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Sample records for 18f-labelled boronophenylalanine depending

  1. 18F-Labeling Using Click Cycloadditions

    PubMed Central

    Ross, Tobias L.

    2014-01-01

    Due to expanding applications of positron emission tomography (PET) there is a demand for developing new techniques to introduce fluorine-18 (t 1/2 = 109.8 min). Considering that most novel PET tracers are sensitive biomolecules and that direct introduction of fluorine-18 often needs harsh conditions, the insertion of 18F in those molecules poses an exceeding challenge. Two major challenges during 18F-labeling are a regioselective introduction and a fast and high yielding way under mild conditions. Furthermore, attention has to be paid to functionalities, which are usually present in complex structures of the target molecule. The Cu-catalyzed azide-alkyne cycloaddition (CuAAC) and several copper-free click reactions represent such methods for radiolabeling of sensitive molecules under the above-mentioned criteria. This minireview will provide a quick overview about the development of novel 18F-labeled prosthetic groups for click cycloadditions and will summarize recent trends in copper-catalyzed and copper-free click 18F-cycloadditions. PMID:25003110

  2. One-step 18F labeling of biomolecules using organotrifluoroborates

    PubMed Central

    Liu, Zhibo; Lin, Kuo-Shyan; Bénard, François; Pourghiasian, Maral; Kiesewetter, Dale O; Perrin, David M; Chen, Xiaoyuan

    2017-01-01

    Herein we present a general protocol for the functionalization of biomolecules with an organotrifluoroborate moiety so that they can be radiolabeled with aqueous 18F fluoride (18F−) and used for positron emission tomography (PET) imaging. Among the β+-emitting radionuclides, fluorine-18 (18F) is the isotope of choice for PET, and it is produced, on-demand, in many hospitals worldwide. Organotrifluoroborates can be 18F-labeled in one step in aqueous conditions via 18F–19F isotope exchange. This protocol features a recently designed ammoniomethyltrifluoroborate, and it describes the following: (i) a synthetic strategy that affords modular synthesis of radiolabeling precursors via a copper-catalyzed ‘click’ reaction; and (ii) a one-step 18F-labeling method that obviates the need for HPLC purification. Within 30 min, 18F-labeled PET imaging probes, such as peptides, can be synthesized in good chemical and radiochemical purity (>98%), satisfactory radiochemical yield of 20–35% (n > 20, non-decay corrected) and high specific activity of 40–111 GBq/µmol (1.1–3.0 Ci/µmol). The entire procedure, including the precursor preparation and 18F radiolabeling, takes 7–10 d. PMID:26313478

  3. Rerouting the metabolic pathway of (18)F-labeled peptides: the influence of prosthetic groups.

    PubMed

    Richter, Susan; Wuest, Melinda; Bergman, Cody N; Way, Jenilee D; Krieger, Stephanie; Rogers, Buck E; Wuest, Frank

    2015-02-18

    Current translational cancer research is directed to the development of high affinity peptide ligands for targeting neuropeptide receptors overexpressed in different types of cancer. Besides their desired high binding affinity to the receptor, the suitability of radiolabeled peptides as targeting vectors for molecular imaging and therapy depends on additional aspects such as high tumor-to-background ratio, favorable clearance pattern from nontarget tissue, and sufficient metabolic stability in vivo. This study reports how a switch from the prosthetic group, N-succinimidyl-4-[(18)F]fluorobenzoate ([(18)F]SFB), to 2-deoxy-2-[(18)F]fluoro-d-glucose ([(18)F]FDG) effects the metabolic pathway of an (18)F-labeled bombesin derivative, QWAV-Sar-H-FA01010-Tle-NH2. (18)F-Labeled bombesin derivatives represent potent peptide ligands for selective targeting of gastrin-releasing peptide (GRP) receptor-expressing prostate cancer. Radiosynthesis of (18)F-labeled bombesin analogues [(18)F]FBz-Ava-BBN2 and [(18)F]FDG-AOAc-BBN2 was achieved in good radiochemical yields of ~50% at a specific activity exceeding 40 GBq/μmol. Both nonradioactive compounds FBz-Ava-BBN2 and FDG-AOAc-BBN2 inhibited binding of [(125)I]Tyr(4)-bombesin(1-14) in PC3 cells with IC50 values of 9 and 16 nM, respectively, indicating high inhibitory potency. Influence of each prosthetic group was further investigated in PC3 mouse xenografts using dynamic small animal PET imaging. In comparison to [(18)F]FBz-Ava-BBN2, total tumor uptake levels were doubled after injection of [(18)F]FDG-AOAc-BBN2 while renal elimination was increased. Blood clearance and in vivo metabolic stability were similar for both compounds. The switch from [(18)F]SFB to [(18)F]FDG as the prosthetic group led to a significant reduction in lipophilicity which resulted in more favorable renal clearance and increased tumor uptake. The presented single step radiolabeling-glycosylation approach represents an innovative strategy for site

  4. (18)F-labelled metomidate analogues as adrenocortical imaging agents.

    PubMed

    Erlandsson, Maria; Karimi, Farhad; Lindhe, Orjan; Långström, Bengt

    2009-05-01

    Two- and one-step syntheses of (18)F-labelled analogues of metomidate, such as 2-[(18)F]fluoroethyl 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylate (1), 2-[(18)F]fluoroethyl 1-[(1R)-1-(4-chlorophenyl)ethyl]-1H-imidazole-5-carboxylate (2), 2-[(18)F]fluoroethyl 1-[(1R)-1-(4-bromophenyl)ethyl]-1H-imidazole-5-carboxylate (3), 3-[(18)F]fluoropropyl 1-[(1R)-1-(4-bromophenyl)ethyl]-1H-imidazole-5-carboxylate (4) and 3-[(18)F]fluoropropyl 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylate (5) are presented. Analogues 1-5 were prepared by a two-step reaction sequence that started with the synthesis of either 2-[(18)F]fluoroethyl 4-methylbenzenesulfonate or 3-[(18)F]fluoropropyl 4-methylbenzenesulfonate. These were used as (18)F-alkylating agents in the second step, in which they reacted with the ammonium salt of a 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylic acid. One-step-labelling syntheses of 1, 2 and 5 were also explored. Analogues 1-4 were biologically validated by frozen-section autoradiography and organ distribution. Metabolite analysis was performed for 2 and 3. The radiochemical yield of the two-step synthesis was in the range of 10-29% and that of the one-step synthesis was 25-37%. Using microwave irradiation in the one-step synthesis of 1 and 2 increased the radiochemical yield to 46+/-3% and 79+/-30%, respectively. Both the frozen-section autoradiography and organ distribution results indicated that analogue 2 has a potential as an adrenocortical imaging agent, having the highest degree of specific adrenal binding and best ratio of adrenal to organ uptake among the compounds studied.

  5. Synthesis and Reactivity of (18)F-Labeled α,α-Difluoro-α-(aryloxy)acetic Acids.

    PubMed

    Khotavivattana, Tanatorn; Calderwood, Samuel; Verhoog, Stefan; Pfeifer, Lukas; Preshlock, Sean; Vasdev, Neil; Collier, Thomas L; Gouverneur, Véronique

    2017-02-03

    In this work, we describe the (18)F-labeling of α,α-difluoro-α-(aryloxy)acetic acid derivatives and demonstrate that these building blocks are amenable to post-(18)F-fluorination functionalization. Protodecarboxylation offers a new entry to (18)F-difluoromethoxyarene, and the value of this approach is further demonstrated with coupling processes leading to representative (18)F-labeled TRPV1 inhibitors and TRPV1 antagonists.

  6. 18F-Labelled Intermediates for Radiosynthesis by Modular Build-Up Reactions: Newer Developments

    PubMed Central

    Ermert, Johannes

    2014-01-01

    This brief review gives an overview of newer developments in 18F-chemistry with the focus on small 18F-labelled molecules as intermediates for modular build-up syntheses. The short half-life (<2 h) of the radionuclide requires efficient syntheses of these intermediates considering that multistep syntheses are often time consuming and characterized by a loss of yield in each reaction step. Recent examples of improved synthesis of 18F-labelled intermediates show new possibilities for no-carrier-added ring-fluorinated arenes, novel intermediates for tri[18F]fluoromethylation reactions, and 18F-fluorovinylation methods. PMID:25343144

  7. (18)F-labeled positron emission tomographic radiopharmaceuticals in oncology: an overview of radiochemistry and mechanisms of tumor localization.

    PubMed

    Vallabhajosula, Shankar

    2007-11-01

    Molecular imaging is the visualization, characterization, and measurement of biological processes at the molecular and cellular levels in a living system. At present, positron emission tomography/computed tomography (PET/CT) is one the most rapidly growing areas of medical imaging, with many applications in the clinical management of patients with cancer. Although [(18)F]fluorodeoxyglucose (FDG)-PET/CT imaging provides high specificity and sensitivity in several kinds of cancer and has many applications, it is important to recognize that FDG is not a "specific" radiotracer for imaging malignant disease. Highly "tumor-specific" and "tumor cell signal-specific" PET radiopharmaceuticals are essential to meet the growing demand of radioisotope-based molecular imaging technology. In the last 15 years, many alternative PET tracers have been proposed and evaluated in preclinical and clinical studies to characterize the tumor biology more appropriately. The potential clinical utility of several (18)F-labeled radiotracers (eg, fluoride, FDOPA, FLT, FMISO, FES, and FCH) is being reviewed by several investigators in this issue. An overview of design and development of (18)F-labeled PET radiopharmaceuticals, radiochemistry, and mechanism(s) of tumor cell uptake and localization of radiotracers are presented here. The approval of clinical indications for FDG-PET in the year 2000 by the Food and Drug Administration, based on a review of literature, was a major breakthrough to the rapid incorporation of PET into nuclear medicine practice, particularly in oncology. Approval of a radiopharmaceutical typically involves submission of a "New Drug Application" by a manufacturer or a company clearly documenting 2 major aspects of the drug: (1) manufacturing of PET drug using current good manufacturing practices and (2) the safety and effectiveness of a drug with specific indications. The potential routine clinical utility of (18)F-labeled PET radiopharmaceuticals depends also on

  8. Effect of methoxy group position on biological properties of (18)F-labeled benzyl triphenylphosphonium cations.

    PubMed

    Chen, Shuting; Zhao, Zuoquan; Zhang, Ying; Fang, Wei; Lu, Jie; Zhang, Xianzhong

    2017-06-01

    (18)F-labeled phosphonium cations targeting mitochondrial membrane potential would be promising for positron emission tomography (PET) myocardial perfusion imaging (MPI). The purpose of this study was to examine the influence of additional methoxy group and its different positions on myocardium uptake and pharmacokinetics properties of (18)F-labeled benzyl triphenylphosphonium cations. In this study, three novel (18)F-labeled phosphonium cations, [(18)F]4-(fluoromethyl)benzyltris(4-methoxyphenyl) phosphonium cation (1b), [(18)F]4-(fluoromethyl)benzyltris(2-methoxyphenyl) phosphonium cation (2b) and [(18)F]4-(fluoromethyl)benzyltris(3-methoxyphenyl) phosphonium cation (3b), were efficiently prepared by a One-Pot method starting from the substitution of non-carried-added fluoride-18. Radiotracers were purified by HPLC. Physicochemical properties, in vitro cell uptake assay, in vivo mice biodistribution and rat micro-PET imaging were investigated. Results suggested that the position of methoxy group exhibited significant effect on the biological properties of (18)F-labeled benzyl triphenylphosphonium cations. The addition of methoxy group on orth- or meta-position of the radiotracers accelerated the radioactivity clearance from liver. The para-radiotracer had the highest uptake in the heart and other non-targeting organs. According to the biodistribution data, 2b (ortho-) displayed the fastest liver clearance and highest heart-to-background ratios. And its rat micro-PET images at 60min post-injection revealed a good visualization of heart and favorable heart-to-background contrast. Nevertheless, 2b exhibited a lower initial liver uptake and quicker liver clearance compared with (99m)Tc-sestamibi. The ortho- compound (2b) displayed the most favorable biological properties as a potential MPI agent to acquire high contrast images early after injection. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Convergent synthesis and evaluation of (18)F-labeled azulenic COX2 probes for cancer imaging.

    PubMed

    Nolting, Donald D; Nickels, Michael; Tantawy, Mohammed N; Yu, James Y H; Xie, Jingping; Peterson, Todd E; Crews, Brenda C; Marnett, Larry; Gore, John C; Pham, Wellington

    2012-01-01

    The overall objectives of this research are to (i) develop azulene-based positron emission tomography (PET) probes and (ii) image COX2 as a potential biomarker of breast cancer. Several lines of research have demonstrated that COX2 is overexpressed in breast cancer and that its presence correlates with poor prognoses. While other studies have reported that COX2 inhibition can be modulated and used beneficially as a chemopreventive strategy in cancer, no viable mechanism for achieving that approach has yet been developed. This shortfall could be circumvented through in vivo imaging of COX2 activity, particularly using sensitive imaging techniques such as PET. Toward that goal, our laboratory focuses on the development of novel (18)F-labled COX2 probes. We began the synthesis of the probes by transforming tropolone into a lactone, which was subjected to an [8 + 2] cycloaddition reaction to yield 2-methylazulene as the core ring of the probe. After exploring numerous synthetic routes, the final target molecule and precursor PET compounds were prepared successfully using convergent synthesis. Conventional (18)F labeling methods caused precursor decomposition, which prompted us to hypothesize that the acidic protons of the methylene moiety between the azulene and thiazole rings were readily abstracted by a strong base such as potassium carbonate. Ultimately, this caused the precursors to disintegrate. This observation was supported after successfully using an (18)F labeling strategy that employed a much milder phosphate buffer. The (18)F-labeled COX2 probe was tested in a breast cancer xenograft mouse model. The data obtained via successive whole-body PET/CT scans indicated probe accumulation and retention in the tumor. Overall, the probe was stable in vivo and no defluorination was observed. A biodistribution study and Western blot analysis corroborate with the imaging data. In conclusion, this novel COX2 PET probe was shown to be a promising agent for cancer imaging

  10. Convergent synthesis and evaluation of 18F-labeled azulenic COX2 probes for cancer imaging

    PubMed Central

    Nolting, Donald D.; Nickels, Michael; Tantawy, Mohammed N.; Yu, James Y. H.; Xie, Jingping; Peterson, Todd E.; Crews, Brenda C.; Marnett, Larry; Gore, John C.; Pham, Wellington

    2013-01-01

    The overall objectives of this research are to (i) develop azulene-based positron emission tomography (PET) probes and (ii) image COX2 as a potential biomarker of breast cancer. Several lines of research have demonstrated that COX2 is overexpressed in breast cancer and that its presence correlates with poor prognoses. While other studies have reported that COX2 inhibition can be modulated and used beneficially as a chemopreventive strategy in cancer, no viable mechanism for achieving that approach has yet been developed. This shortfall could be circumvented through in vivo imaging of COX2 activity, particularly using sensitive imaging techniques such as PET. Toward that goal, our laboratory focuses on the development of novel 18F-labled COX2 probes. We began the synthesis of the probes by transforming tropolone into a lactone, which was subjected to an [8 + 2] cycloaddition reaction to yield 2-methylazulene as the core ring of the probe. After exploring numerous synthetic routes, the final target molecule and precursor PET compounds were prepared successfully using convergent synthesis. Conventional 18F labeling methods caused precursor decomposition, which prompted us to hypothesize that the acidic protons of the methylene moiety between the azulene and thiazole rings were readily abstracted by a strong base such as potassium carbonate. Ultimately, this caused the precursors to disintegrate. This observation was supported after successfully using an 18F labeling strategy that employed a much milder phosphate buffer. The 18F-labeled COX2 probe was tested in a breast cancer xenograft mouse model. The data obtained via successive whole-body PET/CT scans indicated probe accumulation and retention in the tumor. Overall, the probe was stable in vivo and no defluorination was observed. A biodistribution study and Western blot analysis corroborate with the imaging data. In conclusion, this novel COX2 PET probe was shown to be a promising agent for cancer imaging and

  11. (18) F-Labeling of Sensitive Biomolecules for Positron Emission Tomography.

    PubMed

    Krishnan, Hema S; Ma, Longle; Vasdev, Neil; Liang, Steven H

    2017-07-13

    Positron emission tomography (PET) imaging study of fluorine-18 labeled biomolecules is an emerging and rapidly growing area for preclinical and clinical research. The present review focuses on recent advances in radiochemical methods for incorporating fluorine-18 into biomolecules via "direct" or "indirect" bioconjugation. Recently developed prosthetic groups and pre-targeting strategies, as well as representative examples in (18) F-labeling of biomolecules in PET imaging research studies are highlighted. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Enhanced Aqueous Suzuki–Miyaura Coupling Allows Site-Specific Polypeptide 18F-Labeling

    PubMed Central

    2013-01-01

    The excesses of reagents used in protein chemistry are often incompatible with the reduced or even inverse stoichiometries used for efficient radiolabeling. Analysis and screening of aqueous Pd(0) ligand systems has revealed the importance of a guanidine core and the discovery of 1,1-dimethylguanidine as an enhanced ligand for aqueous Suzuki–Miyaura cross-coupling. This novel Pd catalyst system has now allowed the labeling of small molecules, peptides, and proteins with the fluorine-18 prosthetic [18F]4-fluorophenylboronic acid. These findings now enable site-specific protein 18F-labeling under biologically compatible conditions using a metal-triggered reaction. PMID:23991754

  13. Al18F-Labeling Of Heat-Sensitive Biomolecules for Positron Emission Tomography Imaging

    PubMed Central

    Cleeren, Frederik; Lecina, Joan; Ahamed, Muneer; Raes, Geert; Devoogdt, Nick; Caveliers, Vicky; McQuade, Paul; Rubins, Daniel J; Li, Wenping; Verbruggen, Alfons; Xavier, Catarina; Bormans, Guy

    2017-01-01

    Positron emission tomography (PET) using radiolabeled biomolecules is a translational molecular imaging technology that is increasingly used in support of drug development. Current methods for radiolabeling biomolecules with fluorine-18 are laborious and require multistep procedures with moderate labeling yields. The Al18F-labeling strategy involves chelation in aqueous medium of aluminum mono[18F]fluoride ({Al18F}2+) by a suitable chelator conjugated to a biomolecule. However, the need for elevated temperatures (100-120 °C) required for the chelation reaction limits its widespread use. Therefore, we designed a new restrained complexing agent (RESCA) for application of the AlF strategy at room temperature. Methods. The new chelator RESCA was conjugated to three relevant biologicals and the constructs were labeled with {Al18F}2+ to evaluate the generic applicability of the one-step Al18F-RESCA-method. Results. We successfully labeled human serum albumin with excellent radiochemical yields in less than 30 minutes and confirmed in vivo stability of the Al18F-labeled protein in rats. In addition, we efficiently labeled nanobodies targeting the Kupffer cell marker CRIg, and performed µPET studies in healthy and CRIg deficient mice to demonstrate that the proposed radiolabeling method does not affect the functional integrity of the protein. Finally, an affibody targeting HER2 (PEP04314) was labeled site-specifically, and the distribution profile of (±)-[18F]AlF(RESCA)-PEP04314 in a rhesus monkey was compared with that of [18F]AlF(NOTA)-PEP04314 using whole-body PET/CT. Conclusion. This generic radiolabeling method has the potential to be a kit-based fluorine-18 labeling strategy, and could have a large impact on PET radiochemical space, potentially enabling the development of many new fluorine-18 labeled protein-based radiotracers. PMID:28824726

  14. Al(18)F-Labeling Of Heat-Sensitive Biomolecules for Positron Emission Tomography Imaging.

    PubMed

    Cleeren, Frederik; Lecina, Joan; Ahamed, Muneer; Raes, Geert; Devoogdt, Nick; Caveliers, Vicky; McQuade, Paul; Rubins, Daniel J; Li, Wenping; Verbruggen, Alfons; Xavier, Catarina; Bormans, Guy

    2017-01-01

    Positron emission tomography (PET) using radiolabeled biomolecules is a translational molecular imaging technology that is increasingly used in support of drug development. Current methods for radiolabeling biomolecules with fluorine-18 are laborious and require multistep procedures with moderate labeling yields. The Al(18)F-labeling strategy involves chelation in aqueous medium of aluminum mono[(18)F]fluoride ({Al(18)F}(2+)) by a suitable chelator conjugated to a biomolecule. However, the need for elevated temperatures (100-120 °C) required for the chelation reaction limits its widespread use. Therefore, we designed a new restrained complexing agent (RESCA) for application of the AlF strategy at room temperature. Methods. The new chelator RESCA was conjugated to three relevant biologicals and the constructs were labeled with {Al(18)F}(2+) to evaluate the generic applicability of the one-step Al(18)F-RESCA-method. Results. We successfully labeled human serum albumin with excellent radiochemical yields in less than 30 minutes and confirmed in vivo stability of the Al(18)F-labeled protein in rats. In addition, we efficiently labeled nanobodies targeting the Kupffer cell marker CRIg, and performed µPET studies in healthy and CRIg deficient mice to demonstrate that the proposed radiolabeling method does not affect the functional integrity of the protein. Finally, an affibody targeting HER2 (PEP04314) was labeled site-specifically, and the distribution profile of (±)-[(18)F]AlF(RESCA)-PEP04314 in a rhesus monkey was compared with that of [(18)F]AlF(NOTA)-PEP04314 using whole-body PET/CT. Conclusion. This generic radiolabeling method has the potential to be a kit-based fluorine-18 labeling strategy, and could have a large impact on PET radiochemical space, potentially enabling the development of many new fluorine-18 labeled protein-based radiotracers.

  15. Pancreatic cancer detected by positron emission tomography with 18F-labelled deoxyglucose: method and first results.

    PubMed

    Bares, R; Klever, P; Hellwig, D; Hauptmann, S; Fass, J; Hambuechen, U; Zopp, L; Mueller, B; Buell, U; Schumpelick, V

    1993-07-01

    In order to evaluate the utility of positron emission tomography (PET) with 18F-labelled deoxyglucose (FDG) for detection of pancreatic cancer 15 patients with pancreatic masses shown by computed tomography were investigated. Static PET scans covering an axial field of view of 15 cm were obtained 45 min after intravenous injection of 150-300 MBq FDG. Focally increased FDG accumulation was present in 12 out of 13 patients with histologically proven adenocarcinoma, in particular in eight of nine lymph node and four of five liver metastases. Scans of two patients with chronic pancreatitis confirmed by surgery revealed a normal FDG distribution. Contrast between tumour and normal tissue depended the metabolic situation prior to FDG injection. High ratios were found in fasting patients whereas no elevated FDG uptake was measured in an insulin-dependent diabetic suffering from carcinoma of the pancreatic head. We conclude that FDG PET might have the potential for detection and even differentiation of pancreatic carcinoma from chronic pancreatitis. Further studies are necessary to substantiate these preliminary findings and to optimize results in diabetic patients.

  16. New Chelators for Low Temperature Al(18)F-Labeling of Biomolecules.

    PubMed

    Cleeren, Frederik; Lecina, Joan; Billaud, Emilie M F; Ahamed, Muneer; Verbruggen, Alfons; Bormans, Guy M

    2016-03-16

    The Al(18)F labeling method is a relatively new approach that allows radiofluorination of biomolecules such as peptides and proteins in a one-step procedure and in aqueous solution. However, the chelation of the {Al(18)F}(2+) core with the macrocyclic chelators NOTA or NODA requires heating to 100-120 °C. Therefore, we have developed new polydentate ligands for the complexation of {Al(18)F}(2+) with good radiochemical yields at a temperature of 40 °C. The stability of the new Al(18)F-complexes was tested in phosphate buffered saline (PBS) at pH 7.4 and in rat serum. The stability of the Al(18)F-L3 complex was found to be comparable to that of the previously reported Al(18)F-NODA complex up to 60 min in rat serum. Moreover, the biodistribution of Al(18)F-L3 in healthy mice showed the absence of in vivo defluorination since no significant bone uptake was observed, whereas the major fraction of activity at 60 min p.i. was observed in liver and intestines, indicating hepatobiliary clearance of the radiolabeled ligand. The acyclic chelator H3L3 proved to be a good lead candidate for labeling of heat-sensitive biomolecules with fluorine-18. In order to obtain a better understanding of the different factors influencing the formation and stability of the complex, we carried out more in-depth experiments with ligand H3L3. As a proof of concept, we successfully conjugated the new AlF-chelator with the urea-based PSMA inhibitor Glu-NH-CO-NH-Lys to form Glu-NH-CO-NH-Lys(Ahx)L3, and a biodistribution study in healthy mice was performed with the Al(18)F-labeled construct. This new class of AlF-chelators may have a great impact on PET radiochemical space as it will stimulate the rapid development of new fluorine-18 labeled peptides and other heat-sensitive biomolecules.

  17. Synthesis of [18F]-labelled Maltose Derivatives as PET Tracers for Imaging Bacterial Infection

    PubMed Central

    Namavari, Mohammad; Gowrishankar, Gayatri; Hoehne, Aileen; Jouannot, Erwan; Gambhir, Sanjiv S

    2015-01-01

    Purpose To develop novel positron emission tomography (PET) agents for visualization and therapy monitoring of bacterial infections. Procedures It is known that maltose and maltodextrins are energy sources for bacteria. Hence, 18F-labelled maltose derivatives could be a valuable tool for imaging bacterial infections. We have developed methods to synthesize 4-O-(α-D-glucopyranosyl)-6-deoxy-6-[18F]fluoro-D-glucopyranoside (6-[18F]fluoromaltose) and 4-O-(α-D-glucopyranosyl)-1-deoxy-1-[18F]fluoro-D-glucopyranoside (1-[18F]fluoromaltose) as bacterial infection PET imaging agents. 6-[18F]fluoromaltose was prepared from precursor 1,2,3-tri-O-acetyl-4-O-(2′,3′,-di-O-acetyl-4′,6′-benzylidene-α-D-glucopyranosyl)-6-deoxy-6-nosyl-D-glucopranoside (5). The synthesis involved the radio-fluorination of 5 followed by acidic and basic hydrolysis to give 6-[18F]fluoromaltose. In an analogous procedure, 1-[18F]fluoromaltose was synthesized from 2,3, 6-tri-O-acetyl-4-O-(2′,3′,4′,6-tetra-O-acetyl-α-D-glucopyranosyl)-1-deoxy-1-O-triflyl-D-glucopranoside (9). Stability of 6-[18F]fluoromaltose in phosphate-buffered saline (PBS) and human and mouse serum at 37 °C was determined. Escherichia coli uptake of 6-[18F]fluoromaltose was examined. Results A reliable synthesis of 1- and 6-[18F]fluoromaltose has been accomplished with 4–6 and 5–8 % radiochemical yields, respectively (decay-corrected with 95 % radiochemical purity). 6-[18F]fluoromaltose was sufficiently stable over the time span needed for PET studies (~96 % intact compound after 1-h and ~65 % after 2-h incubation in serum). Bacterial uptake experiments indicated that E. coli transports 6-[18F]fluoromaltose. Competition assays showed that the uptake of 6-[18F]fluoromaltose was completely blocked by co-incubation with 1 mM of the natural substrate maltose. Conclusion We have successfully synthesized 1- and 6-[18F]fluoromaltose via direct fluorination of appropriate protected maltose precursors. Bacterial uptake

  18. sup 18 F-labeled insulin: A prosthetic group methodology for incorporation of a positron emitter into peptides and proteins

    SciTech Connect

    Shai, Y.; Kirk, K.L.; Channing, M.A.; Dunn, B.B.; Lesniak, M.A.; Eastman, R.C.; Finn, R.D.; Roth, J.; Jacobson, K.A. )

    1989-05-30

    In the present study we synthesize {sup 18}F-labeled insulin of high specific radioactivity. A new prosthetic group methodology, in which ({sup 18}F)fluoride displaces a bromide group of 4-(bromomethyl)-benzoylamine intermediates, was used. The 4-(fluoromethyl)benzoyl product was chemically stable. {sup 18}F-Labeled insulin retains the essential biological properties of native insulin, as measured in vitro by binding to insulin receptors on human cells and stimulation of glucose metabolism in rat adipocytes. The overall process can be carried out speedily to yield a product of sufficient purity to permit in vivo studies. The method appears to be applicable to a wide variety of peptides.

  19. 18F-Labeled Insulin: A Prosthetic Group Methodology for Incorporation of a Positron Emitter into Peptides and Proteins†

    PubMed Central

    Shai, Yechiel; Kirk, Kenneth L.; Channing, Michael A.; Dunn, Bonnie B.; Lesniak, Maxine A.; Eastman, Richard C.; Finn, Ronald D.; Roth, Jesse; Jacobson, Kenneth A.

    2012-01-01

    In the present study we synthesize 18F-labeled insulin of high specific radioactivity. A new prosthetic group methodology, in which [18F]fluoride displaces a bromide group of 4-(bromomethyl)-benzoylamine intermediates, was used. The 4-(fluoromethyl)benzoyl product was chemically stable. 18F-Labeled insulin retains the essential biological properties of native insulin, as measured in vitro by binding to insulin receptors on human cells and stimulation of glucose metabolism in rat adipocytes. The overall process can be carried out speedily to yield a product of sufficient purity to permit in vivo studies. The method appears to be applicable to a wide variety of peptides. PMID:2669963

  20. Mild and regiospecific synthesis of 18F-labelled vinyl fluoride using [18F]fluorine reacted with silane.

    PubMed

    Di Raddo, P; Diksic, M

    1985-12-01

    A labelled vinyl fluoride of biological interest was prepared in good radiochemical yield by direct fluorination of the corresponding silane. The synthesis of 18F-labelled 4-fluoroantipyrine, a cerebral blood flow tracer, involved the reaction of 4-(trimethylsilyl) antipyrine with [18F]F2 (0.5% fluorine in neon) or 5% F2 in nitrogen in freon-11 as solvent. A radiochemical (chemical) yield of about 18% (42%) was obtained in a 25-min synthesis. The radiochemical and chemical purity of the final products was 99% after purification by HPLC.

