory of Open Access Journals (Sweden)

    Sílvio Éder Dias da Silva

    2008-12-01

    Full Text Available Esta pesquisa tem como objetivos descrever as representações sociais de mulheres amazônidas sobre o exame Papanicolau e analisar as implicações desta para o cuidado de si mesmas. Trata-se de um estudo qualitativo-exploratório com o uso da Teoria das representações sociais. A coleta de dados foi realizada no período de janeiro a dezembro de 2007, com o emprego de duas técnicas: a entrevista semi-estruturada com perguntas abertas e a observação livre. Para a interpretação desses dados foi utilizada a técnica de análise de conteúdo temático. A pesquisa teve como resultado três unidades temáticas, assim denominadas: O exame Papanicolau - um cuidado com a saúde da mulher; Tabus e crenças sobre o exame Papanicolau; e Uma prática de cuidado de si mesma: o exame Papanicolau. No estudo observamos que as mulheres temem muito ter câncer cérvico-uterino e, por esse motivo, representam o exame Papanicolau como uma prática de cuidado de si mesma.Esta investigación tiene como objetivos describir las representaciones sociales de mujeres amazônidas sobre el examen Papanicolau y analizar las implicaciones de esta para el cuidado de sí misma. Se trata de un estudio cualitativo-exploratorio con el uso de la Teoría de las representaciones sociales. La colecta de dados fue realizada en el periodo de enero a diciembre de 2007, con el empleo de dos técnicas: la entrevista semi-estructurada con preguntas abiertas y la observación libre. Para la interpretación de esos dados fue utilizada la técnica de análisis de contenido temático. La investigación tuvo como resultado tres unidades temáticas, así denominadas: El examen Papanicolau - un cuidado con la salud de la mujer; Tabúes y creencias sobre el examen Papanicolau; y el Una práctica de cuidado de sí misma: el examen Papanicolau. En el estudio observamos que las mujeres temen mucho tener cáncer cérvico-uterino y, por ese motivo, representan el examen Papanicolau como una pr

  6. Representações sociais de mulheres amazônidas sobre o exame papanicolau: implicações para a saúde da mulher

    OpenAIRE

    SILVA, Sílvio Éder Dias da; VASCONCELOS, Esleane Vilela; SANTANA, Mary Elizabeth de; Lima, Vera Lúcia de Azevedo; Carvalho,Francileni da Luz; Mar,Dayse Farias

    2008-01-01

    Esta pesquisa tem como objetivos descrever as representações sociais de mulheres amazônidas sobre o exame Papanicolau e analisar as implicações desta para o cuidado de si mesmas. Trata-se de um estudo qualitativo-exploratório com o uso da Teoria das representações sociais. A coleta de dados foi realizada no período de janeiro a dezembro de 2007, com o emprego de duas técnicas: a entrevista semi-estruturada com perguntas abertas e a observação livre. Para a interpretação desses dados foi utili...

  7. [[sup 3]H]imidacloprid: synthesis of a candidate radioligand for the nicotinic acetylcholine receptor

    Energy Technology Data Exchange (ETDEWEB)

    Latli, B.; Casida, J.E. (California Univ., Berkeley, CA (United States). Dept. of Entomological Sciences)

    1992-08-01

    Imidacloprid is an exceptionally potent insecticide known from physiological studies to act at the nicotinic acetylcholine receptor. To prepare [[sup 3]H]imidacloprid as a candidate radioligand, 6-chloronicotinoyl chloride was reduced with NaB[sup 2]H[sub 4] (in model studies) or NaB[sup 3]H[sub 4] in absolute ethanol to 2-chloro-5-pyridinylmethanol which was transformed to 2-chloro-5-chloromethylpyridine on refluxing with thionyl chloride. Coupling with 4,5-dihydro-N-nitro-1H-imidazol-2-amine then gave [[sup 2]H[sub 2

  8. A New Positron Emission Tomography (PET) Radioligand for Imaging Sigma-1 Receptors in Living Subjects

    DEFF Research Database (Denmark)

    James, Michelle L; Shen, Bin; Zavaleta, Cristina L

    2012-01-01

    Sigma-1 receptor (S1R) radioligands have the potential to detect and monitor various neurological diseases. Herein we report the synthesis, radiofluorination and evaluation of a new S1R ligand 6-(3-fluoropropyl)-3-(2-(azepan-1-yl)ethyl)benzo[d]thiazol-2(3H)-one ([(18)F]FTC-146, [(18)F]13). [(18)F....... These results indicate that [(18)F]13 is a promising candidate radiotracer for further evaluation as a tool for studying S1Rs in living subjects....

  9. Radiosynthesis and characterisation of a potent and selective GPR139 agonist radioligand

    DEFF Research Database (Denmark)

    Kuhne, Sebastiaan; Nøhr, Anne Cathrine; Marek, AleŠ

    2016-01-01

    Compound 1 is a selective and potent agonist of the G protein-coupled receptor GPR139 (EC50 = 39 nM). In this study, we describe the synthesis, radiolabelling and in vitro evaluation of [3H]-1 for the characterisation of GPR139 and its spatial expression in the brain using autoradiography. Two...... to discriminate [3H]-1 binding to wildtype mice brains from GPR139 knockout mice brains and total binding from non-specific binding in CHO-k1 cells stably expressing human GPR139 receptor. Based on these experiments we conclude that [3H]-1 is not a suitable radioligand for the characterisation of GPR139....

  10. Radioligand binding analysis of α 2 adrenoceptors with [11C]yohimbine in brain in vivo: Extended Inhibition Plot correction for plasma protein binding

    DEFF Research Database (Denmark)

    Phan, Jenny-Ann; Landau, Anne M.; Jakobsen, Steen

    2017-01-01

    Inhibition Plot introduced here yielded an estimate of the volume of distribution of non-displaceable ligand in brain tissue that increased with the increase of the free fraction of the radioligand in plasma. The resulting binding potentials of the radioligand declined by 50-60% in the presence of unlabeled...

  11. Radioligand dissociation measurements: potential interference of rebinding and allosteric mechanisms and physiological relevance of the biological model systems.

    Science.gov (United States)

    Vauquelin, Georges; Van Liefde, Isabelle

    2012-07-01

    In many situations, optimal drug therapy requires continuing high levels of target occupancy and this notion has led pharmacologists to focus their attention on the rate by which drug candidates dissociate from their target. To this end, radioligand dissociation experiments are often carried out on in vitro models, such as intact cells and the membranes thereof, but the interpretation of the collected data is sometimes ambiguous. Pharmacodynamics is concerned about what the drug does to the target and, in this respect, allosteric modulation constitutes a quite novel, very promising research topic. The ability of unlabeled drugs to accelerate radioligand dissociation is often advocated to be a hallmark of such mechanism. Yet, the present computerized simulations reveal that competitive drugs produce the same effect by preventing hindered diffusion- and "forced proximity"-related rebinding of the radioligand. Herein, the authors provide hints to discern among those mechanisms. A critical, but constructive appraisal of radioligand dissociation binding data leads to the viewpoint that, from a physiological perspective, dissociation from confluent target-expressing plated cells, when in a naïve medium, is likely to provide the most pertinent insight in that ligand's in vivo residence time.

  12. (11)C-labeling and preliminary evaluation of pimavanserin as a 5-HT2A receptor PET-radioligand

    DEFF Research Database (Denmark)

    Andersen, Valdemar L; Hansen, Hanne D; Herth, Matthias M

    2015-01-01

    Pimavanserin is a selective serotonin 2A receptor (5-HT2AR) inverse agonist that has shown promise for treatment of psychotic symptoms in patients with Parkinson's disease. Here, we detail the (11)C-labeling and subsequently evaluate pimavanserin as a PET-radioligand in pigs. [(11)C...

  13. Synthesis of Sulochrin-125I and Its Binding Affinity as α-Glucosidase Inhibitor using Radioligand Binding Assay (RBA Method

    Directory of Open Access Journals (Sweden)

    W. Lestari

    2014-04-01

    Full Text Available Most of diabetics patients have type 2 diabetes mellitus or non insulin dependent diabetes mellitus. Treatment type 2 diabetes mellitus can be done by inhibiting α-glucosidase enzyme which converts carbohydrates into glucose. Sulochrin is one of the potential compounds which can inhibit the function of α-glucosidase enzyme. This study was carried out to obtain data of sulochrin binding with α-glucosidase enzyme as α-glucosidase inhibitor using Radioligand Binding Assay (RBA method. Primary reagent required in RBA method is labeled radioactive ligand (radioligand. In this study, the radioligand was sulochrin-125I and prior to sulochrin-125I synthesis, the sulochrin-I was synthesized. Sulochrin-I and sulochrin-125I were synthesized and their bindings were studied using Radioligand Binding Assay method. Sulochrin-I was synthesized with molecular formula C17H15O7I and molecular weight 457.9940. Sulochrin-125I was synthesized from sulochrin-I by isotope exchange method. From the RBA method, dissociation constant (Kd and maximum binding (Bmax were obtained 26.316 nM and Bmax 9.302 nM respectively. This low Kd indicated that sulochrin was can bind to α-glucosidase

  14. [11C]AZ10419096 - a full antagonist PET radioligand for imaging brain 5-HT1B receptors.

    Science.gov (United States)

    Lindberg, Anton; Nag, Sangram; Schou, Magnus; Takano, Akihiro; Matsumoto, Junya; Amini, Nahid; Elmore, Charles S; Farde, Lars; Pike, Victor W; Halldin, Christer

    2017-11-01

    The serotonergic system is widely present in all regions of the central nervous system (CNS) and plays a key modulatory role in many of its functions. Positron emission tomography (PET) is used to study several serotonin receptors in CNS in vivo. The G-protein coupled receptor 5-HT1B is mostly present in the occipital cortex and in midbrain and is linked to several psychiatric disorders. There is evidence that agonist PET radioligands for neuroreceptors are more sensitive to endogenous neurotransmitters than antagonists. Our previously developed 5-HT1B receptor PET radioligand, [11C]AZ10419369, is now considered a partial agonist. In this work we are aiming to develop a full antagonist PET radioligand for imaging brain 5-HT1B receptors, and evaluate its sensitivity to increased endogenous serotonin concentration. [11C]AZ10419096 was synthesized by rapid methylation of the prepared corresponding N-desmethyl precursor with [11C]methyl triflate. Five PET measurements were performed in cynomolgus monkeys, consisting of two at baseline, one after treatment of a monkey with a 5-HT1B antagonist, AR-A000002, and two in which fenfluramine was administered during scanning to induce endogenous serotonin release. [11C]AZ10419096 was synthesized in high yield and purity within 30 min, including purification, formulation and sterile filtration. The baseline PET measurements demonstrated [11C]AZ10419096 to have favorable radioligand characteristics, including high specific binding in brain regions that have high 5-HT1B density, such as occipital cortex and globus pallidus, as well as subsequent rapid elimination from brain and a minor abundance of lipophilic radiometabolites in plasma. AR-A00002 completely blocked radioligand receptor-specific binding. Fenfluramine produced a distinct displacement of radioligand consistent with an expected increase of synaptic endogenous serotonin concentration. [11C]AZ10419096, a full 5-HT1B antagonist PET radioligand, demonstrates high specific

  15. In vivo evaluation of new carfentanil-based radioligands for the mu opiate receptor

    Energy Technology Data Exchange (ETDEWEB)

    Jewett, Douglas M.; Kilbourn, Michael R. E-mail: mkilbour@umich.edu

    2004-04-01

    Eight derivatives of [{sup 11}C]carfentanil were evaluated as alternative mu opiod receptor radioligands with the potential for lower pharmacological activity, faster pharmacokinetics, and/or lower non-specific binding. Derivatives with aryl ring substituents or alkyl group substitutions were prepared in carbon-11 labeled form and examined for initial brain uptake and regional brain tissue pharmacokinetics in mouse brain. Promising derivatives with chloro, methoxy and methyl substituents on one aryl ring were then evaluated for specific binding in an equilibrium infusion rat model of regional brain distributions. Although no derivatives were identified with improved pharmacokinetics or lower non-specific binding, several derivatives show acceptable in vivo specific binding properties and may deserve further evaluation as less potent and thus safer compounds for in vivo imaging studies.

  16. (11)C-labeling and preliminary evaluation of vortioxetine as a PET radioligand.

    Science.gov (United States)

    Andersen, Valdemar L; Hansen, Hanne D; Herth, Matthias M; Knudsen, Gitte M; Kristensen, Jesper L

    2014-06-01

    Vortioxetine is a new multi-modal drug against major depressive disorder with high affinity for a range of different serotonergic targets in the CNS. We report the (11)C-labeling of vortioxetine with [(11)C]MeI using a Suzuki-protocol that allows for the presence of an unprotected amine. Preliminary evaluation of [(11)C]vortioxetine in a Danish Landrace pig showed rapid brain uptake and brain distribution in accordance with the pharmacological profile, all though an unexpected high binding in cerebellum was also observed. [(11)C]vortioxetine displayed slow tracer kinetics with peak uptake after 60 min and with limited wash-out from the brain. Further studies are needed but this radioligand may prove to be a valuable tool in unraveling the clinical effects of vortioxetine. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. (3H)bunazosin, a novel selective radioligand of alpha 1 adrenoceptors in human prostates

    Energy Technology Data Exchange (ETDEWEB)

    Yamada, S.; Suzuki, M.; Matsuoka, Y.; Kato, Y.; Kimura, R.; Maruyama, M.; Kawabe, K. (School of Pharmaceutical Sciences, University of Shizuoka (Japan))

    1991-09-01

    The binding properties of a new radioligand, (3H)bunazosin, were studied in membranes of human prostates with benign prostatic hypertrophy (BPH). Specific binding of (3H)bunazosin was saturable, reversible, and of high affinity (Kd = 0.55 {plus minus} 0.04 nM). The density of (3H)bunazosin binding sites (Bmax) was 676 {plus minus} 33 fmol/mg. protein. (3H)Bunazosin rapidly associated with its binding sites in membranes of human prostates and reached steady state by 20 min. at 25C. The rate constants for association and dissociation of (3H)bunazosin binding were calculated to be 0.11 {plus minus} 0.01/nM/min. and 0.05 {plus minus} 0.02/min. (n = 4), respectively. Seven alpha 1 adrenoceptor antagonists competed with (3H)bunazosin for the binding sites in the rank order: R-(-)-YM-12617 greater than prazosin greater than SGB-1534 greater than bunazosin greater than terazosin greater than naftopidil greater than urapidil. In parallel studies with (3H)bunazosin, the Kd and Bmax values for (3H)prazosin binding in human prostates were slightly lower. There was a similarity in the potency and rank order of seven alpha 1, adrenoceptor antagonists for the inhibition of (3H) bunazosin and (3H)prazosin binding in human prostates. The new (3H)bunazosin binding assay in human prostates is remarkable for its low degree of nonspecific binding as compared to (3H)prazosin, especially at high ligand concentrations. Thus, (3H)bunazosin may become a useful radioligand for the further analysis of the alph 1 adrenoceptor binding sites in human prostates.

  18. Preclinical evaluation of new radioligand of cholecystokinin/gastrin receptors in endocrine tumors xenograft nude mice

    Energy Technology Data Exchange (ETDEWEB)

    Brillouet, S. [Department of Nuclear Medicine, Institut Claudius Regaud, Toulouse (France) and Inserm U563, Therapeutic Innovation and Molecular Oncologic Department, Institut Claudius Regaud, Toulouse (France)]. E-mail: brillouet.severine@claudiusregaud.fr; Caselles, O. [Department of Nuclear Medicine, Institut Claudius Regaud, Toulouse (France); Dierickx, L.O. [Department of Nuclear Medicine, Institut Claudius Regaud, Toulouse (France); Mestre, B. [CNRS, LSPCMIB-UMR5068, Universite Paul Sabatier, Toulouse (France); Nalis, J. [Department of Nuclear Medicine, Institut Claudius Regaud, Toulouse (France); Picard, C. [CNRS, LSPCMIB-UMR5068, Universite Paul Sabatier, Toulouse (France); Favre, G. [Inserm U563, Therapeutic Innovation and Molecular Oncologic Department, Institut Claudius Regaud, Toulouse (France); Poirot, M. [Inserm U563, Therapeutic Innovation and Molecular Oncologic Department, Institut Claudius Regaud, Toulouse (France); Silvente-Poirot, S. [Inserm U563, Therapeutic Innovation and Molecular Oncologic Department, Institut Claudius Regaud, Toulouse (France); Courbon, F. [Department of Nuclear Medicine, Institut Claudius Regaud, Toulouse (France)

    2007-02-01

    The cholecystokinin(CCK)/gastrin 2 receptors (R-CCK2) are overexpressed in 90% of medullary thyroid cancers (MTC) and in 60% of small cell lung cancers but not or poorly in corresponding healthy tissues. They represent a relevant target for the diagnosis and internal targeted radiotherapy of these tumors. Although previous studies have demonstrated the feasibility of radiolabeled CCK/gastrin to target CCK-2 receptor-expressing tissues in animals and patients, some problems remained unsolved to identify an optimum candidate for in vivo targeting of R-CCK2-expressing tumors. By a rational approach and 'in silico' drug design, we synthesized a new CCK-derivative with high affinity for the R-CCK2. The aim of this study was to achieve the radiolabeling of a new radioligand, to assess its efficacy using a published CCK radioligand ({sup 111}In-DTPA-CCK8) as a control for the R-CCK2 targeting. This new CCK-derivative was radiolabeled with {sup 111}In. Nude mice, bearing the human MTC TT tumors and NIH-3T3 cell line expressing a tumorigenic mutant of the R-CCK2, were injected with this radiolabeled peptide. In vivo planar scintigraphies were acquired. Thereafter, biodistribution studies (%ID/g tissue) were done. The conditions of radiolabelling were optimized to obtain a radiochemical purity >90%. Scintigraphic images of xenograft mice showed significant tumor uptake with a target to nontarget ratio higher than two. These results were confirmed by the biodistribution studies which showed as expected a significant activity in the spleen, the liver and the kidneys. Therefore, this new radiolabeled compound is a promised new candidate for molecular imaging and internal radiotherapy for R-CCK2 tumor targeting.

  19. Synthesis and investigation of a radioiodinated F3 peptide analog as a SPECT tumor imaging radioligand.

    Science.gov (United States)

    Bhojani, Mahaveer S; Ranga, Rajesh; Luker, Gary D; Rehemtulla, Alnawaz; Ross, Brian D; Van Dort, Marcian E

    2011-01-01

    A radioiodinated derivative of the tumor-homing F3 peptide, (N-(2-{3-[(125)I]Iodobenzoyl}aminoethyl)maleimide-F3Cys peptide, [(125)I]IBMF3 was developed for investigation as a SPECT tumor imaging radioligand. For this purpose, we custom synthesized a modified F3 peptide analog (F3Cys) incorporating a C-terminal cysteine residue for site-specific attachment of a radioiodinated maleimide conjugating group. Initial proof-of-concept Fluorescence studies conducted with AlexaFluor 532 C(5) maleimide-labeled F3Cys showed distinct membrane and nuclear localization of F3Cys in MDA-MB-435 cells. Additionally, F3Cys conjugated with NIR fluorochrome AlexaFluor 647 C(2) maleimide demonstrated high tumor specific uptake in melanoma cancer MDA-MB-435 and lung cancer A549 xenografts in nude mice whereas a similarly labeled control peptide did not show any tumor uptake. These results were also confirmed by ex vivo tissue analysis. No-carrier-added [(125)I]IBMF3 was synthesized by a radioiododestannylation approach in 73% overall radiochemical yield. In vitro cell uptake studies conducted with [(125)I]IBMF3 displayed a 5-fold increase in its cell uptake at 4 h when compared to controls. SPECT imaging studies with [(125)I]IBMF3 in tumor bearing nude mice showed clear visualization of MDA-MB-435 xenografts on systemic administration. These studies demonstrate a potential utility of F3 peptide-based radioligands for tumor imaging with PET or SPECT techniques.

  20. Preclinical evaluation of new radioligand of cholecystokinin/gastrin receptors in endocrine tumors xenograft nude mice

    Science.gov (United States)

    Brillouet, S.; Caselles, O.; Dierickx, L. O.; Mestre, B.; Nalis, J.; Picard, C.; Favre, G.; Poirot, M.; Silvente-Poirot, S.; Courbon, F.

    2007-02-01

    The cholecystokinin(CCK)/gastrin 2 receptors (R-CCK2) are overexpressed in 90% of medullary thyroid cancers (MTC) and in 60% of small cell lung cancers but not or poorly in corresponding healthy tissues. They represent a relevant target for the diagnosis and internal targeted radiotherapy of these tumors. Although previous studies have demonstrated the feasibility of radiolabeled CCK/gastrin to target CCK-2 receptor-expressing tissues in animals and patients, some problems remained unsolved to identify an optimum candidate for in vivo targeting of R-CCK2-expressing tumors. By a rational approach and " in silico" drug design, we synthesized a new CCK-derivative with high affinity for the R-CCK2. The aim of this study was to achieve the radiolabeling of a new radioligand, to assess its efficacy using a published CCK radioligand ( 111In-DTPA-CCK8) as a control for the R-CCK2 targeting. This new CCK-derivative was radiolabeled with 111In. Nude mice, bearing the human MTC TT tumors and NIH-3T3 cell line expressing a tumorigenic mutant of the R-CCK2, were injected with this radiolabeled peptide. In vivo planar scintigraphies were acquired. Thereafter, biodistribution studies (%ID/g tissue) were done. The conditions of radiolabelling were optimized to obtain a radiochemical purity >90%. Scintigraphic images of xenograft mice showed significant tumor uptake with a target to nontarget ratio higher than two. These results were confirmed by the biodistribution studies which showed as expected a significant activity in the spleen, the liver and the kidneys. Therefore, this new radiolabeled compound is a promised new candidate for molecular imaging and internal radiotherapy for R-CCK2 tumor targeting.

  1. The impact of trauma-focused group therapy upon HIV sexual risk behaviors in the NIDA Clinical Trials Network "Women and trauma" multi-site study.

    Science.gov (United States)

    Hien, Denise A; Campbell, Aimee N C; Killeen, Therese; Hu, Mei-Chen; Hansen, Cheri; Jiang, Huiping; Hatch-Maillette, Mary; Miele, Gloria M; Cohen, Lisa R; Gan, Weijin; Resko, Stella M; DiBono, Michele; Wells, Elizabeth A; Nunes, Edward V

    2010-04-01

    Women in drug treatment struggle with co-occurring problems, including trauma and post-traumatic stress disorder (PTSD), which can heighten HIV risk. This study examines the impact of two group therapy interventions on reduction of unprotected sexual occasions (USO) among women with substance use disorders (SUD) and PTSD. Participants were 346 women recruited from and receiving treatment at six community-based drug treatment programs participating in NIDA's Clinical Trials Network. Participants were randomized to receive 12-sessions of either seeking safety (SS), a cognitive behavioral intervention for women with PTSD and SUD, or women's health education (WHE), an attention control psychoeducational group. Participants receiving SS who were at higher sexual risk (i.e., at least 12 USO per month) significantly reduced the number of USO over 12-month follow up compared to WHE. High risk women with co-occurring PTSD and addiction may benefit from treatment addressing coping skills and trauma to reduce HIV risk.

  2. Novel Radioligands for Cyclic Nucleotide Phosphodiesterase Imaging with Positron Emission Tomography: An Update on Developments Since 2012

    Directory of Open Access Journals (Sweden)

    Susann Schröder

    2016-05-01

    Full Text Available Cyclic nucleotide phosphodiesterases (PDEs are a class of intracellular enzymes that inactivate the secondary messenger molecules, cyclic adenosine monophosphate (cAMP and cyclic guanosine monophosphate (cGMP. Thus, PDEs regulate the signaling cascades mediated by these cyclic nucleotides and affect fundamental intracellular processes. Pharmacological inhibition of PDE activity is a promising strategy for treatment of several diseases. However, the role of the different PDEs in related pathologies is not completely clarified yet. PDE-specific radioligands enable non-invasive visualization and quantification of these enzymes by positron emission tomography (PET in vivo and provide an important translational tool for elucidation of the relationship between altered expression of PDEs and pathophysiological effects as well as (pre-clinical evaluation of novel PDE inhibitors developed as therapeutics. Herein we present an overview of novel PDE radioligands for PET published since 2012.

  3. Radiosynthesis and in vivo evaluation of novel radioligands for PET imaging of cerebral 5-HT7 receptors

    DEFF Research Database (Denmark)

    Hansen, Hanne D; Herth, Matthias M; Ettrup, Anders

    2014-01-01

    in the living brain. Here, we present the radiosynthesis and in vivo evaluation of Cimbi-712 (3-{4-[4-(4-methylphenyl)piperazine-1-yl]butyl}p-1,3-dihydro-2H-indol-2-one) and Cimbi-717 (3-{4-[4-(3-methoxyphenyl)piperazine-1-yl]butyl}-1,3-dihydro-2H-indol-2-one) as selective 5-HT7R PET radioligands in the pig......The serotonin (5-hydroxytryptamine [5-ΗΤ]) 7 receptor (5-HT7R) is the most recently discovered 5-HT receptor, and its physiologic and possible pathophysiologic roles are not fully elucidated. So far, no suitable 5-HT7R PET radioligand is available, thus limiting the investigation of this receptor...

  4. Evaluation of σ-1 receptor radioligand 18F-FTC-146 in rats and squirrel monkeys using PET

    DEFF Research Database (Denmark)

    James, Michelle L; Shen, Bin; Nielsen, Carsten Haagen

    2014-01-01

    -FTC-146 was observed in rat plasma. Preliminary monkey PET/MRI studies demonstrated specific accumulation of (18)F-FTC-146 in the brain (mainly in cortical structures, cerebellum, and vermis) that could be attenuated by pretreatment with haloperidol. HPLC of monkey plasma suggested radioligand metabolism...... chromatography (HPLC). Preliminary PET/MRI of squirrel monkey brain was conducted along with HPLC assessment of (18)F-FTC-146 stability in monkey plasma and human serum. RESULTS: Biodistribution studies showed that (18)F-FTC-146 accumulated in S1R-rich rat organs, including the lungs, pancreas, spleen, and brain....... Pretreatment with known S1R compounds, haloperidol, or BD1047, before radioligand administration, significantly attenuated (18)F-FTC-146 accumulation in all rat brain regions by approximately 85% (P

  5. A bispecific Tribody PET radioligand for visualization of amyloid-beta protofibrils – a new concept for neuroimaging

    OpenAIRE

    Syvänen, Stina; Fang, Xiaotian T; Hultqvist, Greta; Meier, Silvio R.; Lannfelt, Lars; Sehlin, Dag

    2017-01-01

    Antibodies are highly specific for their target molecules, but their poor brain penetrance has restricted their use as PET ligands for imaging of targets within the CNS. The aim of this study was to develop an antibody-based radioligand, using the Tribody(TM) format, for PET imaging of soluble amyloid-beta (All) protofibrils, which are suggested to cause neurodegeneration in Alzheimer's disease. Antibodies, even when expressed in smaller engineered formats, are large molecules that do not ent...

  6. A New Nonlinear Regression Approach That Allows Detection of Inter-Individual Differences in Single-Point Radioligand Binding Studies

    Science.gov (United States)

    2000-08-01

    Georgetown U. Med. Ctr., 3900 Reservoir Rd., Washington, DC 20007; 2Applied Mathematics Program, Johns Hopkins University, 9601 Medical Center Dr., Rockville...TERMS Nonlinear regresion , Monte-Carlo 15. NUMBER OF PAGES randomization, Scheffe’s test, radioligand binding 16. PRICE CODE 24 17. SECURITY 18...appropriate for this situation. Indeed, here it is necessary to formulate this problem as a multiple linear regression model expressed with the aid of

  7. Detection and quantification of remote microglial activation in rodent models of focal ischaemia using the TSPO radioligand CLINDE

    Energy Technology Data Exchange (ETDEWEB)

    Arlicot, Nicolas [Universite Francois Rabelais de Tours, CHRU de Tours (France). UMR Inserm U 930, CNRS ERL 3106; UFR Sciences Pharmaceutiques, Laboratoire de Biophysique, Tours (France); Petit, Edwige; Toutain, Jerome; Divoux, Didier; Roussel, Simon; Bernaudin, Myriam [Universite de Caen Basse-Normandie, Universite Paris-Descartes, CNRS, CEA CYCERON, Caen (France). Equipe CERVOxy ' ' Hypoxie et Physiopathologie cerebrovasculaire' ' , UMR 6232 CI-NAPS; Katsifis, Andrew [ANSTO, Radiopharmaceuticals Research Institute, Menai (Australia); Bodard, Sylvie; Guilloteau, Denis; Chalon, Sylvie [Universite Francois Rabelais de Tours, CHRU de Tours (France). UMR Inserm U 930, CNRS ERL 3106

    2010-12-15

    Neuroinflammation is involved in stroke pathophysiology and might be imaged using radioligands targeting the 18 kDa translocator protein (TSPO). We studied microglial reaction in brain areas remote from the primary lesion site in two rodent models of focal cerebral ischaemia (permanent or transient) using [{sup 125}I]-CLINDE, a promising TSPO single photon emission computed tomography radioligand. In a mouse model of permanent middle cerebral artery occlusion (MCAO), ex vivo autoradiographic studies demonstrated, besides in the ischaemic territory, accumulation of [{sup 125}I]-CLINDE in the ipsilateral thalamus with a binding that progressed up to 3 weeks after MCAO. [{sup 125}I]-CLINDE binding markedly decreased in animals pre-injected with either unlabelled CLINDE or PK11195, while no change was observed with flumazenil pre-treatment, demonstrating TSPO specificity. In rats subjected to transient MCAO, [{sup 125}I]-CLINDE binding in the ipsilateral thalamus and substantia nigra pars reticulata (SNr) was significantly higher than that in contralateral tissue. Moreover, [{sup 125}I]-CLINDE binding in the thalamus and SNr was quantitatively correlated to the ischaemic volume assessed by MRI in the cortex and striatum, respectively. Clinical consequences of secondary neuronal degeneration in stroke might be better treated thanks to the discrimination of neuronal processes using in vivo molecular imaging and potent TSPO radioligands like CLINDE to guide therapeutic interventions. (orig.)

  8. (11)C-labeling and preliminary evaluation of vortioxetine as a PET radioligand

    DEFF Research Database (Denmark)

    Andersen, Valdemar L; Hansen, Hanne D; Herth, Matthias M

    2014-01-01

    Vortioxetine is a new multi-modal drug against major depressive disorder with high affinity for a range of different serotonergic targets in the CNS. We report the (11)C-labeling of vortioxetine with [(11)C]MeI using a Suzuki-protocol that allows for the presence of an unprotected amine. Prelimin......Vortioxetine is a new multi-modal drug against major depressive disorder with high affinity for a range of different serotonergic targets in the CNS. We report the (11)C-labeling of vortioxetine with [(11)C]MeI using a Suzuki-protocol that allows for the presence of an unprotected amine....... Preliminary evaluation of [(11)C]vortioxetine in a Danish Landrace pig showed rapid brain uptake and brain distribution in accordance with the pharmacological profile, all though an unexpected high binding in cerebellum was also observed. [(11)C]vortioxetine displayed slow tracer kinetics with peak uptake...... after 60min and with limited wash-out from the brain. Further studies are needed but this radioligand may prove to be a valuable tool in unraveling the clinical effects of vortioxetine....

  9. New Radioligands for Describing the Molecular Pharmacology of MT1 and MT2 Melatonin Receptors

    Science.gov (United States)

    Legros, Céline; Matthey, Ulrich; Grelak, Teresa; Pedragona-Moreau, Sandrine; Hassler, Werner; Yous, Saïd; Thomas, Emmanuel; Suzenet, Franck; Folleas, Benoît; Lefoulon, François; Berthelot, Pascal; Caignard, Daniel-Henri; Guillaumet, Gérald; Delagrange, Philippe; Brayer, Jean-Louis; Nosjean, Olivier; Boutin, Jean A.

    2013-01-01

    Melatonin receptors have been studied for several decades. The low expression of the receptors in tissues led the scientific community to find a substitute for the natural hormone melatonin, the agonist 2-[125I]-iodomelatonin. Using the agonist, several hundreds of studies were conducted, including the discovery of agonists and antagonists for the receptors and minute details about their molecular behavior. Recently, we attempted to expand the panel of radioligands available for studying the melatonin receptors by using the newly discovered compounds SD6, DIV880, and S70254. These compounds were characterized for their affinities to the hMT1 and hMT2 recombinant receptors and their functionality in the classical GTPγS system. SD6 is a full agonist, equilibrated between the receptor isoforms, whereas S70254 and DIV880 are only partial MT2 agonists, with Ki in the low nanomolar range while they have no affinity to MT1 receptors. These new tools will hopefully allow for additions to the current body of information on the native localization of the receptor isoforms in tissues. PMID:23698757

  10. New Radioligands for Describing the Molecular Pharmacology of MT1 and MT2 Melatonin Receptors

    Directory of Open Access Journals (Sweden)

    Olivier Nosjean

    2013-04-01

    Full Text Available Melatonin receptors have been studied for several decades. The low expression of the receptors in tissues led the scientific community to find a substitute for the natural hormone melatonin, the agonist 2-[125I]-iodomelatonin. Using the agonist, several hundreds of studies were conducted, including the discovery of agonists and antagonists for the receptors and minute details about their molecular behavior. Recently, we attempted to expand the panel of radioligands available for studying the melatonin receptors by using the newly discovered compounds SD6, DIV880, and S70254. These compounds were characterized for their affinities to the hMT1 and hMT2 recombinant receptors and their functionality in the classical GTPS system. SD6 is a full agonist, equilibrated between the receptor isoforms, whereas S70254 and DIV880 are only partial MT2 agonists, with Ki in the low nanomolar range while they have no affinity to MT1 receptors. These new tools will hopefully allow for additions to the current body of information on the native localization of the receptor isoforms in tissues.

  11. Biological evaluation of two iodine-123-labeled D-glucose acetals prepared as glucose transporter radioligands

    Energy Technology Data Exchange (ETDEWEB)

    Brunet-Desruet, Marie-Dominique; Ghezzi, Catherine; Morin, Christophe; Comet, Michel; Fagret, Daniel

    1998-07-01

    Two iodinated acetals of D-glucose, 4,6-(R)-O-(2'-iodoethylidene)-{alpha}, {beta}-D-glucose and 4,6-(R)-O-(4'-iodobenzylidene)-{alpha}, {beta}-D-glucose , were prepared and their potential as suitable SPECT radioligands for imaging of glucose transporters was studied. Both are analogs of acetal D-glucose derivatives, which are known to bind to the exofacial sites of the glucose transport protein (GluT). To assess whether iodinated acetals 1 and 2 interacted with the glucose transporter, they were tested in vitro in human erythrocytes (GluT1) and neonatal rat cardiomyocytes (GluT4). The results indicated that 1 and 2 had a very low affinity for the glucose transporter and probably accumulated in cells. Study of their tissue distribution was carried out in the mouse in vivo: Both compounds showed fast tissue clearance with preferential renal elimination. It is concluded that iodinated acetals of D-glucose 1 and 2 are not suitable for GluT targeting in vivo.

  12. Synthesis and evaluation of translocator 18 kDa protein (TSPO) positron emission tomography (PET) radioligands with low binding sensitivity to human single nucleotide polymorphism rs6971.

    Science.gov (United States)

    Zanotti-Fregonara, Paolo; Zhang, Yi; Jenko, Kimberly J; Gladding, Robert L; Zoghbi, Sami S; Fujita, Masahiro; Sbardella, Gianluca; Castellano, Sabrina; Taliani, Sabrina; Martini, Claudia; Innis, Robert B; Da Settimo, Federico; Pike, Victor W

    2014-10-15

    The imaging of translocator 18 kDa protein (TSPO) in living human brain with radioligands by positron emission tomography (PET) has become an important means for the study of neuroinflammatory conditions occurring in several neuropsychiatric disorders. The widely used prototypical PET radioligand [(11)C](R)-PK 11195 ([(11)C](R)-1; [N-methyl-(11)C](R)-N-sec-butyl-1-(2-chlorophenyl)-N-methylisoquinoline-3-carboxamide) gives a low PET signal and is difficult to quantify, whereas later generation radioligands have binding sensitivity to a human single nucleotide polymorphism (SNP) rs6971, which imposes limitations on their utility for comparative quantitative PET studies of normal and diseased subjects. Recently, azaisosteres of 1 have been developed with improved drug-like properties, including enhanced TSPO affinity accompanied by moderated lipophilicity. Here we selected three of these new ligands (7-9) for labeling with carbon-11 and for evaluation in monkey as candidate PET radioligands for imaging brain TSPO. Each radioligand was readily prepared by (11)C-methylation of an N-desmethyl precursor and was found to give a high proportion of TSPO-specific binding in monkey brain. One of these radioligands, [(11)C]7, the direct 4-azaisostere of 1, presents many radioligand properties that are superior to those reported for [(11)C]1, including higher affinity, lower lipophilicity, and stable quantifiable PET signal. Importantly, 7 was also found to show very low sensitivity to the human SNP rs6971 in vitro. Therefore, [(11)C]7 now warrants evaluation in human subjects with PET to assess its utility for imaging TSPO in human brain, irrespective of subject genotype.

  13. Seslerio uliginosae-Scorzoneretum purpureae (Festuco-Brometea class in the Nida Basin (Małopolska Upland after 90 years

    Directory of Open Access Journals (Sweden)

    Krystyna Towpasz

    2012-10-01

    Full Text Available Seslerio uliginosae-Scorzoneretum purpureae is the only xerothermic community of the Festuco-Brometea class, where a rare species known as Sesleria uliginosa occurs in Poland. A couple of sites hosting this association in the Nida Basin were described in the 1920s and 1950s. All these stands are now situated in the areas designated as xerothermic nature reserves. The study aimed at describing the present-day characteristics of this rare association, the most likely being endemic in Poland, as well as the changes that have occurred in it. The species diversity and the contribution of xerothermic plants have decreased significantly in terms of their number and cover coefficient. Some of the diagnostic species of the association have become extremely rare. Sesleria uliginosa is the only one without visible changes in their dominant position in the community. Mosses, that have played a significant role before, were among the vanished species. At the same time, an increase in number and cover of mesophilous meadows species was observed. Mesophilous grasses belong to the group of species growing in significance in the phytocoenoses. The observed changes in species composition were reflected in a statistically significant increase of nitrogen indicator value. The slow process of succession observed in the Seslerio-Scorzoneretum purpureae could be attributed to the lack of appropriate land use, e.g. mowing and grazing that have been ceased in the nature reserves.

  14. Synthesis of carbon-11 labeled celecoxib derivatives as new candidate PET radioligands for imaging of inflammation

    Energy Technology Data Exchange (ETDEWEB)

    Gao Mingzhang; Wang Min [Department of Radiology, Indiana University School of Medicine, 1345 West 16th Street, L3-208, Indianapolis, IN 46202 (United States); Miller, Kathy D. [Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202 (United States); Hutchins, Gary D. [Department of Radiology, Indiana University School of Medicine, 1345 West 16th Street, L3-208, Indianapolis, IN 46202 (United States); Zheng Qihuang [Department of Radiology, Indiana University School of Medicine, 1345 West 16th Street, L3-208, Indianapolis, IN 46202 (United States)], E-mail: qzheng@iupui.edu

    2009-11-15

    Cyclooxygenase (prostaglandin endoperoxide synthase or COX) enzyme represents a particularly attractive target in inflammation processes for the development of both therapeutic agents and imaging agents. This study was designed to develop new radioligands for imaging of inflammation using the biomedical imaging technique positron emission tomography (PET). Carbon-11 labeled celecoxib derivatives, [{sup 11}C]methyl 2-(4-(5-p-tolyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)phenylsulfonamidooxy) acetate ([{sup 11}C]6e), [{sup 11}C]methyl 2-methyl-2-(4-(5-p-tolyl-3-(trifluoromethyl)-1H-pyrazol-1-yl) phenylsulfonamidooxy)propanoate ([{sup 11}C]6f), [{sup 11}C]methyl 2-(4-(5-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl) phenylsulfonamidooxy)acetate ([{sup 11}C]6g), and [{sup 11}C]methyl 2-methyl-2-(4-(5-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl) phenylsulfonamidooxy)propanoate ([{sup 11}C]6h), were prepared by O-[{sup 11}C]methylation of their corresponding precursors using [{sup 11}C]CH{sub 3}OTf under basic condition and isolated by a simplified solid-phase extraction (SPE) method in 50-60% radiochemical yields based on [{sup 11}C]CO{sub 2} and decay corrected to end of bombardment (EOB). The overall synthesis time from EOB was 15-20 min, the radiochemical purity was >99%, and the specific activity at end of synthesis (EOS) was 111-185 GBq/{mu}mol.

  15. 3-Pyridyl ethers as SPECT radioligands for imaging nicotinic acetylcholine receptors

    Energy Technology Data Exchange (ETDEWEB)

    Henderson, D.J.; Eberl, S.; Thomson, S.; Smith, A.; Allan, R.D.; Fulham, M.J.; Loiacono, R.; Kassiou, M. E-mail: mkassiou@med.usyd.edu.au

    2004-05-01

    To develop a suitable single photon emission computed tomography (SPECT) radioligand for neuronal nicotinic acetylcholine receptors (nAChRs) that displays faster in vivo kinetics than 5-[{sup 123}I]iodo-A-85380, we synthesised the radioiodinated analogue of A-84543. 5-[{sup 123}I]Iodo-A-84543 was prepared by electrophilic iododestannylation in a modest yield of 23%. In the baboon brain, 5-[{sup 123}I]iodo-A-85380 displayed a profile consistent with the known distribution of nAChRs, however, 5-[{sup 123}I]iodo-A-84543 displayed a homogenous uptake with no preferential localisation in regions known to contain nAChRs. To examine the effect of halogen substitution on the 3-pyridyl ether, A-84543, the 5-chloro, 5-bromo and 5-iodo analogues were synthesised and evaluated with respect to nAChR binding. In vitro binding data revealed that halogen substitution at the 5-position of A-84543 was not well tolerated with an increase in halogen size resulting in lower binding towards nAChRs. The 5-chloro analogue 4 displayed highest affinity, K{sub i}=1.3 nM, compared to the 5-bromo and 5-iodo compounds, 5 K{sub i}=3.3 nM and 3 K{sub i}=40.8 nM, respectively. Taken together, these results clearly indicate that 5-[{sup 123}I]iodo-A-84543 is not suitable for the study of nAChRs in vivo using SPECT.

  16. {sup 18}F-labeled benzylpiperidine benzisoxazole: a potential radioligand for in vivo mapping of acetylcholinesterase

    Energy Technology Data Exchange (ETDEWEB)

    Lee, S. Y.; Choi, Y. S.; Kim, Y. R.; Baek, J. Y.; Kim, S. E.; Choi, Y.; Lee, K. H.; Kim, B. T. [Sungkyunkwon University College of Medicine, Seoul (Korea, Republic of)

    2002-07-01

    Acetylcholinesterase (AChE) has been an important cholinergic marker for diagnosis of Alzheimer's disease since biochemical finding on severe loss of its activity in this disease. In this study, benzylpiperidine benzisoxazole (1), a potent AChE inhibitor (IC{sub 50}=0.33 nM), was labeled with {sup 18}F and evaluated for in vivo mapping of AChE. Fluorine-substituted derivatives of 1 were synthesized and their in vitro binding affinities to AChE were measured using Ellmans method. 4-[{sup 18}F]F-1 was selected and synthesized by reductive alkylation of the piperidine precursor with 4-[{sup 18}F]fluorobenzaldehyde. In vitro autoradiography was performed by incubating rat brain coronal slices with the radioligand at 4 .deg. C for 60 min, and in vivo tissue distribution studies were carried out in mice. In vitro assay data showed that fluorine-substituted derivatives of 1 exhibited similar binding affinities to the unsubstituted ligand (1). 4-[{sup 18}F]F-1 was synthesized in 25-50% radiochemical yield and with high specific activity (>37 GBq/{mu}mol). In autoradiograms of 4-[{sup 18}F]F-1, high uptake in striatal region was clearly shown, which was completely inhibited in the presence of the unlabeled ligand. Tissue distribution studies demonstrated that the order of uptake was well correlated with the known density of AChE in mouse brain and results of the in vitro autoradiography, showing a high striatum to cerebellum uptake ratio (3 at 90 min). This study demonstrated that 4-[{sup 18}F]F-1 may be a good candidate for in vivo mapping of AChE.

  17. A novel radioligand for glycine transporter 1: characterization and use in autoradiographic and in vivo brain occupancy studies

    Energy Technology Data Exchange (ETDEWEB)

    Zeng Zhizhen [Imaging, Merck Research Laboratories, West Point, PA 19486 (United States)], E-mail: zhizhen_zeng@merck.com; O' Brien, Julie A. [Sleep and Psychiatric Disorders, Merck Research Laboratories, West Point, PA 19486 (United States); Lemaire, Wei [Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486 (United States); O' Malley, Stacey S.; Miller, Patricia J. [Imaging, Merck Research Laboratories, West Point, PA 19486 (United States); Zhao Zhijian [Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486 (United States); Wallace, Michael A. [Drug Metabolism, Merck Research Laboratories, Rahway, NJ 07065 (United States); Raab, Conrad [Drug Metabolism, Merck Research Laboratories, West Point, PA 19486 (United States); Lindsley, Craig W. [Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486 (United States); Departments of Pharmacology and Chemistry, Vanderbilt University, Nashville, TN 37232 (United States); Sur, Cyrille; Williams, David L. [Imaging, Merck Research Laboratories, West Point, PA 19486 (United States)

    2008-04-15

    Introduction: In an effort to develop agents to test the NMDA hypofunction hypothesis of schizophrenia, benchmark compounds from a program to discover potent, selective, competitive glycine transporter 1 (GlyT1) inhibitors were radiolabeled in order to further study the detailed pharmacology of these inhibitors and the distribution of GlyT1 in brain. We here report the in vitro characterization of [{sup 35}S](S)-2-amino-4-chloro-N-(1-(4-phenyl-1-(propylsulfonyl)piperidin-4-yl) ethyl)benzamide ([{sup 35}S]ACPPB), a radiotracer developed from a potent and selective non-sarcosine-derived GlyT1 inhibitor, its use in autoradiographic studies to localize (S)-2-amino-6-chloro-N-(1-(4-phenyl-1-(propylsulfonyl)piperidin-4-yl)ethyl) benzamide (ACPPB) binding sites in rat and rhesus brain and for in vivo occupancy assays of competitive GlyT1 inhibitors. Methods: Functional potencies of unlabeled compounds were characterized by [{sup 14}C]glycine uptake into JAR (human placental choriocarcinoma) cells and synaptosomes. Radioligand binding studies were performed with tissue homogenates. Autoradiographic studies were performed on tissue slices. Results: ACPPB is a potent (K{sub d}=1.9 nM), selective, GlyT1 inhibitor that, when radiolabeled with [{sup 35}S], is a well-behaved radioligand with low nondisplaceable binding. Autoradiographic studies of rat and rhesus brain slices with this ligand showed that specific binding sites were plentiful and nonhomogeneously distributed, with high levels of binding in the brainstem, cerebellar white matter, thalamus, cortical white matter and spinal cord gray matter. In vivo studies demonstrate displaceable binding of [{sup 35}S]ACPPB in rat brain tissues following iv administration of this radioligand. Conclusions: This is the first report of detailed anatomical localization of GlyT1 using direct radioligand binding, and the first demonstration that an in vivo occupancy assay is feasible, suggesting that it may also be feasible to develop

  18. (E)-[{sup 125}I]-5-AOIBV: a SPECT radioligand for the vesicular acetylcholine transporter

    Energy Technology Data Exchange (ETDEWEB)

    Emond, Patrick [INSERM U619, 37000 Tours (France); Universite Francois-Rabelais de Tours, CHRU, Hopital Bretonneau, Service de Medecine nucleaire, 37000 Tours (France); Mavel, Sylvie [INSERM U619, 37000 Tours (France); Universite Francois-Rabelais de Tours, CHRU, Hopital Bretonneau, Service de Medecine nucleaire, 37000 Tours (France)], E-mail: sylvie.mavel@univ-tours.fr; Zea-Ponce, Yolanda [INSERM U619, 37000 Tours (France); Universite Francois-Rabelais de Tours, CHRU, Hopital Bretonneau, Service de Medecine nucleaire, 37000 Tours (France); Kassiou, Michael [Discipline of Medical Radiation Sciences, Brain and Mind Research Institute, University of Sydney, NSW 2050 (Australia); School of Chemistry, University of Sydney, NSW 2006 (Australia); Garreau, Lucette; Bodard, Sylvie; Drossard, Marie-Laure; Chalon, Sylvie; Guilloteau, Denis [INSERM U619, 37000 Tours (France); Universite Francois-Rabelais de Tours, CHRU, Hopital Bretonneau, Service de Medecine nucleaire, 37000 Tours (France)

    2007-11-15

    The premise that, over the course of Alzheimer's disease (AD), changes in the levels of the vesicular acetylcholine transporter (VAChT) occur in parallel with changes to other cholinergic marker proteins provides the basis for the applicability of benzovesamicol derivatives as radioligands for AD studies by single photon emission computed tomography or positron emission tomography. We report the synthesis of enantiopure benzovesamicol derivatives: (R,R) or (S,S)-(E)-2-hydroxy-5-(3-iodoprop-2-en-1-oxy)-3- (4-phenylpiperidino)tetralin [(R,R)-AOIBV: K{sub d}=0.45 nM or (S,S)-5-AOIBV: K{sub d}=4.3 nM] and their corresponding tributyltin precursors for radioiodination. (R,R or S,S)-5-AOIBV was labeled with iodine-125 from their corresponding n-tributyltin precursors. Both compounds were obtained with radiochemical and optical purity greater than 97% and in radiochemical yields ranging 34-36%. To determine if these compounds could provide an advantage when compared to [{sup 125}I]-iodo benzovesamicol (IBVM), IBVM was also labeled and used as the reference compound in all ex vivo experiments. Ex vivo biodistribution experiments in rats revealed that [{sup 125}I]-(R,R)-5-AOIBV displayed the most suitable pharmacological profile as the radioactivity distribution corresponded well with the known VAChT brain density. Moreover, pre-injection of vesamicol prevented the uptake of [{sup 125}I]-(R,R)-5-AOIBV in striatum, cortex and hippocampus, demonstrating selectivity for the VAChT. However, even if time activity curves of [{sup 125}I]-(R,R)-5-AOIBV confirmed that this compound could be used to visualize the VAChT in vivo, at each point of the kinetic study, [{sup 125}I]-(R,R)-5-AOIBV showed a lower specific binding compared to [{sup 125}I]-IBVM. These results made [{sup 125}I]-( R,R)-5-AOIBV inferior to [{sup 125}I]-IBVM for the VAChT exploration in vivo.

  19. German Multicenter Study Investigating 177Lu-PSMA-617 Radioligand Therapy in Advanced Prostate Cancer Patients.

    Science.gov (United States)

    Rahbar, Kambiz; Ahmadzadehfar, Hojjat; Kratochwil, Clemens; Haberkorn, Uwe; Schäfers, Michael; Essler, Markus; Baum, Richard P; Kulkarni, Harshad R; Schmidt, Matthias; Drzezga, Alexander; Bartenstein, Peter; Pfestroff, Andreas; Luster, Markus; Lützen, Ulf; Marx, Marlies; Prasad, Vikas; Brenner, Winfried; Heinzel, Alexander; Mottaghy, Felix M; Ruf, Juri; Meyer, Philipp Tobias; Heuschkel, Martin; Eveslage, Maria; Bögemann, Martin; Fendler, Wolfgang Peter; Krause, Bernd Joachim

    2017-01-01

    177Lu-labeled PSMA-617 is a promising new therapeutic agent for radioligand therapy (RLT) of patients with metastatic castration-resistant prostate cancer (mCRPC). Initiated by the German Society of Nuclear Medicine, a retrospective multicenter data analysis was started in 2015 to evaluate efficacy and safety of 177Lu-PSMA-617 in a large cohort of patients. One hundred forty-five patients (median age, 73 y; range, 43-88 y) with mCRPC were treated with 177Lu-PSMA-617 in 12 therapy centers between February 2014 and July 2015 with 1-4 therapy cycles and an activity range of 2-8 GBq per cycle. Toxicity was categorized by the common toxicity criteria for adverse events (version 4.0) on the basis of serial blood tests and the attending physician's report. The primary endpoint for efficacy was biochemical response as defined by a prostate-specific antigen decline ≥ 50% from baseline to at least 2 wk after the start of RLT. A total of 248 therapy cycles were performed in 145 patients. Data for biochemical response in 99 patients as well as data for physician-reported and laboratory-based toxicity in 145 and 121 patients, respectively, were available. The median follow-up was 16 wk (range, 2-30 wk). Nineteen patients died during the observation period. Grade 3-4 hematotoxicity occurred in 18 patients: 10%, 4%, and 3% of the patients experienced anemia, thrombocytopenia, and leukopenia, respectively. Xerostomia occurred in 8%. The overall biochemical response rate was 45% after all therapy cycles, whereas 40% of patients already responded after a single cycle. Elevated alkaline phosphatase and the presence of visceral metastases were negative predictors and the total number of therapy cycles positive predictors of biochemical response. The present retrospective multicenter study of 177Lu-PSMA-617 RLT demonstrates favorable safety and high efficacy exceeding those of other third-line systemic therapies in mCRPC patients. Future phase II/III studies are warranted to

  20. Synthesis and biological evaluation of I-125/I-123-labelled analogues of citalopram and escitalopram as potential radioligands for imaging of the serotonin transporter

    DEFF Research Database (Denmark)

    Madsen, Jacob; Elfving, Betina; Frokjaer, Vibe G.

    2011-01-01

    Two novel radioligands for the serotonin transporter (SERT), [I-125]{3-[5-iodo-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-1-yl]-propyl}-dimethylamine ([I-125]-2) and S-[I-125]{3-[5-iodo-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-1-yl]-propyl}-dimethylamine ([I-125]-(S)-2) were synthesized in a ...... of the radioligand in imaging cortical SERT distribution in vivo. These data suggest that the iodine-labelled derivatives of citalopram and escitalopram are not superior to another SPECT tracer for the SERT, namely [I-123] ADAM....

  1. Synthesis and in vitro evaluation of a selective antagonist and the corresponding radioligand for the prostaglandin D2 receptor CRTH2

    DEFF Research Database (Denmark)

    Ulven, Trond; Gallen, Michael J; Nielsen, Mads C

    2007-01-01

    Synthesis and preliminary in vitro biological evaluation of a selective high-affinity CRTH2 antagonist is described. The stability of an N-benzyl group facilitated synthesis of the corresponding radioligand by tritiation of a brominated precursor. The compound [(3)H]TRQ11238 represents the first ...

  2. Test-retest reliability of the novel 5-HT1B receptor PET radioligand [11C]P943.

    Science.gov (United States)

    Saricicek, Aybala; Chen, Jason; Planeta, Beata; Ruf, Barbara; Subramanyam, Kalyani; Maloney, Kathleen; Matuskey, David; Labaree, David; Deserno, Lorenz; Neumeister, Alexander; Krystal, John H; Gallezot, Jean-Dominique; Huang, Yiyun; Carson, Richard E; Bhagwagar, Zubin

    2015-03-01

    [(11)C]P943 is a novel, highly selective 5-HT1B PET radioligand. The aim of this study was to determine the test-retest reliability of [(11)C]P943 using two different modeling methods and to perform a power analysis with each quantification technique. Seven healthy volunteers underwent two PET scans on the same day. Regions of interest (ROIs) were the amygdala, hippocampus, pallidum, putamen, insula, frontal, anterior cingulate, parietal, temporal and occipital cortices, and cerebellum. Two multilinear radioligand quantification techniques were used to estimate binding potential: MA1, using arterial input function data, and the second version of the multilinear reference tissue model analysis (MRTM2), using the cerebellum as the reference region. Between-scan percent variability and intraclass correlation coefficients (ICC) were used to assess test-retest reliability. We also performed power analyses to determine the method that would allow the least number of subjects using within-subject or between-subject study designs. A voxel-wise ICC analysis for MRTM2 BPND was performed for the whole brain and all the ROIs studied. Mean percent variability between two scans across regions ranged between 0.4 % and 12.4 % for MA1 BPND, 0.5 % and 11.5 % for MA1 BPP, 16.7 % and 28.3 % for MA1 BPF, and between 0.2 % and 5.4 % for MRTM2 BPND. The power analyses showed a greater number of subjects were required using MA1 BPF compared with other outcome measures for both within-subject and between-subject study designs. ICC values were the highest using MRTM2 BPND and the lowest with MA1 BPF in ten ROIs. Small regions and regions with low binding had lower ICC values than large regions and regions with high binding. Reliable measures of 5-HT1B receptor binding can be obtained using the novel PET radioligand [(11)C]P943. Quantification of 5-HT1B receptor binding with MRTM2 BPND and with MA1 BPP provided the least variability and optimal power for within-subject and between

  3. Development of two fluorine-18 labeled PET radioligands targeting PDE10A and in vivo PET evaluation in nonhuman primates.

    Science.gov (United States)

    Stepanov, Vladimir; Takano, Akihiro; Nakao, Ryuji; Amini, Nahid; Miura, Shotaro; Hasui, Tomoaki; Kimura, Haruhide; Taniguchi, Takahiko; Halldin, Christer

    2017-10-23

    Phosphodiesterase 10A (PDE10A) is a member of the PDE enzyme family that degrades cyclic adenosine and guanosine monophosphates (cAMP and cGMP). Based on the successful development of [11C]T-773 as PDE10A positron emission tomography (PET) radioligand, in this study our aim was to develop and evaluate fluorine-18 analogs of [11C]T-773. [18F]FM-T-773-d2 and [18F]FE-T-773-d4 were synthesized from the same precursor used for 11C-labeling of T-773 in a two-step approach via 18F-fluoromethylation and 18F-fluoroethylation, respectively, using corresponding deuterated synthons. A total of 12 PET measurements were performed in seven non-human primates. First, baseline PET measurements were performed using High Resolution Research Tomograph system with both [18F]FM-T-773-d2 and [18F]FE-T-773-d4; the uptake in whole brain and separate brain regions, as well as the specific binding and tissue ratio between putamen and cerebellum, was examined. Second, baseline and pretreatment PET measurements using MP-10 as the blocker were performed for [18F]FM-T-773-d2 including arterial blood sampling with radiometabolite analysis in four NHPs. Both [18F]FM-T-773-d2 and [18F]FE-T-773-d4 were successfully radiolabeled with an average molar activity of 293 ± 114 GBq/μmol (n=8) for [18F]FM-T-773-d2 and 209 ± 26 GBq/μmol (n=4) for [18F]FE-T-773-d4, and a radiochemical yield of 10% (EOB, n=12, range 3%-16%). Both radioligands displayed high brain uptake (~5.5% of injected radioactivity for [18F]FM-T-773-d2 and ~3.5% for [18F]FE-T-773-d4 at the peak) and a fast washout. Specific binding reached maximum within 30 min for [18F]FM-T-773-d2 and after approximately 45 min for [18F]FE-T-773-d4. [18F]FM-T-773-d2 data fitted well with kinetic compartment models. BPND values obtained indirectly through compartment models were correlated well with those obtained by SRTM. BPND calculated with SRTM was 1.0-1.7 in the putamen. The occupancy with 1.8 mg/kg of MP-10 was approximately 60%. [18F]FM-T-773-d2

  4. Evaluation of the superselective radioligand [123I]PE2I for imaging of the dopamine transporter in SPECT

    DEFF Research Database (Denmark)

    Ziebell, Morten

    2011-01-01

    than [123I]FP-CIT. Because of its fast kinetic properties, quantification of [123I]PE2I binding to DAT is possible using kinetic or graphical analysis following bolus injection of tracer or as a combination of bolus and constant infusion. Based on preliminary bolus trials we have been able to calculate...... a B/I ratio of [123I]PE2I. This B/I ratio (2.7h) gave rise to steady state conditions and excellent reproducibility. Further, manual delineation of ROI directly on SPECT images performed equally well to a MRI-defined probability map based ROI delineation in terms of intrasubject variability of binding...... the more laborious B/I design it is currently to be considered the best radioligand for imaging the DAT in the human brain with SPECT....

  5. Evaluation of the superselective radioligand [123I]PE2I for imaging of the dopamine transporter in SPECT

    DEFF Research Database (Denmark)

    Ziebell, Morten

    than [123I]FP-CIT. Because of its fast kinetic properties, quantification of [123I]PE2I binding to DAT is possible using kinetic or graphical analysis following bolus injection of tracer or as a combination of bolus and constant infusion. Based on preliminary bolus trials we have been able to calculate...... a B/I ratio of [123I]PE2I. This B/I ratio (2.7h) gave rise to steady state conditions and excellent reproducibility. Further, manual delineation of ROI directly on SPECT images performed equally well to a MRI-defined probability map based ROI delineation in terms of intrasubject variability of binding...... the more laborious B/I design it is currently to be considered the best radioligand for imaging the DAT in the human brain with SPECT....

  6. Flavonoids from Perovskia atriplicifolia and Their in Vitro Displacement of the Respective Radioligands for Human Opioid and Cannabinoid Receptors.

    Science.gov (United States)

    Tarawneh, Amer; León, Francisco; Pettaway, Sara; Elokely, Khaled M; Klein, Michael L; Lambert, Janet; Mansoor, Arsala; Cutler, Stephen J

    2015-06-26

    Bioassay-guided fractionation of the leaves of Perovskia atriplicifolia (Russian sage) resulted in the isolation of four previously known flavonoid derivatives, 5-hydroxy-6,7,3',4'-tetramethoxyflavone (1), 5,7-dihydroxy-6,3',4'-trimethoxyflavone (2), 5-hydroxy-6,7,4'-trimethoxyflavone (3), and 5,7-dihydroxy-6,4'-dimethoxyflavone (4). Compounds 1, 3, and 4 showed displacement of the radioligand for the cloned human δ opioid receptor with Ki values ranging from 3.1 to 26.0 μM. In addition, the binding mode of the compounds in the active site of the δ opioid receptor was investigated through molecular modeling algorithms. This study may have implications in better understanding non-nitrogenous δ opioid receptor ligands.

  7. Application of radioligand receptor binding assays in the search for CNS active principles from Chinese medicinal plants.

    Science.gov (United States)

    Zhu, M; Bowery, N G; Greengrass, P M; Phillipson, J D

    1996-11-01

    Extracts of Schefflera bodinieri and S. delavayi (Araliaceae), Celastrus angulatus and C. orbiculatus (Celastraceae), Clerodendrum mandarinorum and C. bungei (Verbenaceae), Periploca callophylla and P. forrestii (Asclepiadaceae), Alangium platanifolium (Alangiaceae) and Uncaria rhynchophylla (Rubiaceae) were assessed for CNS activity against 18 radioligand receptor binding assays. The receptors used were alpha 1-, alpha 2- and beta-adrenoceptors, 5HT-1, 5HT-1A, 5HT-2, opiate, adenosine-1, benzodiazepine, Ca+2 channel, sulphonylureas, dopamine-1, dopamine-2, muscarinic, histamine-1, Na+/K+ ATPase, GABAA and GABAB. The results indicate that these ligand-receptor binding assays are useful for understanding the mode of action of herbal medicines and for bioassay guided fractionation of plant active ingredients.

  8. Preparation of (/sup 11/C)buprenorphine - a potential radioligand for the study of the opiate receptor system in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Luthra, S.K.; Pike, V.W.; Brady, F.; Horlock, P.L.; Prenant, C.; Crouzel, C.

    1987-01-01

    A method is described for the preparation of (/sup 11/C)buprenorphine in high specific activity, based on the reaction of N-(de-cyclopropylmethyl)buprenorphine with ''no carrier added'' (1-/sup 11/C)cyclopropanecarbonyl chloride followed by reduction with lithium aluminium hydride. The (1-/sup 11/C)cyclopropanecarbonyl chloride is itself prepared from cyclotron-produced (/sup 11/C)carbon dioxide. The overall preparation time is 57 min from the end of radionuclide production, and the radiochemical yield is ca 20%, (decay-corrected from (/sup 11/C)-carbon dioxide). (/sup 11/C)Buprenophine has potential as a radio-ligand for the study of the opiate receptor system in vivo by means of position emission tomography.

  9. Preclinical testing of F-18 and I-123 radioligands involving autoradiography and a phosphor-imaging device

    Energy Technology Data Exchange (ETDEWEB)

    Gatley, S.J.; Pyatt, B.; Gifford, A.N. [Brookhaven National Lab., Upton, NY (United States)] [and others

    1997-05-01

    During the development and validation of a receptor-binding radiopharmaceutical it is necessary to assess its brain regional distribution. Film contact autoradiography (AR) points such distributions to be evaluated on a fine anatomical scale, and avoids the inherent risk a microdissection experiments of missing interesting localization pattern. However, in vivo film AR may require a 1000-fold higher activity of a F-18 or I-123 radioligand than microdissection. In addition to health physics considerations, problems with receptor saturation can easily occur after injecting, say, 10 mCi into a 250g rat. A less commonly appreciated problem even with in vitro AR, using slide-mounted brain sections, is that it may be impossible to use sufficient F-18 to obtain acceptable images using film, because of receptor saturation. Phosphorimaging is superior in sensitivity to film by a factor of 10-50, and so relaxes constraints on injected activities and specific activities. Furthermore, it is also superior to film in terms of dynamic range and linearity of response. We have recently used phosphorimaging in two situations where film AR gave unsatisfactory results. (1) the novel cannabinoid CB1 receptor radioligand, I-123 AM281, was injected intravenously at 800 microcurie per rat. Animals were sacrificed at 2 h, frozen and whole body sections prepared. I-123 was clearly visualized in discrete brain areas (substantia nigra, globus pallidus, entopeduncular nucleus , hippocampus and cerebellum) consistent with the distribution of CB1 receptors previously demonstrated only in in vitro studies. (2) Rat brain sections were thaw mounted on gelatin/alum coated glass and incubated with the novel nicotinic acetylcholine receptor ligand F-18 2{prime}-fluoro-2{prime} nor-chloroepibatidine (1 nM).

  10. Synthesis and evaluation of N-(methylthiophenyl)picolinamide derivatives as PET radioligands for metabotropic glutamate receptor subtype 4.

    Science.gov (United States)

    Kil, Kun-Eek; Poutiainen, Pekka; Zhang, Zhaoda; Zhu, Aijun; Kuruppu, Darshini; Prabhakar, Shilpa; Choi, Ji-Kyung; Tannous, Bakhos A; Brownell, Anna-Liisa

    2016-01-01

    In recent years, mGlu4 has received great research attention because of the potential benefits of mGlu4 activation in treating numerous brain disorders, such as Parkinson's disease (PD). A specific mGlu4 PET radioligand could be an important tool in understanding the role of mGlu4 in both healthy and disease conditions, and also for the development of new drugs. In this study, we synthesized four new N-(methylthiophenyl)picolinamide derivatives 11-14. Of these ligands, 11 and 14 showed high in vitro binding affinity for mGlu4 with IC50 values of 3.4nM and 3.1nM, respectively, and suitable physicochemical parameters. Compound 11 also showed enhanced metabolic stability and good selectivity to other mGluRs. [(11)C]11 and [(11)C]14 were radiolabeled using the [(11)C]methylation of the thiophenol precursors 20a and 20c with [(11)C]CH3I in 19.0% and 34.8% radiochemical yields (RCY), and their specific activities at the end of synthesis (EOS) were 496±138GBq/μmol (n=6) and 463±263GBq/μmol (n=4), respectively. The PET studies showed that [(11)C]11 accumulated fast into the brain and had higher uptake, slower washout and 25% better contrast than [(11)C]2, indicating improved imaging characteristics as PET radiotracer for mGlu4 compared to [(11)C]2. Therefore, [(11)C]11 will be a useful radioligand to investigate mGlu4 in different biological applications. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Pathfinder to EXIST: ProtoEXIST

    Science.gov (United States)

    Garson, A. B., III; Allen, B.; Baker, R. G.; Barthelmy, S. D.; Burke, M.; Burnham, J.; Chammas, N.; Collins, J.; Cook, W. R.; Copete, A.; Gehrels, N.; Gauron, T.; Grindlay, J.; Harrison, F. A.; Hong, J.; Howell, J.; Krawczynski, H.; Labov, S.; Said, B.; Sheikh Sheikh, S.

    2008-04-01

    We describe the ProtoEXIST instrument, our fist-generation wide-field hard X-ray imaging (20 - 600 keV) balloon-borne telescope. The ProtoEXIST program is a pathfinder for the Energetic X-ray Imaging Survey Telescope (EXIST), a candidate for the Black Hole Finder Probe. ProtoEXIST consists of two independent coded-aperture telescopes using pixellated (2.5mm pitch) CZT detectors. The two telescopes will provide performance comparison of two shielding configurations, for optimization of the EXIST design. We report on the science goals and designs of both ProtoEXIST and EXIST and their implications for hard X-ray astronomy and astrophysics.

  12. Methods for synthesizing tritium-labelled Idazoxan-(RX 781094) (2-(2-imidazolinyl)-1,4-benzodioxane) of high specific activity: an antagonistic radioligand selective for presynaptic. cap alpha. /sub 2/ -adrenoreceptors

    Energy Technology Data Exchange (ETDEWEB)

    Guillaumet, G.; Coudert, G.; Clement, R.; Ponchant, P.; Pichat, L.

    1986-08-01

    Four methods of syntheses of IDAZOXAN (RX 781094) (2-(2-imidazolinyl)-1,4-benzodioxane) labelled with tritium are described. This selective radioligand is a presynaptic ..cap alpha../sub 2/-adrenoreceptor antagonist.

  13. A1 adenosine receptor inhibition of cyclic AMP formation and radioligand binding in the guinea-pig cerebral cortex.

    Science.gov (United States)

    Alexander, S P; Curtis, A R; Kendall, D A; Hill, S J

    1994-12-01

    1. A1 adenosine receptors were investigated by radioligand binding and functional studies in slices and particulate preparations from guinea-pig cerebral cortex. 2. Binding of the adenosine receptor antagonist radioligand, 8-cyclopentyl-[3H]-1,3-dipropylxanthine (DPCPX) to guinea-pig cerebral cortical membranes exhibited high density (1410 +/- 241 fmol mg-1 protein) and high affinity (Kd 3.8 +/- 0.3 nM). 3. [3H]-DPCPX binding to guinea-pig cerebral cortical membranes was displaced in a monophasic manner by adenosine receptor antagonists with the rank order of affinity (Ki values, nM): DPCPX (6) < xanthine amine congener (XAC, 153) < PD 115,199 (308). 4. Agonist displacement of [3H]-DPCPX binding was biphasic and exhibited the following rank order at the low affinity site (Ki values): 2-chloro-N6-cyclopentyl-adenosine (CCPA, 513 nM) = N6-R-phenylisopropyladenosine (R-PIA, 526 nM) = N6-cyclopentyladenosine (CPA, 532 nM) < 2-chloroadenosine (2CA, 3.2 microM) = 5'-N-ethylcarboxamidoadenosine (NECA, 4.6 microM) < N6-S-phenylisopropyladenosine (S-PIA, 19.9 microM). 5. In cerebral cortical slices, [3H]-DPCPX binding was displaced by antagonists and agonists in an apparently monophasic manner with the rank order of affinity (Ki values, nM): DPCPX (14) < XAC (45) < R-PIA (266) < PD 115,199 (666) < S-PIA (21000). 6. Cyclic AMP accumulation stimulated by 30 microM forskolin in guinea-pig cerebral cortical slices was inhibited by R-PIA, CCPA and CPA up to 1 microM in a concentration-dependent fashion with IC50 values of 14, 18, and 22 nM, respectively. All three analogues inhibited the forskolin response to a similar extent (82-93% inhibition). NECA, S-PTA and 2CA failed to inhibit the forskolin response, but rather enhanced the accumulation of cyclic AMP at concentrations of 100 nM or greater, presumably through activation of A2b adenosine receptors coupled to stimulation of cyclic AMP accumulation in guinea-pig cerebral cortical slices.7. The inhibition of forskolin

  14. Synthesis of the enantiomers of [N-methyl-[sup 11]C]PK 11195 and comparison of their behaviours as radioligands for PK binding sites in rats

    Energy Technology Data Exchange (ETDEWEB)

    Shah, Farah; Hume, S.P.; Pike, V.W.; Ashworth, S.; McDermott, J. (Hammersmith Hospital, London (United Kingdom). M.R.C. Cyclotron Unit)

    1994-05-01

    The enantiomers of [N-methyl-[sup 11]C]PK 11195, a radioligand for PET studies of PK (peripheral benzodiazepine) binding sites, have been prepared from the newly synthesized N-desmethyl-enantiomers by [sup 11]C-methylation with N.C.A. [[sup 11]C]iodomethane. The brain uptake and retention of each enantiomer was compared with that of the racemic radioligand after i.v. administration into normal rats and into rats with focal cortical lesions. The observed differences are consistent with the approximately 2-fold greater affinity of the R-enantiomer for PK binding sites reported in vitro and imply that the use of this entantiomer would have advantages over the use of the racemate currently used for PET studies. (author).

  15. Translocator protein (18 kDa) polymorphism (rs6971) explains in-vivo brain binding affinity of the PET radioligand [18F]-FEPPA

    Science.gov (United States)

    Mizrahi, Romina; Rusjan, Pablo M; Kennedy, James; Pollock, Bruce; Mulsant, Benoit; Suridjan, Ivonne; De Luca, Vincenzo; Wilson, Alan A; Houle, Sylvain

    2012-01-01

    [18F]-FEPPA binds to the 18-kDa translocator protein (TSPO) and is used in positron emission tomography (PET) to detect microglial activation. However, quantitative interpretations of the PET signal with new generation TSPO PET radioligands are confounded by large interindividual variability in binding affinity. This presents as a trimodal distribution, reflecting high-affinity binders (HABs), low-affinity binder (LAB), and mixed-affinity binders (MABs). Here, we show that one polymorphism (rs6971) located in exon 4 of the TSPO gene, which results in a nonconservative amino-acid substitution from alanine to threonine (Ala147Thr) in the TSPO protein, predicts [18F]-FEPPA total distribution volume in human brains. In addition, [18F]-FEPPA exhibits clearly different features in the shape of the time activity curves between genetic groups. Testing for the rs6971 polymorphism may allow quantitative interpretation of TSPO PET studies with new generation of TSPO PET radioligands. PMID:22472607

  16. Cerebellum Can Serve As a Pseudo-Reference Region in Alzheimer Disease to Detect Neuroinflammation Measured with PET Radioligand Binding to Translocator Protein.

    Science.gov (United States)

    Lyoo, Chul Hyoung; Ikawa, Masamichi; Liow, Jeih-San; Zoghbi, Sami S; Morse, Cheryl L; Pike, Victor W; Fujita, Masahiro; Innis, Robert B; Kreisl, William Charles

    2015-05-01

    Alzheimer disease (AD) is associated with an increase in the brain of the 18-kDa translocator protein (TSPO), which is overexpressed in activated microglia and reactive astrocytes. Measuring the density of TSPO with PET typically requires absolute quantitation with arterial blood sampling, because a reference region devoid of TSPO does not exist in the brain. We sought to determine whether a simple ratio method could substitute for absolute quantitation of binding with (11)C-PBR28, a second-generation radioligand for TSPO. (11)C-PBR28 PET imaging was performed in 21 healthy controls, 11 individuals with mild cognitive impairment, and 25 AD patients. Group differences in (11)C-PBR28 binding were compared using 2 methods. The first was the gold standard method of calculating total distribution volume (V(T)), using the 2-tissue-compartment model with the arterial input function, corrected for plasma-free fraction of radiotracer (f(P)). The second method used a ratio of brain uptake in target regions to that in cerebellum-that is, standardized uptake value ratio (SUVR). Using absolute quantitation, we confirmed that TSPO binding (V(T)/f(P)) was greater in AD patients than in healthy controls in expected temporoparietal regions and was not significantly different among the 3 groups in the cerebellum. When the cerebellum was used as a pseudo-reference region, the SUVR method detected greater binding in AD patients than controls in the same regions as absolute quantification and in 1 additional region, suggesting SUVR may have greater sensitivity. Coefficients of variation of SUVR measurements were about two-thirds lower than those of absolute quantification, and the resulting statistical significance was much higher for SUVR when comparing AD and healthy controls (e.g., P < 0.0005 for SUVR vs. P = 0.023 for VT/fP in combined middle and inferior temporal cortex). To measure TSPO density in AD patients and control subjects, a simple ratio method SUVR can substitute for

  17. An experimental study on (131)I-CHIBA-1001: a radioligand for α7 nicotinic acetylcholine receptors.

    Science.gov (United States)

    Yin, Lei; Zhao, Qian; Li, Ling; Zhang, Su Lei; Chen, Xue Qi; Ma, Chao; Kang, Lei; Liu, Meng; Zhang, Chun Li; Yan, Ping; Wang, Rong Fu

    2013-01-01

    The α7 nicotinic acetylcholine receptors (nAChRs) play a vital role in the pathophysiology of neuropsychiatric diseases such as Alzheimer's disease and depression. However, there is currently no suitable positron emission tomography (PET) or Single-Photon Emission Computed Tomography (SPECT) radioligands for imaging α7 nAChRs in brain. Here our aim is to radiosynthesize a novel SPECT radioligand (131)I-CHIBA-1001 for whole body biodistribution study and in vivo imaging of α7 nAChRs in brain. (131)I-CHIBA-1001 was radiosynthesized by chloramine-T method. Different conditions of reaction time and temperature were tested to get a better radiolabeling yield. Radiolabeling yield and radiochemical purities of (131)I-CHIBA-1001 were analyzed by thin layer chromatography (TLC) and high-performance liquid chromatography (HPLC) system. Whole body biodistribution study was performed at different time points post injection of (131)I-CHIBA-1001 in KM mice. Monkey subject was used for in vivo SPECT imaging in brain. The radiolabeling yield of (131)I-CHIBA-1001 reached 96% within 1.5∼2.0 h at 90∼95°C. The radiochemical purity reached more than 99% after HPLC purification. (131)I-CHIBA-1001 was highly stable in saline and fresh human serum in room temperature and 37°C separately. The biodistribution data of brain at 15, 30, and 60 min were 11.05±1.04%ID/g, 8.8±0.04%ID/g and 6.28±1.13%ID/g, respectively. In experimental SPECT imaging, the distribution of radioactivity in the brain regions was paralleled with the distribution of α7 nAChRs in the monkey brain. Moreover, in the blocking SPECT imaging study, the selective α7 nAChR agonist SSR180711 blocked the radioactive uptake in the brain successfully. The CHIBA-1001 can be successfully radiolabeled with (131)I using the chloramine-T method. (131)I-CHIBA-1001 can successfully accumulate in the monkey brain and image the α7 acetylcholine receptors. (131)I-CHIBA-1001 can be a candidate for imagingα7 acetylcholine

  18. An experimental study on (131I-CHIBA-1001: a radioligand for α7 nicotinic acetylcholine receptors.

    Directory of Open Access Journals (Sweden)

    Lei Yin

    Full Text Available OBJECTIVE: The α7 nicotinic acetylcholine receptors (nAChRs play a vital role in the pathophysiology of neuropsychiatric diseases such as Alzheimer's disease and depression. However, there is currently no suitable positron emission tomography (PET or Single-Photon Emission Computed Tomography (SPECT radioligands for imaging α7 nAChRs in brain. Here our aim is to radiosynthesize a novel SPECT radioligand (131I-CHIBA-1001 for whole body biodistribution study and in vivo imaging of α7 nAChRs in brain. METHOD: (131I-CHIBA-1001 was radiosynthesized by chloramine-T method. Different conditions of reaction time and temperature were tested to get a better radiolabeling yield. Radiolabeling yield and radiochemical purities of (131I-CHIBA-1001 were analyzed by thin layer chromatography (TLC and high-performance liquid chromatography (HPLC system. Whole body biodistribution study was performed at different time points post injection of (131I-CHIBA-1001 in KM mice. Monkey subject was used for in vivo SPECT imaging in brain. RESULT: The radiolabeling yield of (131I-CHIBA-1001 reached 96% within 1.5∼2.0 h at 90∼95°C. The radiochemical purity reached more than 99% after HPLC purification. (131I-CHIBA-1001 was highly stable in saline and fresh human serum in room temperature and 37°C separately. The biodistribution data of brain at 15, 30, and 60 min were 11.05±1.04%ID/g, 8.8±0.04%ID/g and 6.28±1.13%ID/g, respectively. In experimental SPECT imaging, the distribution of radioactivity in the brain regions was paralleled with the distribution of α7 nAChRs in the monkey brain. Moreover, in the blocking SPECT imaging study, the selective α7 nAChR agonist SSR180711 blocked the radioactive uptake in the brain successfully. CONCLUSION: The CHIBA-1001 can be successfully radiolabeled with (131I using the chloramine-T method. (131I-CHIBA-1001 can successfully accumulate in the monkey brain and image the α7 acetylcholine receptors. (131I-CHIBA-1001 can be a

  19. [11C]MADAM Used as a Model for Understanding the Radiometabolism of Diphenyl Sulfide Radioligands for Positron Emission Tomography (PET.

    Directory of Open Access Journals (Sweden)

    Fabienne Gourand

    Full Text Available In quantitative PET measurements, the analysis of radiometabolites in plasma is essential for determining the exact arterial input function. Diphenyl sulfide compounds are promising PET and SPECT radioligands for in vivo quantification of the serotonin transporter (SERT and it is therefore important to investigate their radiometabolism. We have chosen to explore the radiometabolic profile of [11C]MADAM, one of these radioligands widely used for in vivo PET-SERT studies. The metabolism of [11C]MADAM/MADAM was investigated using rat and human liver microsomes (RLM and HLM in combination with radio-HPLC or UHPLC/Q-ToF-MS for their identification. The effect of carrier on the radiometabolic rate of the radioligand [11C]MADAM in vitro and in vivo was examined by radio-HPLC. RLM and HLM incubations were carried out at two different carrier concentrations of 1 and 10 μM. Urine samples after perfusion of [11C]MADAM/MADAM in rats were also analysed by radio-HPLC. Analysis by UHPLC/Q-ToF-MS identified the metabolites produced in vitro to be results of N-demethylation, S-oxidation and benzylic hydroxylation. The presence of carrier greatly affected the radiometabolism rate of [11C]MADAM in both RLM/HLM experiments and in vivo rat studies. The good concordance between the results predicted by RLM and HLM experiments and the in vivo data obtained in rat studies indicate that the kinetics of the radiometabolism of the radioligand [11C]MADAM is dose-dependent. This issue needs to be addressed when the diarylsulfide class of compounds are used in PET quantifications of SERT.

  20. Neurokinin-3 Receptor Binding in Guinea Pig, Monkey, and Human Brain: In Vitro and in Vivo Imaging Using the Novel Radioligand, [18F]Lu AF10628.

    Science.gov (United States)

    Varnäs, Katarina; Finnema, Sjoerd J; Stepanov, Vladimir; Takano, Akihiro; Tóth, Miklós; Svedberg, Marie; Møller Nielsen, Søren; Khanzhin, Nikolay A; Juhl, Karsten; Bang-Andersen, Benny; Halldin, Christer; Farde, Lars

    2016-08-01

    Previous autoradiography studies have suggested a marked interspecies variation in the neuroanatomical localization and expression levels of the neurokinin 3 receptor, with high density in the brain of rat, gerbil, and guinea pig, but at the time offered no conclusive evidence for its presence in the human brain. Hitherto available radioligands have displayed low affinity for the human neurokinin 3 receptor relative to the rodent homologue and may thus not be optimal for cross-species analyses of the expression of this protein. A novel neurokinin 3 receptor radioligand, [(18)F]Lu AF10628 ((S)-N-(cyclobutyl(3-fluorophenyl)methyl)-8-fluoro-2-((3-[(18)F]-fluoropropyl)amino)-3-methyl-1-oxo-1,2-dihydroisoquinoline-4-carboxamide), was synthesized and used for autoradiography studies in cryosections from guinea pig, monkey, and human brain as well as for positron emission tomography studies in guinea pig and monkey. The results confirmed previous observations of interspecies variation in the neurokinin 3 receptor brain localization with more extensive distribution in guinea pig than in primate brain. In the human brain, specific binding to the neurokinin 3 receptor was highest in the amygdala and in the hypothalamus and very low in other regions examined. Positron emission tomography imaging showed a pattern consistent with that observed using autoradiography. The radioactivity was, however, found to accumulate in skull bone, which limits the use of this radioligand for in vivo quantification of neurokinin 3 receptor binding. Species differences in the brain distribution of neurokinin 3 receptors should be considered when using animal models for predicting human neurokinin 3 receptor pharmacology. For positron emission tomography imaging of brain neurokinin 3 receptors, additional work is required to develop a radioligand with more favorable in vivo properties. © The Author 2016. Published by Oxford University Press on behalf of CINP.

  1. Development of a PET radioligand for the central 5-HT{sub 1B} receptor: radiosynthesis and characterization in cynomolgus monkeys of eight radiolabeled compounds

    Energy Technology Data Exchange (ETDEWEB)

    Andersson, Jan D., E-mail: j.d.andersson@ki.s [Psychiatry Section, Department of Clinical Neuroscience, Karolinska Institutet, Karolinska University Hospital, SE-17176 Stockholm (Sweden); Pierson, M. Edward [AstraZeneca Pharmaceuticals, CNS Discovery, Wilmington, DE 19850 (United States); Finnema, Sjoerd J.; Gulyas, Balazs [Psychiatry Section, Department of Clinical Neuroscience, Karolinska Institutet, Karolinska University Hospital, SE-17176 Stockholm (Sweden); Heys, Richard; Elmore, Charles S. [AstraZeneca Pharmaceuticals, CNS Discovery, Wilmington, DE 19850 (United States); Farde, Lars [AstraZeneca Pharmaceuticals, Neuroscience Clinical, SE-15185 Soedertaelje (Sweden); Halldin, Christer [Psychiatry Section, Department of Clinical Neuroscience, Karolinska Institutet, Karolinska University Hospital, SE-17176 Stockholm (Sweden)

    2011-02-15

    Introduction: The serotonin 1B (5-HT{sub 1B}) receptor has been implicated in several psychiatric disorders and is a potential pharmacological target in the treatment of depression. The aim of this study was to develop a radioligand for positron emission tomography (PET) imaging of the 5-HT{sub 1B} receptor in the primate brain in vivo. Methods: Eight carboxamide radioligands (1-8) from three different core structures were radiolabeled with carbon-11 employing N-methylation with [{sup 11}C]methyl triflate on the piperazine structural moiety. In vivo PET evaluation of each radioligand was performed in cynomolgus monkeys and included analysis of radioactive metabolites measured in plasma using high-performance liquid chromatography. Results: In a total of 12 radiosynthesis of the eight radioligands, the mean decay corrected yield was 11%, and the mean specific radioactivity was 299 GBq/{mu}mol (8075 Ci/mmol) at time of administration. Of the eight tested candidates, [{sup 11}C]6 demonstrated the most promising in vivo characteristics, showing high binding in 5-HT{sub 1B} receptor-rich regions and low binding in the cerebellum. When inspecting data from all eight compounds, lipophilicity appeared as a physicochemical property that could be related to favorable in vivo imaging characteristics. Conclusion: Candidate [{sup 11}C]6, i.e., [{sup 11}C]AZ10419369, exhibited high binding potentials in regions known to contain 5-HT{sub 1B} receptors and was nominated for further preclinical characterization and PET examination in human subjects.

  2. Evaluation of PET Imaging Performance of the TSPO Radioligand [18F]DPA-714 in Mouse and Rat Models of Cancer and Inflammation.

    Science.gov (United States)

    Zheng, Jinzi; Winkeler, Alexandra; Peyronneau, Marie-Anne; Dollé, Frédéric; Boisgard, Raphaël

    2016-02-01

    Many radioligands have been explored for imaging the 18-kDa translocator protein (TSPO), a diagnostic and therapeutic target for inflammation and cancer. Here, we investigated the TSPO radioligand [(18)F]DPA-714 for positron emission tomography (PET) imaging of cancer and inflammation. [(18)F]DPA-714 PET imaging was performed in 8 mouse and rat models of breast and brain cancer and 4 mouse and rat models of muscular and bowel inflammation. [(18)F]DPA-714 showed different uptake levels in healthy organs and malignant tissues of mice and rats. Although high and displaceable [(18)F]DPA-714 binding is observed ex vivo, TSPO-positive PET imaging of peripheral lesions of cancer and inflammation in mice did not show significant lesion-to-background signal ratios. Slower [(18)F]DPA-714 metabolism and muscle clearance in mice compared to rats may explain the elevated background signal in peripheral organs in this species. Although TSPO is an evolutionary conserved protein, inter- and intra-species differences call for further exploration of the pharmacological parameters of TSPO radioligands.

  3. Low frequency of pendrin autoantibodies detected using a radioligand binding assay in patients with autoimmune thyroid disease.

    Science.gov (United States)

    Kemp, E Helen; Sandhu, Harpreet K; Watson, Philip F; Weetman, Anthony P

    2013-02-01

    Pendrin is a transmembrane protein located at the apical end of the thyrocyte in which it mediates the efflux of iodide through the thyroid follicular cell. Recently pendrin was described as a significant antibody target in Japanese patients with Graves' disease (GD) or autoimmune hypothyroidism (AH) using an immunoblotting assay. However, a subsequent study failed to verify this in autoimmune thyroid disease (ATD) patients of Tunisian origin. The aim of the current study was to evaluate a UK population of patients with ATD for the presence of pendrin autoantibodies using a novel radioligand binding assay (RBA). Sera from 71 GD and 66 AH patients and 28 healthy controls were evaluated for pendrin autoantibody reactivity in RBAs. The results indicated that 8.8% of patients with ATD (9.9% GD and 7.6% AH) were positive for pendrin autoantibodies. Overall, the frequency of pendrin autoantibodies did not differ significantly between the ATD patient cohorts and the healthy control group: P = .186 and P = .317 for GD and AH patients, respectively. Pendrin autoantibodies, detected using a novel RBA, are not widely prevalent in UK patients with ATD, nor do they differ in frequency between GD and AH. These autoantibodies are therefore unlikely to be a useful marker for disease diagnosis, although the role that pendrin may play as an autoantigen in the initiation or maintenance of thyroid autoimmunity remains to be established.

  4. Kinetic modeling of the serotonin 5-HT1B receptor radioligand [11C]P943 in humans

    Science.gov (United States)

    Gallezot, Jean-Dominique; Nabulsi, Nabeel; Neumeister, Alexander; Planeta-Wilson, Beata; Williams, Wendol A; Singhal, Tarun; Kim, Sunhee; Maguire, R Paul; McCarthy, Timothy; Frost, J James; Huang, Yiyun; Ding, Yu-Shin; Carson, Richard E

    2010-01-01

    [11C]P943 is a new radioligand recently developed to image and quantify serotonin 5-Hydroxytryptamine (5-HT1B) receptors with positron emission tomography (PET). The purpose of this study was to evaluate [11C]P943 for this application in humans, and to determine the most suitable quantification method. Positron emission tomography data and arterial input function measurements were acquired in a cohort of 32 human subjects. Using arterial input functions, compartmental modeling, the Logan graphical analysis, and the multilinear method MA1 were tested. Both the two tissue-compartment model and MA1 provided good fits of the PET data and reliable distribution volume estimates. Using the cerebellum as a reference region, BPND binding potential estimates were computed. [11C]P943 BPND estimates were significantly correlated with in vitro measurements of the density of 5-HT1B receptors, with highest values in the occipital cortex and pallidum. To evaluate noninvasive methods, two- and three-parameter graphical analyses, Simplified Reference Tissue Models (SRTM and SRTM2), and Multilinear Reference Tissue Models (MRTM and MRTM2) were tested. The MRTM2 model provided the best correlation with MA1 binding-potential estimates. Parametric images of the volume of distribution or binding potential of [11C]P943 could be computed using both MA1 and MRTM2. The results show that [11C]P943 provides quantitative measurements of 5-HT1B binding potential. PMID:19773803

  5. Requirements for existing buildings

    DEFF Research Database (Denmark)

    Thomsen, Kirsten Engelund; Wittchen, Kim Bjarne

    This report collects energy performance requirements for existing buildings in European member states by June 2012.......This report collects energy performance requirements for existing buildings in European member states by June 2012....

  6. Dopaminergic modulation of mitral cell activity in the frog olfactory bulb: a combined radioligand binding-electrophysiological study

    Energy Technology Data Exchange (ETDEWEB)

    Duchamp, A.; Moyse, E.; Delaleu, J.-C.; Coronas, V.; Duchamp-Viret, P. [Laboratoire de Physiologie Neurosensorielle, Universite Claude Bernard and CNRS, F69622 Villeurbanne (France)

    1997-04-28

    Dopamine content in the amphibian olfactory bulb is supplied by interneurons scattered among mitral cells in the external plexiform/mitral cell layer. In mammals, dopamine has been found to be involved in various aspects of bulbar information processing by influencing mitral cell odour responsiveness. Dopamine action in the bulb depends directly on the localization of its receptor targets, found to be mainly of the D{sub 2} type in mammals. The present study assessed, in the frog, both the anatomical localization of D{sub 2}-like, radioligand-labelled receptors of dopamine and the in vivo action of dopamine on unitary mitral cell activity in response to odours delivered over a wide range of concentrations. The [{sup 125}I]iodosulpride-labelled D{sub 2} binding sites were visualized on frozen sagittal sections of frog brains by film radioautography. The sites were found to be restricted to the external plexiform/mitral cell layer; other layers of the olfactory bulb were devoid of specific labelling. Electrophysiological recordings of mitral unit activity revealed that dopamine or its agonist apomorphine induced a drastic reduction of spontaneous firing rate of mitral cells in most cases without altering odour intensity coding properties of these cells. Moreover, pre-treatment with the D{sub 2} antagonist eticlopride blocked the dopamine-induced reduction of mitral cell spontaneous activity.In the frog olfactory bulb, both anatomical localization of D{sub 2}-like receptors and functional data on dopamine involvement in information processing differ from those reported in mammals. This suggests a phylogenetic evolution of dopamine action in the olfactory bulb. In the frog, anatomical data perfectly corroborate electrophysiological results, together strongly suggesting a direct action of dopamine on mitral cells. In a physiologically operating system, such an action would result in a global improvement of signal-to-noise ratio. (Copyright (c) 1997 Elsevier Science B

  7. Candidate PET radioligands for cannabinoid CB{sub 1} receptors: [{sup 18}F]AM5144 and related pyrazole compounds

    Energy Technology Data Exchange (ETDEWEB)

    Li Zizhong [Center for Translational Neuroimaging, Brookhaven National Laboratory, Upton, NY 11973 (United States); Gifford, Andrew [Center for Translational Neuroimaging, Brookhaven National Laboratory, Upton, NY 11973 (United States); Liu Qian [Center for Drug Discovery, Northeastern University, Boston, MA 02115 (United States); Thotapally, Rajesh [Center for Drug Discovery, Northeastern University, Boston, MA 02115 (United States); Ding Yushin [Center for Translational Neuroimaging, Brookhaven National Laboratory, Upton, NY 11973 (United States); Makriyannis, Alexandros [Center for Drug Discovery, Northeastern University, Boston, MA 02115 (United States); Gatley, S. John [Center for Translational Neuroimaging, Brookhaven National Laboratory, Upton, NY 11973 (United States) and Center for Drug Discovery, Northeastern University, Boston, MA 02115 (United States)]. E-mail: s.gatley@neu.edu

    2005-05-01

    Introduction: The mammalian brain contains abundant G protein-coupled cannabinoid CB{sub 1} receptors that respond to {delta}{sup 9}-tetrahydrocannabinol, the active ingredient of cannabis. The availability of a positron emission tomography (PET) radioligand would facilitate studies of the addictive and medicinal properties of compounds that bind to this receptor. Among the known classes of ligands for CB{sub 1} receptors, the pyrazoles are attractive targets for radiopharmaceutical development because they are antagonists and are generally less lipophilic than the other classes. Methods: A convenient high-yield synthesis of N-(4-[{sup 18}F]fluorophenyl)-5-(4-bromophenyl)-1-(2,4-dichlorophenyl)- 1H-pyrazole-3-carboxamide (AM5144) was devised by coupling the appropriate pyrazole-3-carboxyl chloride compound with 4-[{sup 18}F]fluoroaniline. The labeled precursor was synthesized from 1-[{sup 18}F]fluoro-4-nitrobenzene in 60% radiochemical yield for 10 min using an improved procedure involving sodium borohydride reduction with cobalt chloride catalysis. The product was purified by HPLC to give a specific activity >400 mCi/{mu}mol and a radiochemical purity >95%, and a PET study was conducted in a baboon. Results: Although the regional uptake of AM5144 in baboon brain was consistent with binding to cannabinoid CB{sub 1} receptors, absolute uptake at <0.003% injected radioactivity per cubic centimeter was lower than the previously reported uptake of the radioiodinated pyrazole AM281. Conclusions: The relatively poor brain uptake of AM5144 and other pyrazole CB{sub 1} receptor ligands is not surprising because of their high lipophilicity as compared with most brain PET radiotracers. However, for nine pyrazole compounds for which rodent data are available, brain uptake and calculated logP values are not correlated. Thus, high logP values should not preclude evaluation of radiotracers for targets such as the CB{sub 1} receptor that may require very lipophilic ligands.

  8. [{sup 11}C]-MeJDTic: a novel radioligand for {kappa}-opioid receptor positron emission tomography imaging

    Energy Technology Data Exchange (ETDEWEB)

    Poisnel, Geraldine; Oueslati, Farhana; Dhilly, Martine; Delamare, Jerome [Groupe de Developpements Methodologiques en Tomographie par Emission de Positons, DSV/DRM UMR CEA 2E, Universite de Caen-Basse Normandie, Centre Cyceron, 14074 Caen Cedex (France); Perrio, Cecile [Groupe de Developpements Methodologiques en Tomographie par Emission de Positons, DSV/DRM UMR CEA 2E, Universite de Caen-Basse Normandie, Centre Cyceron, 14074 Caen Cedex (France)], E-mail: perrio@cyceron.fr; Debruyne, Daniele [Groupe de Developpements Methodologiques en Tomographie par Emission de Positons, DSV/DRM UMR CEA 2E, Universite de Caen-Basse Normandie, Centre Cyceron, 14074 Caen Cedex (France)], E-mail: debruyne@cyceron.fr; Barre, Louisa [Groupe de Developpements Methodologiques en Tomographie par Emission de Positons, DSV/DRM UMR CEA 2E, Universite de Caen-Basse Normandie, Centre Cyceron, 14074 Caen Cedex (France)

    2008-07-15

    Introduction: Radiopharmaceuticals that can bind selectively the {kappa}-opioid receptor may present opportunities for staging clinical brain disorders and evaluating the efficiency of new therapies related to stroke, neurodegenerative diseases or opiate addiction. The N-methylated derivative of JDTic (named MeJDTic), which has been recently described as a potent and selective antagonist of {kappa}-opioid receptor in vitro, was labeled with carbon-11 and evaluated for in vivo imaging the {kappa}-opioid receptor in mice. Methods: [{sup 11}C]-MeJDTic was prepared by methylation of JDTic with [{sup 11}C]-methyl triflate. The binding of [{sup 11}C]-MeJDTic to {kappa}-opioid receptor was investigated ex vivo by biodistribution and competition studies using nonfasted male CD1 mice. Results: [{sup 11}C]-MeJDTic exhibited a high and rapid distribution in peripheral organs. The uptake was maximal in lung where the {kappa} receptor is largely expressed. [{sup 11}C]-MeJDTic rapidly crossed the blood-brain barrier and accumulated in the brain regions of interest (hypothalamus). The parent ligand remained the major radioactive compound in brain during the experiment. Chase studies with U50,488 (a {kappa} referring agonist), morphine (a {mu} agonist) and naltrindole (a {delta} antagonist) demonstrated that this uptake was the result of specific binding to the {kappa}-opioid receptor. Conclusion: These findings suggested that [{sup 11}C]-MeJDTic appeared to be a promising selective 'lead' radioligand for {kappa}-opioid receptor PET imaging.

  9. Repeated PSMA-targeting radioligand therapy of metastatic prostate cancer with {sup 131}I-MIP-1095

    Energy Technology Data Exchange (ETDEWEB)

    Afshar-Oromieh, Ali; Haberkorn, Uwe [Heidelberg University Hospital, Department of Nuclear Medicine, Heidelberg (Germany); German Cancer Research Center, Clinical Cooperation Unit Nuclear Medicine, Heidelberg (Germany); Zechmann, Christian; Mier, Walter; Spohn, Fabian; Debus, Nils; Kratochwil, Clemens [Heidelberg University Hospital, Department of Nuclear Medicine, Heidelberg (Germany); Armor, Thomas [Progenics Pharmaceuticals, Inc., New York, NY (United States); Holland-Letz, Tim [German Cancer Research Center, Department of Biostatistics, Heidelberg (Germany); Babich, John [Weill Cornell Medicine, Division of Radiopharmaceutical Sciences, Department of Radiology, New York, NY (United States); Weill Cornell Medicine, Citigroup Biomedical Imaging Center, New York, NY (United States); Weill Cornell Medicine, Meyer Cancer Center, New York, NY (United States)

    2017-06-15

    Prostate-specific membrane antigen (PSMA)-targeting radioligand therapy (RLT) was introduced in 2011. The first report described the antitumor and side effects of a single dose. The aim of this analysis was to evaluate toxicity and antitumor activity after single and repetitive therapies. Thirty-four men with metastatic castration-resistant prostate cancer received PSMA-RLT with {sup 131}I-MIP-1095. Twenty-three patients received a second, and three patients a third dose, timed at PSA progression after an initial response to the preceding therapy. The applied doses were separated in three groups: <3.5, 3.5-5.0 and >5.0 GBq. Antitumor and side-effects were analyzed by blood samples and other clinical data. Follow-up was conducted for up to 5 years. The best therapeutic effect was achieved by the first therapy. A PSA decline of ≥50% was achieved in 70.6% of the patients. The second and third therapies were significantly less effective. There was neither an association between the applied activity and PSA response or the time-to-progression. Hematologic toxicities were less prevalent but presented in a higher percentage of patients with increasing number of therapies. After hematologic toxicities, xerostomia was the second most frequent side effect and presented more often and with higher intensity after the second or third therapy. The first dose of RLT with {sup 131}I-MIP-1095 presented with low side effects and could significantly reduce the tumor burden in a majority of patients. The second and third therapies were less effective and presented with more frequent and more intense side effects, especially hematologic toxicities and xerostomia. (orig.)

  10. 5-tert-Butyl-2-(4'-[{sup 18}F]fluoropropynylphenyl)-1,3-dithiane oxides: potential new GABA{sub A} receptor radioligands

    Energy Technology Data Exchange (ETDEWEB)

    Li Xuehe; Jung, Yong-Woon; Snyder, Scott E.; Blair, Joseph; Sherman, Philip S.; Desmond, Timothy; Frey, Kirk A. [Department of Radiology, University of Michigan Medical School, Ann Arbor, MI 48109 (United States); Kilbourn, Michael R. [Department of Radiology, University of Michigan Medical School, Ann Arbor, MI 48109 (United States)], E-mail: mkilbour@umich.edu

    2008-07-15

    As potential new ligands targeting the binding site of {gamma}-aminobutyric acid (GABA) receptor ionophore, trans-5-tert-butyl-2-(4'-fluoropropynylphenyl)-2-methyl-1,1-dioxo-1, 3-dithiane (1) and cis/trans-5-tert-butyl-2-(4'-fluoropropynylphenyl)-2-methyl-1,1,3, 3-tetroxo-1,3-dithiane (2) were selected for radiolabeling and initial evaluation as in vivo imaging agents for positron emission tomography (PET). Both compounds exhibited identical high in vitro binding affinities (K{sub i}=6.5 nM). Appropriate tosylate-substituted ethynyl precursors were prepared by multistep syntheses involving stepwise sulfur oxidation and chromatographic isolation of desired trans isomers. Radiolabeling was accomplished in one step using nucleophilic [{sup 18}F]fluorination. In vivo biodistribution studies with trans-[{sup 18}F]1 and trans-[{sup 18}F]2 showed significant initial uptake into mouse brain and gradual washout, with heterogeneous regional brain distributions and higher retention in the cerebral cortex and cerebellum and lower retention in the striatum and pons-medulla. These regional distributions of the new radioligands correlated with in vitro and ex vivo measures of standard radioligands binding to the ionophore- and benzodiazepine-binding sites of GABA{sub A} receptor in rodent brain. A comparison of these results with previously prepared radiotracers for other neurochemical targets, including successes and failures as in vivo radioligands, suggests that higher-affinity compounds with increased retention in target brain tissues will likely be needed before a successful radiopharmaceutical for human PET imaging can be identified.

  11. Biodistribution and radiation dosimetry of the 18 kDa translocator protein (TSPO) radioligand [{sup 18}F]FEDAA1106: a human whole-body PET study

    Energy Technology Data Exchange (ETDEWEB)

    Takano, Akihiro; Gulyas, Balazs; Varrone, Andrea; Karlsson, Per; Sjoholm, Nils; Halldin, Christer [Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Stockholm (Sweden); Larsson, Stig; Jonsson, Cathrine; Odh, Richard [Karolinska Institutet, Department of Nuclear Medicine, Stockholm (Sweden); Sparks, Richard [CDE Dosimetry Services, Inc., Knoxville, TN (United States); Tawil, Nabil Al [Karolinska University Hospital, Karolinska Trial Alliance, Stockholm (Sweden); Hoffmann, Anja; Zimmermann, Torsten; Thiele, Andrea [Bayer Schering Pharma AG, Berlin (Germany)

    2011-11-15

    [{sup 18}F]FEDAA1106 is a recently developed positron emission tomography (PET) radioligand for in vivo quantification of the 18 kDa translocator protein [TSPO or, as earlier called, the peripheral benzodiazepine receptor (PBR)]. TSPO imaging is expected to be useful for the clinical evaluation of neuroinflammatory diseases. The aim of this study was to provide dosimetry estimates for [{sup 18}F]FEDAA1106 based on human whole-body PET measurements. PET scans were performed for a total of 6.6 h after the injection of 183.8 {+-} 9.1 MBq of [{sup 18}F]FEDAA1106 in six healthy subjects. Regions of interest were drawn on coronal images. Estimates of the absorbed doses of radiation were calculated using the OLINDA software. Peak uptake was largest in lungs, followed by liver, small intestine, kidney, spleen and other organs. Peak values of the percent injected dose (%ID) at a time after radioligand injection were calculated for the lungs (27.1%ID at 0.2 h), liver (21.1%ID at 0.6 h), small intestine (10.4%ID at 6.3 h), kidney (4.9%ID at 1.8 h) and spleen (4.6%ID at 0.6 h). The largest absorbed dose was found in the spleen (0.12 mSv/MBq), followed by kidneys (0.094 mSv/MBq). The calculated mean effective dose was 0.036 mSv/MBq. Based on the distribution and dose estimates, the estimated radiation burden of [{sup 18}F]FEDAA1106 is moderately higher than that of [{sup 18}F]fluorodeoxyglucose (FDG). In clinical studies, the administered activity of this radioligand ought to be adjusted in line with regional regulations. This result would be helpful for further clinical TSPO imaging studies. (orig.)

  12. Biodistribution of [{sup 18}f] SR144385 and [{sup 18}f] SR147963: selective radioligands for positron emission tomographic studies of brain cannabinoid receptors

    Energy Technology Data Exchange (ETDEWEB)

    Mathews, William B. E-mail: bmathews@petscan.nm.jhu.edu; Scheffel, Ursula; Finley, Paige; Ravert, Hayden T.; Frank, Richard A.; Rinaldi-Carmona, Murielle; Barth, Francis; Dannals, Robert F

    2000-11-01

    [{sup 18}F] SR144385 and [{sup 18}F] SR147963 were synthesized in a multistep reaction in which fluorine-18 was introduced by nucleophilic halogen displacement on a bromo precursor. The fluorine-18-labeled intermediate was deprotected and coupled with the appropriate alkyl amine to give the final products. Both radioligands had appropriate regional brain distribution for cannabinoid receptors with a target to nontarget ratio of 1.7 for [{sup 18}F] SR147963 and 2.5 for [{sup 18}F] SR144385 at 60 and 90 min postinjection, respectively. The uptake of both tracers was blocked with a 1 mg/kg dose of SR141716A.

  13. Design and Investigation of a [18F]-Labeled Benzamide Derivative as a High Affinity Dual Sigma Receptor Subtype Radioligand for Prostate Tumor Imaging.

    Science.gov (United States)

    Yang, Dongzhi; Comeau, Anthony; Bowen, Wayne D; Mach, Robert H; Ross, Brian D; Hong, Hao; Van Dort, Marcian E

    2017-03-06

    High overexpression of sigma (σ) receptors (σ1 and σ2 subtypes) in a variety of human solid tumors has prompted the development of σ receptor-targeting radioligands, as imaging agents for tumor detection. A majority of these radioligands to date target the σ2 receptor, a potential marker of tumor proliferative status. The identification of approximately equal proportions of both σ receptor subtypes in prostate tumors suggests that a high affinity, dual σ receptor-targeting radioligand could potentially provide enhanced tumor targeting efficacy in prostate cancer. To accomplish this goal, we designed a series of ligands which bind to both σ receptor subtypes with high affinity. Ligand 3a in this series, displaying optimal dual σ receptor subtype affinity (σ1, 6.3 nM; σ2, 10.2 nM) was radiolabeled with fluorine-18 (18F) to give [18F]3a and evaluated as a σ receptor-targeting radioligand in the mouse PC-3 prostate tumor model. Cellular assays with PC-3 cells demonstrated that a major proportion of [18F]3a was localized to cell surface σ receptors, while ∼10% of [18F]3a was internalized within cells after incubation for 3.5 h. Serial PET imaging in mice bearing PC-3 tumors revealed that uptake of [18F]3a was 1.6 ± 0.8, 4.4 ± 0.3, and 3.6 ± 0.6% ID/g (% injection dose per gram) in σ receptor-positive prostate tumors at 15 min, 1.5 h, and 3.5 h postinjection, respectively (n = 3) resulting in clear tumor visualization. Blocking studies conducted with haloperidol (a nonselective inhibitor for both σ receptor subtypes) confirmed that the uptake of [18F]3a was σ receptor-mediated. Histology analysis confirmed similar expression of σ1 and σ2 in PC-3 tumors which was significantly greater than its expression in normal organs/tissues such as liver, kidney, and muscle. Metabolite studies revealed that >50% of radioactivity in PC-3 tumors at 30 min postinjection represented intact [18F]3a. Prominent σ receptor-specific uptake of [18F]3a in prostate tumors

  14. Evaluation of sup 3 H-paroxetine as a radioligand for in vivo study of 5-hydroxytryptamine uptake sites in mouse brain

    Energy Technology Data Exchange (ETDEWEB)

    Hashimoto, Kenji; Goromaru, Tsuyoshi (Fukuyama Univ., Hiroshima (Japan). Faculty of Pharmacy and Pharmaceutical Sciences)

    1990-08-01

    The distribution of radioactivity in the mouse brain after intravenous administration of {sup 3}H-paroxetine was in descending order hypothalamus > cerebral cortex > cerebellum. The radioactivity in the hypothalamus and cerebral cortex after injection of {sup 3}H-paroxetine was significantly decreased by treatment with 6-nitroquipazine or paroxetine. HPLC and TLC analyses show that no radioactive metabolites were found in the mouse brain 3 h after intravenous administration of {sup 3}H-paroxetine. The present results indicate that {sup 3}H-paroxetine would be a suitable radioligand for in vivo study of 5-HT uptake sites in mouse brain.

  15. [{sup 11}C]S.L.(25.1188), a new radioligand to study the monoamine oxidase type B with PET: preclinical characterisation

    Energy Technology Data Exchange (ETDEWEB)

    Saba, W.; Valette, H.; Peyronneau, M.A.; Bramoulle, Y.; Coulon, C.; Dolle, F.; Bottlaender, M. [Service Hospitalier Frederic Joliot, IIBM/DSV, 91 - Orsay (France); Curet, O.; George, P. [Sanofi-Aventis, 92 - Bagneux (France)

    2008-02-15

    Introduction. - Monoamine oxidase (M.A.O.) is a flavin containing enzyme, that catalyzes the oxidative deamination of various amines and neurotransmitters. Two isoforms exist, M.A.O.-A and M.A.O.-B. Variations in M.A.O. activity may be associated to human disease such as Parkinson and Alzheimer disease. Few radiotracers have been developed for M.A.O. PET studies such as [{sup 11}C]deprenyl, an irreversible M.A.O.-B inhibitor. Recently an oxazolidinone derivative, S.L.- 25.1188 ((S)-5-methoxy-methyl-3-[6-(4,4,4-tri-fluoro butoxy)- benzo[d]isoxazol-3-yl]-oxazolidin-2-one), belonging to a new generation of selective and reversible M.A.O.-B inhibitors was developed and showed in vitro a high selectivity for M.A.O.B. [1]. The aim of this study was to characterize [{sup 11}C]S.L.- 25.1188 as radioligand for in vivo PET examination of M.A.O.-B. Materials and methods. - PET studies of the brain distribution were carried out in male Papio anubis baboons. Selectivity and reversibility of [{sup 11}C]S.L.-25.1188 binding for M.A.O.-B was assessed by pre-treatment or displacement experiments (30 min before and after tracer injection, respectively) using reference ligands for M.A.O.-B (deprenyl: 2 mg/kg i.v. and lazabemide: 0.5 mg/kg i.v.) or by displacement experiments using unlabelled S.L.-25.1188 (1 mg/kg, i.v., 30 min after tracer injection). Distribution volume (D.V.) was calculated using 2-tissue-compartment model. The saturable binding following pre-treatment with deprenyl was considered as the specific binding. Results. - After injection, [1{sup 1C}]S.L.-25.1188 presents a rapid phase of distribution in blood (about 5 min), followed by a elimination with T1/2 of 75 min. The Blood to plasma concentration ratio was constant during the experimentation (0.9 {+-} .04) consistent with a similar kinetic of [{sup 11}C]S.L.- 25.1188 in both blood and plasma. Metabolism analysis showed that [{sup 11}C]S.L.-25.1188 is stable in vivo. In the brain, uptake in different areas was

  16. Synthesis and characterization of EADAM: a selective radioligand for mapping the brain serotonin transporters by positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Jarkas, Nachwa [Department of Radiology, Division of Radiological Sciences, Emory University, Atlanta, GA 30322 (United States); McConathy, Jonathan [Department of Radiology, Division of Radiological Sciences, Emory University, Atlanta, GA 30322 (United States); Department of Psychiatry and Behavior Sciences, Emory University, Atlanta, GA 30322 (United States); Votaw, John R. [Department of Radiology, Division of Radiological Sciences, Emory University, Atlanta, GA 30322 (United States); Voll, Ronald J. [Department of Radiology, Division of Radiological Sciences, Emory University, Atlanta, GA 30322 (United States); Malveaux, Eugene [Department of Radiology, Division of Radiological Sciences, Emory University, Atlanta, GA 30322 (United States); Camp, Vernon M. [Department of Radiology, Division of Radiological Sciences, Emory University, Atlanta, GA 30322 (United States); Williams, Larry [Department of Radiology, Division of Radiological Sciences, Emory University, Atlanta, GA 30322 (United States); Goodman, Robin R. [Department of Radiology, Division of Radiological Sciences, Emory University, Atlanta, GA 30322 (United States); Kilts, Clinton D. [Department of Psychiatry and Behavior Sciences, Emory University, Atlanta, GA 30322 (United States); Goodman, Mark M. [Department of Radiology, Division of Radiological Sciences, Emory University, Atlanta, GA 30322 (United States) and Department of Psychiatry and Behavior Sciences, Emory University, Atlanta, GA 30322 (United States)]. E-mail: mgoodma@emory.edu

    2005-01-01

    , radioactivity in the striatum, thalamus and brainstem was significantly reduced. These results support the candidacy of [{sup 11}C]EADAM as a radioligand for visualizing brain SERT using PET.

  17. In vivo inhibition of neutral endopeptidase enhances the diagnostic potential of truncated gastrin (111)In-radioligands.