  1. Synthesis and preliminary evaluation of [18F]-labeled 2-oxoquinoline derivatives for PET imaging of cannabinoid CB2 receptor

    PubMed Central

    Turkman, Nashaat; Paolillo, Vincenzo; Shavrin, Aleksander; Yeh, Hsin Hsien; Flores, Leo; Soghomonian, Suren; Ravinovich, Brian; Volgin, Andrei; Gelovani, Juri; Alauddin, Mian

    2011-01-01

    Introduction The cannabinoid receptor type 2 (CB2) is an important target for development of drugs and imaging agents for diseases, such as neuroinflammation, neurodegeneration, and cancer. Recently we reported synthesis and results of in vitro receptor binding of a focused library of fluorinated 2-oxoquinoline derivatives as CB2 receptor ligands. Some of the compounds demonstrated as good CB2-specific ligands with Ki values in the nanomolar to sub-nanomolar concentrations; therefore, we pursued the development of their 18F-labeled analogues that should be useful for PET imaging of CB2 receptor expression. Here, we report the radiosynthesis of two 18F-labeled 2-oxoquinoline derivatives, and preliminary in vitro and ex-vivo evaluation of one compound as a CB2-specific radioligand. Methods 4-[18F]Fluorobenzyl amine [18F]-3 was prepared by radiofluorination of 4-cyano-N,N,N-trimethylanilinium triflate salt followed by reduction with LiAlH4 and then coupled with acid chlorides 11 and 12 to afford [18F]-13 and [18F]-14. In vitro CB2 receptor binding assay was performed using U87 cells transduced with CB2- and CB1-receptor. Ex-vivo autoradiography was performed with [18F]-14 on spleen, CB2- and CB1-expressing and wild type U87 subcutaneous tumors grown in mice. Results The radiochemical yields of [18F]-13 and [18F]-14 were 10%-15.0% with an average of 12% (n=10); radiochemical purity was > 99% with specific activity 1200 mCi/μmole. The dissociation constant Kd for [18F]-14 was 3.4 nM. Ex-vivo autoradiography showed accumulation of [18F]-14 in the CB2-expressing tumor. Conclusion Two new [18F]-labeled CB2 ligands have been synthesized. Compound [18F]-14 appears to be a potential PET imaging agent for the assessment of CB2 receptor expression in vivo. PMID:22226022

  2. Comparison of Two Site-Specifically 18F-Labeled Affibodies for PET Imaging of EGFR Positive Tumors

    PubMed Central

    2015-01-01

    The epidermal growth factor receptor (EGFR) serves as an attractive target for cancer molecular imaging and therapy. Our previous positron emission tomography (PET) studies showed that the EGFR-targeting affibody molecules 64Cu-DOTA-ZEGFR:1907 and 18F-FBEM-ZEGFR:1907 can discriminate between high and low EGFR-expression tumors and have the potential for patient selection for EGFR-targeted therapy. Compared with 64Cu, 18F may improve imaging of EGFR-expression and is more suitable for clinical application, but the labeling reaction of 18F-FBEM-ZEGFR:1907 requires a long synthesis time. The aim of the present study is to develop a new generation of 18F labeled affibody probes (Al18F-NOTA-ZEGFR:1907 and 18F-CBT-ZEGFR:1907) and to determine whether they are suitable agents for imaging of EGFR expression. The first approach consisted of conjugating ZEGFR:1907 with NOTA and radiolabeling with Al18F to produce Al18F-NOTA-ZEGFR:1907. In a second approach the prosthetic group 18F-labeled-2-cyanobenzothiazole (18F-CBT) was conjugated to Cys-ZEGFR:1907 to produce 18F-CBT-ZEGFR:1907. Binding affinity and specificity of Al18F-NOTA-ZEGFR:1907 and 18F-CBT-ZEGFR:1907 to EGFR were evaluated using A431 cells. Biodistribution and PET studies were conducted on mice bearing A431 xenografts after injection of Al18F-NOTA-ZEGFR:1907 or 18F-CBT-ZEGFR:1907 with or without coinjection of unlabeled affibody proteins. The radiosyntheses of Al18F-NOTA-ZEGFR:1907 and 18F-CBT-ZEGFR:1907 were completed successfully within 40 and 120 min with a decay-corrected yield of 15% and 41% using a 2-step, 1-pot reaction and 2-step, 2-pot reaction, respectively. Both probes bound to EGFR with low nanomolar affinity in A431 cells. Although 18F-CBT-ZEGFR:1907 showed instability in vivo, biodistribution studies revealed rapid and high tumor accumulation and quick clearance from normal tissues except the bones. In contrast, Al18F-NOTA-ZEGFR:1907 demonstrated high in vitro and in vivo stability, high tumor uptake

  3. Design, synthesis and evaluation of (18)F-labeled bradykinin B1 receptor-targeting small molecules for PET imaging.

    PubMed

    Zhang, Zhengxing; Kuo, Hsiou-Ting; Lau, Joseph; Jenni, Silvia; Zhang, Chengcheng; Zeisler, Jutta; Bénard, François; Lin, Kuo-Shyan

    2016-08-15

    Two fluorine-18 ((18)F) labeled bradykinin B1 receptor (B1R)-targeting small molecules, (18)F-Z02035 and (18)F-Z02165, were synthesized and evaluated for imaging with positron emission tomography (PET). Z02035 and Z02165 were derived from potent antagonists, and showed high binding affinity (0.93±0.44 and 2.80±0.50nM, respectively) to B1R. (18)F-Z02035 and (18)F-Z02165 were prepared by coupling 2-[(18)F]fluoroethyl tosylate with their respective precursors, and were obtained in 10±5 (n=4) and 22±14% (n=3), respectively, decay-corrected radiochemical yield with >99% radiochemical purity. (18)F-Z02035 and (18)F-Z02165 exhibited moderate lipophilicity (LogD7.4=1.10 and 0.59, respectively), and were stable in mouse plasma. PET imaging and biodistribution studies in mice showed that both tracers enabled visualization of the B1R-positive HEK293T::hB1R tumor xenografts with better contrast than control B1R-negative HEK293T tumors. Our data indicate that small molecule antagonists can be used as pharmacophores for the design of B1R-targeting PET tracers.

  4. Synthesis and evaluation of 18F-labeled ATP competitive inhibitors of topoisomerase II as probes for imaging topoisomerase II expression

    PubMed Central

    Daumar, Pierre; Zeglis, Brian M.; Ramos, Nicholas; Divilov, Vadim; Sevak, Kuntal Kumar; Pillarsetty, NagaVaraKishore; Lewis, Jason S.

    2015-01-01

    Type II topoisomerase (Topo-II) is an ATP-dependent enzyme that is essential in the transcription, replication, and chromosome segregation processes and, as such, represents an attractive target for cancer therapy. Numerous studies indicate that the response to treatment with Topo-II inhibitors is highly dependent on both the levels and the activity of the enzyme. Consequently, a non-invasive assay to measure tumoral Topo-II levels has the potential to differentiate responders from non-responders. With the ultimate goal of developing a radiofluorinated tracer for positron emission tomography (PET) imaging, we have designed, synthesized, and evaluated a set of fluorinated compounds based on the structure of the ATP-competitive Topo-II inhibitor QAP1. Compounds 18 and 19b showed inhibition of Topo-II in in vitro assays and exhibited moderate, Topo-II level dependent cytotoxicity in SK-BR-3 and MCF-7 cell lines. Based on these results, 18F-labeled analogs of these two compounds were synthesized and evaluated as PET probes for imaging Topo-II overexpression in mice bearing SK-BR-3 xenografts. [18F]-18 and [18F]-19b were synthesized from their corresponding protected tosylated derivatives by fluorination and subsequent deprotection. Small animal PET imaging studies indicated that both compounds do not accumulate in tumors and exhibit poor pharmacokinetics, clearing from the blood pool very rapidly and getting metabolized over. The insights gained from the current study will surely aid in the design and construction of future generations of PET agents for the non-invasive delineation of Topo-II expression. PMID:25240701

  5. Comparison of 18F-Labeled Fluoroalkylphosphonium Cations with 13N-NH3 for PET Myocardial Perfusion Imaging.

    PubMed

    Kim, Dong-Yeon; Kim, Hyeon Sik; Reder, Sybille; Zheng, Jin Hai; Herz, Michael; Higuchi, Takahiro; Pyo, A Young; Bom, Hee-Seung; Schwaiger, Markus; Min, Jung-Joon

    2015-10-01

    Despite substantial advances in the diagnosis of cardiovascular disease, there is a need for 18F-labeled myocardial perfusion agents for the diagnosis of ischemic heart disease because current PET tracers for myocardial perfusion imaging have a short half-life that limits their widespread clinical use in PET. Thus, 18F-labeled fluoroalkylphosphonium derivatives (18F-FATPs), including (5-18F-fluoropentyl)triphenylphosphonium cation (18F-FPTP), (6-18F-fluorohexyl)triphenylphosphonium cation (18F-FHTP), and (2-(2-18F-fluoroethoxy)ethyl)triphenylphosphonium cation (18F-FETP), were synthesized. The myocardial extraction and image quality of the 18F-FATPs were compared with those of 13N-NH3 in rat models. The first-pass extraction fraction (EF) values of the 18F-FATPs (18F-FPTP, 18F-FHTP, 18F-FETP) and 13N-NH3 were measured in isolated rat hearts perfused with the Langendorff method (flow velocities, 0.5, 4.0, 8.0, and 16.0 mL/min). Normal and myocardial infarction rats were imaged with small-animal PET after intravenous injection of 37 MBq of 18F-FATPs and 13N-NH3. To determine pharmacokinetics, a region of interest was drawn around the heart, and time-activity curves of the 18F-FATPs and 13N-NH3 were generated to obtain the counts per pixel per second. Defect size was analyzed on the basis of polar map images of 18F-FATPs and 13N-NH3. The EF values of 18F-FATPs and 13N-NH3 were comparable at low flow velocity (0.5 mL/min), whereas at higher flows EF values of 18F-FATPs were significantly higher than those of 13N-NH3 (4.0, 8.0, and 16.0 mL/min, P<0.05). Myocardium-to-liver ratios of 18F-FPTP, 18F-FHTP, 18F-FETP, and 13N-NH3 were 2.10±0.30, 4.36±0.20, 3.88±1.03, and 0.70±0.09, respectively, 10 min after injection, whereas myocardium-to-lung ratios were 5.00±0.25, 4.33±0.20, 7.98±1.23, and 2.26±0.14, respectively. Although 18F-FATPs and 13N-NH3 sharply delineated myocardial perfusion defects, defect size on the 13N-NH3 images was significantly smaller than on the

  6. Preclinical characterization of a novel class of 18F-labeled PET tracers for amyloid-β.

    PubMed

    Brockschnieder, Damian; Schmitt-Willich, Heribert; Heinrich, Tobias; Varrone, Andrea; Gulyás, Balázs; Toth, Miklos; Andersson, Jan; Boemer, Ulf; Krause, Sabine; Friebe, Matthias; Dinkelborg, Ludger; Halldin, Christer; Dyrks, Thomas

    2012-11-01

    Imaging of amyloid-β (Aβ) plaques by PET is more and more integrated into concepts for Alzheimer disease (AD) diagnosis and drug development. The objective of this study was to find novel chemical entities that can be transformed into (18)F-labeled Aβ tracers with favorable brain washout kinetics and low background signal. High-throughput screening of a large chemical library was used to identify new ligands for fibrillar aggregates of Aβ(1-42) peptide. Thirty-two fluorinated derivatives were synthesized and tested for their affinity toward AD brain homogenate. Twelve ligands have been radiolabeled with (18)F. The pharmacokinetic properties of the radioligands were investigated in mouse and monkey biodistribution studies. Binding characteristics were determined by autoradiography of AD brain sections in vitro and using amyloid precursor protein transgenic mice in vivo. The systematic search for Aβ imaging agents revealed several fluorinated derivatives with nanomolar affinity for Aβ. The fluoropyridyl derivative BAY 1008472 showed a high initial brain uptake (6.45 percentage injected dose per gram at 2 min) and rapid brain washout (ratio of percentage of injected dose per gram of tissue at 2 and 30 min after injection, 9.2) in mice. PET studies of healthy rhesus monkeys confirmed the high initial brain uptake of BAY 1008472 (2.52 standardized uptake value at peak) and a fast elimination of total radioactivity from gray and white matter areas (ratio of standardized uptake value at peak uptake and 60 min 11.0). In autoradiographic analysis, BAY 1008472 selectively detected Aβ deposits in human AD brain sections with high contrast and did not bind to τ- or α-synuclein pathologies. Finally, ex vivo autoradiography of brain sections from amyloid precursor protein-transgenic mice confirmed that BAY 1008472 is indeed suitable for the in vivo detection of Aβ plaques. A new chemical class of Aβ tracers has been identified by high-throughput screening. The

  7. A high-affinity [18F]-labeled phosphoramidate peptidomimetic PSMA-targeted inhibitor for PET imaging of prostate cancer

    PubMed Central

    Ganguly, Tanushree; Dannoon, Shorouk; Hopkins, Mark R.; Murphy, Stephanie; Cahaya, Hendry; Blecha, Joseph E.; Jivan, Salma; Drake, Christopher R.; Barinka, Cyril; Jones, Ella F.; VanBrocklin, Henry F.; Berkman, Clifford E.

    2015-01-01

    Introduction In this study, a structurally modified phosphoramidate scaffold, with improved prostate-specific membrane antigen (PSMA) avidity, stability and in vivo characteristics, as a PET imaging agent for prostate cancer (PCa), was prepared and evaluated. Methods p-Fluorobenzoyl-aminohexanoate and 2-(3-hydroxypropyl)glycine were introduced into the PSMA-targeting scaffold yielding phosphoramidate 5. X-ray crystallography was performed on the PSMA/5 complex. [18F]5 was synthesized, and cell uptake and internalization studies were conducted in PSMA(+) LNCaP and CWR22Rv1 cells and PSMA(−) PC-3 cells. In vivo PET imaging and biodistribution studies were performed at 1 and 4 h post injection in mice bearing CWR22Rv1 tumor, with or without blocking agent. Results The crystallographic data showed interaction of the p-fluorobenzoyl group with an arene-binding cleft on the PSMA surface. In vitro studies revealed elevated uptake of [18F]5 in PSMA(+) cells (2.2% in CWR22Rv1 and 12.1% in LNCaP) compared to PSMA(−) cells (0.08%) at 4 h. In vivo tumor uptake of 2.33% ID/g and tumor-to-blood ratio of 265:1 was observed at 4 h. Conclusions We have successfully synthesized, radiolabeled and evaluated a new PSMA-targeted PET agent. The crystal structure of the PSMA/5 complex highlighted the interactions within the arene-binding cleft contributing to the overall complex stability. The high target uptake and rapid non-target clearance exhibited by [18F]5 in PSMA(+) xenografts substantiates its potential use for PET imaging of PCa. Advances in Knowledge The only FDA-approved imaging agent for PCa, Prostascint®, targets PSMA but suffers from inherent shortcomings. The data acquired in this manuscript confirmed that our new generation of [18F]-labeled PSMA inhibitor exhibited promising in vivo performance as a PET imaging agent for PCa and is well-positioned for subsequent clinical trials. Implications for Patient Care Our preliminary data demonstrate that this tracer possesses

  8. Fluorine-18 labeling of small molecules: the use of 18F-labeled aryl fluorides derived from no-carrier-added [18F]fluoride as labeling precursors.

    PubMed

    Wuest, F

    2007-01-01

    The favourable long-half life, the ease of production and the low energy of the emitted positron make 18F an ideal radionuclide for PET imaging. Radiochemistry of 18F basically relies on two distinctive types of reactions: nucleophilic and electrophilic reactions. All syntheses of 18F-labeled radiotracers are based on either [18F]fluoride ion or [18F]fluorine gas as simple primary labeling precursors which are obtained directly from the cyclotron. They can be applied either directly to the radiosynthesis or they can be transformed into more complex labeling precursors enabling the multi-step build-up of organic tracer molecules. The topic of this review is a survey on the application of several 18F-labeled aryl fluorides as building blocks derived from no-carrier-added (n.c.a.) [18F] fluoride to build up small monomeric PET radiotracers at high specific radioactivity by multi-step synthesis procedures.

  9. The Effect of the Prosthetic Group on the Pharmacologic Properties of 18F-labeled Rhodamine B, a Potential Myocardial Perfusion Agent for PET

    PubMed Central

    Bartholomä, Mark D.; Gottumukkala, Vijay; Zhang, Shaohui; Baker, Amanda; Dunning, Patricia; Fahey, Frederic H.; Treves, S. Ted; Packard, Alan B.

    2013-01-01

    We recently reported the development of the 2-[18F]fluoroethyl ester of rhodamine B as a potential positron emission tomography (PET) tracer for myocardial perfusion imaging. This compound, which was prepared using a [18F]fluoroethyl prosthetic group, has significant uptake in the myocardium in rats, but also demonstrates relatively high liver uptake and is rapidly hydrolyzed in vivo in mice. We have now prepared 18F-labeled rhodamine B using three additional prosthetic groups (propyl, diethylene glycol, and triethylene glycol) and found that the prosthetic group has a significant effect on the in vitro and in vivo properties of these compounds. Of the esters prepared to date, the diethylene glycol ester is superior in terms of in vitro stability and pharmacokinetics. These observations suggest that the prosthetic group plays a significant role in determining the pharmacological properties of 18F-labeled compounds. They also support the value of continued investigation of 18F-labeled rhodamines as PET radiopharmaceuticals for myocardial perfusion imaging. PMID:23210516

  10. Synthesis and evaluation of an (18)F-labeled pyrimidine-pyridine amine for targeting CXCR4 receptors in gliomas.

    PubMed

    Demoin, Dustin Wayne; Shindo, Masahiro; Zhang, Hanwen; Edwards, Kimberly J; Serganova, Inna; Pillarsetty, Naga Vara Kishore; Lewis, Jason S; Blasberg, Ronald G

    2016-10-01

    Chemokine receptor-4 (CXCR4, fusin, CD184) is expressed on several tissues involved in immune regulation and is upregulated in many diseases including malignant gliomas. A radiolabeled small molecule that readily crosses the blood-brain barrier can aid in identifying CXCR4-expressing gliomas and monitoring CXCR4-targeted therapy. In the current work, we have synthesized and evaluated an [(18)F]-labeled small molecule based on a pyrimidine-pyridine amine for its ability to target CXCR4. The nonradioactive standards and the nitro precursor used in this study were prepared using established methods. An HPLC method was developed to separate the nitro-precursor from the nonradioactive standard and radioactive product. The nitro-precursor was radiolabeled with (18)F under inert, anhydrous conditions using the [(18)F]-kryptofix 2.2.2 complex to form the desired N-(4-(((6-[(18)F]fluoropyridin-2-yl)amino)methyl)benzyl)pyrimidin-2-amine ([(18)F]-3). The purified radiolabeled compound was used in serum stability, partition coefficient, cellular uptake, and in vivo cancer targeting studies. [(18)F]-3 was synthesized in 4-10% decay-corrected yield (to start of synthesis). [(18)F]-3 (tR ≈ 27 min) was separated from the precursor (tR ≈ 30 min) using a pentafluorophenyl column with an isocratic solvent system. [(18)F]-3 displayed acceptable serum stability over 2 h. The amount of [(18)F]-3 bound to the plasma proteins was determined to be > 97%. The partition coefficient (LogD7.4) is 1.4 ± 0.5. Competitive in vitro inhibition indicated 3 does not inhibit uptake of (67)Ga-pentixafor. Cell culture media incubation and ex vivo urine analysis indicate rapid metabolism of [(18)F]-3 into hydrophilic metabolites. Thus, in vitro uptake of [(18)F]-3 in CXCR4 overexpressing U87 cells (U87 CXCR4) and U87 WT indicated no specific binding. In vivo studies in mice bearing U87 CXCR4 and U87 WT tumors on the left and right shoulders were carried out using [(18)F]-3 and (68)Ga-pentixafor on

  11. Synthesis and in vitro and in vivo evaluation of an (18)F-labeled neuropeptide Y analogue for imaging of breast cancer by PET.

    PubMed

    Hofmann, Sven; Maschauer, Simone; Kuwert, Torsten; Beck-Sickinger, Annette G; Prante, Olaf

    2015-04-06

    Imaging of Y1R expression in breast cancer is still a challenging task. Herein, we report a suitable (18)F-labeled high-molecular-weight glycopeptide for imaging of peripheral neuropeptide Y (NPY) Y1 receptor (Y1R)-positive tumors by preclinical small-animal positron emission tomography (PET). The Y1R-preferring NPY [F(7),P(34)]NPY analogue was functionalized with an alkyne-bearing propargylglycine (Pra) in position 4. The corresponding fluoroglycosylated (FGlc) peptide analogue [Pra(4)(FGlc),F(7),P(34)]NPY and its (18)F-labeled analogue were synthesized by click chemistry-based fluoroglycosylation. The radiosynthesis was performed by (18)F-fluoroglycosylation starting from the 2-triflate of the β-mannosylazide and the alkyne peptide [Pra(4),F(7),P(34)]NPY. The radiosynthesis of the(18)F-labeled analogue was optimized using a minimum amount of peptide precursor (40 nmol), proceeding with an overall radiochemical yield of 20-25% (nondecay corrected) in a total synthesis time of 75 min with specific activities of 40-70 GBq/μmol. In comparison to NPY and [F(7),P(34)]NPY, in vitro Y1R and Y2R activation studies with the cold [Pra(4)(FGlc),F(7),P(34)]NPY on stably transfected COS-7 cells displayed a high potency for the induction of Y1R-specific inositol accumulation (pEC50 = 8.5 ± 0.1), whereas the potency at Y2R was significantly decreased. Internalization studies on stably transfected HEK293 cells confirmed a strong glycopeptide-mediated Y1R internalization and a substantial Y1R subtype selectivity over Y2R. In vitro autoradiography with Y1R-positive MCF-7 tumor tissue slices indicated high specific binding of the (18)F-labeled glycopeptide, when binding was reduced by 95% ([Pra(4),F(7),P(34)]NPY) and by 86% (BIBP3226 Y1R antagonist) in competition studies. Biodistribution and small-animal PET studies on MCF-7 breast tumor-bearing nude mice revealed radiotracer uptake in the MCF-7 tumor of 1.8%ID/g at 20 min p.i. and 0.7%ID/g at 120 min p.i. (n = 3-4), increasing

  12. Analysis of 18F-labelled synthesis products on TLC plates: comparison of radioactivity scanning, film autoradiography, and a phosphoimaging technique.

    PubMed

    Kämäräinen, Eeva-Liisa; Haaparanta, Merja; Siitari-Kauppi, Marja; Koivula, Teija; Lipponen, Tiina; Solin, Olof

    2006-09-01

    We compared radioactivity scanning, film autoradiography, and digital photostimulated luminescence (PSL) autoradiography (phosphoimaging technique) in detection of radioactivity on thin-layer chromatography (TLC) plates. TLC combined with radioactivity detection is rapid, simple, and relatively flexible. Here, (18)F-labelled synthesis products were analyzed by TLC and the radioactivity distribution on the plates determined using the three techniques. Radioactivity scanning is appropriate only with good chromatographic resolution and previously validated scanning parameters. Film autoradiography exhibits poor linearity if radioactivity varies greatly. PSL provides high sensitivity and resolution and superior linearity compared with the other methods.

  13. Preparation of 18F-labeled peptides using the copper(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition.

    PubMed

    Gill, Herman S; Marik, Jan

    2011-10-13

    An optimized procedure for preparing fluorine-18 ((18)F)-labeled peptides by the copper-catalyzed azide-alkyne 1,3-dipolar cyloaddition (CuAAC) is presented here. The two-step radiosynthesis begins with the microwave-assisted nucleophilic (18)F-fluorination of a precursor containing a terminal p-toluenesulfonyl, terminal azide and polyethylene glycol backbone. The resulting (18)F-fluorinated azide-containing building block is coupled to an alkyne-decorated peptide by the CuAAC. The reaction is accelerated by the copper(I)-stabilizing ligand bathophenanthroline disulfonate and can be performed in either reducing or nonreducing conditions (e.g., to preserve disulfide bonds). After an HPLC purification, (18)F-labeled peptide can be obtained with a 31 ± 6% radiochemical yield (n = 4, decay-corrected from (18)F-fluoride elution) and a specific activity of 39.0 ± 12.4 Ci μmol(-1) within 77 ± 4 min.

  14. 18F-labeled resin microspheres as surrogates for 90Y resin microspheres used in the treatment of hepatic tumors: a radiolabeling and PET validation study

    NASA Astrophysics Data System (ADS)

    Selwyn, R. G.; Avila-Rodriguez, M. A.; Converse, A. K.; Hampel, J. A.; Jaskowiak, C. J.; McDermott, J. C.; Warner, T. F.; Nickles, R. J.; Thomadsen, B. R.

    2007-12-01

    90Y-labeled resin microspheres (SIR-Spheres®) are currently used to treat patients with primary and metastatic solid liver tumors. This treatment is typically palliative since patients have exhausted all other standard treatment options. Improving the quality of life and extending patient survival are typical benchmarks for tracking patient response. However, the current method for predicting microsphere biodistributions with 99mTc-labeled macroaggregated albumin (MAA) does not correlate well with patient response. This work presents the development of a new 18F-labeled resin microsphere to serve as a surrogate for the treatment microsphere and to employ the superior resolution and sensitivity of positron emission tomography (PET). The 18F microsphere biodistributions were determined in a rabbit using PET imaging and histological review. The PET-based uptake ratio was shown to agree with the histological findings to better than 3%. In addition, the radiolabeling process was shown to be rapid, efficient and relatively stable in vivo.

  15. In vivo biodistribution of two ( sup 18 F)-labelled muscarinic cholinergic receptor ligands: 2-( sup 18 F)- and 4-( sup 18 F)-fluorodexetimide

    SciTech Connect

    Wilson, A.A.; Scheffel, U.A.; Dannals, R.F.; Stathis, M.; Ravert, H.T.; Wagner, H.N. Jr. )

    1991-01-01

    Two ({sup 18}F)-labelled analogues of the potent muscarinic cholinergic receptor (m-AChR) antagonist, dexetimide, were evaluated as potential ligands for imaging m-AChR by positron emission tomography (PET). Intravenous administration of both 2-({sup 18}F)- or 4-({sup 18}F)-fluorodexetimide resulted in high brain uptake of radioactivity in mice. High binding levels were observed in m-AChR rich areas, such as cortex and striatum, with low levels in the receptor-poor cerebellum. Uptake of radioactivity was saturable and could be blocked by pre-administration of dexetimide or atropine. Drugs with different sites of action were ineffective at blocking receptor binding. The results indicate that both radiotracers are promising candidates for use in PET studies.

  16. ASSESSMENT OF THE LOCAL EXPOSURE OF SKIN ON HANDS OF NUCLEAR MEDICINE WORKERS HANDLING 18F-LABELLED RADIOPHARMACEUTICALS: PRELIMINARY CZECH STUDY.

    PubMed

    Hudzietzová, J; Fülöp, M; Sabol, J; Doležal, J

    2016-12-01

    The article summarises some preliminary results of the assessment of the exposure of hands of workers manipulating (18)F-labelled radiopharmaceuticals based on personal monitoring at two nuclear medicine clinics in the Czech Republic. The measurements were carried out using special thermoluminescence dosemeters the readings of which could be interpreted in terms of the personal dose equivalent Hp(0.07) approximating the equivalent dose to the skin at various locations on the surface of both hands. The results have shown that out of 21 workers monitored, ∼43 % (preparation and applications of radiopharmaceuticals) may reach an exposure equal to three-tenth of the annual dose limit to the skin. At the same time, it can also be concluded that in ∼10 % cases of workers, the relevant dose limit may be exceeded. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  17. Early identification of antigen-specific immune responses in vivo by [18F]-labeled 3'-fluoro-3'-deoxy-thymidine ([18F]FLT) PET imaging.

    PubMed

    Aarntzen, Erik H J G; Srinivas, Mangala; De Wilt, Johannes H W; Jacobs, Joannes F M; Lesterhuis, W Joost; Windhorst, Albert D; Troost, Esther G; Bonenkamp, Johannes J; van Rossum, Michelle M; Blokx, Willeke A M; Mus, Roel D; Boerman, Otto C; Punt, Cornelis J A; Figdor, Carl G; Oyen, Wim J G; de Vries, I Jolanda M

    2011-11-08

    Current biomarkers are unable to adequately predict vaccine-induced immune protection in humans with infectious disease or cancer. However, timely and adequate assessment of antigen-specific immune responses is critical for successful vaccine development. Therefore, we have developed a method for the direct assessment of immune responses in vivo in a clinical setting. Melanoma patients with lymph node (LN) metastases received dendritic cell (DC) vaccine therapy, injected intranodally, followed by [(18)F]-labeled 3'-fluoro-3'-deoxy-thymidine ([(18)F]FLT) PET at varying time points after vaccination. Control LNs received saline or DCs without antigen. De novo immune responses were readily visualized in treated LNs early after the prime vaccination, and these signals persisted for up to 3 wk. This selective [(18)F]FLT uptake was markedly absent in control LNs, although tracer uptake in treated LNs increased profoundly with as little as 4.5 × 10(5) DCs. Immunohistochemical staining confirmed injected DC dispersion to T-cell areas and resultant activation of CD4(+) and CD8(+) T cells. The level of LN tracer uptake significantly correlates to the level of circulating antigen-specific IgG antibodies and antigen-specific proliferation of T cells in peripheral blood. Furthermore, this correlation was not observed with [(18)F]-labeled fluoro-2-deoxy-2-D-glucose. Therefore, [(18)F]FLT PET offers a sensitive tool to study the kinetics, localization, and involvement of lymphocyte subsets in response to vaccination. This technique allows for early discrimination of responding from nonresponding patients in anti-cancer vaccination and aid physicians in individualized decisionmaking.

  18. Synthesis and pre-clinical evaluation of an 18F-labeled single-chain antibody fragment for PET imaging of epithelial ovarian cancer

    PubMed Central

    Sharma, Sai Kiran; Wuest, Melinda; Way, Jenilee D; Bouvet, Vincent R; Wang, Monica; Wuest, Frank R

    2016-01-01

    Anti-CA125 antibodies have been used in immunoassays to quantify levels of shed antigen in the serum of patients who are under surveillance for epithelial ovarian cancer (EOC). However, there is currently no molecular imaging probe in the clinic for the assessment of CA125 expression in vivo. The present study describes the development of an 18F-labeled single-chain variable fragment (scFv) for PET imaging of CA125 in preclinical EOC models. Anti-CA125 scFv was derived from MAb-B43.13 by recombinant expression of the fragment in E.coli. Fragment scFv-B43.13 was purified via immobilized metal affinity chromatography and characterized for antigen binding via immuno-staining and flow cytometry. Prosthetic group N-succinimidyl 4-[18F]fluorobenzoate ([18F]SFB) was used for radiolabeling of scFv-B43.13. Preclinical ovarian cancer models were developed based on ovarian cancer cell lines OVCAR3 (CA125-positive) and SKOV3 (CA125-negative) in NIH-III mice. The radiopharmacological profile of 18F-labeled scFv-B43.13 ([18F]FBz-scFv-B43.13) was studied with PET. [18F]FBz-scFv-B43.13 was prepared in radiochemical yields of 3.7 ± 1.8% (n = 5) at an effective specific activity of 3.88 ± 0.76 GBq/µmol (n = 5). The radiotracer demonstrated selective uptake in CA125-positive OVCAR3 cells and virtually no uptake in CA125-negative SKOV3 cells. Standardized uptake values (SUV) of radioactivity uptake in OVCAR3 tumors was 0.5 (n = 3) and 0.3 (n = 2) in SKOV3 tumors after 60 min post injection (p.i.). PMID:27508105

  19. Fully automated production of diverse 18F-labeled PET tracers on the ELIXYS multi-reactor radiosynthesizer without hardware modification

    PubMed Central

    Lazari, Mark; Collins, Jeffrey; Shen, Bin; Farhoud, Mohammed; Yeh, Daniel; Maraglia, Brandon; Chin, Frederick T.; Nathanson, David A.; Moore, Melissa; van Dam, R. Michael

    2015-01-01

    Fully-automated radiosynthesizers are continuing to be developed to meet the growing need for the reliable production of positron emission tomography (PET) tracers made under current good manufacturing practice (cGMP) guidelines. There is a current trend towards supporting “kit-like” disposable cassettes that come preconfigured for particular tracers, thus eliminating the need for cleaning protocols between syntheses and enabling quick transitions to synthesizing other tracers. Though ideal for production, these systems are often limited for the development of novel tracers due to pressure, temperature, and chemical compatibility considerations. This study demonstrates the versatile use of the ELIXYS fully-automated radiosynthesizer to adapt and produce eight different 18F-labeled PET tracers of varying complexity. Methods Three reactor syntheses of D-[18F]FAC, L-[18F]FMAU, and D-[18F]FEAU along with the one reactor syntheses of D-[18F]FEAU, [18F]FDG, [18F]FLT, [18F]Fallypride, [18F]FHBG, and [18F]SFB were all produced using ELIXYS without the need for any hardware modifications or reconfiguration. Synthesis protocols were adapted, and slightly modified from literature, but not fully optimized. Furthermore, [18F]FLT, [18F]FDG, and [18F]Fallypride were produced sequentially on the same day and used for preclinical imaging of A431 tumor-bearing SCID mice and wild-type BALB/c mice, respectively. To assess future translation to the clinical setting, several batches of tracers were subjected to a full set of quality control tests. Results All tracers were produced with radiochemical yields comparable to those in literature. [18F]FLT, [18F]FDG, and [18F]Fallypride were successfully used to image the mice with results consistent with literature. All tracers subjected to clinical quality control tests passed. Conclusion The ELIXYS radiosynthesizer facilitates rapid tracer development and is capable of producing multiple 18F-labeled PET tracers suitable for clinical

  20. First 18F-labeled ligand for PET imaging of uPAR: In vivo studies in human prostate cancer xenografts☆

    PubMed Central

    Persson, Morten; Liu, Hongguang; Madsen, Jacob; Cheng, Zhen; Kjaer, Andreas

    2014-01-01

    Urokinase-type plasminogen activator receptor (uPAR) is overexpressed in human prostate cancer and uPAR has been found to be associated with metastatic disease and poor prognosis. AE105 is a small linear peptide with high binding affinity to uPAR. We synthesized an N-terminal NOTA-conjugated version (NOTA-AE105) for development of the first 18F-labeled uPAR positron-emission-tomography PET ligand using the Al18F radiolabeling method. In this study, the potential of 18F-AlF-NOTA-AE105 to specifically target uPAR-positive prostate tumors was investigated. Methods NOTA-conjugated AE105 was synthesized and radiolabeled with 18F-AlF according to a recently published optimized protocol. The labeled product was purified by reverse phase high performance liquid chromatography RP-HPLC. The tumor targeting properties were evaluated in mice with subcutaneously inoculated PC-3 xenografts using small animal PET and ex vivo biodistribution studies. uPAR-binding specificity was studied by coinjection of an excess of a uPAR antagonist peptide AE105 analogue (AE152). Results NOTA-AE105 was labeled with 18F-AlF in high radiochemical purity (> 92%) and yield (92.7%) and resulted in a specific activity of greater than 20 GBq/μmol. A high and specific tumor uptake was found. At 1 h post injection, the uptake of 18F-AlF-NOTA-AE105 in PC-3 tumors was 4.22 ± 0.13%ID/g. uPAR-binding specificity was demonstrated by a reduced uptake of 18F-AlF-NOTA-AE105 after coinjection of a blocking dose of uPAR antagonist at all three time points investigated. Good tumor-to-background ratio was observed with small animal PET and confirmed in the biodistribution analysis. Ex vivo uPAR expression analysis on extracted tumors confirmed human uPAR expression that correlated close with tumor uptake of 18F-AlF-NOTA-AE105. Conclusion The first 18F-labeled uPAR PET ligand, 18F-AlF-NOTA-AE105, has successfully been prepared and effectively visualized noninvasively uPAR positive prostate cancer. The favorable in

  1. Synthesis of a potent and selective (18)F-labeled delta-opioid receptor antagonist derived from the Dmt-Tic pharmacophore for positron emission tomography imaging.

    PubMed

    Ryu, Eun Kyoung; Wu, Zhanhong; Chen, Kai; Lazarus, Lawrence H; Marczak, Ewa D; Sasaki, Yusuke; Ambo, Akihiro; Salvadori, Severo; Ren, Chuancheng; Zhao, Heng; Balboni, Gianfranco; Chen, Xiaoyuan

    2008-03-27

    Identification and pharmacological characterization of two new selective delta-opioid receptor antagonists, derived from the Dmt-Tic pharmacophore, of potential utility in positron emission tomography (PET) imaging are described. On the basis of its high delta selectivity, H-Dmt-Tic--Lys(Z)-OH (reference compound 1) is a useful starting point for the synthesis of (18)F-labeled compounds prepared by the coupling of N-succinimidyl 4-[ (18)F]fluorobenzoate ([(18)F]SFB) with Boc-Dmt-Tic--Lys(Z)-OH under slightly basic conditions at 37 degrees C for 15 min, deprotection with TFA, and HPLC purification. The total synthesis time was 120 min, and the decay-corrected radiochemical yield of [(18)F]- 1 was about 25-30% ( n = 5) starting from [(18)F]SFB ( n = 5) with an effective specific activity about 46 GBq/micromol. In vitro autoradiography studies showed prominent uptake of [ (18)F]- 1 in the striatum and cortex with significant blocking by 1 and UFP-501 (selective delta-opioid receptor antagonist), suggesting high specific binding of [(18)F]- 1 to delta-opioid receptors. Noninvasive microPET imaging studies revealed the absence of [(18)F]- 1 in rat brain, since it fails to cross the blood-brain barrier. This study demonstrates the suitability of [ (18)F]- 1 for imaging peripheral delta-opioid receptors.

  2. Radiosynthesis and evaluation of an 18F-labeled positron emission tomography (PET) radioligand for metabotropic glutamate receptor subtype 4 (mGlu4).

    PubMed

    Kil, Kun-Eek; Poutiainen, Pekka; Zhang, Zhaoda; Zhu, Aijun; Choi, Ji-Kyung; Jokivarsi, Kimmo; Brownell, Anna-Liisa

    2014-11-13

    Four 4-phthalimide derivatives of N-(3-chlorophenyl)-2-picolinamide were synthesized as potential ligands for the PET imaging of mGlu4 in the brain. Of these compounds, N-(3-chloro-4-(4-fluoro-1,3-dioxoisoindolin-2-yl)phenyl)-2-picolinamide (3, KALB001) exhibited improved binding affinity (IC50 = 5.1 nM) compared with ML128 (1) and was subsequently labeled with (18)F. When finally formulated in 0.1 M citrate buffer (pH 4) with 10% ethanol, the specific activity of [(18)F]3 at the end of synthesis (EOS) was 233.5 ± 177.8 GBq/μmol (n = 4). The radiochemical yield of [(18)F]3 was 16.4 ± 4.8% (n = 4), and the purity was over 98%. In vivo imaging studies in a monkey showed that the radiotracer quickly penetrated the brain with the highest accumulation in the brain areas known to express mGlu4. Despite some unfavorable radiotracer properties like fast washout in rodent studies, [(18)F]3 is the first (18)F-labeled mGlu4 radioligand, which can be further modified to improve pharmacokinetics and brain penetrability for future human studies.

  3. Synthesis and Evaluation of 18F-labeled Pyridaben Analogues for Myocardial Perfusion Imaging in Mice, Rats and Chinese mini-swine

    PubMed Central

    Mou, Tiantian; Zhao, Zuoquan; You, Linyi; Li, Yesen; Wang, Qian; Fang, Wei; Lu, Jie; Peng, Cheng; Zhang, Xianzhong

    2016-01-01

    This study reports three novel 18F-labeled pyridaben analogues for potential myocardial perfusion imaging (MPI). Three precursors and the corresponding nonradioactive compounds were synthesized and characterized. The radiolabeled tracers were obtained by substituting tosyl with 18F. The total radiosynthesis time of these tracers was 70–90 min. Typical decay-corrected radiochemical yields were 47–58%, with high radiochemical purities (>98%). Tracers were evaluated as MPI agents in vitro, ex vivo and in vivo. In the mouse biodistribution study, all three radiotracers showed high initial heart uptake (34–54% ID/g at 2 min after injection) and fast liver clearance. In the microPET imaging study, [18F]Fmpp2 produced heart images with good quality in both mice and rats. In the whole-body PET/CT images of mini-swine, [18F]Fmpp2 showed excellent initial heart standardized uptake value (SUV) (7.12 at 5 min p.i.) and good retention (5.75 at 120 min p.i.). The heart/liver SUV ratios were 4.12, 5.42 and 5.99 at 30, 60 and 120 min after injection, respectively. The favorable biological properties of [18F]Fmpp2 suggest that it is worth further investigation as a potential MPI agent. PMID:27646847

  4. Radiosynthesis and Evaluation of an 18F-Labeled Positron Emission Tomography (PET) Radioligand for Metabotropic Glutamate Receptor Subtype 4 (mGlu4)

    PubMed Central

    2015-01-01

    Four 4-phthalimide derivatives of N-(3-chlorophenyl)-2-picolinamide were synthesized as potential ligands for the PET imaging of mGlu4 in the brain. Of these compounds, N-(3-chloro-4-(4-fluoro-1,3-dioxoisoindolin-2-yl)phenyl)-2-picolinamide (3, KALB001) exhibited improved binding affinity (IC50 = 5.1 nM) compared with ML128 (1) and was subsequently labeled with 18F. When finally formulated in 0.1 M citrate buffer (pH 4) with 10% ethanol, the specific activity of [18F]3 at the end of synthesis (EOS) was 233.5 ± 177.8 GBq/μmol (n = 4). The radiochemical yield of [18F]3 was 16.4 ± 4.8% (n = 4), and the purity was over 98%. In vivo imaging studies in a monkey showed that the radiotracer quickly penetrated the brain with the highest accumulation in the brain areas known to express mGlu4. Despite some unfavorable radiotracer properties like fast washout in rodent studies, [18F]3 is the first 18F-labeled mGlu4 radioligand, which can be further modified to improve pharmacokinetics and brain penetrability for future human studies. PMID:25330258

  5. Single-step High-yield Radiosynthesis and Evaluation of a Sensitive 18F-Labeled Ligand for Imaging Brain Peripheral Benzodiazepine Receptors with PET

    PubMed Central

    Briard, Emmanuelle; Zoghbi, Sami S.; Siméon, Fabrice G.; Imaizumi, Masao; Gourley, Jonathan P.; Shetty, H. Umesha; Lu, Shuiyu; Fujita, Masahiro; Innis, Robert B.; Pike, Victor W.

    2009-01-01

    Elevated levels of peripheral benzodiazepine receptors (PBR) are associated with activated microglia in their response to inflammation. Hence, PBR imaging in vivo is valuable for investigating brain inflammatory conditions. Sensitive, easily prepared and readily available radioligands for imaging with positron emission tomography (PET) are desirable for this purpose. We describe a new 18F-labeled PBR radioligand, namely [18F]N-fluoroacetyl-N-(2,5-dimethoxybenzyl)-2-phenoxyaniline ([18F]9). [18F]9 was produced easily through a single and highly efficient step, the reaction of [18F]fluoride ion with the corresponding bromo precursor, 8. Ligand 9 exhibited high affinity for PBR in vitro. PET showed that [18F]9 was avidly taken into monkey brain and gave a high ratio of PBR-specific to nonspecific binding. [18F]9 was devoid of defluorination in rat and monkey and gave predominantly polar radiometabolite(s). In rat, a low level radiometabolite of intermediate lipophilicity was identified as [18F]2-fluoro-N-(2-phenoxyphenyl)acetamide ([18F]11). [18F]9 is a promising radioligand for future imaging of PBR in living human brain. PMID:19119848

  6. Synthesis and pre-clinical evaluation of a new class of high-affinity (18)F-labeled PSMA ligands for detection of prostate cancer by PET imaging.

    PubMed

    Kelly, James; Amor-Coarasa, Alejandro; Nikolopoulou, Anastasia; Kim, Dohyun; Williams, Clarence; Ponnala, Shashikanth; Babich, John W

    2017-04-01

    Current clinical imaging of PSMA-positive prostate cancer by positron emission tomography (PET) mainly features (68)Ga-labeled tracers, notably [(68)Ga]Ga-PSMA-HBED-CC. The longer half-life of fluorine-18 offers significant advantages over Ga-68, clinically and logistically. We aimed to develop high-affinity PSMA inhibitors labeled with fluorine-18 as alternative tracers for prostate cancer. Six triazolylphenyl ureas and their alkyne precursors were synthesized from the Glu-urea-Lys PSMA binding moiety. PSMA affinity was determined in a competitive binding assay using LNCaP cells. The [(18)F]triazoles were isolated following a Cu(I)-catalyzed click reaction between the alkynes and [(18)F]fluoroethylazide. The (18)F-labeled compounds were evaluated in nude mice bearing LNCaP tumors and compared to [(68)Ga]Ga-PSMA-HBED-CC and [(18)F]DCFPyL. Biodistribution studies of the two tracers with the highest imaged-derived tumor uptake and highest PSMA affinity were undertaken at 1 h, 2 h and 4 h post-injection (p.i.), and co-administration of PMPA was used to determine whether uptake was PSMA-specific. F-18-labeled triazolylphenyl ureas were prepared with a decay-corrected RCY of 20-40 %, >98 % radiochemical and chemical purity, and specific activity of up to 391 GBq/μmol. PSMA binding (IC50) ranged from 3-36 nM. The position of the triazole influenced tumor uptake (3 > 4 > 2), and direct conjugation of the triazole with the phenylurea moiety was preferred to insertion of a spacer group. Image-derived tumor uptake ranged from 6-14 %ID/g at 2 h p.i., the time of maximum tumor uptake; uptake of [(68)Ga]Ga-PSMA-HBED-CC and [(18)F]DCFPyL was 5-6 %ID/g at 1-3 h p.i., the time of maximum tumor uptake. Biodistribution studies of the two most promising compounds gave maximum tumor uptakes of 10.9 ± 1.0 % and 14.3 ± 2.5 %ID/g, respectively, as compared to 6.27 ± 1.44 %ID/g for [(68)Ga]Ga-PSMA-HBED-CC. Six [(18)F]triazolylphenyl ureas were prepared in

  7. Noninvasive positron emission tomography imaging of cell death using a novel small-molecule probe, (18)F labeled bis(zinc(II)-dipicolylamine) complex.

    PubMed

    Wang, Hongliang; Tang, Xiaolan; Tang, Ganghua; Huang, Tingting; Liang, Xiang; Hu, Kongzhen; Deng, Huaifu; Yi, Chang; Shi, Xinchong; Wu, Kening

    2013-08-01

    The synthetic bis(zinc(II)-dipicolylamine) (DPAZn2) coordination complexes are known to have a high specific and selective affinity to target the exposed phosphatidylserine (PS) on the surface of dead and dying cells. An (18)F-labeled DPAZn2 complex (4-(18)F-Fluoro-benzoyl-bis(zinc(II)-dipicolylamine), (18)F-FB-DPAZn2) as positron emission tomography (PET) tracer was developed and evaluated for in vivo imaging of tumor treated with a chemical agent. The in vitro cell stain studies revealed that fluorescent DPAZn2 complexes (Dansyl-DPAZn2) stained the same cells (apoptotic and necrotic cells) as fluorescein isothiocyanate (FITC) labeled Annexin V (FITC-Annexin V). The radiosynthesis of (18)F-FB-DPAZn2 was achieved through the amidation the precursor bis(2,2'-dipicolylamine) derivative (DPA2) with the prosthetic group N-succinimidyl-4-[(18)F]-fluorobenzoate ((18)F-SFB) and chelation with zinc nitrate. In the biodistribution study, the fast clearance of (18)F-FB-DPAZn2 from blood and kidney was observed and high uptake in liver and intestine within 90 min postinjection was also found. For the PET imaging, significantly higher tumor uptake of (18)F-FB-DPAZn2 was observed in the adriamycin (ADM)-treated Hepa1-6 hepatocellular carcinoma-bearing mice than that in the untreated tumor-model mice, while a slightly decreased tumor uptake of (18)F-FDG was found in the ADM-treated tumor-bearing mice. The results indicate that (18)F-FB-DPAZn2 has the similar capability of apoptosis detection as FITC-Annexin V and seems to be a potential PET tracer for noninvasive evaluation and monitoring of anti-tumor chemotherapy. The high uptake of (18)F-FB-DPAZn2 in the abdomen needs to optimize the structure for improving its pharmacokinetics characteristics in the future work.

  8. Synthesis and evaluation of an (18) F-labeled derivative of F3 for targeting surface-expressed nucleolin in cancer and tumor endothelial cells.

    PubMed

    Lam, Phoebe Y H; Hillyar, Christopher R T; Able, Sarah; Vallis, Katherine A

    2016-10-01

    The surface overexpression of nucleolin provides an anchor for the specific attachment of biomolecules to cancer and angiogenic endothelial cells. The peptide F3 is a high-affinity ligand of the nucleolin receptor (NR) that has been investigated as a carrier to deliver biologically active molecules to tumors for both therapeutic and imaging applications. A site-specific PEGylated F3 derivative was radiolabeled with [(18) F]Al-F. The binding affinity and cellular distribution of the compound was assessed in tumor (H2N) and tumor endothelial (2H-11) cells. Specific uptake via the NR was demonstrated by the siRNA knockdown of nucleolin in both cell lines. The partition and the plasma stability of the compound were assessed at 37°C. The enzyme-mediated site-specific modification of F3 to give NODA-PEG-F3 (NP-F3) was achieved. Radiolabeling with [(18) F]Al-F gave (18) F-NP-F3. (18) F-NP-F3 demonstrated high affinity for cancer and tumor endothelial cells. The siRNA knockdown of nucleolin resulted in a binding affinity reduction of 50% to 60%, confirming cell surface binding via the NR. NP-F3 was stable in serum for 2 h. (18) F-NP-F3 is reported as the first (18) F-labeled F3 derivative. It was obtained in a site-specific, high-yield, and efficient manner and binds to surface NR in the low nanomolar range, suggesting it has potential as a tumor and angiogenesis tracer.

  9. In vivo characterisation of a therapeutically relevant self-assembling (18) F-labelled β-sheet forming peptide and its hydrogel using positron emission tomography.

    PubMed

    Morris, O; Elsawy, M A; Fairclough, M; Williams, K J; Mcmahon, A; Grigg, J; Forster, D; Miller, A F; Saiani, A; Prenant, C

    2017-08-01

    Positron emission tomography (PET) and fluorescence labelling have been used to assess the pharmacokinetics, biodistribution and eventual fate of a hydrogel-forming nonapeptide, FEFKFEFKK (F9), in healthy mice, using (18) F-labelled and fluorescein isothiocyanate (FITC)-labelled F9 analogues. F9 was site-specifically radiolabelled with 2-[(18) F]fluoro-3-pyridinecarboxaldehyde ([(18) F]FPCA) via oxime bond formation. [(18) F]FPCA-F9 in vivo fate was evaluated both as a solution, following intravenous administration, and as a hydrogel when subcutaneously injected. The behaviour of FITC-F9 hydrogel was assessed following subcutaneous injection. [(18) F]FPCA-F9 demonstrated high plasma stability and primarily renal excretion; [(18) F]FPCA-F9 when in solution and injected into the bloodstream displayed prompt bladder uptake (53.4 ± 16.6 SUV at 20 minutes postinjection) and rapid renal excretion, whereas [(18) F]FPCA-F9 hydrogel, formed by co-assembly of [(18) F]FPCA-F9 monomer with unfunctionalised F9 peptide and injected subcutaneously, showed gradual bladder accumulation of hydrogel fragments (3.8 ± 0.4 SUV at 20 minutes postinjection), resulting in slower renal excretion. Gradual disaggregation of the F9 hydrogel from the site of injection was monitored using FITC-F9 hydrogel in healthy mice (60 ± 3 over 96 hours), indicating a biological half-life between 1 and 4 days. The in vivo characterisation of F9, both as a gel and a solution, highlights its potential as a biomaterial. Copyright © 2017 The Authors Journal of Labelled Compounds and Radiopharmaceuticals Published by John Wiley & Sons Ltd.

  10. In Vitro and In Vivo Evaluation of a 18F-Labeled High Affinity NOTA Conjugated Bombesin Antagonist as a PET Ligand for GRPR-Targeted Tumor Imaging

    PubMed Central

    Velikyan, Irina; Lindeberg, Gunnar; Sörensen, Jens; Larhed, Mats; Antoni, Gunnar; Sandström, Mattias; Tolmachev, Vladimir; Orlova, Anna

    2013-01-01

    Expression of the gastrin-releasing peptide receptor (GRPR) in prostate cancer suggests that this receptor can be used as a potential molecular target to visualize and treat these tumors. We have previously investigated an antagonist analog of bombesin (D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2, RM26) conjugated to 1,4,7-triazacyclononane-N,N',N''-triacetic acid (NOTA) via a diethylene glycol (PEG2) spacer (NOTA-P2-RM26) labeled with 68Ga and 111In. We found that this conjugate has favorable properties for in vivo imaging of GRPR-expression. The focus of this study was to develop a 18F-labelled PET agent to visualize GRPR. NOTA-P2-RM26 was labeled with 18F using aluminum-fluoride chelation. Stability, in vitro binding specificity and cellular processing tests were performed. The inhibition efficiency (IC50) of the [natF]AlF-NOTA-P2-RM26 was compared to that of the natGa-loaded peptide using 125I-Tyr4-BBN as the displacement radioligand. The pharmacokinetics and in vivo binding specificity of the compound were studied. NOTA-P2-RM26 was labeled with 18F within 1 h (60-65% decay corrected radiochemical yield, 55 GBq/µmol). The radiopeptide was stable in murine serum and showed high specific binding to PC-3 cells. [natF]AlF-NOTA-P2-RM26 showed a low nanomolar inhibition efficiency (IC50=4.4±0.8 nM). The internalization rate of the tracer was low. Less than 14% of the cell-bound radioactivity was internalized after 4 h. The biodistribution of [18F]AlF-NOTA-P2-RM26 demonstrated rapid blood clearance, low liver uptake and low kidney retention. The tumor uptake at 3 h p.i. was 5.5±0.7 %ID/g, and the tumor-to-blood, -muscle and -bone ratios were 87±42, 159±47, 38±16, respectively. The uptake in tumors, pancreas and other GRPR-expressing organs was significantly reduced when excess amount of non-labeled peptide was co-injected. The low uptake in bone suggests a high in vivo stability of the Al-F bond. High contrast PET image was obtained 3 h p.i. The initial biological

  11. In vitro and in vivo evaluation of a (18)F-labeled high affinity NOTA conjugated bombesin antagonist as a PET ligand for GRPR-targeted tumor imaging.

    PubMed

    Varasteh, Zohreh; Aberg, Ola; Velikyan, Irina; Lindeberg, Gunnar; Sörensen, Jens; Larhed, Mats; Antoni, Gunnar; Sandström, Mattias; Tolmachev, Vladimir; Orlova, Anna

    2013-01-01

    Expression of the gastrin-releasing peptide receptor (GRPR) in prostate cancer suggests that this receptor can be used as a potential molecular target to visualize and treat these tumors. We have previously investigated an antagonist analog of bombesin (D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2, RM26) conjugated to 1,4,7-triazacyclononane-N,N',N''-triacetic acid (NOTA) via a diethylene glycol (PEG2) spacer (NOTA-P2-RM26) labeled with (68)Ga and (111)In. We found that this conjugate has favorable properties for in vivo imaging of GRPR-expression. The focus of this study was to develop a (18)F-labelled PET agent to visualize GRPR. NOTA-P2-RM26 was labeled with (18)F using aluminum-fluoride chelation. Stability, in vitro binding specificity and cellular processing tests were performed. The inhibition efficiency (IC50) of the [(nat)F]AlF-NOTA-P2-RM26 was compared to that of the (nat)Ga-loaded peptide using (125)I-Tyr(4)-BBN as the displacement radioligand. The pharmacokinetics and in vivo binding specificity of the compound were studied. NOTA-P2-RM26 was labeled with (18)F within 1 h (60-65% decay corrected radiochemical yield, 55 GBq/µmol). The radiopeptide was stable in murine serum and showed high specific binding to PC-3 cells. [(nat)F]AlF-NOTA-P2-RM26 showed a low nanomolar inhibition efficiency (IC50=4.4±0.8 nM). The internalization rate of the tracer was low. Less than 14% of the cell-bound radioactivity was internalized after 4 h. The biodistribution of [(18)F]AlF-NOTA-P2-RM26 demonstrated rapid blood clearance, low liver uptake and low kidney retention. The tumor uptake at 3 h p.i. was 5.5±0.7 %ID/g, and the tumor-to-blood, -muscle and -bone ratios were 87±42, 159±47, 38±16, respectively. The uptake in tumors, pancreas and other GRPR-expressing organs was significantly reduced when excess amount of non-labeled peptide was co-injected. The low uptake in bone suggests a high in vivo stability of the Al-F bond. High contrast PET image was obtained 3 h p

  12. PET imaging of apoptosis in tumor-bearing mice and rabbits after paclitaxel treatment with 18F-Labeled recombinant human His10-annexin V

    PubMed Central

    Qin, Haidong; Zhang, Ming-Rong; Xie, Lin; Hou, Yanjie; Hua, Zichun; Hu, Minjin; Wang, Zizheng; Wang, Feng

    2015-01-01

    Monitoring response to chemo- or radiotherapy is of great importance in clinical practice. Apoptosis imaging serves as a very useful tool for the early evaluation of tumor response. The goal of this study was PET imaging of apoptosis with 18F-labeled recombinant human annexin V linked with 10 histidine tag (18F-rh-His10-annexin V) in nude mice bearing an A549 tumor and rabbits bearing a VX2 lung cancer after paclitaxel therapy. 18F-rh-His10-annexin V was prepared by conjugation of rh-His10-annexin V with N-succinimidyl 4-[18F]fluorobenzoate. Biodistribution was determined in mice by the dissection method and small-animal PET. Single-dose paclitaxel (175 mg/m2) was used to induce apoptosis in A549 and VX2 tumor models. 18F-rh-His10-annexin V was injected into A549 mice and VX rabbits to acquire dynamic and static PET images 72 h after paclitaxel treatment. The uptake of 18F-rh-His10-annexin V in apoptotic cells 4 h after induction was 6.45±0.52 fold higher than that in non-induced cells. High focal uptake of 18F-rh-His10-annexin V was visualized in A549 (SUVmax: 0.35±0.13) and VX2 (0.41±0.23) tumor models after paclitaxel treatment, whereas lower uptake was found in the corresponding tumors before treatment (A549 SUVmax: 0.04±0.02; VX2: 0.009±0.002). The apoptotic index was 75.61±11.56% in the treated VX2 cancer, much higher than that in the untreated VX2 (8.03±2.81%). This study demonstrated the feasibility of 18F-rh-His10-annexin V for the detection of apoptosis after chemotherapy in A549 and VX2 tumor models. PMID:25625024

  13. Radiosynthesis and preliminary PET evaluation of (18)F-labeled 2-(1-(3-fluorophenyl)-2-oxo-5-(pyrimidin-2-yl)-1,2-dihydropyridin-3-yl)benzonitrile for imaging AMPA receptors.

    PubMed

    Yuan, Gengyang; Jones, Graham B; Vasdev, Neil; Liang, Steven H

    2016-10-01

    To prompt the development of (18)F-labeled positron emission tomography (PET) tracers for the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, we have prepared (18)F-labeled 2-(1-(3-fluorophenyl)-2-oxo-5-(pyrimidin-2-yl)-1,2-dihydropyridin-3-yl)benzonitrile ([(18)F]8). The radiosynthesis was achieved by a one-pot two-step method that utilized a spirocyclic hypervalent iodine(III) mediated radiofluorination to prepare the (18)F-labeled 1-bromo-3-fluorobenzene ([(18)F]15) intermediate with K(18)F. A subsequent copper(I) iodide mediated coupling reaction was carried out with 2-(2-oxo-5-(pyrimidin-2-yl)-1,2-dihydropyridin-3-yl)benzonitrile (10) to [(18)F]8 in 10±2% uncorrected radiochemical yield relative to starting (18)F-fluoride with >99% radiochemical purity and 29.6±7.4Gbq/μmol specific activity at the time of injection. PET imaging studies with the title radiotracer in normal mice demonstrated good brain uptake (peak standardized uptake value (SUV)=2.3±0.1) and warrants further in vivo validation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Evaluation of Chemotherapy Response in VX2 Rabbit Lung Cancer with 18F-Labeled C2A Domain of Synaptotagmin I

    PubMed Central

    Wang, Feng; Fang, Wei; Zhang, Ming-Rong; Zhao, Ming; Liu, Biao; Wang, Zizheng; Hua, Zichun; Yang, Min; Kumata, Katsushi; Hatori, Akiko; Yamasaki, Tomoteru; Yanamoto, Kazuhiko; Suzuki, Kazutoshi

    2013-01-01

    The C2A domain of synaptotagmin I can target apoptotic cells by binding to exposed anionic phospholipids. The goal of this study was to synthesize and develop 18F-labeled C2A-gluta-thione-S-transferase (GST) as a molecular imaging probe for the detection of apoptosis and to assess the response of paclitaxel chemotherapy in VX2 rabbit lung cancer. Methods 18F-C2A-GST was prepared by labeling C2A-GST with N-succinimidyl 4-18F-fluorobenzoate (18F-SFB). 18F-C2A-GST was confirmed by high-performance liquid chromatography and sodium dodecyl sulfate polyacrylamide gel electrophoresis. The binding of 18F-C2A-GST toward apoptosis was validated in vitro using camptothecin-induced Jurkat cells. Biodistribution of 18F-C2A-GST was determined in mice by a dissection method and small-animal PET. Single-dose paclitaxel was used to induce apoptosis in rabbits bearing VX2 tumors (n = 6), and 2 VX2 rabbits without treatment served as control. 18F-C2A-GST PET was performed before and at 72 h after therapy, and 18F-FDG PET/CT was also performed before treatment. To confirm the presence of apoptosis, tumor tissue was analyzed and activated caspase-3 was measured. Results 18F-C2A-GST was obtained with more than 95% radiochemical purity and was stable for 4 h after formulation. 18F-C2A-GST bound apoptotic cells specifically. Biodistribution in mice showed that 18F-C2A-GST mainly excreted from the kidneys and rapidly cleared from blood and nonspecific organs. High focal uptake of 18F-C2A-GST in the tumor area was determined after therapy, whereas no significant uptake before therapy was found in the tumor with 18F-FDG–avid foci. The maximum standardized uptake value after therapy was 0.47 ± 0.28, significantly higher than that in the control (0.009 ± 0.001; P < 0.001). The apoptotic index was 79.81% ± 8.73% in the therapy group, significantly higher than that in the control (5.03% ± 0.81%; P < 0.001). Activated caspase-3 after paclitaxel treatment increased to 69.55% ± 16.27% and

  15. Preclinical Evaluation of 18F-Labeled Anti-HER2 Nanobody Conjugates for Imaging HER2 Receptor Expression by ImmunoPET

    PubMed Central

    Vaidyanathan, Ganesan; McDougald, Darryl; Choi, Jaeyeon; Koumarianou, Eftychia; Weitzel, Douglas; Osada, Takuya; Lyerly, H. Kim; Zalutsky, Michael R.