    Science.gov (United States)

    Kaloudi, Aikaterini; Nock, Berthold A; Lymperis, Emmanouil; Sallegger, Werner; Krenning, Eric P; de Jong, Marion; Maina, Theodosia

    2015-11-01

    Radiolabeled gastrin analogs represent attractive candidates for diagnosis and therapy of cholecystokinin subtype-2 receptor (CCK2R)-expressing tumors. Radiolabeled des(Glu)5-gastrins show favorably low renal accumulation, but localize poorly in CCK2R-positive lesions. We introduce herein three truncated [DOTA-DGlu(10)]gastrin(10-17) analogs, with oxidation-susceptible Met(15) replaced by: (1), (2), or (3), and study the profile of [(111)In]1/2/3 during in vivo inhibition of neutral endopeptidase (NEP) in comparison to the non-truncated [ ([(111)In]4) reference. Blood samples collected from mice 5 min postinjection (pi) of [(111)In]1/2/3/4 without or with phosphoramidon (PA) coinjection were analyzed by RP-HPLC. Biodistribution was conducted in SCID mice bearing A431-CCK2R(+) or AR42J xenografts 4h after administration of [(111)In]1/2/3/4 without or with PA coinjection. Firstly, we observed remarkable increases in the amount of radiopeptides detected intact in the blood of PA-treated mice at 5 min pi compared to controls. Secondly, we noted impressive enhancement of [(111)In]1/2/3 localization in AR42J and A431-CCK2R(+) tumors in mice after PA coinjection. Specifically, the uptake of [(111)In]1 at 4h pi increased from 2.6 ± 0.3%ID/g to 13.3 ± 3.5%ID/g in the AR42J tumors and from 4.3 ± 0.6%ID/g to 20.4 ± 3.6%ID/g in the A431-CCK2R(+) xenografts, with comparable improvements noted for [(111)In]2 and [(111)In]3 as well. Thirdly, renal uptake remained favorably low and unaffected by PA (85%ID/g) increased even further by PA (>140%ID/g). In situ inhibition of NEP represents a promising new tool to enhance the diagnostic efficacy of biodegradable gastrin radioligands in the visualization of CCK2R-positive lesions in man. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Preclinical Evaluation of 18F-PF-05270430, a Novel PET Radioligand for the Phosphodiesterase 2A Enzyme

    Science.gov (United States)

    Chen, Laigao; Nabulsi, Nabeel; Naganawa, Mika; Zasadny, Kenneth; Skaddan, Marc B.; Zhang, Lei; Najafzadeh, Soheila; Lin, Shu-fei; Helal, Christopher J.; Boyden, Tracey L.; Chang, Cheng; Ropchan, Jim; Carson, Richard E.; Villalobos, Anabella

    2016-01-01

    The enzyme phosphodiesterase 2A (PF-05270430) is a potential target for development of novel therapeutic agents for the treatment of cognitive impairments. The goal of the present study was to evaluate the PDE2A ligand 18F-PF-05270430, 4-(3-fluoroazetidin-1-yl)-7-methyl-5-(1-methyl-5-(4-(trifluoromethyl)phenyl)-1H-pyrazol-4-yl)imidazo[1,5-f][1,2,4]triazine, in nonhuman primates. Methods: 18F-PF-05270430 was radiolabeled by 2 methods via nucleophilic substitution of its tosylate precursor. Tissue metabolite analysis in rodents and PET imaging in nonhuman primates under baseline and blocking conditions were performed to determine the pharmacokinetic and binding characteristics of the new radioligand. Various kinetic modeling approaches were assessed to select the optimal method for analysis of imaging data. Results: 18F-PF-05270430 was synthesized in greater than 98% radiochemical purity and high specific activity. In the nonhuman primate brain, uptake of 18F-PF-05270430 was fast, with peak concentration (SUVs of 1.5–1.8 in rhesus monkeys) achieved within 7 min after injection. The rank order of uptake was striatum > neocortical regions > cerebellum. Regional time–activity curves were well fitted by the 2-tissue-compartment model and the multilinear analysis-1 (MA1) method to arrive at reliable estimates of regional distribution volume (VT) and binding potential (BPND) with 120 min of scan data. Regional VT values (MA1) ranged from 1.28 mL/cm3 in the cerebellum to 3.71 mL/cm3 in the putamen, with a BPND of 0.25 in the temporal cortex and 1.92 in the putamen. Regional BPND values estimated by the simplified reference tissue model (SRTM) were similar to those from MA1. Test–retest variability in high-binding regions (striatum) was 4% ± 6% for MA1 VT, 13% ± 6% for MA1 BPND, and 13% ± 7% SRTM BPND, respectively. Pretreatment of animals with the PDE2A inhibitor PF-05180999 resulted in a dose-dependent reduction of 18F-PF-05270430 specific binding, with a half

  19. {sup 177}Lu-PSMA-617 radioligand therapy and outcome in patients with metastasized castration-resistant prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Braeuer, Axel; Grubert, Lena Sophie; Roll, Wolfgang; Schaefers, Michael; Rahbar, Kambiz [University Hospital Muenster, Department of Nuclear Medicine, Muenster (Germany); Schrader, Andres Jan; Boegemann, Martin [University Hospital Muenster, Department of Urology, Muenster (Germany)

    2017-09-15

    Radioligand therapies targeting prostate-specific membrane antigen (PSMA) have been established for the treatment of metastasized castration-resistant prostate cancer (mCRPC) in the last decade and show promising response rates and a favourable toxicity profile. The aim of this study was to evaluate the overall survival (OS) and to identify parameters predicting outcome in mCRPC patients treated with {sup 177}Lu-PSMA-617. Between December 2014 and January 2017, 59 consecutive patients (median age 72 years); interquartile range, (IQR, 66-76 years) with mCRPC, who had been treated with at least one next-generation antihormonal drug as well as chemotherapy, were included in this study. Biochemical response was evaluated using Prostate Cancer Working Group 3 (PCWG3) criteria. Survival was evaluated using Kaplan-Meier estimates and Cox regression proportional hazards model. Toxicity was assessed using Common Toxicity Criteria for Adverse Events (CTCAE). The study was approved by the local ethics committee. The 59 patients were treated with a total of 159 cycles (median 3 cycles, range 1-7) of {sup 177}Lu-PSMA-617 (median dose 6.11 GBq, IQR 5.9-6.3 GBq). The median follow-up was 24 weeks (IQR 15-36 weeks). Follow-up data for at least 12 weeks (PCWG3) were available in 76% (45) of the patients. For outcome results data from all patients treated with at least one cycle were analysed. A decline in prostate-specific antigen (PSA) of ≥50% occurred in 53%, and a decline in PSA of any amount in 91% of patients. The estimated median OS was 32 weeks. An initial alkaline phosphatase (ALP) level <220 U/L and a PSA decline after the first cycle were associated with a longer OS (56 vs. 28 weeks, p < 0.01, and 56 vs. 29 weeks, p = 0.04, respectively). The median estimated PSA progression-free survival (PPFS) was 18 weeks. Only ALP level <220 U/L was significantly associated with a longer PPFS (41 vs. 18 weeks, p < 0.01). A PSA decline after the first cycle of {sup 177}Lu-PSMA-617

  20. The EXIST OIRT

    Science.gov (United States)

    Allen, Branden; Golisano, C.; Kutyrev, A.; Moseley, H.; Grindlay, J.; Hong, J.; EXIST Team

    2009-01-01

    The EXIST Optical / Infrared Telescope (OIRT) has been integrated into the EXIST concept design for the determination GRB redshifts on orbit and to preform follow up source identification and studies following the generation of a trigger from the EXIST high energy telescope (HET). The base OIRT main design has been inherited from the NextView OIRT has been operating in low earth orbit since September of 2007 and is currently being used for the acquisition of geospatial data. After reconfiguration of the instrumentation for astrophysical observations the OIRT will have an angular resolution of 0.15" and a 5'×5' field of view and be sensitive to emission in the range of 0.4 $\\mu$m - 2.2 $\\mu$m. Passive cooling of the tertiary, secondary, and primary mirrors will enable observation into the Ks$ band.

  1. Does Unconscious Racism Exist?

    Science.gov (United States)

    Quillian, Lincoln

    2008-01-01

    This essay argues for the existence of a form of unconscious racism. Research on implicit prejudice provides good evidence that most persons have deeply held negative associations with minority groups that can lead to subtle discrimination without conscious awareness. The evidence for implicit attitudes is briefly reviewed. Criticisms of the…

  2. Synthesis, radiolabeling and in vivo evaluation of [11C](R)-1-[4-[2-(4-methoxyphenyl)phenyl]piperazin-1-yl]-3-(2-pyrazinyloxy)-2-propanol, a potential PET radioligand for the 5-HT7 receptor

    DEFF Research Database (Denmark)

    Hansen, Hanne Demant; Lacivita, Enza; Di Pilato, Pantaleo

    2014-01-01

    In the search for a novel serotonin 7 (5-HT7) receptor PET radioligand we synthesized and evaluated a new series of biphenylpiperazine derivatives in vitro. Among the studied compounds, (R)-1-[4-[2-(4-methoxyphenyl)phenyl]piperazin-1-yl]-3-(2-pyrazinyloxy)-2-propanol ((R)-16), showed the best com...

  3. Serotonin transporters in dopamine transporter imaging: a head-to-head comparison of dopamine transporter SPECT radioligands 123I-FP-CIT and 123I-PE2I

    DEFF Research Database (Denmark)

    Ziebell, Morten; Holm-Hansen, Signe; Thomsen, Gerda

    2010-01-01

    Current SPECT radioligands available for in vivo imaging of the dopamine transporter (DAT) also show affinity for monoamine transporters other than DAT, especially the serotonin transporter (SERT). The effect of this lack of selectivity for in vivo imaging is unknown. In this study, we compared...

  4. Simultaneous determination of protein-free and total positron emission tomography radioligand concentrations in plasma using high-performance frontal analysis followed by mixed micellar liquid chromatography: application to [11C]PBR28 in human plasma.

    Science.gov (United States)

    Nakao, Ryuji; Amini, Nahid; Halldin, Christer

    2013-09-17

    A two-dimensional liquid chromatographic (LC) system was developed for the determination of protein-free and total (free + bound forms) positron emission tomography (PET) radioligand concentrations in plasma by direct plasma injection. The unbound PET radioligand was first analyzed by high-performance frontal analysis using a short gel-filtration column and phosphate buffered saline solution as the mobile phase. All the collected effluent from the gel-filtration column was then transferred to the second dimension consisting of a monolithic C-18 column and mixed (anionic and nonionic surfactants) micellar eluent for determination of the total PET radioligand concentration. The simultaneous analysis of protein binding and radiometabolism of [(11)C]PBR28 was completed within 11 min without any pretreatment of plasma and employing a single analytical system. This system allowed highly sensitive analysis of total [(11)C]PBR28 with a limit of detection (LOD) of 1.6 becquerel (Bq). The LOD for the determination of unbound [(11)C]PBR28 was 21 Bq. Finally, simultaneous measurements of protein binding and radiometabolism of [(11)C]PBR28 in human plasma were achieved for up to 50 min after radioligand administration.

  5. Evaluation in vitro and in animals of a new {sup 11}C-labeled PET radioligand for metabotropic glutamate receptors 1 in brain

    Energy Technology Data Exchange (ETDEWEB)

    Zanotti-Fregonara, Paolo; Liow, Jeih-San; Zoghbi, Sami S.; Clark, David T.; Morse, Cheryl; Pike, Victor W. [National Institute of Mental Health, National Institutes of Health, Molecular Imaging Branch, Bethesda, MD (United States); Barth, Vanessa N.; Rhoads, Emily; Siuda, Edward; Heinz, Beverly A.; Nisenbaum, Eric; Dressman, Bruce; Joshi, Elizabeth; Luffer-Atlas, Debra; Fisher, Matthew J.; Masters, John J.; Goebl, Nancy; Kuklish, Steven L.; Tauscher, Johannes [Eli Lilly and Co., Indianapolis, IN (United States); Innis, Robert B. [National Institute of Mental Health, National Institutes of Health, Molecular Imaging Branch, Bethesda, MD (United States); National Institute of Mental Health, Molecular Imaging Branch, Bethesda, MD (United States)

    2013-02-15

    Two allosteric modulators of the group I metabotropic glutamate receptors (mGluR1 and mGluR5) were evaluated as positron emission tomography (PET) radioligands for mGluR1. LY2428703, a full mGluR1 antagonist (IC{sub 50} 8.9 nM) and partial mGluR5 antagonist (IC{sub 50} 118 nM), and LSN2606428, a full mGluR1 and mGluR5 antagonist (IC{sub 50} 35.3 nM and 10.2 nM, respectively) were successfully labeled with {sup 11}C and evaluated as radioligands for mGluR1. The pharmacology of LY2428703 was comprehensively assessed in vitro and in vivo, and its biodistribution was investigated by liquid chromatography-mass spectrometry/mass spectrometry, and by PET imaging in the rat. In contrast, LSN2606428 was only evaluated in vitro; further evaluation was stopped due to its unfavorable pharmacological properties and binding affinity. {sup 11}C-LY2428703 showed promising characteristics, including: (1) high potency for binding to human mGluR1 (IC{sub 50} 8.9 nM) with no significant affinity for other human mGlu receptors (mGluR2 through mGluR8); (2) binding to brain displaceable by administration of an mGluR1 antagonist; (3) only one major radiometabolite in both plasma and brain, with a negligible brain concentration (with 3.5 % of the total radioactivity in cerebellum) and no receptor affinity; (4) a large specific and displaceable signal in the mGluR1-rich cerebellum with no significant in vivo affinity for mGluR5, as shown by PET studies in rats; and (5) lack of substrate behavior for efflux transporters at the blood-brain barrier, as shown by PET studies conducted in wild-type and knockout mice. {sup 11}C-LY2428703, a new PET radioligand for mGluR1 quantification, displayed promising characteristics both in vitro and in vivo in rodents. (orig.)

  6. Test-retest reliability of the novel 5-HT{sub 1B} receptor PET radioligand [{sup 11}C]P943

    Energy Technology Data Exchange (ETDEWEB)

    Saricicek, Aybala [Yale University, Department of Psychiatry, New Haven, CT (United States); Connecticut Mental Health Center, Abraham Ribicoff Research Facilities, New Haven, CT (United States); Izmir Katip Celebi University, Department of Psychiatry, Izmir (Turkey); Chen, Jason; Ruf, Barbara [Yale University, Department of Psychiatry, New Haven, CT (United States); Planeta, Beata; Labaree, David; Gallezot, Jean-Dominique; Huang, Yiyun [Yale University, PET Center, Department of Diagnostic Radiology, New Haven, CT (United States); Subramanyam, Kalyani; Maloney, Kathleen [Yale University, Department of Psychiatry, New Haven, CT (United States); Connecticut Mental Health Center, Abraham Ribicoff Research Facilities, New Haven, CT (United States); Matuskey, David [Yale University, Department of Psychiatry, New Haven, CT (United States); Connecticut Mental Health Center, Abraham Ribicoff Research Facilities, New Haven, CT (United States); Yale University, PET Center, Department of Diagnostic Radiology, New Haven, CT (United States); Deserno, Lorenz [Charite - Universitaetsmedizin Berlin, Department of Psychiatry and Psychotherapy, Campus Charite Mitte, Berlin (Germany); Max-Planck-Institute for Human Cognitive and Brain Sciences, Leipzig, Berlin (Germany); Neumeister, Alexander [Yale University, Department of Psychiatry, New Haven, CT (United States); Mount Sinai School of Medicine, Department of Psychiatry, New York, NY (United States); VA Connecticut Healthcare System, Clinical Neuroscience Division, VA National Center for PTSD, West Haven, CT (United States); Krystal, John H. [Yale University, Department of Psychiatry, New Haven, CT (United States); Connecticut Mental Health Center, Abraham Ribicoff Research Facilities, New Haven, CT (United States); VA Connecticut Healthcare System, Clinical Neuroscience Division, VA National Center for PTSD, West Haven, CT (United States); Carson, Richard E. [Connecticut Mental Health Center, Abraham Ribicoff Research Facilities, New Haven, CT (United States); Bhagwagar, Zubin [Yale University, Department of Psychiatry, New Haven, CT (United States); Connecticut Mental Health Center, Abraham Ribicoff Research Facilities, New Haven, CT (United States); Bristol-Myers Squibb, Wallingford, CT (United States)

    2014-11-27

    [{sup 11}C]P943 is a novel, highly selective 5-HT{sub 1B} PET radioligand. The aim of this study was to determine the test-retest reliability of [{sup 11}C]P943 using two different modeling methods and to perform a power analysis with each quantification technique. Seven healthy volunteers underwent two PET scans on the same day. Regions of interest (ROIs) were the amygdala, hippocampus, pallidum, putamen, insula, frontal, anterior cingulate, parietal, temporal and occipital cortices, and cerebellum. Two multilinear radioligand quantification techniques were used to estimate binding potential: MA1, using arterial input function data, and the second version of the multilinear reference tissue model analysis (MRTM2), using the cerebellum as the reference region. Between-scan percent variability and intraclass correlation coefficients (ICC) were used to assess test-retest reliability. We also performed power analyses to determine the method that would allow the least number of subjects using within-subject or between-subject study designs. A voxel-wise ICC analysis for MRTM2 BP{sub ND} was performed for the whole brain and all the ROIs studied. Mean percent variability between two scans across regions ranged between 0.4 % and 12.4 % for MA1 BP{sub ND}, 0.5 % and 11.5 % for MA1 BP{sub P}, 16.7 % and 28.3 % for MA1 BP{sub F}, and between 0.2 % and 5.4 % for MRTM2 BP{sub ND}. The power analyses showed a greater number of subjects were required using MA1 BP{sub F} compared with other outcome measures for both within-subject and between-subject study designs. ICC values were the highest using MRTM2 BP{sub ND} and the lowest with MA1 BP{sub F} in ten ROIs. Small regions and regions with low binding had lower ICC values than large regions and regions with high binding. Reliable measures of 5-HT{sub 1B} receptor binding can be obtained using the novel PET radioligand [{sup 11}C]P943. Quantification of 5-HT{sub 1B} receptor binding with MRTM2 BP{sub ND} and with MA1 BP{sub P

  7. Background Studies for EXIST

    Science.gov (United States)

    Wilson, Colleen A.; Pendleton, G. N.; Fishman, G. J.

    2004-01-01

    We present results from a study of the trapped proton and electron background for several orbital inclinations and altitudes. This study includes time dependent effects. In addition we describe a 3 component cosmic background model developed at the University of Southampton, UK. The three components are cosmic diffuse gamma rays, atmospheric albedo gamma rays, and cosmic ray protons. We present examples of how this model was applied to BATSE and discuss its application to EXIST.

  8. Sociodemographic and Substance Use Disorder Determinants of HIV Sexual Risk Behavior in Men and Women in Outpatient Drug Treatment in the NIDA National Drug Abuse Treatment Clinical Trials Network.

    Science.gov (United States)

    Kidd, Jeremy D; Tross, Susan; Pavlicova, Martina; Hu, Mei-Chen; Campbell, Aimee N C; Nunes, Edward V

    2017-06-07

    Sexual risk behavior is now the primary vector of HIV transmission among substance users in the United States with gender as a crucial moderator of risk behavior. The purpose of this study was to examine gender differences in factors (age, race/ethnicity, education) that predict main-partner unprotected sexual occasions (USO) using the unique platform of two parallel NIDA National Drug Abuse Treatment Clinical Trials Network gender-specific safer sex intervention trials. Baseline assessments of male (N = 430) and female (N = 377) participants included demographic characteristics; past 3-month sexual activity; and a diagnostic assessment for alcohol, cocaine/stimulant, and opioid use disorders. Using mixed effects generalized linear modeling of the main outcome USO, two-way interactions of gender with age, race/ethnicity, and education were evaluated and adjusted by alcohol, cocaine/stimulant, or opioid use disorder. When adjusted for alcohol use disorder, the interaction of education and gender was significant. For men, a high school or greater education was significantly associated with more USO compared to men with less than high school. For women, greater than high school education was significantly associated with less USO compared to women with a high school education. None of the other interactions were significant when adjusted for cocaine/stimulant or opioid use disorder. Conclusions/Importance: This study demonstrates gender differences in the relationship of education, alcohol use disorder, and main-partner USO in individuals in substance abuse treatment. This underscores the importance of considering demographic and substance use factors in HIV sexual risk behavior and in crafting prevention messages for this population.

  9. Existing chemicals: international activities.

    Science.gov (United States)

    Purchase, J F

    1989-01-01

    The standards of care used in the protection of the health and safety of people exposed to chemicals has increased dramatically in the last decade. Standards imposed by regulation and those adopted by industry have required a greater level of knowledge about the hazards of chemicals. In the E.E.C., the 6th amendment of the dangerous substances directive imposed the requirement that al new chemicals should be tested according to prescribed programme before introduction on to the market. The development of a European inventory of existing chemicals was an integral part of the 6th amendment. It has now become clear that increased standards of care referred to above must be applied to the chemicals on the inventory list. There is, however, a considerable amount of activity already under way in various international agencies. The OECD Chemicals Programme has been involved in considering the problem of existing chemicals for some time, and is producing a priority list and action programme. The International Programme on Chemical Safety produces international chemical safety cards, health and safety guides and environmental health criteria documents. The international register of potentially toxic compounds (part of UNEP) has prepared chemical data profiles on 990 compounds. The International Agency for Research on Cancer prepared monographs on the carcinogenic risk of chemicals to man. So far 42 volumes have been prepared covering about 900 substances. IARC and IPCS also prepare periodic reports on ongoing research on carcinogenicity or toxicity (respectively) of chemicals. The chemical industry through ECETOC (the European Chemical Industry Ecology and Toxicology Centre) has mounted a major initiative on existing chemicals. Comprehensive reviews of the toxicity of selected chemicals are published (Joint Assessment of Commodity Chemicals). In its technical report no. 30 ECETOC lists reviews and evaluations by major national and international organisations, which provides

  10. Do multiquark hadrons exist

    Energy Technology Data Exchange (ETDEWEB)

    Weinstein, J.; Isgur, N.

    1982-03-08

    The qqq-barq-bar system has been examined by solving the four-particle Schroedinger equation variationally. The main findings are that: (1) qqq-barq-bar bound states normally do not exist, (2) the cryptoexotic 0/sup + +/ sector of this system with KK-bar quantum numbers is probably the only exception to (1) and its bound states can be identified with the S* and delta just below KK-bar threshold, (3) qqq-barq-bar bound states provide a model for the weak binding and color-singlet clustering observed in nuclei, and (4) there is no indication that this system has strong resonances.

  11. Synthesis and evaluation of the racemate and individual enantiomers of C-11 labeled methylphenidate as radioligands for the presynaptic dopaminergic neuron

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Y.S.; Fowler, J.S.; Volkow, N.D. [Brookhaven National Lab., Upton, NY (United States)] [and others

    1994-05-01

    Methylphenidate (MP, ritalin) is a psychostimulant drug widely used to treat attention deficit hyperactivity disorder and narcolepsy. Its therapeutic properties are attributed to inhibition of the dopamine (DA) transporter enhancing synaptic DA. MP has two chiral centers and is marketed as the dl-threo racemic form. However, its pharmacological activity is believed due solely to the d-enantiomer. We have synthesized [{sup 11}C]d,l-threo-methylphenidate ([{sup 11}C]MP) in order to examine its pharmacokinetics in vivo and to examine its suitability as a radioligand for PET studies of the presynaptic DA neuron. [{sup 11}C]MP was prepared by O-{sup 11}C-alkylation of a protected derivative of ritalinic acid with labeled methyl iodide. Serial studies at baseline and after treatment with methylphenidate (0.5 mg/kg, 20 min prior); GBR 12909 (1.5 mg/kg; 30 min prior); tomoxetine (1.5 mg/kg, 20 min prior) and citalopram (2.0 mg/kg, 30 min prior) were performed to assess non-specific binding and binding to the DA, norepinephrine and serotonin transporters respectively. Only MP and GBR 12909 changed the SR/CB distribution volume ratio (decrease of 38 and 37% respectively) demonstrating selectivity for DA transporters over other monoamine transporters. We then pursued the synthesis of enantiomerically pure C-{sup 11} labeled d- and l-MP by using enantiomerically pure protected d- and l-ritalinic acids as precursors. A striking difference in SR/CB ratio (3.3 and 1.1 for d- and l-respectively at 1 hr. after i.v. injections) strongly suggests that the pharmacological specificity of MP resides entirely in the d-isomer and the binding of l-isomer was mostly non-specific. Further evaluations are underway. Radioligand reversibility, selectivity and the fact that MP is an approved drug are advantages of using [{sup 11}C]MP.

  12. Repowering existing plants

    Energy Technology Data Exchange (ETDEWEB)

    Steazel, W.C.; Sopocy, D.M.; Pace, S.E.

    1998-07-01

    Increased competition among power generation companies, changes in generating system load requirements, lower allowable plant emissions, and changes in fuel availability and cost accentuate the need to closely assess the economics and performances of older electric generation units. Generally, decisions must be made as to whether these units should be retired and replaced with new generation capacity, whether capacity should be purchased from other generation companies, or if these existing units should be repowered. These decisions usually require the evaluation of many factors including; environmental discharge limits, permitting requirements, generating load demand increases, options for increasing the benefits of using existing facilities (e.g.; increasing efficiency and output), fuel cost increases, transmission requirements and access, optional plant designs. Many of these factors need to be used in the analysis based on a range rather than one specific value to test for changes in the selection of the best option because of future uncertainties. Usually complicated analysis results because of all the factors involved. Computer products that integrate performance and financial analysis can provide substantial value by enabling the user to evaluate the applicable plant options and range of input. The SOAPP (State-of-the-Art Power Plant) family of software products provides easy to use tools for rapid, thorough and economical evaluation of plant option. Repowering evaluation methodology typically used in the US, technology options, and available SOAPP repowering software are reviewed in this paper.

  13. Existence of Minkowski space

    CERN Document Server

    Wagner, Serge

    2016-01-01

    Physics textbooks present Minkowski space as an almost pure mathematical construct, without any explicit restriction on a domain where it is applicable in physics. Meanwhile, its physical meaning cannot but follow the same premises as those which underlies the special relativity theory: motion of free point particles and propagation of electromagnetic waves. However, the common formalism of coordinate transformations between any two inertial frames appears too ponderous to infer the existence of Minkowski space. For this reason, the time dilation and retardation, the contraction of the length along and the spatial invariance across the direction of relative motion of two frames are presented in a coordinate-free manner. This results in the transformation between two frames in the form of relationships between the time moments and the components of the position vector of a given event, along and across the directions of the frames' motion. The obtained transformation rules for the components of the position ve...

  14. Lebesgue Sets Immeasurable Existence

    Directory of Open Access Journals (Sweden)

    Diana Marginean Petrovai

    2012-12-01

    Full Text Available It is well known that the notion of measure and integral were released early enough in close connection with practical problems of measuring of geometric figures. Notion of measure was outlined in the early 20th century through H. Lebesgue’s research, founder of the modern theory of measure and integral. It was developed concurrently a technique of integration of functions. Gradually it was formed a specific area todaycalled the measure and integral theory. Essential contributions to building this theory was made by a large number of mathematicians: C. Carathodory, J. Radon, O. Nikodym, S. Bochner, J. Pettis, P. Halmos and many others. In the following we present several abstract sets, classes of sets. There exists the sets which are not Lebesgue measurable and the sets which are Lebesgue measurable but are not Borel measurable. Hence B ⊂ L ⊂ P(X.

  15. EXIST Perspective for SFXTs

    Science.gov (United States)

    Ubertini, Pietro; Sidoli, L.; Sguera, V.; Bazzano, A.

    2009-12-01

    Supergiant Fast X-ray Transients (SFXTs) are one of the most interesting (and unexpected) results of the INTEGRAL mission. They are a new class of HMXBs displaying short hard X-ray outbursts (duration less tha a day) characterized by fast flares (few hours timescale) and large dinamic range (10E3-10E4). The physical mechanism driving their peculiar behaviour is still unclear and highly debated: some models involve the structure of the supergiant companion donor wind (likely clumpy, in a spherical or non spherical geometry) and the orbital properties (wide separation with eccentric or circular orbit), while others involve the properties of the neutron star compact object and invoke very low magnetic field values (B 1E14 G, magnetars). The picture is still highly unclear from the observational point of view as well: no cyclotron lines have been detected in the spectra, thus the strength of the neutron star magnetic field is unknown. Orbital periods have been measured in only 4 systems, spanning from 3.3 days to 165 days. Even the duty cycle seems to be quite different from source to source. The Energetic X-ray Imaging Survey Telescope (EXIST), with its hard X-ray all-sky survey and large improved limiting sensitivity, will allow us to get a clearer picture of SFXTs. A complete census of their number is essential to enlarge the sample. A long term and continuous as possible X-ray monitoring is crucial to -(1) obtain the duty cycle, -(2 )investigate their unknown orbital properties (separation, orbital period, eccentricity),- (3) to completely cover the whole outburst activity, (4)-to search for cyclotron lines in the high energy spectra. EXIST observations will provide crucial informations to test the different models and shed light on the peculiar behaviour of SFXTs.

  16. Mauriac syndrome still exists.

    Science.gov (United States)

    Dias, Joana; Martins, Sofia; Carvalho, Susana; Marques, Olinda; Antunes, Ana

    2013-05-01

    Mauriac syndrome (MS) is a rare complication of type 1 diabetes mellitus (DM1). It is related to low insulin concentrations and is less common since longer-acting insulins became available. It is characterized by hepatomegaly, growth and puberty delay, and the presence of elevated transaminases and serum lipids. The aim of this study was to describe the patients from a pediatric diabetic population that fulfill the criteria of MS. A retrospective analysis of the pediatric diabetic population with diagnostic criteria of MS currently followed at Hospital de Braga, was performed. From a population of 91 patients with DM1 18 years, 6 patients with the criteria for MS were identified: 5 girls, and 1 boy. The age at presentation was 13-17 years, with a minimum interval between DM1 diagnosis and MS criteria of 4 years. All the patients were prescribed intensive insulin therapy (median daily insulin dose: 0.88 U/kg). All had a previous history of poor glycemic control before the diagnosis of MS with glycated hemoglobin (HbA1c) between 8.8 and 12.9%. Increase of hepatic enzymes was present in all the patients; 4 of them had associated hepatomegaly. All the girls presented puberty delay and cushingoid features. None of the patients presented short stature and 5 of them presented mixed dyslipidemia. Although MS is an ancient entity described in DM1, it still exists, particularly in adolescent females. Being aware of MS is of extreme importance since most of the clinical features are reversible with better glycemic control. Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.

  17. El uso de bases de datos curatoriales para reconstruir la historia del conocimiento taxonómico: un ejemplo con papiliónidas y piéridas mexicanas (Insecta: Lepidoptera Use of curatorial data bases as an element to reconstruct taxonomic knowdlege: an example with Mexican papilionids and pierids (Insecta: Lepidoptera

    Directory of Open Access Journals (Sweden)

    Leonor Oñate-Ocaña

    2010-08-01

    Full Text Available El objetivo de este trabajo es conocer la cronología de la información sobre mariposas papiliónidas y piéridas de México, así como los patrones de recolección y los recolectores más destacados a partir de una base de datos curatoriales y fuentes bibliográficas. La base cuenta con 40 752 registros de ejemplares albergados en 12 museos y/o registrados en 145 fuentes bibliográficas. Se destaca el alcance que tiene el uso de las bases de datos curatoriales en la reconstrucción histórica del conocimiento de un grupo, tomando como ejemplo las mariposas papilónidas y piéridas mexicanas.The aim of this paper is to determine the chronology of the information on papilionid and pierid butterflies of Mexico, as well as the patterns of collection and who were the most active collectors from a curatorial databases and bibliography. The database has record of 40 752 records of individuals housed in 12 museums and/or recorded in 145 bibliographic sources. The relevance of this work is to highlight the amplitude of curatorial databases for the reconstruction of the historical knowledge of a biological group, taking Mexican papilionid and pierid butterflies as an example.

  18. Evaluation of radioiodinated (2S,{alpha}S)-2-({alpha}-(2-iodophenoxy)benzyl)morpholine as a radioligand for imaging of norepinephrine transporter in the heart

    Energy Technology Data Exchange (ETDEWEB)

    Kiyono, Yasushi [Biomedical Imaging Research Center, University of Fukui, Fukui 910-1193 (Japan); Radioisotopes Research Laboratory, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Kyoto 606-8507 (Japan)], E-mail: ykiyono@u-fukui.ac.jp; Sugita, Taku [Department of Pathofunctional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501 (Japan); Ueda, Masashi [Radioisotopes Research Laboratory, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Kyoto 606-8507 (Japan); Kawashima, Hidekazu [Department of Nuclear Medicine and Diagnostic Imaging, Graduate School of Medicine, Kyoto University, Kyoto 606-8507 (Japan); Kanegawa, Naoki; Kuge, Yuji [Department of Pathofunctional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501 (Japan); Fujibayashi, Yasuhisa [Biomedical Imaging Research Center, University of Fukui, Fukui 910-1193 (Japan); Saji, Hideo [Department of Pathofunctional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501 (Japan)

    2008-02-15

    Introduction: The norepinephrine transporter (NET) is located presynaptically on noradrenergic nerve terminals and plays a critical role in the regulation of the synaptic norepinephrine (NE) concentration via the reuptake of NE. Changes in NET have been recently reported in several cardiac failures. Therefore, a NET-specific radioligand is useful for in vivo assessment of changes in NET density in various cardiac disorders. Recently, we developed a radioiodinated reboxetine analogue, (2S,{alpha}S)-2-({alpha}-(2-iodophenoxy)benzyl)morpholine ((S,S)-IPBM), for NET imaging. In the current study, we assessed the applicability of radioiodinated (S,S)-IPBM to NET imaging in the heart. Methods: The NET affinity and selectivity were measured from the ability to displace specific [{sup 3}H]nisoxetine and (S,S)-[{sup 125}I]IPBM binding to rat heart membrane, respectively. To evaluate the distribution of (S,S)-[{sup 125}I]IPBM in vivo, biodistribution experiment was performed in rats. With the use of several monoamine transporter binding agents, pharmacological blocking experiments were performed in rats. Results: In vitro binding assays showed that the affinity of (S,S)-IPBM to NET was similar to those of the well-known NET-specific binding agents, nisoxetine and desipramine. Furthermore, (S,S)-[{sup 125}I]IPBM binding was inhibited by nisoxetine and desipramine, but not by dopamine or serotonin transporter binding agents. These data indicated that (S,S)-IPBM had high affinity and selectivity for NET in vitro. Biodistribution studies in rats showed rapid and high uptake of (S,S)-[{sup 125}I]IPBM by the heart and rapid clearance from the blood. The heart-to-blood ratio was 31.9 at 180 min after the injection. The administration of nisoxetine and desipramine decreased (S,S)-[{sup 125}I]IPBM accumulation in the heart, but injection of fluoxetine and GBR12909 had little influence. Conclusions: Radioiodinated (S,S)-IPBM is a potential radioligand for NET imaging in the heart.

  19. Synthesis and preliminary biological evaluation of radiolabeled 5-BDBD analogs as new candidate PET radioligands for P2X4 receptor.

    Science.gov (United States)

    Wang, Min; Gao, Mingzhang; Meyer, Jill A; Peters, Jonathan S; Zarrinmayeh, Hamideh; Territo, Paul R; Hutchins, Gary D; Zheng, Qi-Huang

    2017-07-15

    P2X4 receptor has become an interesting molecular target for treatment and PET imaging of neuroinflammation and associated brain diseases such as Alzheimer's disease. This study reports the first design, synthesis, radiolabeling and biological evaluation of new candidate PET P2X4 receptor radioligands using 5-BDBD, a specific P2X4 receptor antagonist, as a scaffold. 5-(3-Hydroxyphenyl)-1-[11C]methyl-1,3-dihydro-2H-benzofuro[3,2-e][1,4]diazepin-2-one (N-[11C]Me-5-BDBD analog, [11C]9) and 5-(3-Bromophenyl)-1-[11C]methyl-1,3-dihydro-2H-benzofuro[3,2-e][1,4]diazepin-2-one (N-[11C]Me-5-BDBD, [11C]8c) were prepared from their corresponding desmethylated precursors with [11C]CH3OTf through N-[11C]methylation and isolated by HPLC combined with SPE in 30-50% decay corrected radiochemical yields with 370-1110GBq/µmol specific activity at EOB. 5-(3-[18F]Fluorophenyl)-1,3-dihydro-2H-benzofuro[3,2-e][1,4]diazepin-2-one ([18F]F-5-BDBD, [18F]5a) and 5-(3-(2-[18F]fluoroethoxy)phenyl)-1,3-dihydro-2H-benzofuro[3,2-e][1,4]diazepin-2-one ([18F]FE-5-BDBD, [18F]11) were prepared from their corresponding nitro- and tosylated precursors by nucleophilic substitution with K[18F]F/Kryptofix 2.2.2 and isolated by HPLC-SPE in 5-25% decay corrected radiochemical yields with 111-740GBq/µmol specific activity at EOB. The preliminary biological evaluation of radiolabeled 5-BDBD analogs indicated these new radioligands have similar biological activity with their parent compound 5-BDBD. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Effects of [3H]-BIDN, a novel bicyclic dinitrile radioligand for GABA-gated chloride channels of insects and vertebrates

    Science.gov (United States)

    Rauh, James J; Benner, Eric; Schnee, Michael E; Cordova, Daniel; Holyoke, Caleb W; Howard, Michael H; Bai, Donglin; Buckingham, Steven D; Hutton, Michael L; Hamon, Alain; Roush, Richard T; Sattelle, David B

    1997-01-01

    The radiolabelled bicyclic dinitrile, [3H]-3,3-bis-trifluoromethyl-bicyclo[2.2.1]heptane-2,2-dicarbonitrile ([3H]-BIDN), exhibited, specific binding of high affinity to membranes of the southern corn rootworm (Diabrotica undecimpunctata howardi) and other insects. A variety of γ-aminobutyric acid (GABA) receptor convulsants, including the insecticides heptachlor (IC50, 35±3 nM) and dieldrin (IC50, 93±7 nM), displaced [3H]-BIDN from rootworm membranes. When tested at 100 μM, 1-(4-ethynylphenyl)-4-n-propyl-2,6,7-trioxabicyclo[2.2.2]octane(EBOB), 4-t-butyl-2,6,7-trioxa-1-phosphabicyclo[2.2.2]octane-1-thione (TBPS), 1-phenyl-4-t-butyl-2,6,7-trioxabicyclo[2.2.2]octane (TBOB) and picrotoxin failed to displace 50% of [3H]-BIDN binding to rootworm membranes indicating that the bicyclic dinitrile radioligand probes a site distinct from those identified by other convulsant radioligands. Dissociation studies showed that dieldrin, ketoendrin, toxaphene, heptachlor epoxide and α and β endosulphan displace bound [3H]-BIDN from rootworm membranes by a competitive mechanism. Rat brain membranes were also shown to possess a population of saturable, specific [3H]-BIDN binding sites, though of lower affinity than in rootworm and with a different pharmacological profile. Of the insecticidal GABAergic convulsants that displaced [3H]-BIDN from rootworm, cockroach (Periplaneta americana) and rat brain membranes, many were more effective in rootworm. Functional GABA-gated chloride channels of rootworm nervous system and of cockroach nerve and muscle were blocked by BIDN, whereas cockroach neuronal GABAB receptors were unaffected. Expression in Xenopus oocytes of either rat brain mRNA, or cDNA-derived RNA encoding a GABA receptor subunit (Rdl) that is expressed widely in the nervous system of Drosophila melanogaster resulted in functional, homo-oligomeric GABA receptors that were blocked by BIDN. Thus, BIDN probes a novel site on GABA-gated Cl− channels to which a number of

  1. Preclinical evaluation of [{sup 18}F]2FNQ1P as the first fluorinated serotonin 5-HT{sub 6} radioligand for PET imaging

    Energy Technology Data Exchange (ETDEWEB)

    Becker, Guillaume [Universite Claude Bernard Lyon 1, CNRS INSERM, Lyon Neuroscience Research Center, Lyon (France); Hospices Civils de Lyon, Lyon (France); Colomb, Julie [Universite Claude Bernard Lyon 1, CNRS, Institute of Chemistry and Biochemistry, Villeurbanne (France); Sgambato-Faure, Veronique; Tremblay, Leon [Universite Claude Bernard Lyon 1, CNRS, Cognitive Neuroscience Center, Bron (France); Billard, Thierry [Universite Claude Bernard Lyon 1, CNRS, Institute of Chemistry and Biochemistry, Villeurbanne (France); CERMEP-Imaging Platform, Groupement Hospitalier Est, Lyon (France); Zimmer, Luc [Universite Claude Bernard Lyon 1, CNRS INSERM, Lyon Neuroscience Research Center, Lyon (France); Hospices Civils de Lyon, Lyon (France); CERMEP-Imaging Platform, Groupement Hospitalier Est, Lyon (France)

    2014-10-21

    Brain serotonin 6 receptor (5-HT{sub 6}) is one of the most recently identified serotonin receptors. It is a potent therapeutic target for psychiatric and neurological diseases, e.g. schizophrenia and Alzheimer's disease. Since no specific fluorinated radioligand has yet been successfully used to study this receptor by positron emission tomography (PET) neuroimaging, the objective of the present study was to study the first 5-HT{sub 6} {sup 18}F-labelled radiotracer. 2FNQ1P, inspired by the quinolone core of a previous radiotracer candidate, GSK215083, was selected according its 5-HT{sub 6} affinity and selectivity and was radiolabelled by {sup 18}F nucleophilic substitution. The cerebral distribution of [{sup 18}F]2FNQ1P was studied in vivo in rats, cats and macaque monkeys. The chemical and radiochemical purities of [{sup 18}F]2FNQ1P were >98 %. In rats, in vitro competition with the 5-HT{sub 6} antagonist, SB258585, revealed that the radioligand was displaced dose dependently. Rat microPET studies showed low brain uptake of [{sup 18}F]2FNQ1P, reversed by the P-glycoprotein inhibitor, cyclosporin. On the contrary, PET scans in cats showed good brain penetration and specific striatal binding blocked after pretreatment with unlabelled 2FNQ1P. PET scans in macaque monkeys confirmed high specific binding in both cortical and subcortical regions, specifically decreased by pretreatment with the 5-HT{sub 6} receptor antagonist, SB258585. 2FNQ1P was initially selected because of its suitable characteristics for 5-HT{sub 6} receptor probing in vitro in terms of affinity and specificity. Although in vivo imaging in rats cannot be considered as predictive of the clinical characteristics of the radiotracer, [{sup 18}F]2FNQ1P appeared to be a suitable 5-HT{sub 6} PET tracer in feline and primate models. These preclinical results encourage us to pursue the clinical development of this first fluorinated 5-HT{sub 6} PET radiotracer. (orig.)

  2. Synthesis and evaluation of 2-({sup 18}F)fluoro-A85380, a radioligand for {alpha}{sub 4}{beta}{sub 2} nicotinic acetylcholine receptor imaging

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Eun Kyoung; Choe, Yearn Seong; Kim, Sang Eun; Hwang, Sae Hwan; Paik, Jin Young; Choi, Yong; Lee, Kyung Han; Kim, Byung Tae [School of Medicine, Sungkyunkwan Univ., Seoul (Korea, Republic of)

    2002-08-01

    Nicotinic acetylcholine receptors (nAChRs), which mediate excitatory neurotransmission, are known to participate in various neurophysiological functions. Severe losses of nAChRs have been noted in Alzheimer's and Parkinson's diseases. Therefore, noninvasive and quantitative imaging of nAChRs would offer a better understanding on the function of these receptors. In this study, 2 -({sup 18}F)fluoro-A85380 ([{sup 18}F]1), an {alpha}{sub 4}{beta}{sub 2} nAChRs radioligand, was prepared using one HPLC purification and evaluated in mouse brain, and the results were compared with those in the literature. ({sup 18}F)1 was prepared by ({sup 18}F)fluorination of the iodo precursor followed by acidic deprotection and then purified by HPLC. Tissue distribution studies were performed in mouse brain at the indicated time points and the result was expressed as %ID/g. Inhibition studies were also carried out with pretreatment of various ligands. One HPLC purification method gave the desired product in 15-20% radiochemical yield and with high specific activity (38-55 GBq/{mu}mol). Tissue distribution studies showed that ({sup 18}F)1 specifically labeled nAChRs in mouse brain with a high thalamus to cerebellum uptake ratio (13.8 at 90 min). Inhibition studies demonstrated selective binding of ({sup 18}F)1 to nAChRs, blocking the uptake of the ({sup 18}F) 1 in nAChR-rich regions by selective ligands such as cytisine and nicotine which are well-known nAChRs agonists. This study demonstrated that the ({sup 18}F)1 produced by the method using one HPLC purification gave the results similar to those reported in the lieterature. Therefore, this synthetic method can be readily applied to the routine preparation of ({sup 18}F)1, a PET radioligand for {alpha}{sub 4}{beta}{sub 2} nAChRs imaging.

  3. Synthesis and in vitro evaluation of no-carrier-added 2-(3-(4-(4-[{sup 18}F]fluorobenzyl)piperazin-1-yl)propyl)benzo[d]thiazole, a potential dopamine D{sub 4} receptor radioligand

    Energy Technology Data Exchange (ETDEWEB)

    Li, Gu-Cai; Zhang, Ru [Hunan Institute of Engineering, Hunan Xiangtan (China). College of Chemistry and Chemical Engineering; Xia, Jiao-yun [Changsha Univ. of Science and Technology (China). School of Chemistry and Biology Engineering

    2016-07-01

    The dopamine D{sub 4} receptor has been shown to play important roles in some central nervous system pathologies. Specific radioligands for the D{sub 4} receptor may be useful to understand the function of the D{sub 4} receptor and its correlations with various disorders. 2-(3-(4-(4-[{sup 18}F]Fluorobenzyl)piperazin-1-yl)propyl)benzo[d]thiazole ([{sup 18}F]4) was synthesized through a one-pot two-step procedure with total yield 18.6% (decay corrected). The specific activity of the radioligand was 112 GBq/μmol and its radiochemical purity was >95.0%. Its affinity and selectivity for dopamine D{sub 2}-like receptors were measured through in vitro receptor binding evaluation and the K{sub i} value for the D{sub 4} receptor was determined to be 2.9±0.2 nM, and its selectivity for the dopamine D{sub 4} receptor is 709-fold versus D{sub 2long} receptor, 823-fold versus D{sub 3} receptor. The partition coefficient (Log D) of it was determined to be 2.6±0.1 through octanol-water partition experiment. The ligand presents desirable combination of lipophilicity, affinity and selectivity for the dopamine D{sub 4} receptor. The results suggested that the radioligand shows promises for the in vivo study of the dopamine D{sub 4} receptor.

  4. Effects of anesthesia and species on the uptake or binding of radioligands in vivo in the Göttingen minipig

    DEFF Research Database (Denmark)

    Alstrup, Aage Kristian Olsen; Landau, Anne M.; Holden, James E.

    2013-01-01

    Progress in neuroscience research often involves animals, as no adequate alternatives exist to animal models of living systems. However, both the physiological characteristics of the species used and the effects of anesthesia raise questions of common concern. Here, we demonstrate the confounding...

  5. Specific in vivo binding to the norepinephrine transporter demonstrated with the PET radioligand, (S,S)-[{sup 11}C]MeNER

    Energy Technology Data Exchange (ETDEWEB)

    Schou, Magnus; Halldin, Christer E-mail: christer.halldin@ks.se; Sovago, Judit; Pike, Victor W.; Gulyas, Balazs; Mozley, P. David; Johnson, David P.; Hall, Haakan; Innis, Robert B.; Farde, Lars

    2003-10-01

    (S,S)-2-({alpha}-(2-Methoxyphenoxy)benzyl)morpholine (MeNER), an O-methyl analog of the selective and potent norepinephrine transporter (NET) inhibitor, (S,S)-reboxetine, and its less active enantiomer, (R,R)-MeNER, have each been radiolabeled by O-methylation of their corresponding phenolic precursors in good yields from [{sup 11}C]methyl iodide or [{sup 11}C]methyl triflate. Radiochemical purities were >99% and specific radioactivity at time of injection was about 74 GBq/{mu}mol. Autoradiographic examination of (S,S)-[{sup 11}C]MeNER binding to human brain slices post mortem indicated specific binding in a brain region including the locus coeruleus. PET examination of both [{sup 11}C]MeNER enantiomers in a cynomolgus monkey demonstrated a higher specific binding of the (S,S)-enantiomer with ratios of 1.4-1.6 in the lower brainstem, mesencephalon and thalamus to striatum. Pretreatment with the NET ligand, desipramine, decreased the specific binding of (S,S)-[{sup 11}C]MeNER. Labeled metabolites of [{sup 11}C]MeNER were all more polar. (S,S)-[{sup 11}C]MeNER is a good lead compound in the search for a selective radioligand for quantitation of NET in the human brain in vivo.

  6. Identification and Profiling of a Selective and Brain Penetrant Radioligand for in Vivo Target Occupancy Measurement of Casein Kinase 1 (CK1) Inhibitors.

    Science.gov (United States)

    Wager, Travis T; Galatsis, Paul; Chandrasekaran, Ramalakshmi Y; Butler, Todd W; Li, Jianke; Zhang, Lei; Mente, Scot; Subramanyam, Chakrapani; Liu, Shenping; Doran, Angela C; Chang, Cheng; Fisher, Katherine; Grimwood, Sarah; Hedde, Joseph R; Marconi, Michael; Schildknegt, Klaas

    2017-09-20

    To enable the clinical development of our CNS casein kinase 1 delta/epsilon (CK1δ/ε) inhibitor project, we investigated the possibility of developing a CNS positron emission tomography (PET) radioligand. For this effort, we focused our design and synthesis efforts on the initial CK1δ/ε inhibitor HTS hits with the goal of identifying a compound that would fulfill a set of recommended PET ligand criteria. We identified [3H]PF-5236216 (9) as a tool ligand that meets most of the key CNS PET attributes including high CNS MPO PET desirability score and kinase selectivity, CNS penetration, and low nonspecific binding. We further used [3H]-9 to determine the binding affinity for PF-670462, a literature CK1δ/ε inhibitor tool compound. Lastly, [3H]-9 was used to measure in vivo target occupancy (TO) of PF-670462 in mouse and correlated TO with CK1δ/ε in vivo pharmacology (circadian rhythm modulation).

  7. Characterisation of [11C]PR04.MZ in Papio anubis baboon: A selective high-affinity radioligand for quantitative imaging of the dopamine transporter

    Energy Technology Data Exchange (ETDEWEB)

    Riss P. J.; Fowler J.; Riss, P.J.; Hooker, J.M.; Shea, C.; Xu, Y.; Carter, P.; Warner, D.; Ferrari V.; Kim, S.W.; Aigbirhio, F.I.; Fowler, J.S.; Roesch, F.

    2011-10-25

    N-(4-fluorobut-2-yn-1-yl)-2{beta}-carbomethoxy-3{beta}-(4{prime}-tolyl)nortropane (PR04.MZ, 1) is a PET radioligand for the non-invasive exploration of the function of the cerebral dopamine transporter (DAT). A reliable automated process for routine production of the carbon-11 labelled analogue [{sup 11}C]PR04.MZ ([{sup 11}C]-1) has been developed using GMP compliant equipment. An adult female Papioanubis baboon was studied using a test-retest protocol with [{sup 11}C]-1 in order to assess test-retest reliability, metabolism and CNS distribution profile of the tracer in non-human primates. Blood sampling was performed throughout the studies for determination of the free fraction in plasma (fP), plasma input functions and metabolic degradation of the radiotracer [{sup 11}C]-1. Time-activity curves were derived for the putamen, the caudate nucleus, the ventral striatum, the midbrain and the cerebellum. Distribution volumes (VT) and non-displaceable binding potentials (BPND) for various brain regions and the blood were obtained from kinetic modelling. [{sup 11}C]-1 shows promising results as aselective marker of the presynaptic dopamine transporter. With the reliable visualisation of the extra-striatal dopaminergic neurons and no indication on labelled metabolites, the tracer provides excellent potential for translation into man.

  8. Fish somatostatin sst3 receptor: comparison of radioligand and GTPgammaS binding, adenylate cyclase and phospholipase C activities reveals different agonist-dependent pharmacological signatures.

    Science.gov (United States)

    Siehler, S; Nunn, C; Zupanc, G K H; Hoyer, D

    2005-01-01

    1 The fish somatostatin receptor 3 (fsst3) is one of the few somatostatin (SRIF) receptors cloned from a non-mammalian species so far. Here we extended our earlier characterization of this receptor by investigating the guanine nucleotide sensitivity of agonist radioligand binding at the fsst3 receptor recombinantly expressed in CCL39 (Chinese hamster lung fibroblast) cells. Further, we measured somatostatin (SRIF) and cortistatin (CST) analogues stimulated GTPgammaS binding, inhibition of forskolin-stimulated adenylate cyclase (FSAC) and stimulation of phospholipase C (PLC) activities. The present transductional data were then compared with previous radioligand binding and/or second messenger features determined for fsst3 and/or human SRIF receptors (hsst2, hsst3 and hsst5). 2 The GTP analogue guanylylimidodiphosphate (GppNHp) inhibited binding of [125I]CGP 23996 and [125I][Tyr3octreotide by 72 and 83% suggesting preferential labelling of G-protein-coupled fsst3 receptors. By contrast, [125I]LTT-SRIF28 and [125I][Tyr10]CST14 binding was rather GppNHp insensitive (42 and 35% inhibition) suggesting labelling of both coupled and non-coupled receptor states. These results might explain the apparent higher receptor densities determined in saturation experiments with [125I]LTT-SRIF28 and [125I][Tyr10]CST14 (4470 and 4030 fmol mg(-1)) compared with [125I]CGP 23996 and [125I][Tyr3]octreotide (3420 and 1520 fmol mg(-1)). 3 SRIF14 (10 microm)-stimulated specific [35S]GTPgammaS binding by three-fold; SRIF28 and octreotide displayed full agonism, whereas most other ligands displayed 60-80% intrinsic activity compared with SRIF14. SRIF14 and SRIF28 inhibited forskolin-stimulated AC (FSAC) activity by 60%; all tested ligands except BIM 23056 inhibited FSAC with comparable high intrinsic activities. SRIF14 stimulated PLC activity five- to six-fold, as determined by measuring total [3H] IP(x) accumulation; it was rather insensitive to pertussis toxin (PTX, 100 ng ml(-1), 21

  9. Selectivity of muscarinic antagonists in radioligand and in vivo experiments for the putative M1, M2 and M3 receptors.

    Science.gov (United States)

    Doods, H N; Mathy, M J; Davidesko, D; van Charldorp, K J; de Jonge, A; van Zwieten, P A

    1987-07-01

    In the present study we investigated the nature of the muscarinic receptors present in the hippocampus, sympathetic ganglia, atria and salivary glands of the rat. The heterogeneity of the muscarinic receptors was examined both in vivo and in radioligand binding experiments. To study whether the receptors present in the investigated tissues are indeed distinct subtypes we determined the potencies of antagonists in both systems. It is proposed that there are three different binding sites present in hippocampal, atrial and submandibular membranes and we suggest to classify them as M1, M2 and M3, respectively. Both in vivo and in vitro pirenzepine appears to possess high affinity for M1 receptors, whereas 4-diphenylacetoxy-N-methylpiperidine methobromide and dicyclomine show high affinity for both M1 and M3 receptors. AF-DX 116 (11-2[[2-[(diethylamino)methyl]-1-piperidinyl]acetyl]-5, 11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepine-6-one) displayed high affinity for M2 receptors.

  10. Receptor binding characterization of the benzodiazepine radioligand sup 125 I-Ro16-0154: Potential probe for SPECT (Single Photon Emission Computed Tomography) brain imaging

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, E.W.; Woods, S.W.; Zoghbi, S.; Baldwin, R.M.; Innis, R.B. (Yale Univ., West Haven, CT (USA)); McBride, B.J. (Medi-Physics, Inc., Emeryville, CA (USA))

    1990-01-01

    The binding of an iodinated benzodiazepine (BZ) radioligand has been characterized, particularly in regard to its potential use as a neuroreceptor brain imaging agent with SPECT (Single Photon Emission Computed Tomography). Ro16-0154 is an iodine-containing BZ antagonist and a close analog of Ro15-1788. In tissue homogenates prepared from human and monkey brain, the binding of {sup 125}I-labeled Ro16-0154 was saturable, of high affinity, and had high ratios of specific to non-specific binding. Physiological concentrations of NaCl enhanced specific binding approximately 15% compared to buffer without this salt. Kinetic studies of association and dissociation demonstrated a temperature dependent decrease in affinity with increasing temperature. Drug displacement studies confirmed that {sup 125}I-Ro16-0154 binds to the central type BZ receptor: binding is virtually identical to that of {sup 3}H-Ro15-1788 except that {sup 125}I-Ro16-0154 shows an almost 10 fold higher affinity at 37{degree}C. These in vitro results suggest that {sup 123}I-labeled Ro16-0154 shows promise as a selective, high affinity SPECT probe of the brain's BZ receptor.

  11. Existence and Detection of Fireballs,

    Science.gov (United States)

    An attempt is made to analyze critically the experimental proofs indicating the existence of fireballs. Some ideas are presented on methods of the...properties of fireballs if their existence will be checked by other methods. (Author)

  12. PET imaging evaluation of [{sup 18}F]DBT-10, a novel radioligand specific to α{sub 7} nicotinic acetylcholine receptors, in nonhuman primates

    Energy Technology Data Exchange (ETDEWEB)

    Hillmer, Ansel T.; Zheng, Ming-Qiang; Li, Songye; Lin, Shu-fei; Holden, Daniel; Labaree, David; Ropchan, Jim; Carson, Richard E.; Huang, Yiyun [Yale University, PET Center, 801 Howard Ave, PO Box 208048, New Haven, CT (United States); Scheunemann, Matthias; Teodoro, Rodrigo; Deuther-Conrad, Winnie; Brust, Peter [Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Leipzig (Germany)

    2016-03-15

    Positron emission tomography (PET) radioligands specific to α{sub 7} nicotinic acetylcholine receptors (nAChRs) afford in vivo imaging of this receptor for neuropathologies such as Alzheimer's disease, schizophrenia, and substance abuse. This work aims to characterize the kinetic properties of an α{sub 7}-nAChR-specific radioligand, 7-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-2-[{sup 18}F]-fluorodibenzo[b,d]thiophene 5,5-dioxide ([{sup 18}F]DBT-10), in nonhuman primates. [{sup 18}F]DBT-10 was produced via nucleophilic substitution of the nitro-precursor. Four Macaca mulatta subjects were imaged with [{sup 18}F]DBT-10 PET, with measurement of [{sup 18}F]DBT-10 parent concentrations and metabolism in arterial plasma. Baseline PET scans were acquired for all subjects. Following one scan, ex vivo analysis of brain tissue was performed to inspect for radiolabeled metabolites in brain. Three blocking scans with 0.69 and 1.24 mg/kg of the α{sub 7}-nAChR-specific ligand ASEM were also acquired to assess dose-dependent blockade of [{sup 18}F]DBT-10 binding. Kinetic analysis of PET data was performed using the metabolite-corrected input function to calculate the parent fraction corrected total distribution volume (V{sub T}/f{sub P}). [{sup 18}F]DBT-10 was produced within 90 min at high specific activities of 428 ± 436 GBq/μmol at end of synthesis. Metabolism of [{sup 18}F]DBT-10 varied across subjects, stabilizing by 120 min post-injection at parent fractions of 15-55 %. Uptake of [{sup 18}F]DBT-10 in brain occurred rapidly, reaching peak standardized uptake values (SUVs) of 2.9-3.7 within 30 min. The plasma-free fraction was 18.8 ± 3.4 %. No evidence for radiolabeled [{sup 18}F]DBT-10 metabolites was found in ex vivo brain tissue samples. Kinetic analysis of PET data was best described by the two-tissue compartment model. Estimated V{sub T}/f{sub P} values were 193-376 ml/cm{sup 3} across regions, with regional rank order of thalamus > frontal cortex > striatum

  13. Molecular imaging of {sigma} receptors: synthesis and evaluation of the potent {sigma}{sub 1} selective radioligand [{sup 18}F]fluspidine

    Energy Technology Data Exchange (ETDEWEB)

    Fischer, Steffen; Hiller, Achim; Deuther-Conrad, Winnie; Scheunemann, Matthias; Steinbach, Joerg; Brust, Peter [Institute of Radiopharmacy, Forschungszentrum Dresden-Rossendorf, Research Site Leipzig, Interdisciplinary Isotope Research, Leipzig (Germany); Wiese, Christian; Grosse Maestrup, Eva; Schepmann, Dirk; Wuensch, Bernhard [Institut fuer Pharmazeutische und Medizinische Chemie der Westfaelischen Wilhelms-Universitaet Muenster, Muenster (Germany)

    2011-03-15

    Neuroimaging of {sigma}{sub 1} receptors in the human brain has been proposed for the investigation of the pathophysiology of neurodegenerative and psychiatric diseases. However, there is a lack of suitable {sup 18}F-labelled PET radioligands for that purpose. The selective {sigma}{sub 1} receptor ligand [{sup 18}F]fluspidine (1'-benzyl-3-(2-[{sup 18}F]fluoroethyl)-3H-spiro[[2]benzofuran-1,4'-piperidine]) was synthesized by nucleophilic {sup 18}F{sup -} substitution of the tosyl precursor. In vitro receptor binding affinity and selectivity were assessed by radioligand competition in tissue homogenate and autoradiographic approaches. In female CD-1 mice, in vivo properties of [{sup 18}F]fluspidine were evaluated by ex vivo brain section imaging and organ distribution of intravenously administered radiotracer. Target specificity was validated by organ distribution of [{sup 18}F]fluspidine after treatment with 1 mg/kg i.p. of the {sigma} receptor antagonist haloperidol or the emopamil binding protein (EBP) inhibitor tamoxifen. In vitro metabolic stability and in vivo metabolism were investigated by LC-MS{sup n} and radio-HPLC analysis. [{sup 18}F]Fluspidine was obtained with a radiochemical yield of 35-45%, a radiochemical purity of {>=} 99.6% and a specific activity of 150-350 GBq/{mu}mol (n = 6) within a total synthesis time of 90-120 min. In vitro, fluspidine bound specifically and with high affinity to {sigma}{sub 1} receptors (K{sub i} = 0.59 nM). In mice, [{sup 18}F]fluspidine rapidly accumulated in brain with uptake values of 3.9 and 4.7%ID/g and brain to blood ratios of 7 and 13 at 5 and 30 min after intravenous application of the radiotracer, respectively. By ex vivo autoradiography of brain slices, resemblance between binding site occupancy of [{sup 18}F]fluspidine and the expression of {sigma}{sub 1} receptors was shown. The radiotracer uptake in the brain as well as in peripheral {sigma}{sub 1} receptor expressing organs was significantly

  14. Overall survival and response pattern of castration-resistant metastatic prostate cancer to multiple cycles of radioligand therapy using [{sup 177}Lu]Lu-PSMA-617

    Energy Technology Data Exchange (ETDEWEB)

    Ahmadzadehfar, Hojjat; Wegen, Simone; Yordanova, Anna; Kuerpig, Stefan; Eppard, Elisabeth; Wei, Xiao; Schlenkhoff, Carl; Essler, Markus [University Hospital Bonn, Department of Nuclear Medicine, Bonn (Germany); Fimmers, Rolf [University of Bonn, Institute for Medical Biometry, Informatics and Epidemiology, Bonn (Germany); Hauser, Stefan [University Hospital Bonn, Department of Urology, Bonn (Germany)

    2017-08-15

    Up to 30% of patients with castration-resistant prostate cancer (CRPC) do not show any response to the first cycle of radioligand therapy (RLT) with [{sup 177}Lu]Lu-PSMA-617 (Lu-PSMA). We evaluated patient response to the second and third cycles of RLT in patients that underwent at least three cycles. The second aim of this study was to calculate the median overall survival (OS) of responders and non-responders after the first cycle and after all three cycles of RLT. CRPC patients were treated with Lu-PSMA, with a median interval of 8 weeks between each cycle. The tumour marker prostate-specific antigen (PSA) was used as the marker for response evaluation. Fifty-two patients underwent a total of 190 cycles of RLT (3-6 cycles per patient). Of these, 80.8% showed a decline in PSA 2 months after the first cycle, with 44.2% showing a PSA decline of ≥50%. When compared to baseline PSA, 73.1% showed a PSA decline after the third cycle. 50% of patients that did not show any response to the first cycle also did not respond to the second and third cycles. The median OS was 60 weeks in all patients. The median OS was significantly longer for patients that showed any PSA decline after the first cycle compared to patients without PSA decline (68 vs. 33 weeks). There was a significant difference in median OS between responders and non-responders for a change in PSA after the third cycle compared to baseline PSA. Patients with a positive response to RLT, regardless of the rate of decline, had a significantly longer median OS. Of the patients that did not show any response to the first cycle, 50% responded to the second or third cycles. (orig.)

  15. Iodine-123 N-methyl-4-iododexetimide: a new radioligand for single-photon emission tomographic imaging of myocardial muscarinic receptors

    Energy Technology Data Exchange (ETDEWEB)

    Hicks, R.J. [Heidelberg Hospital, Melbourne, VIC (Australia); Kassiou, M. [Biomedicine and Health Div., Australian Nuclear Science and Technology Organisation, Sydney, NSW (Australia); Eu, P. [Heidelberg Hospital, Melbourne, VIC (Australia); Katsifis, A.G. [Biomedicine and Health Div., Australian Nuclear Science and Technology Organisation, Sydney, NSW (Australia); Garra, M. [Heidelberg Hospital, Melbourne, VIC (Australia); Power, J. [Heidelberg Hospital, Melbourne, VIC (Australia); Najdovski, L. [Biomedicine and Health Div., Australian Nuclear Science and Technology Organisation, Sydney, NSW (Australia); Lambrecht, R.M. [Biomedicine and Health Div., Australian Nuclear Science and Technology Organisation, Sydney, NSW (Australia)

    1995-04-01

    Cardiac muscarinic receptor ligands suitable for positron emission tomography have previously been characterised. Attempts to develop radioligands of these receptors suitable for single-photon emission tomographic (SPET) imaging have not been successful due to high lung retention and high non-specific binding of previously investigated potential tracers. The purpose of this study was to evaluate the biodistribution and in vivo imaging characteristics of a new radiopharmaceutical, [{sup 123}I]N-methyl-4-iododexetimide. Biodistribution studies performed in rats showed high cardiac uptake (2.4% ID/g) 10 min after injection with a heart to lung activity ratio of 5:1. Specificity and stereoselectivity of cardiac binding were demonstrated using blocking experiments in rats. Dynamic imaging studies in anaesthetised greyhounds demonstrated rapid and high myocardial uptake and low lung binding with stable heart to lung activity ratios of >2.5:1 between 10 and 30 min, making SPET imaging feasible. Administration of an excess of an unlabelled muscarinic antagonist, methyl-quinuclidinyl benzylate rapidly displaced myocardial activity to background levels and the pharmacologically inactive enantiomer, [{sup 123}I]N-methyl-4-iodolevetimide, had no detectable cardiac uptake, indicating specific and stereoselective muscarinic receptor binding. SPET revealed higher activity in the inferior than in the anterior wall, this being consistent with previously described regional variation of cardiac parasympathetic innervation. [{sup 123}I]N-methyl-4-iododexetimide shows promise as an imaging agent for muscarinic receptor distribution in the heart and may be helpful in evaluating diverse cardiac diseases associated with altered muscarinic receptor function, including heart failure and diabetic heart disease. (orig.)

  16. Quantification of dopaminergic neurotransmission SPECT studies with {sup 123}I-labelled radioligands. A comparison between different imaging systems and data acquisition protocols using Monte Carlo simulation

    Energy Technology Data Exchange (ETDEWEB)

    Crespo, Cristina; Aguiar, Pablo [Universitat de Barcelona - IDIBAPS, Unitat de Biofisica i Bioenginyeria, Departament de Ciencies Fisiologiques I, Facultat de Medicina, Barcelona (Spain); Gallego, Judith [Universitat Politecnica de Catalunya, Institut de Tecniques Energetiques, Barcelona (Spain); Institut de Bioenginyeria de Catalunya, Barcelona (Spain); Cot, Albert [Universitat de Barcelona - IDIBAPS, Unitat de Biofisica i Bioenginyeria, Departament de Ciencies Fisiologiques I, Facultat de Medicina, Barcelona (Spain); Universitat Politecnica de Catalunya, Seccio d' Enginyeria Nuclear, Departament de Fisica i Enginyeria Nuclear, Barcelona (Spain); Falcon, Carles; Ros, Domenec [Universitat de Barcelona - IDIBAPS, Unitat de Biofisica i Bioenginyeria, Departament de Ciencies Fisiologiques I, Facultat de Medicina, Barcelona (Spain); CIBER en Bioingenieria, Biomateriales y Nanomedicina (CIBER-BBN), Barcelona (Spain); Bullich, Santiago [Hospital del Mar, Center for Imaging in Psychiatry, CRC-MAR, Barcelona (Spain); Pareto, Deborah [CIBER en Bioingenieria, Biomateriales y Nanomedicina (CIBER-BBN), Barcelona (Spain); PRBB, Institut d' Alta Tecnologia, Barcelona (Spain); Sempau, Josep [Universitat Politecnica de Catalunya, Institut de Tecniques Energetiques, Barcelona (Spain); CIBER en Bioingenieria, Biomateriales y Nanomedicina (CIBER-BBN), Barcelona (Spain); Lomena, Francisco [IDIBAPS, Servei de Medicina Nuclear, Hospital Clinic, Barcelona (Spain); Calvino, Francisco [Universitat Politecnica de Catalunya, Institut de Tecniques Energetiques, Barcelona (Spain); Universitat Politecnica de Catalunya, Seccio d' Enginyeria Nuclear, Departament de Fisica i Enginyeria Nuclear, Barcelona (Spain); Pavia, Javier [CIBER en Bioingenieria, Biomateriales y Nanomedicina (CIBER-BBN), Barcelona (Spain); IDIBAPS, Servei de Medicina Nuclear, Hospital Clinic, Barcelona (Spain)

    2008-07-15

    {sup 123}I-labelled radioligands are commonly used for single-photon emission computed tomography (SPECT) imaging of the dopaminergic system to study the dopamine transporter binding. The aim of this work was to compare the quantitative capabilities of two different SPECT systems through Monte Carlo (MC) simulation. The SimSET MC code was employed to generate simulated projections of a numerical phantom for two gamma cameras equipped with a parallel and a fan-beam collimator, respectively. A fully 3D iterative reconstruction algorithm was used to compensate for attenuation, the spatially variant point spread function (PSF) and scatter. A post-reconstruction partial volume effect (PVE) compensation was also developed. For both systems, the correction for all degradations and PVE compensation resulted in recovery factors of the theoretical specific uptake ratio (SUR) close to 100%. For a SUR value of 4, the recovered SUR for the parallel imaging system was 33% for a reconstruction without corrections (OSEM), 45% for a reconstruction with attenuation correction (OSEM-A), 56% for a 3D reconstruction with attenuation and PSF corrections (OSEM-AP), 68% for OSEM-AP with scatter correction (OSEM-APS) and 97% for OSEM-APS plus PVE compensation (OSEM-APSV). For the fan-beam imaging system, the recovered SUR was 41% without corrections, 55% for OSEM-A, 65% for OSEM-AP, 75% for OSEM-APS and 102% for OSEM-APSV. Our findings indicate that the correction for degradations increases the quantification accuracy, with PVE compensation playing a major role in the SUR quantification. The proposed methodology allows us to reach similar SUR values for different SPECT systems, thereby allowing a reliable standardisation in multicentric studies. (orig.)

  17. Population-based input function modeling for [(18)F]FMPEP-d 2, an inverse agonist radioligand for cannabinoid CB1 receptors: validation in clinical studies.

    Science.gov (United States)

    Zanotti-Fregonara, Paolo; Hirvonen, Jussi; Lyoo, Chul Hyoung; Zoghbi, Sami S; Rallis-Frutos, Denise; Huestis, Marilyn A; Morse, Cheryl; Pike, Victor W; Innis, Robert B

    2013-01-01

    Population-based input function (PBIF) may be a valid alternative to full blood sampling for quantitative PET imaging. PBIF is typically validated by comparing its quantification results with those obtained via arterial sampling. However, for PBIF to be employed in actual clinical research studies, its ability to faithfully capture the whole spectrum of results must be assessed. The present study validated a PBIF for [(18)F]FMPEP-d 2, a cannabinoid CB1 receptor radioligand, in healthy volunteers, and also attempted to utilize PBIF to replicate three previously published clinical studies in which the input function was acquired with arterial sampling. The PBIF was first created and validated with data from 42 healthy volunteers. This PBIF was used to assess the retest variability of [(18)F]FMPEP-d 2, and then to quantify CB1 receptors in alcoholic patients (n = 18) and chronic daily cannabis smokers (n = 29). Both groups were scanned at baseline and after 2-4 weeks of monitored drug abstinence. PBIF yielded accurate results in the 42 healthy subjects (average Logan-distribution volume (V T) was 13.3±3.8 mL/cm(3) for full sampling and 13.2±3.8 mL/cm(3) for PBIF; R(2) = 0.8765, pCB1 receptors in alcoholic subjects, without significant change after abstinence. However, a small PBIF-V T bias of -9% was unexpectedly observed in cannabis smokers. This bias led to substantial errors, including a V T decrease in regions that had shown no downregulation in the full input function. Simulated data showed that the original findings could only have been replicated with a PBIF bias between -6% and +4%. Despite being initially well validated in healthy subjects, PBIF may misrepresent clinical protocol results and be a source of variability between different studies and institutions.

  18. Quantification of dopaminergic neurotransmission SPECT studies with 123I-labelled radioligands. A comparison between different imaging systems and data acquisition protocols using Monte Carlo simulation.

    Science.gov (United States)

    Crespo, Cristina; Gallego, Judith; Cot, Albert; Falcón, Carles; Bullich, Santiago; Pareto, Deborah; Aguiar, Pablo; Sempau, Josep; Lomeña, Francisco; Calviño, Francisco; Pavía, Javier; Ros, Domènec

    2008-07-01

    (123)I-labelled radioligands are commonly used for single-photon emission computed tomography (SPECT) imaging of the dopaminergic system to study the dopamine transporter binding. The aim of this work was to compare the quantitative capabilities of two different SPECT systems through Monte Carlo (MC) simulation. The SimSET MC code was employed to generate simulated projections of a numerical phantom for two gamma cameras equipped with a parallel and a fan-beam collimator, respectively. A fully 3D iterative reconstruction algorithm was used to compensate for attenuation, the spatially variant point spread function (PSF) and scatter. A post-reconstruction partial volume effect (PVE) compensation was also developed. For both systems, the correction for all degradations and PVE compensation resulted in recovery factors of the theoretical specific uptake ratio (SUR) close to 100%. For a SUR value of 4, the recovered SUR for the parallel imaging system was 33% for a reconstruction without corrections (OSEM), 45% for a reconstruction with attenuation correction (OSEM-A), 56% for a 3D reconstruction with attenuation and PSF corrections (OSEM-AP), 68% for OSEM-AP with scatter correction (OSEM-APS) and 97% for OSEM-APS plus PVE compensation (OSEM-APSV). For the fan-beam imaging system, the recovered SUR was 41% without corrections, 55% for OSEM-A, 65% for OSEM-AP, 75% for OSEM-APS and 102% for OSEM-APSV. Our findings indicate that the correction for degradations increases the quantification accuracy, with PVE compensation playing a major role in the SUR quantification. The proposed methodology allows us to reach similar SUR values for different SPECT systems, thereby allowing a reliable standardisation in multicentric studies.

  19. Labelling and biological evaluation of [{sup 11}C]methoxy-Sch225336: a radioligand for the cannabinoid-type 2 receptor

    Energy Technology Data Exchange (ETDEWEB)

    Evens, Nele [Laboratory for Radiopharmacy, K.U.Leuven, Leuven 3000 (Belgium); Bosier, Barbara [Department of Pharmaceutical Chemistry and Radiopharmacy, U.C.L., Brussels 1200 (Belgium); Lavey, Brian J.; Kozlowski, Joseph A. [Schering Plough Research Institute, Kenilworth, NJ 07033 (United States); Vermaelen, Peter [Division of Nuclear Medicine, K.U.Leuven, Leuven 3000 (Belgium); Baudemprez, Luc; Busson, Roger [Laboratory of Medicinal Chemistry, K.U.Leuven, Leuven 3000 (Belgium); Lambert, Didier M. [Department of Pharmaceutical Chemistry and Radiopharmacy, U.C.L., Brussels 1200 (Belgium); Van Laere, Koen [Division of Nuclear Medicine, K.U.Leuven, Leuven 3000 (Belgium); Verbruggen, Alfons M. [Laboratory for Radiopharmacy, K.U.Leuven, Leuven 3000 (Belgium); Bormans, Guy M. [Laboratory for Radiopharmacy, K.U.Leuven, Leuven 3000 (Belgium)], E-mail: guy.bormans@pharm.kuleuven.be

    2008-10-15

    Introduction: The cannabinoid type 2 receptor (CB{sub 2} receptor) is part of the endocannabinoid system and has been suggested as mediator of a number of central and peripheral inflammatory processes. In the present study, we have synthesized N-[(1s)-1-[4-[[4-methoxy-2-[(4-[{sup 11}C]methoxyphenyl)sulfonyl) -phenyl]sulfonyl] phenyl]ethyl]methanesulfonamide ([{sup 11}C]methoxy-Sch225336) and evaluated this new tracer agent as a potential positron emission tomography radioligand for the in vivo visualization of CB{sub 2} receptors. Methods: Sch225336 was demethylated and the resulting phenol precursor was radiolabelled with a carbon-11 methyl group by methylation using [{sup 11}C]methyl iodide, followed by purification by high-performance liquid chromatography. The log P of [{sup 11}C]methoxy-Sch225336 and its biodistribution in normal mice were determined. Enhancement of brain uptake by inhibition of blood-brain barrier (BBB) efflux transporters was studied. Mouse plasma was analysed to quantify the formation of radiometabolites. The affinity of Sch225336 for the human cannabinoid type 1 and type 2 receptor was determined. Results: [{sup 11}C]methoxy-Sch225336 was obtained with a decay corrected radiochemical yield of about 30% and a specific activity of 88.8 GBq/{mu}mol (end of synthesis). After intravenous injection in mice, the compound is rapidly cleared from the blood through the hepatobiliary pathway and does not show particular retention in any of the major organs. Polar metabolites were found in mouse plasma. Brain uptake was low despite the favourable log P value of 2.15, which is partly due to efflux by BBB pumps. Conclusion: [{sup 11}C]methoxy-Sch225336 is a good candidate for in vivo imaging of the CB{sub 2} receptor, although the low blood-brain barrier penetration limits its potential for central nervous system imaging.

  20. Kierkegaardovo pojetí existence

    OpenAIRE

    Janatová, Kristýna

    2016-01-01

    The topic of the bachelor thesis is "Kierkegaard's conception of existence". There are both the life of the Danish philosopher Søren Kierkegaard and his philosophy discussed. The issue of human existence is analysed with its main three stages which are focused on aesthetics, ethics and religion. These stages of existence are at first described and afterwards compared with each other. The aesthetic represents the first stage of life and the religious stage is considered to be the highest aim o...

  1. Changes in Binding of [123I]CLINDE, a High-Affinity Translocator Protein 18 kDa (TSPO) Selective Radioligand in a Rat Model of Traumatic Brain Injury

    DEFF Research Database (Denmark)

    Donat, Cornelius K; Gaber, Khaled; Meixensberger, Jürgen

    2016-01-01

    microglia cells and upregulated in response to brain injury and therefore a potential biomarker of the neuroinflammatory processes. Second-generation radioligands of TSPO, such as [(123)I]CLINDE, have a higher signal-to-noise ratio as the prototype ligand PK11195. [(123)I]CLINDE has been employed in human...... studies using single-photon emission computed tomography to image the neuroinflammatory response after stroke. In this study, we used the same tracer in a rat model of TBI to determine changes in TSPO expression. Adult Sprague-Dawley rats were subjected to moderate controlled cortical impact injury...

  2. Investigation of models with temporal and spatial interference in image based dosimetry of {sup 177}Lu-labelled radioligand therapies

    Energy Technology Data Exchange (ETDEWEB)

    Delker, Andreas

    2016-07-12

    In targeted radio ligand therapy determination of the regional distribution of the radiation dose is mandatory for the development of therapy strategies which aim for maximizing the therapeutic effect on the tumor, while reducing radiation exposure to healthy tissue. For this purpose, after administration of the therapeutic agent, sequential measurements with a scintillation camera are required to quantitatively assess the kinetics and distribution of the radiopharmaceutical in the body. To improve the accuracy and robustness of existing dosimetric concepts, the kinetic of Lu-177-DOTATATE, a radiopharmaceutical for the treatment of patients with neuroendocrine tumors, was examined in depth. Subsequently, the findings from this study were used to carry out the first image-based dosimetry for the new active substance Lu-177-PSMA, a radiopharmaceutical for the treatment of patients with metastatic prostate cancer. Due to the specific distribution pattern of this ligand, overlay effects in the 2-dimensional (2-D) planar projection were observed. Therefore a quantitative 3-dimensional (3-D) SPECT imaging technique was established and optimized for dosimetry. To characterize the dynamics of Lu-177-DOTATATE, whole-body planar projections of 105 patients were recorded at 1, 24, 48 and 72 h after injection. Furthermore, the first hour beginning with the start of the therapeutic agent administration was measured in 12 time frames with duration of 5 min each. An optimal dose model was introduced for the kidneys, for those being a risk organ in this therapy, which consisted of three phases: a linear increase of tracer accumulation during infusion, followed by a 2-phase model being described by a bi-exponential decline. This full data model served as a basis for comparison with reduced data models based on mono-exponentials which made use of all four (at 1, 24, 48 and 72 h after injection) or the last three whole-body scintigraphies. The established quantitative 3-D SPECT

  3. Characterization of [{sup 11}C]Lu AE92686 as a PET radioligand for phosphodiesterase 10A in the nonhuman primate brain

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Kai-Chun; Stepanov, Vladimir; Amini, Nahid; Martinsson, Stefan; Takano, Akihiro; Halldin, Christer [Karolinska Institutet, Karolinska University Hospital, Department of Clinical Neuroscience, Center for Psychiatric Research, Stockholm (Sweden); Nielsen, Jacob [H. Lundbeck A/S, Synaptic Transmission, Valby (Denmark); Bundgaard, Christoffer; Bang-Andersen, Benny [H. Lundbeck A/S, Discovery Chemistry and DMPK, Valby (Denmark); Grimwood, Sarah [Pfizer Inc., Neuroscience and Pain Research Unit, Cambridge, MA (United States); Farde, Lars [Karolinska Institutet, Karolinska University Hospital, Department of Clinical Neuroscience, Center for Psychiatric Research, Stockholm (Sweden); AstraZeneca PET Science Center at Karolinska Institutet, Personalized Health Care and Biomarkers, Stockholm (Sweden); Finnema, Sjoerd J. [Karolinska Institutet, Karolinska University Hospital, Department of Clinical Neuroscience, Center for Psychiatric Research, Stockholm (Sweden); Yale University, Department of Radiology and Biomedical Imaging, New Haven, CT (United States)

    2017-02-15

    [{sup 11}C]Lu AE92686 is a positron emission tomography (PET) radioligand that has recently been validated for examining phosphodiesterase 10A (PDE10A) in the human striatum. [{sup 11}C]Lu AE92686 has high affinity for PDE10A (IC{sub 50} = 0.39 nM) and may also be suitable for examination of the substantia nigra, a region with low density of PDE10A. Here, we report characterization of regional [{sup 11}C]Lu AE92686 binding to PDE10A in the nonhuman primate (NHP) brain. A total of 11 PET measurements, seven baseline and four following pretreatment with unlabeled Lu AE92686 or the structurally unrelated PDE10A inhibitor MP-10, were performed in five NHPs using a high resolution research tomograph (HRRT). [{sup 11}C]Lu AE92686 binding was quantified using a radiometabolite-corrected arterial input function and compartmental and graphical modeling approaches. Regional time-activity curves were best described with the two-tissue compartment model (2TCM). However, the distribution volume (V{sub T}) values for all regions were obtained by the Logan plot analysis, as reliable cerebellar V{sub T} values could not be derived by the 2TCM. For cerebellum, a proposed reference region, V{sub T} values increased by ∝30 % with increasing PET measurement duration from 63 to 123 min, while V{sub T} values in target regions remained stable. Both pretreatment drugs significantly decreased [{sup 11}C]Lu AE92686 binding in target regions, while no significant effect on cerebellum was observed. Binding potential (BP{sub ND}) values, derived with the simplified reference tissue model (SRTM), were 13-17 in putamen and 3-5 in substantia nigra and correlated well to values from the Logan plot analysis. The method proposed for quantification of [{sup 11}C]Lu AE92686 binding in applied studies in NHP is based on 63 min PET data and SRTM with cerebellum as a reference region. The study supports that [{sup 11}C]Lu AE92686 can be used for PET examinations of PDE10A binding also in substantia

  4. Population-based input function modeling for [(18F]FMPEP-d 2, an inverse agonist radioligand for cannabinoid CB1 receptors: validation in clinical studies.

    Directory of Open Access Journals (Sweden)

    Paolo Zanotti-Fregonara

    Full Text Available Population-based input function (PBIF may be a valid alternative to full blood sampling for quantitative PET imaging. PBIF is typically validated by comparing its quantification results with those obtained via arterial sampling. However, for PBIF to be employed in actual clinical research studies, its ability to faithfully capture the whole spectrum of results must be assessed. The present study validated a PBIF for [(18F]FMPEP-d 2, a cannabinoid CB1 receptor radioligand, in healthy volunteers, and also attempted to utilize PBIF to replicate three previously published clinical studies in which the input function was acquired with arterial sampling.The PBIF was first created and validated with data from 42 healthy volunteers. This PBIF was used to assess the retest variability of [(18F]FMPEP-d 2, and then to quantify CB1 receptors in alcoholic patients (n = 18 and chronic daily cannabis smokers (n = 29. Both groups were scanned at baseline and after 2-4 weeks of monitored drug abstinence.PBIF yielded accurate results in the 42 healthy subjects (average Logan-distribution volume (V T was 13.3±3.8 mL/cm(3 for full sampling and 13.2±3.8 mL/cm(3 for PBIF; R(2 = 0.8765, p<0.0001 and test-retest results were comparable to those obtained with full sampling (variability: 16%; intraclass correlation coefficient: 0.89. PBIF accurately replicated the alcoholism study, showing a widespread ∼20% reduction of CB1 receptors in alcoholic subjects, without significant change after abstinence. However, a small PBIF-V T bias of -9% was unexpectedly observed in cannabis smokers. This bias led to substantial errors, including a V T decrease in regions that had shown no downregulation in the full input function. Simulated data showed that the original findings could only have been replicated with a PBIF bias between -6% and +4%.Despite being initially well validated in healthy subjects, PBIF may misrepresent clinical protocol results and be a source of

  5. Preclinical evaluation and test-retest studies of [{sup 18}F]PSS232, a novel radioligand for targeting metabotropic glutamate receptor 5 (mGlu{sub 5})

    Energy Technology Data Exchange (ETDEWEB)

    Milicevic Sephton, Selena; Mueller Herde, Adrienne; Keller, Claudia; Ruedisuehli, Sonja; Schibli, Roger; Kraemer, Stefanie D.; Ametamey, Simon M. [Center for Radiopharmaceutical Sciences of ETH, PSI and USZ, Zurich (Switzerland); Mu, Linjing [University Hospital Zuerich, Department of Nuclear Medicine, Zuerich (Switzerland); Auberson, Yves [Novartis Institutes for Biomedical Research, Novartis Pharma AG, Basel (Switzerland)

    2015-01-15

    properties and is a promising radioligand for PET imaging of mGlu{sub 5} in humans. (orig.)

  6. Radiosynthesis and in vivo evaluation of [{sup 11}C]MP-10 as a positron emission tomography radioligand for phosphodiesterase 10A

    Energy Technology Data Exchange (ETDEWEB)

    Plisson, Christophe, E-mail: Christophe.2.plisson@gsk.com [GlaxoSmithKline, Clinical Imaging Centre Hammersmith Hospital, London, W12 0NN (United Kingdom); Salinas, Cristian [GlaxoSmithKline, Clinical Imaging Centre Hammersmith Hospital, London, W12 0NN (United Kingdom); Weinzimmer, David; Labaree, David; Lin, Shu-Fei; Ding, Yu-Shin [Yale University PET Center, Yale University School of Medicine, PO Box 208048 New Haven, CT (United States); Jakobsen, Steen [Aarhus PET Centre, Aarhus Sygehus, Norrebrogade 44, DK-8000 Aarhus C (Denmark); Smith, Paul W. [GlaxoSmithKline, Clinical Imaging Centre Hammersmith Hospital, London, W12 0NN (United Kingdom); Eiji, Kawanishi [Medicinal Chemistry Research Laboratories II, Research Division, Mitsubishi Tanabe Pharma Corporation, Saitama 335-8505 (Japan); Carson, Richard E. [Yale University PET Center, Yale University School of Medicine, PO Box 208048 New Haven, CT (United States); Gunn, Roger N.; Rabiner, Eugenii A. [GlaxoSmithKline, Clinical Imaging Centre Hammersmith Hospital, London, W12 0NN (United Kingdom)

    2011-08-15

    Introduction: The aim of this study was to evaluate a newly reported positron emission tomography (PET) radioligand [{sup 11}C]MP-10, a potent and selective inhibitor of the central phosphodiesterase 10A enzyme (PDE10A) in vivo, using PET. Methods: A procedure was developed for labeling MP-10 with carbon-11. [{sup 11}C]MP-10 was evaluated in vivo both in the pig and baboon brain. Results: Alkylation of the corresponding desmethyl compound with [{sup 11}C]methyl iodide produced [{sup 11}C]MP-10 with good radiochemical yield and specific activity. PET studies in the pig showed that [{sup 11}C]MP-10 rapidly entered the brain reaching peak tissue concentration at 1-2 min postadministration, followed by washout from the tissue. Administration of a selective PDE10A inhibitor reduced the binding in all brain regions to the levels of the cerebellum, demonstrating the saturability and selectivity of [{sup 11}C]MP-10 binding. In the nonhuman primate, the brain tissue kinetics of [{sup 11}C]MP-10 were slower, reaching peak tissue concentrations at 30-60 min postadministration. In both species, the observed rank order of regional brain signal was striatum>diencephalon>cortical regions=cerebellum, consistent with the known distribution and concentration of PDE10A. [{sup 11}C]MP-10 brain kinetics were well described by a two-tissue compartment model, and estimates of total volume of distribution (V{sub T}) were obtained. Blocking studies with unlabeled MP-10 revealed the suitability of the cerebellum as a reference tissue and enabled the estimation of regional binding potential (BP{sub ND}) as the outcome measure of specific binding. Quantification of [{sup 11}C]MP-10 binding using the simplified reference tissue model with cerebellar input function produced BP{sub ND} estimates consistent with those obtained by the two-tissue compartment model. Conclusion: We demonstrated that [{sup 11}C]MP-10 possesses good characteristics for the in vivo quantification of the PDE10A in the

  7. Selective affinity of the benzodiazepines quazepam and 2-oxo-quazepam for BZ1 binding site and demonstration of H-2-oxo-quazepam as a BZ1 selective radioligand

    Energy Technology Data Exchange (ETDEWEB)

    Billard, W.; Crosby, G.; Iorio, L.; Chipkin, R.; Barnett, A.

    1988-01-01

    Quazepam and 2-oxo-quazepam are novel benzodiazepines containing a trifluoroethyl substituent on the ring nitrogen at position number1. Detailed competition binding experiments (25 to 30 concs.) at 4/sup 0/C were undertaken with these compounds versus /sup 3/H-flunitrazepam using synaptic membranes from rat cortex or cerebellum. Unlike other benzodiazepines, both quazepam and 2-oxo-quazepam distinguished two populations of /sup 3/H-flunitrazepam binding sites in rat cortex which were present in roughly equal proportions and for which the compounds displayed a greater than 20-fold difference in affinity. In cerebellum, no such discrimination of sites was noted for 2-oxo-quazepam, but quazepam did distinguish a small, low affinity population of sites. /sup 3/H-2-oxo-quazepam was prepared and used in competition studies to substantiate the conclusion that these compounds discriminate two populations of benzodiazepine sites in rat cortex. This new radioligand was shown to specifically label BZ binding sites with high affinity in a saturable manner. The competition experiments were then conducted using /sup 3/H-2-oxo-quazepam at a radioligand concentration sufficiently low to ensure that only the higher affinity binding sites which 2-oxo-quazepam discriminates would be occupied. 15 references, 3 figures, 4 tables.

  8. Existing Steel Railway Bridges Evaluation

    Directory of Open Access Journals (Sweden)

    Vičan Josef

    2016-12-01

    Full Text Available The article describes general principles and basis of evaluation of existing railway bridges based on the concept of load-carrying capacity determination. Compared to the design of a new bridge, the modified reliability level for existing bridges evaluation should be considered due to implementation of the additional data related to bridge condition and behaviour obtained from regular inspections. Based on those data respecting the bridge remaining lifetime, a modification of partial safety factors for actions and materials could be respected in the bridge evaluation process. A great attention is also paid to the specific problems of determination of load-caring capacity of steel railway bridges in service. Recommendation for global analysis and methodology for existing steel bridge superstructure load-carrying capacity determination are described too.

  9. Existence of mesons after deconfinement

    NARCIS (Netherlands)

    F. Brau (Fabian); F. Buisseret

    2007-01-01

    textabstractWe investigate the possibility for a quark-antiquark pair to form a bound state at temperatures higher than the critical one ($T>T_c$), thus after deconfinement. Our main goal is to find analytical criteria constraining the existence of such mesons. Our formalism relies on a Schrödinger

  10. Limitations of existing web services

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. Limitations of existing web services. Uploading or downloading large data. Serving too many user from single source. Difficult to provide computer intensive job. Depend on internet and its bandwidth. Security of data in transition. Maintain confidentiality of data ...

  11. Performance of Existing Hydrogen Stations

    Energy Technology Data Exchange (ETDEWEB)

    Sprik, Samuel [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Kurtz, Jennifer M [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Ainscough, Christopher D [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Saur, Genevieve [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Peters, Michael C [National Renewable Energy Laboratory (NREL), Golden, CO (United States)

    2017-12-01

    In this presentation, the National Renewable Energy Laboratory presented aggregated analysis results on the performance of existing hydrogen stations, including performance, operation, utilization, maintenance, safety, hydrogen quality, and cost. The U.S. Department of Energy funds technology validation work at NREL through its National Fuel Cell Technology Evaluation Center (NFCTEC).

  12. Human Rights Being and Existence

    Directory of Open Access Journals (Sweden)

    Xabier Etexeberria

    2013-05-01

    Full Text Available The ontological perspective in the approach to human rights is subject to different traps,against which measures must be taken. But it also faces us to the challenge of precisely specifying what they are and how are they to be based. In this paper we try to face this challenge, paying attention to avoid the traps above mentioned. The first part of it is focused on being-existence of human rights,trying to specify critically their «places»: social reality, laws and, in a founding sense, human dignity.The second part takes the category being-essence as reference, asking about the kind of being of humanrights in their different types. This «kind» will show itself densely mediated by cultural diversity andtemporality-historicity. What is really pretended with this reflection is to contribute to the cause of thesocial existence of human rights.

  13. The EXIST Mission Concept Study

    Science.gov (United States)

    Fishman, Gerald J.; Grindlay, J.; Hong, J.

    2008-01-01

    EXIST is a mission designed to find and study black holes (BHs) over a wide range of environments and masses, including: 1) BHs accreting from binary companions or dense molecular clouds throughout our Galaxy and the Local Group, 2) supermassive black holes (SMBHs) lying dormant in galaxies that reveal their existence by disrupting passing stars, and 3) SMBHs that are hidden from our view at lower energies due to obscuration by the gas that they accrete. 4) the birth of stellar mass BHs which is accompanied by long cosmic gamma-ray bursts (GRBs) which are seen several times a day and may be associated with the earliest stars to form in the Universe. EXIST will provide an order of magnitude increase in sensitivity and angular resolution as well as greater spectral resolution and bandwidth compared with earlier hard X-ray survey telescopes. With an onboard optical-infra red (IR) telescope, EXIST will measure the spectra and redshifts of GRBs and their utility as cosmological probes of the highest z universe and epoch of reionization. The mission would retain its primary goal of being the Black Hole Finder Probe in the Beyond Einstein Program. However, the new design for EXIST proposed to be studied here represents a significant advance from its previous incarnation as presented to BEPAC. The mission is now less than half the total mass, would be launched on the smallest EELV available (Atlas V-401) for a Medium Class mission, and most importantly includes a two-telescope complement that is ideally suited for the study of both obscured and very distant BHs. EXIST retains its very wide field hard X-ray imaging High Energy Telescope (HET) as the primary instrument, now with improved angular and spectral resolution, and in a more compact payload that allows occasional rapid slews for immediate optical/IR imaging and spectra of GRBs and AGN as well as enhanced hard X-ray spectra and timing with pointed observations. The mission would conduct a 2 year full sky survey in

  14. Turbulence: does energy cascade exist?

    CERN Document Server

    Josserand, Christophe; Lehner, Thierry; Pomeau, Yves

    2016-01-01

    To answer the question whether a cascade of energy exists or not in turbulence, we propose a set of correlation functions able to test if there is an irreversible transfert of energy, step by step, from large to small structures. These tests are applied to real Eulerian data of a turbulent velocity flow, taken in the wind grid tunnel of Modane, and also to a prototype model equation for wave turbulence. First we demonstrate the irreversible character of the flow by using multi-time correlation function at a given point of space. Moreover the unexpected behavior of the test function leads us to connect irreversibility and finite time singularities (intermittency). Secondly we show that turbulent cascade exists, and is a dynamical process, by using a test function depending on time and frequency. The cascade shows up only in the inertial domain where the kinetic energy is transferred more rapidly (on average) from the wavenumber $k_{1}$ to $k_{2}$ than from $k_{1}$ to $k'_{2}$ larger than $k_{2}$.

  15. Straightening: existence, uniqueness and stability

    Science.gov (United States)

    Destrade, M.; Ogden, R. W.; Sgura, I.; Vergori, L.

    2014-01-01

    One of the least studied universal deformations of incompressible nonlinear elasticity, namely the straightening of a sector of a circular cylinder into a rectangular block, is revisited here and, in particular, issues of existence and stability are addressed. Particular attention is paid to the system of forces required to sustain the large static deformation, including by the application of end couples. The influence of geometric parameters and constitutive models on the appearance of wrinkles on the compressed face of the block is also studied. Different numerical methods for solving the incremental stability problem are compared and it is found that the impedance matrix method, based on the resolution of a matrix Riccati differential equation, is the more precise. PMID:24711723

  16. EXIST OIRT Camera and Spectrometer

    Science.gov (United States)

    Kutyrev, Alexander; Moseley, S. H.; Golisano, C.; Gong, Q.; Allen, B.; Grindlay, J.; Hong, J.; Woodgate, B.; EXIST Team

    2009-01-01

    The EXIST mission includes a 1.1m infrared and visible telescope which provides the capability to locate, identify, and obtain spectra of GRB afterglows at redshifts up to z 20. To allow rapid identification and spectroscopic follow up, the instruments will provide wide band imaging, covering the full error circle of the Gamma Ray Telescope (GRT), low spectral resolution slitless spectroscopy, and high resolution integral field spectroscopy. The integral field unit will have a small field of view of 2" x 2" to study diffuse objects, e.g. GRB host galaxies. The instrumentation capabilities will allow this telescope quickly identify the afterglow, measure its brightness curves, redshift, measure spectral characteristics of the GRBs, and measure absorption spectra of the intervening intergalactic medium. With this instrument, high redshift GRBs become important tools for observing the processes through which the universe is ionized.

  17. Why do interstellar grains exist?

    Science.gov (United States)

    Seab, C. G.; Hollenbach, D. J.; Mckee, C. F.; Tielens, Alexander G. G. M.

    1986-01-01

    There exists a discrepancy between calculated destruction rates of grains in the interstellar medium and postulated sources of new grains. This problem was examined by modelling the global life cycle of grains in the galaxy. The model includes: grain destruction due to supernovae shock waves; grain injection from cool stars, planetary nebulae, star formation, novae, and supernovae; grain growth by accretion in dark clouds; and a mixing scheme between phases of the interstellar medium. Grain growth in molecular clouds is considered as a mechanism or increasing the formation rate. To decrease the shock destruction rate, several new physical processes, such as partial vaporization effects in grain-grain collisions, breakdown of the small Larmor radius approximation for betatron acceleration, and relaxation of the steady-state shock assumption are included.

  18. Does the mental lexicon exist?

    Directory of Open Access Journals (Sweden)

    Lucilene Bender de Sousa

    2015-09-01

    Full Text Available One of the central and mostintriguing components of language processing to researchers is the mentallexicon. The term was used for the first time by Ann Triesman in 1961 and westill do not have clear answers on how it is structured and how muchinformation it contains, or even if there is something to be called a mentallexicon. For some time, mental lexicon has been compared to a mental dictionaryboth storing and organizing word knowledge; however, they are surely differentin structure and quantity/quality of information. Neuroimaging studies havealso tried to bring contributions to these questions. Some researchers believethat there are many lexicons, one for each level of stored information (ULLMAN,2007: orthographic, phonological, semantic and syntactic lexicons. Another group of researchers (MCCLELLAND;ROGERS, 2003; SEIDENBERG, 1997, etc. postulates the existence of only onelexicon where all information levels are integrated. Recently, a new audaciousproposal has been done by Elman (2009, the inexistence of a mental lexicon. Inthis paper, we discuss the different views of mental lexicon structure andcontent. We try to proceed on the discussion of Elman’s new proposal andconfront it to data obtained by behavioral, neuroimaging and computationalstudies.

  19. Comparative Evaluation of the Translocator Protein Radioligands {sup 11}C-DPA-713, {sup 18}F-DPA- 714, and {sup 11}C-PK11195 in a Rat Model of Acute Neuro-inflammation

    Energy Technology Data Exchange (ETDEWEB)

    Chauveau, F.; Van Camp, N.; Dolle, F.; Kuhnast, B.; Hinnen, F.; Damont, A.; Boutin, H.; Tavitian, B. [CEA, DSV, I2BM, LIME, Orsay (France); Chauveau, F.; Van Camp, N.; Boutin, H; Tavitian, B. [INSERM, U803, Orsay (France); Chauveau, F. [CREATIS-LRMN, CNRS, UMR 5220, and INSERM, U630, Bron (France); Boutin, H. [Faculty of Life Sciences, AV Hill Building, University of Manchester, Manchester (GB); James, M. [Brain and Mind Research Institute, University of Sydney, Sydney, New South Wales (Australia); Kassiou, M. [Discipline of Medical Radiation Sciences, University of Sydney, Sydney, New SouthWales (Australia); Kassiou, M. [School of Chemistry, University of Sydney, Sydney, New SouthWales (Australia)

    2009-07-01

    Overexpression of the translocator protein, TSPO (18 kDa), formerly known as the peripheral benzodiazepine receptor, is a hallmark of activation of cells of monocytic lineage (micro-glia and macrophages) during neuro-inflammation. Radiolabeling of TSPO ligands enables the detection of neuro-inflammatory lesions by PET. Two new radioligands, {sup 11}C-labeled N, N-diethyl-2-[2-(4- methoxy-phenyl)-5, 7-dimethylpyrazolo[1, 5-a]pyrimidin-3-yl] acetamide (DPA-713) and {sup 18}F-labeled N, N-diethyl-2-(2-(4-(2- fluoroethoxy)phenyl)-5, 7-dimethylpyrazolo[1, 5-a]pyrimidin-3-yl) acetamide (DPA-714), both belonging to the pyrazolopyrimidine class, were compared in vivo and in vitro using a rodent model of neuro-inflammation. Methods: {sup 11}C-DPA-713 and {sup 18}F-DPA-714, as well as the classic radioligand {sup 11}C-labeled (R)-N-methyl- N-(1-methylpropyl)-1-(2-chlorophenyl)isoquinoline-3-carboxamide (PK11195), were used in the same rat model, in which intra-striatal injection of (R, S)-a-amino-3-hydroxy-5-methyl-4-isoxazolopropionique gave rise to a strong neuro-inflammatory response. Comparative endpoints included in vitro autoradiography and in vivo imaging on a dedicated small-animal PET scanner under identical conditions. Results: {sup 11}C-DPA-713 and {sup 18}F-DPA-714 could specifically localize the neuro-inflammatory site with a similar signal-to-noise ratio in vitro. In vivo, {sup 18}F-DPA-714 performed better than {sup 11}C-DPA-713 and {sup 11}C-PK11195, with the highest ratio of ipsilateral to contralateral uptake and the highest binding potential. Conclusion: {sup 18}F-DPA-714 appears to be an attractive alternative to {sup 11}C-PK11195 because of its increased bioavailability in brain tissue and its reduced nonspecific binding. Moreover, its labeling with {sup 18}F, the preferred PET isotope for radiopharmaceutical chemistry, favors its dissemination and wide clinical use. {sup 18}F-DPA-714 will be further evaluated in longitudinal studies of neuro

  20. Estudio mediante EIS de capas lantánidas de conversión desarrolladas mediante activación térmica sobre aleaciones de Al-Mg

    Directory of Open Access Journals (Sweden)

    Bethencourt, M.

    2005-12-01

    Full Text Available Nowadays, a lot of anticorrosive treatments that can be used as alternative processes to Cr(IV-based treatments are developing. Some of them involve the use of lanthanide compounds. The present work show a morphologic and anticorrosive study of conversion coatings developed on samples of AA5083 alloy from Ce (III solutions, by treatments of immersion to 323K in baths of cerium salts. SEM/EDS analysis of treated sampled shows the existence of an heterogeneous coating composed of an aluminium hydroxide/oxide on the metallic matrix and Ce island over cathodic intermetallic. Protected with conversion coatings, AA5083 samples were immersed in NaCl and EIS tests were registered both to evaluate the protection degree of the developed coatings and to characterize the individual contribution of the electrochemical response of the system.

    En la actualidad, se encuentran en desarrollo una gran variedad de tratamientos anticorrosivos que pueden emplearse como alternativas a los basados en Cr(VI. Algunos conllevan el empleo de lantánidos. En este trabajo, se lleva a cabo un estudio de las características morfológicas y anticorrosivas de capas desarrolladas sobre la aleación AA5083 a partir de disoluciones de Ce(III, mediante tratamientos de inmersión a 323K en baños de sal de cerio. Estudios SEM/EDS sobre la muestras tratadas han puesto de manifiesto la existencia de una capa heterogénea formada por una película de óxido/hidróxido de aluminio sobre la matriz y una serie de islas dispersas de cerio, sobre los intermetálicos catódicos. Para evaluar el grado de protección de las capas de conversión desarrolladas, así como para caracterizar la contribución individual de la respuesta electroquímica del sistema en NaCl, se han llevado a cabo ensayos de EIS.

  1. The use of a modified [3H]4-DAMP radioligand binding assay with increased selectivity for muscarinic M3 receptor shows that cortical CHRM3 levels are not altered in mood disorders.

    Science.gov (United States)

    Jeon, Won Je; Gibbons, Andrew S; Dean, Brian

    2013-12-02

    [(3)H]4-DAMP is a radioligand that has been used to quantify levels of the muscarinic receptor CHRM3 protein in situ. However, in addition to high affinity binding to CHRM3, [(3)H]4-DAMP binds with low affinity to CHRM1 confounding the potential to discriminate between changes in these two muscarinic receptors. We have developed a [(3)H]4-DAMP binding assay, optimised for measuring CHRM3 protein levels in the cortex, with minimal selectivity towards CHRM1. The selectivity of our assay towards CHRM3 was confirmed using recombinant receptor-expressing, cell lysate preparations. [(3)H]4-DAMP binding levels were similar between wildtype and CHRM1 knockout mice, confirming that the amount of [(3)H]4-DAMP binding to CHRM1 was negligible. We used this assay to measure CHRM3 protein levels in the frontal pole, obtained post-mortem from subjects with bipolar disorder (n = 15), major depressive disorder (n = 15) and matched controls (n = 20) and showed that [(3)H]4-DAMP binding was not altered in either bipolar disorder or major depressive disorder. Western blotting confirmed that CHRM3 protein levels were unchanged in these subjects. © 2013.

  2. High School and Youth Trends. NIDA InfoFacts

    Science.gov (United States)

    National Institute on Drug Abuse (NIDA), 2011

    2011-01-01

    Since 1975 the Monitoring the Future (MTF) survey has measured drug, alcohol, and cigarette use and related attitudes among adolescent students nationwide. Survey participants report their drug use behaviors across three time periods: lifetime, past year, and past month; for some drugs, daily use is also reported. Initially, the survey included…

  3. Kinetic evaluation and test-retest reproducibility of [11C]UCB-J, a novel radioligand for positron emission tomography imaging of synaptic vesicle glycoprotein 2A in humans.

    Science.gov (United States)

    Finnema, Sjoerd J; Nabulsi, Nabeel B; Mercier, Joël; Lin, Shu-Fei; Chen, Ming-Kai; Matuskey, David; Gallezot, Jean-Dominique; Henry, Shannan; Hannestad, Jonas; Huang, Yiyun; Carson, Richard E

    2017-01-01

    Synaptic vesicle glycoprotein 2A (SV2A) is ubiquitously present in presynaptic terminals. Here we report kinetic modeling and test-retest reproducibility assessment of the SV2A positron emission tomography (PET) radioligand [ 11 C]UCB-J in humans. Five volunteers were examined twice on the HRRT after bolus injection of [ 11 C]UCB-J. Arterial blood samples were collected for measurements of radiometabolites and free fraction. Regional time-activity curves were analyzed with 1-tissue (1T) and 2-tissue (2T) compartment models to estimate volumes of distribution ( V T ). Parametric maps were generated using the 1T model. [ 11 C]UCB-J metabolized fairly quickly, with parent fraction of 36 ± 13% at 15 min after injection. Plasma free fraction was 32 ± 1%. Regional time-activity curves displayed rapid kinetics and were well described by the 1T model, except for the cerebellum and hippocampus. V T values estimated with the 2T model were similar to 1T values. Parametric maps were of high quality and V T values correlated well with time activity curve (TAC)-based estimates. Shortening of acquisition time from 120 min to 60 min had a negligible effect on V T values. The mean absolute test-retest reproducibility for V T was 3-9% across regions. In conclusion, [ 11 C]UCB-J exhibited excellent PET tracer characteristics and has potential as a general purpose tool for measuring synaptic density in neurodegenerative disorders.

  4. 7 CFR 1718.52 - Existing mortgages.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 11 2010-01-01 2010-01-01 false Existing mortgages. 1718.52 Section 1718.52... AGRICULTURE LOAN SECURITY DOCUMENTS FOR ELECTRIC BORROWERS Mortgage for Distribution Borrowers § 1718.52 Existing mortgages. Nothing contained in this subpart amends, invalidates, terminates or rescinds any...

  5. Structural reliability of existing city bridges

    NARCIS (Netherlands)

    Hellebrandt, L.; Steenbergen, R.; Vrouwenvelder, T.; Blom, K.

    2015-01-01

    Full probabilistic reliability analysis may be valuable for assessing existing structures. Measures for increasing the safety level are quite costly for existing structures and may be unnecessary when such a decision is grounded on a conservative analysis for determining the structural reliability.

  6. Existence of solutions of functional differential inclusions

    Directory of Open Access Journals (Sweden)

    A. Anguraj

    1992-01-01

    Full Text Available We prove the existence of solutions of a functional differential inclusion. By using the variation of parameters formula we convert the functional differential inclusion into an integral inclusion and prove the existence of a fixed point of the set-valued mapping with the help of the Kakutani-Bohnenblust-Karlin fixed point theorem.

  7. On determining if a specular point exists

    DEFF Research Database (Denmark)

    Rusch, W; Sørensen, O

    1979-01-01

    A technique is presented whereby the existence of a specular point on a convex surface of revolution can be determined without actually finding it. Only the evaluation of two simple algebraic expressions is involved. Should a specular point be found not to exist, a search procedure has been thereby...

  8. On the existence of consistent price systems

    DEFF Research Database (Denmark)

    Bayraktar, Erhan; Pakkanen, Mikko S.; Sayit, Hasanjan

    2014-01-01

    We formulate a sufficient condition for the existence of a consistent price system (CPS), which is weaker than the conditional full support condition (CFS). We use the new condition to show the existence of CPSs for certain processes that fail to have the CFS property. In particular this condition...

  9. Existence test for asynchronous interval iterations

    DEFF Research Database (Denmark)

    Madsen, Kaj; Caprani, O.; Stauning, Ole

    1997-01-01

    In the search for regions that contain fixed points ofa real function of several variables, tests based on interval calculationscan be used to establish existence ornon-existence of fixed points in regions that are examined in the course ofthe search. The search can e.g. be performed...... as a synchronous (sequential) interval iteration:In each iteration step all components of the iterate are calculatedbased on the previous iterate. In this case it is straight forward to base simple interval existence and non-existencetests on the calculations done in each step of the iteration. The search can also...... be performed as an asynchronous (parallel) iteration: Only a few components are changed in each stepand this calculation is in general based on components from differentprevious iterates. For the asynchronous iteration it turns out thatsimple tests of existence and non-existence can be based...

  10. EXIST's Gamma-Ray Burst Sensitivity

    Science.gov (United States)

    Band, D. L.; Grindlay, J. E.; Hong, J.; Fishman, G.; Hartmann, D. H.; Garson, A., III; Krawczynski, H.; Barthelmy, S.; Gehrels, N.; Skinner, G.

    2008-02-01

    We use semianalytic techniques to evaluate the burst sensitivity of designs for the EXIST hard X-ray survey mission. Applying these techniques to the mission design proposed for the Beyond Einstein program, we find that with its very large field of view and faint gamma-ray burst detection threshold, EXIST will detect and localize approximately two bursts per day, a large fraction of which may be at high redshift. We estimate that EXIST's maximum sensitivity will be ~4 times greater than that of Swift's Burst Alert Telescope. Bursts will be localized to better than 40'' at threshold, with a burst position as good as a few arcseconds for strong bursts. EXIST's combination of three different detector systems will provide spectra from 3 keV to more than 10 MeV. Thus, EXIST will enable a major leap in the understanding of bursts, their evolution, environment, and utility as cosmological probes.

  11. Wykrzyknik - istnienie - zmiana (Exclamation - Existence - Change

    Directory of Open Access Journals (Sweden)

    Maciej Karpiński

    2011-06-01

    Full Text Available It, what exists, so to say, demands for the addressee – the thing exists in the face of (for something (or somebody. In other words, the existence is the relation. The competitive conception of the existence outside the relation (existence isolated leads to the contradiction. The existential proposition ‘Some A exists’, understoodliterally, is the pleonasm. It tends to treat the existential proposition as the conventional figure, expressing the simple act of an A affirmation (the exclamation ‘A!’. The existence’s relation should not be narrowed down only to the relation of perception(esse est percipi. It is needed to be understood widely, as every relation, in which something influences on whatever (that is, some change occurs. This influence (change can take place both inside or outside the consciousness. The existing thing, the influence exerted by it, and the change, occurred as the result of this influence, are identical. Thanks to it, we can eliminate difficulties connected withfinding ‘the point of contact’ between modules of the existence’s relation (that is, ‘the place’ where existing thing and its addressee are connected. The existence, as the relation of influence-change, is modal and gradual (as regards both intensity and extensiveness: the thing, in different aspects, can exist more or less. Theoretically, discussed relation can be symmetrical or antisymmetrical. The concept of error should be redefined. The error concerning the existence (resp. the nonexistence of specified thing, must not mean the incompatibility between this thing and the perception (widely: between this thing and the change causedby this thing in its addressee. The existence is the unity of the thing-perception (resp. the thing-influence-change. That is why the incompatibility can occur only between the state of thing-perception (resp. the thing-influence-change and the related state of duty. The conception of the existence as the relation

  12. EXIST: The Next Large GRB Observatory

    Science.gov (United States)

    Fishman, Gerald J.

    2003-01-01

    Studies have begun on the EXIST (Energetic X-ray Imaging Survey Telescope) Mission as a Black Hole Survey 'Einstein Probe', a major element in the new NASA Beyond Einstein Program in the Office of Space Science. This program was approved by the US Congress, in February 2003 as part of the NASA FY2004 NASA budget. EXIST is planned as a very wide-field coded aperture telescope and a positional accuracy for GRBs better than one arc-minute. The baseline detectors are Cadmium-Zinc-Telluride (CZT), with a total sensitive area of approximately 8 m2. EXIST will use SWIFT as a pathfinder mission; the findings of SWIFT will refine the scientific objectives of EXIST and will help to determine many of its design parameters. EXIST will study early star and galaxy formation at high redshifts through observations of thousands of GRBs, their afterglows and host galaxies. It is intended that the international GRB community will play a large role in EXIST through direct participation as well as with complementary observational programs, both space-based and ground-based. Some preliminary design features and capabilities of the EXIST Mission will be presented.

  13. The impact of repeated cycles of radioligand therapy using [177Lu]Lu-PSMA-617 on renal function in patients with hormone refractory metastatic prostate cancer.

    Science.gov (United States)

    Yordanova, Anna; Becker, Anja; Eppard, Elisabeth; Kürpig, Stefan; Fisang, Christian; Feldmann, Georg; Essler, Markus; Ahmadzadehfar, Hojjat

    2017-08-01

    [177Lu]Lu-PSMA-617 is a well-tolerated therapy for the treatment of metastatic prostate cancer. However, because of the mainly renal excretion of the tracer, the kidneys are one of the most limiting organs. The purpose of this study was to examine the post-therapeutic changes in renal function over time and to identify risk factors for developing renal toxicity. We also tested the reliability of markers for renal function monitoring. Fifty-five patients with castrate-resistant metastatic prostate cancer treated with at least three cycles of [177Lu]Lu-PSMA-617 were investigated. Renal function was assessed through laboratory tests (creatinine, GFR, cystatin C) and Tc-99 m-MAG3 measurements. Adverse events were classified according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. To identify risk factors for renal toxicity, we used Pearson's correlation coefficient and the corresponding p values. None of the 55 patients experienced severe nephrotoxicity (grade 3/4). In 14 patients (25%), we observed increased creatinine levels of CTC 1° or 2°. There were 16 cases of increased GFR (grade 1/2). At the baseline, only 14 patients had elevated cystatin C. However, post-therapeutic cystatin C was elevated in 32 patients (58%). A significant effect on renal function was found for age (p = 0.049), hypertension (p = 0.001) and pre-existing kidney disease (p = 0.001). The most reliable predictive markers of nephrotoxicity were TER-MAG3 and cystatin C. Renal toxicity in patients treated with [177Lu]Lu-PSMA-617 was low. There was no (sub)acute grade 3 or 4 nephrotoxicity.

  14. The impact of repeated cycles of radioligand therapy using [{sup 177}Lu]Lu-PSMA-617 on renal function in patients with hormone refractory metastatic prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yordanova, Anna; Becker, Anja; Eppard, Elisabeth; Kuerpig, Stefan; Essler, Markus; Ahmadzadehfar, Hojjat [University Hospital Bonn, Department of Nuclear Medicine, Bonn (Germany); Fisang, Christian [University Hospital Bonn, Department of Urology, Bonn (Germany); Feldmann, Georg [University Hospital Bonn, Department of Internal Medicine, MED3, Bonn (Germany)

    2017-08-15

    [{sup 177}Lu]Lu-PSMA-617 is a well-tolerated therapy for the treatment of metastatic prostate cancer. However, because of the mainly renal excretion of the tracer, the kidneys are one of the most limiting organs. The purpose of this study was to examine the post-therapeutic changes in renal function over time and to identify risk factors for developing renal toxicity. We also tested the reliability of markers for renal function monitoring. Fifty-five patients with castrate-resistant metastatic prostate cancer treated with at least three cycles of [{sup 177}Lu]Lu-PSMA-617 were investigated. Renal function was assessed through laboratory tests (creatinine, GFR, cystatin C) and Tc-99 m-MAG3 measurements. Adverse events were classified according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. To identify risk factors for renal toxicity, we used Pearson's correlation coefficient and the corresponding p values. None of the 55 patients experienced severe nephrotoxicity (grade 3/4). In 14 patients (25%), we observed increased creatinine levels of CTC 1 or 2 . There were 16 cases of increased GFR (grade 1/2). At the baseline, only 14 patients had elevated cystatin C. However, post-therapeutic cystatin C was elevated in 32 patients (58%). A significant effect on renal function was found for age (p = 0.049), hypertension (p = 0.001) and pre-existing kidney disease (p = 0.001). The most reliable predictive markers of nephrotoxicity were TER-MAG3 and cystatin C. Renal toxicity in patients treated with [{sup 177}Lu]Lu-PSMA-617 was low. There was no (sub)acute grade 3 or 4 nephrotoxicity. (orig.)

  15. EXISTENCE OF MATTER IN THE UNIVERSE

    OpenAIRE

    Aksakallı, Cengiz

    2016-01-01

    This study was conducted as an attempt to determine the process of existence of the universe  and whether there is another volume that restricts the universe because of the metric expansion of space, and to determine whether there may be a new universe or existence  in the case of extinction of all the universe by way of mathematical and physical functions.This study was conducted as an attempt to determine the process of existence of the universe  and whether there is another volume that res...

  16. Pre-Existing Condition Insurance Plan Data

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Affordable Care Act created the new Pre-Existing Condition Insurance Plan (PCIP) program to make health insurance available to Americans denied coverage by...

  17. LANDFIRE (90m) Existing Vegetation Type

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This map depicts the distribution of existing vegetation types contained in the LANDFIRE dataset. All 30-meter EVT grids were resampled to 90-meter grids and merged...

  18. Policy on Existing Stocks of Pesticide Products

    Science.gov (United States)

    This statement establishes general principles the Agency generally will apply in determining whether and under what conditions to allow the sale and use of existing stocks of pesticides for which the registration has been amended, canceled, or suspended.

  19. Functional interpretation and the existence property

    DEFF Research Database (Denmark)

    Jørgensen, Klaus Frovin

    2004-01-01

    It is shown that functional interpretation can be used to show the existence property of intuitionistic number theory. On the basis of truth variants a comparison is then made between realisability and functional interpretation showing a structural difference between the two.......It is shown that functional interpretation can be used to show the existence property of intuitionistic number theory. On the basis of truth variants a comparison is then made between realisability and functional interpretation showing a structural difference between the two....