    2016-01-01

    The human growth factor receptor type 2 (HER2) is overexpressed in breast as well as other types of cancer. ImmunoPET, a noninvasive imaging procedure that could assess HER2 status in both primary and metastatic lesions simultaneously, could be a valuable tool for optimizing application of HER2-targeted therapies in individual patients. Herein, we have evaluated the tumor targeting potential of the 5F7 anti-HER2 Nanobody (single-domain antibody fragment; ~13 kDa) after 18F labeling by two methods. Methods The 5F7 Nanobody was labeled with 18F using the novel residualizing label N-succinimidyl 3-((4-(4-18F-fluorobutyl)-1H-1,2,3-triazol-1-yl)methyl)-5-(guanidinomethyl)benzoate (18F-SFBTMGMB; 18F-RL-I) and also via the most commonly utilized 18F protein labeling prosthetic agent, N-succinimidyl 3-18F-fluorobenzoate (18F-SFB). For comparison, 5F7 Nanobody was also labeled using the residualizing radioiodination agent N-succinimidyl 4-guanidinomethyl-3-125I-iodobenzoate (125I-SGMIB). Paired label (18F/125I) internalization assays and biodistribution studies were performed on HER2-expressing BT474M1 breast carcinoma cells and in mice with BT474M1 subcutaneous xenografts, respectively. Micro positron emission tomography/computed tomography (microPET/CT) imaging of 5F7 Nanobody labeled using 18F-RL-I also was performed. Results Internalization assays indicated that intracellularly retained radioactivity for 18F-RL-I-5F7 was similar to that for co-incubated 125I-SGMIB-5F7, while that for 18F-SFB-5F7 was lower than co-incubated 125I-SGMIB-5F7 and decreased with time. BT474M1 tumor uptake of 18F-RL-I-5F7 was 28.97 ± 3.88 %ID/g at 1 h and 36.28 ± 14.10 %ID/g at 2 h, reduced by >90% trastuzumab blocking, indicating HER2-specificity of uptake, and also 26–28% higher (P < 0.05) than that of 18F-SFB-5F7. At 2 h, the tumor-to-blood ratio for 18F-RL-I-5F7 (47.4 ± 13.1) was significantly higher (P < 0.05) than for 18F-SFB-5F7 (25.4 ± 10.3); however, kidney uptake was 28–36

  16. Preclinical Evaluation of 18F-Labeled Anti-HER2 Nanobody Conjugates for Imaging HER2 Receptor Expression by Immuno-PET.

    PubMed

    Vaidyanathan, Ganesan; McDougald, Darryl; Choi, Jaeyeon; Koumarianou, Eftychia; Weitzel, Douglas; Osada, Takuya; Lyerly, H Kim; Zalutsky, Michael R

    2016-06-01

    The human growth factor receptor type 2 (HER2) is overexpressed in breast as well as other types of cancer. Immuno-PET, a noninvasive imaging procedure that could assess HER2 status in both primary and metastatic lesions simultaneously, could be a valuable tool for optimizing application of HER2-targeted therapies in individual patients. Herein, we have evaluated the tumor-targeting potential of the 5F7 anti-HER2 Nanobody (single-domain antibody fragment; ∼13 kDa) after (18)F labeling by 2 methods. The 5F7 Nanobody was labeled with (18)F using the novel residualizing label N-succinimidyl 3-((4-(4-(18)F-fluorobutyl)-1H-1,2,3-triazol-1-yl)methyl)-5-(guanidinomethyl)benzoate ((18)F-SFBTMGMB; (18)F-RL-I) and also via the most commonly used (18)F protein-labeling prosthetic agent N-succinimidyl 3-(18)F-fluorobenzoate ((18)F-SFB). For comparison, 5F7 Nanobody was also labeled using the residualizing radioiodination agent N-succinimidyl 4-guanidinomethyl-3-(125)I-iodobenzoate ((125)I-SGMIB). Paired-label ((18)F/(125)I) internalization assays and biodistribution studies were performed on HER2-expressing BT474M1 breast carcinoma cells and in mice with BT474M1 subcutaneous xenografts, respectively. Small-animal PET/CT imaging of 5F7 Nanobody labeled using (18)F-RL-I also was performed. Internalization assays indicated that intracellularly retained radioactivity for (18)F-RL-I-5F7 was similar to that for coincubated (125)I-SGMIB-5F7, whereas that for (18)F-SFB-5F7 was lower than coincubated (125)I-SGMIB-5F7 and decreased with time. BT474M1 tumor uptake of (18)F-RL-I-5F7 was 28.97 ± 3.88 percentage injected dose per gram of tissue (%ID/g) at 1 h and 36.28 ± 14.10 %ID/g at 2 h, reduced by more than 90% on blocking with trastuzumab, indicating HER2 specificity of uptake, and was also 26%-28% higher (P < 0.05) than that of (18)F-SFB-5F7. At 2 h, the tumor-to-blood ratio for (18)F-RL-I-5F7 (47.4 ± 13.1) was significantly higher (P < 0.05) than for (18)F-SFB-5F7 (25.4 ± 10

  17. Boron neutron capture therapy and 18F-labelled borophenylalanine positron emission tomography: a critical and clinical overview of the literature.

    PubMed

    Evangelista, Laura; Jori, Giulio; Martini, Domenico; Sotti, Guido

    2013-04-01

    Positron emission tomography (PET) is considered one of the most useful tool for molecular imaging both in clinical and preclinical research for in vivo assessing of biochemical and pharmacological processes. Boron neutron capture therapy (BNCT) is a biologically-targeted radiotherapy that can selectively hit the tumour cells, saving the surrounding normal tissue. Boron 10 ((10)B) is the isotope widely used for this purpose, and acts as killer for tumor cells, releasing highly reactive α and (7)Li-particles when it absorbs a thermal neutron. The basic requirements for a successful BNCT treatment are firstly that the boron-containing compound/material has to be delivered to the neoplastic tissue, and secondly the amount of boron atoms concentrated inside/around the cancer cells must be sufficient for an optimal therapeutic response. The irradiation of tissue or organ with therapeutic doses of thermal neutrons can lead to a selective, complete ablation of the malignant lesion. Specific carriers have been developed for BNCT: para-borophenylalanine (BPA), represents one of them and the most employed in clinical trials to preferentially deliver boron to the malignancy. For the in vivo examination of pharmacokinetic, accumulation and metabolism characteristics of L-B-BPA, a positron-labeled boronophenylalanine analogue, L-(18)F-(10)BPA was proposed and its pharmaco-properties were non-invasively evaluated by PET imaging. Herein, we summarize BNCT principles and applications, boron carrier and boron imaging with PET, PET-guided BNCT and other studied and employed tracers for PET in order to optimizeBNCT. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Distribution and binding of 18F-labeled and 125I-labeled analogues of ACI-80, a prospective molecular imaging biomarker of disease: a whole hemisphere post mortem autoradiography study in human brains obtained from Alzheimer's disease patients.

    PubMed

    Gulyás, Balázs; Spenger, Christian; Beliczai, Zsuzsa; Gulya, Károly; Kása, Péter; Jahan, Mahabuba; Jia, Zhisheng; Weber, Urs; Pfeifer, Andrea; Muhs, Andreas; Willbold, Dieter; Halldin, Christer

    2012-01-01

    One of the major pathological landmarks of Alzheimer's disease and other neurodegenerative diseases is the presence of amyloid deposits in the brain. The early non-invasive visualization of amyloid is a major objective of recent diagnostic neuroimaging approaches, including positron emission tomography (PET), with an eye on follow-up of disease progression and/or therapy efficacy. The development of molecular imaging biomarkers with binding affinity to amyloid in the brain is therefore in the forefront of imaging biomarker and radiochemistry research. Recently, a dodecamer peptide (amino acid sequence=QSHYRHISPAQV; denominated D1 or ACI-80) was identified as a prospective ligand candidate, binding with high ex vivo affinity to L-Aβ-amyloid (K(d): 0.4 μM). In order to assess the ligand's capacity to visualize amyloid in Alzheimer's disease (AD), two (125)I labeled and three (18)F labeled analogues of the peptide were synthesized and tested in post mortem human autoradiography experiments using whole hemisphere brain slices obtained from deceased AD patients and age matched control subjects. The (18)F-labeled radioligands showed more promising visualization capacity of amyloid that the (125)I-labeled radioligands. In the case of each (18)F radioligands the grey matter uptake in the AD brains was significantly higher than that in control brains. Furthermore, the grey matter: white matter uptake ratio was over ~2, the difference being significant for each (18)F-radioligands. The regional distribution of the uptake of the various radioligands systematically shows a congruent pattern between the high uptake regions and spots in the autoradiographic images and the disease specific signals obtained in adjacent or identical brain slices labeled with histological, immunohistochemical or autoradiographic stains for amyloid deposits or activated astrocytes. The present data, using post mortem human brain autoradiography in whole hemisphere human brains obtained from deceased

  19. PET Imaging of Extracellular pH in Tumors with 64Cu- and 18F-Labeled pHLIP Peptides: A Structure–Activity Optimization Study

    PubMed Central

    2016-01-01

    pH (low) insertion peptides (pHLIP peptides) target acidic extracellular environments in vivo due to pH-dependent cellular membrane insertion. Two variants (Var3 and Var7) and wild-type (WT) pHLIP peptides have shown promise for in vivo imaging of breast cancer. Two positron emitting radionuclides (64Cu and 18F) were used to label the NOTA- and NO2A-derivatized Var3, Var7, and WT peptides for in vivo biodistribution studies in 4T1 orthotopic tumor-bearing BALB/c mice. All of the constructs were radiolabeled with 64Cu or [18F]-AlF in good yield. The in vivo biodistribution of the 12 constructs in 4T1 orthotopic allografted female BALB/c mice indicated that NO2A-cysVar3, radiolabeled with either 18F (4T1 uptake; 8.9 ± 1.7%ID/g at 4 h p.i.) or 64Cu (4T1 uptake; 8.2 ± 0.9%ID/g at 4 h p.i. and 19.2 ± 1.8% ID/g at 24 h p.i.), shows the most promise for clinical translation. Additional studies to investigate other tumor models (melanoma, prostate, and brain tumor models) indicated the universality of tumor targeting of these tracers. From this study, future clinical translation will focus on 18F- or 64Cu-labeled NO2A-cysVar3. PMID:27396694

  20. 18F: Labeling Chemistry and Labeled Compounds

    NASA Astrophysics Data System (ADS)

    Ross, T. L.; Wester, H. J.

    Positron emission tomography (PET) is a unique tool for the investigation, localization, and quantification of physiological activities in vivo by tracing the involved or accompanying biochemical processes. Because of its nuclear and chemical properties, fluorine-18, which is commonly produced by a cyclotron using the 18O(p,n)18F or the 20Ne(d,α)18F nuclear process, is a nearly ideal positron emitting radionuclide. Its half-life of 109.7 min permits tracer syntheses and imaging protocols extending over hours and allows distribution of 18F-radiopharmaceuticals to hospitals and facilities lacking a cyclotron. The low maximum positron energy of 635 keV results in low radiation doses, short ranges in tissue, and therefore in excellent imaging resolution. Introduction of 18F-fluorine, either via nucleophilic strategies using [18F]F- or electrophilic routes using molecular [18F]F2, permits the synthesis of a broad spectrum of compounds within a time compatible with the half-life. Although fluorine is only slightly larger than a hydrogen atom, changes in the physiological behavior of bioactive compounds as a result of alteration in metabolic stability, lipophilicity, affinity to the target, or other structures, etc., are often observed even after F-for-H or F-for-OH substitutions. In this chapter, an overview of the scope and limitations of the 18F-chemistry is given. Fluorination strategies, routes, and synthetic aspects are exemplified, as far as possible, by established and selected 18F-radiopharmaceuticals with clinical relevance or with potential for further clinical application.

  1. Synthesis and Evaluation of Two 18F-Labeled 6-Iodo-2-(4′-N,N-dimethylamino)phenylimidazo[1,2-a]pyridine Derivatives as Prospective Radioligands for β-Amyloid in Alzheimer’s Disease

    PubMed Central

    Cai, Lisheng; Chin, Frederick T.; Pike, Victor W.; Toyama, Hiroshi; Liow, Jeih-San; Zoghbi, Sami S.; Modell, Kendra; Briard, Emmanuelle; Shetty, H. Umesha; Sinclair, Kathryn; Donohue, Sean; Tipre, Dnyanesh; Kung, Mei-Ping; Dagostin, Claudio; Widdowson, David A.; Green, Michael; Gao, Weiyi; Herman, Mary M.; Ichise, Masanori; Innis, Robert B.

    2014-01-01

    This study evaluated 18F-labeled IMPY [6-iodo-2-(4′-N,N-dimethylamino)phenylimidazo[1,2-a]pyridine] derivatives as agents for imaging β-amyloid plaque with positron emission tomography (PET). The precursor for radiolabeling and reference compounds was synthesized in up to five steps from commercially accessible starting materials. One of the two N-methyl groups of IMPY was substituted with either a 3-fluoropropyl (FPM-IMPY) or a 2-fluoroethyl (FEM-IMPY) group. FPM-IMPY and FEM-IMPY were found to have moderate affinity for Aβ- aggregates with Ki = 27 ± 8 and 40 ± 5 nM, respectively. A “one-pot” method for 18F-2-fluoroethylation and 18F-3-fluoropropylation of the precursor was developed. The overall decay-corrected radiochemical yields were 26–51%. In PET experiments with normal mouse, high uptake of activity was obtained in the brain after iv injection of each probe: 6.4% ID/g for [18F]FEM-IMPY at 1.2 min, and 5.7% ID/g for [18F]FPM-IMPY at 0.8 min. These values were similar to those of [123I/125I]IMPY (7.2% ID/g at 2 min). Polar and nonpolar radioactive metabolites were observed in both plasma and brain homogenates after injection of [18F]FEM or [18F]FPM-IMPY. In contrast to the single-exponential washout of [123I/125I]IMPY, the washouts of brain activity for the two fluorinated analogues were biphasic, with an initial rapid phase over 20 min and a subsequent much slower phase. Residual brain activity at 2 h, which may represent polar metabolites trapped in the brain, was 4.5% ID/g for [18F]FEM-IMPY and 2.1% ID/g for [18F]FPM-IMPY. Substantial skull uptake of [18F]fluoride was also clearly observed. With a view to slow the metabolism of [18F]FEM-IMPY, an analogue was prepared with deuteriums substituted for the four ethyl hydrogens. However, D4-[18F]FEM-IMPY showed the same brain uptake and clearance as the protio analogue. Metabolism of the [18F]FEM-IMPY was appreciably slower in rhesus monkey than in mouse. Autoradiography of postmortem brain sections

  2. Enantioselective synthesis of L-(-)-4- boronophenylalanine (L-BPA)

    DOEpatents

    Samsel, E.G.

    1992-10-20

    A method of making substantially pure L-BPA is disclosed. The method includes the steps of reacting 4-bromobenzaldehyde with ethylene glycol to form 4-bromobenzaldehyde ethylene glycol acetal, sequentially reacting 4-bromobenzaldehyde ethyleneglycol acetal with Mg to produce the Grignard reagent and thereafter reacting with tributyl borate and then converting to an acid environment to form 4-boronobenzaldehyde, reacting 4-boronobenzaldehyde with diethanol amine to form 4-boronobenzaldehyde diethanolamine ester, condensing the 4-boronobenzaldehyde diethanolamine ester with 2-phenyl-2-oxazolin-5-one to form an azlactone, reacting the azlactone with an alkali metal hydroxide to form z-[alpha]-benzoylamino-4boronocinnamic acid, asymmetrically hydrogenating the z-[alpha]-benzoylamino-4-boronocinnamic acid in the presence of a catalyst of a cheltate complex of rhodium (I) with chiral bisphosphines to form L-(+)-N-benzoyl-4-boronophenylalanine, and thereafter acidifying the L-(+)-N-benzoyl-4-boronophenylalanine in an organic medium to produce L-BPA. 3 figs.

  3. Enantioselective synthesis of L-(-)-4- boronophenylalanine (L-BPA)

    DOEpatents

    Samsel, Edward G.

    1992-01-01

    A method of making substantially pure L-BPA is disclosed. The method includes the steps of reacting 4-bromobenzaldehyde with ethylene glycol to form 4-bromobenzaldehyde ethylene glycol acetal, sequentially reacting 4-bromobenzaldehyde ethyleneglycol acetal with Mg to produce the Grignard reagent and thereafter reacting with tributyl borate and then converting to an acid environment to form 4-boronobenzaldehyde, reacting 4-boronobenzaldehyde with diethanol amine to form 4-boronobenzaldehyde diethanolamine ester, condensing the 4-boronobenzaldehyde diethanolamine ester with 2-phenyl-2-oxazolin-5-one to form an azlactone, reacting the azlactone with an alkali metal hydroxide to form z-.alpha.-benzoylamino-4-boronocinnamic acid, asymmetrically hydrogenating the z-.alpha.-benzoylamino-4-boronocinnamic acid in the presence of a catalyst of a cheltate complex of rhodium (I) with chiral bisphosphines to form L-(+)-N-benzoyl-4-boronophenylalanine, and thereafter acidifying the L-(+)-N-benzoyl-4-boronophenylalanine in an organic medium to produce L-BPA.

  4. A Phase 1 biodistribution study of p-boronophenylalanine

    SciTech Connect

    Coderre, J.A.

    1991-01-01

    The objectives of the Phase I BPA biodistribution study are as follows: Objective 1: To establish the safety of orally administered boronophenylalanine (BPA) as determined by monitoring of patient's vital signs and by clinical analysis of blood before and after BPA administration. Objective 2: To establish BPA pharmacokinetics by monitoring the rates of boron absorption into and clearance from the blood and the rate of urinary excretion of boron. Objective 3: To measure the amount of boron incorporated into human tumors (melanoma, glioma, and breast carcinoma) using samples obtained at surgery or biopsy. This report presents the results obtained from the first thirteen patients entered into the study. Three additional glioblastoma patients have been studied recently at Stony Brook, the tissues are still being analyzed.

  5. A Phase 1 biodistribution study of p-boronophenylalanine

    SciTech Connect

    Coderre, J.A.

    1991-12-31

    The objectives of the Phase I BPA biodistribution study are as follows: Objective 1: To establish the safety of orally administered boronophenylalanine (BPA) as determined by monitoring of patient`s vital signs and by clinical analysis of blood before and after BPA administration. Objective 2: To establish BPA pharmacokinetics by monitoring the rates of boron absorption into and clearance from the blood and the rate of urinary excretion of boron. Objective 3: To measure the amount of boron incorporated into human tumors (melanoma, glioma, and breast carcinoma) using samples obtained at surgery or biopsy. This report presents the results obtained from the first thirteen patients entered into the study. Three additional glioblastoma patients have been studied recently at Stony Brook, the tissues are still being analyzed.

  6. N-Succinimidyl 3-((4-(4-[(18)F]fluorobutyl)-1H-1,2,3-triazol-1-yl)methyl)-5-(guanidinomethyl)benzoate ([(18)F]SFBTMGMB): a residualizing label for (18)F-labeling of internalizing biomolecules.

    PubMed

    Vaidyanathan, Ganesan; McDougald, Darryl; Choi, Jaeyeon; Pruszynski, Marek; Koumarianou, Eftychia; Zhou, Zhengyuan; Zalutsky, Michael R

    2016-01-28

    Residualizing labeling methods for internalizing peptides and proteins are designed to trap the radionuclide inside the cell after intracellular degradation of the biomolecule. The goal of this work was to develop a residualizing label for the (18)F-labeling of internalizing biomolecules based on a template used successfully for radioiodination. N-Succinimidyl 3-((4-(4-[(18)F]fluorobutyl)-1H-1,2,3-triazol-1-yl)methyl)-5-(bis-Boc-guanidinomethyl)benzoate ([(18)F]SFBTMGMB-Boc2) was synthesized by a click reaction of an azide precursor and [(18)F]fluorohexyne in 8.5 ± 2.8% average decay-corrected radiochemical yield (n = 15). An anti-HER2 nanobody 5F7 was labeled with (18)F using [(18)F]SFBTMGMB ([(18)F]RL-I), obtained by the deprotection of [(18)F]SFBTMGMB-Boc2, in 31.2 ± 6.7% (n = 5) conjugation efficiency. The labeled nanobody had a radiochemical purity of >95%, bound to HER2-expressing BT474M1 breast cancer cells with an affinity of 4.7 ± 0.9 nM, and had an immunoreactive fraction of 62-80%. In summary, a novel residualizing prosthetic agent for labeling biomolecules with (18)F has been developed. An anti-HER2 nanobody was labeled using this prosthetic group with retention of affinity and immunoreactivity to HER2.

  7. N-Succinimidyl 3-((4-(4-[18F]fluorobutyl)-1H-1,2,3-triazol-1-yl)methyl)-5-(guanidinomethyl)benzoate ([18F]SFBTMGMB): A Residualizing Label for 18F-labeling of internalizing biomolecules

    PubMed Central

    Vaidyanathan, Ganesan; McDougald, Darryl; Choi, Jaeyeon; Pruszynski, Marek; Koumarianou, Eftychia; Zhou, Zhengyuan; Zalutsky, Michael R.

    2015-01-01

    Residualizing labeling methods for internalizing peptides and proteins are designed to trap the radionuclide inside the cell after intracellular degradation of the biomolecule. The goal of this work was to develop a residualizing label for the 18F-labeling of internalizing biomolecules based on a template used successfully for radioiodination. N-succinimidyl 3-((4-(4-[18F]fluorobutyl)-1H-1,2,3-triazol-1-yl)methyl)-5-(bis-Boc-guanidinomethyl)benzoate (Boc2-[18F]SFBTMGMB) was synthesized by click reaction of an azide precursor and [18F]fluorohexyne in 8.5 ± 2.8% average decay-corrected radiochemical yield (n =15). An anti-HER2 nanobody 5F7 was labeled with 18F using [18F]SFBTMGMB ([18F]RL-I), obtained by the deprotection of Boc2-[18F]SFBTMGMB, in 31.2 ± 6.7% (n =5) conjugation efficiency. Thus labeled nanobody had a radiochemical purity of >95%, bound to the HER2-expressing BT474M1 breast cancer cells with an affinity of 4.7 ± 0.9 nM, and had an immunoreactive fraction of 62–80%. In summary, a novel residualizing prosthetic agent for labeling biomolecules with 18F has been developed. An anti-HER2 nanobody was labeled using this prosthetic group with retention of affinity and immunoreactivity to HER2. PMID:26645790

  8. Improved treatment planning for boron neutron capture therapy for glioblastoma multiforme using fluorine-18 labeled boronophenylalanine and positron emission tomography.

    PubMed

    Nichols, Trent L; Kabalka, George W; Miller, Laurence F; Khan, Mohammad K; Smith, Gary T

    2002-10-01

    Boron neutron capture therapy (BNCT) is a cancer brachytherapy based upon the thermal neutron reaction: 10B(n,alpha)7Li. The efficacy of the treatment depends primarily upon two conditions being met: (a) the preferential concentration of a boronated compound in the neoplasm and (b) an adequate fluence of thermal neutrons delivered to the neoplasm. The boronated amino acid, para-boronophenylalanine (BPA), is the agent widely used in clinical trials to deliver 10B to the malignancy. Positron emission tomography (PET) can be used to generate in vivo boron distribution maps by labeling BPA with the positron emitting nuclide fluorine-18. The incorporation of the PET-derived boron distribution maps into current treatment planning protocols is shown to provide improved treatment plans. Using previously established protocols, six patients with glioblastoma had 18BPA PET scans. The PET distribution maps obtained were used in the conventional BNCT treatment codes. The isodose curves derived from the PET data are shown to differ both qualitatively and quantitatively from the conventional isodose curves that were derived from calculations based upon the assumption of uniform uptake of the pharmaceutical in tumor and normal brain regions. The clinical course of each of the patients who eventually received BNCT (five of the six patients) was compared using both sets of isodose calculations. The isodose contours based upon PET derived distribution data appear to be more consistent with the patients' clinical course.

  9. Accumulation of boron in malignant and normal cells incubated in vitro with boronophenylalanine, mercaptoborane or boric acid.

    PubMed

    Capala, J; Makar, M S; Coderre, J A

    1996-11-01

    The short (< 10 microns) ranges of alpha and 7Li particles produced during boron neutron capture therapy (BNCT) make the partitioning of the boronated drug within and without the cell of critical importance. The evaluation of the potential usefulness of a boron-containing substance for BNCT requires information about its intracellular accumulation. In the present report, an in vitro method is described for direct measurement of intracellular boron based on rapid centrifugation of cells through a layer of mineral oil and silicon oil to strip away extracellular growth medium. The intracellular concentrations of boronophenylalanine (BPA), mercaptoborane (BSH) and horic acid in malignant cells and in normal cells have been compared. The accumulation ratio is defined as the ratio of the intracellular to the extracellular boron concentration. Boric acid showed an accumulation ratio of 1 while the ratios for BSH and BPA were dependent on cell type and tended to be greater for BPA than for BSH in malignant but not in normal cells.

  10. A Phase 1 trial of intravenous boronophenylalanine-fructose complex in patients with glioblastoma multiforme

    SciTech Connect

    Bergland, R.; Elowitz, E.; Chadha, M.; Coderre, J.A.; Joel, D.

    1996-10-01

    Boron neutron capture therapy (BNCT) of glioblastoma multiforme was initially performed at the Brookhaven National Laboratory in the early 1950`s While this treatment for malignant brain tumors has continued in Japan, new worldwide interest has been stimulated by the development of new and more selective boron compounds. Boronophenylalanine (BPA) is a blood-brain barrier penetrating compound that has been used in BNCT of malignant melanomas. SPA has been employed experimentally in BNCT of rat gliosarcoma and has potential use in the treatment of human glioblastoma. As a preface to clinical BNCT trials, we studied the biodistribution of SPA in patients with glioblastoma.

  11. RADIOSYNTHESIS AND CHIRAL SEPARATION OF C-11 LABELED BORONOPHENYLALANINE FOR BNCT STUDIES WITH PET.

    SciTech Connect

    STUDENOV,A.; DING,Y.S.; FERRIERI,R.; MIURA,M.; CODERRE,J.; FOWLER,J.S.

    2001-06-10

    The overall goal of this research is to combine two powerful methodologies, boron neutron capture therapy (BNCT) and positron emission tomography (PET), to advance the treatment of patients with malignant brain tumors. BNCT is a method to selectively deliver lethal alpha radiation to a tumor through the administration of a boron-10 containing drug, and irradiation of the tumor area with neutrons [1]. L-Boronophenylalanine (L-{sup 10}BPA) is a boron-10 containing amino acid currently used for BNCT [4]. In order to perform neutron dosimetry, it is essential to determine tumor boron-10 levels in the course of the therapy. PET has the ability to measure the concentration of drugs labeled with positron-emitting isotopes in the human body [2]. 2-Fluoro-4-borono-phenylalanine ([{sup 18}F]FBPA) has been labeled as a surrogate marker for L-BPA for pharmacokinetic studies in brain tumor patients [3]. However, [{sup 18}F]FBPA is a different drug than L-BPA because it contains a fluorine atom. We report here the labeling of L-BPA with C-11, which has the advantage of being chemically identical to L-BPA. Carbon-11 is also well suited to repeated studies within the same PET scanning session.

  12. Boron neutron capture therapy of ocular melanoma and intracranial glioma using p-boronophenylalanine

    SciTech Connect

    Coderre, J.A.; Greenberg, D.; Micca, P.L.; Joel, D.D.; Saraf, S. ); Packer, S. . Div. of Ophthalmology)

    1990-01-01

    During conventional radiotherapy, the dose that can be delivered to the tumor is limited by the tolerance of the surrounding normal tissue within the treatment volume. Boron Neutron Capture Therapy (BNCT) represents a promising modality for selective tumor irradiation. The key to effective BNCT is selective localization of {sup 10}B in the tumor. We have shown that the synthetic amino acid p-boronophenylalanine (BPA) will selectively deliver boron to melanomas and other tumors such as gliosarcomas and mammary carcinomas. Systemically delivered BPA may have general utility as a boron delivery agent for BNCT. In this paper, BNCT with BPA is used in treatment of experimentally induced gliosarcoma in rats and nonpigmented melanoma in rabbits. The tissue distribution of boron is described, as is response to the BNCT. 6 refs., 4 figs., 1 tab.

  13. Inborn errors in metabolism and 4-boronophenylalanine-fructose-based boron neutron capture therapy.

    PubMed

    Laakso, Juha; Ruokonen, Inkeri; Lapatto, Risto; Kallio, Merja

    2003-11-01

    Infusions of boronophenylalanine-fructose complex (BPA-F), at doses up to 900 mg/kg of BPA and 860 mg/kg of fructose, have been used to deliver boron to cancer tissue for boron neutron capture therapy (BNCT). In patients with phenylketonuria (PKU), phenylalanine accumulates, which is harmful in the long run. PKU has been an exclusion criterion for BPA-F-mediated BNCT. Fructose is harmful to individuals with hereditary fructose intolerance (HFI) in amounts currently used in BNCT. The harmful effects are mediated through induction of hypoglycemia and acidosis, which may lead to irreversible organ damage or even death. Consequently, HFI should be added as an exclusion criterion for BNCT if fructose-containing solutions are used in boron carriers. Non-HFI subjects may also develop symptoms, such as gastrointestinal pain, if the fructose infusion rate is high. We therefore recommend monitoring of glucose levels and correcting possible hypoglycemia promptly. Except for some populations with extremely low PKU prevalence, HFI and PKU prevalences are similar, approximately 1 or 2 per 20,000.

  14. Biodistribution of boronophenylalanine in patients with glioblastoma multiforme: boron concentration correlates with tumor cellularity.

    PubMed

    Coderre, J A; Chanana, A D; Joel, D D; Elowitz, E H; Micca, P L; Nawrocky, M M; Chadha, M; Gebbers, J O; Shady, M; Peress, N S; Slatkin, D N

    1998-02-01

    Boron-10 (10B) concentrations were measured in 107 surgical samples from 15 patients with glioblastoma multiforme who were infused with 95 atom% 10B-enriched p-boronophenylalanine (BPA) intravenously for 2 h just prior to surgery at doses ranging from 98 to 290 mg BPA/kg body weight. The blood 10B concentration reached a maximum at the end of the infusion (ranging from 9.3 to 26.0 microg 10B/g) and was proportional to the amount of BPA infused. The boron concentrations in excised tumor samples ranged from 2.7 to 41.3 microg 10B/g over the range of administered BPA doses and varied considerably among multiple samples from individual patients and among patients at the same BPA dose. A morphometric index of the density of viable-appearing tumor cells in histological sections obtained from samples adjacent to, and macroscopically similar to, the tumor samples used for boron analysis correlated linearly with the boron concentrations. From that correlation it is estimated that 10B concentrations in glioblastoma tumor cells were over four times greater than concurrent blood 10B concentrations. Thus, in the dose range of 98 to 290 mg BPA/kg, the accumulation of boron in tumor cells is a linear function of BPA dose and the variations observed in boron concentrations of tumor specimens obtained surgically are largely due to differences in the proportion of nontumor tissue (i.e. necrotic tissue, normal brain) present in the samples submitted for boron analysis. The tumor:blood 10B concentration ratio derived from this analysis provides a rationale for estimating the fraction of the radiation dose to viable tumor cells resulting from the boron neutron capture reaction based on measured boron concentrations in the blood at the time of BNCT without the need for analysis of tumor samples from individual patients.

  15. Dose-response analysis for boron neutron capture therapy of the B16 murine melanoma using p-boronophenylalanine

    SciTech Connect

    Coderre, J.A.; Micca, P.L.; Slatkin, D.N.; Makar, M.S.

    1990-01-01

    Boron Neutron Capture Therapy (BNCT) of a well-pigmented B16 melanoma implanted subcutaneously in the mouse thigh has been carried out at the Brookhaven Medical Research Reactor (BMRR) using the synthetic amino acid p-boronophenylalanine (BPA) as the boron delivery agent. The response of the B16 melanoma to BNCT was compared with the response to 250 kVp x-rays using both tumor growth delay and in vivo/in vitro assay that measures clonogenic survival. These experiments allow a comparison of tumor growth delay, log cell kill and damage to normal tissues produced by BNCT or photon irradiation.

  16. Proton nuclear magnetic resonance measurement of p-boronophenylalanine (BPA): A therapeutic agent for boron neutron capture therapy

    PubMed Central

    Zuo, C. S.; Prasad, P. V.; Busse, Paul; Tang, L.; Zamenhof, R. G.