  20. Optimality and existence for Lipschitz equations

    Directory of Open Access Journals (Sweden)

    Johnny Henderson

    1988-01-01

    Full Text Available Solutions of certain boundary value problems are shown to exist for the nth order differential equation y(n=f(t,y,y′,…,y(n−1, where f is continuous on a slab (a,b×Rn and f satisfies a Lipschitz condition on the slab. Optimal length subintervals of (a,b are determined, in terms of the Lipschitz coefficients, on which there exist unique solutions.

  1. [{sup 18}F]F15599, a novel 5-HT{sub 1A} receptor agonist, as a radioligand for PET neuroimaging

    Energy Technology Data Exchange (ETDEWEB)

    Lemoine, Laetitia; Verdurand, Mathieu [Universite de Lyon, Laboratory of Neuropharmacology, Lyon (France); CERMEP - Imagerie du Vivant, PET Department, Lyon (France); Vacher, Bernard; Blanc, Elodie; Newman-Tancredi, Adrian [Centre de Recherches Pierre Fabre, Castres (France); Le Bars, Didier [CERMEP - Imagerie du Vivant, PET Department, Lyon (France); Zimmer, Luc [Universite de Lyon, Laboratory of Neuropharmacology, Lyon (France); CERMEP - Imagerie du Vivant, PET Department, Lyon (France); CERMEP - Imagerie du Vivant, ANIMAGE Department, Lyon (France)

    2010-03-15

    The serotonin-1A (5-HT{sub 1A}) receptor is implicated in the pathophysiology of major neuropsychiatric disorders. Thus, the functional imaging of 5-HT{sub 1A} receptors by positron emission tomography (PET) may contribute to the understanding of its role in those pathologies and their therapeutics. These receptors exist in high- and low-affinity states and it is proposed that agonists bind preferentially to the high-affinity state of the receptor and therefore could provide a measure of the functional 5-HT{sub 1A} receptors. Since all clinical PET 5-HT{sub 1A} radiopharmaceuticals are antagonists, it is of great interest to develop a{sup 18}F labelled agonist. F15599 (3-chloro-4-fluorophenyl-(4-fluoro-4{l_brace}[(5-methyl-pyrimidin-2-ylmethyl)-amino]-methyl{r_brace}-piperidin-1-yl)-methanone) is a novel ligand with high affinity and selectivity for 5-HT{sub 1A} receptors and is currently tested as an antidepressant. In pharmacological tests in rat, it exhibits preferential agonist activity at post-synaptic 5-HT{sub 1A} receptors in cortical brain regions. Here, its nitro-precursor was synthesised and radiolabelled via a fluoronucleophilic substitution. Radiopharmacological evaluations included in vitro and ex vivo autoradiography in rat brain and PET scans on rats and cats. Results were compared with simultaneous studies using [{sup 18}F]MPPF, a validated 5-HT{sub 1A} antagonist radiopharmaceutical. The chemical and radiochemical purities of [{sup 18}F]F15599 were >98%. In vitro [{sup 18}F ]F15599 binding was consistent with the known 5-HT{sub 1A} receptors distribution (hippocampus, dorsal raphe nucleus, and notably cortical areas) and addition of Gpp(NH)p inhibited [{sup 18}F ]F15599 binding, consistent with a specific binding to G protein-coupled receptors. In vitro binding of [{sup 18}F]F15599 was blocked by WAY100635 and 8-OH-DPAT, respectively, prototypical 5-HT{sub 1A} antagonist and agonist. The ex vivo and in vivo studies demonstrated that the radiotracer

  2. Transcendental Self and the Feeling of Existence

    Directory of Open Access Journals (Sweden)

    Apaar Kumar

    2016-06-01

    Full Text Available In this essay, I investigate one aspect of Kant’s larger theory of the transcendental self. In the Prolegomena, Kant says that the transcendental self can be represented as a feeling of existence. In contrast to the view that Kant errs in describing the transcendental self in this fashion, I show that there exists a strand in Kant’s philosophy that permits us to interpret the representation of the transcendental self as a feeling of existence—as the obscurely conscious and temporally inaccessible modification of the state of the discursive subject, which is built into all the representations of such a subject. I also provide an account of how the transcendental self can be legitimately understood both as an epistemic condition for the possibility of experience as well as the representation of a non-naturalistic feeling of existence.

  3. The Existence of Public Protection Unit

    Directory of Open Access Journals (Sweden)

    Moh. Ilham A. Hamudy

    2014-12-01

    Full Text Available This article is about the Public Protection Unit (Satlinmas formerly known as civil defence (Hansip. This article is a summary of the results of the desk study and fieldwork conducted in October-November 2013 in the town of Magelang and Surabaya. This study used descriptive qualitative approach to explore the combined role and existence Satlinmas. The results of the study showed, the existence of the problem Satlinmas still leave many, including, first, the legal basis for the establishment of Satlinmas. Until now, there has been no new regulations governing Satlinmas. Existing regulations are too weak and cannot capture the times. Second, the formulation of concepts and basic tasks and functions Satlinmas overlap with other institutions. Third, Satlinmas image in society tend to fade and abused. Fourth, Satlinmas incorporation into the Municipal Police deemed not appropriate, because different philosophy.

  4. Existing bridge evaluation using deficiency point method

    Directory of Open Access Journals (Sweden)

    Vičan Josef

    2016-01-01

    Full Text Available In the transforming EU countries, transportation infrastructure has a prominent position in advancing industry and society. Recent developments show, that attention should be moved from the design of new structures towards the repair and reconstruction of existing ones to ensure and increase their satisfactory structural reliability and durability. The problem is very urgent because many construction projects, especially transport infrastructure, in most European countries are more than 50-60 years old and require rehabilitations based on objective evaluations. Therefore, the paper presents methodology of existing bridge evaluation based on reliability concept using Deficiency Point Method. The methodology was prepared from the viewpoint to determine the priority order for existing bridge rehabilitation.

  5. Robustness and health monitoring of existing bridges

    OpenAIRE

    Casas Rius, Joan Ramon

    2015-01-01

    The paper shows how the robustness concept, mainly developed and thought for the design of new structures, and the monitoring by suitable sensors based on fiber optics can also play a relevant role in the safety and management of existing bridges. A new approach of robustness more related to the long-term and service life of bridges is presented and its advantages in the decision-making process during the management of existing bridges are highlighted and afterwards applied on a real brid...

  6. Radiosynthesis of [{sup 11}C]D.P.A.-713, [{sup 11}C]D.P.A.-715 and [{sup 11}C]clinme, selected carbon-11-labelled novel potential radioligands for imaging the peripheral benzodiazepine receptors with PET

    Energy Technology Data Exchange (ETDEWEB)

    Dolle, F.; Thominiaux, C.; Hinnen, F.; Demphel, S.; Le helleix, S.; Chauveau, F.; Boutin, H.; Herard, A.S.; Hantraye, P.; Tavitian, B. [Service Hospitalier Frederic Joliot, I2BM/DSV, 91 - Orsay (France); Kassiou, M.; James, M.; Creelman, A.; Fulton, R. [Sydney Univ., Brain and Mind Research Institute, NSW (Australia); Kassiou, M. [Sydney Univ., Discipline of Medical Radiations, Sciences and School of Chemistry, NSW (Australia); Katsifis, A.; Greguric, I.; Mattner, F.; Loch, C. [Radiopharmaceuticals Research Institute, ANSTO, NSW (Australia); Selleri, S. [Degli Studi di Firenze Univ., Dipt. di Scienze Farmaceutiche (Italy)

    2008-02-15

    {sup 11}C P.K.11195 is not only the oldest, but also the most widely used PET radiotracer for in vivo imaging of the peripheral benzodiazepine receptors (P.B.R. or translocator protein (18 kDa, T.S.P.O.). With the aim of developing a new PET imaging probe for the in vivo study of the P.B.R., two pyrazol [1,5-a]pyrimidineacetamides (D.P.A.-713 and D.P.A.-715) and one imidazol[1,2-a]pyridine-acetamide (C.L.I.N.M.E.) were radiolabelled with the positron emitters carbon{sup 11} (half life: 20.38 min) [1-5]. Briefly, C.L.I.N.M.E. (2-[6-chloro-2(4-iodophenyl)-imidazol[1,2-a]pyridin-3-yl] -N-ethyl-N-methyl-acetamide) was labelled at its methyl-acetamide moity chain from the corresponding nor-analogue using[{sup 11}C]methyl iodide (in D.M.S.O./D.M.F (100/200 {mu}L) containing powdered K.O.H. (3-5 mg) at 110 degrees C for 3 min. D.P.A.-713 (N,N-diethyl-2-[2-(4-methoxy-phenyl)-5,7-dimethyl-pyrazolo[1,5-a]pyrimidin -3-yl]acetamide) and D.P.A.-715 (N,N-diethyl-2-[2-(4-methoxy-phenyl)-5,7-bis-tri-fluoro-methyl-pyrazolo [1,5-a]pyrimidin-3-yl]acetamide) were labelled at their aromatic methoxy groups from the corresponding nor-derivatives using [{sup 11}C]methyl triflate (in acetone (300{mu}L) containing aq. 3 M NaOH (4{mu}L) at 110 degrees C for 1 min). All radioligands were purified using semi preparative Zorbax reverse phase H.P.L.C., were adequately formulated for in vivo injection within 30 min and were found to be > 95% chemically and radiochemically pure. (N.C.)

  7. Foucault, Counselling and the Aesthetics of Existence

    Science.gov (United States)

    Peters, Michael A.

    2005-01-01

    Michel Foucault was drawn late in life to study the "arts of the self" in Greco-Roman culture as a basis, following Nietzsche, for what he called an "aesthetics of existence." By this, he meant a set of creative and experimental processes and techniques by which an individual turns him- or herself into a work of art. For Nietzsche, it was above…

  8. Proof That Chronic Lyme Disease Exists

    Directory of Open Access Journals (Sweden)

    Daniel J. Cameron

    2010-01-01

    Full Text Available The evidence continues to mount that Chronic Lyme Disease (CLD exists and must be addressed by the medical community if solutions are to be found. Four National Institutes of Health (NIH trials validated the existence and severity of CLD. Despite the evidence, there are physicians who continue to deny the existence and severity of CLD, which can hinder efforts to find a solution. Recognizing CLD could facilitate efforts to avoid diagnostic delays of two years and durations of illness of 4.7 to 9 years described in the NIH trials. The risk to society of emerging antibiotic-resistant organisms should be weighed against the societal risks associated with failing to treat an emerging population saddled with CLD. The mixed long-term outcome in children could also be examined. Once we accept the evidence that CLD exists, the medical community should be able to find solutions. Medical professionals should be encouraged to examine whether: (1 innovative treatments for early LD might prevent CLD, (2 early diagnosis of CLD might result in better treatment outcomes, and (3 more effective treatment regimens can be developed for CLD patients who have had prolonged illness and an associated poor quality of life.

  9. Modeling Truth Existence in Truth Discovery.

    Science.gov (United States)

    Zhi, Shi; Zhao, Bo; Tong, Wenzhu; Gao, Jing; Yu, Dian; Ji, Heng; Han, Jiawei

    2015-08-01

    When integrating information from multiple sources, it is common to encounter conflicting answers to the same question. Truth discovery is to infer the most accurate and complete integrated answers from conflicting sources. In some cases, there exist questions for which the true answers are excluded from the candidate answers provided by all sources. Without any prior knowledge, these questions, named no-truth questions, are difficult to be distinguished from the questions that have true answers, named has-truth questions. In particular, these no-truth questions degrade the precision of the answer integration system. We address such a challenge by introducing source quality, which is made up of three fine-grained measures: silent rate, false spoken rate and true spoken rate. By incorporating these three measures, we propose a probabilistic graphical model, which simultaneously infers truth as well as source quality without any a priori training involving ground truth answers. Moreover, since inferring this graphical model requires parameter tuning of the prior of truth, we propose an initialization scheme based upon a quantity named truth existence score, which synthesizes two indicators, namely, participation rate and consistency rate. Compared with existing methods, our method can effectively filter out no-truth questions, which results in more accurate source quality estimation. Consequently, our method provides more accurate and complete answers to both has-truth and no-truth questions. Experiments on three real-world datasets illustrate the notable advantage of our method over existing state-of-the-art truth discovery methods.

  10. Conservation and Development Options existing on Uluguru ...

    African Journals Online (AJOL)

    Conservation and Development Options existing on Uluguru Mountains, Tanzania. ... Tanzania Journal of Forestry and Nature Conservation ... Abstract. Effective management of projects on Uluguru Mountains requires that both development and conservation options are weighed and that opportunities and challenges are ...

  11. 36 CFR 9.33 - Existing operations.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Existing operations. 9.33 Section 9.33 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR... permit may be continued for the term of that permit, exclusive of any renewal period whether mandatory or...

  12. Factorial Structure of the Existence Scale

    NARCIS (Netherlands)

    Brouwers, Tomic, W. A.

    2015-01-01

    Existential meaning in life is becoming an increasingly important measure of personal assessment. In search of a suitable instrument to measure existential meaning, the authors reviewed several measures. Eventually, they selected the Existence Scale (ES), doing so on theoretical grounds. The ES is a

  13. Transforming existing content into reusable Learning Objects

    NARCIS (Netherlands)

    Doorten, Monique; Giesbers, Bas; Janssen, José; Daniels, Jan; Koper, Rob

    2003-01-01

    Please cite as: Doorten, M., Giesbers, B., Janssen, J., Daniëls, J, & Koper, E.J.R., (2004). Transforming existing content into reusable learning objects. In R. McGreal, Online Education using Learning Objects (pp. 116-127). London: RoutledgeFalmer.

  14. 7 CFR 15b.18 - Existing facilities.

    Science.gov (United States)

    2010-01-01

    ... access to otherwise inaccessible areas or features of historic properties; (ii) Using audio-visual... visits, delivery of services at alternate accessible sites, alteration of exiting facilities and... significant alteration in its existing facilities, the recipient may, as an alternative, refer the handicapped...

  15. Implementation of ventilation in existing schools

    DEFF Research Database (Denmark)

    Hviid, Christian Anker; Petersen, Steffen

    ; they evaluate both scientific and practical implementation The analyses lead to a list of criteria associated with the implementation of ventilation in existing schools. Generic retrofitting scenarios which prioritize energy savings, indoor climate and building/facade integration are assembled and illustrated...

  16. Human organisms begin to exist at fertilization.

    Science.gov (United States)

    Miller, Calum; Pruss, Alexander

    2017-09-01

    Eugene Mills has recently argued that human organisms cannot begin to exist at fertilization because the evidence suggests that egg cells persist through fertilization and simply turn into zygotes. He offers two main arguments for this conclusion: that 'fertilized egg' commits no conceptual fallacy, and that on the face of it, it looks as though egg cells survive fertilization when the process is watched through a microscope. We refute these arguments and offer several reasons of our own to think that egg cells do not survive fertilization, appealing to various forms of essentialism regarding persons, fission cases, and a detailed discussion of the biological facts relevant to fertilization and genetics. We conclude that it is plausible, therefore, that human organisms begin to exist at fertilization - or, at the very least, that there are grounds for thinking that they existed as zygotes which do not apply to the prior egg cells. While this does not entail that human persons begin to exist at this point, it nevertheless has considerable significance for this latter question. © 2017 John Wiley & Sons Ltd.

  17. "Giftedness Science": Does It Exist at All?

    Science.gov (United States)

    David, Hanna

    2012-01-01

    In this commentary, the author finds that the target article, "Cultural Variation and Dominance in a Globalised Knowledge-Economy: Towards a Culture-Sensitive Research Paradigm in the Science of Giftedness", has three substantial failures: (1) an unproven, even incorrect assumption about the existence of bias in the "science of giftedness" due to…

  18. Gambling on the existence of other universes

    CERN Document Server

    Sangalli, Arturo

    2016-01-01

    Speculations and theories about the existence of other worlds have a long history. In recent times, the arguments have shifted away from their typical philosophical and theological character to supposedly become more objective thanks to their scientific underpinnings. A prime example of this is the current parallel universes or multiverse theory, which has the support of a number of famous cosmologists. In this article, we contend that the claim for the existence of those parallel universes, as presented in Max Tegmark's book "Our Mathematical Universe", rests crucially on some questionable probability arguments involving infinity. As a result, a doubt is cast over the multiverse hypothesis: Is it more credible than the counterarguments based on philosophical and metaphysical considerations?

  19. Co-existence in multispecies biofilm communities

    DEFF Research Database (Denmark)

    Røder, Henriette Lyng

    environment to evaluate their biofilm formation capability. It was found that multispecies consortia could lead to increased biofilm formation compared to mono species growth. This shows how co-localized isolates are able to influence biofilm production in a community with high relevance for food safety...... and production. The analysis was further extended in manuscript 3, in which the effect of social interac-tions on biofilm formation in multispecies co-cultures isolated from a diverse range of environments was examined. The question raised was whether the interspecific interactions of co-existing bacteria...... generally lead to enhanced biofilm formation in complex communities. We showed that bacteria, expected to have co-existed for a long time, generated more biofilm biomass in co-culture. This was further tested against random co-cultures of bacteria, which supported the conclusion. Discovering that some...

  20. Overview of Existing Wind Energy Ordinances

    Energy Technology Data Exchange (ETDEWEB)

    Oteri, F.

    2008-12-01

    Due to increased energy demand in the United States, rural communities with limited or no experience with wind energy now have the opportunity to become involved in this industry. Communities with good wind resources may be approached by entities with plans to develop the resource. Although these opportunities can create new revenue in the form of construction jobs and land lease payments, they also create a new responsibility on the part of local governments to ensure that ordinances will be established to aid the development of safe facilities that will be embraced by the community. The purpose of this report is to educate and engage state and local governments, as well as policymakers, about existing large wind energy ordinances. These groups will have a collection of examples to utilize when they attempt to draft a new large wind energy ordinance in a town or county without existing ordinances.

  1. Sustainability in the existing building stock

    DEFF Research Database (Denmark)

    Elle, Morten; Nielsen, Susanne Balslev; Hoffmann, Birgitte

    2005-01-01

    sustainable building. In other words: the question is if it sensible to talk about a ‘sustainable building’ without taking the activities in the building into account? In many contexts, maintenance of the existing building stock is not a hot political topic. Facilities management can, however, be a vehicle......This paper explores the role of Facilities Management in the relation to sustainable development in the existing building stock. Facilities management is a concept still developing as the management of buildings are becoming more and more professional. Many recognize today that facilities......, QRWfacilities management’s most important contribution to sustainable development in the built environment. Space management is an essential tool in facilities management – and it could be considered a powerful tool in sustainable development; remembering that the building not being built is perhaps the most...

  2. Co-existence of agricultural production systems.

    Science.gov (United States)

    Jank, Bernhard; Rath, Johannes; Gaugitsch, Helmut

    2006-05-01

    Strategies and best practices for the co-existence of GM and non-GM crops need to be developed and implemented with the participation of farmers and other stakeholders. According to the principle of 'subsidiarity', decisions should be made by the lowest authority possible. When applying this concept to the case of GM crops, the affected society should determine their use and management in a regional decision-making process. Public participation is better accomplished at a lower level, and democratic deficits in decision-making on GMOs are better resolved, enabling farmers to manage or avoid GM crops. Ultimately, voluntary GMO-free zones might be a tool for sustainable co-existence and GM-free production and GMO-free zones might create a specific image for marketing regional products and services, such as tourism.

  3. LOVE’S SYMPHONY: MULTIPLICITY OF EXISTENCE

    Directory of Open Access Journals (Sweden)

    CHRISTINE McNEILL-MATTESON

    2016-05-01

    Full Text Available Love, although universal in thought, is explicitly complex and articulately multi-defined in almost every idea and expression. Love written is timeless from the molecules we possess within us, to the cosmos we study and explore. We can only exist and continue to exist in harmony with creation. Harmony reaches far beyond galaxies and universes, flowing backinto the most separate of the smallest molecules. Within all common denominators of harmony there is love: the very catalyst of harmony itself. This paper will look at harmony from a poetic point of view and examine how it is expressed always in the context of the mystery of sentience and conscience from human biology to the divine cosmos

  4. Does H4SO5 exist?

    Science.gov (United States)

    Murillo, Fernando; Vargas-Caamal, Alba; Pan, Sudip; Cabellos, José Luis; Mora-Fonz, Miguel J; Muñoz-Castro, Alvaro; Restrepo, Albeiro; Merino, Gabriel

    2017-07-14

    The possible existence of H4SO5 in aqueous sulfuric acid is analyzed in detail. For bare H4SO5, the computed free energy barrier for the exergonic transformation of H4SO5 into the H2SO4H2O complex is only 3.8 kcal mol-1. The presence of water or sulfuric acid catalyzes the dehydration to such an extent that it becomes almost a barrierless process. In the gas phase, dehydration of H4SO5 is an autocatalytic reaction as the water molecule produced by the decomposition of one H4SO5 molecule induces further dissociation. Thus, in solution, the surrounding water molecules make the para-sulfuric acid a very vulnerable species to exist. The simulated Raman spectra also corroborate the absence of H4SO5 in solution.

  5. The Italian contribution to the EXIST mission

    Science.gov (United States)

    Natalucci, L.; Tagliaferri, G.; Caraveo, P.; Pareschi, G.; Ubertini, P.; Villa, G.

    The EXIST Mission is a proposed multi-wavelength observatory to carry out the most sensitive hard X-ray survey and census of SMBH as well as the most powerful follow-up of Gamma Ray Bursts (GRBs). This mission will carry a large area (4.5m2) CdZnTe modular detector with an angular resolution of ˜2arcmin, sensitive in the energy range 5-600 keV, and a near infrared telescope with cooled mirror with outstanding sensitivity and capability of measuring onboard the redshift of many GRBs. Italy will contribute to EXIST with the provision of a soft X-ray telescope sensitive in the energy range 0.1-10 keV with an effective area approximately equivalent to one mirror module of XMM-Newton. We will describe hereafter the characteristics and performance of this instrument together with its capability of performing serendipitous surveys.

  6. PET radioligand injection for pig neuroimaging

    DEFF Research Database (Denmark)

    Alstrup, Aage Kristian Olsen; Munk, Ole Lajord; Landau, Anne M.

    2018-01-01

    Pigs are useful models in neuroimaging studies with positron emission tomography. Radiolabeled ligands are injected intravenously at the start of the scan and in pigs, the most easily accessible route of administration is the ear vein. However, in brain studies the short distance between the brai...

  7. A General Existence Thorem of Zero Points

    NARCIS (Netherlands)

    Herings, P.J.J.; Koshevoy, G.A.; Talman, A.J.J.; Yang, Z.F.

    2002-01-01

    Let X be a non-empty, compact, convex set in Rn and ° an upper semi-continuous mapping from X to the collection of non-empty, compact, convex subsets of Rn.It is well known that such a mapping has a stationary point on X, i.e. there exists a point in X satisfying that its image under ° has a

  8. Maximising the value of existing buildings.

    Science.gov (United States)

    McCorkindale, Graham

    2012-10-01

    Graham McCorkindale, who heads the Health and Wellbeing strand at multi-disciplinary architecture, town planning, interior design, and landscape architecture practice, Keppie Design, examines how architects can best support the NHS at a time of major change by refocusing design skills hitherto focused on creating new healthcare facilities on the need to work within the existing estate--'maximising utilisation and getting best value from any available spend'.

  9. Business Plan for Existing Venture: Papu Cafe

    OpenAIRE

    Truc, Nha

    2017-01-01

    Finland is considered as one of the potential markets for specialty coffee industry with the high amount of coffee consumption. The aim of this research is developing a business plan for existing business – Papu Cafe in the center of Helsinki, Finland. In this research, the author focuses on investigating the entrepreneurship and coffee industry in Finland, the characteristics of coffee drinking trends. Besides, it is essential to understand the purpose of conducting a business plan for ...

  10. On the existence of persistently outperforming firms

    OpenAIRE

    Capasso, M.; Cefis, E.; Frenken, K.

    2014-01-01

    This study analyses persistence in growth rates for a data set of manufacturing firms of all sizes. Previous quantile autoregressions of firm growth rates show that extreme growth events are likely to be negatively correlated over time, thus questioning the existence of persistent outperformers. By supplementing the quantile regression analyses with transition probability matrices, our study shows that "bouncing" firms coexist with persistent outperformers. This result is shown to be robust f...

  11. Partial Cooperative Equilibria: Existence and Characterization

    Directory of Open Access Journals (Sweden)

    Amandine Ghintran

    2010-09-01

    Full Text Available We study the solution concepts of partial cooperative Cournot-Nash equilibria and partial cooperative Stackelberg equilibria. The partial cooperative Cournot-Nash equilibrium is axiomatically characterized by using notions of rationality, consistency and converse consistency with regard to reduced games. We also establish sufficient conditions for which partial cooperative Cournot-Nash equilibria and partial cooperative Stackelberg equilibria exist in supermodular games. Finally, we provide an application to strategic network formation where such solution concepts may be useful.

  12. The slowdown in existing home sales

    OpenAIRE

    Krainer, John

    2014-01-01

    Sales of existing homes slowed noticeably over the second half of 2013, reflecting a more drawn-out recovery than expected for housing markets. A main reason for the slowdown is higher mortgage rates that have made financing more costly nationwide. Sales appear to be slowing even more in distressed markets, where real estate investors had bought up single-family homes to convert into rental properties following the housing bust. Evidence suggests that investors may be retreating from these ma...

  13. Does evaporation paradox exist in China?

    Directory of Open Access Journals (Sweden)

    Z. T. Cong

    2009-03-01

    Full Text Available One expected consequence of global warming is the increase in evaporation. However, lots of observations show that the rate of evaporation from open pans of water has been steadily decreasing all over the world in the past 50 years. The contrast between expectation and observation is called "evaporation paradox". Based on data from 317 weather stations in China from 1956 to 2005, the trends of pan evaporation and air temperature were obtained and evaporation paradox was analyzed. The conclusions include: (1 From 1956 to 2005, pan evaporation paradox existed in China as a whole while pan evaporation kept decreasing and air temperature became warmer and warmer, but it does not apply to Northeast and Southeast China; (2 From 1956 to 1985, pan evaporation paradox existed narrowly as a whole with unobvious climate warming trend, but it does not apply to Northeast China; (3 From 1986 to 2005, in the past 20 years, pan evaporation paradox did not exist for the whole period while pan evaporation kept increasing, although it existed in South China. Furthermore, the trend of other weather factors including sunshine duration, windspeed, humidity and vapor pressure deficit, and their relations with pan evaporation are discussed. As a result, it can be concluded that pan evaporation decreasing is caused by the decreasing in radiation and wind speed before 1985 and pan evaporation increasing is caused by the decreasing in vapor pressure deficit due to strong warming after 1986. With the Budyko curve, it can be concluded that the actual evaporation decreased in the former 30 years and increased in the latter 20 year for the whole China.

  14. Overview of EXIST mission science and implementation

    Science.gov (United States)

    Grindlay, J.; Gehrels, N.; Bloom, J.; Coppi, P.; Soderberg, Al.; Hong, J.; Allen, B.; Barthelmy, S.; Tagliaferri, G.; Moseley, H.; Kutyrev, A.; Fabbiano, G.; Fishman, G.; Ramsey, B.; Della Ceca, R.; Natalucci, L.; Ubertini, P., III

    2010-07-01

    The Energetic X-ray Imaging Survey Telescope (EXIST) is designed to i) use the birth of stellar mass black holes, as revealed by cosmic Gamma-Ray Bursts (GRBs), as probes of the very first stars and galaxies to exist in the Universe. Both their extreme luminosity (~104 times larger than the most luminous quasars) and their hard X-ray detectability over the full sky with wide-field imaging make them ideal "back-lights" to measure cosmic structure with X-ray, optical and near-IR (nIR) spectra over many sight lines to high redshift. The full-sky imaging detection and rapid followup narrowfield imaging and spectroscopy allow two additional primary science objectives: ii) novel surveys of supermassive black holes (SMBHs) accreting as very luminous but rare quasars, which can trace the birth and growth of the first SMBHs as well as quiescent SMBHs (non-accreting) which reveal their presence by X-ray flares from the tidal disruption of passing field stars; and iii) a multiwavelength Time Domain Astrophysics (TDA) survey to measure the temporal variability and physics of a wide range of objects, from birth to death of stars and from the thermal to non-thermal Universe. These science objectives are achieved with the telescopes and mission as proposed for EXIST described here.

  15. Do retroperitoneal extragonadal germ cell tumours exist?

    Science.gov (United States)

    Punjani, Nahid; Winquist, Eric; Power, Nicholas

    2015-01-01

    Extragonadal germ cell tumours (GCTs) have been described arising in midline structures. Although primary retroperitoneal extragonadal GCTs (RPGCTs) comprise 30% to 40% of these, their existence as a genuine disease has been questioned. Our study evaluated clinicopathological findings to examine this question in RPGCT patients at our centre. Data from 414 men between 1980 and 2014 treated at London Health Sciences Centre with chemotherapy for testicular GCTs were reviewed retrospectively. Primary RPGCT was defined as pathologically diagnosed GCT with no evidence of GCT in the testes by physical exam or ultrasound. Patients thought to have primary RPGCT at the time of initial diagnosis were identified from an electronic database and data were extracted. In total, 18 men with a diagnosis of metastatic RPGCT were identified. Four were excluded due to ultrasound reports that were incomplete or suggested malignancy. The remaining 14 patients had negative or non-specific ultrasounds, and all received platinum-based combination chemotherapy. Ten patients (71%) underwent post-chemotherapy RP lymph node dissections; of those 8 (57%) who underwent orchiectomy, none had corresponding pathologically normal testicular tissue. RPGCT patients present with more advanced disease stage. Our study sample size is limited, but the findings are consistent with existing literature suggesting that primary RPGCTs may not exist as a unique disease, but instead may represent metastatic disease from a clinically occult testicular primary. By corollary, viable malignant germ cells may be present in testes of patients with presumed primary RPGCT, and may persist as a site of residual malignant disease after chemotherapy.

  16. Conditions for the existence of clines.

    Science.gov (United States)

    Nagylaki, T

    1975-07-01

    A very general partial differential equation in space and time satisfied by the gene frequency in a monoecious population distributed continuously over an arbitrary habitat is derived. The treatment is restricted to a single diallelic locus in the absence of mutation and random drift, and it is supposed that time is continuous, births and deaths occur at random, and migration is independent of genotype. With the further assumptions that migration is isotropic and homogeneous, the population density is constant and uniform (as permitted by the population regulation mechanism included in the formulation), and Hardy-Weinberg proportions obtain locally, this partial differential equation reduces to the simplest multidimensional generalization of the classical Fisher-Haldane cline model. The efficacy of migration and selection in maintaining genetic variability at equilibrium in this model is investigated by deducing conditions for the existence of clines under various circumstances. The effects of the degree of dominance, a neutral belt between the regions where a particular allele is advantageous and deleterious, finiteness of the habitat, and habitat dimensionality are evaluated. Provided at least one of the alleles is favored only in a finite region, excluding the special case in which its total effective selective coefficient is zero, if conditions for supporting a cline are too unfavorable because migration is too strong, selection is too weak, or both, a cline cannot exist at all. Thus, unless there is overdominance, the population must be monomorphic. It is possible for a cline which can barely exist under the prevailing ecological circumstances to show a large amount of variation in gene frequency.

  17. Existence of collateral Equilibrium without survival assumption

    Directory of Open Access Journals (Sweden)

    Jaime Orrillo

    2011-03-01

    Full Text Available This paper shows the existence of a collateral equilibrium without assuming any hypotheses on the strict positivity, be they individual initial endowments, including the ex post initial endowments, or aggregated initial endowments. Because of dropping the strict positivity of social initial endowment we fail to get an equilibrium. Instead, we get a quasi-equilibrium. Then, appealing to the concept of irreducibility (introduced by McKenzie in 1959 which is adapted to the collateral model, we show that the quasi-equilibrium is indeed a legitime equilibrium.

  18. Existing cometary data and future needs

    Science.gov (United States)

    Rahe, J.

    1981-01-01

    To assist scientists studying comets and their interaction with the interplanetary medium, compilations of existing cometary observations and data plans for additional publication are reported. The works cited include updates and/or supplements to: (1) the Catalogue of Cometary Orbits, (2) Physical Characteristics of Comets, (3) the Atlas of Representative Cometary Spectra, (4) the Atlas Cometas-Viento Solar, (5) the Isophotometrischer Atlas der Kometen, and (6) the Atlas of Cometary Forms. An Atlas of Cometary Spectra and an Atlas of Comet Halley 1910 (II) photographs and spectra are in preparation.

  19. Does the Kuleshov Effect really Exist?

    DEFF Research Database (Denmark)

    Barratt, Daniel; Cabak Rédei, Anna

    2013-01-01

    , sadness, and hunger/neutral conditions with equivalent stimuli. For each film sequence, the participant was asked: to rate the valence of the depicted person’s emotion; to rate how aroused the person appeared to be; and to identify the type of emotion that the person was feeling. The participant’s eye...... movements were recorded throughout the experiment using a remote eye-tracker (SMI iView X RED). A preliminary analysis of the results suggests that some sort of Kuleshov effect does in fact exist. For the different emotional conditions, the participants tended to choose the appropriate emotion more...

  20. Does the Kuleshov Effect Really Exist?

    DEFF Research Database (Denmark)

    Barratt, Daniel; Rédei, Anna Cabak; Innes-Ker, Åse

    2016-01-01

    to replicate Kuleshov’s original experiment using an improved experimental design. In a behavioral and eye tracking study, 36 participants were each presented with 24 film sequences of neutral faces across six emotional conditions. For each film sequence, the participants were asked to evaluate the emotion...... of the target person in terms of valence, arousal, and category. The participants’ eye movements were recorded throughout. The results suggest that some sort of Kuleshov effect does in fact exist. For each emotional condition, the participants tended to choose the appropriate category more frequently than...... between the emotional conditions....

  1. Do ‘African’ universities exist?

    DEFF Research Database (Denmark)

    2015-01-01

    This chapter provides a background for understanding the book. We outline some of the debates in which the individual chapters are situated and thereby show how the book contributes to and fills gaps in existing research. After providing a short history of African universities, the chapter...... by arguing that it is incorrect to talk about African universities as a certain type of university due to the different colonial heritage. However, universities in Africa are facing a number of similar challenges related to the European heritage of the university for instance what counts as legitimate...

  2. Energy Savings Measure Packages. Existing Homes

    Energy Technology Data Exchange (ETDEWEB)

    Casey, Sean [National Renewable Energy Lab. (NREL), Golden, CO (United States); Booten, Chuck [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    2011-11-01

    This document presents the most cost effective Energy Savings Measure Packages (ESMP) for existing mixed-fuel and all electric homes to achieve 15% and 30% savings for each BetterBuildings grantee location across the United States. These packages are optimized for minimum cost to homeowners for source energy savings given the local climate and prevalent building characteristics (i.e. foundation types). Maximum cost savings are typically found between 30% and 50% energy savings over the reference home; this typically amounts to $300 - $700/year.

  3. Weighing Supermassive Black Holes with EXIST

    Science.gov (United States)

    Coppi, Paolo S.; Pappadakis, I.; ScienceTeam, EXIST

    2009-12-01

    The EXIST mission concept features a wide field of view telescope that scans the full sky every two orbits at hard X-ray energies (5-600 keV) as well as a high resolution (R 3000) near infrared/optical spectrograph that can be quickly slewed to new targets. These two instruments will enable us to extend supermassive black hole timing studies (reverberation mapping and power spectrum break determination) from the current sample of 30 objects to well over 300, including highly obscured ones. We present examples of the direct black hole mass determinations such studies will enable.

  4. Serum biochemistry profile determination for wild loggerhead sea turtles nesting in Campos dos Goytacazes, Rio de Janeiro, Brazil Determinação do perfil bioquímico sérico de tartarugas marinhas de vida livre da espécie em nidação em Campos dos Goytacazes, Rio de Janeiro, Brasil

    Directory of Open Access Journals (Sweden)

    Daphne Wrobel Goldberg

    2011-01-01

    ecossistemas. As análises bioquímicas são exames bastante utilizados na detecção de doenças e na avaliação do estado geral dos animais. Apesar disso, os dados na literatura para tartarugas marinhas ainda são escassos, e a maioria dos estudos utiliza um pequeno número de animais, sendo a maior parte deles de cativeiro. O presente estudo tem por objetivo realizar o perfil bioquímico de indivíduos do sexo feminino de tartarugas marinhas de vida livre da espécie Caretta caretta em processo de nidação, bem como estabelecer a correlação do perfil bioquímico destes animais com seu tamanho. Os valores médios obtidos poderão ser utilizados posteriormente como comparativo para avaliação do estado geral e para o diagnóstico de doenças de diversas populações de tartarugas marinhas. Foram utilizadas 28 fêmeas em período reprodutivo, em Farol de São Thomé (21°45'15"S - 41°19'28"W, no município de Campos dos Goytacazes, região norte-fluminense. As amostras foram coletadas sem anticoagulante, através de venopunção do seio venoso cervical dorsal. Os valores médios encontrados para as variáveis cálcio, fósforo, colesterol e triglicerídeos demonstram a correlação desses componentes com o processo de vitelogênese e a formação do ovo. O fato de as fêmeas reduzirem a alimentação, no período que antecede a postura dos ovos, influenciou a concentração média de uréia (35,25mg dL-1, sódio (147mEq L-1, potássio, ácido úrico e lipídios. As variáveis vinculadas ao tamanho das tartarugas apresentaram correlação positiva com enzimas ALT e AST, sugerindo que animais com maior volume hepático apresentam maior atividade enzimática.

  5. Neutralino dark matter stars can not exist

    Science.gov (United States)

    Dai, De-Chang; Stojkovic, Dejan

    2009-08-01

    Motivated by the recent ``Cosmos Project" observation of dark-matter concentrations with no ordinary matter in the same place, we study the question of the existence of compact objects made of pure dark matter. We assume that the dark matter is neutralino, and compare its elastic and annihilation cross sections. We find that the two cross sections are of the same order of magnitude. This result has a straightforward and important consequence that neutralinos comprising a compact object can not achieve thermal equilibrium. To substantiate our arguments, by solving Oppenheimer-Volkoff equation we constructed a model of the star made of pure neutralinos. We explicitly showed that the condition for the thermal equilibrium supported by the Fermi pressure is never fulfilled inside the star. This neutralino state can not be described by the Fermi-Dirac distribution. Thus, a stable neutralino star, which is supported by the Fermi pressure, can not exist. We also estimated that a stable star can not contain more than a few percents of neutralinos, most of the mass must be in the form of the standard model particles.

  6. Existence families, functional calculi and evolution equations

    CERN Document Server

    deLaubenfels, Ralph

    1994-01-01

    This book presents an operator-theoretic approach to ill-posed evolution equations. It presents the basic theory, and the more surprising examples, of generalizations of strongly continuous semigroups known as 'existent families' and 'regularized semigroups'. These families of operators may be used either to produce all initial data for which a solution in the original space exists, or to construct a maximal subspace on which the problem is well-posed. Regularized semigroups are also used to construct functional, or operational, calculi for unbounded operators. The book takes an intuitive and constructive approach by emphasizing the interaction between functional calculus constructions and evolution equations. One thinks of a semigroup generated by A as etA and thinks of a regularized semigroup generated by A as etA g(A), producing solutions of the abstract Cauchy problem for initial data in the image of g(A). Material that is scattered throughout numerous papers is brought together and presented in a fresh, ...

  7. Repowering existing coal fired power plants

    Energy Technology Data Exchange (ETDEWEB)

    Stenzel, W.C.; Sopocy, E.M.; Pace, S.E.

    1997-12-31

    Increased competition among power generating companies, changes in generating system load requirements, lower allowable plant emissions, and changes in fuel availability and cost accentuate the need to closely assess the economics and performance of older electric generating units. Generally, decisions must be made as to whether these units should be retired and replaced with new generation capacity, whether capacity should be purchased from other generation companies, or if these existing units should be repowered. These decisions usually require the evaluation of many factors including: environmental discharge limits, permitting requirements, generating load demand increases, options for increasing the benefits of using existing facilities (e.g., increasing efficiency and output), fuel cost increases, transmission requirements and access, and optional plant designs. Many of these factors need to be used in the analysis based on a range rather than one specific value to test for changes in the selection of the best option because of future uncertainties. Usually complicated analysis results because of all the factors involved. Computer products that integrate performance and financial analysis can provide substantial value by enabling the user to evaluate the applicable plant options and range of input. The SOAPP (State-of-the-Art Power Plant) family of software products provides easy-to-use tools for rapid, thorough and economical evaluation of plant options. Repowering evaluation methodology typically used in the United States, technology options, and available SOAPP repowering software are reviewed in this paper. 14 figs.

  8. The existence of cords in olecranon bursae.

    Science.gov (United States)

    Ecker, Jeff; Ebert, Jay R; Taheri, Arash; Mathew, Ravi K; Chee, Derserri Y; Breidahl, William

    2015-10-01

    The purpose of this study was to document the existence of transverse cords in olecranon bursae in patients undergoing excision of the bursa and to describe the unique clinical presentation of patients with these cords. A retrospective study was performed on 24 patients who had surgery to excise an olecranon bursa between 2006 and 2011. The patient's history, preoperative radiographs, ultrasound images, intraoperative photographs, and findings on histologic analysis were reviewed in all cases. Nine olecranon bursae had cords (cord group) and 15 did not have cords (noncord group). All patients in the cord group were male manual laborers, and nearly all had olecranon enthesophytes (n = 8). Patients in the noncord group had associated medical conditions or an infection. A higher level of satisfaction was reported in the noncord group after surgical excision. This study documents the existence of transverse cords oriented at right angles to the long axis of the olecranon. Olecranon bursae with cords have a unique presentation and are found in male manual workers, are nearly always associated with an olecranon enthesophyte, and do not present with infections. Copyright © 2015 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

  9. EXOSOMES: CAN DOCTORS STILL IGNORE THEIR EXISTENCE?

    Directory of Open Access Journals (Sweden)

    Celeste Caruso Bavisotto

    2013-04-01

    Full Text Available With this invited commentary we want to draw the attention of young medical doctors, the main readers of this journal, towards the existence and importance of a group of nanovesicles released by human cells: the exosomes. These vesicles are incontinently secreted as a mean of cell-to-cell communication. They are involved in a number of physiologic processes as well as in the pathogenesis of, virtually, all human diseases. They can be isolated from all biological fluids, like blood, urine, sweat, sperm, crevicular fluid, bile, etc., and their composition in terms of proteins, RNA and lipids is different in pathology that in physiologic conditions. It is therefore possible to predict that they will become an important diagnostic and therapeutic tool in medicine.

  10. Worldwide overview of existing haemovigilance systems.

    Science.gov (United States)

    Faber, Jean-Claude

    2004-10-01

    Haemovigilance is a "quality process" with the aim to improve quality and increase safety of blood transfusion, taking into account that haemovigilance covers and surveys all activities of the blood transfusion chain from donors to recipients. Haemovigilance is indispensable when it comes to safety and quality of blood transfusions. Within the European Union (EU), the European Blood Directive requires haemovigilance in each Member State: the intention has been to rely on the existing or developing national systems. There are significant differences in haemovigilance around the world, in terms of definition, organisational schemes, state of development and implementation. These differences are more pronounced outside the EU: in some countries, even basic traceability causes a problem while in others systems similar as the most developed ones in the EU are implemented.

  11. The enhancement of existing DES Maplet interface

    Science.gov (United States)

    Abdullah, Nur Lina; Mutalip, Rasidah Abdull; Abdullah, Kamilah

    2014-07-01

    This study pertains to the process of Data Encryption Standard, DES. DES consists of encryption and decryption processes linked with mathematical elements such as algebra and number theory. Preliminary, studies revealed that most of mathematics students face a problem in understanding the complicated process of DES. In modern learning methods, learning environment becomes more interesting with the use of computer and a variety of mathematical software packages. Several mathematical softwares such as Maple, Mathematica, Mathlab and Sage were developed in order to fulfill the specific calculation requirements. Correspondingly, motivated from that, this study incorporated with Maple to enhance the existing DES Maplet interface to be more interactive and user-friendly compared to the original version.

  12. On the existence of Levi Foliations

    Directory of Open Access Journals (Sweden)

    RENATA N. OSTWALD

    2001-03-01

    Full Text Available Let L be a real 3 dimensional analytic variety. For each regular point p L there exists a unique complex line l p on the space tangent to L at p. When the field of complex line p l p is completely integrable, we say that L is Levi variety. More generally; let L M be a real subvariety in an holomorphic complex variety M. If there exists a real 2 dimensional integrable distribution on L which is invariant by the holomorphic structure J induced by M, we say that L is a Levi variety. We shall prove: Theorem. Let be a Levi foliation and let be the induced holomorphic foliation. Then, admits a Liouvillian first integral. In other words, if is a 3 dimensional analytic foliation such that the induced complex distribution defines an holomorphic foliation ; that is, if is a Levi foliation; then admits a Liouvillian first integral--a function which can be constructed by the composition of rational functions, exponentiation, integration, and algebraic functions (Singer 1992. For example, if f is an holomorphic function and if theta is real a 1-form on ; then the pull-back of theta by f defines a Levi foliation : f*theta = 0 which is tangent to the holomorphic foliation : df = 0. This problem was proposed by D. Cerveau in a meeting (see Fernandez 1997.Seja L Ì uma variedade real de dimensão 3. Para todo ponto regular p Î L existe uma única reta complexa l p no espaço tangente à L em p. Quando o campo de linhas complexas p l p é completamente integrável, dizemos que L é uma variedade de Levi. Mais geralmente, seja L Ì M uma subvariedade real em uma variedade analítica complexa. Se existe uma distribuição real integrável de dimensão 2 em L que é invariante pela estrutura holomorfa J induzida pela variedade complexa M, dizemos que L é uma variedade de Levi. Vamos provar: Teorema. Seja uma folheação de Levi e seja a folheação holomorfa induzida. Então tem integral primeira Liouvilliana. Em outras palavras, se é uma folheação real de

  13. Synaesthesia: the existing state of affairs.

    Science.gov (United States)

    Hochel, Matej; Milán, Emilio G

    2008-02-01

    In synaesthesia one type of stimulation evokes the sensation of another, such as when hearing a sound produces photisms--that is, mental percepts of colours. In the past, the idiosyncrasy of this phenomenon, as well as the natural mistrust of scientists towards the subjective, consigned synaesthesia to the periphery of scientific interest. However, the landscape has changed radically in the last two decades. The labour of many researchers, inside as well as outside of cognitive neuroscience, has transformed synaesthesia into a scientific reality whose existence can be demonstrated and studied empirically. The present paper summarizes and reflects on our current knowledge concerning synaesthesia in all its aspects (cognition, behaviour, neurology, genetics, and demographics).

  14. Compilation of Existing Neutron Screen Technology

    Directory of Open Access Journals (Sweden)

    N. Chrysanthopoulou

    2014-01-01

    Full Text Available The presence of fast neutron spectra in new reactors is expected to induce a strong impact on the contained materials, including structural materials, nuclear fuels, neutron reflecting materials, and tritium breeding materials. Therefore, introduction of these reactors into operation will require extensive testing of their components, which must be performed under neutronic conditions representative of those expected to prevail inside the reactor cores when in operation. Due to limited availability of fast reactors, testing of future reactor materials will mostly take place in water cooled material test reactors (MTRs by tailoring the neutron spectrum via neutron screens. The latter rely on the utilization of materials capable of absorbing neutrons at specific energy. A large but fragmented experience is available on that topic. In this work a comprehensive compilation of the existing neutron screen technology is attempted, focusing on neutron screens developed in order to locally enhance the fast over thermal neutron flux ratio in a reactor core.

  15. Gender Existence: Correlation between Equality and Identity

    Directory of Open Access Journals (Sweden)

    Svitlana Storozhuk

    2017-02-01

    Full Text Available The article deals with the conceptual vision of gender content in its relation to sex taking into account the extremes to which researchers of gender issues and social movements have resorted to and considering the role and place of men and women in social and cultural life. On this background wrongfulness of such approaches is justified, according to which gender and sex are identified. It is shown in this article that these notions have different meanings and represent different dimensions of human existence. Thus, in contrast to sex, which reveals the physiological differences between men and women, gender is a socio cultural construct which sets the «matrix» of gender interaction at every historical stage of social and cultural life by offering their own vision of gender equality. Alongside with other ideas we substantiate the idea that gender equality is possible only in the social aspect.

  16. Review of existing reactive transport software

    Energy Technology Data Exchange (ETDEWEB)

    Glassley, W., LLNL

    1998-02-03

    Simulations of thermal and hydrological evolution following the potential emplacement of a subterranean nuclear waste repository at Yucca Mountain, NV provide data that suggest the inevitability of dependent, simultaneous chemical evolution in this system. These chemical changes will modify significantly both the magnitude and structure of local porosity and permeability; hence, they will have a dynamic feedback effect on the evolving thermal and hydrological regime. Yet, despite this intimate interdependence of transport and chemical processes, a rigorous quantitative analysis of the post- emplacement environment that incorporates this critical feedback mechanism has not been completed to date. As an initial step in this direction, the present document outlines the fundamental chemical and transport processes that must be accounted for in such an analysis, and reviews the inventory of existing software that encodes these processed in explicitly coupled form. A companion report describes the prioritization of specific capabilities that are needed for modeling post-emplacement reactive transport at Yucca Mountain.

  17. Welfare Economics: A Story of Existence

    Directory of Open Access Journals (Sweden)

    Khalid Iqbal

    2017-06-01

    Full Text Available The purpose of this study is to explore that, despite severe challenges, welfare economics still exists. This descriptive study is conducted through some specific time line developments in this field. Economists are divided over the veracity and survival of the welfare economics. Welfare economics emphasizes on the optimum resource and goods allocation with the objective of better living standard, materialistic gains, social welfare and ethical decisions. It origins back to the political economics and utilitarianism. Adam Smith, Irving Fisher and Pareto contributed significantly towards it. During 1930 to 1940, American and British approaches were developed. Many economists tried to explore the relationship between level of income and happiness. Amartya Sen gave the comparative approach and Tinbergen pioneered the theory of equity. Contemporarily the futuristic restoration of welfare economics is on trial and hopes are alive. This study may be useful to understand the transitional and survival process of welfare economics.

  18. Testing Metadata Existence of Web Map Services

    Directory of Open Access Journals (Sweden)

    Jan Růžička

    2011-05-01

    Full Text Available For a general user is quite common to use data sources available on WWW. Almost all GIS software allow to use data sources available via Web Map Service (ISO/OGC standard interface. The opportunity to use different sources and combine them brings a lot of problems that were discussed many times on conferences or journal papers. One of the problem is based on non existence of metadata for published sources. The question was: were the discussions effective? The article is partly based on comparison of situation for metadata between years 2007 and 2010. Second part of the article is focused only on 2010 year situation. The paper is created in a context of research of intelligent map systems, that can be used for an automatic or a semi-automatic map creation or a map evaluation.

  19. [The depression epidemic does not exist].

    Science.gov (United States)

    van der Feltz-Cornelis, Christina M

    2009-01-01

    There has been much discussion in the media about the question of the existence of a depression epidemic. This leads on to the questions of whether the social and economic approaches are adequate, and what the alternatives are. The concept of the disease 'depression' can be defined using a medical model, or from a patient's or a societal perspective. From a medical perspective, indeed a depression epidemic has ensued from the increased prosperity and the associated decompression of the mortality rate. Society responded with preventative measures and policies aimed at improving functioning in the workplace. However, patients with a major depressive disorder (MDD) who are eligible for treatment are often not motivated to take it up, or are undertreated. Research is necessary in order to explore what patients think about the identification and treatment of depression. The confusion regarding the concept of depression found in the media, needs to be cleared.

  20. Do Bare Rocks Exist on the Moon?

    Science.gov (United States)

    Allen, Carlton; Bandfield, Joshua; Greenhagen, Benjamin; Hayne, Paul; Leader, Frank; Paige, David

    2017-01-01

    Astronaut surface observations and close-up images at the Apollo and Chang'e 1 landing sites confirm that at least some lunar rocks have no discernable dust cover. However, ALSEP (Apollo Lunar Surface Experiments Package) measurements as well as astronaut and LADEE (Lunar Atmosphere and Dust Environment Explorer) orbital observations and laboratory experiments possibly suggest that a fine fraction of dust is levitated and moves across and above the lunar surface. Over millions of years such dust might be expected to coat all exposed rock surfaces. This study uses thermal modeling, combined with Diviner (a Lunar Reconnaissance Orbiter experiment) orbital lunar eclipse temperature data, to further document the existence of bare rocks on the lunar surface.

  1. The pastor as model for peaceful existence

    Directory of Open Access Journals (Sweden)

    Terence Cooke

    2011-06-01

    Full Text Available Many people are disillusioned in the democratic South Africa. That is because they went out from the assumption that with the dawn of democracy, violence would disappear. Unfortunately this did not happen. As with most things in life it is not an either � or, but a both � and scenario. In fact, violence is part of the democratic system. Real peace between men and powers can only be the peace of God, the peace which alone heals all disorder. The peace of the world is at best peaceful coexistence, not peace.In South Africa we have a negotiated agreement to peaceful coexistence, and sometimes, for example, after the miracle of the 1994 election and the euphoria of the World Cups of 1995, 2007 and 2010, we may even think we have achieved real peace. It is indeed in these times of euphoria that the people of South Africa may be tempted to lower our aim and settle for second best thinking that we have arrived.Model is used not in the sense of the pastor being an example of a peaceful existence to be followed. It is rather used in the sense that a pastor in his or her professional capacity has the knowledge of the meaning of the term �peaceful existence� and also the hermeneutic competency to apply that knowledge in concrete situations. This opens the exiting possibility that pastors can become travel companions on the road to real peace.The different aspects of being a pastor, office bearer, professional and person, each contribute to the pastor being a model for peace. It must be emphasised that the different aspects always work together as a unity and the strength of the pastor as a model for a peaceful existence is in the simultaneous application of these aspects in the context in which the pastor lives.

  2. The high energy telescope on EXIST

    Science.gov (United States)

    Hong, J.; Grindlay, J. E.; Allen, B.; Barthelmy, S. D.; Skinner, G. K.; Gehrels, N.

    2009-08-01

    The Energetic X-ray Imaging Survey Telescope (EXIST) is a proposed next generation multi-wavelength survey mission. The primary instrument is a High Energy telescope (HET) that conducts the deepest survey for Gamma-ray Bursts (GRBs), obscured-accreting and dormant Supermassive Black Holes and Transients of all varieties for immediate followup studies by the two secondary instruments: a Soft X-ray Imager (SXI) and an Optical/Infrared Telescope (IRT). EXIST will explore the early Universe using high redshift GRBs as cosmic probes and survey black holes on all scales. The HET is a coded aperture telescope employing a large array of imaging CZT detectors (4.5 m2, 0.6 mm pixel) and a hybrid Tungsten mask. We review the current HET concept which follows an intensive design revision by the HET imaging working group and the recent engineering studies in the Instrument and Mission Design Lab at the Goddard Space Flight Center. The HET will locate GRBs and transients quickly (<10-30 sec) and accurately (< 20") for rapid (< 1-3 min) onboard followup soft X-ray and optical/IR (0.3-2.2 μm) imaging and spectroscopy. The broad energy band (5-600 keV) and the wide field of view (~90° × 70&° at 10% coding fraction) are optimal for capturing GRBs, obscured AGNs and rare transients. The continuous scan of the entire sky every 3 hours will establish a finely-sampled long-term history of many X-ray sources, opening up new possibilities for variability studies.

  3. Energy consumptions in existing buildings; Les consommations d'energie des batiments existants

    Energy Technology Data Exchange (ETDEWEB)

    Nuss, St. [Ecole Nationale Superieure des Arts et Industries de Strasbourg, 78 - Saint-Remy-Les-Chevreuse (France)]|[Costic, 78 - Sainte Remy les Chevreuses (France)

    2002-05-01

    This document presents a sectoral analysis of the energy consumptions in existing French buildings: 1) - residential sector: social buildings, private dwellings; 2) - tertiary sector: office buildings, hotels, commercial buildings, school buildings, hospitals; 3) - industry; 4) - general status. (J.S.)

  4. ECOLOGICAL CONDITIONS OF EXISTENCE OF MYCOBACTERIA POPULATIONS

    Directory of Open Access Journals (Sweden)

    R. A. Nuratinov

    2014-01-01

    Full Text Available Abstract. Aim. Adaptation possibilities of mycobacteria in the conditions of existence in the external environment and habitats of animals and man are studied. Adaptation mechanisms, which have pathogenic mycobacteria, allow them to survive long and circulate in the environment, which leads to special sanitary and epidemiological value of pathogens of tuberculosis. Location. Russia, Dagestan.Results. Mycobacterium tuberculosis has a high resistance to influence of cold, heat, chemical and physical factors, moisture and light. They carry high and low temperatures, while more than a year pathogenic properties, and even more in the dark and without sunlight. It should be noted that the stability of pathogenic species of mycobacteria in the external environment is relatively lower than that of saprophytes, capable of quickly adapting to the external environment. Raonin’s groups have more widespread in environment, in water, soil, air, plants, and habitats of animals, products of plant and animal origin and their often isolated from clinical samples.Main conclusions. Environmental conditions define the intensity of habitats of any species of mycobacteria in certain landscapes and their circulation in macroorganism. The impact of the various elements of the environment both in the macro- and microorganisms is a response that was the basis for the development of the doctrine about “limiting factors”. This concept applies not only to the necessary for mycobacteria chemical elements, but also to all the other environmental factors (temperature, humidity, aeration conditions etc. Minimum and maximum intensity factors determine the limits of endurance species. Beyond these limits, due to sharply expressed extreme conditions and is portable microorganism existence of species is not possible. The most favorable for the species optimum intensity of environmental factors, usually occupied a middle position. This provision is significantly

  5. Measuring Input Thresholds on an Existing Board

    Science.gov (United States)

    Kuperman, Igor; Gutrich, Daniel G.; Berkun, Andrew C.

    2011-01-01

    A critical PECL (positive emitter-coupled logic) interface to Xilinx interface needed to be changed on an existing flight board. The new Xilinx input interface used a CMOS (complementary metal-oxide semiconductor) type of input, and the driver could meet its thresholds typically, but not in worst-case, according to the data sheet. The previous interface had been based on comparison with an external reference, but the CMOS input is based on comparison with an internal divider from the power supply. A way to measure what the exact input threshold was for this device for 64 inputs on a flight board was needed. The measurement technique allowed an accurate measurement of the voltage required to switch a Xilinx input from high to low for each of the 64 lines, while only probing two of them. Directly driving an external voltage was considered too risky, and tests done on any other unit could not be used to qualify the flight board. The two lines directly probed gave an absolute voltage threshold calibration, while data collected on the remaining 62 lines without probing gave relative measurements that could be used to identify any outliers. The PECL interface was forced to a long-period square wave by driving a saturated square wave into the ADC (analog to digital converter). The active pull-down circuit was turned off, causing each line to rise rapidly and fall slowly according to the input s weak pull-down circuitry. The fall time shows up as a change in the pulse width of the signal ready by the Xilinx. This change in pulse width is a function of capacitance, pulldown current, and input threshold. Capacitance was known from the different trace lengths, plus a gate input capacitance, which is the same for all inputs. The pull-down current is the same for all inputs including the two that are probed directly. The data was combined, and the Excel solver tool was used to find input thresholds for the 62 lines. This was repeated over different supply voltages and

  6. Effectiveness of Existing International Nuclear Liability Regime

    Energy Technology Data Exchange (ETDEWEB)

    Al-Doais, Salwa; Kessel, Daivd [KEPCO International Nuclear Graduate School, Daejeon (Korea, Republic of)

    2015-10-15

    The first convention was the Paris Convention on Third Party Liability in the Field of Nuclear Energy (the Paris Convention) had been adopted on 29 July 1960 under the auspices of the OECD, and entered into force on 1 April 1968. In 1963,the Brussels Convention - supplementary to the Paris Convention- was adopted in to provide additional funds to compensate damage as a result of a nuclear incident where Paris Convention funds proved to be insufficient. The IAEA's first convention was the Vienna Convention on Civil Liability for Nuclear Damage (the Vienna Convention) which adopted on 21 May 1963,and entered into force in 1977. Both the Paris Convention and the Vienna Convention laid down very similar nuclear liability rules based on the same general principles. The broad principles in these conventions can be summarized as follows: 1- The no-fault liability principle (strict liability) 2- Liability is channeled exclusively to the operator of the nuclear installation (legal channeling) 3- Only courts of the state in which the nuclear accident occurs would have jurisdiction (exclusive jurisdiction) 4- Limitation of the amount of liability and the time frame for claiming damages (limited liability) 5- The operator is required to have adequate insurance or financial guarantees to the extent of its liability amount (liability must be financially secured). 6- Liability is limited in time. Compensation rights are extinguished after specific time. 7- Non-discrimination of victims on the grounds of nationality, domicile or residence. Nuclear liability conventions objective is to provide adequate compensation payments to victims of a nuclear accident. Procedures for receiving these compensation are controlled by some rules such as exclusive jurisdiction, that rule need a further amendment to ensure the effectiveness of the exiting nuclear liability regime . Membership of the Conventions is a critical issue, because the existence of the conventions without being party to

  7. ProtoEXIST: advanced prototype CZT coded aperture telescopes for EXIST

    Science.gov (United States)

    Allen, Branden; Hong, Jaesub; Grindlay, Josh; Barthelmy, Scott D.; Baker, Robert G.; Gehrels, Neil A.; Garson, Trey; Krawczynski, Henric S.; Cook, Walter R.; Harrison, Fiona A.; Apple, Jeffrey A.; Ramsey, Brian D.

    2010-07-01

    ProtoEXIST1 is a pathfinder for the EXIST-HET, a coded aperture hard X-ray telescope with a 4.5 m2 CZT detector plane a 90x70 degree field of view to be flown as the primary instrument on the EXIST mission and is intended to monitor the full sky every 3 h in an effort to locate GRBs and other high energy transients. ProtoEXIST1 consists of a 256 cm2 tiled CZT detector plane containing 4096 pixels composed of an 8x8 array of individual 1.95 cm x 1.95 cm x 0.5 cm CZT detector modules each with a 8 x 8 pixilated anode configured as a coded aperture telescope with a fully coded 10° x 10° field of view employing passive side shielding and an active CsI anti-coincidence rear shield, recently completed its maiden flight out of Ft. Sumner, NM on the 9th of October 2009. During the duration of its 6 hour flight on-board calibration of the detector plane was carried out utilizing a single tagged 198.8 nCi Am-241 source along with the simultaneous measurement of the background spectrum and an observation of Cygnus X-1. Here we recount the events of the flight and report on the detector performance in a near space environment. We also briefly discuss ProtoEXIST2: the next stage of detector development which employs the NuSTAR ASIC enabling finer (32×32) anode pixilation. When completed ProtoEXIST2 will consist of a 256 cm2 tiled array and be flown simultaneously with the ProtoEXIST1 telescope.

  8. Does occupational health nursing exist in India?

    Science.gov (United States)

    Tiwari, Rajnarayan R; Sharma, Anjali; Zodpey, Sanjay P; Khandare, Shobha M

    2014-01-01

    Occupational health services are important to develop healthy and productive work forces, which should be delivered through occupational health team. Occupational health nurse (OHN) is an important member of this team and is required to apply nursing principles in conserving the health of workers in occupational settings. This article attempts to map the occupational health nursing courses in India and design competencies and curriculum for such a course. Information through the Internet, printed journals, and perspectives of the key stakeholders were the principal sources of data. In India, there is a need to initiate a course on occupational health nursing to provide occupational health services for the organized and unorganized sector workforce. A certificate course for occupational health nursing for 3-4 months duration offered through contact session mode can be an opportune beginning. However, to cater employed nurses an online course can be another effective alternative. The theoretical part should essentially include modules on occupational diseases, industrial hygiene, and occupational health legislation, whereas the modules on practical aspects can include visits to industries. Taking into account the existing norms of Indian Factories Act for hazardous units of organized sector an estimated 1,34,640 OHNs are required. There is a need-supply gap in the number of occupational health nursing manpower in India, which can be attributed to the absence of any course to train such manpower.

  9. On the Existence of Evolutionary Learning Equilibriums

    Directory of Open Access Journals (Sweden)

    Masudul Alam Choudhury

    2011-12-01

    Full Text Available The usual kinds of Fixed-Point Theorems formalized on the existence of competitive equilibrium that explain much of economic theory at the core of economics can operate only on bounded and closed sets with convex mappings. But these conditions are hardly true of the real world of economic and financial complexities and perturbations. The category of learning sets explained by continuous fields of interactive, integrative and evolutionary behaviour caused by dynamic preferences at the individual and institutional and social levels cannot maintain the assumption of closed, bounded and convex sets. Thus learning sets and multi-system inter-temporal relations explained by pervasive complementarities and  participation between variables and entities, and evolution by learning, have evolutionary equilibriums. Such a study requires a new methodological approach. This paper formalizes such a methodology for evolutionary equilibriums in learning spaces. It briefly points out the universality of learning equilibriums in all mathematical structures. For a particular case though, the inter-systemic interdependence between sustainable development and ethics and economics in the specific understanding of learning domain is pointed out.

  10. Evaluation and modification of existing CETP.

    Science.gov (United States)

    Sharma, Bhavisha; Shah, A R

    2013-07-01

    For the development of small and medium scale industries in various Gujarat industrial development corporation (GIDC) areas and in clusters of industrial areas, the common effluent treatment plant (CETP) has always been found advantageous in view of cost of treatment, operation and maintenance and disposal of residues being produced. In small scale industrial units due to market requirement, product changes and quantity enhancement are taking place. Due to such changes, the effluent characteristics are continuously changing which affects performance of CETP. Hence it has been found necessary to study continuously the performance, evaluation and modification in the working of the CETP. This paper contains a case study of one of the existing CETP near Baroda which is facing the problem of disposal of treated effluent in which the important parameters like COD, BOD, Suspended Solid, NH3-N and oil and grease were analyzed. Based on the characterization of wastewater, the various treatability studies were carried out on CETP wastewater. To comply with disposal standard prescribed by Effluent Channel Project Ltd.(ECPL)* and Gujarat Pollution Control Board (GPCB) for discharge of industrial effluent into channel, various treatments in form of ammonia stripping, coagulation and flocculation, biological treatment, filtration and chlorination are suggested.

  11. David Barker: the revolution that anticipates existence

    Directory of Open Access Journals (Sweden)

    Italo Farnetani

    2014-01-01

    Full Text Available David Barker is the man who “anticipated" the existence of babies by focusing attention on the importance of the fetus and what takes place during intrauterine life. Barker was one of the physicians who in the last decades brought about the greatest changes in medicine, changes so important as to represent a veritable revolution in medical thought. According to Barker's studies, the embryo obviously has a genetic complement coming from the mother and father, but from the very first stages of development it begins to undergo the influence of the outside environment, just as occurs for adults whose biological, psychological and pathological aspects are influenced by the environment to a not well-established percentage between genetic complement and epigenetics. Much of our future lives as adults is decided in our mothers' wombs. If Barker's discovery was revolutionary from the cultural standpoint, it was even more so from the strictly medical one. Barker's research method was rigid from the methodological standpoint, but innovative and speculative in its working hypotheses, with a humanistic slant. Barker's idea has another practical corollary: it is evident that the role of obstetricians, perinatologists and neonatologists is more and more relevant in medicine and future prevention. Unquestionably, besides the enormous merits of his clinical research, among the benefits that Barker has contributed there is that of having helped us to see things from new points of view. Not only is the neonate (and even more so the fetus not an adult of reduced proportions, but perhaps the neonate is the "father" of the adult person.

  12. Diving with pre-existing medical conditions.

    Science.gov (United States)

    Lippmann, John; McD Taylor, David; Stevenson, Christopher; Williams, Jo; Mitchell, Simon J

    2017-09-01

    This is the second report based on a survey of Divers Alert Network Asia-Pacific (DAN AP) members who dive with cardiovascular and respiratory conditions and diabetes. It examines the medical management of the divers' conditions, any diving modifications used to mitigate the risk and outcomes. An online cross-sectional survey was sent to 833 divers who had declared a targeted medical condition when applying for DAN AP membership between July 2009 and August 2013. Two-hundred-and-sixty-eight respondents (32%) provided sufficient information on their conditions to be included in the analyses. These included ischaemic heart disease (31), arrhythmias (20), cardiac septal defects (31), other cardiac conditions (10), hypertension (127), diabetes (25), asthma (40) and pneumothorax (5). Forty-nine per cent had sought specialist diving medical advice about their condition and 23% reported modifying their diving practices to mitigate their risk. The cohort had completed 183,069 career dives, 57,822 of these since being diagnosed with their medical condition. There were 27 individuals who reported having decompression illness (25 of whom were subsequently diagnosed with a persistent foramen ovale), and two individuals who experienced an arrhythmia during diving. Some DAN AP members are diving with medical conditions which could potentially impact the safety of their diving. A minority modified their diving practices to mitigate the risk of their condition and approximately half sought specialist diving medical advice. The incidence of diving-related problems precipitated by known and managed pre-existing health conditions seems low but further studies of larger cohorts and incorporating fatality data would be necessary to confirm this. These results are limited by the 32% response rate and potential for bias towards selection of those most careful with their health.

  13. Does Glocal Political Power Already Exist?

    Directory of Open Access Journals (Sweden)

    Lorenzo Ornaghi

    2017-05-01

    Full Text Available Large periods of history are usually characterized by equally important moments of change in scientific knowledge and, in particular, in the understanding of political power. We still need to study in depth whether the former provokes (almost of out necessity the latter, or whether they are “great” because they are favored by the innovation of the paradigms of knowledge. The passage from medieval universalism to the particularism of the modern age represents an extremely interesting analogy when compared to the transformations that are now underway. The example of John of Salisbury’s Policratus, the starting point of this article, is illuminating in our comprehension of the relevance of the interweaving between the persistence of the ancient forms of recognition of power and the search for new forms. The existence of glocal realities is already a fact. Even if it is relatively easy to recognize these realities (a business, a university, a humanitarian association, not a few of the same “parts” which constitute the traditional organization of the State, it is more difficult to define the specific characteristics of the power at their disposal. Moving from the widening gap between “actual” power and “potential” power, the article examines the motives for which the classical definitions of power are always becoming more insufficient in understanding the role now emerging from glocal realities. And, in particular, by looking at how the “command-obedience” relationship is changing also as a consequence of communication networks and information technology, the article analyzes that specific “contamination” within global elements and local elements, which seems to be the main base of glocal political power.

  14. Existence and non-existence of transition fronts in mixed ignition-monostable media

    Science.gov (United States)

    Graham, Cole; Shean Lim, Tau; Ma, Andrew; Weber, David

    2018-02-01

    We study transition fronts for one-dimensional reaction–diffusion equations with compactly-perturbed ignition-monostable reactions. We establish an almost sharp condition on reactions which characterizes the existence and non-existence of fronts. In particular, we prove that a strong inhomogeneity in the reaction prevents formation of transition fronts, while a weak inhomogeneity gives rise to a front. Our work extends the results and methods introduced in Nolen et al 2012 (Arch. Ration. Mech. Anal. 203 217–46), which studied the same question in inhomogeneous KPP media.

  15. Life on Titan: Theorem of existance

    Science.gov (United States)

    Potashko, O.

    Volcanoes engender life on heavenly bodies; they are pacemakers of life[1]. All planets during their period of formation pass through volcanism hence - all planets and their satellites pass through life. Tracks of life If we want to find tracks of life -- most promising places are places with volcanic activity, current or past. In the case of just-in-time volcanic activity we have 100% probability to find a life. Therefore the most perspective ``search for life'' are Io and comets, further would be Venus, Jupiter, Saturn, their satellites and first of all -- Titan. Titan has atmosphere. It might be result of high volcanic activity -- from one side, from other side atmosphere is a necessary condition development life from procaryota to eucaryota. Existence of a planet means that all its elements after hydrogen formed just there inside a planet. The forming of the elements leads to the formation of mineral and organic substances and further to the organic life. Development of the life depends upon many factors, e.g. the distance from star/s. The intensity of the processes of the element formation is inversely to the distance from the star. Therefore we may suppose that the intensity of the life in Mercury was very high. Hence we may detect tracks of life in Mercury, particularly near volcanoes. The distance from the star is only one parameter and now Titan looks very active -- mainly due to interior reason. Its atmosphere compounds are analogous to comet tail compounds. Their collation may lead to interesting result as progress occurs at one of them. Volcanic activity is as a source of life origin as well a reason for a death of life. It depends upon the thickness of planet crust. In the case of small thickness of a crust the probability is high that volcanoes may destroy a life on a planet -- like Noachian deluge. Destroying of the life under volcano influences doesn't lead to full dead. As result we would have periodic Noachian deluge or nuclear winter. These

  16. The Census of SFXTs with EXIST

    Science.gov (United States)

    Bazzano, Angela; Sidoli, L.; Sguera, V.; Ubertini, P.; Natalucci, L.; Grindlay, J.

    2010-03-01

    One of the most intriguing discoveries obtained by the INTEGRAL mission is the identification of a new class of hard X-ray transients, the Supergiant Fast X-ray Transients (SFXTs). They are a subclass of High Mass X-ray Binaries, with 20 members to date (10 firmly identified, the others are candidates), hosting an OB supergiant donor and displaying short X-ray outbursts with fast flares on brief timescales of hours and large flux variability in the range 10E3-10E5. The Energetic X-ray Imaging Survey Telescope (EXIST), with its hard X-ray imaging (5-600 keV) all-sky deep survey and large improved limiting sensitivity, will explore the transient X-ray Universe to get a clearer picture of this new class of puzzling transients, whose actual physical mechanism driving the emission is still unknown. Some models involve the structure of the supergiant wind and the orbital parameters, others invoke very low magnetic field values (B1E14 G, magnetars). Orbital parameters are largely unknown, as well as the duty cycles. No cyclotron lines have been detected to date, except in IGRJ18483-0311, where a hint for a cyclotron line at 3.3 keV has been found, implying a neutron star magnetic field of a few time 1E11 G. The magnetic field in all other SFXTs is unknown. A complete census of the number of these sources is essential to enlarge the sample and possibly discover different SFXTs sub-classes. A long term and continuous as possible X-ray monitoring of SFXTs is crucial to (1)-obtain the duty cycle, (2)-investigate their orbital parameters and search periodicities predicted by some models, (3)-to completely cover the whole outburst activity (now possible only for SFXTs with periodically recurrent X-ray flaring activity), (4)-to search for cyclotron lines in the high energy spectra which will allow a direct measurement of the neutron star magnetic field.

  17. A precariedade humana e a existência estilizada Human precariousness and stylized existence

    Directory of Open Access Journals (Sweden)

    Rita Paiva

    2013-04-01

    Full Text Available Este artigo tematiza o desamparo vivenciado pela consciência ante a ausência de bases sólidas para seus anseios de felicidade e para suas representações simbólicas. Com esse propósito, toma como objeto de reflexão um dos ensaios filosóficos de Albert Camus, O mito de Sísifo, equacionando a possibilidade de uma ética que estilize a vida, sem que se minimize a dolorosa precariedade da existência humana. Posteriormente, em diálogo com alguns textos de M. Foucault, a reflexão procura estabelecer os vínculos possíveis entre a ética camusiana e a ética como uma estética da existência, tal como pensada entre os gregos antigos.This article discusses the helplessness experienced by the consciousness vis-à-vis the absence of solid bases for its longings for happiness and for its symbolic representations. For this purpose, the object of reflection of the article is one of Albert Camus' philosophical essays, The Myth of Sisyphus, and we inquire into the possibility of an ethics that stylizes life without minimizing the painful precariousness of human existence. Making reference to certain texts by Foucault, we attempt to establish possible connections between Camus' ethics and an ethics of the aesthetics of existence as found in the thinkers of ancient Greece.

  18. Spinning Q-balls in Abelian Gauge Theories with positive potentials: existence and non existence

    OpenAIRE

    Mugnai, Dimitri; Rinaldi, Matteo

    2012-01-01

    We study the existence of cylindrically symmetric electro-magneto-static solitary waves for a system of a nonlinear Klein-Gordon equation coupled with Maxwell's equations in presence of a positive mass and of a nonnegative nonlinear potential. Nonexistence results are provided as well.

  19. Existence and non-existence of solutions for a p(x-biharmonic problem

    Directory of Open Access Journals (Sweden)

    Ghasem A. Afrouzi

    2015-06-01

    Full Text Available In this article, we study the following problem with Navier boundary conditions $$\\displaylines{ \\Delta (|\\Delta u|^{p(x-2}\\Delta u+|u|^{p(x-2}u =\\lambda |u|^{q(x-2}u +\\mu|u|^{\\gamma(x-2}u\\quad \\text{in } \\Omega,\\cr u=\\Delta u=0 \\quad \\text{on } \\partial\\Omega. }$$ where $\\Omega$ is a bounded domain in $\\mathbb{R}^{N}$ with smooth boundary $\\partial \\Omega$, $N\\geq1$. $p(x,q(x$ and $\\gamma(x$ are continuous functions on $\\overline{\\Omega}$, $\\lambda$ and $\\mu$ are parameters. Using variational methods, we establish some existence and non-existence results of solutions for this problem.

  20. Existence and non-existence results for a nonlinear heat equation

    Directory of Open Access Journals (Sweden)

    Canan Celik

    2007-02-01

    Full Text Available In this study, we consider the nonlinear heat equation $$displaylines{ u_{t}(x,t = Delta u(x,t + u(x,t^p quad hbox{in } Omega imes (0,T,cr Bu(x,t = 0 quad hbox{on } partialOmega imes (0,T,cr u(x,0 = u_0(x quad hbox{in } Omega,}$$ with Dirichlet and mixed boundary conditions, where $Omega subset mathbb{R}^n$ is a smooth bounded domain and $p = 1+ 2 /n$ is the critical exponent. For an initial condition $u_0 in L^1$, we prove the non-existence of local solution in $L^1$ for the mixed boundary condition. Our proof is based on comparison principle for Dirichlet and mixed boundary value problems. We also establish the global existence in $L^{1+epsilon}$ to the Dirichlet problem, for any fixed $epsilon > 0$ with $|u_0|_{1+epsilon}$ sufficiently small.

  1. 40 CFR 417.84 - Pretreatment standards for existing sources.

    Science.gov (United States)

    2010-07-01

    ...) EFFLUENT GUIDELINES AND STANDARDS SOAP AND DETERGENT MANUFACTURING POINT SOURCE CATEGORY Manufacture of Liquid Soaps Subcategory § 417.84 Pretreatment standards for existing sources. Any existing source...

  2. Black Hole Caught Zapping Galaxy into Existence?

    Science.gov (United States)

    2009-11-01

    , construction and operation of powerful ground-based observing facilities enabling astronomers to make important scientific discoveries. ESO also plays a leading role in promoting and organising cooperation in astronomical research. ESO operates three unique world-class observing sites in Chile: La Silla, Paranal and Chajnantor. At Paranal, ESO operates the Very Large Telescope, the world's most advanced visible-light astronomical observatory. ESO is the European partner of a revolutionary astronomical telescope ALMA, the largest astronomical project in existence. ESO is currently planning a 42-metre European Extremely Large optical/near-infrared Telescope, the E-ELT, which will become "the world's biggest eye on the sky".

  3. 48 CFR 27.405-4 - Other existing data.

    Science.gov (United States)

    2010-10-01

    ... CONTRACTING REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS Rights in Data and Copyrights 27.405-4 Other existing data. (a) Except for existing works pursuant to 27.405-2 or commercial computer software pursuant to 27...

  4. 40 CFR 417.64 - Pretreatment standards for existing sources.

    Science.gov (United States)

    2010-07-01

    ...) EFFLUENT GUIDELINES AND STANDARDS SOAP AND DETERGENT MANUFACTURING POINT SOURCE CATEGORY Manufacture of Soap Flakes and Powders Subcategory § 417.64 Pretreatment standards for existing sources. Any existing...

  5. 40 CFR 417.24 - Pretreatment standards for existing sources.

    Science.gov (United States)

    2010-07-01

    ...) EFFLUENT GUIDELINES AND STANDARDS SOAP AND DETERGENT MANUFACTURING POINT SOURCE CATEGORY Fatty Acid Manufacturing by Fat Splitting Subcategory § 417.24 Pretreatment standards for existing sources. Any existing...

  6. 40 CFR 417.74 - Pretreatment standards for existing sources.

    Science.gov (United States)

    2010-07-01

    ...) EFFLUENT GUIDELINES AND STANDARDS SOAP AND DETERGENT MANUFACTURING POINT SOURCE CATEGORY Manufacture of Bar Soaps Subcategory § 417.74 Pretreatment standards for existing sources. Any existing source subject to...

  7. Existence of pareto equilibria for multiobjective games without compactness

    OpenAIRE

    Shiraishi, Yuya; Kuroiwa, Daishi

    2013-01-01

    In this paper, we investigate the existence of Pareto and weak Pareto equilibria for multiobjective games without compactness. By employing an existence theorem of Pareto equilibria due to Yu and Yuan([10]), several existence theorems of Pareto and weak Pareto equilibria for the multiobjective games are established in a similar way to Flores-B´azan.

  8. 46 CFR 184.115 - Applicability to existing vessels.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Applicability to existing vessels. 184.115 Section 184... 100 GROSS TONS) VESSEL CONTROL AND MISCELLANEOUS SYSTEMS AND EQUIPMENT General Provisions § 184.115 Applicability to existing vessels. (a) An existing vessel need not comply with §§ 184.402(c), 184.404, 184.410...

  9. 77 FR 47572 - Retrospective Analysis of Existing Rules

    Science.gov (United States)

    2012-08-09

    ... COMMISSION 19 CFR Chapter II Retrospective Analysis of Existing Rules AGENCY: International Trade Commission... July 11, 2011, the Commission recently adopted its Plan for Retrospective Analysis of Existing Rules... submitted in connection with the Commission's Preliminary Plan for Retrospective Analysis of Existing Rules...

  10. Synthesis and evaluation of 1-[l brace]1-[5-(2'-[[sup 18]F]fluoroethyl)-2-thienyl]cyclohexyl[r brace]piperidine as a potential in vivo radioligand for the NMDA receptor-channel complex. [N-methyl-D-aspartate receptor

    Energy Technology Data Exchange (ETDEWEB)

    Orita, Kazuhiro; Sasaki, Shigeki; Maeda, Minoru (Kyushu Univ., Fukuoka (Japan). Faculty of Pharmaceutical Sciences); Hashimoto, Atsushi; Nishikawa, Toru (National Inst. of Neuroscience, Tokyo (Japan)); Yugami, Tomoko; Umezu, Kohei (Mitsubishi Kasei Corp., Yokohama (Japan). Research Center)

    1993-10-01

    1-[l brace]1-[5-(2'-[[sup 18]F]Fluoroethyl)-2-thienyl]cyclohexyl[r brace]piperidine ([sup 18]FE-TCP) was prepared a fluorine-substituted analogue of the potent NMDA receptor channel blocker, 1-[1-(2-thienyl)cyclohexyl]piperidine (TCP), by the mesylate displacement with [[sup 18]F]fluoride ion with isolated radiochemical yields of 6-12%, and the synthesis time including a two step HPLC purification was 120 min. The regional distribution in rat brain after i.v. injection of [sup 18]FE-TCP was heterogeneous and similar to the known distribution of phencyclidine recognition sites, with hippocampus-cerebellum, striatum-cerebellum and cerebral cortex-cerebellum concentration ratios of 2.08, 1.7 and 1.54, respectively, 15 min post-injection. Furthermore, this localized regional cerebral distribution was blocked by co-injection with the unlabelled FE-TCP or pretreatment with cis-2-hydroxymethyl-r-1-(N-piperidyl)-1-(2-thienyl)cyclohexane, with the greatest reductions seen in the hippocampus followed by the striatum and cerebral cortex. However, relatively low receptor binding affinity and high non-specific binding due to its high lipophilicity suggest that [sup 18]FE-TCP may not be a suitable radioligand for in vivo PET investigations of the NMDA receptor-channel complex. (Author).

  11. Synthesis of ethyl 8-fluoro-5,6-dihydro-5-(/sup 11/C)methyl-6-oxo-4H-imidazo(1,5-a)(1,4)benzodiazepine-3-carboxylate (RO 15. 1788-/sup 11/C): a specific radioligand for the in vivo study of central benzodiazepine receptors by positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Maziere, M.; Hantraye, P.; Prenant, C.; Sastre, J.; Comar, D. (CEA, 91 - Orsay (France). Service Hospitalier Frederic Joliot)

    1984-10-01

    A method of labelling ethyl 8-fluoro-5,6-dihydro-5-(/sup 11/C) methyl-6-oxo-4H-imidazo(1,5-a)(1,4)benzodiazepine-3-carboxylate (RO 15.1788 /sup 11/C), a benzodiazepine antagonist with carbon-11 has been developed. RO 15.1788-/sup 11/C was prepared by methylation of the nor derivative by I/sup 11/CH/sub 3/. About 100 mCi (maximum 153 mCi, 5.66 GBq) of the chemically and radiochemically pure labelled product were obtained within 25 min with a specific activity on average of 1100 mCi/..mu.. mol (maximum 1740 mCi/..mu..mol-64.4 GBq/..mu..mol). Preliminary results obtained after i.v. administration in the baboon have shown RO 15.1788-/sup 11/C to be of interest as a benzodiazepine radioligand for the in vivo study of benzodiazepine receptors by positron emission tomography.

  12. Existence of minimizers in restricted Hartree-Fock theory

    Directory of Open Access Journals (Sweden)

    Fabian Hantsch

    2014-02-01

    Full Text Available In this note we establish the existence of ground states for atoms within several restricted Hartree-Fock theories. It is shown, for example, that there exists a ground state for closed shell atoms with N electrons and nuclear charge $Z \\geq N-1$. This has to be compared with the general Hartree-Fock theory where the existence of a minimizer is known for $Z >N-1$ only.

  13. Pre-existing Antibody: Biotherapeutic Modality-Based Review

    OpenAIRE

    Gorovits, Boris; Clements-Egan, Adrienne; Birchler, Mary; Liang, Meina; Myler, Heather; Peng, Kun; Purushothama, Shobha; Rajadhyaksha, Manoj; Salazar-Fontana, Laura; Sung, Crystal; Xue, Li

    2016-01-01

    Pre-existing antibodies to biotherapeutic drugs have been detected in drug-naïve subjects for a variety of biotherapeutic modalities. Pre-existing antibodies are immunoglobulins that are either specific or cross-reacting with a protein or glycan epitopes on a biotherapeutic compound. Although the exact cause for pre-existing antibodies is often unknown, environmental exposures to non-human proteins, glycans, and structurally similar products are frequently proposed as factors. Clinical conseq...

  14. What Can We Learn About Blazars With Exist Mission?

    Science.gov (United States)

    Siemiginowska, Aneta

    2010-01-01

    The EXIST mission provides a great opportunity to study blazars. Recent Fermi results confirmed the spectral differences between two classes of blazars in the gamma-ray band, e.g. BL Lacs and Flat Spectrum Radio Quasars. EXIST will provide data in the the lower energy band where the origin of the gamma-rays in these two classes can be constrained. We will discuss model constraints that can be placed with the new data from EXIST.

  15. INFORMATION SECURITY RISK ASSESSMENT USING EXISTING LEGAL AND METHODOLOGICAL BASE

    Directory of Open Access Journals (Sweden)

    A. I. Trubei

    2015-01-01

    Full Text Available The article provides a survey of the existing regulatory framework for information security riskmanagement. Practical methods for information security risk and vulnerability assessment are proposed.

  16. Expandable External Payload Carrier for Existing Launch Vehicles Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Numerous existing launch vehicles have excess performance that is not being optimized. By taking advantage of excess, unused, performance, additional NASA...

  17. 40 CFR 63.1157 - Emission standards for existing sources.

    Science.gov (United States)

    2010-07-01

    ... Facilities and Hydrochloric Acid Regeneration Plants § 63.1157 Emission standards for existing sources. (a... percent. (b) Hydrochloric acid regeneration plants. (1) No owner or operator of an existing affected plant shall cause or allow to be discharged into the atmosphere from the affected plant any gases that contain...

  18. Same Time Same Place: Do MALL Classrooms Exist?

    Science.gov (United States)

    Byrne, Jason

    2016-01-01

    This paper seeks to help clarify whether Mobile-Assisted Language Learning (MALL) is primarily an independent self-study activity or whether MALL classrooms exist. The research hypothesised that a large number of users frequently using specific MALL apps, at the same time and in the same city location, may indicate the existence of MALL…

  19. Comparative performance evaluation of an existing and modified ...

    African Journals Online (AJOL)

    A comparative performance evaluation of an existing and modified acha dehuller was carried out. The modifications undertaken on the existing dehuller were for the cylinder type, cylinder-concave clearance, cylinder speed and hopper opening. The modified acha dehuller was run at a higher cylinder and fan speeds of ...

  20. Neural Network for Optimization of Existing Control Systems

    DEFF Research Database (Denmark)

    Madsen, Per Printz

    1995-01-01

    The purpose of this paper is to develop methods to use Neural Network based Controllers (NNC) as an optimization tool for existing control systems.......The purpose of this paper is to develop methods to use Neural Network based Controllers (NNC) as an optimization tool for existing control systems....

  1. 18 CFR 430.21 - Protection of existing users.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 2 2010-04-01 2010-04-01 false Protection of existing users. 430.21 Section 430.21 Conservation of Power and Water Resources DELAWARE RIVER BASIN COMMISSION SPECIAL REGULATIONS GROUND WATER PROTECTION AREA: PENNSYLVANIA § 430.21 Protection of existing users. (a...

  2. 42 CFR 137.3 - Effect on existing Tribal rights.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Effect on existing Tribal rights. 137.3 Section 137.3 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES INDIAN HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES TRIBAL SELF-GOVERNANCE General Provisions § 137.3 Effect on existing...

  3. 40 CFR 408.184 - Pretreatment standards for existing sources.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 28 2010-07-01 2010-07-01 true Pretreatment standards for existing sources. 408.184 Section 408.184 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Hand-Butchered Salmon Processing Subcategory § 408.184 Pretreatment standards for existing sources. Any...

  4. On existence and stability of solutions for higher order semilinear ...

    Indian Academy of Sciences (India)

    Dirichlet problem; dual variational method; existence of solutions; stability. Abstract. We provide existence and stability results for semilinear Dirichlet problems with nonlinearity satisfying general growth conditions. ... Faculty of Mathematics and Computer Science, University of Lodz, Banacha 22, 90-238 Lodz, Poland ...

  5. Rehabilitation of Existing Structures Subjected to Extreme Events

    Directory of Open Access Journals (Sweden)

    Corneliu Bob

    2007-01-01

    Full Text Available The paper presents the characteristics of existing structures under extreme actions, general and specific rehabilitation solutions detailed for reinforced concrete and masonry structures. Rehabilitation of different types of existing structures are described: a reinforced concrete framed structure presenting major detailing vulnerabilities at seismic actions; an apartment house affected by an explosion; two masonry buildings affected by a recent earthquake.

  6. Existence of a secondary flow for a temperature dependent viscous ...

    African Journals Online (AJOL)

    We model a viscous fluid flowing between parallel plates. The viscosity depends on temperature. We investigate the properties of the velocity and we show that the temperature and velocity fields have two solutions. The existence of two velocity solutions is new. This means that there exist secondary flows. Journal of the ...

  7. Existence theory for nonlinear functional boundary value problems

    Directory of Open Access Journals (Sweden)

    Bapurao Dhage

    2004-01-01

    Full Text Available In this paper the existence of a solution of a general nonlinear functional two point boundary value problem is proved under mixed generalized Lipschitz and Carath\\'eodory conditions. An existence theorem for extremal solutions is also proved under certain monotonicity and weaker continuity conditions. Examples are provided to illustrate the theory developed in this paper.

  8. 40 CFR 463.15 - Pretreatment standards for existing sources.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 29 2010-07-01 2010-07-01 false Pretreatment standards for existing sources. 463.15 Section 463.15 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Heating Water Subcategory § 463.15 Pretreatment standards for existing sources. (a) PSES for bis(2...

  9. Existence of Positive Solutions of Neutral Differential Equations

    Directory of Open Access Journals (Sweden)

    B. Dorociaková

    2012-01-01

    Full Text Available The paper contains some suffcient conditions for the existence of positive solutions which are bounded below and above by positive functions for the nonlinear neutral differential equations of higher order. These equations can also support the existence of positive solutions approaching zero at infinity.

  10. Existence of longitudinal waves in pre-stressed anisotropic elastic ...

    Indian Academy of Sciences (India)

    existence and propagation of longitudinal waves in pre-stressed anisotropic elastic medium. These expressions involve not only the direction and elastic stiffness of the medium, but also the pre- stresses present in the medium. Changes in conditions for the existence of longitudinal waves in orthotropic, monoclinic and ...

  11. Design analysis of an existing acha (digitariaexilis) dehulling machine

    African Journals Online (AJOL)

    An existing acha dehulling machine was improved upon by re-designing. The performance of the existing dehulling machine was first evaluated to determine the required modification. Improvements were undertaken in the cylinder speed, cylinder-concave clearance, hopper slope and opening, cylinder type and fan speed.

  12. I doubt, therefore African philosophy exists | Ramose | South African ...

    African Journals Online (AJOL)

    In this essay the question whether or not African philosophy exists is considered through an examination of the meaning of doubt. In St. Augustine and Descartes the basic presupposition with regard to doubt is the indubitable certainty that the doubting subject must exist before there can be any doubt at all. By parity of ...

  13. Existence of a Unique Zero of Nonlinear Systems

    DEFF Research Database (Denmark)

    Bao, Paul; Anton, François; Rokne, Jon

    2007-01-01

    Existence statements for zeros of nonlinear equations are established via the interval Newton method generalizing previous theorems requiring regularity of the inclusion for the Jacobian.......Existence statements for zeros of nonlinear equations are established via the interval Newton method generalizing previous theorems requiring regularity of the inclusion for the Jacobian....

  14. The solution of location problems with certain existing facility structures

    DEFF Research Database (Denmark)

    Juel, Henrik; Love, Robert F.

    1983-01-01

    It is known that in the Euclidean distance case, the optimal minisum location of a new facility in relation to four existing facilities is at the intersection of the two lines joining two pairs of the facilities. The authors extend this concept to minisum problems having any even number of existing...... facilities and characterized by generalized distance norms...

  15. The shame of existing: an extreme form of shame.

    Science.gov (United States)

    Wille, Robbert

    2014-08-01

    This paper presents 'the shame of existing' as a form of shame that is deeper and more extensive than those customarily encountered. 'The shame of existing' is defined as shame about existing as we are and especially at the fact that we are. It is accompanied by merciless and total rejection of the subject's self and by feelings of extreme worthlessness and inferiority coupled with the all-pervasive conviction that it would be better not to exist. On the basis of clinical material, consideration is given to the specific transference and countertransference aspects of analyses in which the shame of existing constitutes an important part of the patient's pathology. Disturbance of handling and holding by the primary objects right from birth is suggested as the earliest developmental basis of the shame of existing. This disturbance is attributed to hate and rejection of the infant by the primary objects and to the infant's not being touched emotionally and physically and not having its right to exist acknowledged. The paper begins with an introduction to shame as an affect and as a concept in psychoanalytic theory. Copyright © 2014 Institute of Psychoanalysis.

  16. Pre-existing Antibody: Biotherapeutic Modality-Based Review.

    Science.gov (United States)

    Gorovits, Boris; Clements-Egan, Adrienne; Birchler, Mary; Liang, Meina; Myler, Heather; Peng, Kun; Purushothama, Shobha; Rajadhyaksha, Manoj; Salazar-Fontana, Laura; Sung, Crystal; Xue, Li

    2016-03-01

    Pre-existing antibodies to biotherapeutic drugs have been detected in drug-naïve subjects for a variety of biotherapeutic modalities. Pre-existing antibodies are immunoglobulins that are either specific or cross-reacting with a protein or glycan epitopes on a biotherapeutic compound. Although the exact cause for pre-existing antibodies is often unknown, environmental exposures to non-human proteins, glycans, and structurally similar products are frequently proposed as factors. Clinical consequences of the pre-existing antibodies vary from an adverse effect on patient safety to no impact at all and remain highly dependent on the biotherapeutic drug modality and therapeutic indication. As such, pre-existing antibodies are viewed as an immunogenicity risk factor requiring a careful evaluation. Herein, the relationships between biotherapeutic modalities to the nature, prevalence, and clinical consequences of pre-existing antibodies are reviewed. Initial evidence for pre-existing antibody is often identified during anti-drug antibody (ADA) assay development. Other interfering factors known to cause false ADA positive signal, including circulating multimeric drug target, rheumatoid factors, and heterophilic antibodies, are discussed.

  17. A coupled chemotaxis-fluid model: Global existence

    KAUST Repository

    Liu, Jian-Guo

    2011-09-01

    We consider a model arising from biology, consisting of chemotaxis equations coupled to viscous incompressible fluid equations through transport and external forcing. Global existence of solutions to the Cauchy problem is investigated under certain conditions. Precisely, for the chemotaxis-Navier- Stokes system in two space dimensions, we obtain global existence for large data. In three space dimensions, we prove global existence of weak solutions for the chemotaxis-Stokes system with nonlinear diffusion for the cell density.© 2011 Elsevier Masson SAS. All rights reserved.

  18. The amazing vitality of things that don’t exist

    DEFF Research Database (Denmark)

    Tarp, Sven

    2016-01-01

    This contribution moves in the grey zone between lexicographical reality and fiction. It starts three hundred years ago and presents some dictionaries that do not exist. It then follows the historical development and shows how these dictionaries recently have got company by lexicographical theories...... that flourish although they do not exist either. It argues that this mess has been created and have survived until our days because some lexicographers follow their personal preferences instead of being faithful to their empirical basis. The contribution sends an optimistic message praising the vitality...... of the non-existing dictionaries and theories....

  19. The EXIST Mission for High-Energy Astrophysics

    Science.gov (United States)

    Fishman, G. J.; Grindlay, J. E.; Hong, J.

    2006-01-01

    The Energetic X-ray Imaging Survey Telescope (EXIST), under study to be the Black Hole Finder Probe in NASA's Beyond Einstein Program, would image the sky every 95min in the energy range 1 OkeV to 600 keV. Although the main scientific objectives of EXIST are the systematic, all-sky survey of heavily obscured AGNs and gamma-ray bursts, there is a substantial capability of EXIST for the observation of transient and persistent hard x-ray lines from several astrophysical sources.

  20. The Performance-Potential Dilemma. Does It Exist?

    Science.gov (United States)

    1978-09-01

    AFIT/OSM/SM-785..3 / MAR15 1979 >aTHE PERFORMANCE-POTENTIAL Dr LEMMA - -DOES IT EXIST ? w• THESIS AFIT/GSIA/SM-78S-3 Drew W. Browning Capt USAF C-,2...Approved for public release; distribution unlimited. 7 ( 13 003 ~AFIT/GSM/SM-78S-3 / " THE PERFORMANCE-POT ENTIA L DI/ 2LEMMV-OES IT EXIST ¢’ T /i...widely varied perceptions do exist , many organizational dvsfunc- "cons inay occur. This research effort examines Air Force officers’ perceptions, both

  1. Existence of solutions for elliptic systems with critical Sobolev exponent

    Directory of Open Access Journals (Sweden)

    Pablo Amster

    2002-06-01

    Full Text Available We establish conditions for existence and for nonexistence of nontrivial solutions to an elliptic system of partial differential equations. This system is of gradient type and has a nonlinearity with critical growth.

  2. Branding in children: a barbaric practice still exists in India.

    Science.gov (United States)

    Patra, Pratap Kumar

    2016-01-01

    Branding is an inhuman traditional practice most commonly employed to treat various disorders in neonates and children in certain community in India. Though stringent law exists to prevent such harmful practices, cases of branding is not uncommon in current era.

  3. Existence of Weak Solutions for a Nonlinear Elliptic System

    Directory of Open Access Journals (Sweden)

    Gilbert RobertP

    2009-01-01

    Full Text Available We investigate the existence of weak solutions to the following Dirichlet boundary value problem, which occurs when modeling an injection molding process with a partial slip condition on the boundary. We have in ; in ; , and on .

  4. Report on the Pre-existing Condition Insurance Plan Program

    Data.gov (United States)

    U.S. Department of Health & Human Services — Before the Affordable Care Act, Americans with pre-existing conditions who did not receive health coverage through their employers had few affordable options to get...

  5. Existence for a class of discrete hyperbolic problems

    Directory of Open Access Journals (Sweden)

    Luca Rodica

    2006-01-01

    Full Text Available We investigate the existence and uniqueness of solutions to a class of discrete hyperbolic systems with some nonlinear extreme conditions and initial data, in a real Hilbert space.

  6. Problem of mathematical deduction of the existence of black holes

    Directory of Open Access Journals (Sweden)

    Yuan-Shun Chin

    1990-01-01

    Full Text Available The mathematical proof of existence of Black Hole is based on the assumption of mass being independent of speed. Considering the effect of special relativity of the dependence of mass with speed there is no Black hole.

  7. Non-existence of limit cycles for planar vector fields

    Directory of Open Access Journals (Sweden)

    Jaume Gine

    2014-03-01

    Full Text Available This article presents sufficient conditions for the non-existence of limit cycles for planar vector fields. Classical methods for the nonexistence of limit cycles are connected with the theory developed here.

  8. Existence results for anisotropic discrete boundary value problems

    Directory of Open Access Journals (Sweden)

    Avci Avci

    2016-06-01

    Full Text Available In this article, we prove the existence of nontrivial weak solutions for a class of discrete boundary value problems. The main tools used here are the variational principle and critical point theory.

  9. A corrosion monitoring system for existing reinforced concrete structures.

    Science.gov (United States)

    2015-05-01

    This study evaluated a multi-parameter corrosion monitoring system for existing reinforced concrete structures in chloride-laden service environments. The system was fabricated based on a prototype concrete corrosion measurement system that : had bee...

  10. What history tells us XXXV. Enhancers: Their existence and ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Biosciences; Volume 39; Issue 5. What history tells us XXXV. Enhancers: Their existence and characteristics have raised puzzling issues since their discovery. Michel Morange. Series Volume 39 Issue 5 December 2014 pp 741-745 ...

  11. Verification of the existence of food security projects in Limpopo ...

    African Journals Online (AJOL)

    Verification of the existence of food security projects in Limpopo Province, South Africa. ... at district level and are knowledgeable about developmental issues. ... Frequency tables and charts were computed on a computer spreadsheet.

  12. Monthly Pre-Existing Condition Insurance Plan Enrollment

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Affordable Care Act created the new Pre-Existing Condition Insurance Plan (PCIP) program to make health insurance available to Americans denied coverage by...

  13. Background Studies for the Black Hole Finder Probe EXIST

    Science.gov (United States)

    Garson, Alfred, III; Sturner, S.; Skinner, G.; Krawczynski, H.; Hong, J.; Grindlay, J.

    2009-12-01

    The Energetic X-ray Imaging Survey Telescope (EXIST) will provide a wide field of view survey of the hard X-ray sky in order to detect and locate black holes of many different mass scales and redshifts. EXIST's High Energy Telescope (HET) will use 5mm-thick CZT detectors and be sensitive from 5 -600 keV. As fluctuations in background rates will largely determine the sensitivity of EXIST's CZT detectors, predicting and understanding the background rates from multiple components found in low Earth orbit are crucial to the feasibility of science objectives and mission design. We report on new Monte Carlo simulations of the background environment expected for EXIST's orbit. We validate our results by comparing simulated and observed background rates for Swift's Burst Alert Telescope. This is work is supported by NASA under contract NNX07AH37G.

  14. Reproducibility in Psychological Science: When Do Psychological Phenomena Exist?

    OpenAIRE

    Iso-Ahola, Seppo E.

    2017-01-01

    Scientific evidence has recently been used to assert that certain psychological phenomena do not exist. Such claims, however, cannot be made because (1) scientific method itself is seriously limited (i.e., it can never prove a negative); (2) non-existence of phenomena would require a complete absence of both logical (theoretical) and empirical support; even if empirical support is weak, logical and theoretical support can be strong; (3) statistical data are only one piece of evidence and cann...

  15. Existence of solutions to quasilinear Schrodinger equations with indefinite potential

    Directory of Open Access Journals (Sweden)

    Zupei Shen

    2015-04-01

    Full Text Available In this article, we study the existence and multiplicity of solutions of the quasilinear Schrodinger equation $$ -u''+V(xu-(|u| ^2''u=f(u $$ on $\\mathbb{R}$, where the potential $V$ allows sign changing and the nonlinearity satisfies conditions weaker than the classical Ambrosetti-Rabinowitz condition. By a local linking theorem and the fountain theorem, we obtain the existence and multiplicity of solutions for the equation.

  16. Postpneumonectomy syndrome and pre-existing thoracic scoliosis.

    Science.gov (United States)

    Bobbio, Antonio; Alifano, Marco; Magdeleinat, Pierre; Regnard, Jean François

    2002-01-01

    We report a case of postpneumonectomy syndrome in a 75-year-old man operated on for right lung cancer 18 months previously. The patient had a pre-existing severe thoracic scoliosis. Treatment involved positioning of an expandable silastic prosthesis in the postpneumonectomy cavity. A favorable outcome was observed. We think that a pre-existing scoliosis could be considered as a potentially predisposing factor to the development of the syndrome.

  17. Collection Level Description: A review of existing practice

    OpenAIRE

    Powell, Andy; Bull, Rob; Fisk, Martin; Hamilton, Martin; Kelly, Brian; Lester, Ray; Matheson, Ann; Methven, Patricia; Murray, Jim; Nicholoson, Dennis; Russell, Rosemary

    1999-01-01

    This study reviews existing practice for providing collection level descriptions, as it exists in the library, archival, museum and Internet communities. It originated from discussions at MODELS workshops [MODELS], where the need for a review of different approaches to collection level description was identified, particularly in the context of phase 3 of the Electronic Libraries Programme [ELIB]. The study was taken forward by UKOLN as a MODELS recommendation.

  18. Non-existence criteria for Laurent polynomial first integrals

    Directory of Open Access Journals (Sweden)

    Shaoyun Shi

    2003-01-01

    Full Text Available In this paper we derived some simple criteria for non-existence and partial non-existence Laurent polynomial first integrals for a general nonlinear systems of ordinary differential equations $\\dot x = f(x$, $x \\in \\mathbb{R}^n$ with $f(0 = 0$. We show that if the eigenvalues of the Jacobi matrix of the vector field $f(x$ are $\\mathbb{Z}$-independent, then the system has no nontrivial Laurent polynomial integrals.

  19. Existence of excited states for a nonlinear Dirac equation

    Energy Technology Data Exchange (ETDEWEB)

    Balabane, M.; Cazenave, T.; Douady, A.; Merle, F.

    1988-01-21

    We prove the existence of infinitely many stationary states for the nonlinear Dirac equation. Seeking eigenfunctions splitted in spherical coordinates leads to analyse a nonautonomous dynamical system in R/sup 2/. The number of eigenfunctions is given by the number of intersections of the stable manifold of the origin with the curve of admissible data. This proves the existence of infinitely many stationary states ordered by the number of nodes of the components

  20. Existence of solitary waves in dipolar quantum gases

    KAUST Repository

    Antonelli, Paolo

    2011-02-01

    We study a nonlinear Schrdinger equation arising in the mean field description of dipolar quantum gases. Under the assumption of sufficiently strong dipolar interactions, the existence of standing waves, and hence solitons, is proved together with some of their properties. This gives a rigorous argument for the possible existence of solitary waves in BoseEinstein condensates, which originate solely due to the dipolar interaction between the particles. © 2010 Elsevier B.V. All rights reserved.

  1. Study of structural reliability of existing concrete structures

    Science.gov (United States)

    Druķis, P.; Gaile, L.; Valtere, K.; Pakrastiņš, L.; Goremikins, V.

    2017-10-01

    Structural reliability of buildings has become an important issue after the collapse of a shopping center in Riga 21.11.2013, caused the death of 54 people. The reliability of a building is the practice of designing, constructing, operating, maintaining and removing buildings in ways that ensure maintained health, ward suffered injuries or death due to use of the building. Evaluation and improvement of existing buildings is becoming more and more important. For a large part of existing buildings, the design life has been reached or will be reached in the near future. The structures of these buildings need to be reassessed in order to find out whether the safety requirements are met. The safety requirements provided by the Eurocodes are a starting point for the assessment of safety. However, it would be uneconomical to require all existing buildings and structures to comply fully with these new codes and corresponding safety levels, therefore the assessment of existing buildings differs with each design situation. This case study describes the simple and practical procedure of determination of minimal reliability index β of existing concrete structures designed by different codes than Eurocodes and allows to reassess the actual reliability level of different structural elements of existing buildings under design load.

  2. ProtoEXIST2: Advanced Wide-field Imaging CZT Detector Development For The HET On The Proposed EXIST Mission

    Science.gov (United States)

    Hong, JaeSub; Allen, B.; Grindlay, J.; Barthelmy, S.; Baker, R.; Gehrels, N.; Cook, W.; Kaye, S.; Harrison, F.

    2010-03-01

    We describe our development of ProtoEXIST2, the advanced CZT imaging detector and wide field telescope prototype for the High Energy Telescope (HET) on the proposed Energetic X-ray Imaging Survey Telescope (EXIST) mission. EXIST is a multi-wavelength Medium class mission which would explore the early Universe using high redshift Gamma-ray Bursts and survey black holes on all scales. ProtoEXIST2 will demonstrate the feasibility of a large scale imaging module (256 cm2) with a close-tiled array of fine pixel (0.6 mm) CZT with a balloon flight test in 2010 or 2011. This second generation close-tiled CZT imager follows ProtoEXIST1, which had a recent successful balloon flight (see Allen et al in this meeting) using the same area CZT detector module (256 cm2) but with larger pixel size (2.5mm). For signal readout and event processing, we use the Direct-Bond (DB) ASIC, developed for the NuSTAR mission to be used in a close-tiled 2 x 2 array of 2x2 cm2 CZT detectors, each with 32x32 pixels. The DB-ASIC is attractive for a large scale implementation of tiled imaging CZT detectors given its low noise and power consumption (70uW/pixel). We are developing readout for the DB-ASIC that incorporates our back-end FPGA readout architecture developed for ProtoEXIST1 in order to accomplish the 256 cm2 detector module area with totally vertical integration (i.e. no auxialliary boards to the sides of the module. This is required to tile large numbers of modules into the very large total area (4.5m^2) proposed for the HET on EXIST. We review the design of the EXIST/HET and its optimum shielding in light of our ProtoEXIST1 balloon flight and our plan for future development of ProtoEXIST3, a final EXIST/HET detector module that would incorporate a still lower power version of the DB ASIC.

  3. The Energetic X-ray Imaging Survey Telescope (EXIST)

    Science.gov (United States)

    Grindlay, Jonathan E.

    2009-01-01

    The Energetic X-ray Imaging Survey Telescope (EXIST) is a proposed hard X-ray imaging all-sky deep survey mission recommended by the Report of the 2001 Decadal Survey. It is a strong candidate to be the Black Hole Finder Probe, one of the three "Einstein Probes" in the Beyond Einstein Program. In its new more evolved form, the EXIST mission now includes a simplified, but more sensitive, very large area and field of view imaging hard X-ray telescope as well as a 1.1m optical-NIR telescope (0.3-2.5microns) for rapid ( 100sec) followup imaging and spectra and thus prompt redshifts of high-z GRBs. The IRT will also permit identification and galaxy spectra for a significant fraction of the obscured AGNs detected in the EXIST full sky survey. The primary science objectives for EXIST are to: 1) study the earliest stars, re-ionization, and development of structure in the universe with prompt hard X-ray and prompt followup NIR measurements of GRBs at z >7, 2) constrain the accretion luminosity of the universe by measurements of high luminosity obscured AGN at z 0-2.5, low luminosity AGN at z 10X the area of Swift/BAT and much broader energy band, as well deep NIR coverage with a passively cooled mirror, EXIST greatly surpasses any previous or proposed mission for wide-field imaging and spectroscopy of GRBs and black holes on all scales.

  4. GRB Probes of the High-z Universe with EXIST

    Science.gov (United States)

    Grindlay, Jonathan; EXIST Team

    2009-05-01

    The Energetic X-ray Imaging Survey Telescope (EXIST) mission concept was selected for further study under the Astrophysics Strategic Mission Concept Study (ASMCS) program. The mission design is optimized for study of high-z GRBs as probes of the early Universe. With a 4.5 m2 imaging 5-600 keV (CZT) detector imaging a 90°×70° (>10% coding fraction) field of view with 2' resolution and 5σ sources, EXIST will perform rapid (exist, and spectra for studies of the host galaxy and local re-ionization bubble as well as intervening cosmic structure. With ~600 GRBs/yr expected, EXIST will open a new era in studies of the early Universe as well as carry out a rich program of AGN and transient-source science. An overview of the GRB science objectives and a brief discussion of the overall mission design and operations is given, and example high-z GRB spectra are shown. EXIST is being proposed to the Astro2010 Decadal Survey as a Medium Class mission that could be launched as early as 2017.

  5. Existence of bounded positive solutions of a nonlinear differential system

    Directory of Open Access Journals (Sweden)

    Sabrine Gontara

    2012-04-01

    Full Text Available In this article, we study the existence and nonexistence of solutions for the system $$displaylines{ frac{1}{A}(Au''=pu^{alpha }v^{s}quad hbox{on }(0,infty , cr frac{1}{B}(Bu''=qu^{r}v^{eta }quad hbox{on }(0,infty , cr Au'(0=0,quad u(infty =a>0, cr Bv'(0=0,quad v(infty =b>0, }$$ where $alpha ,eta geq 1$, $s,rgeq 0$, p,q are two nonnegative functions on $(0,infty $ and A, B satisfy appropriate conditions. Using potential theory tools, we show the existence of a positive continuous solution. This allows us to prove the existence of entire positive radial solutions for some elliptic systems.

  6. Existence of non-Abelian vortices with product gauge groups

    Energy Technology Data Exchange (ETDEWEB)

    Han, Xiaosen, E-mail: xiaosenhan@gmail.com [Institute of Contemporary Mathematics, School of Mathematics, Henan University, Kaifeng, Henan 475004 (China); Taida Institute for Mathematical Sciences, Center for Advanced Study in Theoretical Science, National Taiwan University, Taipei, 10617, Taiwan (China); Lin, Chang-Shou [Taida Institute for Mathematical Sciences, Center for Advanced Study in Theoretical Science, National Taiwan University, Taipei, 10617, Taiwan (China)

    2014-01-15

    In this paper we establish several sharp existence and uniqueness theorems for some non-Abelian vortex models arising in supersymmetric gauge field theories. We prove these results by studying a family of systems of elliptic equations with exponential nonlinear terms in both doubly periodic-domain and planar cases. In the doubly periodic-domain case we obtain some necessary and sufficient conditions, each explicitly expressed in terms of a single inequality interestingly relating the vortex numbers, to coupling parameters and size of the domain, for the existence of solutions to these systems. In the planar case we establish the existence results for any vortex numbers and coupling parameters. Sharp decay estimates for the planar solutions are also obtained. Furthermore, the solutions are unique, which give rise to the quantized integrals in all cases.

  7. Exploring The Transient X-ray Sky With Exist

    Science.gov (United States)

    Soderberg, Alicia Margarita; EXIST Transient Science Working Group

    2009-01-01

    The Energetic X-ray Imaging Survey Telescope (EXIST) is a proposed hard X-ray imaging all-sky deep survey mission that will provide an unprecedented sensitivity as well as monitoring and localization capabilities to X-ray transients. One of the three major science cases for EXIST is the discovery and study of X-ray transients in the local Universe. This includes shock breakout emission from core-collapse supernovae, outbursts from ULXs and SSSs, coronal activity from flare stars, tidal disruption events, QPOs and SGR superflares. The unique optical/IR follow-up capabilities provided by EXIST's on-board IR Telescope will revolutionize our broadband understanding of these transient high-energy phenomena, in conjunction with ground-based surveys such as Pan-STARRS and LSST.

  8. Confusing medical terms: disease that may or may not exist.

    Science.gov (United States)

    Cohen, H K S; Luther, A; Hart, C A

    2013-07-01

    Patients often quote diseases or illnesses that either do not exist per se or are hard to prove that they exist. Often symptoms are vague and, therefore, difficult for patients to qualify in a language clinicians can understand, interpret and act upon. Physicians often perpetuate this by giving 'diagnoses of exclusion', or using poor explanations, oversimplifications, conflicting diagnostic criteria or vague historical terms that have now evolved into something else. However, the history taker must be able to interpret the subtle language barrier that exists between doctor and patient. In this short review of the literature, some commonly quoted conditions are examined more closely to try and understand further the terminology used by both patients and clinicians alike.

  9. Existence of periodic solutions for a semilinear ordinary differential equation

    Directory of Open Access Journals (Sweden)

    Petr Girg

    1998-11-01

    Full Text Available Dancer [3] found a necessary and sufficient condition for the existence of periodic solutions to the equation $$ ddot x +g_1(dot x + g_0(x = f(t,.$$ His condition is based on a functional that depends on the solution to the above equation with $g_0=0$. However, that solution is not always explicitly known which makes the condition unverifiable in practical situations. As an alternative, we find computable bounds for the functional that provide a sufficient condition and a necessary condition for the existence of solutions.

  10. Obstructions to the Existence of Sasaki-Einstein Metrics

    CERN Document Server

    Gauntlett, J P; Sparks, J; Yau, S T; Gauntlett, Jerome P.; Martelli, Dario; Sparks, James; Yau, Shing-Tung

    2007-01-01

    We describe two simple obstructions to the existence of Ricci-flat Kahler cone metrics on isolated Gorenstein singularities or, equivalently, to the existence of Sasaki-Einstein metrics on the links of these singularities. In particular, this also leads to new obstructions for Kahler-Einstein metrics on Fano orbifolds. We present several families of hypersurface singularities that are obstructed, including 3-fold and 4-fold singularities of ADE type that have been studied previously in the physics literature. We show that the AdS/CFT dual of one obstruction is that the R-charge of a gauge invariant chiral primary operator violates the unitarity bound.

  11. Existing and Expected Service Quality of Grameenphone Users in Bangladesh

    Directory of Open Access Journals (Sweden)

    Azmat Ullah

    2015-12-01

    Full Text Available The Grameenphone (GP is a market leader in the telecommunication industry in Bangladesh. This study investigates the existing and expected service quality of Grameenphone users in Bangladesh. The Study reveals that there are significant gap between existing and expected perceived service network, 3G, customer care, physical facilities, billing cost, information service, mobile banking and GP offers. The study concludes that customer satisfaction is a dynamic phenomenon. Maintaining desired level of customer satisfaction requires corporate proactive responsiveness in accessing, building & retaining satisfied customers for sustainable competitive advantages in the marketplace.

  12. Existing PON Infrastructure Supported Hybrid Fiber-Wireless Sensor Networks

    DEFF Research Database (Denmark)

    Yu, Xianbin; Zhao, Ying; Deng, Lei

    2012-01-01

    We propose a hybrid fiber wireless sensor network based on the existing PON infrastructure. The feasibility of remote sensing and PON convergence is experimentally proven by transmitting direct-sequence spread-spectrum wireless sensing and 2.5Gbps GPON signals.......We propose a hybrid fiber wireless sensor network based on the existing PON infrastructure. The feasibility of remote sensing and PON convergence is experimentally proven by transmitting direct-sequence spread-spectrum wireless sensing and 2.5Gbps GPON signals....