    2015-01-01

    Noninvasive in vivo quantitation of boron is necessary for obtaining pharmacokinetic data on candidate boronated delivery agents developed for boron neutron capture therapy (BNCT). Such data, in turn, would facilitate the optimization of the temporal sequence of boronated drug infusion and neutron irradiation. Current approaches to obtaining such pharmacokinetic data include: positron emission tomography employing F-18 labeled boronated delivery agents (e.g., p-boronophenylalanine), ex vivo neutron activation analysis of blood (and very occasionally tissue) samples, and nuclear magnetic resonance (NMR) techniques. In general, NMR approaches have been hindered by very poor signal to noise achieved due to the large quadrupole moments of B-10 and B-11 and (in the case of B-10) very low gyromagnetic ratio, combined with low physiological concentrations of these isotopes under clinical conditions. This preliminary study examines the feasibility of proton NMR spectroscopy for such applications. We have utilized proton NMR spectroscopy to investigate the detectability of p-boronophenylalanine fructose (BPA-f) at typical physiological concentrations encountered in BNCT. BPA-f is one of the two boron delivery agents currently undergoing clinical phase-I/II trials in the U.S., Japan, and Europe. This study includes high-resolution 1H spectroscopic characterization of BPA-f to identify useful spectral features for purposes of detection and quantification. The study examines potential interferences, demonstrates a linear NMR signal response with concentration, and presents BPA NMR spectra in ex vivo blood samples and in vivo brain tissues. PMID:10435522

  17. An improved strategy for the synthesis of [18F]-labeled arabinofuranosyl nuclosides

    PubMed Central

    Zhang, Hanwen; Cantorias, Melchor V.; Pillarsetty, NagaVaraKishore; Burnazi, Eva M.; Cai, Shangde; Lewis, Jason S.

    2012-01-01

    The expression of the herpes simplex virus type-1 thymidine kinase (HSV1-tk) gene can be imaged efficaciously using a variety of 2′-[18F]fluoro-2′-deoxy-1-b-D-arabinofuranosyl-uracil derivatives [[18F]-FXAU, X= I(iodo), E(ethyl), and M(methyl)]. However, the application of these derivatives in clinical and translational studies has been impeded by their complicated and long syntheses (3–5 h). To remedy these issues, in the study at hand we have investigated whether microwave or combined catalysts could facilitate the coupling reaction between sugar and nucleobase and, further, have probed the feasibility of establishing a novel approach for [18F]-FXAU synthesis. We have demonstrated that the rate of the trimethylsilyl trifluoromethanesulfonate (TMSOTf)-catalyzed coupling reaction between the 2-deoxy-sugar and uracil derivatives at 90°C can be significantly accelerated by microwave-driven heating or by the addition of Lewis acid catalyst (SnCl4). Further, we have observed that the stability of the α- and β-anomers of [18F]-FXAU derivatives differs during the hydrolysis step. Using the microwave-driven heating approach, overall decay-corrected radiochemical yields of 19–27% were achieved for [18F]-FXAU in 120 min at a specific activity of >22 MBq/nmol (595 Ci/mmol). Ultimately, we believe that these high yielding syntheses of [18F]-FIAU, [18F]-FMAU and [18F]-FEAU will facilitate routine production for clinical applications. PMID:22819195

  18. 18F-Labeled Silicon-Based Fluoride Acceptors: Potential Opportunities for Novel Positron Emitting Radiopharmaceuticals

    PubMed Central

    Bernard-Gauthier, Vadim; Wängler, Carmen; Wängler, Bjoern; Schirrmacher, Ralf

    2014-01-01

    Background. Over the recent years, radiopharmaceutical chemistry has experienced a wide variety of innovative pushes towards finding both novel and unconventional radiochemical methods to introduce fluorine-18 into radiotracers for positron emission tomography (PET). These “nonclassical” labeling methodologies based on silicon-, boron-, and aluminium-18F chemistry deviate from commonplace bonding of an [18F]fluorine atom (18F) to either an aliphatic or aromatic carbon atom. One method in particular, the silicon-fluoride-acceptor isotopic exchange (SiFA-IE) approach, invalidates a dogma in radiochemistry that has been widely accepted for many years: the inability to obtain radiopharmaceuticals of high specific activity (SA) via simple IE. Methodology. The most advantageous feature of IE labeling in general is that labeling precursor and labeled radiotracer are chemically identical, eliminating the need to separate the radiotracer from its precursor. SiFA-IE chemistry proceeds in dipolar aprotic solvents at room temperature and below, entirely avoiding the formation of radioactive side products during the IE. Scope of Review. A great plethora of different SiFA species have been reported in the literature ranging from small prosthetic groups and other compounds of low molecular weight to labeled peptides and most recently affibody molecules. Conclusions. The literature over the last years (from 2006 to 2014) shows unambiguously that SiFA-IE and other silicon-based fluoride acceptor strategies relying on 18F− leaving group substitutions have the potential to become a valuable addition to radiochemistry. PMID:25157357

  19. Clinical Experience with (18)F-Labeled Small Molecule Inhibitors of Prostate-Specific Membrane Antigen.

    PubMed

    Rowe, Steven P; Gorin, Michael A; Salas Fragomeni, Roberto A; Drzezga, Alexander; Pomper, Martin G

    2017-04-01

    Prostate cancer (PCa) is the most common noncutaneous malignancy diagnosed in men. Despite the large number of men who will suffer from PCa at some point during their lives, conventional imaging modalities for this important disease (contrast-enhanced computed tomography, bone scan, and MR imaging) have provided only marginal to moderate success in appropriately guiding patient management in certain clinical contexts. In this review, the authors discuss radiofluorinated small molecule radiotracers that have been developed to bind to the transmembrane glycoprotein prostate-specific membrane antigen, a target that is nearly universally overexpressed on PCa epithelial cells.

  20. Improved 18F Labeling of Peptides with a Fluoride-Aluminum-Chelate Complex

    PubMed Central

    McBride, William J.; D’Souza, Christopher A.; Sharkey, Robert M.; Karacay, Habibe; Rossi, Edmund A.; Chang, Chien-Hsing; Goldenberg, David M.

    2010-01-01

    We reported previously the feasibility to radiolabel peptides with fluorine-18 (18F) using a rapid, one-pot, method that first mixes 18F− with Al3+, and then binds the (Al18F)2+ complex to a NOTA ligand on the peptide. In this report, we examined several new NOTA ligands and determined how temperature, reaction time, and reagent concentration affected the radiolabeling yield. Four structural variations of the NOTA ligand had isolated radiolabeling yields ranging from 5.8% to 87% under similar reaction conditions. All of the Al18F NOTA complexes were stable in vitro in human serum and those that were tested in vivo also were stable. The radiolabeling reactions were performed at 100°C and the peptides could be labeled in as little as five minutes. The IMP467 peptide could be labeled up to 115 GBq/μmol (3100 Ci/mmol), with a total reaction and purification time of 30 min without chromatographic purification. PMID:20540570

  1. Synthesis and evaluation of 18F labeled alanine derivatives as potential tumor imaging agents

    PubMed Central

    Wang, Limin; Zha, Zhihao; Qu, Wenchao; Qiao, Hongwen; Lieberman, Brian P.; Plössl, Karl; Kung, Hank F.

    2012-01-01

    Introduction This paper reports the synthesis and labeling of 18F alanine derivatives. We also investigate their biological characteristics as potential tumor imaging agents mediated by alanine-serine-cysteine preferring (ASC) transporter system. Methods Three new 18F alanine derivatives were prepared from corresponding tosylate-precursors through a two-step labelling reaction. In vitro uptake studies to evaluate and to compare these three analogs were carried out in 9L glioma and PC-3 prostate cancer cell lines. Potential transport mechanisms, protein incorporation and stability of 3-(1-[18F]fluoromethyl)-L-alanine (L[18F]FMA) were investigated in 9L glioma cells. Its biodistribution was determined in a rat-bearing 9L tumor model. PET imaging studies were performed on rat bearing 9L glioma tumors and transgenic mouse carrying spontaneous generated M/tomND tumor (mammary gland adenocarcinoma). Results New 18F alanine derivatives were prepared with 7–34% uncorrected radiochemical yields, excellent enantiomeric purity (>99%) and good radiochemical purity (>99%). In vitro uptake of the L-[18F]FMA in 9L glioma and PC-3 prostate cancer cells was higher than those observed for other two alanine derivatives and [18F]FDG in first 1 h. Inhibition of cell uptake studies suggested that L-[18F]FMA uptake in 9L glioma was predominantly via transport system ASC. After entering into cells, L-[18F]FMA remained stable and was not incorporated into protein within 2 h. In vivo biodistribution studies demonstrated that L-[18F]FMA had relatively high uptake in liver and kidney. Tumor uptake was fast, reaching a maximum within 30 min. The tumor-to-muscle, tumor-to-blood and tumor-to-brain ratios at 60 min post injection were 2.2, 1.9 and 3.0, respectively. In PET imaging studies, tumors were visualized with L-[18F]FMA in both 9L rat and transgenic mouse. Conclusion L-[18F]FMA showed promising properties as a PET imaging agent for up-regulated ASC transporter associated with tumor proliferation. PMID:22542392

  2. Central nervous system tolerance to boron neutron capture therapy with p-boronophenylalanine.

    PubMed

    Morris, G M; Coderre, J A; Micca, P L; Fisher, C D; Capala, J; Hopewell, J W

    1997-01-01

    A rat spinal cord model was used to evaluate the effects of boron neutron capture irradiation on the central nervous system (CNS), using a range of doses of the boron delivery agent p-boronophenylalanine (BPA). Three doses of BPA 700, 1000 and 1600 mg kg(-1) were used to establish the biodistribution of boron-10 (10B) in blood, spinal cord and brain over a 3-h period after intraperitoneal (i.p.) administration. At the lowest dose of BPA used, blood 10B levels remained relatively stable over the 3-h sampling period. With the two higher doses of BPA, blood 10B concentrations were greatest at 1 h after BPA administration, and thereafter exhibited a biphasic clearance profile. The largest decline in blood 10B levels occurred between 1 and 2 h after i.p. injection and was most pronounced (approximately 45%) in the highest BPA dose group. Considered overall, 10B concentrations were marginally lower in the spinal cord than in the brain. Levels of 10B in both of these organs showed a slow but progressive increase with time after administration of BPA. The 10B concentration ratio for blood relative to CNS tissue increased with BPA dosage and reached a peak value of approximately 10:1 in the highest BPA dose group, at 1 h after i.p. injection. However, at 3 h after injection the 10B concentration ratios had decreased to approximately 3:1 in all of the BPA dose groups. After irradiation with thermal neutrons in combination with BPA at blood 10B concentrations of approximately 42 and approximately 93 microg g(-1), myelopathy developed after latent intervals of 20.0 +/- 0.6 and 20.0 +/- 1.2 weeks respectively. ED50 values (+/- s.e.) for the incidence of myelopathy were calculated from probit-fitted curves, and were 17.5 +/- 0.7 and 25.0 +/- 0.6 Gy after irradiation with thermal neutrons at blood 10B levels of approximately 42 and approximately 93 microg g(-1) respectively. The compound biological effectiveness (CBE) factor values, estimated from these data, were 0.67 +/- 0

  3. Central nervous system tolerance to boron neutron capture therapy with p-boronophenylalanine.

    PubMed Central

    Morris, G. M.; Coderre, J. A.; Micca, P. L.; Fisher, C. D.; Capala, J.; Hopewell, J. W.

    1997-01-01

    A rat spinal cord model was used to evaluate the effects of boron neutron capture irradiation on the central nervous system (CNS), using a range of doses of the boron delivery agent p-boronophenylalanine (BPA). Three doses of BPA 700, 1000 and 1600 mg kg(-1) were used to establish the biodistribution of boron-10 (10B) in blood, spinal cord and brain over a 3-h period after intraperitoneal (i.p.) administration. At the lowest dose of BPA used, blood 10B levels remained relatively stable over the 3-h sampling period. With the two higher doses of BPA, blood 10B concentrations were greatest at 1 h after BPA administration, and thereafter exhibited a biphasic clearance profile. The largest decline in blood 10B levels occurred between 1 and 2 h after i.p. injection and was most pronounced (approximately 45%) in the highest BPA dose group. Considered overall, 10B concentrations were marginally lower in the spinal cord than in the brain. Levels of 10B in both of these organs showed a slow but progressive increase with time after administration of BPA. The 10B concentration ratio for blood relative to CNS tissue increased with BPA dosage and reached a peak value of approximately 10:1 in the highest BPA dose group, at 1 h after i.p. injection. However, at 3 h after injection the 10B concentration ratios had decreased to approximately 3:1 in all of the BPA dose groups. After irradiation with thermal neutrons in combination with BPA at blood 10B concentrations of approximately 42 and approximately 93 microg g(-1), myelopathy developed after latent intervals of 20.0 +/- 0.6 and 20.0 +/- 1.2 weeks respectively. ED50 values (+/- s.e.) for the incidence of myelopathy were calculated from probit-fitted curves, and were 17.5 +/- 0.7 and 25.0 +/- 0.6 Gy after irradiation with thermal neutrons at blood 10B levels of approximately 42 and approximately 93 microg g(-1) respectively. The compound biological effectiveness (CBE) factor values, estimated from these data, were 0.67 +/- 0

  4. Boron neutron capture therapy of glioblastoma multiforme using the p- boronophenylalanine-fructose complex and epithermal neutrons

    SciTech Connect

    Coderre, J.A.; Chanana, A.D.; Joel, D.D.; Liu, H.B.; Slatkin, D.N.; Wielopolski, L.; Bergland, R.; Elowitz, E.; Chadha, M.

    1994-12-31

    The amino acid analogue p-boronophenylalanine (BPA) is under investigation as a neutron capture agent for BNCT of glioblastoma multiforme. A series of patients undergoing surgical removal of tumor received BPA orally as the free amino acid. Favorable tumor/blood boron concentration ratios were obtained but the absolute amount of boron in the tumor would have been insufficient for BNCT. BPA can be solubilized at neutral pH by complexation with fructose (BPA-F). Studies with rats suggest that intraperitoneal injection of BPA-F complex produces a much higher tumor boron concentration to rat intracerebral 9L gliosarcoma that were possible with oral BPA. Higher boron concentrations have allowed higher tumor radiation doses to be delivered while maintaining the dose to the normal brain vascular endothelium below the threshold of tolerance. The experience to date of the administration of BPA-F to one patient is provided in this report.

  5. Biodistribution of boron concentration on melanoma-bearing hamsters after administration of p-, m-, o-boronophenylalanine.

    PubMed

    Hiratsuka, J; Yoshino, K; Kondoh, H; Imajo, Y; Mishima, Y

    2000-04-01

    Although p-boronophenylalanine (p-BPA), a boronate analogue of tyrosine, has proven to be one of the most successful compounds for boron neutron capture therapy (BNCT) of malignant melanoma, the selective uptake mechanism of this compound into melanoma cells is not well understood. Therefore, the relationship between the structure of BPA and its specific affinity to melanoma cells appears worthy of investigation. In the present study, m- and o-boronophenylalanine (m- and o-BPA) were administered to melanoma-bearing hamsters and their uptake was measured. The time courses (0.5, 2.0, 4.0 and 48.0 h) of boron concentrations in melanoma, normal skin, and blood were determined in male Syrian (golden) hamsters bearing Greene's melanomas following a single intraperitoneal injection of either p-, m- or o-BPA (100 mg/kg of BPA fructose in 1.0 ml of saline). The boron concentrations in these tissues were measured by inductively coupled plasma-atomic emission spectrometry (ICP-AES). In melanoma, the order of boron uptake was p- > m- > o-BPA at all time points, and the boron concentrations obtained with p-BPA and m-BPA resembled each other in that they had a peak at 2 h after administration and decreased with time. The melanoma/skin boron concentration ratio of p-BPA had a peak at 4 h after administration and the ratio ranged between 7/1 and 8/1. On the other hand, m-BPA and o-BPA had a peak at 2 h and their ratios ranged between 4/1 and 5/1. The difference in the accumulations of p-BPA and m-BPA could be due to a difference in the property of p-BPA as a tyrosine analogue for melanin synthesis. The accumulation of m-BPA into melanoma might indicate the baseline level of metabolism-related amino acid transport. Our experimental findings indicate that this melanin synthesis, or the structural analogy between the boron compound and tyrosine as a precursor of melanin, is an important factor in the increased accumulation of p-BPA in melanoma cells.

  6. ET-14OPTIMISATION OF BORONOPHENYLALANINE (BPA) DELIVERY AND LAT1 EXPRESSION FOR THE CLINICAL APPLICATION OF BORON NEUTRON CAPTURE THERAPY (BNCT) IN GLIOBLASTOMA

    PubMed Central

    Cruickshank, Garth; Detta, Allah; Green, Stuart; Lockyer, Nick; Ngoga, Desire; Ghani, Zahir; Phoenix, Ben

    2014-01-01

    BNCT is a biologically targeted radiotherapy where preferential boron uptake interacts with a neutron beam in cancerous cells causing irreparable alpha DNA damage. This requires the delivery of at least 30 parts per million (ppm) of 10B into tumour tissue and <10ppm 10B in healthy tissue. Renewed interest arises from the advent of ‘accelerator’ technology and the recognition of specific uptake transporter in tumour cells. We report an optimising pharmacokinetic and tissue uptake study in glioblastoma patients to determine the route of delivering a new formulation of (p-boronophenylalanine, BPA), its pharmacokinetics, toxicity profile, and LAT1 dependent cellular uptake for a clinical trial. Using inductively-coupled plasma mass spectrometry (ICP-MS), secondary ion mass spectrometry (SIMS) and immunohistochemistry (IHC), boron was measured in blood, urine, cerebrospinal fluid (CSF), extracellular fluid (ECFmicrodialysis), and tissue prior to, during and post BPA infusions in newly-diagnosed patients (n = 10). Tumour and brain-around tumour (BAT) tissue were sampled at 2.5h and 3.5h post-infusion. Tumour and BAT, IHC expression levels of the BPA transporter L-amino acid transporter 1 (LAT-1) were recorded, and cellular boron levels, estimated in SIMS images.LAT1 dependent BPA uptake was also determined. There was no toxicity with BPA given at 375mg/kg as a 2h intravenous or intracarotid infusion with or without pre-infusion mannitol-induced BBB disruption. The Pk profile indicates highest plasma-to-brain concentration gradient from intracarotid infusion and BBB manipulation,with high boron concentrations in the brain compartment. SIMS boron ratio in tumour vs BAT was 0.96 intravenous,1.85 IV + mannitol BBB-D and 2.40 intracarotid cohorts, confirming improved delivery of boron. Tumour and BAT uptake varied, but sustained uptake in BAT (>30ppm boron) indicates potential BNCT targeting after surgery. Tumour boron uptake is governed by LAT-1 behaviour rather than BBB

  7. Boronophenylalanine, a boron delivery agent for boron neutron capture therapy, is transported by ATB0,+, LAT1 and LAT2.

    PubMed

    Wongthai, Printip; Hagiwara, Kohei; Miyoshi, Yurika; Wiriyasermkul, Pattama; Wei, Ling; Ohgaki, Ryuichi; Kato, Itsuro; Hamase, Kenji; Nagamori, Shushi; Kanai, Yoshikatsu

    2015-03-01

    The efficacy of boron neutron capture therapy relies on the selective delivery of boron carriers to malignant cells. p-Boronophenylalanine (BPA), a boron delivery agent, has been proposed to be localized to cells through transporter-mediated mechanisms. In this study, we screened aromatic amino acid transporters to identify BPA transporters. Human aromatic amino acid transporters were functionally expressed in Xenopus oocytes and examined for BPA uptake and kinetic parameters. The roles of the transporters in BPA uptake were characterized in cancer cell lines. For the quantitative assessment of BPA uptake, HPLC was used throughout the study. Among aromatic amino acid transporters, ATB(0,+), LAT1 and LAT2 were found to transport BPA with Km values of 137.4 ± 11.7, 20.3 ± 0.8 and 88.3 ± 5.6 μM, respectively. Uptake experiments in cancer cell lines revealed that the LAT1 protein amount was the major determinant of BPA uptake at 100 μM, whereas the contribution of ATB(0,+) became significant at 1000 μM, accounting for 20-25% of the total BPA uptake in MCF-7 breast cancer cells. ATB(0,+), LAT1 and LAT2 transport BPA at affinities comparable with their endogenous substrates, suggesting that they could mediate effective BPA uptake in vivo. The high and low affinities of LAT1 and ATB(0,+), respectively, differentiate their roles in BPA uptake. ATB(0,+), as well as LAT1, could contribute significantly to the tumor accumulation of BPA at clinical dose.

  8. A high-affinity [18F]-labeled phosphoramidate peptidomimetic PSMA-targeted inhibitor for PET imaging of prostate cancer

    DOE PAGES

    Ganguly, Tanushree; Dannoon, Shorouk; Hopkins, Mark R.; ...

    2015-06-09

    Here in this study, a structurally modified phosphoramidate scaffold, with improved prostate-specific membrane antigen (PSMA) avidity, stability and in vivo characteristics, as a PET imaging agent for prostate cancer (PCa), was prepared and evaluated. p-Fluorobenzoyl-aminohexanoate and 2-(3-hydroxypropyl)glycine were introduced into the PSMA-targeting scaffold yielding phosphoramidate 5. X-ray crystallography was performed on the PSMA/5 complex. [18F]5 was synthesized, and cell uptake and internalization studies were conducted in PSMA(+) LNCaP and CWR22Rv1 cells and PSMA(-) PC-3 cells. In vivo PET imaging and biodistribution studies were performed at 1 and 4 h post injection in mice bearing CWR22Rv1 tumor, with or without blockingmore » agent. The crystallographic data showed interaction of the p-fluorobenzoyl group with an arene-binding cleft on the PSMA surface. In vitro studies revealed elevated uptake of [18F]5 in PSMA(+) cells (2.2% in CWR22Rv1 and 12.1% in LNCaP) compared to PSMA(-) cells (0.08%) at 4 h. In vivo tumor uptake of 2.33% ID/g and tumor-to-blood ratio of 265:1 was observed at 4 h. In conclusion, we have successfully synthesized, radiolabeled and evaluated a new PSMA-targeted PET agent. The crystal structure of the PSMA/5 complex highlighted the interactions within the arene-binding cleft contributing to the overall complex stability. The high target uptake and rapid non-target clearance exhibited by [18F]5 in PSMA(+) xenografts substantiates its potential use for PET imaging of PCa.« less

  9. 18F-labeling and biodistribution of the novel fluoro-quinolone antimicrobial agent, trovafloxacin (CP 99,219).

    PubMed

    Babich, J W; Rubin, R H; Graham, W A; Wilkinson, R A; Vincent, J; Fischman, A J

    1996-11-01

    [18F]CP 99,219 [(1 alpha, 5 alpha, 6 alpha)-7-(6-amino-3-azabicyclo [3.1.0]hex-3-yl)-1-(2,4-difluorophenyl)-6-fluoro-1, 4-dihydro-4-oxo-1, 8-naphthyridine-3-carboxylic acid] was prepared by 18F for 19F exchange followed by reverse-phase HPLC purification. Studies of the effects of reaction time and temperature on 18F incorporation demonstrated that heating 1.0 mg of CP 99,219 in 0.5 cc of DMSO with 4.5 mg of K2CO3 and 24 mg of Kryptofix for 15 min at 160 degrees C results in the optimal compromise between radiochemical yield and purity. This method routinely provides radiochemical yields of 15-30% [EOS] with radiochemical purities of > 97%. Varying the concentration of CP 99,219 in the reaction mixture had no effect on yield. Biodistribution studies in rats demonstrated that significant concentrations of drug accumulate in most tissues. The tissues with the highest concentrations of drug were intestine, liver, kidney, and stomach.

  10. Preclinical evaluation of an 18F-labelled β1-adrenoceptor selective radioligand based on ICI 89,406

    PubMed Central

    Law, Marilyn P.; Wagner, Stefan; Kopka, Klaus; Renner, Christiane; Pike, Victor W.; Schober, Otmar; Schäfers, Michael

    2010-01-01

    Purpose Radioligand binding studies indicate a down-regulation of myocardial β1-adrenoceptors (β1-AR) in cardiac disease which may or may not be associated with a decrease in β2-ARs. We have chosen ICI 89,406, a β1-selective AR antagonist, as the lead structure to develop new β1-AR radioligands for PET and have synthesised a fluoro-ethoxy derivative (F-ICI). Methods (S)-N-[2-[3-(2-Cyano-phenoxy)-2-hydroxy-propylamino]-ethyl]-N′-[4-(2-[18F]fluoro-ethoxy)-phenyl]-urea ((S)-[18F]F-ICI) was synthesised. Myocardial uptake of radioactivity after intravenous injection of (S)-[18F]F-ICI into adult CD1 mice or Wistar rats was assessed with positron emission tomography (PET) and postmortem dissection. Metabolism was assessed by high-performance liquid chromatography analysis of plasma and urine. Results The heart was visualised with PET after injection of (S)-[18F]F-ICI but neither unlabelled F-ICI nor propranolol (non-selective β-AR antagonist) injected 15 min after (S)-[18F]F-ICI affected myocardial radioactivity. Ex vivo dissection demonstrated that predosing with propranolol or CGP 20712 (β1-selective AR-antagonist) did not affect myocardial radioactivity. Radiometabolites rapidly appeared in plasma and both (S)-[18F]F-ICI and radiometabolites accumulated in urine. Conclusions Myocardial uptake of (S)-[18F]F-ICI after intravenous injection was mainly at sites unrelated to β1-ARs. (S)-[18F]F-ICI is not a suitable β1-selective-AR radioligand for PET. PMID:20447564

  11. A series of 18F-labelled pyridinylphenyl amides as subtype-selective radioligands for the dopamine D3 receptor.

    PubMed

    Hocke, Carsten; Maschauer, Simone; Hübner, Harald; Löber, Stefan; Utz, Wolfgang; Kuwert, Torsten; Gmeiner, Peter; Prante, Olaf

    2010-06-07

    Synthesis, biological activity, and structure-selectivity relationship (SSR) studies of a novel series of potential dopamine D3 receptor radioligands as imaging agents for positron emission tomography (PET) are reported. Considering a structurally diverse library of D3 ligands, SSR studies were performed for a new series of fluorinated pyridinylphenyl amides using CoMFA and CoMSIA methods. The in vitro D3 affinities of the predicted series of biphenyl amide ligands 9 a-d revealed single-digit to sub-nanomolar potencies (K(i)=0.52-1.6 nM), displaying excellent D3 selectivity over the D2 subtype of 110- to 210-fold for the test compounds 9 a-c. Radiofluorination by nucleophilic substitution of Br or NO(2) by (18)F led to radiochemical yields of 66-92 % for [(18)F]9 a-d. However, the specific activities of [(18)F]9 b and [(18)F]9 d were insufficient, rendering their use for in vivo studies impossible. Biodistribution studies of [(18)F]9 a and [(18)F]9 c using rat brain autoradiography revealed accumulation in the ventricles, thus indicating insufficient biokinetic properties of [(18)F]9 a and [(18)F]9 c for D3 receptor imaging in vivo.

  12. 18F-labeled Single-Stranded DNA Aptamer for PET Imaging of Protein Tyrosine Kinase-7 Expression

    PubMed Central

    Wang, Lu; Wang, Zhe; Yang, Xiangyu; Dewhurst, Andrew; Ma, Ying; Zhu, Guizhi; Niu, Gang; Kiesewetter, Dale O.; Vasdev, Neil; Liang, Steven H.; Chen, Xiaoyuan

    2016-01-01

    Protein tyrosine kinase-7 (PTK7), a member of receptor tyrosine kinase superfamily initially identified as colon carcinoma kinase-4 (CCK-4), is highly expressed in various human malignancies. Its expression was found to correlate with aggressive biological behaviors such as increased cell proliferation, invasiveness and migration. Despite the importance and unmet need of imaging PTK7 in vivo, there is currently no clinically-relevant method to visualize tumoral PTK7 expression noninvasively such as PET or SPECT. This study aims to develop a specific, selective and high affinity PET radioligand based on single-stranded DNA (ssDNA) aptamer to address this challenge. Methods Sgc8, a 41-oligonucleotide that targets to PTK7, was labeled with F-18 using a two-step radiochemical synthesis, which featured a direct one-step radiofluorination on the distinctive spirocyclic hypervalent iodine(III) precursor to give 18F-fluorobenzyl azide followed by copper mediated “click” conjugation with Sgc8-alkyne. 18F-Sgc8 was evaluated in vitro and in vivo in two cell lines, HCT116 and U87MG, which express high and low amounts of PTK7, respectively. Results Sgc8 was labeled efficiently with F-18 in an isolated radiochemical yield of 62 ± 2%, non-decay-corrected (ndc) based on 18F-fluorobenzyl azide. 18F-Tr-Sgc8 was found to possess high affinity binding to both cell lines, with IC50 values for HCT116 as 2.7 ± 0.6 nM and U87MG as 16.9 ± 2.1 nM. In vivo PET imaging clearly visualized PTK7 expression in HCT116 xenografted mice with tumor uptake of 0.76 ± 0.09 %ID/g at 30 min post-injection (p.i.) for the subcutaneous tumor model and greater than 1.5 %ID/g for the liver metastasis model. U87MG xenograft tumors had much lower tracer accumulation (0.13 ± 0.06 %ID/g at 30 min p.i.), which was consistent with the lower expression of PTK7 in this tumor model. The labeled aptamer was rapidly cleared from the blood through the kidneys and bladder to give high tumor-to-blood and tumor-to-muscle ratios of 7.29 ± 1.51 and 10.25 ± 2.08, respectively. Conclusions The F-18 radiolabeling methodology shown here is a very robust procedure for labeling aptamers and similar chemical moieties, and can be applied to many different targets. Quantification of PTK7 using 18F-Tr-Sgc8 may be suitable for clinical translation and might help in the future to select and monitor appropriate therapies. PMID:26315836

  13. Dosimetry of 18F-Labeled Tyrosine Kinase Inhibitor SKI-249380, a Dasatinib-Tracer for PET Imaging

    PubMed Central

    Dunphy, Mark P. S.; Zanzonico, Pat; Veach, Darren; Somwar, Romel; Pillarsetty, Nagavarakishore; Lewis, Jason; Larson, Steven

    2011-01-01

    Purpose To obtain estimates of human normal-organ radiation doses of 18F-SKI-249380, as a prerequisite step towards first-in-human trial. 18F-SKI-249380 is a first-of-its-kind PET tracer for imaging the in vivo pharmacokinetics of dasatinib, an investigational targeted therapy for solid malignancies. Procedures Isoflurane-anesthetized mice received tracer dose via tail vein. Organ time-integrated activity coefficients, fractional urinary and hepatobiliary excretion, and total-body clearance kinetics were derived from PET data, with allometric extrapolation to the Standard Man anatomic model and normal-organ-absorbed dose calculations using OLINDA/EXM software. Results The human effective dose was 0.031 mSv/MBq. The critical organ was the upper large intestine, with a dose equivalent of 0.25 mSv/MBq. A 190-MBq administered activity of 18F-SKI-249380 is thus predicted to expose an adult human to radiation doses generally comparable to those of routinely used diagnostic radiopharmaceuticals. Conclusions Animal-based human dose estimates support first-in-human testing of 18F-SKI-249380. PMID:21161687

  14. Green approaches to late-stage fluorination: radiosyntheses of (18)F-labelled radiopharmaceuticals in ethanol and water.

    PubMed

    Stewart, Megan N; Hockley, Brian G; Scott, Peter J H

    2015-10-11

    Green strategies for late-stage fluorination with (18)F, in which ethanol and water are the only solvents used throughout the entire radiolabeling process (azeotropic drying, nucleophilic fluorination, purification and formulation), have been developed and applied to the radiosyntheses of a range of radiopharmaceuticals commonly employed in clinical PET imaging.

  15. Novel 18F labeling strategy for polyester-based NPs for in vivo PET-CT imaging.

    PubMed

    Di Mauro, Primiano Pio; Gómez-Vallejo, Vanessa; Baz Maldonado, Zuriñe; Llop Roig, Jordi; Borrós, Salvador

    2015-03-18

    Drug-loaded nanocarriers and nanoparticulate systems used for drug release require a careful in vivo evaluation in terms of physicochemical and pharmacokinetic properties. Nuclear imaging techniques such as positron emission tomography (PET) are ideal and noninvasive tools to investigate the biodistribution and biological fate of the nanostructures, but the incorporation of a positron emitter is required. Here we describe a novel approach for the (18)F-radiolabeling of polyester-based nanoparticles. Our approach relies on the preparation of the radiolabeled active agent 4-[(18)F]fluorobenzyl-2-bromoacetamide ([(18)F]FBBA), which is subsequently coupled to block copolymers under mild conditions. The labeled block copolymers are ultimately incorporated as constituent elements of the NPs by using a modified nano coprecipitation method. This strategy has been applied in the current work to the preparation of peptide-functionalized NPs with potential applications in drug delivery. According to the measurements of particle size and zeta potential, the radiolabeling process did not result in a statistically significant alteration of the physicochemical properties of the NPs. Moreover, radiochemical stability studies showed no detachment of the radioactivity from NPs even at 12 h after preparation. The radiolabeled NPs enabled the in vivo quantification of the biodistribution data in rats using a combination of imaging techniques, namely, PET and computerized tomography (CT). Low accumulation of the nanoparticles in the liver and their elimination mainly via urine was found. The different biodistribution pattern obtained for the "free" radiolabeled polymer suggests chemical and radiochemical integrity of the NPs under investigation. The strategy reported here may be applied to any polymeric NPs containing polymers bearing a nucleophile, and hence our novel strategy may find application for the in vivo and noninvasive investigation of a wide range of NPs.

  16. Specific killing effect of 10B1-para-boronophenylalanine in thermal neutron capture therapy of malignant melanoma: in vitro radiobiological evaluation

    SciTech Connect

    Ichihashi, M.; Nakanishi, T.; Mishima, Y.

    1982-03-01

    A 10B-dopa analogue, 10B1-para-boronophenylalanine (10B1-BPA) has been found to have a marked melanoma killing effect as expressed by the Do value, 0.9-1.2 X 10(12) n/cm2. The Do value of the neutron alone is 2.8 X 10(12) n/cm2. After the introduction of high LET irradiation into radiotherapy, its higher energy deposition in the target cancer cells is one of the major problems currently to be solved. This can be achieved by our thermal neutron capture therapy in the order of cellular dimensions when we have highly tumor-seeking 10B-compounds available. Our present evidence seems to indicate that our new 10B1-BPA can highly concentrate 10B into melanoma cells, to as much as 11 times the level of the medium in the in vitro system.

  17. Quantitative bioimaging of p-boronophenylalanine in thin liver tissue sections as a tool for treatment planning in boron neutron capture therapy.

    PubMed

    Reifschneider, Olga; Schütz, Christian L; Brochhausen, Christoph; Hampel, Gabriele; Ross, Tobias; Sperling, Michael; Karst, Uwe

    2015-03-01

    An analytical method using laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) was developed and applied to assess enrichment of 10B-containing p-boronophenylalanine-fructose (BPA-f) and its pharmacokinetic distribution in human tissues after application for boron neutron capture therapy (BNCT). High spatial resolution (50 μm) and limits of detection in the low parts-per-billion range were achieved using a Nd:YAG laser of 213 nm wavelength. External calibration by means of 10B-enriched standards based on whole blood proved to yield precise quantification results. Using this calibration method, quantification of 10B in cancerous and healthy tissue was carried out. Additionally, the distribution of 11B was investigated, providing 10B enrichment in the investigated tissues. Quantitative imaging of 10B by means of LA-ICP-MS was demonstrated as a new option to characterise the efficacy of boron compounds for BNCT.

  18. Cellular effect of thermal neutron capture treatment using 10B1-para-boronophenylalanine: lethal effect on melanoma cells with different degrees of X-ray sensitivity.

    PubMed

    Utsumi, H; Tano, K; Mizuma, N; Kobayashi, T; Ichihashi, M

    1996-09-01

    We studied the effect of neutron capture treatment using 10B-compound on X-ray sensitive P-39 and X-ray resistant G-361 human melanoma cell lines, and found a high lethal effect of boron neutron capture therapy in comparison with conventional ionizing radiation. The P-39 line was sensitive to thermal neutron radiation, and extremely sensitive to bleomycin treatment, whereas the G-361 line was resistant to both forms of treatment; however, the two cell lines had similar sensitivity to thermal neutron radiation after pretreatment with 10B1-para-boronophenylalanine (10B1-BPA, 200 micrograms/ml medium). These results show that the thermal neutron capture products (a 7Li nucleus and alpha particle) are highly damaging and short range in tumor cells and thus more efficiently inactivate melanoma cells irrespective of x-ray sensitivity, than conventional X-ray-irradiation.

  19. L-Boronophenylalanine-Mediated Boron Neutron Capture Therapy for Malignant Glioma Progressing After External Beam Radiation Therapy: A Phase I Study

    SciTech Connect

    Kankaanranta, Leena; Seppaelae, Tiina; Koivunoro, Hanna; Vaelimaeki, Petteri; Beule, Annette; Collan, Juhani; Kortesniemi, Mika; Uusi-Simola, Jouni; Kotiluoto, Petri; Auterinen, Iiro; Seren, Tom; Paetau, Anders; Saarilahti, Kauko; Savolainen, Sauli; Joensuu, Heikki

    2011-06-01

    Purpose: To investigate the safety of boronophenylalanine-mediated boron neutron capture therapy (BNCT) in the treatment of malignant gliomas that progress after surgery and conventional external beam radiation therapy. Methods and Materials: Adult patients who had histologically confirmed malignant glioma that had progressed after surgery and external beam radiotherapy were eligible for this Phase I study, provided that >6 months had elapsed from the last date of radiation therapy. The first 10 patients received a fixed dose, 290 mg/kg, of L-boronophenylalanine-fructose (L-BPA-F) as a 2-hour infusion before neutron irradiation, and the remaining patients were treated with escalating doses of L-BPA-F, either 350 mg/kg, 400 mg/kg, or 450 mg/kg, using 3 patients on each dose level. Adverse effects were assessed using National Cancer Institute Common Toxicity Criteria version 2.0. Results: Twenty-two patients entered the study. Twenty subjects had glioblastoma, and 2 patients had anaplastic astrocytoma, and the median cumulative dose of prior external beam radiotherapy was 59.4 Gy. The maximally tolerated L-BPA-F dose was reached at the 450 mg/kg level, where 4 of 6 patients treated had a grade 3 adverse event. Patients who were given >290 mg/kg of L-BPA-F received a higher estimated average planning target volume dose than those who received 290 mg/kg (median, 36 vs. 31 Gy [W, i.e., a weighted dose]; p = 0.018). The median survival time following BNCT was 7 months. Conclusions: BNCT administered with an L-BPA-F dose of up to 400 mg/kg as a 2-hour infusion is feasible in the treatment of malignant gliomas that recur after conventional radiation therapy.

  20. Subcellular localization of p-boronophenylalanine-delivered boron-10 in the rat 9L gliosarcoma: Cryogenic preparation in vitro and in vivo

    SciTech Connect

    Bennett, B.D.; Mumford-Zisk, J.; Morrison, G.H.; Coderre, J.A.

    1994-10-01

    A well-characterized in vitro cryogenic preparation for ion microscopic isotope imaging, which minimizes redistribution of diffusible species, was used to determine the distribution of boron in GS-9L gliosarcoma cells incubated with the boron neutron capture therapy agent, p-boronophenylalanine (BPA). At the subcellular level, boron from BPA distributes relatively homogeneously within the glioma cell. Boron from BPA was eliminated rapidly, indicating that most is unbound. Thus a large pool of boron is susceptible to diffusion artifact. Removal of this artifact increases the degree of confidence in microdosimetric results inferred from the homogeneous subcellular distribution. The ion microscopic imaging of boron in subcutaneous tumors cryofixed in situ was achieved in rats treated with BPA. Boron signals from BPA were adequate to image microdistributions at the 1-{mu}m resolution level. As in the in vitro case, boron did not localize discretely at the subcellular level. However, boron heterogeneity was seen at the tissue level. Physiologically valid cellular potassium and sodium levels were seen, which demonstrates minimized redistribution artifact. Future tissue studies designed to correlate ion microscopic boron images to microscopic structure are feasible using cryogenic sample preparation and ion microscopy. 32 refs., 4 figs.

  1. Boronophenylalanine, a boron delivery agent for boron neutron capture therapy, is transported by ATB0,+, LAT1 and LAT2

    PubMed Central

    Wongthai, Printip; Hagiwara, Kohei; Miyoshi, Yurika; Wiriyasermkul, Pattama; Wei, Ling; Ohgaki, Ryuichi; Kato, Itsuro; Hamase, Kenji; Nagamori, Shushi; Kanai, Yoshikatsu

    2015-01-01

    The efficacy of boron neutron capture therapy relies on the selective delivery of boron carriers to malignant cells. p-Boronophenylalanine (BPA), a boron delivery agent, has been proposed to be localized to cells through transporter-mediated mechanisms. In this study, we screened aromatic amino acid transporters to identify BPA transporters. Human aromatic amino acid transporters were functionally expressed in Xenopus oocytes and examined for BPA uptake and kinetic parameters. The roles of the transporters in BPA uptake were characterized in cancer cell lines. For the quantitative assessment of BPA uptake, HPLC was used throughout the study. Among aromatic amino acid transporters, ATB0,+, LAT1 and LAT2 were found to transport BPA with Km values of 137.4 ± 11.7, 20.3 ± 0.8 and 88.3 ± 5.6 μM, respectively. Uptake experiments in cancer cell lines revealed that the LAT1 protein amount was the major determinant of BPA uptake at 100 μM, whereas the contribution of ATB0,+ became significant at 1000 μM, accounting for 20–25% of the total BPA uptake in MCF-7 breast cancer cells. ATB0,+, LAT1 and LAT2 transport BPA at affinities comparable with their endogenous substrates, suggesting that they could mediate effective BPA uptake in vivo. The high and low affinities of LAT1 and ATB0,+, respectively, differentiate their roles in BPA uptake. ATB0,+, as well as LAT1, could contribute significantly to the tumor accumulation of BPA at clinical dose. PMID:25580517

  2. Selectivity of boron carriers for boron neutron capture therapy: pharmacological studies with borocaptate sodium, L-boronophenylalanine and boric acid in murine tumors.

    PubMed

    Gregoire, V; Begg, A C; Huiskamp, R; Verrijk, R; Bartelink, H

    1993-04-01

    Borocaptate sodium (BSH) and L-boronophenylalanine (L-BPA) are two boron carriers used for boron neutron capture therapy (BNCT) in the treatment of glioblastoma and melanoma, respectively. The suitability of these two compounds was evaluated on the basis of pharmacokinetic studies aiming at characterizing their biodistribution, tumor uptake and tumor selectivity. Boric acid was also used as a reference compound since it is nonselective and relatively freely diffusible. The compounds were investigated in two tumor models, a B16 pigmented melanoma and the RIF1 sarcoma. Mice were sacrificed after different boron doses at various post-injection times and tissue and plasma levels measured using inductively coupled plasma atomic emission spectroscopy (ICP-AES). The proposed minimum effective tumor boron concentration of 15 ppm was achieved in both tumor models for the three compounds tested, although only for L-BPA in the melanoma was this achieved when tumor-plasma ratios were above 1. In the RIF1 model, maximum tumor concentrations of 44 and 31 ppm B were reached after administration of 50 micrograms B/g body weight for boric acid and BSH, respectively. After administration of 12.5 micrograms B/g of L-BPA, maximum concentrations of 15 and 21 ppm were found in the RIF1 and B16 models, respectively. Tumor-plasma ratios (TPR) for BSH remained close to or below unity at all times studied in both tumors. Brain levels of BSH were very low, however, leading to tumor-brain ratios markedly greater than 1 at all times. L-BPA and boric acid showed TPR values above unity in both tumor models, reaching 3.2 in B16.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. SIMS ion microscopy imaging of boronophenylalanine (BPA) and 13C15N-labeled phenylalanine in human glioblastoma cells: Relevance of subcellular scale observations to BPA-mediated boron neutron capture therapy of cancer

    NASA Astrophysics Data System (ADS)

    Chandra, Subhash; Lorey, Daniel R., II

    2007-02-01

    p-Boronophenylalanine (BPA) is a clinically approved boron neutron capture therapy (BNCT) agent currently being used in clinical trials of glioblastoma multiforme, melanoma and liver metastases. Secondary ion mass spectrometry (SIMS) observations from the Cornell SIMS Laboratory provided support for using a 6 h infusion of BPA, instead of a 2 h infusion, for achieving higher levels of boron in brain tumor cells. These observations were clinically implemented in Phase II experimental trials of glioblastoma multiforme in Sweden. However, the mechanisms for higher BPA accumulation with longer infusions have remained unknown. In this work, by using 13C15N-labeled phenylalanine and T98G human glioblastoma cells, comparisons between the 10B-delivery of BPA and the accumulation of labeled phenylalanine after 2 and 6 h treatments were made with a Cameca IMS-3f SIMS ion microscope at 500 nm spatial resolution in fast frozen, freeze-fractured, freeze-dried cells. Due to the presence of the Na-K-ATPase in the plasma membrane of most mammalian cells, the cells maintain an approximately 10/1 ratio of K/Na in the intracellular milieu. Therefore, the quantitative imaging of these highly diffusible species in the identical cell in which the boron or labeled amino acid was imaged provides a rule-of-thumb criterion for validation of SIMS observations and the reliability of the cryogenic sampling. The labeled phenylalanine was detected at mass 28, as the 28(13C15N)- molecular ion. Correlative analysis with optical and confocal laser scanning microscopy revealed that fractured freeze-dried glioblastoma cells contained well-preserved ultrastructural details with three discernible subcellular regions: a nucleus or multiple nuclei, a mitochondria-rich perinuclear cytoplasmic region and the remaining cytoplasm. SIMS analysis revealed that the overall cellular signals of both 10B from BPA and 28CN- from labeled phenylalanine increased approximately 1.6-fold between the 2 and 6 h exposures

  4. Long-term infusions of p-boronophenylalanine for boron neutron capture therapy: evaluation using rat brain tumor and spinal cord models.

    PubMed

    Morris, G M; Micca, P L; Nawrocky, M M; Weissfloch, L E; Coderre, J A

    2002-12-01

    Rat 9L gliosarcoma cells infiltrating the normal brain have been shown previously to accumulate only approximately 30% as much boron as the intact tumor after administration of the boronated amino acid p-boronophenylalanine (BPA). Long-term i.v. infusions of BPA were shown previously to increase the boron content of these infiltrating tumor cells significantly. Experiments to determine whether this improved BPA distribution into infiltrating tumor cells after a long-term i.v. infusion improves tumor control after BNCT in this brain tumor model and whether it has any deleterious effects in the response of the rat spinal cord to BNCT are the subjects of the present report. BPA was administered in a fructose solution at a dose of 650 mg BPA/kg by single i.p. injection or by i.v. infusion for 2 h or 6 h, at 330 mg BPA/kg h(-1). At 1 h after the end of either the 2-h or the 6-h infusion, the CNS:blood (10)B partition ratio was 0.9:1. At 3 h after the single i.p. injection, the ratio was 0.6:1. After spinal cord irradiations, the ED(50) for myeloparesis was 14.7 +/- 0.4 Gy after i.p. administration of BPA and 12.9 +/- 0.3 Gy in rats irradiated after a 6-h i.v. infusion of BPA; these values were significantly different (P < 0.001). After irradiation with 100 kVp X rays, the ED(50) was 18.6 +/- 0.1 Gy. The boron compound biological effectiveness (CBE) factors calculated for the boron neutron capture dose component were 1.2 +/- 0.1 for the i.p. BPA administration protocol and 1.5 +/- 0.1 after irradiation using the 6-h i.v. BPA infusion protocol (P < 0.05). In the rat 9L gliosarcoma brain tumor model, the blood boron concentrations at 1 h after the end of the 2-h infusion (330 mg BPA/kg h(-1); n = 15) or after the 6-h infusion (190 mg BPA/kg h(-1); n = 13) were 18.9 +/- 2.2 microg 10B/g and 20.7 +/- 1.8 microg 10B/g, respectively. The irradiation times were adjusted individually, based on the preirradiation blood sample, to deliver a predicted 50% tumor control dose of 8

  5. Design, synthesis and evaluation in an LPS rodent model of neuroinflammation of a novel (18)F-labelled PET tracer targeting P2X7.

    PubMed

    Fantoni, Enrico Raffaele; Dal Ben, Diego; Falzoni, Simonetta; Di Virgilio, Francesco; Lovestone, Simon; Gee, Antony

    2017-12-01

    The P2X7 receptor has been shown to play a fundamental role in the initiation and sustenance of the inflammatory cascade. The development of a novel fluorine-18 PET tracer superior and with a longer half-life to those currently available is a promising step towards harnessing the therapeutic and diagnostic potential offered by this target. Inspired by the known antagonist A-804598, the present study outlines the design via molecular docking, synthesis and biological evaluation of the novel P2X7 tracer [(18)F]EFB. The tracer was radiolabelled via a three-step procedure, in vitro binding assessed in P2X7-transfected HEK293 and in B16 cells by calcium influx assays and an initial preclinical evaluation was performed in a lipopolysaccharide (LPS)-injected rat model of neuroinflammation. The novel tracer [(18)F]EFB was synthesised in 210 min in 3-5% decay-corrected radiochemical yield (DC RCY), >99% radiochemical purity (RCP) and >300 GBq/μmol and fully characterised. Functional assays showed that the compound binds with nM K i to human, rat and mouse P2X7 receptors. In vivo, [(18)F]EFB displayed a desirable distribution profile, and while it showed low blood-brain barrier penetration, brain uptake was quantifiable and displayed significantly higher mean longitudinal uptake in inflamed versus control rat CNS regions. [(18)F]EFB demonstrates strong in vitro affinity to human and rodent P2X7 and limited yet quantifiable BBB penetration. Considering the initial promising in vivo data in an LPS rat model with elevated P2X7 expression, this work constitutes an important step in the development of a radiotracer useful for the diagnosis and monitoring of clinical disorders with associated neuroinflammatory processes.

  6. Sulfonation of Tyrosine as a Method to Improve Biodistribution of Peptide-Based Radiotracers: Novel (18)F-Labelled Cyclic RGD Analogues.

    PubMed

    Haskali, Mohammad Baqir; Denoyer, Delphine; Noonan, Wayne; Cullinane, Carleen; Rangger, Christine; Pouliot, Normand; Haubner, Roland; Roselt, Peter D; Hicks, Rodney J; Hutton, Craig A

    2017-02-13

    The labeling of peptides with positron emitting radionuclides has long held the promise of a wide range of PET agents possessing high affinity and selectivity. Not surprisingly, controlling the biodistribution of these agents has proven to be a major challenge in their successful application. Modification of peptide hydrophilicity in order to increase renal clearance has been a common endeavor to improve overall biodistribution. Herein, we examine the effect of site-specific sulfonation of tyrosine moieties in cyclic(RGDyK) peptides as a means to enhance their hydrophilicity and improve their biodistribution. The novel sulfonated cyclic(RGDyK) peptides were conjugated directly to 4-nitrophenyl 2-[18F]fluoropropionate and the biodistribution of the radiolabeled peptides was compared with that of their non-sulfonated, clinically relevant counterparts, [18F]GalactoRGD and [18F]FPPRGD2. Site-specific sulfonation of the tyrosine residues was shown to increase hydrophilicity and improve biodistribution of the RGD peptides, despite contributing just 79 Da towards the MW, compared with 189 Da for both the 'Galacto' and mini-PEG moieties, suggesting this may be a broadly applicable approach to enhancing biodistribution of radiolabelled peptides.

  7. Specific, reversible binding of [18F]benperidol to baboon D2 receptors: PET evaluation of an improved 18F-labeled ligand.

    PubMed

    Moerlein, S M; Perlmutter, J S; Welch, M J

    1995-08-01

    [18F]Benperidol ([18F]BP), a positron-emitting analogue of the dopaminergic D2 antagonist benperidol, was evaluated as a radiopharmaceutical for use with positron emission tomography (PET). PET imaging of baboons after i.v. injection of [18F]BP indicated that the radiofluorinated ligand rapidly localized in vivo within dopaminergic receptor-rich cerebral tissues, and that selective disposition was retained for over 2 h. Pretreatment of an animal with unlabeled receptor-specific antagonists prior to injection of [18F]BP confirmed that the radioligand bound specifically to central D2 receptors in vivo, and not to S2 or D1 receptors. [18F]BP bound to D2 receptors in a reversible manner; unlabeled eticlopride displaced D2 receptor-bound [18F]BP in vivo. The radioligand was metabolized in the periphery to polar metabolites which are not expected to cross the blood-brain barrier. [18F]BP has advantages over other tracers as a radiopharmaceutical for PET study of central D2 receptor activity, and can be applied for noninvasive evaluation of the interaction of unlabeled drugs with central D2 receptor sites.

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

    PubMed

    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 ((18)F) to give [(18)F]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 [(18)F]3a was localized to cell surface σ receptors, while ∼10% of [(18)F]3a was internalized within cells after incubation for 3.5 h. Serial PET imaging in mice bearing PC-3 tumors revealed that uptake of [(18)F]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 [(18)F]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 [(18)F]3a. Prominent σ receptor-specific uptake of [(18)F]3a in prostate tumors and its subsequent clear visualization with PET imaging indicate potential utility for the diagnosis of prostate carcinoma.

  9. Reusable electrochemical cell for rapid separation of [18F]fluoride from [18O]water for flow-through synthesis of 18F-labeled tracers

    PubMed Central

    Sadeghi, Saman; Liang, Vincent; Cheung, Shilin; Woo, Suh; Wu, Curtis; Ly, Jimmy; Deng, Yuliang; Eddings, Mark; van Dam, R. Michael

    2015-01-01

    A brass-platinum electrochemical micro flow cell was developed to extract [18F]fluoride from an aqueous solution and release it into an organic based solution, suitable for subsequent radio-synthesis, in a fast and reliable manner. This cell does not suffer electrode erosion and is thus reusable while operating faster by enabling increased voltages. By optimizing temperature, trapping and release potentials, flow rates, and electrode materials, an overall [18F]fluoride trapping and release efficiency of 84±5% (n=7) was achieved. X-ray photoelectron spectroscopy (XPS) was used to analyze electrode surfaces of various metal-metal systems and the findings were correlated with the performance of the electrochemical cell. To demonstrate the reactivity of the released [18F]fluoride, the cell was coupled to a flow-through reactor and automated synthesis of [18F]FDG with a repeatable decay-corrected yield of 56±4% (n=4) was completed in <15 min. A multi-human dose of 5.92 GBq [18F]FDG was also demonstrated. PMID:23474380

  10. No-carrier-added nucleophilic 18F-labelling in an electrochemical cell exemplified by the routine production of [18F]altanserin.

    PubMed

    Hamacher, K; Coenen, H H

    2006-09-01

    A new type of electrochemical cell with anodic deposition of no-carrier-added [(18)F]fluoride and variable reaction volume has been developed. The reactor is designed for small reaction volumes and non-thermal drying of [(18)F]fluoride. The implementation of this reactor into a complete remotely controlled synthesis device is described for the routine production of [(18)F]altanserin. A radiochemical yield of 23+/-5% was obtained via cryptate-mediated nucleophilic (18)F-fluorination. Batches of up to 6 GBq [(18)F]altanserin, suitable for human application, with a molar activity of >500 GBq/micromol were obtained within 75 min.

  11. Development of Purine-Derived 18F-Labeled Pro-drug Tracers for Imaging of MRP1 Activity with PET

    PubMed Central

    2014-01-01

    Multidrug resistance-associated protein 1 (MRP1) is a drug efflux transporter that has been implicated in the pathology of several neurological diseases and is associated with development of multidrug resistance. To enable measurement of MRP1 function in the living brain, a series of 6-halopurines decorated with fluorinated side chains have been synthesized and evaluated as putative pro-drug tracers. The tracers were designed to undergo conjugation with glutathione within the brain and hence form the corresponding MRP1 substrate tracers in situ. 6-Bromo-7-(2-[18F]fluoroethyl)purine showed good brain uptake and rapid metabolic conversion. Dynamic PET imaging demonstrated a marked difference in brain clearance rates between wild-type and mrp1 knockout mice, suggesting that the tracer can allow noninvasive assessment of MRP1 activity in vivo. PMID:24456310

  12. Cell cycle dependence of boron uptake from two boron compounds used for clinical neutron capture therapy.

    PubMed

    Yoshida, F; Matsumura, A; Shibata, Y; Yamamoto, T; Nakauchi, H; Okumura, M; Nose, T

    2002-12-10

    In neutron capture therapy, it is important that the boron is selectively uptaken by tumor cells. In the present study, we used flow cytometry to sort the cells in the G0/G1 phase and those in the G2/M phase, and the boron concentration in each fraction was measured with inductively coupled plasma atomic emission spectroscopy. The results revealed that sodium borocaptate and boronophenylalanine (BPA), were associated with higher rates of boron uptake in the G2/M than in the G0/G1 phase. However, the difference was more prominent in the case of BPA. The G2/M:G0/G1 ratio decreased as a function of exposure time in BPA containing culture medium, thereby indicating the cell cycle dependency of BPA uptake. Such heterogeneity of boron uptake by tumor cells should be considered for microdosimetry.

  13. Development and Successful Validation of Simple and Fast TLC Spot Tests for Determination of Kryptofix® 2.2.2 and Tetrabutylammonium in 18F-Labeled Radiopharmaceuticals

    PubMed Central

    Kuntzsch, Matthias; Lamparter, Denis; Brüggener, Nils; Müller, Marco; Kienzle, Gabriele J.; Reischl, Gerald

    2014-01-01

    Kryptofix® 2.2.2 (Kry) or tetrabutylammonium (TBA) are commonly used as phase transfer catalysts in 18F-radiopharmaceutical productions for positron emission tomography (PET). Due to their toxicity, quality control has to be performed before administration of the tracer to assure that limit concentration of residual reagent is not reached. Here, we describe the successful development and pharmaceutical validation (for specificity, accuracy and detection limit) of a simplified color spot test on TLC plates. We were able to prove its applicability as a general, time and resources saving, easy to handle and reliable method in daily routine analyzing 18F-tracer formulations for Kry (in [18F]FDG or [18F]FECh) or TBA contaminations (in [18F]FLT) with special regard to complex matrix compositions. PMID:24830987

  14. (18)F-Labeled 1,4-Dioxa-8-azaspiro[4.5]decane Derivative: Synthesis and Biological Evaluation of a σ1 Receptor Radioligand with Low Lipophilicity as Potent Tumor Imaging Agent.

    PubMed

    Xie, Fang; Bergmann, Ralf; Kniess, Torsten; Deuther-Conrad, Winnie; Mamat, Constantin; Neuber, Christin; Liu, Boli; Steinbach, Jörg; Brust, Peter; Pietzsch, Jens; Jia, Hongmei

    2015-07-23

    We report the syntheses and evaluation of series of novel piperidine compounds with low lipophilicity as σ1 receptor ligands. 8-(4-(2-Fluoroethoxy)benzyl)-1,4-dioxa-8-azaspiro[4.5]decane (5a) possessed high affinity (K(i) = 5.4 ± 0.4 nM) for σ1 receptors and selectivity for σ2 receptors (30-fold) and the vesicular acetylcholine transporter (1404-fold). [(18)F]5a was prepared using a one-pot, two-step labeling procedure in an automated synthesis module, with a radiochemical purity of >95%, and a specific activity of 25-45 GBq/μmol. Cellular association, biodistribution, and autoradiography with blocking experiments indicated specific binding of [(18)F]5a to σ1 receptors in vitro and in vivo. Small animal positron emission tomography (PET) imaging using mouse tumor xenograft models demonstrated a high accumulation in human carcinoma and melanoma. Treatment with haloperidol significantly reduced the accumulation of the radiotracer in tumors. These findings suggest that radiotracer with suitable lipophilicity and appropriate affinity for σ1 receptors could be used for tumor imaging.

  15. Dual mode fluorescent (18)F-PET tracers: efficient modular synthesis of rhodamine-[cRGD]2-[(18)F]-organotrifluoroborate, rapid, and high yielding one-step (18)F-labeling at high specific activity, and correlated in vivo PET imaging and ex vivo fluorescence.

    PubMed

    Liu, Zhibo; Radtke, Mark Alex; Wong, May Q; Lin, Kuo-Shyan; Yapp, Donald T; Perrin, David M

    2014-11-19

    The design of dual mode fluorescent-PET peptidic tracers that can be labeled with [(18)F]fluoride at high specific activity and high yield has been challenged by the short half-life of (18)F and its aqueous indolence toward nucleophilic displacement, that often necessitates multistep reactions that start with punctiliously dry conditions. Here we present a modular approach to constructing a fluorescent dimeric peptide with a pendant radioprosthesis that is labeled in water with [(18)F]fluoride ion in a single, user-friendly step. The modular approach starts with grafting a new zwitterionic organotrifluoroborate radioprosthesis onto a pentaerythritol core with three pendent alkynes that enable successive grafting of a bright fluorophore (rhodamine) followed by two peptides (cylcoRGD). The construct is labeled with [(18)F]fluoride via isotope exchange within 20 min in a single step at high specific activity (>3 Ci/μmol) and in good yield to provide 275 mCi and high radiochemical purity. Neither drying of the [(18)F]fluoride ion solution nor HPLC purification of the labeled tracer is required. Facile chemical synthesis of this dual mode tracer along with a user-friendly one-step radiolabeling method affords very high specific activity. In vivo PET images of the dual mode tracer are acquired at both high and low specific activities. At very high specific activity, i.e., 3.5 Ci/μmol, tumor uptake is relatively high (5.5%ID/g), yet the associated mass is below the limits of fluorescent detection. At low specific activity, i.e., 0.01 Ci/μmol, tumor uptake in the PET image is reduced by approximately 50% (2.9%ID/g), but the greater associated mass enables fluorescence detection in the tumor. These data highlight a facile production of a dual mode fluorescent-PET tracer which is validated with in vivo and ex vivo images. These data also define critical limitations for the use of dual mode tracers in small animals.

  16. Synthesis of 2'-deoxy-2'-[18F]fluoro-beta-D-arabinofuranosyl nucleosides, [18F]FAU, [18F]FMAU, [18F]FBAU and [18F]FIAU, as potential PET agents for imaging cellular proliferation. Synthesis of [18F]labelled FAU, FMAU, FBAU, FIAU.

    PubMed

    Mangner, Thomas J; Klecker, Raymond W; Anderson, Lawrence; Shields, Anthony F

    2003-04-01

    An efficient and reliable synthesis of 2'-deoxy-2'-[(18)F]fluoro-beta-D-arabinofuranosyl nucleosides is presented. Overall decay-corrected radiochemical yields of 35-45% of 4 analogs, FAU, FMAU, FBAU and FIAU are routinely obtained in >98% radiochemical purity and with specific activities of greater than 3 Ci/micromol (110 MBq/micromol) in a synthesis time of approximately 3 hours. When approximately 220 mCi (8.15 GBq) of starting [(18)F]fluoride is used, 25 -30 mCi (0.93 -1.11 GBq) of product (enough to image two patients sequentially) is typically obtained.