  13. Myotoxicity of telbivudine in pre-existing muscle damage

    Directory of Open Access Journals (Sweden)

    Ay Leyla

    2010-11-01

    Full Text Available Abstract Objectives It is unknown if telbivudine causes muscle damage only in patients with pre-existing muscle pathology. Case report A 27 yo male of African origin received telbivudine for hepatitis B during 3 months. Three weeks after initiation of the drug he developed myalgia, and tiredness. Creatine-kinase increased from 278 U/l (n, Conclusions Telbivudine appears to cause accelerated muscle toxicity if given to patients who already have muscle damage. Patients under telbivudine should be closely monitored for muscular side effects and those with pre-existing muscle damage should not receive the drug.

  14. FMDP reactor alternative summary report. Volume 1 - existing LWR alternative

    Energy Technology Data Exchange (ETDEWEB)

    Greene, S.R.; Bevard, B.B. [and others

    1996-10-07

    Significant quantities of weapons-usable fissile materials [primarily plutonium and highly enriched uranium (HEU)] are becoming surplus to national defense needs in both the United States and Russia. These stocks of fissile materials pose significant dangers to national and international security. The dangers exist not only in the potential proliferation of nuclear weapons but also in the potential for environmental, safety, and health (ES&H) consequences if surplus fissile materials are not properly managed. This document summarizes the results of analysis concerned with existing light water reactor plutonium disposition alternatives.

  15. AGN Science With The EXIST Hard X-ray Satellite

    Science.gov (United States)

    Coppi, Paolo S.; EXIST AGN Science Working Group

    2009-01-01

    With its large collection area, broad-band energy coverage from 10 to 600 keV, and all-sky monitoring capability, the proposed EXIST hard X-ray satellite mission will provide an unrivaled census of transient AGN activity in the nearby( zEXIST AGN hard X-ray survey coupled with a follow-up survey using the on-board optical/near-infrared telescope (IRT) will significantly advance our understanding of AGN physics and of how the AGN phenomenon fits into the overall process of galaxy formation.

  16. The Anterolateral Ligament Does Exist: An Anatomic Description.

    Science.gov (United States)

    Zaffagnini, Stefano; Grassi, Alberto; Marcheggiani Muccioli, Giulio Maria; Raggi, Federico; Romagnoli, Matteo; Bondi, Alice; Calderone, Salvatore; Signorelli, Cecilia

    2018-01-01

    The debate around the existence, anatomy, and role of the so-called anterolateral ligament of the knee represents one of the main sources of recent controversy among orthopedic surgeons. In the modern era of sports medicine, several content experts have contributed to the understanding of the anatomy of the anterolateral aspect of the knee. This article analyzes the historical, phylogenetic, anatomic, arthroscopic, and radiological evidence regarding the anterolateral ligament. The existence of the anterolateral ligament as a distinct ligamentous structure and its exact anatomic features are still matters of controversy and ongoing study. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. On the existence of best proximity points for generalized contractions

    Directory of Open Access Journals (Sweden)

    V. Vetrivel

    2014-04-01

    Full Text Available In this article we establish the existence of a unique best proximity point for some generalized non self contractions on a metric space in a simpler way using a geometric result. Our results generalize some recent best proximity point theorems and several fixed point theorems proved by various authors.

  18. Improvement Design of an Existing Atomized Kerosene Stove for ...

    African Journals Online (AJOL)

    The existing atomized kerosene stove being used in some households in Nigeria does not give room for primary air fuel mixture but secondary one before combustion. This in turn leads to higher specific fuel consumption and ultimately lower thermal efficiency (resulting from low combustion efficiency) of the stove. In order ...

  19. Incorporating existing network information into gene network inference.

    Directory of Open Access Journals (Sweden)

    Scott Christley

    2009-08-01

    Full Text Available One methodology that has met success to infer gene networks from gene expression data is based upon ordinary differential equations (ODE. However new types of data continue to be produced, so it is worthwhile to investigate how to integrate these new data types into the inference procedure. One such data is physical interactions between transcription factors and the genes they regulate as measured by ChIP-chip or ChIP-seq experiments. These interactions can be incorporated into the gene network inference procedure as a priori network information. In this article, we extend the ODE methodology into a general optimization framework that incorporates existing network information in combination with regularization parameters that encourage network sparsity. We provide theoretical results proving convergence of the estimator for our method and show the corresponding probabilistic interpretation also converges. We demonstrate our method on simulated network data and show that existing network information improves performance, overcomes the lack of observations, and performs well even when some of the existing network information is incorrect. We further apply our method to the core regulatory network of embryonic stem cells utilizing predicted interactions from two studies as existing network information. We show that including the prior network information constructs a more closely representative regulatory network versus when no information is provided.

  20. On the existence of weak solutions of quantum stochastic differential ...

    African Journals Online (AJOL)

    We establish further results concerning the existence, uniqueness and stability of weak solutions of quantum stochastic differential equations (QSDEs). Our results are achieved by considering a more general Lipschit condition on the coefficients than our previous considerations in [1]. We exhibit a class of Lipschitzian ...

  1. DOES A LATIN-AMERICAN SECURITY COMMUNITY EXIST?

    Directory of Open Access Journals (Sweden)

    FRANCISCO S. BARROSO CORTÉS

    2017-09-01

    Similarly, the article points out the main characteristics that the Latin American security community would present, and the challenges and handicaps to overcome. To conclude, the article demonstrates how the integration process in this special field continues on, even though the existing context characterized by austerity and a low level of insecurity.

  2. Facilities improvement for sustainability of existing public office ...

    African Journals Online (AJOL)

    The study examined the building design features of a cosmopolitan public office building in Abuja. The features were classified into Spatial Plan, Structure and Facilities, to determine which of the 3 variables requires urgent sustainable improvement from end-users' perspective in existing public office buildings in developing ...

  3. Facilities Improvement for Sustainability of Existing Public Office ...

    African Journals Online (AJOL)

    Sultan

    Facilities Improvement for Sustainability of Existing Public Office. Buildings in Nigeria. Adeyemi, A. 1*; Martin, D. 2. ; Kasim, R. 2 and Adeyemi, A.I. 2. 1Faculty of Environmental Technology, Abubakar Tafawa Balewa University,. Bauchi. 2Faculty of Technology Management and Business, Universiti Tun Hussein Onn.

  4. Priors & prejudice : using existing knowledge in social science research

    NARCIS (Netherlands)

    Van Wesel, F.

    2011-01-01

    Researchers in the social sciences usually start their research with the formulation of research goals and questions, which, together with studying the existing literature, lead to the formulation of hypotheses. Next, data is collected using experiments or questionnaires and is subsequently

  5. 24 CFR 100.203 - Reasonable modifications of existing premises.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Reasonable modifications of existing premises. 100.203 Section 100.203 Housing and Urban Development Regulations Relating to Housing and Urban Development OFFICE OF ASSISTANT SECRETARY FOR EQUAL OPPORTUNITY, DEPARTMENT OF HOUSING AND...

  6. Responsible agricultural investment: drawing upon best practices in existing initiatives

    National Research Council Canada - National Science Library

    Mirza, Hafiz; Goodman, Zoe; Agostini, Atrid

    2015-01-01

    ...) by assessing how RAI principles can draw upon best practices from existing initiatives. To facilitate the discussion, we first propose a typology for categorizing initiates to regulate investment in agriculture. Then we assess the best practices in ten key areas that RAI principles should consider.

  7. Existence of aNew Force in Colloidal Systems Hydrophobic ...

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 7; Issue 4. Existence of a New Force in Colloidal Systems – Hydrophobic Attraction Between Macroscopic Surfaces. B Sudhir Sanjeev Kumar. General Article Volume 7 Issue 4 April 2002 pp 67-81 ...

  8. Improvement of an existing low cost wooden groundnut sheller ...

    African Journals Online (AJOL)

    An existing manually operated groundnut sheller was re-designed, fabricated and tested. About 90% of the components of the 18 kg./hr capacity rasp-bar sheller, equipped with a kernelcleaning device, were fabricated using the sawn wood of Cordia millennii. A one-off prototype of the sheller was produced at a total cost of ...

  9. 42 CFR 136.118 - Effect on existing rights.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Effect on existing rights. 136.118 Section 136.118 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES INDIAN HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES INDIAN HEALTH Grants for Development, Construction, and Operation of...

  10. Situation Analysis Of The Existing Infant Feeding Pattern At The ...

    African Journals Online (AJOL)

    Situation Analysis Of The Existing Infant Feeding Pattern At The commencement Of The Prevention Of Mother To Child Transmission (PMTCT) of HIV ... their babies exclusively for six months and 259(50.8%) initiated breastfeeding within one hour of birth; both were associated with at least secondary level of education.

  11. Existence and Policy Effectiveness in Feedback Nash LQ-Games

    Directory of Open Access Journals (Sweden)

    Nicola Acocella

    2008-12-01

    Full Text Available This paper illustrates how the classical theory of economic policy can profitably be used to verify some properties of the Linear Nash Feedback Equilibrium in difference LQ-games. In particular, we find that both a necessary condition for the equilibrium existence and a sufficient condition for policy ineffectiveness can be defined in the terms of the simple Tinbergen counting rule.

  12. 31 CFR 370.26 - What limitations exist on liability?

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false What limitations exist on liability? 370.26 Section 370.26 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FISCAL SERVICE, DEPARTMENT OF THE TREASURY BUREAU OF THE PUBLIC DEBT ELECTRONIC TRANSACTIONS AND FUNDS...

  13. 31 CFR 370.15 - What limitations exist on liability?

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false What limitations exist on liability? 370.15 Section 370.15 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FISCAL SERVICE, DEPARTMENT OF THE TREASURY BUREAU OF THE PUBLIC DEBT ELECTRONIC TRANSACTIONS AND FUNDS...

  14. 31 CFR 370.41 - What limitations exist on liability?

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false What limitations exist on liability? 370.41 Section 370.41 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FISCAL SERVICE, DEPARTMENT OF THE TREASURY BUREAU OF THE PUBLIC DEBT ELECTRONIC TRANSACTIONS AND FUNDS...

  15. Probable existence of a Gondwana transcontinental rift system in ...

    Indian Academy of Sciences (India)

    The study indicates a rift system spanning from Arabian plate in the north and extending to southern part of Africa that passes through Indus basin, western part of India and Madagascar, and existed from Late Carboniferous to Early Jurassic. Extensions related to the opening of Neo-Tethys led to the formation of a number of ...

  16. 78 FR 30218 - Pre-Existing Condition Insurance Plan Program

    Science.gov (United States)

    2013-05-22

    ... distributed by spreading funding for the maximum period of time by setting new payment rates in the federally...: Interim final rule with comment period. SUMMARY: This interim final rule with comment period sets the payment rates for covered services furnished to individuals enrolled in the Pre-Existing Condition...

  17. Sonographic assessment of pregnancy co-existing with uterine ...

    African Journals Online (AJOL)

    EB

    Objectives: To assess sonographically the frequency of occurrence and effect of uterine myomas co-existing with pregnancy. Methods: A longitudinal study was conducted during a period of 23 ... but the fibroids are usually innocent bystanders.4 They cause only 2% to 3% of cases of infertility. Fibroids that block one or both ...

  18. Bilinguals' Existing Languages Benefit Vocabulary Learning in a Third Language

    Science.gov (United States)

    Bartolotti, James; Marian, Viorica

    2017-01-01

    Learning a new language involves substantial vocabulary acquisition. Learners can accelerate this process by relying on words with native-language overlap, such as cognates. For bilingual third language learners, it is necessary to determine how their two existing languages interact during novel language learning. A scaffolding account predicts…

  19. Duodenal Diverticulum Co-Existing with a Bleeding Duodenal Ulcer ...

    African Journals Online (AJOL)

    Background: Duodenal diverticula are characterized by the presence of sac-like mucosal herniations through weak points in the duodenal wall. Duodenal diverticula co-existing with a bleeding duodenal ulcer is rare. Objective: The objective of this case report is to illustrate an uncommon case of two duodenal diverticula ...

  20. Communicative Competence: Existing Concepts and Prospects for Further Development

    Science.gov (United States)

    Zascerinska, Jelena

    2010-01-01

    Communicative competence is set out to be of the eight key competences which individuals need for personal fulfilment and development, active citizenship, social inclusion and employment (European Commission 2004, p. 3). The success of the sustainable development of communicative competence requires existing concepts of communicative competence…

  1. Existing biosafety regulations in Kenya | Thitai | African Crop ...

    African Journals Online (AJOL)

    Existing biosafety regulations in Kenya. GNW Thitai. Abstract. No Abstract. Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT · http://dx.doi.org/10.4314/acsj.v3i3.54519 · AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians ...

  2. Existence of extremal periodic solutions for quasilinear parabolic equations

    Directory of Open Access Journals (Sweden)

    Siegfried Carl

    1997-01-01

    bounded domain under periodic Dirichlet boundary conditions. Our main goal is to prove the existence of extremal solutions among all solutions lying in a sector formed by appropriately defined upper and lower solutions. The main tools used in the proof of our result are recently obtained abstract results on nonlinear evolution equations, comparison and truncation techniques and suitably constructed special testfunction.

  3. Existence of solutions for mixed Volterra-Fredholm integral equations

    Directory of Open Access Journals (Sweden)

    Asadollah Aghajani

    2012-08-01

    Full Text Available In this article, we give some results concerning the continuity of the nonlinear Volterra and Fredholm integral operators on the space $L^{1}[0,infty$. Then by using the concept of measure of weak noncompactness, we prove an existence result for a functional integral equation which includes several classes of nonlinear integral equations. Our results extend some previous works.

  4. Natural Hazards Evaluation of Existing Buildings. Building Science Series 61.

    Science.gov (United States)

    Culver, Charles G.; And Others

    A methodology is presented for survey and evaluation of existing buildings to determine the risk to life safety under natural hazard conditions and estimate the amount of expected damage. Damage to both structural and nonstructural building components resulting from the extreme natural environments encountered in earthquakes, hurricanes, and…

  5. Inhibition of existing denitrification enzyme activity by chloramphenicol

    Science.gov (United States)

    Brooks, M.H.; Smith, R.L.; Macalady, D.L.

    1992-01-01

    Chloramphenicol completely inhibited the activity of existing denitrification enzymes in acetylene-block incubations with (i) sediments from a nitrate-contaminated aquifer and (ii) a continuous culture of denitrifying groundwater bacteria. Control flasks with no antibiotic produced significant amounts of nitrous oxide in the same time period. Amendment with chloramphenicol after nitrous oxide production had begun resulted in a significant decrease in the rate of nitrous oxide production. Chloramphenicol also decreased (>50%) the activity of existing denitrification enzymes in pure cultures of Pseudomonas denitrificans that were harvested during log- phase growth and maintained for 2 weeks in a starvation medium lacking electron donor. Short-term time courses of nitrate consumption and nitrous oxide production in the presence of acetylene with P. denitrificans undergoing carbon starvation were performed under optimal conditions designed to mimic denitrification enzyme activity assays used with soils. Time courses were linear for both chloramphenicol and control flasks, and rate estimates for the two treatments were significantly different at the 95% confidence level. Complete or partial inhibition of existing enzyme activity is not consistent with the current understanding of the mode of action of chloramphenicol or current practice, in which the compound is frequently employed to inhibit de novo protein synthesis during the course of microbial activity assays. The results of this study demonstrate that chloramphenicol amendment can inhibit the activity of existing denitrification enzymes and suggest that caution is needed in the design and interpretation of denitrification activity assays in which chloramphenicol is used to prevent new protein synthesis.

  6. 47 CFR 22.165 - Additional transmitters for existing systems.

    Science.gov (United States)

    2010-10-01

    .... (b) Antenna structure registration. Certain antenna structures must be registered with the Commission... contours of the additional transmitter(s) must be totally encompassed by the composite interfering contour... composite service area contour and predicted interfering contour, respectively, of the existing station on...

  7. Strength characteristics for the structural assessment of existing concrete structures

    NARCIS (Netherlands)

    Vervuurt, A.; Courage, W.; Steenbergen, R.

    2013-01-01

    For the assessment of the in situ compressive strength in structures and precast concrete components EN 13791 applies. Among others, this standard may be adopted when doubt arises about the compressive strength in the structure. However, for assessing the structural safety of existing structures of

  8. On the existence of hydrodynamic instability in single diffusive ...

    Indian Academy of Sciences (India)

    Appl. 175 (1993) 458), to establish mathematically, the existence of hydrodynamic instability in single diffusive bottom heavy systems, when considered in the more general framework of the boundary conditions of the type specified by Beavers and Joseph (J. Fluid Mech. 30 (1967) 197), in the parameter regime T 0 2 > 1 ...

  9. Existence Results for Solutions of Nonlinear Fractional Differential Equations

    Directory of Open Access Journals (Sweden)

    Ali Yakar

    2012-01-01

    which generate a closed set. The existence of solutions for nonlinear fractional differential equations involving Riemann-Liouville differential operator in a closed set is obtained by utilizing various types of coupled upper and lower solutions. Furthermore, these results are extended to the finite systems of nonlinear fractional differential equations leading to more general results.

  10. Educating for Immortality: Spinoza and the Pedagogy of Gradual Existence

    Science.gov (United States)

    Dahlbeck, Johan

    2015-01-01

    This article begins with the question: What is it to live? It is argued that, from a Spinozistic perspective, to live is not an either/or kind of matter. Rather, it is something that inevitably comes in degrees. The idea is that through good education and proper training a person can learn to increase his or her degree of existence by acquiring…

  11. Existence of global attractor for the Trojan Y Chromosome model

    Directory of Open Access Journals (Sweden)

    Xiaopeng Zhao

    2012-04-01

    Full Text Available This paper is concerned with the long time behavior of solution for the equation derived by the Trojan Y Chromosome (TYC model with spatial spread. Based on the regularity estimates for the semigroups and the classical existence theorem of global attractors, we prove that this equations possesses a global attractor in $H^k(\\Omega^4$ $(k\\geq 0$ space.

  12. Impact of Rand devaluation on existing and planned REIPPPP Projects

    CSIR Research Space (South Africa)

    Milazi, DBK

    2016-06-01

    Full Text Available Outside of these critical elements, several other factors exist that have a bearing on the bankability of a utility scale renewable energy project. Among the most important of these are the financial risks that respective parties are exposed...

  13. How to inject consumerism into your existing health plans.

    Science.gov (United States)

    Havlin, Linda J; McAllister, Michael F; Slavney, David H

    2003-09-01

    Consumerism seeks to create a behavior change on the part of consumers so that they become accountable, knowledgeable and actively engaged in managing their health. It can be used in any existing health plan through targeted plan design changes and consumer education efforts. Employers have many options in addition to consumer-directed health plans (CDHPs).

  14. Existence of solutions for fractional differential inclusions with boundary conditions

    Directory of Open Access Journals (Sweden)

    Dandan Yang

    2010-07-01

    Full Text Available This article concerns the existence of solutions for fractional-order differential inclusions with boundary-value conditions. The main tools are based on fixed point theorems due to Bohnerblust-Karlin and Leray-Schauder together with a continuous selection theorem for upper semi-continuous multi-valued maps.

  15. Does Absolute Synonymy exist in Owere-Igbo? | Omego | AFRREV ...

    African Journals Online (AJOL)

    Among Igbo linguistic researchers, determining whether absolute synonymy exists in Owere–Igbo, a dialect of the Igbo language predominantly spoken by the people of ... This researcher employed various tests such as substitution or interchangeability method, contrastive method and statistical method to test for absolute ...

  16. Fracture testing of existing structures without the need for repairs

    NARCIS (Netherlands)

    Walters, C.L.; Bruchhausen, M.; Lapetite, J.M.; Duvalois, W.

    2017-01-01

    It is sometimes necessary to find the toughness of existing structures without damaging them. Examples of this scenario include situations in which the material is suspected of being brittle or service life extensions. However, fracture testing is inherently destructive. Removing material for Charpy

  17. A quantitative analysis of the marked asymmetry existing between ...

    African Journals Online (AJOL)

    The pelvic girdle musculature of eleven of the eighteen southern African Mabuya species described by Branch (1988) was examined, using differences in mass to emphasize the marked asymmetry existing between partners of certain muscle pairs. The lighter muscles expressed as indices of their heavier partners gave a ...

  18. The application, benefits and challenges of retrofitting the existing buildings

    Science.gov (United States)

    Khairi, Muhammad; Jaapar, Aini; Yahya, Zaharah

    2017-11-01

    Sustainable development has been the main topic of debate for years in some countries such as United Kingdom, United State of America and Malaysia. Depletion of natural resources, global warming, economics uncertainty and health issues are some of the reasons behind sustainable development movements, it is not just a political debate in the parliament but more towards collective works among sectors in order to minimizing the negative impact of development to the environment and other living organism. Retrofit an existing building is one of the solutions to reduce the dependency on constructing new buildings. There are huge numbers of existing building stocks that suitable to be retrofitted such as historical buildings, offices, residential, warehouse, factories, vacant buildings and other historical buildings. Therefore, the aim of this research is to provide information on the application, benefits and challenges of retrofitting an existing building. Two buildings were chosen as case studies following by site visits and observation to the buildings. The data were then compared in a table form. Primary and secondary sources were also used for this research. The application of retrofit should be promoted across the construction and conservation industries since it has significant tangible and intangible benefits. It is one of the most environmentally friendly and efficient solutions to optimize the energy performance and could also helps to extend the life of the existing building or historical buildings while ensuring optimum thermal comfort for the occupants which leads to higher productivity.

  19. Building OOC layers on top of existing courses

    DEFF Research Database (Denmark)

    Bang, Jørgen; Dalsgaard, Christian; Kjær, Arne

    2016-01-01

    prefer the term "Open Online Courses", MOOCs (Massive Open Online Courses) without the M. This paper will present our approach to building OOCs on top of existing campusbased courses at Aarhus University, Denmark. Consequently, participants of an 'OOC track' will engage in collaboration and discussions...

  20. Existence of localized solutions for a classical nonlinear Dirac field

    Energy Technology Data Exchange (ETDEWEB)

    Cazenave, T.; Vazquez, L.

    1986-05-01

    We prove the existence of stationary states for nonlinear Dirac equations of the form: iota..gamma..sup(..mu..)dsub(..mu..)psi-mpsi+F(anti psipsi)psi=0. We seek solutions which are separable in spherical coordinates and we use a shooting method for solving the associated problem of ordinary differential equations. (orig.).

  1. Micro and Small Enterprise Sector and Existing Support System with ...

    African Journals Online (AJOL)

    Micro and Small Enterprise Sector and Existing Support System with emphasis on High-Tech oriented Entrepreneurship in Kenya. ... national support. This weakness has undermined the development of indigenous labor intensive and local resource-using technologies. Key Words: micro and small enterprises, technology ...

  2. TECHNOGENIC EXISTENCE AND JUSTICE PROBLEM IN ETHICS OF RELIGIOUS EXISTENTIALISM

    Directory of Open Access Journals (Sweden)

    N. I. Mushinskij

    2007-01-01

    Full Text Available Ethics of religious existentialism interprets a category of Justice from humanistic positions. The problem of Justice takes a great significance under modem conditions. Kierkegaard’s philosophy considers this problem in relation to Luther’s theology. Karl Jaspers develops “freedom philosophy” in context of the technogenic existence.

  3. TECHNOGENIC EXISTENCE AND JUSTICE PROBLEM IN ETHICS OF RELIGIOUS EXISTENTIALISM

    OpenAIRE

    N. I. Mushinskij

    2007-01-01

    Ethics of religious existentialism interprets a category of Justice from humanistic positions. The problem of Justice takes a great significance under modem conditions. Kierkegaard’s philosophy considers this problem in relation to Luther’s theology. Karl Jaspers develops “freedom philosophy” in context of the technogenic existence.

  4. Existence results for impulsive semilinear damped differential inclusions

    Directory of Open Access Journals (Sweden)

    Mouffak Benchohra

    2003-06-01

    Full Text Available In this paper we investigate the existence of mild solutions for first and second order impulsive semilinear evolution inclusions in separable Banach spaces. By using suitable fixed point theorems, we study the case when the multivalued map has convex and nonconvex values.

  5. SPATIALLY-BALANCED SURVEY DESIGN FOR GROUNDWATER USING EXISTING WELLS

    Science.gov (United States)

    Many states have a monitoring program to evaluate the water quality of groundwater across the state. These programs rely on existing wells for access to the groundwater, due to the high cost of drilling new wells. Typically, a state maintains a database of all well locations, in...

  6. Environmental policy evaluation under co-existing evaluation imaginaries

    NARCIS (Netherlands)

    Kunseler, E.M.; Vasileiadou, E.

    2016-01-01

    This article examines what the co-existence of different evaluation imaginaries – understandings of what environmental policy evaluation ‘is’ and ‘should do’ – means for everyday evaluation practice. We present a case study in which we show how these different understandings influence the evaluation

  7. Runaway pacemaker: a still existing complication and therapeutic guidelines

    DEFF Research Database (Denmark)

    Mickley, H; Andersen, C; Nielsen, L H

    1989-01-01

    Runaway pacemaker is a rare, but still existing potential lethal complication in permanent pacemakers. Within 4 1/2 years, we saw two cases of runaway pacemaker in patients with multiprogrammable, VVI pacemakers (Siemens-Elema, Model 668). In both cases a pacemaker-induced ventricular tachycardia...

  8. Declassified: Struggle for Existence (We Used to Eat Lunch Together)

    Science.gov (United States)

    Pickett, Brian

    2011-01-01

    The play, "Declassified: Struggle for Existence (We Used to Eat Lunch Together)," is based on the classic play "Antigone" and was written as part of a college-credit elective the author teaches at Queensborough Community College, geared toward local area high school students. The students were one day away from the scheduled…

  9. 40 CFR 463.35 - Pretreatment standards for existing sources.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 29 2010-07-01 2010-07-01 false Pretreatment standards for existing sources. 463.35 Section 463.35 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS PLASTICS MOLDING AND FORMING POINT SOURCE CATEGORY Finishing Water...

  10. 40 CFR 463.25 - Pretreatment standards for existing sources.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 29 2010-07-01 2010-07-01 false Pretreatment standards for existing sources. 463.25 Section 463.25 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS PLASTICS MOLDING AND FORMING POINT SOURCE CATEGORY Cleaning Water...

  11. Priority setting for existing chemicals : automated data selection routine

    NARCIS (Netherlands)

    Haelst, A.G. van; Hansen, B.G.

    2000-01-01

    One of the four steps within Council Regulation 793/93/EEC on the evaluation and control of existing chemicals is the priority setting step. The priority setting step is concerned with selecting high-priority substances from a large number of substances, initially starting with 2,474

  12. Existence results for non-autonomous elliptic boundary value problems

    Directory of Open Access Journals (Sweden)

    V. Anuradha

    1994-07-01

    Full Text Available $$-Delta u(x = lambda f(x, u;quad x in Omega$$ $$u(x + alpha(x frac{partial u(x}{partial n} = 0;quad x in partial Omega$$ where $lambda > 0$, $Omega$ is a bounded region in $Bbb{R}^N$; $N geq 1$ with smooth boundary $partial Omega$, $alpha(x geq 0$, $n$ is the outward unit normal, and $f$ is a smooth function such that it has either sublinear or restricted linear growth in $u$ at infinity, uniformly in $x$. We also consider $f$ such that $f(x, u u leq 0$ uniformly in $x$, when $|u|$ is large. Without requiring any sign condition on $f(x, 0$, thus allowing for both positone as well as semipositone structure, we discuss the existence of at least three solutions for given $lambda in (lambda_{n}, lambda_{n + 1}$ where $lambda_{k}$ is the $k$-th eigenvalue of $-Delta$ subject to the above boundary conditions. In particular, one of the solutions we obtain has non-zero positive part, while another has non-zero negative part. We also discuss the existence of three solutions where one of them is positive, while another is negative, for $lambda$ near $lambda_{1}$, and for $lambda$ large when $f$ is sublinear. We use the method of sub-super solutions to establish our existence results. We further discuss non-existence results for $lambda$ small.

  13. Existence and properties of p-tupling fixed points

    OpenAIRE

    Epstein, Henri

    2000-01-01

    We prove the existence of fixed points of p-tupling renormalization operators for interval and circle mappings having a critical point of arbitrary real degree r > 1. Some properties of the resulting maps are studied: analyticity, univalence, behavior as $r$ tends to infinity.

  14. Higher-order factors of personality: Do they exist?

    NARCIS (Netherlands)

    Ashton, M.C.; Lee, K.; Goldberg, L.R.; de Vries, R.E.

    2009-01-01

    Scales that measure the Big Five personality factors are often substantially intercorrelated. These correlations are sometimes interpreted as implying the existence of two higher order factors of personality. The authors show that correlations between measures of broad personality factors do not

  15. Existence of positive solutions for systems of second order multi ...

    Indian Academy of Sciences (India)

    In this paper, we establish the existence of positive solutions for systems of second order multi-point boundary value problems on time scales by applying Guo– Krasnosel'skii fixed point theorem. Author Affiliations. K R Prasad1 N Sreedhar2 M A S Srinivas3. Department of Applied Mathematics, Andhra University, ...

  16. 5 CFR 9701.506 - Impact on existing agreements.

    Science.gov (United States)

    2010-01-01

    ... Section 9701.506 Administrative Personnel DEPARTMENT OF HOMELAND SECURITY HUMAN RESOURCES MANAGEMENT SYSTEM (DEPARTMENT OF HOMELAND SECURITY-OFFICE OF PERSONNEL MANAGEMENT) DEPARTMENT OF HOMELAND SECURITY HUMAN RESOURCES MANAGEMENT SYSTEM Labor-Management Relations § 9701.506 Impact on existing agreements...

  17. Existence of positive solutions to semilinear elliptic problems with ...

    Indian Academy of Sciences (India)

    57

    Existence of positive solutions to semilinear elliptic problems with nonlinear boundary condition. Chan-Gyun Kim and Eun Kyoung Lee. Department of Mathematics Education, Pusan National University,. Busan, 609-735, Korea. Abstract. In this paper, a semilinear elliptic equation with a nonlinear boundary condition and a ...

  18. A Comparison of Existing Optimisation Techniques with the ...

    African Journals Online (AJOL)

    In this paper we give a review of methods that have been used to solve the channel assignment problem and propose a new algorithm, namely the univariate marginal distribution algorithm. The existing techniques that are described are the simulated annealing, graph colouring, neural networks, genetic algorithms and ...

  19. 40 CFR 417.134 - Pretreatment standards for existing sources.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 28 2010-07-01 2010-07-01 true Pretreatment standards for existing sources. 417.134 Section 417.134 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS SOAP AND DETERGENT MANUFACTURING POINT SOURCE CATEGORY Chlorosulfonic...

  20. 40 CFR 417.54 - Pretreatment standards for existing sources.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 28 2010-07-01 2010-07-01 true Pretreatment standards for existing sources. 417.54 Section 417.54 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS SOAP AND DETERGENT MANUFACTURING POINT SOURCE CATEGORY Glycerine...

  1. 40 CFR 417.94 - Pretreatment standards for existing sources.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 28 2010-07-01 2010-07-01 true Pretreatment standards for existing sources. 417.94 Section 417.94 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS SOAP AND DETERGENT MANUFACTURING POINT SOURCE CATEGORY Oleum Sulfonation...

  2. 40 CFR 417.124 - Pretreatment standards for existing sources.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 28 2010-07-01 2010-07-01 true Pretreatment standards for existing sources. 417.124 Section 417.124 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS SOAP AND DETERGENT MANUFACTURING POINT SOURCE CATEGORY Sulfamic Acid...

  3. 40 CFR 417.104 - Pretreatment standards for existing sources.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 28 2010-07-01 2010-07-01 true Pretreatment standards for existing sources. 417.104 Section 417.104 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS SOAP AND DETERGENT MANUFACTURING POINT SOURCE CATEGORY Air-SO3 Sulfation...

  4. 40 CFR 417.14 - Pretreatment standards for existing sources.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 28 2010-07-01 2010-07-01 true Pretreatment standards for existing sources. 417.14 Section 417.14 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS SOAP AND DETERGENT MANUFACTURING POINT SOURCE CATEGORY Soap Manufacturing...

  5. 40 CFR 417.34 - Pretreatment standards for existing sources.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 28 2010-07-01 2010-07-01 true Pretreatment standards for existing sources. 417.34 Section 417.34 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS SOAP AND DETERGENT MANUFACTURING POINT SOURCE CATEGORY Soap Manufacturing...

  6. 40 CFR 417.44 - Pretreatment standards for existing sources.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 28 2010-07-01 2010-07-01 true Pretreatment standards for existing sources. 417.44 Section 417.44 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS SOAP AND DETERGENT MANUFACTURING POINT SOURCE CATEGORY Glycerine...

  7. 40 CFR 417.114 - Pretreatment standards for existing sources.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 28 2010-07-01 2010-07-01 true Pretreatment standards for existing sources. 417.114 Section 417.114 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS SOAP AND DETERGENT MANUFACTURING POINT SOURCE CATEGORY SO3 Solvent and...

  8. Foreign Language Reading Anxiety: Does It Really Exist?

    Science.gov (United States)

    Subasi, Gonca

    2014-01-01

    Recent research on foreign language anxiety appears to support the existence of language skill specific anxiety. The principal goal of the present study is to confirm empirically that foreign language (FL) reading anxiety is a specific anxiety type distinguishable from the more general types of FL anxiety (FLA) in the Turkish EFL context. There is…

  9. Existence and concentration of solution for a class of fractional ...

    Indian Academy of Sciences (India)

    36

    Existence and concentration of solution for a class of fractional Hamiltonian systems with subquadratic potential. César E. Torres Ledesma. Departamento de Matemáticas,. Universidad Nacional de Trujillo. Av. Juan Pablo II s/n Trujillo, Perú. (ctl 576@yahoo.es, ctorres@dim.uchile.cl). Abstract. In this article we consider the ...

  10. The SXI telescope on board EXIST: scientific performances

    Science.gov (United States)

    Natalucci, L.; Bazzano, A.; Campana, S.; Caraveo, P.; Della Ceca, R.; Grindlay, J. E.; Panessa, F.; Pareschi, G.; Ramsey, B.; Tagliaferri, G.; Ubertini, P.; Villa, G.

    2009-08-01

    The SXI telescope is one of the three instruments on board EXIST, a multiwavelenght observatory in charge of performing a global survey of the sky in hard X-rays searching for Supermassive Black Holes. One of the primary objectives of EXIST is also to study with unprecedented sensitivity the most unknown high energy sources in the Universe, like high redshift GRBs, which will be pointed promptly by the Spacecraft by autonomous trigger based on hard X-ray localization on board. The recent addition of a soft X-ray telescope to the EXIST payload complement, with an effective area of 950 cm2 in the energy band 0.2-3 keV and extended response up to 10 keV will allow to make broadband studies from 0.1 to 600 keV. In particular, investigations of the spectra components and states of AGNs and monitoring of variability of sources, study of the prompt and afterglow emission of GRBs since the early phases, which will help to constrain the emission models and finally, help the identification of sources in the EXIST hard X-ray survey and the characterization of the transient events detected. SXI will also perform surveys: a scanning survey with sky coverage ~ 2 π and limiting flux of ~ 5 × 10-14 cgs plus other serendipitous. We give an overview of the SXI scientific performance and also describe the status of its design emphasizing how it has been derived by the scientific requirements.

  11. EXIST deep observations of the Galactic Center Region

    Science.gov (United States)

    Fiocchi, M.; Natalucci, L.; Grindlay, J. E.; Ubertini, P.; Bazzano, A.

    2010-07-01

    The EXIST observatory planned for launch in the next decade will carry outstanding contributions in both Galactic and Extragalactic science with a sensitivity about 10-20 better respect to the flown hard X-ray missions and full sky survey capability. Designed mainly for the survey of SMBH and transients, thanks to the wide field of view (~70x90deg) and large effective area of the High Energy Telescope (HET), the study of spectra and variability at all timescales of all types of Galactic sources will be made possible. EXIST will be also capable to study in detail the Galactic Center (GC) in the hard X-rays. This crowded region as observed recently by Chandra, Integral and Swift has been found to possibly host a high number of high energy sources. In this work we report on the capabilities of EXIST to image the GC region and to detect and characterize the different classes of sources on the basis of their known spectral and variability properties. EXIST will perform the crucial observation tests to study the emission from Sgr A*, using the simultaneous observations of IR and X-ray flares, searching for periodicity to study the Keplerian flow with NIR and/or X QPO, confirm or not the high energy counterpart of SgrA* detected by INTEGRAL and define the spectral shape of the high energy tail. Finally, EXIST can effectively and continuously monitor spectra from Sgr B2 to confirm the correlation of the iron line emission with the hard X-ray continuum and establish its origin.

  12. The EXIST view of Supermassive Black Holes in the Universe

    Science.gov (United States)

    Della Ceca, R.; Ghisellini, G.; Tagliaferri, G.; Foschini, L.; Pareschi, G.; Tavecchio, F.; Coppi, P.; Grindlay, J. E.; Fiocchi, M. T.; Natalucci, L.; Panessa, F.; Ubertini, P.

    With its large collection area, broad-band energy coverage from optical/NIR (0.3 to 2.2 micron) to soft/hard X-ray (0.1-600 keV), all-sky monitoring capability, and on-board follow-up, the proposed Energetic X-ray Imaging Survey Telescope mission (EXIST, see L. Natalucci contribution at this conference) has been designed to properly tackle the study of the AGN phenomenon and the role that SMBH play in the Universe. In particular EXIST will carry out an unprecedented survey above 10 keV (a factor ~20 increase in hard X-ray sensitivity compared to current and prior X-ray missions) of SMBH activity, not just in space but also in time and over a significant expanded energy range; this strategy will overcome previous selection biases, will break the "multi-wavelength" identification bottleneck and will dramatically increase the number of AGN detected above 10 keV that are amenable to detailed follow-up studies (~50000 AGN are expected). We discuss here on few selected AGN science topics enabled by the unique combination of EXIST's instruments. In particular EXIST will enable major progress in understanding: i) when and where SMBH are active in the Universe (by revealing and measuring heavily obscured accretion in the local - zEXIST's ability to find powerful, but very rare blazars, enables it to probe the appearance of the very first SMBH in the Universe allowing us to set strong constraints on the models of SMBH formation and early growth in the Universe.

  13. Method to investigate and plan the application of low temperature district heating to existing hydraulic radiator systems in existing buildings

    DEFF Research Database (Denmark)

    Tunzi, Michele; Østergaard, Dorte Skaarup; Svendsen, Svend

    2016-01-01

    This study presents a method to adapt existing hydronic systems in buildings to take advantage of low temperature district heating (LTDH). Plate radiators connected to double string heating circuits were considered in an optimization procedure, based on supply and return temperatures, to obtain t...

  14. Regulatory Approaches for Adding Capacity to Existing Hydropower Facilities

    Energy Technology Data Exchange (ETDEWEB)

    Levine, Aaron L. [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Curtis, Taylor L. [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Kazerooni, Borna [National Renewable Energy Laboratory (NREL), Golden, CO (United States)

    2017-10-24

    In 2015, hydroelectric generation accounted for more than 6 percent of total net electricity generation in the United States and 46 percent of electricity generation from all renewables. The United States has considerable hydroelectric potential beyond what is already being developed. Nearly 7 GW of this potential is found by adding capacity to existing hydropower facilities. To optimize the value of hydroelectric generation, the U.S. Department of Energy's Hydropower Vision Study highlights the importance of adding capacity to existing facilities. This report provides strategic approaches and considerations for Federal Energy Regulatory Commission licensed and exempt hydropower facilities seeking to increase generation capacity, which may include increases from efficiency upgrades. The regulatory approaches reviewed for this report include capacity and non-capacity amendments, adding capacity during relicensing, and adding capacity when converting a license to a 10-MW exemption.

  15. Regularized Tyler's Scatter Estimator: Existence, Uniqueness, and Algorithms

    Science.gov (United States)

    Sun, Ying; Babu, Prabhu; Palomar, Daniel P.

    2014-10-01

    This paper considers the regularized Tyler's scatter estimator for elliptical distributions, which has received considerable attention recently. Various types of shrinkage Tyler's estimators have been proposed in the literature and proved work effectively in the "small n large p" scenario. Nevertheless, the existence and uniqueness properties of the estimators are not thoroughly studied, and in certain cases the algorithms may fail to converge. In this work, we provide a general result that analyzes the sufficient condition for the existence of a family of shrinkage Tyler's estimators, which quantitatively shows that regularization indeed reduces the number of required samples for estimation and the convergence of the algorithms for the estimators. For two specific shrinkage Tyler's estimators, we also proved that the condition is necessary and the estimator is unique. Finally, we show that the two estimators are actually equivalent. Numerical algorithms are also derived based on the majorization-minimization framework, under which the convergence is analyzed systematically.

  16. A new heavy residue upgrading process to retrofit existing refineries

    Energy Technology Data Exchange (ETDEWEB)

    Ghaedian, Maryam; Zarkesh, Jamshid [NIOC-Research Institute of Petroleum Industry (Russian Federation); Khadzhiev, S.; Kadiev, H. [Russian Academy of science (Russian Federation)

    2011-07-01

    Light crude oil reserves have declined and new fields being explored tend to be heavy oil, requiring processes to convert heavy residue to light products. The aim of this paper is to present the use of heavy residue hydroconversion (HRH) to upgrade heavy residues in existing refineries. A case study was carried out on a refinery with 250,000 barrel per day capacity, two cases were examined: the base case and the HRH case. Results showed that HRH provides higher IRR and NPV than the base case for the same investment. The heavy residue hydroconversion process was proved to be a feasible and reliable alternative which could eliminate residue while creating added value in existing refineries.

  17. Toward the Automated Generation of Components from Existing Source Code

    Energy Technology Data Exchange (ETDEWEB)

    Quinlan, D; Yi, Q; Kumfert, G; Epperly, T; Dahlgren, T; Schordan, M; White, B

    2004-12-02

    A major challenge to achieving widespread use of software component technology in scientific computing is an effective migration strategy for existing, or legacy, source code. This paper describes initial work and challenges in automating the identification and generation of components using the ROSE compiler infrastructure and the Babel language interoperability tool. Babel enables calling interfaces expressed in the Scientific Interface Definition Language (SIDL) to be implemented in, and called from, an arbitrary combination of supported languages. ROSE is used to build specialized source-to-source translators that (1) extract a SIDL interface specification from information implicit in existing C++ source code and (2) transform Babel's output to include dispatches to the legacy code.

  18. Percolation Model for the Existence of a Mitochondrial Eve

    CERN Document Server

    Neves, A G M

    2005-01-01

    We look at the process of inheritance of mitochondrial DNA as a percolation model on trees equivalent to the Galton-Watson process. The model is exactly solvable for its percolation threshold $p_c$ and percolation probability critical exponent. In the approximation of small percolation probability, and assuming limited progeny number, we are also able to find the maximum and minimum percolation probabilities over all probability distributions for the progeny number constrained to a given $p_c$. As a consequence, we can relate existence of a mitochondrial Eve to quantitative knowledge about demographic evolution of early mankind. In particular, we show that a mitochondrial Eve may exist even in an exponentially growing population, provided that the average number of children per individual is constrained to a small range depending on the probability $p$ that a newborn child is a female.

  19. Existing sustainable renovation concepts for single-family houses

    DEFF Research Database (Denmark)

    Tommerup, Henrik M.; Vanhoutteghem, Lies; Svendsen, Svend

    2010-01-01

    In the Nordic Innovation Centre Project, SuccessFamilies, the main objective is to change the business environment in order to speed up the implementation of sustainable renovation of single-family houses – proposing new service concepts that will combine both the technical solutions, financing...... concepts. The paper describes a few Nordic examples of full-service models for renovation of single-family houses which entered the market recently and the provisional success of these concepts. The existing Nordic single-family house renovation market is dominated by a craftsman based approach...... with individual solutions, traditional warehouses ”do-it-yourself-shops” and some actors marketing single products. To speed up the implementation of sustainable renovation of single-family houses there is a great need for full-service packages. Existing technical renovation concepts, typically focusing...

  20. Energy Efficiency in the North American Existing Building Stock

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2007-07-01

    This report presents the findings of a new assessment of the techno-economic and policy-related efficiency improvement potential in the North American building stock conducted as part of a wider appraisal of existing buildings in member states of the International Energy Agency. It summarizes results and provides insights into the lessons learned through a broader global review of best practice to improve the energy efficiency of existing buildings. At this time, the report is limited to the USA because of the large size of its buildings market. At a later date, a more complete review may include some details about policies and programs in Canada. If resources are available an additional comprehensive review of Canada and Mexico may be performed in the future.

  1. Higher order factors of personality: do they exist?

    Science.gov (United States)

    Ashton, Michael C; Lee, Kibeom; Goldberg, Lewis R; de Vries, Reinout E

    2009-05-01

    Scales that measure the Big Five personality factors are often substantially intercorrelated. These correlations are sometimes interpreted as implying the existence of two higher order factors of personality. The authors show that correlations between measures of broad personality factors do not necessarily imply the existence of higher order factors and might instead be due to variables that represent same-signed blends of orthogonal factors. Therefore, the hypotheses of higher order factors and blended variables can only be tested with data on lower level personality variables that define the personality factors. The authors compared the higher order factor model and the blended variable model in three participant samples using the Big Five Aspect Scales, and found better fit for the latter model. In other analyses using the HEXACO Personality Inventory, they identified mutually uncorrelated markers of six personality factors. The authors conclude that correlations between personality factor scales can be explained without postulating any higher order dimensions of personality.

  2. Chapter 32: Using an Existing Environment in the VO (IRAF)

    Science.gov (United States)

    Fitzpatrick, M. J.

    IRAF continues to be one of the most widely used systems for optical and infrared data analysis, providing trusted and familiar functionality to users who find themselves with a wealth of new data sources. The VO cannot possibly re-implement large systems such as IRAF using more modern languages/environments, and so it must ultimately rely on legacy software to provide, integrate with, and interface to VO technologies. For a software system, the integration of VO technology should be a natural extension of that system's existing capabilities; for an astronomer, using the VO should be seamless and an added value of the system. By making several key enhancements, and by building some new support software, we are able to use the many existing IRAF tasks in both the client and server sides of the VO.

  3. Gender differences in drinking: why do they still exist?

    Science.gov (United States)

    Holmila, Marja; Raitasalo, Kirsimarja

    2005-12-01

    The paper discusses the kinds of reasoning that have been presented as possible mechanisms and reasons for gender differences in alcohol consumption. An overview of the existing literature from different countries is presented. The existing studies provide a picture of great cultural variance in patterns of alcohol use among men and women. The gender differences in drinking behaviour have been shown to be linked with many aspects of biological differences between men and women leading to women's greater vulnerability to alcohol, of women's and men's differing needs, reasons and motivations in relation to drinking, of gender-specific roles in other areas of life and of ways in which societies regulate peoples' behaviour, often giving women the role of warden or moderator of others' drinking. The gender differences in drinking behaviour continue to be considerable and are found in all cultures studied so far. Several studies have argued for reasons underlying these differences, but they still remain largely unexplained.

  4. A strategic approach for existing buildings to withstand climate change

    DEFF Research Database (Denmark)

    Rasmussen, Torben Valdbjørn

    2012-01-01

    Buildings play a vital economic and social role in society and are vulnerable to climate change. This paper suggests a strategic approach for existing buildings to withstand climate change. It emphasises the most likely climate impacts, including the change in mean year values as well as the extent...... of maximum and minimum extremes, which are pointed out and set against a background of national and international agreements. Assumptions that form the basis for the scenarios are outlined and evaluated in a Danish context and similar evaluations can be drawn for other countries. As climate change progresses...... change for buildings is given. The actions include four stages: a survey of the performance, the impact of climate change, the vulnerability of the existing building stock and climate adaptation needs. This leads to the identification of a risk-based strategic framework for adaptation to climate change...

  5. Does cirrhotic cardiomyopathy exist? 50 years of uncertainty.

    Science.gov (United States)

    Pellicori, Pierpaolo; Torromeo, Concetta; Calicchia, Angela; Ruffa, Alessandra; Di Iorio, Martina; Cleland, John G F; Merli, Manuela

    2013-12-01

    Subtle abnormalities of cardiac structure or function are often identified in patients with liver cirrhosis and have been termed cirrhotic cardiomyopathy. However, in the absence of a precise definition, its diagnosis remains a challenge. Cardiac dysfunction in patients with cirrhosis can often be attributed to concomitant diseases such as hypertension, ischaemic heart disease or excess alcohol consumption in many patients. Further research is required to identify the existence, origin and importance of abnormal cardiac function due specifically to liver disease. Cardiac dysfunction may be masked by treatments given to cirrhotic patients, such as mineral-corticoid receptor antagonists, or by co-existing conditions, such as anaemia. New imaging tests or plasma biomarkers might be able to detect abnormal cardiac function at an early stage of its development.

  6. Existing Noise Level at Railway Stations in Malaysia

    Directory of Open Access Journals (Sweden)

    Shahidan Shahiron

    2017-01-01

    Full Text Available Railway transportation known as one of the most environmental friendly transportation mode. However, the significance problems of railway transportation are noise pollution and negatively impact the wellbeing of the whole community. Unfortunately, there has been lack of public awareness about the noise level produce by the railway transportation in Malaysia. This study investigates the noise level produced by railway transportation in Malaysia specifically by Keretapi Tanah Melayu Berhad (KTMB. Methods of collecting existing noise level at railway stations in Malaysia are briefly discussed in this study. The finding indicates that the noise level produced by the railway transportation in Malaysia which is by KTMB is considered as dangerous to human being and also exceed the noise limit that has been assigned by Department of Environment Ministry of Natural Resources and Environment of Malaysia. A better noise barrier and improved material should be developed to mitigate the existing noise level produced by railway transportations in Malaysia.

  7. Revealing the First Stellar and Supermassive Black Holes to EXIST

    Science.gov (United States)

    Grindlay, J.; Bloom, J.; Coppi, P.; Soderberg, A.; Hong, J.; Moseley, H.; Barthelmy, S.; Tagliaferri, G.; Ghisellini, G.; Della Ceca, R.; Ubertini, P.

    2010-07-01

    The epochs of origin of the first stars and galaxies, and subsequent growth of the first supermassive black holes, are among the most fundamental questions. Observations of the highest redshift Gamma-Ray Bursts (GRBs) will be the most compelling in situ probe of the history of initial star formation and consequent epoch of reionization if their prompt and precise detection can be followed immediately by sensitive near-IR imaging and spectroscopy. Blazars are the persistent analogs of GRBs and for the same reason (beaming) can be observed at highest redshifts where they might best trace the high accretion rate-driven jets and growth of supermassive black holes in galaxies. The proposed EXIST mission can uniquely probe these questions, and many others, given its unparalled combination of sensitivity and spatial-spectral-temporal coverage and resolution. Here we provide a brief summary of the mission design, key science objectives, mission plan and readiness for EXIST, as proposed to Astro2010.

  8. Existence and multiplicity of solutions for nonlinear discrete inclusions

    Directory of Open Access Journals (Sweden)

    Nicu Marcu

    2012-11-01

    Full Text Available A non-smooth abstract result is used for proving the existence of at least one nontrivial solution of an algebraic discrete inclusion. Successively, a multiplicity theorem for the same class of discrete problems is also established by using a locally Lipschitz continuous version of the famous Brezis-Nirenberg theoretical result in presence of splitting. Some applications to tridiagonal, fourth-order and partial difference inclusions are pointed out.

  9. Security Enhancement Using Mutual Authentication in Existing CDMA Systems

    OpenAIRE

    L. Krishna Bharathi; Gnanou Florence Sudha

    2010-01-01

    Even though CDMA2000 wireless networks are being widely deployed as a cellular digital standard around the world, it has some hidden vulnerabilities concerned with security issues. The existing CDMA systems use authentication mechanism by CAVE (Cellular Authentication and Voice Encryption) algorithm. This authentication method has several disadvantages. Only one way authentication is provided, that is, only a base station authenticates a subscriber. And, CAVE algorithm is prone to cryptograph...

  10. Priors & prejudice : using existing knowledge in social science research

    OpenAIRE

    Van Wesel, F.

    2011-01-01

    Researchers in the social sciences usually start their research with the formulation of research goals and questions, which, together with studying the existing literature, lead to the formulation of hypotheses. Next, data is collected using experiments or questionnaires and is subsequently analyzed. Finally, conclusions are drawn based on the research findings. Although this procedure is a logical one, more scientific knowledge can be gained by starting a research project with a sharper focu...

  11. Existence of non-abelian representations of the near hexagon

    Indian Academy of Sciences (India)

    In [5], a new combinatorial model with four types of points and nine types of lines of the slim dense near hexagon (5, 2) ⊗ (5, 2) was provided and it was then used to construct a non-abelain representation of (5, 2) ⊗ (5, 2) in the extraspecial 2-group 2 − 1 + 18 . In this paper, we give a direct proof for the existence of a ...

  12. Non-existence of limit cycles via inverse integrating factors

    Directory of Open Access Journals (Sweden)

    Leonardo Laura-Guarachi

    2011-09-01

    Full Text Available It is known that if a planar differential systems has an inverse integrating factor, then all the limit cycles contained in the domain of definition of the inverse integrating factor are contained in the zero set of this function. Using this fact we give some criteria to rule out the existence of limit cycles. We also present some applications and examples that illustrate our results.

  13. Structural behaviour characterization of existing adobe constructions in Aveiro

    OpenAIRE

    H. Varum; Costa, A; Martins, T.(); Pereira, H; Almeida, J; Rodrigues, H.; D. Silveira

    2007-01-01

    Adobe was a widely used construction material in Aveiro, Portugal, till the middle of the 20th century. Nowadays, adobe can still be found in varied types of constructions, many of which are of cultural, historical, and also architectural recognized value. The existing adobe buildings present an important level of structural damage and, in many cases, are even near to ruin, having the majority a high vulnerability to seismic actions. To face the lack of information concerning the mechanica...

  14. Existence theory for nonlinear volterra integral and differential equations

    Directory of Open Access Journals (Sweden)

    Sikorska Aneta

    2001-01-01

    Full Text Available In this paper we prove the existence theorems for the integrodifferential equation where in first part are functions with values in a Banach space and the integral is taken in the sense of Bochner. In second part are weakly–weakly sequentially continuous functions and the integral is the Pettis integral. Additionaly, the functions and satisfy some boundary conditions and conditions expressed in terms of measure of noncompactness or measure of weak noncompactness.

  15. Existing Model Metrics and Relations to Model Quality

    OpenAIRE

    Mohagheghi, Parastoo; Dehlen, Vegard

    2009-01-01

    This paper presents quality goals for models and provides a state-of-the-art analysis regarding model metrics. While model-based software development often requires assessing the quality of models at different abstraction and precision levels and developed for multiple purposes, existing work on model metrics do not reflect this need. Model size metrics are descriptive and may be used for comparing models but their relation to model quality is not welldefined. Code metrics are proposed to be ...

  16. Existence of a coupled system of fractional differential equations

    Energy Technology Data Exchange (ETDEWEB)

    Ibrahim, Rabha W. [Multimedia unit, Department of Computer System and Technology Faculty of Computer Science & IT, University of Malaya, 50603 Kuala Lumpur (Malaysia); Siri, Zailan [Institute of Mathematical Sciences, University of Malaya, 50603 Kuala Lumpur (Malaysia)

    2015-10-22

    We manage the existence and uniqueness of a fractional coupled system containing Schrödinger equations. Such a system appears in quantum mechanics. We confirm that the fractional system under consideration admits a global solution in appropriate functional spaces. The solution is shown to be unique. The method is based on analytic technique of the fixed point theory. The fractional differential operator is considered from the virtue of the Riemann-Liouville differential operator.

  17. What relation exists between CSR and longevity of firms?

    OpenAIRE

    Jean-Michel SAHUT; Boulerne, Sandrine; MILI, MEDHI; Teulon, Frédéric

    2013-01-01

    The relation between company longevity and its performance is undeniable; however the relationship between sustainability and performance remains the subject of multiple studies which seem to confirm a positive link. But what type of relationship exists between a firm’s longevity and sustainability management? In this paper, we demonstrate that the adoption of corporate social responsibility (CSR) principles explains this link. Therefore, sustainable development policies can create a rampart ...

  18. Local and Global Existence Theorems for the Einstein Equations

    Directory of Open Access Journals (Sweden)

    Alan D. Rendall

    1998-01-01

    Full Text Available This article is a guide to the literature on existence theorems for the Einstein equations which also draws attention to open problems in the field. The local in time Cauchy problem, which is relatively well understood, is treated first. Next global results for solutionswith symmetry are discussed. This is followed by a presentation of global results in the case of small data, and some miscellaneous topics connected with the main theme.

  19. Incentives to Repurpose Existing Drugs for Orphan Indications

    OpenAIRE

    Kwok, Annette K.; Koenigbauer, Fabian M.

    2015-01-01

    The Orphan Drug Act has been successful in providing incentives to find cures for orphan diseases. However, many orphan diseases are still without cure. Therefore, the 114th Congress has introduced the 21st Century Cures Act and the Orphan Product Extension Now Accelerating Cures and Treatment Act of 2015 to further provide incentives to innovators to repurpose existing drugs for treatment of these orphan diseases. However, these bills are currently pending and their ince...

  20. Incentives to Repurpose Existing Drugs for Orphan Indications.

    Science.gov (United States)

    Kwok, Annette K; Koenigbauer, Fabian M

    2015-08-13

    The Orphan Drug Act has been successful in providing incentives to find cures for orphan diseases. However, many orphan diseases are still without cure. Therefore, the 114th Congress has introduced the 21st Century Cures Act and the Orphan Product Extension Now Accelerating Cures and Treatment Act of 2015 to further provide incentives to innovators to repurpose existing drugs for treatment of these orphan diseases. However, these bills are currently pending and their incentives might not go far enough.

  1. Does a causal relation between cardiovascular disease and periodontitis exist?

    DEFF Research Database (Denmark)

    Belstrøm, Daniel; Damgaard, Christian; Nielsen, Claus H

    2012-01-01

    Inflammation is believed to play a central part in the pathogenesis of atherosclerosis, and much attention has been paid to the possible association between atherosclerosis and other inflammatory diseases. Periodontal disease is a common inflammatory disease affecting up to 50% of the adult...... population, and during the past two decades much research has focused on a possible association between periodontitis and cardiovascular disease. Here, we review the existing literature on the association between the two diseases....

  2. The Existence and Application of Unbounded Connected Components

    Directory of Open Access Journals (Sweden)

    Hua Luo

    2014-01-01

    Full Text Available Let X be a Banach space and Cn a family of connected subsets of R×X. We prove the existence of unbounded components in superior limit of {Cn}, denoted by lim¯ Cn, which have prescribed shapes. As applications, we investigate the global behavior of the set of positive periodic solutions to nonlinear first-order differential equations with delay, which can be used for modeling physiological processes.

  3. A função social do historiador existe?

    Directory of Open Access Journals (Sweden)

    Maria Clarice Rodrigues de Souza

    2008-01-01

    Full Text Available The story, on the last years,has been passing for supposed“crises” as for from real existence ofyour social role. A good many are thequestions on the subject of as themewhat achieved directly the act a parthistorical. Inside of this argument, thefeature social of the Historian is putin doubts: he should be the historianonly one real function inside fromsociety? Wherefore serve the story?Are questions what we want to goaboard into the elapse of this text.