  17. Active dependency.

    PubMed

    Bornstein, R F

    1995-02-01

    Although dependency has long been associated with passivity, weakness, and submissiveness, a review of the empirical literature reveals that, in certain situations and settings, dependent persons actually exhibit a variety of active, assertive behaviors. In this article, I: a) trace the historical roots of the dependency-passivity link; b) review empirical studies from developmental, social, and clinical psychology which indicate that, in certain circumstances, dependency is associated with active, assertive behavior on the part of the dependent person; c) offer an alternative conceptual model of dependency that accounts for the entire range of behaviors-both passive and active-that are exhibited by the dependent person; and d) discuss the diagnostic and therapeutic implications of this alternative conceptual model of dependency.

  18. [Tobacco dependence].

    PubMed

    Saito, T; Murakami, S

    1998-10-01

    The present review discusses the potential of nicotine psychic and physical dependence. Since the 1964 Surgeon General's Report on Smoking and Health, much attention has been given to nicotine dependence. Many epidemiological studies indicated that about 50% of smokers could be nicotine dependent; however, few of them had the experience of "progressive neglect of alternative pleasures or interest in favour of smoking." Additionally, some clinical and experimental data indicated that nicotine could not be considered more addictive than cocaine and morphine. As to the physical dependence on nicotine, the nicotine withdrawal syndrome is reported to be observed in about 30% of smokers. However, symptoms of the nicotine withdrawal syndrome are not specific but can appear in smokers put under stress. Several investigators have reported that signs of nicotine withdrawal in experimental animals are weaker than those with opioids, barbiturates and alcohol, and have indicated that it is unclear whether behaviors observed in animal models of nicotine physical dependence are signs of the nicotine withdrawal syndrome. From the current review, it can be considered that the potential for nicotine dependence may not be higher than that for other drug dependence and that nicotine physical dependence potential may be weaker than hitherto believed.

  19. [Affective dependency].

    PubMed

    Scantamburlo, G; Pitchot, W; Ansseau, M

    2013-01-01

    Affective dependency is characterized by emotional distress (insecure attachment) and dependency to another person with a low self-esteem and reassurance need. The paper proposes a reflection on the definition of emotional dependency and the confusion caused by various denominations. Overprotective and authoritarian parenting, cultural and socio-environmental factors may contribute to the development of dependent personality. Psychological epigenetic factors, such as early socio-emotional trauma could on neuronal circuits in prefronto-limbic regions that are essential for emotional behaviour.We also focus on the interrelations between dependent personality, domestic violence and addictions. The objective for the clinician is to propose a restoration of self-esteem and therapeutic strategies focused on autonomy.

  20. Opioid dependence

    PubMed Central

    2009-01-01

    Introduction Dependence on opioids is a multifactorial condition involving genetic and psychosocial factors. There are three approaches to treating opioid dependence. Stabilisation is usually by opioid substitution treatments, and aims to ensure that the drug use becomes independent of mental state (such as craving and mood) and independent of circumstances (such as finance and physical location). The next stage is to withdraw (detox) from opioids. The final aim is relapse prevention. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of drug treatments for stabilisation (maintenance) in people with opioid dependence? What are the effects of drug treatments for withdrawal in people with opioid dependence? What are the effects of drug treatments for relapse prevention in people with opioid dependence? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2008 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 23 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review, we present information relating to the effectiveness and safety of the following interventions: buprenorphine; clonidine; lofexidine; methadone; naltrexone; and ultra-rapid withdrawal regimes. PMID:21696648

  1. [Personality dependence in drug dependence].

    PubMed

    Cormier, D; Reid, N

    1979-11-01

    Is drug dependence more likely to establish itself in persons whose personality structure is already characterized by a psychological dependence which can be looked at from two aspects: cognitive field dependence and emotional dependence? Three groups of 21 subjects each, multiple drug users, users of cannabis and non-users, are studied with the expectation that the first group is more psychologically dependent than the second one, the latter being in turn more dependent than the group of non-users. The situation is not so simple. Hard-drug users appear to be more active than users of cannabis, whereas non-users are even more dynamic individuals. However, in such a study the duration of consumption exercise an important influence because, in this regard, different personality profiles of the two drug-using groups come into play, the users of cannabis presenting a more incoherent picture. The multiple drug addict selected from his natural environment seems to acquire, through his prolonged consumption, a greater perceptual independence and emotional maturity owing to the clandestine nature of his habit, and a more acute and articulate general way of functioning in order to avoid mishaps.

  2. Opioid dependence

    PubMed Central

    2011-01-01

    Introduction Dependence on opioids is a multifactorial condition involving genetic and psychosocial factors. There are three stages to treating opioid dependence. Stabilisation is usually by opioid substitution treatments, and aims to ensure that the drug use becomes independent of mental state (such as craving and mood) and independent of circumstances (such as finance and physical location). The next stage is to withdraw (detox) from opioids. The final stage is relapse prevention. This treatment process contributes to recovery of the individual, which also includes improved overall health and wellbeing, as well as engagement in society. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of drug treatments for stabilisation (maintenance) in people with opioid dependence? What are the effects of drug treatments for withdrawal in people with opioid dependence? What are the effects of drug treatments for relapse prevention in people with opioid dependence? We searched: Medline, Embase, The Cochrane Library, and other important databases up to March 2011 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 26 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review, we present information relating to the effectiveness and safety of the following interventions: buprenorphine; clonidine; lofexidine; methadone; naltrexone; and ultra-rapid withdrawal regimens. PMID:21929827

  3. Phenibut dependence.

    PubMed

    Samokhvalov, Andriy V; Paton-Gay, C Lindsay; Balchand, Kam; Rehm, Jürgen

    2013-02-06

    Phenibut is a γ-aminobutyric acid (GABA) agonist designed and used as an anxiolytic in Russia. In Western countries, phenibut is not a registered medication but is available through online stores as a supplement. We present a case of a patient who used phenibut to self-medicate anxiety, insomnia and cravings for alcohol. While phenibut was helpful initially, the patient developed dependence including tolerance, significant withdrawal symptoms within 3-4 h of last use and failure to fulfil his roles at work and at home. He finally sought medical assistance in our addictions clinic. We have gradually, over the course of 9 weeks, substituted phenibut with baclofen, which has similar pharmacological properties, and then successfully tapered the patient off baclofen. This required approximately 10 mg of baclofen for each gram of phenibut.

  4. Phenibut dependence

    PubMed Central

    Samokhvalov, Andriy V; Paton-Gay, C Lindsay; Balchand, Kam; Rehm, Jürgen

    2013-01-01

    Phenibut is a γ-aminobutyric acid (GABA) agonist designed and used as an anxiolytic in Russia. In Western countries, phenibut is not a registered medication but is available through online stores as a supplement. We present a case of a patient who used phenibut to self-medicate anxiety, insomnia and cravings for alcohol. While phenibut was helpful initially, the patient developed dependence including tolerance, significant withdrawal symptoms within 3–4 h of last use and failure to fulfil his roles at work and at home. He finally sought medical assistance in our addictions clinic. We have gradually, over the course of 9 weeks, substituted phenibut with baclofen, which has similar pharmacological properties, and then successfully tapered the patient off baclofen. This required approximately 10 mg of baclofen for each gram of phenibut. PMID:23391959

  5. Dependency, Empathy, and Altruism.

    ERIC Educational Resources Information Center

    Miller, Shirley Matile

    This study examined the relationship of dependency, empathy, and altruism. It was hypothesized that: (1) dependency would be related in a curvilinear manner to empathy, with children who are moderate in dependency scoring highest in empathy; (2) dependency would be positively related to visible altruism when such prosocial behavior results in…

  6. Dependency, Empathy, and Altruism.

    ERIC Educational Resources Information Center

    Miller, Shirley Matile

    This study examined the relationship of dependency, empathy, and altruism. It was hypothesized that: (1) dependency would be related in a curvilinear manner to empathy, with children who are moderate in dependency scoring highest in empathy; (2) dependency would be positively related to visible altruism when such prosocial behavior results in…

  7. [Dependent patient and interpersonal dependency: psychotherapeutic strategies].

    PubMed

    Versaevel, C

    2012-04-01

    This article is a review of psychotherapies for patients suffering from dependent personality and interpersonal dependency. We synthesized articles making reference to this question, notably those written by Bornstein, author who refers to the dependent personality. We highlighted the psychotherapies that have been the object of an evaluation. The research on the subject is sparse: only eight studies permitting assessment of psychotherapies in this indication in 2005. Besides these psychotherapies, we detailed other approaches which are used by practitioners in these indications. The therapy does not aim at autonomy "at all costs", but that the patient finds a dependence "adapted" to his/her environment. Before starting a therapy, an evaluation is useful to specify the type of dependence. First of all, is there a "pathological" dependence? Is the suffering of the patient secondary to his personality or not supportive enough? Does insight exist? What is the reaction of the patient if we suggest the hypothesis of a dependence on his/her part? Does he/she consider this idea or reject it? Finally, is the dependence primary or secondary? For that purpose, it is necessary to study the biography of the patient and the appearance of the comorbidity over time. The primary dependence is seen in childhood and precedes the other psychological disorders. The secondary dependence follows after the comorbidity and events of life that alter self-esteem (depression, for example). Various therapeutic strategies arise from various currents. The therapies of analytical inspiration recommend replaying the relationship of object and explicitly evoking the transfer. The behavioural and cognitive psychotherapies aim at making the patient identify the cognitions which underlie the dependence, then leading the patient to modify his/her cognition and to behave in a more autonomous way, using the theory of learning. The humanist therapies aim at a therapeutic relationship of acceptance and

  8. [Evaluating tobacco dependance].

    PubMed

    Etter, Jean-François

    2006-11-29

    Good science needs good measurement instruments, and this is also true for the study of tobacco dependence. In this paper, we present and criticize the most frequently used instrument, the Fagerström Test for Nicotine Dependence. This test, published 28 years ago, does not reflect current definitions of dependence. Several alternative approaches to the measurement of tobacco dependence are discussed, and more recent instruments are presented.

  9. Effects of Statistical Dependence.

    DTIC Science & Technology

    1985-01-01

    Some research being carried on deals with concepts of dependence for multicomponent systems. Such dependence arises naturally in reliability work...because of common environmental factors and common sources of material. This article mainly explores modes of positive dependence for bivariate and

  10. Field Dependence and Anxiety.

    ERIC Educational Resources Information Center

    Bergum, Judith E.; Bergum, Bruce O.

    The concept of field dependence/independence is defined by the behavior patterns of individuals. Those who use predominantly internal cues when making judgments on perceptual tasks are considered field independent; those who use predominantly external cues are considered field dependent. To test whether field dependence is related to anxiety,…

  11. [Dependence disorders in psychopathology].

    PubMed

    Fernandez, L; Sztulman, H

    1999-01-01

    Research concerning the psychopathological aspects of dependence implicates a wide range of behaviors reassembled under the term of "dependence behaviors": sexual, medical, alcoholic and tobacco dependencies. Speech samples of dependent subjects show that encountering the object of dependence (product, element, ...) introduces a particular form of organized psychological processes. According to several authors, psychopathological dependence can be attributed to: early personality development; failures in the separation-individuation processes; disorders in mother-infant interactions; and a deficit in the psychological functioning of the subjects. For psychopathology, the dependence cannot be reduced to physiological dependence on the product but is understood rather in terms of a complex process indicative of either specific or non-specific suffering which is addressed by abused substance that represents a solution--the effects of which constitute the addictive process. Understanding this process requires an analysis of the psychopathological dependence from a triple meta-psychological viewpoint (topographical, dynamic, economic). Such analysis allows for a psychoanalytical theoretical interpretation of dependence based on three models: pleasure, narcissism and stress reduction. At the same time, the analysis extends the examination of psychopathological dependence towards issues concerning the body. Such body issues are critically placed between the biological and the psychological processes.

  12. [Cannabis: Use and dependence].

    PubMed

    Dervaux, Alain; Laqueille, Xavier

    2012-12-01

    The main characteristics of cannabis dependence are craving, persistent desire or unsuccessful efforts to cut down or control cannabis use and important social, occupational, or recreational activities given up or reduced because of cannabis use. Withdrawal symptoms include insomnia, irritability, anger, restlessness, depression, mood swings and cravings. Regular cannabis use induces cognitive impairment, especially of attention, episodic memory and working memory. Alcohol and other substances abuse or dependence are frequently found in patients with cannabis dependence. Psychiatric comorbidities are frequent in patients with cannabis dependence, in particular anxiety disorders, mood disorders, and personality disorders. The treatment of cannabis dependence includes behavioral psychotherapy, especially motivational interviewing and cognitive-behavioral therapy, alongside treatment of co-occurring mental health and substance use conditions. There are currently no available pharmacological treatment interventions for cannabis dependence. The treatment of cannabis dependence and withdrawal remains nonspecific. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  13. Dependency Tree Annotation Software

    DTIC Science & Technology

    2015-11-01

    This report presents Dependency Tree Editor (DTE), a software system built as part of a Science and Engineering Apprentice Program (SEAP) summer...internship. The system supports interactive visualization and editing of dependency trees ???a formalism frequently used in computational linguistics to...formats, and it provides numerous options for customizing how dependency trees are displayed. Built entirely in Java, it can run on a wide range of platforms.

  14. Dependent personality disorder

    MedlinePlus

    ... Having problems expressing disagreements with others Exams and Tests Dependent personality disorder is diagnosed based on a psychological evaluation. The health care provider will consider how ...

  15. Dependable Software Technology Exchange

    DTIC Science & Technology

    1993-06-01

    Special Report CMU/SEI-93-SR-04 S~Carnegie-Melion University Software Engineering Institute AD-A267 103 DTIC D•epWebleoftware JEL ECT3 E9 Technology ...16590 ___________ lull! !! l1111 U l111 I lil I --\\t• /" Special Report CMU/SEI-93-SR-04 June 1993 Dependable Software Technology Exchange Charles B...93-SR-4 Dependable Software Technology Exchange Abstract: On March 18 and 19, 1993, the Dependable Real-Time Software project hosted a Dependable

  16. [Alcohol and substance dependence].

    PubMed

    Tsuchida, Hideto; Nishimura, Isao; Fukui, Kenji

    2012-02-01

    In this paper, we have outlined the neurobiological basis of alcohol and drug dependence. The prevalence of drug dependence is a serious social problem in many countries, including Japan. This problem involves many background factors, including those pertaining to medical sciences, socio economics, and politics. First, we briefly describe the findings pertaining to psychotomimetic drugs as a model of schizophrenia. The biological pathogenesis of schizophrenic disorders is still unknown. The symptoms of methamphetamine (MAP) and phencyclidine (PCP) psychoses are very similar to those of schizophrenic disorders involving hallucination or delusion. PCP causes not only positive symptoms but also negative symptoms. Therefore, it has been considered as a more comprehensive model of schizophrenia than other drugs. Furthermore, amotivational syndrome, which is observed in patients with chronic cannabis and organic solvent dependence, is similar to the negative symptoms of schizophrenia. Understanding the neurobiological basis of drug dependence by using the molecular biological approach will provide an important clue for elucidating the mechanisms underlying schizophrenia and endogenous psychiatric disorders. Next, we discuss account for the neurobiological mechanisms underlying drug dependence. The reward system in the brain, which is common for all dependent drugs, has been explained, and the stages of addiction corresponding to the development of drug dependence have been discussed followed. In addition, we have discussed the epigenetics aspects of substance dependence, which is one of the hottest topics in psychiatric genetics. We expect that further studies of the mechanisms underlying drug dependence will aid in elucidating of the pathophysiology of various psychiatric diseases.

  17. Decisions Concerning Directional Dependence

    ERIC Educational Resources Information Center

    von Eye, Alexander; DeShon, Richard P.

    2012-01-01

    In this rejoinder, von Eye and DeShon discuss the decision strategies proposed in their original article ("Directional Dependence in Developmental Research," this issue), as well as the ones proposed by the authors of the commentary (Pornprasertmanit and Little, "Determining Directional Dependency in Causal Associations," this issue). In addition,…

  18. Adam Smith and dependency.

    PubMed

    Ozler, Sule

    2012-06-01

    The focus of this paper is the works and life of Adam Smith, who is widely recognized as the father and founder of contemporary economics. Latent content analysis is applied to his seminal text in economics, An Inquiry into the Nature and Causes of the Wealth of Nations (1776). The results reveal that Smith considers dependence on others a problem and sees the solution to this problem in impersonalized interdependence. In addition, his views on social dependency and personal dependency, reflected in his Lectures on Jurisprudence (1963) and The Theory of Moral Sentiments (1759), are analyzed. This analysis suggests a central tension between dependence and independence in Smith's writings. The personal dependency patterns he exhibited in his life, which also suggest a tension between dependence and independence, are identified through a reading of his biographies. Based on insights from psychoanalytic literature, this paper proposes that developing the ideas in the Wealth of Nations was part of Smith's creative solution to this tension. In particular, his solution to one individual's dependence on another was through a system of impersonalized interdependence. In other words, Smith defended against his personal dependence through his economic theorizing.

  19. Dependent Probability Spaces

    ERIC Educational Resources Information Center

    Edwards, William F.; Shiflett, Ray C.; Shultz, Harris

    2008-01-01

    The mathematical model used to describe independence between two events in probability has a non-intuitive consequence called dependent spaces. The paper begins with a very brief history of the development of probability, then defines dependent spaces, and reviews what is known about finite spaces with uniform probability. The study of finite…

  20. Interactive Visualization of Dependencies

    ERIC Educational Resources Information Center

    Moreno, Camilo Arango; Bischof, Walter F.; Hoover, H. James

    2012-01-01

    We present an interactive tool for browsing course requisites as a case study of dependency visualization. This tool uses multiple interactive visualizations to allow the user to explore the dependencies between courses. A usability study revealed that the proposed browser provides significant advantages over traditional methods, in terms of…

  1. Interactive Visualization of Dependencies

    ERIC Educational Resources Information Center

    Moreno, Camilo Arango; Bischof, Walter F.; Hoover, H. James

    2012-01-01

    We present an interactive tool for browsing course requisites as a case study of dependency visualization. This tool uses multiple interactive visualizations to allow the user to explore the dependencies between courses. A usability study revealed that the proposed browser provides significant advantages over traditional methods, in terms of…

  2. Decisions Concerning Directional Dependence

    ERIC Educational Resources Information Center

    von Eye, Alexander; DeShon, Richard P.

    2012-01-01

    In this rejoinder, von Eye and DeShon discuss the decision strategies proposed in their original article ("Directional Dependence in Developmental Research," this issue), as well as the ones proposed by the authors of the commentary (Pornprasertmanit and Little, "Determining Directional Dependency in Causal Associations," this issue). In addition,…

  3. High Performance, Dependable Multiprocessor

    NASA Technical Reports Server (NTRS)

    Ramos, Jeremy; Samson, John R.; Troxel, Ian; Subramaniyan, Rajagopal; Jacobs, Adam; Greco, James; Cieslewski, Grzegorz; Curreri, John; Fischer, Michael; Grobelny, Eric; George, Alan; Aggarwal, Vikas; Patel, Minesh; Some, Raphael

    2006-01-01

    With the ever increasing demand for higher bandwidth and processing capacity of today's space exploration, space science, and defense missions, the ability to efficiently apply commercial-off-the-shelf (COTS) processors for on-board computing is now a critical need. In response to this need, NASA's New Millennium Program office has commissioned the development of Dependable Multiprocessor (DM) technology for use in payload and robotic missions. The Dependable Multiprocessor technology is a COTS-based, power efficient, high performance, highly dependable, fault tolerant cluster computer. To date, Honeywell has successfully demonstrated a TRL4 prototype of the Dependable Multiprocessor [I], and is now working on the development of a TRLS prototype. For the present effort Honeywell has teamed up with the University of Florida's High-performance Computing and Simulation (HCS) Lab, and together the team has demonstrated major elements of the Dependable Multiprocessor TRLS system.

  4. Compulsivity in opioid dependence.

    PubMed

    Tolomeo, Serenella; Matthews, Keith; Steele, Douglas; Baldacchino, Alex

    2017-09-14

    This study aimed to investigate the relationship between compulsivity versus impulsivity and structural MRI abnormalities in opioid dependence. We recruited 146 participants: i) patients with a history of opioid dependence due to chronic heroin use (n=24), ii) heroin users stabilised on methadone maintenance treatment (n=48), iii) abstinent participants with a history of opioid dependence due to heroin use (n=24) and iv) healthy controls (n=50). Compulsivity was measured using Intra/Extra-Dimensional (IED) Task and impulsivity was measured using the Cambridge Gambling Task (CGT). Structural Magnetic Resonance Imaging (MRI) data were also obtained. As hypothesised, compulsivity was negatively associated with impulsivity (p<0.02). Testing for the neural substrates of compulsivity versus impulsivity, we found a higher compulsivity/impulsivity ratio associated with significantly decreased white matter adjacent to the nucleus accumbens, bed nucleus of stria terminalis and rostral cingulate in the abstinent group, compared to the other opioid dependent groups. In addition, self-reported duration of opioid exposure correlated negatively with bilateral globus pallidus grey matter reductions. Our findings are consistent with Volkow & Koob's addiction models and underline the important role of compulsivity versus impulsivity in opioid dependence. Our results have implications for the treatment of opioid dependence supporting the assertion of different behavioural and biological phenotypes in the opioid dependence and abstinence syndromes. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Visual dependence and BPPV.

    PubMed

    Agarwal, K; Bronstein, A M; Faldon, M E; Mandalà, M; Murray, K; Silove, Y

    2012-06-01

    The increased visual dependence noted in some vestibular patients may be secondary to their vertigo. We examine whether a single, brief vertigo attack, such as in benign paroxysmal positional vertigo (BPPV), modifies visual dependency. Visual dependency was measured before and after the Hallpike manoeuvre with (a) the Rod and Frame and the Rod and Disc techniques whilst seated and (b) the postural sway induced by visual roll-motion stimulation. Three subject groups were studied: 20 patients with BPPV (history and positive Hallpike manoeuvre; PosH group), 20 control patients (history of BPPV but negative Hallpike manoeuvre; NegH group) and 20 normal controls. Our findings show that while both patient groups showed enhanced visual dependency, the PosH and the normal control group decreased visual dependency on repetition of the visual tasks after the Hallpike manoeuvre. NegH patients differed from PosH patients in that their high visual dependency did not diminish on repetition of the visual stimuli; they scored higher on the situational characteristic questionnaire ('visual vertigo' symptoms) and showed higher incidence of migraine. We conclude that long term vestibular symptoms increase visual dependence but a single BPPV attack does not increase it further. Repetitive visual motion stimulation induces adaptation in visual dependence in peripheral vestibular disorders such as BPPV. A positional form of vestibular migraine may underlie the symptoms of some patients with a history of BPPV but negative Hallpike manoeuvre. The finding that they have non adaptable increased visual dependency may explain visuo-vestibular symptoms in this group and, perhaps more widely, in patients with migraine.

  6. Medicare dependent hospitals: Who depends on whom?

    PubMed Central

    Goody, Brigid

    1992-01-01

    Small rural hospitals with a large proportion of Medicare patients currently receive special treatment as Medicare dependent hospitals (MDHs) under the prospective payment system (PPS). Other high Medicare hospitals (HMHs)—both urban and rural— have sought to have the additional per case payments extended to them. Current utilization patterns, the availability of alternative facilities, and the socioeconomic and demographic characteristics of the service areas were examined to determine whether either the current MDH or alternative HMH targeting criteria identify hospitals whose closure might impair access to care for Medicare beneficiaries residing in their service areas. Neither MDHs nor HMHs are substantially different from other hospitals in terms of providing access. While some individual MDHs or HMHs might be considered essential access facilities, alternate criteria should be developed to identify these facilities regardless of the proportion of their patients attributable to the Medicare program. PMID:10127457

  7. Chemical dependence - resources

    MedlinePlus

    Substance use - resources, Drug abuse - resources; Resources - chemical dependence ... National Institute on Drug Abuse -- www.drugabuse.gov Substance Abuse and Mental Health Services Administration -- www.samhsa.gov

  8. Saving, dependency and development.

    PubMed

    Kelley, A C; Schmidt, R M

    1996-01-01

    This study examines the impact of dependency on savings between 65 less developed countries (LDCs) and 23 developed countries over time and cross-sectionally since 1960. The study tests a modified Leff model and the Mason life-cycle framework. Empirical estimates address potential simultaneity between savings and output growth. The price indices of Summers and Heston are used because each country's national accounts are converted from nominal into purchasing-power variables. This eliminates the problems with using exchange rates which vary systematically by level of development with a "true" index of purchasing power. Savings (S/Y) is the percentage share of gross national saving in gross domestic product. Ygr is the growth of per capita income. Y/N gr is the growth in the per capita gross domestic product. Analysis is based on ordinary least squares (OLS) and two-stage least squares techniques, treatment for heteroscedascity, aggregation periods, several definitions of savings, different country samples, and aged dependency and youth dependency. Findings support the Mason variable-growth life-cycle framework that shows that changes in demographic factors accounted for a large part of savings. The relationships in the modified Leff-type model were weak, with the exception of the mildly negative youth and elderly dependency impact in the 1980s. The rate of growth of youth dependency was negative and significant in all cross-sections for the full sample, all panel estimates for both LDCs and the full sample, and in the 1980s for LDCs. In the OLS model, life-cycle effects were weaker, but direct dependency effects were stronger. S/Y over time became slightly more sensitive to changes in life cycle impacts but less sensitive to youth dependency. Demography's impact on savings over time is attributed to the increase in the pace of youth dependency decline and secondarily to its increasing sensitivity to life-cycle effects.

  9. Ultra Dependable Processor

    NASA Astrophysics Data System (ADS)

    Sakai, Shuichi; Goshima, Masahiro; Irie, Hidetsugu

    This paper presents the processor architecture which provides much higher level dependability than the current ones. The features of it are: (1) fault tolerance and secure processing are integrated into a modern superscalar VLSI processor; (2) light-weight effective soft-error tolerant mechanisms are proposed and evaluated; (3) timing errors on random logic and registers are prevented by low-overhead mechanisms; (4) program behavior is hidden from the outer world by proposed address translation methods; (5) information leakage can be avoided by attaching policy tags for all data and monitoring them for each instruction execution; (6) injection attacks are avoided with much higher accuracy than the current systems, by providing tag trackings; (7) the overall structure of the dependable processor is proposed with a dependability manager which controls the detection of illegal conditions and recovers to the normal mode; and (8) an FPGA-based testbed system is developed where the system clock and the voltage are intentionally varied for experiment. The paper presents the fundamental scheme for the dependability, elemental technologies for dependability and the whole architecture of the ultra dependable processor. After showing them, the paper concludes with future works.

  10. Opioid dependence and pregnancy.

    PubMed

    Winklbaur, Bernadette; Jung, Erika; Fischer, Gabriele

    2008-05-01

    The management of opioid dependence during pregnancy has received considerable attention over the past three decades. Recent peer-reviewed literature in the fields of pregnancy and opioid dependence and neonatal abstinence syndrome has been evaluated and discussed. Pregnant opioid-dependent women must be carefully managed to minimize harm to the fetus; therefore, standardized care for maternal health is required. In a multidisciplinary care system opioid maintenance therapy is the recommended treatment approach during pregnancy. Equivalent attention must be given to the treatment of neonatal abstinence syndrome, which occurs in 55-94% of neonates after intrauterine opioid exposure with a 60% likelihood of requiring treatment; heterogeneous rating scales as well as heterogeneous treatment approaches are often responsible for extended hospital stays. Interpretation of available literature is confounded by several methodological flaws. In general, there is still a lack of evidence-based study designs for pharmacological treatment of these patients as well as neonatal abstinence syndrome.

  11. Dependability and performability analysis

    NASA Technical Reports Server (NTRS)

    Trivedi, Kishor S.; Ciardo, Gianfranco; Malhotra, Manish; Sahner, Robin A.

    1993-01-01

    Several practical issues regarding specifications and solution of dependability and performability models are discussed. Model types with and without rewards are compared. Continuous-time Markov chains (CTMC's) are compared with (continuous-time) Markov reward models (MRM's) and generalized stochastic Petri nets (GSPN's) are compared with stochastic reward nets (SRN's). It is shown that reward-based models could lead to more concise model specifications and solution of a variety of new measures. With respect to the solution of dependability and performability models, three practical issues were identified: largeness, stiffness, and non-exponentiality, and a variety of approaches are discussed to deal with them, including some of the latest research efforts.

  12. Anticonvulsants for cocaine dependence.

    PubMed

    Minozzi, S; Amato, L; Davoli, M; Farrell, M; Lima Reisser, A A R L; Pani, P P; Silva de Lima, M; Soares, B; Vecchi, S

    2008-04-16

    Cocaine dependence is a major public health problem that is characterized by recidivism and a host of medical and psychosocial complications. Although effective pharmacotherapy is available for alcohol and heroin dependence none exists currently for cocaine dependence despite two decades of clinical trials primarily involving antidepressant, anti convulsivant and dopaminergic medications. There has been extensive consideration of optimal pharmacological approaches to the treatment of cocaine dependence with consideration of both dopamine antagonists and agonists. Anticonvulsants have been candidates for the treatment of addiction based on the hypothesis that seizure kindling-like mechanisms contribute to addiction. To evaluate the efficacy and the acceptability of anticonvulsants for cocaine dependence We searched the Cochrane Drugs and Alcohol Groups specialised register (issue 4, 2007), MEDLINE (1966 - march 2007), EMBASE (1988 - march 2007), CINAHL (1982- to march 2007) All randomised controlled trials and controlled clinical trials which focus on the use of anticonvulsants medication for cocaine dependence Two authors independently evaluated the papers, extracted data, rated methodological quality Fifteen studies (1066 participants) met the inclusion criteria for this review: the anticonvulsants drugs studied were carbamazepine, gabapentin, lamotrigine, phenytoin, tiagabine, topiramate, valproate. No significant differences were found for any of the efficacy measures comparing any anticonvulsants with placebo. Placebo was found to be superior to gabapentin in diminishing the number of dropouts, two studies, 81 participants, Relative Risk (RR) 3.56 (95% CI 1.07 to 11.82) and superior to phenythoin for side effects, two studies, 56 participants RR 2.12 (95% CI 1.08 to 4.17). All the other single comparisons are not statistically significant. Although caution is needed when assessing results from a limited number of small clinical trials at present there is no

  13. Anticonvulsants for cocaine dependence.

    PubMed

    Minozzi, Silvia; Cinquini, Michela; Amato, Laura; Davoli, Marina; Farrell, Michael F; Pani, Pier Paolo; Vecchi, Simona

    2015-04-17

    Cocaine dependence is a major public health problem that is characterised by recidivism and a host of medical and psychosocial complications. Although effective pharmacotherapy is available for alcohol and heroin dependence, none is currently available for cocaine dependence, despite two decades of clinical trials primarily involving antidepressant, anticonvulsivant and dopaminergic medications. Extensive consideration has been given to optimal pharmacological approaches to the treatment of individuals with cocaine dependence, and both dopamine antagonists and agonists have been considered. Anticonvulsants have been candidates for use in the treatment of addiction based on the hypothesis that seizure kindling-like mechanisms contribute to addiction. To evaluate the efficacy and safety of anticonvulsants for individuals with cocaine dependence. We searched the Cochrane Drugs and Alcohol Group Trials Register (June 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 6), MEDLINE (1966 to June 2014), EMBASE (1988 to June 2014), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to June 2014), Web of Science (1991 to June 2014) and the reference lists of eligible articles. All randomised controlled trials and controlled clinical trials that focus on the use of anticonvulsant medications to treat individuals with cocaine dependence. We used the standard methodological procedures expected by The Cochrane Collaboration. We included a total of 20 studies with 2068 participants. We studied the anticonvulsant drugs carbamazepine, gabapentin, lamotrigine, phenytoin, tiagabine, topiramate and vigabatrin. All studies compared anticonvulsants versus placebo. Only one study had one arm by which the anticonvulsant was compared with the antidepressant desipramine. Upon comparison of anticonvulsant versus placebo, we found no significant differences for any of the efficacy and safety measures. Dropouts: risk ratio (RR) 0.95, 95

  14. Tilidine abuse and dependence.

    PubMed

    Trojan, A; Beil, H W

    1978-11-01

    Tilidine (Valoron) is a new strong analgesic which was introduced into the market in West Germany in 1970. In February 1978 tilidine was placed under the regulations of the German Narcotics Act because it had rapidly become an easily acquired substitute for opiates on the drug scene. Cases have become known where tilidine dependence developed during the treatment of pain in patients without any preceding addiction to other drugs. The relevant literature on tilidine is reviewed in regard to pharmacological, epidemiological and clinical aspects of tilidine dependence and abuse.