  4. Does the {sigma}(1580)((3)/(2)){sup -} resonance exist?

    Energy Technology Data Exchange (ETDEWEB)

    Olmsted, J.; Prakhov, S.; Manley, D.M.; Allgower, C.E.; Bekrenev, V.S.; Briscoe, W.J.; Clajus, M.; Comfort, J.R.; Craig, K.; Grosnick, D.; Isenhower, D.; Knecht, N.; Koetke, D.D.; Kozlenko, N.G.; Kruglov, S.; Kulbardis, A.A.; Lolos, G.; Lopatin, I.V.; Manweiler, R.; Marusic, A.; McDonald, S.; Nefkens, B.M.K.; Papandreou, Z.; Peaslee, D.C.; Phaisangittisakul, N.; Price, J.W.; Ramirez, A.F.; Sadler, M.; Shafi, A.; Spinka, H.; Stanislaus, T.D.S.; Starostin, A.; Staudenmaier, H.M.; Strakovsky, I.I.; Supek, I.; Tippens, W.B

    2004-05-20

    Precise new data for the reaction K{sup -}p{yields}{pi}{sup 0}{lambda} are presented in the c.m. energy range 1565 to 1600 MeV. Our analysis of these data sheds new light on claims for the {sigma}(1580)((3)/(2)){sup -} resonance, which (if it exists with the specified quantum numbers) must be an exotic baryon because of its very low mass. Our results show no evidence for this state.

  5. Does the Sigma(1580)3/2- resonance exist?

    CERN Document Server

    Olmsted, J A; Manley, D M; Allgower, C E; Bekrenev, V S; Briscoe, W J; Clajus, M; Comfort, J R; Craig, K; Grosnick, D P; Isenhower, D; Knecht, N; Koetke, D D; Kozlenko, N G; Kruglov, S; Kulbardis, A A; Lolos, G J; Lopatin, I V; Manweiler, R; Marusic, A; McDonald, S; Nefkens, B M K; Papandreou, Z; Peaslee, D C; Phaisangittisakul, N; Price, J W; Ramírez, A F; Sadler, M E; Shafi, A; Spinka, H M; Stanislaus, T D S; Starostin, A S; Staudenmaier, H M; Strakovsky, I I; Supek, I; Tippens, W B; Tippens, and W.B.

    2003-01-01

    Precise new data for the reaction $K^- p \\to \\pi^0 \\Lambda$ are presented in the c.m. energy range 1565 to 1600 MeV. Our analysis of these data sheds new light on claims for the $\\Sigma(1580){3/2}^-$ resonance, which (if it exists with the specified quantum numbers) must be an exotic baryon because of its very low mass. Our results are decisive and show no evidence for this state.

  6. Global existence result for the generalized Peterlin viscoelastic model

    Czech Academy of Sciences Publication Activity Database

    Lukáčová-Medviďová, M.; Mizerová, H.; Nečasová, Šárka; Renardy, M.

    2017-01-01

    Roč. 49, č. 4 (2017), s. 2950-2964 ISSN 0036-1410 R&D Projects: GA ČR GA13-00522S Institutional support: RVO:67985840 Keywords : Peterlin viscoelastic equations * global existence * weak solutions Subject RIV: BA - General Mathematics Impact factor: 1.648, year: 2016 http://epubs.siam.org/doi/abs/10.1137/16M1068505

  7. Comparative analysis of existing food safety culture evaluation systems

    OpenAIRE

    Jespersen, Lone; Griffiths, Mansel; Wallace, Carol Anne

    2017-01-01

    The purpose of the research was firstly, to analyze existing culture evaluation systems for commonalities and differences in research quality, applied validation strategies, and content. Secondly, to suggest a simple structure of food safety cultural dimensions to help unify the culture evaluation field. To achieve these goals, a comparison of eight culture evaluation models applied to varing degrees in the food industry was conducted. The systems were found to vary significantly in applied v...

  8. The proposed high-energy telescope (HET) for EXIST

    Science.gov (United States)

    Hong, J.; Grindlay, J.; Allen, B.; Skinner, G.; Barthelmy, S.; Gehrels, N.; Garson, A.; Krawczynski, H.; Cook, W.; Harrison, F.; Natalucci, L.; Ubertini, P.

    2010-07-01

    The hard X-ray sky now being studied by INTEGRAL and Swift and soon by NuSTAR is rich with energetic phenomena and highly variable non-thermal phenomena on a broad range of timescales. The High Energy Telescope (HET) on the proposed Energetic X-ray Imaging Survey Telescope (EXIST) mission will repeatedly survey the full sky for rare and luminous hard X-ray phenomena at unprecedented sensitivities. It will detect and localize (<20", at 5σ threshold) X-ray sources quickly for immediate followup identification by two other onboard telescopes - the Soft X-ray imager (SXI) and Optical/Infrared Telescope (IRT). The large array (4.5 m2) of imaging (0.6 mm pixel) CZT detectors in the HET, a coded-aperture telescope, will provide unprecedented high sensitivity (~0.06 mCrab Full Sky in a 2 year continuous scanning survey) in the 5 - 600 keV band. The large field of view (90° × 70°) and zenith scanning with alternating-orbital nodding motion planned for the first 2 years of the mission will enable nearly continuous monitoring of the full sky. A 3y followup pointed mission phase provides deep UV-Optical-IR-Soft X-ray and Hard X-ray imaging and spectroscopy for thousands of sources discovered in the Survey. We review the HET design concept and report the recent progress of the CZT detector development, which is underway through a series of balloon-borne wide-field hard X-ray telescope experiments, ProtoEXIST. We carried out a successful flight of the first generation of fine pixel large area CZT detectors (ProtoEXIST1) on Oct 9, 2009. We also summarize our future plan (ProtoEXIST2 & 3) for the technology development needed for the HET.

  9. GRB Probes of the Early Universe with EXIST

    Science.gov (United States)

    Grindlay, Jonathan E.

    2010-10-01

    With the Swift detection of GRB090423 at z = 8.2, it was confirmed that GRBs are now detectable at (significantly) larger redshifts than AGN, and so can indeed be used as probes of the Early Universe. The Energetic X-ray Imaging Survey Telescope (EXIST) mission has been designed to detect and promptly measure redshifts and both soft X-ray (0.1-10 keV) and simultaneous nUV-nIR (0.3-2.3 microns) imaging and spectra for GRBs out to redshifts z~18, which encompasses (or even exceeds) current estimates for Pop III stars that are expected to be massive and possibly GRB sources. Scaling from Swift for the ~10X greater sensitivity of EXIST, more than 100 GRBs at z>= 8 may be detected and would provide direct constraints on the formation and evolution of the first stars and galaxies. For GRBs at redshifts z>= 8, with Lyman breaks at greater than 1.12 microns, spectra at resolution R = 30 or R = 3000 for afterglows with AB magnitudes brighter than 24 or 20 (respectively) within ~3000 sec of trigger will directly probe the Epoch of Reionization, formation of galaxies, and cosmic star formation rate. The proposed EXIST mission can probe these questions, and many others, given its unparalleled combination of sensitivity and spatial-spectral-temporal coverage and resolution. Here we provide an overview of the key science objectives for GRBs as probes of the early Universe and of extreme physics, and the mission plan and technical readiness to bring this to EXIST.

  10. Surveying From the Farthest to Nearest Black Holes to EXIST

    Science.gov (United States)

    Grindlay, Jonathan E.; EXIST Team

    2010-01-01

    The Energetic X-ray Imaging Survey Telescope (EXIST) mission has been proposed to Astro2010 to conduct the deepest full-sky hard X-ray (5-600 keV) survey for black holes on all scales. With its combination of a very large area (4.5m2) High Energy Telescope (HET; 1.5arcmin imaging from 5-600 keV), Soft X-ray Imager (SXI; 0.1-10keV focusing telescope with 15arcsec psf) and optical-IR Telescope (IRT; 0.3-2.3 microns, with 4arcmin FoV and 0.15arcsec pixels), the EXIST mission has unsurpassed multiwavelength capabilities. It it is designed to detect the highest redshift Gamma-ray Bursts (GRBs), with predicted rates of 600/year and >20/y at z >7 and with prompt SXI localization (exist. And for ULX and stellar mass black holes in the Local Group and Milky Way, the deepest inventory as well as long term variability studies are possible, as well as the first survey for isolated IMBHs accreting from GMCs. The mission combines both scanning (like Fermi/LAT) for increased sensitivity (vs. pointing) and sky coverage as well as followup pointings. The science, instrumentation, and mission overview are presented. As a Medium class mission, and with no new technology required, EXIST could be launched by 2017 to complement Fermi, JWST, ALMA, LOFAR and LSST and other wide-field surveys as well as followup studies planned for the coming decade.

  11. Minimum action curves in degenerate Finsler metrics existence and properties

    CERN Document Server

    Heymann, Matthias

    2015-01-01

    Presenting a study of geometric action functionals (i.e., non-negative functionals on the space of unparameterized oriented rectifiable curves), this monograph focuses on the subclass of those functionals whose local action is a degenerate type of Finsler metric that may vanish in certain directions, allowing for curves with positive Euclidean length but with zero action. For such functionals, criteria are developed under which there exists a minimum action curve leading from one given set to another. Then the properties of this curve are studied, and the non-existence of minimizers is established in some settings. Applied to a geometric reformulation of the quasipotential of Wentzell-Freidlin theory (a subfield of large deviation theory), these results can yield the existence and properties of maximum likelihood transition curves between two metastable states in a stochastic process with small noise. The book assumes only standard knowledge in graduate-level analysis; all higher-level mathematical concept...

  12. Reserves in load capacity assessment of existing bridges

    Science.gov (United States)

    Žitný, Jan; Ryjáček, Pavel

    2017-09-01

    High percentage of all railway bridges in the Czech Republic is made of structural steel. Majority of these bridges is designed according to historical codes and according to the deterioration, they have to be assessed if they satisfy the needs of modern railway traffic. The load capacity assessment of existing bridges according to Eurocodes is however often too conservative and especially, braking and acceleration forces cause huge problems to structural elements of the bridge superstructure. The aim of this paper is to review the different approaches for the determination of braking and acceleration forces. Both, current and historical theoretical models and in-situ measurements are considered. The research of several local European state norms superior to Eurocode for assessment of existing railway bridges shows the big diversity of used local approaches and the conservativeness of Eurocode. This paper should also work as an overview for designers dealing with load capacity assessment, revealing the reserves for existing bridges. Based on these different approaches, theoretical models and data obtained from the measurements, the method for determination of braking and acceleration forces on the basis of real traffic data should be proposed.

  13. Hanford Site background: Evaluation of existing soil radionuclide data

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-07-01

    This report is an evaluation of the existing data on radiological background for soils in the vicinity of the Hanford Site. The primary purpose of this report is to assess the adequacy of the existing data to serve as a radiological background baseline for use in environmental restoration and remediation activities at the Hanford Site. The soil background data compiled and evaluated in this report were collected by the Pacific Northwest Laboratory (PNL) and Washington State Department of Health (DOH) radiation surveillance programs in southeastern Washington. These two programs provide the largest well-documented, quantitative data sets available to evaluate background conditions at the Hanford Site. The data quality objectives (DQOs) considered in this evaluation include the amount of data, number of sampling localities, spatial coverage, number and types of radionuclides reported, frequency of reporting, documentation and traceability of sampling and laboratory methods used, and comparability between sets of data. Although other data on soil radionuclide abundances around the Hanford Site exist, they are generally limited in scope and lack the DQOs necessary for consideration with the PNL and DOH data sets. Collectively, these two sources provide data on the activities of 25 radionuclides and four other parameters (gross alpha, gross beta, total uranium, and total thorium). These measurements were made on samples from the upper 2.5 cm of soil at over 70 localities within the region.

  14. Expansion potential for existing nuclear power station sites

    Energy Technology Data Exchange (ETDEWEB)

    Cope, D. F.; Bauman, H. F.

    1977-09-26

    This report is a preliminary analysis of the expansion potential of the existing nuclear power sites, in particular their potential for development into nuclear energy centers (NECs) of 10 (GW(e) or greater. The analysis is based primarily on matching the most important physical characteristics of a site against the dominating site criteria. Sites reviewed consist mainly of those in the 1974 through 1976 ERDA Nuclear Power Stations listings without regard to the present status of reactor construction plans. Also a small number of potential NEC sites that are not associated with existing power stations were reviewed. Each site was categorized in terms of its potential as: a dispersed site of 5 GW(e) or less; a mini-NEC of 5 to 10 GW(e); NECs of 10 to 20 GW(e); and large NECs of more than 20 GW(e). The sites were categorized on their ultimate potential without regard to political considerations that might restrain their development. The analysis indicates that nearly 40 percent of existing sites have potential for expansion to nuclear energy centers.

  15. Research update, existing buildings research, 1989--1991

    Energy Technology Data Exchange (ETDEWEB)

    MacDonald, J.M.; Ternes, M.P.; Mixon, W.R.; Sharp, T.R.; Kolb, J.O.; Wilkes, K.E. [Oak Ridge National Lab., TN (United States); Diamond, R.C. [Lawrence Berkeley Lab., CA (United States); Judkoff, R. [National Renewable Energy Lab., Golden, CO (United States); Mazzucchi, R.P. [Pacific Northwest Lab., Richland, WA (United States)

    1993-02-01

    This Research Update presents the status of the Existing Buildings Research program of the Office of Building Technologies of the US Department of Energy for the period 1989-199 1. This program covers research on energy efficiency improvements for the residential and commercial buildings in this country. ne Existing Buildings Research program has contributed to significant improvements in energy efficiency of existing buildings by development of improvements to retrofit technologies, by coordinating and conducting research studies on the use of energy efficiency technologies (to reduce barriers and increase use), and by continually evaluating changes in technologies that could improve and maintain buildings energy efficiency. If the energy efficiency of the buildings sector in this country is to be dramatically improved over the next 30 years, we must improve the use of energy efficiency technologies. Improved delivery of measures, improved understanding of how buildings actually perform in the field, and methods for improving operations and maintenance of buildings and energy equipment are all examples of ways to improve the deployment (transfer) of technologies. Much has been learned about technology deployment in buildings in the first five years of the program, and our future plans will be directed at continuing the improvements and making a real contribution to the energy efficiency future of the United States.

  16. Estimation of marginal costs at existing waste treatment facilities.

    Science.gov (United States)

    Martinez-Sanchez, Veronica; Hulgaard, Tore; Hindsgaul, Claus; Riber, Christian; Kamuk, Bettina; Astrup, Thomas F

    2016-04-01

    This investigation aims at providing an improved basis for assessing economic consequences of alternative Solid Waste Management (SWM) strategies for existing waste facilities. A bottom-up methodology was developed to determine marginal costs in existing facilities due to changes in the SWM system, based on the determination of average costs in such waste facilities as function of key facility and waste compositional parameters. The applicability of the method was demonstrated through a case study including two existing Waste-to-Energy (WtE) facilities, one with co-generation of heat and power (CHP) and another with only power generation (Power), affected by diversion strategies of five waste fractions (fibres, plastic, metals, organics and glass), named "target fractions". The study assumed three possible responses to waste diversion in the WtE facilities: (i) biomass was added to maintain a constant thermal load, (ii) Refused-Derived-Fuel (RDF) was included to maintain a constant thermal load, or (iii) no reaction occurred resulting in a reduced waste throughput without full utilization of the facility capacity. Results demonstrated that marginal costs of diversion from WtE were up to eleven times larger than average costs and dependent on the response in the WtE plant. Marginal cost of diversion were between 39 and 287 € Mg(-1) target fraction when biomass was added in a CHP (from 34 to 303 € Mg(-1) target fraction in the only Power case), between -2 and 300 € Mg(-1) target fraction when RDF was added in a CHP (from -2 to 294 € Mg(-1) target fraction in the only Power case) and between 40 and 303 € Mg(-1) target fraction when no reaction happened in a CHP (from 35 to 296 € Mg(-1) target fraction in the only Power case). Although average costs at WtE facilities were highly influenced by energy selling prices, marginal costs were not (provided a response was initiated at the WtE to keep constant the utilized thermal capacity). Failing to systematically

  17. Drug Abuse and the American Adolescent. NIDA Research Monograph 38. A RAUS Review Report.

    Science.gov (United States)

    Lettieri, Dan J., Ed.; Ludford, Jacqueline P., Ed.

    This report reviews five studies dealing with drug abuse and adolescence and presents an overview of the social changes which have contributed to the increased use of marijuana and other illicit drugs. The importance of the longitudinal study as a research tool is emphasized in describing the research projects that deal with the epidemiology of…

  18. 75 FR 36659 - Proposed Collection; Comment Request; Brain Power! The NIDA Junior Scientist Program and the...

    Science.gov (United States)

    2010-06-28

    ... drug addiction; Increase positive attitudes toward science, careers in science, and science as an... understanding of the neurobiology of addiction. Surveys will be administered to parents to obtain parental... techniques or other forms of information technology. FOR FURTHER INFORMATION CONTACT: To request more...

  19. Notas sobre algunas raras Accipítridas y Falcónidas de Colombia

    Directory of Open Access Journals (Sweden)

    Lehmann V. F. C.

    1943-08-01

    Full Text Available Aunque las seis especies a que me refiero en este trabajo fueron ya mencionadas por el doctor A. Dugand en su "Clave Analítica de las, Rapaces Colombianas" (Rev. Acad. Colomb. Cienc. IV, 16; 394-404. 1941 creo de interés hacer conocer los detalles de los ejemplares que he examinado, muchos de los cuales son los únicos que hasta ahora han sido obtenidos en Colombia.

  20. Viability of Existing INL Facilities for Dry Storage Cask Handling

    Energy Technology Data Exchange (ETDEWEB)

    Randy Bohachek; Charles Park; Bruce Wallace; Phil Winston; Steve Marschman

    2013-04-01

    This report evaluates existing capabilities at the INL to determine if a practical and cost effective method could be developed for opening and handling full-sized dry storage casks. The Idaho Nuclear Technology and Engineering Center (INTEC) CPP-603, Irradiated Spent Fuel Storage Facility, provides the infrastructure to support handling and examining casks and their contents. Based on a reasonable set of assumptions, it is possible to receive, open, inspect, remove samples, close, and reseal large bolted-lid dry storage casks at the INL. The capability can also be used to open and inspect casks that were last examined at the TAN Hot Shop over ten years ago. The Castor V/21 and REA-2023 casks can provide additional confirmatory information regarding the extended performance of low-burnup (<45 GWD/MTU) used nuclear fuel. Once a dry storage cask is opened inside CPP-603, used fuel retrieved from the cask can be packaged in a shipping cask, and sent to a laboratory for testing. Testing at the INL’s Materials and Fuels Complex (MFC) can occur starting with shipment of samples from CPP-603 over an on-site road, avoiding the need to use public highways. This reduces cost and reduces the risk to the public. The full suite of characterization methods needed to establish the condition of the fuel exists and MFC. Many other testing capabilities also exist at MFC, but when those capabilities are not adequate, samples can be prepared and shipped to other laboratories for testing. This report discusses how the casks would be handled, what work needs to be done to ready the facilities/capabilities, and what the work will cost.

  1. Viability of Existing INL Facilities for Dry Storage Cask Handling

    Energy Technology Data Exchange (ETDEWEB)

    Bohachek, Randy; Wallace, Bruce; Winston, Phil; Marschman, Steve

    2013-04-30

    This report evaluates existing capabilities at the INL to determine if a practical and cost effective method could be developed for opening and handling full-sized dry storage casks. The Idaho Nuclear Technology and Engineering Center (INTEC) CPP-603, Irradiated Spent Fuel Storage Facility, provides the infrastructure to support handling and examining casks and their contents. Based on a reasonable set of assumptions, it is possible to receive, open, inspect, remove samples, close, and reseal large bolted-lid dry storage casks at the INL. The capability can also be used to open and inspect casks that were last examined at the TAN Hot Shop over ten years ago. The Castor V/21 and REA-2023 casks can provide additional confirmatory information regarding the extended performance of low-burnup (<45 GWD/MTU) used nuclear fuel. Once a dry storage cask is opened inside CPP-603, used fuel retrieved from the cask can be packaged in a shipping cask, and sent to a laboratory for testing. Testing at the INL’s Materials and Fuels Complex (MFC) can occur starting with shipment of samples from CPP-603 over an on-site road, avoiding the need to use public highways. This reduces cost and reduces the risk to the public. The full suite of characterization methods needed to establish the condition of the fuel exists and MFC. Many other testing capabilities also exist at MFC, but when those capabilities are not adequate, samples can be prepared and shipped to other laboratories for testing. This report discusses how the casks would be handled, what work needs to be done to ready the facilities/capabilities, and what the work will cost.

  2. Cost of enlarged operating zone for an existing Francis runner

    Science.gov (United States)

    Monette, Christine; Marmont, Hugues; Chamberland-Lauzon, Joël; Skagerstrand, Anders; Coutu, André; Carlevi, Jens

    2016-11-01

    Traditionally, hydro power plants have been operated close to best efficiency point, the more stable operating condition for which they have been designed. However, because of changes in the electricity market, many hydro power plants operators wish to operate their machines differently to fulfil those new market needs. New operating conditions can include whole range operation, many start/stops, extensive low load operation, synchronous condenser mode and power/frequency regulation. Many of these new operating conditions may impose more severe fatigue damage than the traditional base load operation close to best efficiency point. Under these conditions, the fatigue life of the runner may be significantly reduced and reparation or replacement cost might occur sooner than expected. In order to design reliable Francis runners for those new challenging operating scenarios, Andritz Hydro has developed various proprietary tools and design rules. These are used within Andritz Hydro to design mechanically robust Francis runners for the operating scenarios fulfilling customer's specifications. To estimate residual life under different operating scenarios of an existing runner designed years ago for best efficiency base load operation, Andritz Hydro's design rules and tools would necessarily lead to conservative results. While the geometry of a new runner can be modified to fulfil all conservative mechanical design rules, the predicted fatigue life of an existing runner under off-design operating conditions may appear rather short because of the conservative safety factor included in the calculations. The most precise and reliable way to calculate residual life of an existing runner under different operating scenarios is to perform a strain gauge measurement campaign on the runner. This paper presents the runner strain gage measurement campaign of a mid-head Francis turbine over all the operating conditions available during the test, the analysis of the measurement signals

  3. The myodural bridge existing in the Nephocaena phocaenoides.

    Directory of Open Access Journals (Sweden)

    Pei Liu

    Full Text Available Recent studies have identified that the myodural bridge (MDB between the rectus capitis posterior minor (RCPmi and the cervical spinal dura mater in the posterior atlanto-occipital interspace in humans. And it was supposed that the MDB may play essential physiological roles. As a result, the MDB is possibly a highly conserved structure in the evolution of mammals. However, there is little confirmative description about the existence of the MDB in marine mammals. The objective of this study was to explore the existence and the fiber property of the MDB in the Neophocaena phocaenoides. Six cadavers of the Neophocaena phocaenoides with formalin fixation were used in this study. One was used for head and neck CT scanning and three-dimensional (3D reconstruction and suboccipital region dissection, two were for sectional observation by P45 plastinated sheets of head and neck, and three were for histological analysis of suboccipial structures. This is the first study to demonstrate the existence of the MDB in the aquatic mammals. The rectus capitis dorsal minor (RCDmi originated from the inferior border of the occiput and inserted into the cervical spinal dura mater. At the ventral aspect of the RCDmi, the MDB directly extended through the posterior atlanto-occipital interspace and connected with the cervical spinal dura mater which was consisted of type Ⅰ collagen. In addition, the dorsal atlanto-occipital membrane was not found in the Neophocaena phocaenoides. The tendinous myodural bridge extended from the RCDmi to the spinal dura mater through the posterior atlanto-occipital interspace in the Neophocaena phocaenoides.

  4. The implementation of HPGR mills in existing grinding circuits

    Energy Technology Data Exchange (ETDEWEB)

    Patzelt, N.; Knecht, J.; Longhurst, D. [Krupp Polysius AG, Beckum (Germany)

    1996-12-31

    High pressure grinding mills have been successfully introduced in the industry. They offer the possibilities for capacity increase of existing plants and reduction of operating costs. The plants in operation are running in different applications and modes of operation. They can be installed in a combination with SAG and ball mills or in a stand-alone mode. In combination with other grinding mills, it has to be investigated how the HPGR can be installed to reach the full efficiency. This paper describes the possibilities of implementing high pressure grinding rolls and shows by case studies the potential of savings which could be reached.

  5. Expert Meeting Report. Windows Options for New and Existing Homes

    Energy Technology Data Exchange (ETDEWEB)

    Ojczyck, C. [Univ. of Minnesota, St. Paul, MN (United States); Carmody, J. [Univ. of Minnesota, St. Paul, MN (United States); Haglund, K. [Univ. of Minnesota, St. Paul, MN (United States)

    2013-05-01

    The NorthernSTAR Building America Partnership held an Expert Meeting on Windows Options for New and Existing Homes on November 14, 2011, at the Nolte Building on the campus of the University of Minnesota in Minneapolis, MN. Featured speakers included John Carmody and Pat Huelman of the University of Minnesota, Charlie Curcija of Lawrence Berkeley National Laboratory, Jim Larson of Cardinal Glass Industries, Peter Yost of Building Green, Peter Baker of Building Science Corporation, and Theresa Weston of Du Pont Innovations. Audience participation was actively encouraged during each presentation to uncover need and promote dialog among researchers and industry professionals.

  6. Review of existing residential energy efficiency certification and rating programs

    Energy Technology Data Exchange (ETDEWEB)

    Hendrickson, P.L.

    1986-11-01

    This report was prepared for the Office of Buildings and Community Systems, US Department of Energy (DOE). The principal objective of the report is to present information on existing Home Energy Rating Systems (HERS) and their features. Much of the information in this report updates a 1982 report (PNL-4359), also prepared by the Pacific Northwest Laboratory (PNL) for DOE. Secondary objectives of the report are to qualitatively examine the benefits and costs of HERS programs, review survey results on the attitudes of various user groups toward the programs, and discuss selected design and implementation issues.

  7. Some existence results on nonlinear fractional differential equations.

    Science.gov (United States)

    Baleanu, Dumitru; Rezapour, Shahram; Mohammadi, Hakimeh

    2013-05-13

    In this paper, by using fixed-point methods, we study the existence and uniqueness of a solution for the nonlinear fractional differential equation boundary-value problem D(α)u(t)=f(t,u(t)) with a Riemann-Liouville fractional derivative via the different boundary-value problems u(0)=u(T), and the three-point boundary condition u(0)=β(1)u(η) and u(T)=β(2)u(η), where T>0, t∈I=[0,T], 0<α<1, 0<η

  8. Existence and uniqueness in anisotropic conductivity reconstruction with Faraday's law

    KAUST Repository

    Lee, Min-Gi

    2015-03-18

    We show that three sets of internal current densities are the right amount of data that give the existence and the uniqueness at the same time in reconstructing an anisotropic conductivity in two space dimensions. The curl free equation of Faraday’s law is taken instead of the usual divergence free equation of the electrical impedance to- mography. Boundary conditions related to given current densities are introduced which complete a well determined problem for conductivity reconstruction together with Fara- day’s law.

  9. Preparing Teachers: Expectations and Existing Situation at Faculties of Education

    Directory of Open Access Journals (Sweden)

    Tuba Gökmenoğlu

    2013-04-01

    Full Text Available In-depth interviews were conducted to research the expectations of teacher educators from the prospective teachers and their opinions on the existing facilities provided by the faculty of education. Content analysis, performed on the data collected from a sample of eight teacher educators from different departments in one of the faculties of education, suggested that the expectations from teacher candidates had seven dimensions: content knowledge, pedagogical content knowledge, country specific realities, communication skills, teacher characteristics, scientific knowledge and research skills, and professional development. Regarding the results, implications for teacher education programs were discussed, and suggestions for further research were made

  10. Existence of infinitely many radial solutions for quasilinear Schrodinger equations

    Directory of Open Access Journals (Sweden)

    Gui Bao

    2014-10-01

    Full Text Available In this article we prove the existence of radial solutions with arbitrarily many sign changes for quasilinear Schrodinger equation $$ -\\sum_{i,j=1}^{N}\\partial_j(a_{ij}(u\\partial_iu +\\frac{1}{2}\\sum_{i,j=1}^{N}a'_{ij}(u\\partial_iu\\partial_ju+V(xu =|u|^{p-1}u,~x\\in\\mathbb{R}^N, $$ where $N\\geq3$, $p\\in(1,\\frac{3N+2}{N-2}$. The proof is accomplished by using minimization under a constraint.

  11. Local and Global Existence Theorems for the Einstein Equations

    Directory of Open Access Journals (Sweden)

    Rendall Alan D.

    2000-01-01

    Full Text Available This article is a guide to the literature on existence theorems for the Einstein equations which also draws attention to open problems in the field. The local in time Cauchy problem, which is relatively well understood, is treated first. Next global results for solutions with symmetry are discussed. A selection of results from Newtonian theory and special relativity which offer useful comparisons is presented. This is followed by a survey of global results in the case of small data and results on constructing spacetimes with given singularity structure. The article ends with some miscellaneous topics connected with the main theme.

  12. Existence of Solutions to Hyperbolic Conservation Laws with a Source

    Science.gov (United States)

    Klingenberg, Christian; Lu, Yun-guang

    Existence of solutions to three different systems of Eqs. (1.1), (1.2) and (1.3) coming from physically relevant models is shown, each needing a different proof which are given in Sects. 2, 3 and 4. The unifying theme is the presence of source terms and the general method of proof is vanishing viscosity together with compensated compactness. For system (1.2) entropy-entropy flux pairs of Lax type are constructed and estimates from singular perturbation theory of ODEs are used. For (1.1) and (1.3) weak entropy-entropy flux pairs are constructed following the compensated compactness framework set up by Diperna [4].

  13. Expert Meeting Report: Windows Options for New and Existing Homes

    Energy Technology Data Exchange (ETDEWEB)

    Ojczyk, C.; Carmody, J.; Haglund, K.

    2013-05-01

    The NorthernSTAR Building America Partnership held an Expert Meeting on Windows Options for New and Existing Homes on November 14, 2011 at the Nolte Building on the campus of the University of Minnesota in Minneapolis, MN. Featured speakers included John Carmody and Pat Huelman of the University of Minnesota, Charlie Curcija of Lawrence Berkeley National Laboratory, Jim Larson of Cardinal Glass Industries, Peter Yost of Building Green, Peter Baker of Building Science Corporation, and Theresa Weston of Du Pont Innovations. Audience participation was actively encouraged during each presentation to uncover need and promote dialog among researchers and industry professionals.

  14. O Eu e a existência em Pascal

    Directory of Open Access Journals (Sweden)

    Ivonil Parraz

    2007-12-01

    Full Text Available “Je pense” solitaire de Descartes est source inspirée pour Pascal. En le maintenant dans sa solitude, l'auteur rejaillit la difficulté de, pour la raison, établir quelque lien entre Dieu et l'homme. Les cesuras entre moi et Dieu, résultent, dans Pascal, dans l'impossibilité d'établir objectivement l'existence de moi dans le temps. Notre objectif dans cet article est souligner telles questions.

  15. Fluids, Elasticity, Geometry, and the Existence of Wrinkled Solutions

    Science.gov (United States)

    Acharya, Amit; Chen, Gui-Qiang G.; Li, Siran; Slemrod, Marshall; Wang, Dehua

    2017-12-01

    We are concerned with underlying connections between fluids, elasticity, isometric embedding of Riemannian manifolds, and the existence of wrinkled solutions of the associated nonlinear partial differential equations. In this paper, we develop such connections for the case of two spatial dimensions, and demonstrate that the continuum mechanical equations can be mapped into a corresponding geometric framework and the inherent direct application of the theory of isometric embeddings and the Gauss-Codazzi equations through examples for the Euler equations for fluids and the Euler-Lagrange equations for elastic solids. These results show that the geometric theory provides an avenue for addressing the admissibility criteria for nonlinear conservation laws in continuum mechanics.

  16. Federal metering data analysis needs and existing tools

    Energy Technology Data Exchange (ETDEWEB)

    Henderson, Jordan W. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Fowler, Kimberly M. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2015-07-01

    Agencies have been working to improve their metering data collection, management, and analysis efforts over the last decade (since EPAct 2005) and will continue to address these challenges as new requirements and data needs come into place. Unfortunately there is no “one-size-fits-all” solution. As agencies continue to expand their capabilities to use metered consumption data to reducing resource use and improve operations, the hope is that shared knowledge will empower others to follow suit. This paper discusses the Federal metering data analysis needs and some existing tools.

  17. Eccrine syringofibroadenoma with co-existent squamous cell carcinoma.

    Science.gov (United States)

    Schadt, Courtney R; Boyd, Alan S

    2007-12-01

    Eccrine syringofibroadenoma (ESFA) is a rare, benign adnexal tumor arising most often on the extremities of elderly individuals. It is typically a slow-growing, flesh- to reddish-colored nodule or plaque. Histologically, the tumor consists of anastomosing cords of cuboidal epithelial cells surrounded by a fibrovascular stroma containing plasma cells. The cords contain scattered ductal structures lined with cuboidal cells resembling eccrine ducts. The co-existence of ESFA with squamous cell carcinoma has been described, eliciting the term eccrine syringofibroadenoma. The differential diagnosis includes poroma, porocarcinoma, fibroepithelioma of Pinkus and clear cell acanthoma. ESFA stain positively with epithelial membrane antigen and carcinoembryonic antigen. Cytokeratin studies have been inconsistent.

  18. Mining hydrogeological data from existing AEM datasets for mineral Mining

    Science.gov (United States)

    Menghini, Antonio; Viezzoli, Andrea; Teatini, Pietro; Cattarossi, Andrea

    2017-04-01

    Large amount of existing Airborne Electromagnetic (AEM) data are potentially available all over the World. Originally acquired for mining purposes, AEM data traditionally do not get processed in detail and inverted: most of the orebodies can be easily detected by analyzing just the peak anomaly directly evidenced by voltage values (the so-called "bump detection"). However, the AEM acquisitions can be accurately re-processed and inverted to provide detailed 3D models of resistivity: a first step towards hydrogeological studies and modelling. This is a great opportunity especially for the African continent, where the detection of exploitable groundwater resources is a crucial issue. In many cases, a while after AEM data have been acquired by the mining company, Governments become owners of those datasets and have the opportunity to develop detailed hydrogeological characterizations at very low costs. We report the case in which existing VTEM (Versatile Time Domain Electromagnetic - Geotech Ltd) data, originally acquired to detect gold deposits, are used to improve the hydrogeological knowledge of a roughly 50 km2 pilot-test area in Sierra Leone. Thanks to an accurate processing workflow and an advanced data inversion, based on the Spatially Constrained Inversion (SCI) algorithm, we have been able to resolve the thickness of the regolith aquifer and the top of the granitic-gneiss or greenstone belt bedrock. Moreover, the occurrence of different lithological units (more or less conductive) directly related to groundwater flow, sometimes having also a high chargeability (e.g. in the case of lateritic units), has been detailed within the regolith. The most promising areas to drill new productive wells have been recognized where the bedrock is deeper and the regolith thickness is larger. A further info that was considered in hydrogeological mapping is the resistivity of the regolith, provided that the most permeable layers coincide with the most resistive units. The

  19. Development of mobile platform integrated with existing electronic medical records.

    Science.gov (United States)

    Kim, YoungAh; Kim, Sung Soo; Kang, Simon; Kim, Kyungduk; Kim, Jun

    2014-07-01

    This paper describes a mobile Electronic Medical Record (EMR) platform designed to manage and utilize the existing EMR and mobile application with optimized resources. We structured the mEMR to reuse services of retrieval and storage in mobile app environments that have already proven to have no problem working with EMRs. A new mobile architecture-based mobile solution was developed in four steps: the construction of a server and its architecture; screen layout and storyboard making; screen user interface design and development; and a pilot test and step-by-step deployment. This mobile architecture consists of two parts, the server-side area and the client-side area. In the server-side area, it performs the roles of service management for EMR and documents and for information exchange. Furthermore, it performs menu allocation depending on user permission and automatic clinical document architecture document conversion. Currently, Severance Hospital operates an iOS-compatible mobile solution based on this mobile architecture and provides stable service without additional resources, dealing with dynamic changes of EMR templates. The proposed mobile solution should go hand in hand with the existing EMR system, and it can be a cost-effective solution if a quality EMR system is operated steadily with this solution. Thus, we expect this example to be shared with hospitals that currently plan to deploy mobile solutions.

  20. SOME CONSEQUENCE OF THE EXISTENCE OF LOW-VELOCITY LAYERS

    Directory of Open Access Journals (Sweden)

    M. BATH

    1956-06-01

    Full Text Available The velocities of elastic waves (P and S generally increase with
    depth in the earth. If at some depth this increase is replaced by a decrease
    over an interval of depth, again followed by an increase at some
    greater depth, we have, what we cali a low-velocity layer, provided
    the numerical value of the velocity decrease with depth in at least a
    part of the layer surpasses the criticai value v/r (v = velocity, r = radius;
    see Gutenberg, 1954 b, and Bullen, 1954, pp. 87-89. The most
    marked low-velocity layer (for P waves exists on the inner side of the
    outer core. This low-velocity layer has already been recognized by ali
    seismologists long ago. If a low-velocity layer exists also at the boundary
    of the inner core, is not yet certain. According to Jeffreys there is one,
    whereas Gutenberg does not find suffìcient observational support for it.

  1. APPROACH ON THE EXISTENCE OF INNOVATION IN TOURISM

    Directory of Open Access Journals (Sweden)

    Cristina BURGHELEA

    2015-04-01

    Full Text Available This article aimed to highlight the existence of innovation in tourism based on the international literature. From conceptualization of the research period it was found that definition can be universally valid applied in all sectors of the economy and, equally, in the tertiary sector, where there are tourist services. Coming either from English or French, "innovation" defines both a process and its results. Adapting to the constantly varying wishes of customers, innovation is a key element underpinning the survival and existence of competition in a dynamic environment that is changing radically. Current studies reveal that there are other indirect benefits of innovations such as image enhancement, improved customer loyalty, and ability to attract new ones. In this study, it was paid a special attention to the long-term prospects related to the tourism sector in countries such as Australia, Latin America, Africa, China and emerging markets such as India and Indonesia. This has resulted in tourism expenditure forecast for the period 2013 - 2019 performed using information provided by the Ministry of Business, Innovation and Employment.

  2. Higher-Order Factors of Personality: Do They Exist?

    Science.gov (United States)

    Ashton, Michael C.; Lee, Kibeom; Goldberg, Lewis R.; de Vries, Reinout E.

    2010-01-01

    Scales that measure the Big Five personality factors are often substantially intercorrelated. These correlations are sometimes interpreted as implying the existence of two higher-order factors of personality. We show that correlations between measures of broad personality factors do not necessarily imply the existence of higher-order factors, and might instead be due to variables that represent same-signed blends of orthogonal factors. Therefore, the hypotheses of higher-order factors and blended variables can only be tested with data on lower-level personality variables that define the personality factors. We compared the higher-order factor model and the blended variable model in three participant samples using the Big Five Aspect Scales, and found better fit for the latter model. In other analyses using the HEXACO Personality Inventory, we identified mutually uncorrelated markers of six personality factors. We conclude that correlations between personality factor scales can be explained without postulating any higher-order dimensions of personality. PMID:19458345

  3. Integrating Existing Simulation Components into a Cohesive Simulation System

    Science.gov (United States)

    McLaughlin, Brian J.; Barrett, Larry K.

    2012-01-01

    A tradition of leveraging the re-use of components to help manage costs has evolved in the development of complex system. This tradition continues on in the Joint Polar Satellite System (JPSS) Program with the cloning of the Suomi National Polar-orbiting Partnership (NPP) satellite for the JPSS-1 mission, including the instrument complement. One benefit of re-use on a mission is the availability of existing simulation assets from the systems that were previously built. An issue arises in the continual shift of technology over a long mission, or multi-mission, lifecycle. As the missions mature, the requirements for the observatory simulations evolve. The challenge in this environment becomes re-using the existing components in that ever-changing landscape. To meet this challenge, the system must: establish an operational architecture that minimizes impacts on the implementation of individual components, consolidate the satisfaction of new high-impact requirements into system-level infrastructure, and build in a long-term view of system adaptation that spans the full lifecycle of the simulation system. The Flight Vehicle Test Suite (FVTS) within the JPSS Program is defining and executing this approach to ensure a robust simulation capability for the JPSS multi-mission environment

  4. Assessment and Strengthening of Existing Rc Framed Structures

    Directory of Open Access Journals (Sweden)

    Cătălin Badea

    2006-01-01

    Full Text Available Existing structures built before the 1970s are gravity load designed with inadequate lateral load resistance because earlier codes specified lower levels of seismic loads and many of these structures are still in service beyond their design life. On the other hand, some deterioration of component parts of buildings is encountered in old structures due to the actions of different hazard factors. Theoretical aspects on the risk assessment of the reinforced concrete structures are pre¬sented. The earthquake capacity ratio is analyzed for reinforced concrete framed structure. More attention is paid to the seismic shear force capacity and some new procedures are introduced to estimate the earthquake capacity of existing structures. The assessment, rehabilitation and redesign were performed on an industrial RC framed structure. The main problems comprised local damage due to industrial exploitation of some structural elements (concrete cover dislocated over a large surface, complete corro¬sion of many stirrups, deep corrosion of main reinforcement, some broken reinforcement and weak reinforcement of columns and beams under seismic action. The redesign and reha¬bilitation of the RC structure was performed for both types of damages by using reinforced concrete jacketing solutions.

  5. Optimizing Existing Multistory Building Designs towards Net-Zero Energy

    Directory of Open Access Journals (Sweden)

    Mohammad Y. AbuGrain

    2017-03-01

    Full Text Available Recent global developments in awareness and concerns about environmental problems have led to reconsidering built environment approaches and construction techniques. One of the alternatives is the principle of low/zero-energy buildings. This study investigates the potentials of energy savings in an existing multi-story building in the Mediterranean region in order to achieve net-zero energy as a solution to increasing fossil fuel prices. The Colored building at the Faculty of Architecture, Eastern Mediterranean University, Cyprus was chosen as a target of this study to be investigated and analyzed in order to know how energy efficiency strategies could be applied to the building to reduce annual energy consumption. Since this research objective is to develop a strategy to achieve net-zero energy in existing buildings, case study and problem solving methodologies were applied in this research in order to evaluate the building design in a qualitative manner through observations, in addition to a quantitative method through an energy modeling simulation to achieve desirable results which address the problems. After optimizing the building energy performance, an alternative energy simulation was made of the building in order to make an energy comparison analysis, which leads to reliable conclusions. These methodologies and the strategies used in this research can be applied to similar buildings in order to achieve net-zero energy goals.

  6. Existence of standing waves for Dirac fields with singular nonlinearities

    Energy Technology Data Exchange (ETDEWEB)

    Balabane, M. (Reims Univ., 51 (France). Dept. de Mathematiques Ecole Normale Superieure, 75 - Paris (France)); Cazenave, T. (Paris-6 Univ., 75 (France). Lab. d' Analyse Numerique); Vazquez, L. (Universidad Complutense de Madrid (Spain). Dept. de Fisica Teorica)

    1990-09-01

    We prove the existence of stationary states for nonlinear Dirac equations of the form i {Sigma}{sub {mu}=0}{sup 3} {gamma}{sup {mu}}d{sub {mu}}{psi}-M{psi}+F(anti {psi}{psi}){psi}=0, (E) where M>0 and F is a singular self-interaction. In particular, in the model case where F(s)=-s{sup -{alpha}}, for some 0<{alpha}<1, and for every {omega}>M, there exists a solution of (E) of the form {psi}(t, x)=esup(i{omega}t){phi}(x), where x{sub 0}=t and x=(x{sub 1}, x{sub 2}, x{sub 3}), such that {phi} has compact support. If 0<{alpha}<1/3, then {phi} is of class C{sup 1}. If 1/3<{alpha}<1, then {phi} is continuously differentiable, except on some sphere {l brace}vertical strokexvertical stroke=R{r brace}, where vertical stroke{nabla}{phi}vertical stroke is infinite. (orig.).

  7. Differences exist across insurance schemes in China post-consolidation.

    Science.gov (United States)

    Li, Yang; Zhao, Yinjun; Yi, Danhui; Wang, Xiaojun; Jiang, Yan; Wang, Yu; Liu, Xinchun; Ma, Shuangge

    2017-01-01

    In China, the basic insurance system consists of three schemes: the UEBMI (Urban Employee Basic Medical Insurance), URBMI (Urban Resident Basic Medical Insurance), and NCMS (New Cooperative Medical Scheme), across which significant differences have been observed. Since 2009, the central government has been experimenting with consolidating these schemes in selected areas. This study examines whether differences still exist across schemes after the consolidation. A survey was conducted in the city of Suzhou, collecting data on subjects 45 years old and above with at least one inpatient or outpatient treatment during a period of twelve months. Analysis on 583 subjects was performed comparing subjects' characteristics across insurance schemes. A resampling-based method was applied to compute the predicted gross medical cost, OOP (out-of-pocket) cost, and insurance reimbursement rate. Subjects under different insurance schemes differ in multiple aspects. For inpatient treatments, subjects under the URBMI have the highest observed and predicted gross and OOP costs, while those under the UEBMI have the lowest. For outpatient treatments, subjects under the UEBMI and URBMI have comparable costs, while those under the NCMS have much lower costs. Subjects under the NCMS also have a much lower reimbursement rate. Differences still exist across schemes in medical costs and insurance reimbursement rate post-consolidation. Further investigations are needed to identify the causes, and interventions are needed to eliminate such differences.

  8. Future observations of Galactic Plane Transients with EXIST

    Science.gov (United States)

    Natalucci, Lorenzo

    The recent surveys of the Galactic Plane performed by INTEGRAL and Swift have allowed to discover new classes of hard X-ray sources often associated with transients, like e.g. the highly absorbed massive binaries accreting dense clumps of stellar wind and the fast X-ray transients associated with Supergiant binaries. Transient behavior is common among high energy sources: the recent IBIS 4th catalog contains more that 120 transient objects, i.e. 18% of all sources). Monitoring of the variability and transient behavior of Galactic sources claims for high sensitivity, wide energy coverage from soft X-rays to soft gamma-rays and almost continuous time coverage of individual sources, more than actually achieved with the operational Swift and INTEGRAL missions. This would allow to properly model spectra, reveal source geometries, measure the mass and other properties of the compact objects and the environment conditions around the sources (e.g., stellar wind structure). This difficult task will be accomplished by EXIST, with its large area High Energy Telescope (HET) having 90deg field-of-view covering the 5-600 keV band (and simultaneous coverage in the IR/optical and soft X-rays, down to 0.1 keV when pointing at a target). With EXIST it will be also possible to perform accurate timing studies up to a few 100's keV, thanks to the large detection area of the HET ( 4.5m2 ).

  9. High-Redshift Compton Thick AGN with EXIST

    Science.gov (United States)

    Treister, Ezequiel; Urry, C.; Coppi, P.; Virani, S.

    2009-01-01

    It has been suspected for many years that a large number of heavily obscured, Compton Thick, Active Galactic Nuclei (AGN) should exist at all redshifts, but the exact number of them is still highly uncertain. Recent all-sky surveys with INTEGRAL and Swift are starting to constrain the number of Compton Thick AGN in the local Universe, zEXIST observations. We expect to find a total of 120 Compton Thick AGN at 0.5

  10. The infrared-optical telescope (IRT) of the EXIST observatory.

    Science.gov (United States)

    Kutyrev, Alexander; Bloom, Joshua; Gehrels, Neil; Golisano, Craig; Gong, Quan; Grindlay, Jonathan; Moseley, Samuel; Woodgate, Bruce

    The IRT is a 1.1m visible and infrared passively cooled telescope, which can locate, identify and obtain spectra of GRB afterglows at redshifts up to z 20. It will also acquire optical-IR imaging and spectroscopy of AGN and transients discovered by the EXIST (The Energetic X-ray Imaging Survey Telescope). The IRT imaging and spectroscopic capabilities cover a broad spectral range from 0.32.2m in four bands. The identical fields of view in the four instrument bands are each split in three subfields: imaging, objective prism slitless for the field and objective prism single object slit low resolution spectroscopy, and high resolution long slit on single object. This allows the instrument to do simultaneous broadband photometry or spectroscopy of the same object over the full spectral range, thus greatly improving the efficiency of the observatory and its detection limits. A prompt follow up (within three minutes) of the transient discovered by the EXIST makes IRT a unique tool for detection and study of these events, which is particularly valuable at wavelengths unavailable to the ground based observatories.

  11. Optimizing The Imaging Performance Of The Exist High Energy Telescope

    Science.gov (United States)

    Skinner, Gerald K.; Finger, M. H.; Hong, J.; Jernigan, J. G.; Sturner, S. J.; Allen, B.; Grindlay, J. E.

    2009-01-01

    The baseline concept for the primary instrument of the EXIST mission, the high energy telescope (HET), is a coded mask instrument with a wide field of view and extremely good sensitivity (Hong et al., this meeting). Achieving the performance goals requires an imaging capability close to the statistical photon limit, minimizing systematic errors even when the total integration time is very long. At the same time there is a requirement to be able to reconstruct images on board in near real time in order to detect and localize gamma-ray bursts. This must be done while the spacecraft is scanning the sky with a motion designed to help reduce systematic errors and to provide all-sky coverage. During the 2008 Advanced Mission Concept Study, the Exist Imaging Technical Working Group has investigated and compared numerous alternative designs for the HET. The selected baseline concept meets all of the scientific requirements, while being compatible with spacecraft and launch constraints and with those imposed by the Infra-Red Telescope that forms the other key part of the mission. The approach adopted depends on a unique annular coded mask with two spatial scales, offering good resolution and low background at low energies, with a lower resolution but enhanced sensitivity in the upper part of the energy band. Monte Carlo simulations and analytic analysis techniques have been used to demonstrate the capabilities of the proposed design.

  12. The EXIST Infra-Red Telescope System: Design and Performance

    Science.gov (United States)

    Moseley, Harvey; Golisano, C.; Gong, Q.; Allen, B.; Grindlay, J.; Hong, J.; Kutyrev, A.; Woodgate, B.; EXIST Team

    2010-01-01

    The Infra-Red Telescope is a critical element of the EXIST (Energetic X-Ray Imaging Survey Telescope) observatory. It is a passively cooled 1.1m visible/infrared telescope. The primary goal of the IRT is to obtain photometric and spectroscopic measurements of high redshift (>6) gamma ray burst afterglows to study the nature of these enigmatic events and the their environments, and to use them as probes of the composition and ionization state of the intergalactiic medium of the young universe . The IRT will provide a prompt follow up (within three minutes) of the transient discovered by the EXIST with exceptional NIR sensitivitiy (AB=24 in 100s) surpassing HST in the infrared due to its passively cooled (-30ºC) mirror. Its optical design and spectral coverage is tailored to the high redshift transient events that require prompt pointing, identification, accurate phototmetry and both low and high resolution spectroscopy. Here we describe the telescope, its instrument complement, and the cooling systems which provide its remarkable sensitivity.

  13. The Infrared-Optical Telescope (IRT) of the Exist Observatory

    Science.gov (United States)

    Kutyrev, Alexander; Bloom, Joshua; Gehrels, Neil; Golisano, Craig; Gong, Quan; Grindlay, Jonathan; Moseley, Samuel; Woodgate, Bruce

    2010-01-01

    The IRT is a 1.1m visible and infrared passively cooled telescope, which can locate, identify and obtain spectra of GRB afterglows at redshifts up to z 20. It will also acquire optical-IR, imaging and spectroscopy of AGN and transients discovered by the EXIST (The Energetic X-ray Imaging Survey Telescope). The IRT imaging and spectroscopic capabilities cover a broad spectral range from 0.32.2m in four bands. The identical fields of view in the four instrument bands are each split in three subfields: imaging, objective prism slitless for the field and objective prism single object slit low resolution spectroscopy, and high resolution long slit on single object. This allows the instrument, to do simultaneous broadband photometry or spectroscopy of the same object over the full spectral range, thus greatly improving the efficiency of the observatory and its detection limits. A prompt follow up (within three minutes) of the transient discovered by the EXIST makes IRT a unique tool for detection and study of these events, which is particularly valuable at wavelengths unavailable to the ground based observatories.

  14. The EXIST Infra-Red Telescope System: Design and Performance

    Science.gov (United States)

    Moseley, Samuel H.

    2010-01-01

    The Infra-Red Telescope is a critical element of the EXIST (Energetic X-Ray Imaging Survey Telescope) observatory. It is a passively cooled 1.lm visible/infrared telescope. The primary goal of the IRT is to obtain photometric and spectroscopic measurements of high redshift (>6) gamma ray burst afterglows to study the nature of these enigmatic events and their environments, and to use them as probes of the composition and ionization state of the intergalactic medium of the young universe. The IRT will provide a prompt follow up (within three minutes) of the transient discovered by the EXIST with exceptional NIR sensitivity (AB=24 in 100s) surpassing HST in the infrared due to its passively cooled (- 30 C) mirror. Its optical design and spectral coverage is tailored to the high redshift transient events that require prompt pointing, identification, accurate photometry and both low and high resolution spectroscopy. Here we describe the telescope, its instrument complement, and the cooling systems which provide its remarkable sensitivity

  15. Tracking Object Existence From an Autonomous Patrol Vehicle

    Science.gov (United States)

    Wolf, Michael; Scharenbroich, Lucas

    2011-01-01

    An autonomous vehicle patrols a large region, during which an algorithm receives measurements of detected potential objects within its sensor range. The goal of the algorithm is to track all objects in the region over time. This problem differs from traditional multi-target tracking scenarios because the region of interest is much larger than the sensor range and relies on the movement of the sensor through this region for coverage. The goal is to know whether anything has changed between visits to the same location. In particular, two kinds of alert conditions must be detected: (1) a previously detected object has disappeared and (2) a new object has appeared in a location already checked. For the time an object is within sensor range, the object can be assumed to remain stationary, changing position only between visits. The problem is difficult because the upstream object detection processing is likely to make many errors, resulting in heavy clutter (false positives) and missed detections (false negatives), and because only noisy, bearings-only measurements are available. This work has three main goals: (1) Associate incoming measurements with known objects or mark them as new objects or false positives, as appropriate. For this, a multiple hypothesis tracker was adapted to this scenario. (2) Localize the objects using multiple bearings-only measurements to provide estimates of global position (e.g., latitude and longitude). A nonlinear Kalman filter extension provides these 2D position estimates using the 1D measurements. (3) Calculate the probability that a suspected object truly exists (in the estimated position), and determine whether alert conditions have been triggered (for new objects or disappeared objects). The concept of a probability of existence was created, and a new Bayesian method for updating this probability at each time step was developed. A probabilistic multiple hypothesis approach is chosen because of its superiority in handling the

  16. Reap What You Sow: Which Rural Surgery Training Programs Currently Exist and Do Medical Students Know of Their Existence?

    Science.gov (United States)

    Rossi, Isolina R; Wiegmann, Aaron L; Schou, Pat; Borgstrom, David C; Rossi, Matthew B

    2017-10-24

    There exists an acute need to recruit and train general surgeons for rural communities. To assist medical students interested in rural surgery, the American College of Surgeons (ACS) website lists general surgery residencies, which are tailored to train the rural surgeon by providing exposure to endoscopy, gynecology, urology, orthopedics, and otolaryngology. Another available reference is the American Medical Association Fellowship and Residency Electronic Database (FREIDA). FREIDA allows programs to indicate availability of a rural training scheme. This is an effort to identify programs which demonstrate a commitment to training rural surgeons and evaluate accessibility of this information to medical students. Each ACGME general surgery residency program in the United States and Canada received an electronic survey. They were queried on commitment to training rural surgeons and their ability to provide 3 to 12 months of subspecialty training. Of the 261 programs surveyed, 52 (19.9%) responses were obtained; 11 had established rural tracks and 15 were willing to customize a program. We identified 14 additional rural training programs not identified by either the ACS website or FREIDA. In total, 44 programs identified by ACS, FREIDA, and our survey indicate they can accommodate the rural surgical resident. For a medical student interested in rural surgery, several obstacles must be overcome to find the appropriate residency program. A complete and updated list of established tracks or customizable training schemes does not exist. Review of the ACS website and FREIDA online in addition to our survey has identified 44 of 261 (16.9%) ACGME accredited programs either with an existing rural surgical track or willing to customize their program accommodate a resident. To facilitate the recruitment of medical students into rural surgery, we support the maintenance of a complete and routinely updated list that identifies available training programs. Copyright © 2017

  17. Afinal, existe algum aspecto positivo no modelo da Escola Tradicional?

    Directory of Open Access Journals (Sweden)

    Fernando Henrique Protetti

    2010-03-01

    Full Text Available

    O artigo apresenta elementos de reflexão sobre o campo da educação escolar, relativo às distintas teorias pedagógicas e suas concepções sobre o processo do trabalho educativo. Objetiva-se compreender a relação entre o modelo pedagógico da Escola Tradicional e o debate existente com outras perspectivas pedagógicas, na procura de responder a questão que corresponde ao título do artigo: afinal, existe algum aspecto positivo no modelo pedagógico da Escola Tradicional? Inicialmente, realiza-se a exposição do modelo pedagógico da Escola Tradicional, na definição dos elementos singulares do seu método de ensino. No segundo momento, investigam-se as diferentes críticas recebidas pela Escola Tradicional por meio da exemplificação de duas teorias pedagógicas, Escola Nova e Pedagogia das Competências, com a intenção de identificar as características comuns que envolvem ambas as críticas, a partir da tese que versa sobre a existência de “pedagogias negativas”, a negação de tudo aquilo a que se refere à Educação Tradicional. Finalmente procura-se responder através desta investigação a seguinte questão: a partir da consideração de que todas as críticas recebidas figuram a Escola Tradicional como um modelo pedagógico atrasado e anacrônico, será possível a existências de algum aspecto positivo nesta concepção de trabalho educativo?

  18. Co-existence of Pulmonary, Tonsillar and Laryngeal Tuberculosis

    Directory of Open Access Journals (Sweden)

    Erkan Ceylan

    2013-10-01

    Full Text Available    A 56-year old man applied to otorhinolaryngology clinic with sore throat, dysphagia. During direct examination, left palatine tonsil and tonsil plicas ulcerovegetative lesions were found. In the indirect laryngoscopy, in some regions of the larynx and epiglottis, ulcerovegetative lesions were observed too. Because of suspicion of laryngeal carcinoma and metastasis, punch biopsy of the left palatine tonsil was performed. Chest x-ray and computerized tomography of the thorax revealed two adjacent cavitations in the apicoposterior segment of the left upper lobe. In the histopathologic examination of biopsies, granulomatous structures that proved tuberculosis were observed. In the fiberoptic bronchoscopic analysis, endobronchial lesion was not detected. Acid-fast bacilli were determined in sputum and bronchial lavage in microscopy and culture. The case of this middle aged male patient with co-existence of tonsillar, laryngeal and pulmonary tuberculosis presents the clinical significance of upper airway tuberculosis in terms of its infectiousness and rare occurrence.

  19. Existence of Periodic Solutions for a Modified Growth Solow Model

    Science.gov (United States)

    Fabião, Fátima; Borges, Maria João

    2010-10-01

    In this paper we analyze the dynamic of the Solow growth model with a Cobb-Douglas production function. For this purpose, we consider that the labour growth rate, L'(t)/L(t), is a T-periodic function, for a fixed positive real number T. We obtain the closed form solutions for the fundamental Solow equation with the new description of L(t). Using notions of the qualitative theory of ordinary differential equations and nonlinear functional analysis, we prove that there exists one T-periodic solution for the Solow equation. From the economic point of view this is a new result which allows a more realistic interpretation of the stylized facts.

  20. Existence of Nonsteady Planar Ideal Flows in Anisotropic Plasticity

    Science.gov (United States)

    Alexandrov, S.; Pirumov, A.; Date, P. P.

    2017-12-01

    Ideal plastic flows are those for which all material elements follow minimum work paths. The general equations for steady and nonsteady planar ideal flows in Tresca solids have been given elsewhere. The present paper focuses on nonsteady planar ideal flows in anisotropic plasticity. In particular, the existence of such flows is proven under a certain assumption concerning the orientation of principal stress trajectories at the initial instant. It is also shown that the system of kinematic equations is hyperbolic. This system can be treated separately from the stress equations. The original ideal flow theory is widely used as the basis for inverse methods for the preliminary design of metal forming processes driven by minimum plastic work. The new theory extends this area of application to anisotropic materials.