  15. Time Dependent Fluids

    ERIC Educational Resources Information Center

    Collyer, A. A.

    1974-01-01

    Discusses the flow characteristics of thixotropic and negative thixotropic fluids; various theories underlying the thixotropic behavior; and thixotropic phenomena exhibited in drilling muds, commercial paints, pastes, and greases. Inconsistencies in the terminology used to label time dependent effects are revealed. (CC)

  16. Reference-Dependent Sympathy

    ERIC Educational Resources Information Center

    Small, Deborah A.

    2010-01-01

    Natural disasters and other traumatic events often draw a greater charitable response than do ongoing misfortunes, even those that may cause even more widespread misery, such as famine or malaria. Why is the response disproportionate to need? The notion of reference dependence critical to Prospect Theory (Kahneman & Tversky, 1979) maintains that…

  17. Evolution of Metabolic Dependency

    NASA Astrophysics Data System (ADS)

    Shou, Wenying

    Microbes are often found to have lost their ability to make essential metabolites (auxotrophs) and instead rely on other individuals for these metabolites. How might metabolic dependency evolve to be so common? When microbes live inside a host (endosymbionts), amply host metabolites support auxotrophic endosymbionts. If the host transmits only a small number of endosymbionts to its offspring, then auxotrophic endosymbionts can rise to high frequency simply by chance. On the other hand, auxotrophs have also been observed in abundant free-living bacteria found in ocean water where nutrient supply is low. How might auxotrophs rise to an appreciable frequency in a large population when nutrient supply is low? We have found commonly-encountered conditions that facilitate the evolution of metabolic dependency. Metabolic interactions can in turn shape spatial organization of microbial communities (Momeni et al. (2013) eLife 2, 00230; Momeni et al. (2013) eLife 2, 00960; Estrela and Brown (2013) PLoS Comput Biol 9, e1003398; Muller et al. (2014) PNAS 111, 1037-1042). Rapid evolution of metabolic dependency can contribute to the complexity of microbial communities. Evolution of metabolic dependency.

  18. Reference-Dependent Sympathy

    ERIC Educational Resources Information Center

    Small, Deborah A.

    2010-01-01

    Natural disasters and other traumatic events often draw a greater charitable response than do ongoing misfortunes, even those that may cause even more widespread misery, such as famine or malaria. Why is the response disproportionate to need? The notion of reference dependence critical to Prospect Theory (Kahneman & Tversky, 1979) maintains that…

  19. [Prevention of alcohol dependence].

    PubMed

    Trova, A C; Paparrigopoulos, Th; Liappas, I; Ginieri-Coccossis, M

    2015-01-01

    With the exception of cardiovascular diseases, no other medical condition causes more serious dysfunction or premature deaths than alcohol-related problems. Research results indicate that alcohol dependent individuals present an exceptionally poor level of quality of life. This is an outcome that highlights the necessity of planning and implementing preventive interventions on biological, psychological or social level, to be provided to individuals who make alcohol abuse, as well as to their families. Preventive interventions can be considered on three levels of prevention: (a) primary prevention, which is focused on the protection of healthy individuals from alcohol abuse and dependence, and may be provided on a universal, selective or indicated level, (b) secondary prevention, which aims at the prevention of deterioration regarding alcoholic dependence and relapse, in the cases of individuals already diagnosed with the condition and (c) tertiary prevention, which is focused at minimizing deterioration of functioning in chronically sufferers from alcoholic dependence. The term "quaternary prevention" can be used for the prevention of relapse. As for primary prevention, interventions focus on assessing the risk of falling into problematic use, enhancing protective factors and providing information and health education in general. These interventions can be delivered in schools or in places of work and recreation for young people. In this context, various programs have been applied in different countries, including Greece with positive results (Preventure, Alcolocks, LST, SFP, Alcohol Ignition Interlock Device). Secondary prevention includes counseling and structured help with the delivery of programs in schools and in high risk groups for alcohol dependence (SAP, LST). These programs aim at the development of alcohol refusal skills and behaviors, the adoption of models of behaviors resisting alcohol use, as well as reinforcement of general social skills. In the

  20. Comparing dependent robust correlations.

    PubMed

    Wilcox, Rand R

    2016-11-01

    Let r1 and r2 be two dependent estimates of Pearson's correlation. There is a substantial literature on testing H0  : ρ1  = ρ2 , the hypothesis that the population correlation coefficients are equal. However, it is well known that Pearson's correlation is not robust. Even a single outlier can have a substantial impact on Pearson's correlation, resulting in a misleading understanding about the strength of the association among the bulk of the points. A way of mitigating this concern is to use a correlation coefficient that guards against outliers, many of which have been proposed. But apparently there are no results on how to compare dependent robust correlation coefficients when there is heteroscedasicity. Extant results suggest that a basic percentile bootstrap will perform reasonably well. This paper reports simulation results indicating the extent to which this is true when using Spearman's rho, a Winsorized correlation or a skipped correlation.

  1. Myofilament length dependent activation.

    PubMed

    de Tombe, Pieter P; Mateja, Ryan D; Tachampa, Kittipong; Ait Mou, Younss; Farman, Gerrie P; Irving, Thomas C

    2010-05-01

    The Frank-Starling law of the heart describes the interrelationship between end-diastolic volume and cardiac ejection volume, a regulatory system that operates on a beat-to-beat basis. The main cellular mechanism that underlies this phenomenon is an increase in the responsiveness of cardiac myofilaments to activating Ca(2+) ions at a longer sarcomere length, commonly referred to as myofilament length-dependent activation. This review focuses on what molecular mechanisms may underlie myofilament length dependency. Specifically, the roles of inter-filament spacing, thick and thin filament based regulation, as well as sarcomeric regulatory proteins are discussed. Although the "Frank-Starling law of the heart" constitutes a fundamental cardiac property that has been appreciated for well over a century, it is still not known in muscle how the contractile apparatus transduces the information concerning sarcomere length to modulate ventricular pressure development.

  2. Myofilament length dependent activation

    SciTech Connect

    de Tombe, Pieter P.; Mateja, Ryan D.; Tachampa, Kittipong; Mou, Younss Ait; Farman, Gerrie P.; Irving, Thomas C.

    2010-05-25

    The Frank-Starling law of the heart describes the interrelationship between end-diastolic volume and cardiac ejection volume, a regulatory system that operates on a beat-to-beat basis. The main cellular mechanism that underlies this phenomenon is an increase in the responsiveness of cardiac myofilaments to activating Ca{sup 2+} ions at a longer sarcomere length, commonly referred to as myofilament length-dependent activation. This review focuses on what molecular mechanisms may underlie myofilament length dependency. Specifically, the roles of inter-filament spacing, thick and thin filament based regulation, as well as sarcomeric regulatory proteins are discussed. Although the 'Frank-Starling law of the heart' constitutes a fundamental cardiac property that has been appreciated for well over a century, it is still not known in muscle how the contractile apparatus transduces the information concerning sarcomere length to modulate ventricular pressure development.

  3. Why Density Dependent Propulsion?

    NASA Technical Reports Server (NTRS)

    Robertson, Glen A.

    2011-01-01

    In 2004 Khoury and Weltman produced a density dependent cosmology theory they call the Chameleon, as at its nature, it is hidden within known physics. The Chameleon theory has implications to dark matter/energy with universe acceleration properties, which implies a new force mechanism with ties to the far and local density environment. In this paper, the Chameleon Density Model is discussed in terms of propulsion toward new propellant-less engineering methods.

  4. ARL Arabic Dependency Treebank

    DTIC Science & Technology

    2016-02-10

    Detection for Modern Standard Arabic to English MT” (Tratz, 2014). The LDC is one of the foremost sources of annotated data used in computational... vowel diacritic—the typical indicator of genitive case—was not written, the DET label would appear on one line with the Al definite determiner, the... English dependency label scheme (de Marneffe & Manning, 2008). However, this is to not to say that they may always be interpreted identically. Also

  5. Dependence, Risk, and Vulnerability.

    DTIC Science & Technology

    1981-06-01

    B2 has a great deal. The measurement strategy outlined here will gauge A’s import depen- dence on B2 as greater than A’s import dependence on B1 . One...pp 25 Doctrines: One More Time." 43 pp., Jan 1960. Glee. Devid V.; Hsoi. Ih-Chses: Nu,n, Welter A. AD AOIl 192 PP 283 mnd Penn, David A.. "A Clas of

  6. Dependability and Performability Analysis

    DTIC Science & Technology

    1993-11-01

    NASA Contractor Report 191565 ICASE Report No. 93-85 (0) ii ICASE U DEPENDABILITY AND PERFORMABILITY ANALYSIS Kishor S. Trivedi Gianfranco Ciardo...PERFORMABILITY ANALYSIS1 Kishor S. Trivedi Gianfranco Ciardo Manish Malhotra Robin A. Sahner Department of Electrical Engineering, Duke University...Trivedi, Gianfranco Ci&rdo, Manish Maihotra, and Robin A. Sahner 7. PERFORMING ORGANIZATION NAME(S) AND ADORESS(ES) 8. PERFORMING ORGANIZATION Institute

  7. Is extinction age dependent?

    USGS Publications Warehouse

    Doran, N.A.; Arnold, A.J.; Parker, W.C.; Huffer, F.W.

    2006-01-01

    Age-dependent extinction is an observation with important biological implications. Van Valen's Red Queen hypothesis triggered three decades of research testing its primary implication: that age is independent of extinction. In contrast to this, later studies with species-level data have indicated the possible presence of age dependence. Since the formulation of the Red Queen hypothesis, more powerful tests of survivorship models have been developed. This is the first report of the application of the Cox Proportional Hazards model to paleontological data. Planktonic foraminiferal morphospecies allow the taxonomic and precise stratigraphic resolution necessary for the Cox model. As a whole, planktonic foraminiferal morphospecies clearly show age-dependent extinction. In particular, the effect is attributable to the presence of shorter-ranged species (range < 4 myr) following extinction events. These shorter-ranged species also possess tests with unique morphological architecture. The morphological differences are probably epiphenomena of underlying developmental and heterochronic processes of shorter-ranged species that survived various extinction events. Extinction survivors carry developmental and morphological characteristics into postextinction recovery times, and this sets them apart from species populations established independently of extinction events. Copyright ?? 2006, SEPM (Society for Sedimentary Geology).

  8. Time dependent holography

    NASA Astrophysics Data System (ADS)

    Das, Diptarka

    One of the most important results emerging from string theory is the gauge gravity duality (AdS/CFT correspondence) which tells us that certain problems in particular gravitational backgrounds can be exactly mapped to a particular dual gauge theory a quantum theory very similar to the one explaining the interactions between fundamental subatomic particles. The chief merit of the duality is that a difficult problem in one theory can be mapped to a simpler and solvable problem in the other theory. The duality can be used both ways. Most of the current theoretical framework is suited to study equilibrium systems, or systems where time dependence is at most adiabatic. However in the real world, systems are almost always out of equilibrium. Generically these scenarios are described by quenches, where a parameter of the theory is made time dependent. In this dissertation I describe some of the work done in the context of studying quantum quench using the AdS/CFT correspondence. We recover certain universal scaling type of behavior as the quenching is done through a quantum critical point. Another question that has been explored in the dissertation is time dependence of the gravity theory. Present cosmological observations indicate that our universe is accelerating and is described by a spacetime called de-Sitter(dS). In 2011 there had been a speculation over a possible duality between de-Sitter gravity and a particular field theory (Euclidean SP(N) CFT). However a concrete realization of this proposition was still lacking. Here we explicitly derive the dS/CFT duality using well known methods in field theory. We discovered that the time dimension emerges naturally in the derivation. We also describe further applications and extensions of dS/CFT. KEYWORDS: Holography, AdS/CFT correspondence, Quantum Quench, dS/CFT correspondence, Chaos.

  9. Pharmacotherapy of nicotine dependence.

    PubMed

    Haustein, K O

    2000-06-01

    Withdrawal treatment of cigarette smokers is a task of the utmost urgency in view of the consequences for national health programs and legislative policies of the high morbidity and mortality rates caused by smoking. Smokers need medical consultation in addition to drug-based treatment, but this results in self-willed quitting of the smoking habit in a limited number of smokers only. From the point of view of the criteria of "evidence-based medicine", non-drug methods such as hypnosis therapy and acupuncture are not effective (odds ratio = 1.22). Among the drug-based methods, treatment with nicotine substitution preparations has shown confirmed efficacy in numerous studies (odds ratio 1.63 to 2.67, depending on the application form used) and results in successful withdrawal from the smoking habit in 30-40% of cases. A decisive problem in the initial therapeutic phase appears to be the amount of the applied nicotine dose, but beyond that can be mastered above all by combining 2 or 3 application forms (patchs, chewing gum, nasal spray). Treatment is then continued for 4-12 weeks, depending on the degree of dependence, with successively reduced nicotine dosage. Two controlled studies with disparate designs have been done on bupropion (odds ratio 2.3/3.0). However, further studies are desirable due to concern about undesirable effects of bupropion described recently. Other substances subjected to trials in years past, such as clonidine, lobeline, mecamylamine and antidepressants including buspirone cannot be recommended on the basis of current data for treatment of smokers seeking a withdrawal cure.

  10. Dependent rational providers.

    PubMed

    Brothers, Kyle B

    2011-04-01

    Provider claims to conscientious objection have generated a great deal of heated debate in recent years. However, the conflicts that arise when providers make claims to the "conscience" are only a subset of the more fundamental challenges that arise in health care practice when patients and providers come into conflict. In this piece, the author provides an account of patient-provider conflict from within the moral tradition of St. Thomas Aquinas. He argues that the practice of health care providers should be understood as a form of practical reasoning and that this practical reasoning must necessarily incorporate both "moral" and "professional" commitments. In order to understand how the practical reasoning of provider should account for the needs and commitments of the patient and vice versa, he explores the account of dependence provided by Alasdair MacIntyre in his book Dependent Rational Animals. MacIntyre argues that St. Thomas' account of practical reasoning should be extended and adapted to account for the embodied vulnerability of all humans. In light of this insight, providers must view patients not only as the subjects of their moral reflection but also as fellow humans upon whom the provider depends for feedback on the effectiveness and relevance of her practical reasoning. The author argues that this account precludes responsive providers from adopting either moral or professional conclusions on the appropriateness of interventions outside the individual circumstances that arise in particular situations. The adoption of this orientation toward patients will neither eradicate provider-patient conflict nor compel providers to perform interventions to which they object. But this account does require that providers attend meaningfully to the suffering of patients and seek feedback on whether their intervention has effectively addressed that suffering.

  11. Treatment of nicotine dependence.

    PubMed

    Haxby, D G

    1995-02-01

    Drug and nondrug interventions used in treating nicotine dependence are reviewed. Tobacco use is the leading preventable cause of death in the United States. Risks of smoking-related disease and death decline sharply when smokers quit, but 26% of Americans continue to smoke. Most smokers find it extremely difficult to quit smoking because of their nicotine addiction. Nonpharmacologic interventions used to promote smoking cessation include behavioral therapy, setting a specific date for quitting, receiving advice to quit from a health care professional, follow-up visits to review progress, self-help approaches, group counseling, filtration devices, hypnosis, and acupuncture. The efficacy of these approaches ranges from substantial to almost nil. The only pharmacologic agent with FDA-approved labeling for use in smoking-cessation therapy is nicotine. When used in conjunction with appropriate nonpharmacologic interventions, nicotine-replacement therapy roughly doubles the rate of quitting obtained with placebo. Nicotine-replacement therapies consist of nicotine transdermal (patch) systems and nicotine chewing gum. The nicotine patch is the first-line replacement therapy because it is effective when accompanied by only minimal (as opposed to more intensive) nonpharmacologic interventions and because it is easier to use and comply with than gum. Clonidine, antidepressants, and buspirone require further study to determine what role, if any, they should play in the treatment of nicotine dependence. The stages of smoking cessation are precontemplation, contemplation, action, and maintenance; interventions are selected on the basis of the stage the smoker is in. Nicotine dependence is difficult to treat, but there are aids that boost a smoker's chances of quitting. Nicotine patches and chewing gum offer the most effective pharmacologic options, especially when combined with behavioral interventions and counseling.

  12. Portage and Path Dependence*

    PubMed Central

    Bleakley, Hoyt; Lin, Jeffrey

    2012-01-01

    We examine portage sites in the U.S. South, Mid-Atlantic, and Midwest, including those on the fall line, a geomorphological feature in the southeastern U.S. marking the final rapids on rivers before the ocean. Historically, waterborne transport of goods required portage around the falls at these points, while some falls provided water power during early industrialization. These factors attracted commerce and manufacturing. Although these original advantages have long since been made obsolete, we document the continuing importance of these portage sites over time. We interpret these results as path dependence and contrast explanations based on sunk costs interacting with decreasing versus increasing returns to scale. PMID:23935217

  13. Spatial dependence of thrombolysis

    NASA Astrophysics Data System (ADS)

    Lakshmanan, Hari Hara Sudhan; Zilberman-Rudenko, Jevgenia; McCarty, Owen; Maddala, Jeevan

    2016-11-01

    Thrombolysis under hemodynamic conditions is affected by both transport processes and reactions, thus profoundly dependent on the geometry of blood vessels or vasculature. Although thrombosis has long been observed clinically, a systematic and quantitative understanding has not been established in complex geometries such as vasculature, where various factors would affect thrombogenesis and its stability. A thrombus's location determines the effect of hydrodynamic forces on it and rate of tPA diffusion, that would result in either embolization or formation of micro-aggregates. Preliminary experiments have shown that thrombolysis is not uniform across an entire network with different locations lysing at different rates. Numerical simulations of thrombolysis under hemodynamics in a microfluidic geometry such as a ladder network with a focus on parameters such as reaction rate, shear gradient, velocity and diffusion established the lysis's dependence on geometry. Finite element simulations of blood flow coupled with reactions have been performed in COMSOL and the results were used to develop quantifiable metrics for thrombolysis in a complex geometry.

  14. Megadose bromazepam dependence.

    PubMed

    Bastide, Anaïs; de Codt, Aloïse; Monhonval, Pauline; Bongaerts, Xavier; Tecco, Juan Martin

    2016-09-01

    Benzodiazepines (BZDs) are among the most widely prescribed drugs in developed countries. Since BZDs can produce tolerance and dependence even in a short time, their use is recommended for a very limited time. However, these recommendations have been largely disregarded. The chronic use of BZDs causes a number of serious side effects, i.e. cognitive impairment, falls, traffic accidents, dependence and tolerance. We present the case of a 37 years old woman taking daily doses of 220 mg of bromazepam. The patient's anxiety, depression and cognitive status were evaluated with a battery of questionnaires. A sleep laboratory test was performed in search of sleep apneas and sleepiness during the day. A Cerebral PET SCAN was executed in search of altered cerebral metabolism. Blood concentrations of bromazepam reached 7800 μg/L. Questionnaire evaluations showed significant depression and anxiety but only moderate cognitive impairment. Oxygen saturation was normal throughout the Sleep lab test, respiratory events were very few and sleepiness was moderate with an average latency of 9 minutes. Brain cortical glucose consumption was homogeneously slightly reduced. With doses of bromazepan reaching 15 times the toxic dose, anxiety remained high. Cognition, sleepiness, respiratory sleep events and brain metabolism remained remarkably close to normal.

  15. Velocity dependant splash behaviour

    NASA Astrophysics Data System (ADS)

    Hamlett, C. A. E.; Shirtcliffe, N. J.; McHale, G.; Ahn, S.; Doerr, S. H.; Bryant, R.; Newton, M. I.

    2012-04-01

    Extreme soil water repellency can occur in nature via condensation of volatile organic compounds released during wildfires and can lead to increased erosion rate. Such extreme water repellent soil can be classified as superhydrophobic and shares similar chemical and topographical features to specifically designed superhydrophobic surfaces. Previous studies using high speed videography to investigate single droplet impact behaviour on artificial superhydrophobic have revealed three distinct modes of splash behaviour (rebound, pinned and fragmentation) which are dependent on the impact velocity of the droplet. In our studies, using high-speed videography, we show that such splash behaviour can be replicated on fixed 'model' water repellent soils (hydrophobic glass beads/particles). We show that the type of splash behaviour is dependent on both the size and chemical nature of the fixed particles. The particle shape also influences the splash behaviour as shown by drop impact experiments on fixed sand samples. We have also studied soil samples, as collected from the field, which shows that the type of droplet splash behaviour can lead to enhanced soil particle transport.

  16. Excitability dependent pattern formation

    NASA Astrophysics Data System (ADS)

    Prabhakara, Kaumudi; Gholami, Azam; Bodenschatz, Eberhard

    2014-03-01

    On starvation, the amoebae Dictyostelium discoideum emit the chemo-attractant cyclic adenosine monophosphate (cAMP) at specific frequencies. The neighboring amoebae sense cAMP through membrane receptors and produce their own cAMP. Soon the cells synchronize and move via chemotaxis along the gradient of cAMP. The response of the amoebae to the emission of cAMP is seen as spiral waves or target patterns under a dark field microscope. The causal reasons for the selection of one or the other patterns are still unclear. Here we present a possible explanation based on excitability. The excitability of the amoebae depends on the starvation time because the gene expression changes with starvation. Cells starved for longer times are more excitable. In this work, we mix cells of different excitabilities to study the dependence of the emergent patterns on the excitability. Preliminary results show a transition from spirals to target patterns for specific excitabilities. A phase map of the patterns for different combinations of excitability and number densities is obtained. We compare our findings with numerical simulations of existing theoretical models.

  17. [Frequency dependance of compliance].

    PubMed

    Gayrard, P

    1975-01-01

    Resistance of peripheral or "small" airways is only a small part of the total pulmonary resistance (Raw). Even considerable obstruction in these airways will have little effect on total resistance. Conversely this will lead to inequality in the time constants of units in parallel, and dynamic lung compliance (C dyn) shall fall as respiratory frequence increases. C dyn is measured from simultaneous recordings of transpulmonary pressure (esophageal balloon) and volume obtained from a volume displacement plethysmograph. If Raw and static compliance are found to be normal, the frequency dependance of compliance will result from peripheral airway obstruction only. Early stages of chronic airway obstruction can be established by this method. However this appear not suitable for wide-scale studies.

  18. Solar Diameter Latitude Dependence

    NASA Astrophysics Data System (ADS)

    Emilio, M.; Leister, N. V.; Laclare, F.

    The observing programs of the Sun for determining the fundamental system of reference enable, as a by-product, to measure the apparent solar diameter (Poppe, P.C.R. et al. 1996; Leister et al. 1996; Laclare et al. 1991). The diameter obtained at the Calern Observatory (φ = 43-circ 44' 55''.9; λ = -0h 27m 42s.44) and at Abrahao de Moraes Observatory (OAM) (φ = -23-circ 00'6''.0; λ = 3h 07m 52s.22) was analyzed searching for periodicity evidences. For this we utilized the temporal methods CLEAN and CLEANEST. The analysis in function of heliographic latitude shows a dependence that may be correlated to mode of pulsation non-radial gravity. A discussion is made in terms of physical parameters like temperature luminosity and magnetic field involving the solar radius (Emilio M. 1997; Laclare et al. 1996).

  19. Sequential dependencies in driving.

    PubMed

    Doshi, Anup; Tran, Cuong; Wilder, Matthew H; Mozer, Michael C; Trivedi, Mohan M

    2012-07-01

    The effect of recent experience on current behavior has been studied extensively in simple laboratory tasks. We explore the nature of sequential effects in the more naturalistic setting of automobile driving. Driving is a safety-critical task in which delayed response times may have severe consequences. Using a realistic driving simulator, we find significant sequential effects in pedal-press response times that depend on the history of recent stimuli and responses. Response times are slowed up to 100 ms in particular cases, a delay that has dangerous practical consequences. Further, we observe a significant number of history-related pedal misapplications, which have recently been noted as a cause for concern in the automotive safety community. By anticipating these consequences of sequential context, driver assistance systems could mitigate the effects of performance degradations and thus critically improve driver safety. Copyright © 2012 Cognitive Science Society, Inc.

  20. Anticonvulsants for alcohol dependence.

    PubMed

    Pani, Pier Paolo; Trogu, Emanuela; Pacini, Matteo; Maremmani, Icro

    2014-02-13

    Alcohol dependence is a major public health problem that is characterised by recidivism and a host of medical and psychosocial complications. Besides psychosocial interventions, different pharmacological interventions have been or currently are under investigation through Cochrane systematic reviews. The primary aim of the review is to assess the benefits/risks of anticonvulsants for the treatment of alcohol dependence. We searched the Cochrane Drugs and Alcohol Group Trials Register (October 2013), PubMed (1966 to October 2013), EMBASE (1974 to October 2013) and CINAHL (1982 to October 2013). Randomised controlled trials (RCTs) and controlled clinical trials (CCTs) comparing anticonvulsants alone or in association with other drugs and/or psychosocial interventions versus placebo, no treatment and other pharmacological or psychosocial interventions. We used standard methodological procedures as expected by The Cochrane Collaboration. A total of 25 studies were included in the review (2641 participants). Most participants were male, with an average age of 44 years. Anticonvulsants were compared with placebo (17 studies), other medications (seven studies) and no medication (two studies). The mean duration of the trials was 17 weeks (range four to 52 weeks). The studies took place in the USA, Europe, South America, India and Thailand. Variation was reported in the characteristics of the studies, including their design and the rating instruments used. For many key outcomes, the risk of bias associated with unclear or unconcealed allocation and lack of blinding affected the quality of the evidence.Anticonvulsants versus placebo: For dropouts (16 studies, 1675 participants, risk ratio (RR) 0.94, 95% confidence interval (Cl) 0.74 to 1.19, moderate-quality evidence) and continuous abstinence (eight studies, 634 participants, RR 1.21, 95% Cl 95% 0.97 to 1.52, moderate-quality evidence), results showed no evidence of differences. Moderate-quality evidence suggested that

  1. Comparison of the biological effects of {sup 18}F at different intracellular levels

    SciTech Connect

    Kashino, Genro; Hayashi, Kazutaka; Douhara, Kazumasa; Kobashigawa, Shinko; Mori, Hiromu

    2014-11-07

    Highlights: • We estimated the inductions of DNA DSB in cell treated with {sup 18}F-FDG. • We found that inductions of DNA DSB are dependent on accumulation of {sup 18}F in cell. • Accumulation of {sup 18}F in cell may be indispensable for risk estimation of PET. - Abstract: We herein examined the biological effects of cells treated with {sup 18}F labeled drugs for positron emission tomography (PET). The relationship between the intracellular distribution of {sup 18}F and levels of damaged DNA has yet to be clarified in detail. We used culture cells (Chinese Hamster Ovary cells) treated with two types of {sup 18}F labeled drugs, fluorodeoxyglucose (FDG) and fluorine ion (HF). FDG efficiently accumulated in cells, whereas HF did not. To examine the induction of DNA double strand breaks (DSB), we measured the number of foci for 53BP1 that formed at the site of DNA DSB. The results revealed that although radioactivity levels were the same, the induction of 53BP1 foci was stronger in cells treated with {sup 18}F-FDG than in those treated with {sup 18}F-HF. The clonogenic survival of cells was significantly lower with {sup 18}F-FDG than with {sup 18}F-HF. We concluded that the efficient accumulation of {sup 18}F in cells led to stronger biological effects due to more severe cellular lethality via the induction of DNA DSB.

  2. Pharmacotherapy for nicotine dependence.

    PubMed

    Henningfield, Jack E; Fant, Reginald V; Buchhalter, August R; Stitzer, Maxine L

    2005-01-01

    Approximately 50% of long-term cigarette smokers die prematurely from the adverse effects of smoking, including on cancer, cardiovascular disease, lung disease, or other illness. This risk can be substantially reduced by smoking cessation, with greater benefits occurring the earlier in the smoking career that cessation occurs. However, cessation provides benefits at any stage, including after the onset of smoking-related disease, by improving the prognosis and quality of life. Clinicians can have a significant impact on reducing tobacco use by their patients by following the US Public Health Service Clinical Practice Guidelines. Proven strategies include structured methods of advising cigarette smokers to quit and guidance to facilitate their efforts, as well as the use of various pharmacotherapies. Pharmacotherapies for tobacco dependence include nicotine replacement medications in the form of gum, transdermal patch, lozenge, sublingual tablet, nasal spray, and vapor inhaler formulations. The only nonnicotine medication that has been approved by the US Food and Drug Administration is bupropion. Combination therapies, long-term medication therapies, and harm reduction strategies may further improve outcome with approved medications. Further, new medications such as varenicline and rimonabant are likely to reach tobacco users who are refractory to current treatments. Increasing the treatment options, increasing availability, and reducing the perceived cost of these medications may have an additional public health impact.

  3. Density dependent neurodynamics.

    PubMed

    Halnes, Geir; Liljenström, Hans; Arhem, Peter

    2007-01-01

    The dynamics of a neural network depends on density parameters at (at least) two different levels: the subcellular density of ion channels in single neurons, and the density of cells and synapses at a network level. For the Frankenhaeuser-Huxley (FH) neural model, the density of sodium (Na) and potassium (K) channels determines the behaviour of a single neuron when exposed to an external stimulus. The features of the onset of single neuron oscillations vary qualitatively among different regions in the channel density plane. At a network level, the density of neurons is reflected in the global connectivity. We study the relation between the two density levels in a network of oscillatory FH neurons, by qualitatively distinguishing between three regions, where the mean network activity is (1) spiking, (2) oscillating with enveloped frequencies, and (3) bursting, respectively. We demonstrate that the global activity can be shifted between regions by changing either the density of ion channels at the subcellular level, or the connectivity at the network level, suggesting that different underlying mechanisms can explain similar global phenomena. Finally, we model a possible effect of anaesthesia by blocking specific inhibitory ion channels.

  4. Cyclin-dependent kinases

    PubMed Central

    2014-01-01

    Summary Cyclin-dependent kinases (CDKs) are protein kinases characterized by needing a separate subunit - a cyclin - that provides domains essential for enzymatic activity. CDKs play important roles in the control of cell division and modulate transcription in response to several extra- and intracellular cues. The evolutionary expansion of the CDK family in mammals led to the division of CDKs into three cell-cycle-related subfamilies (Cdk1, Cdk4 and Cdk5) and five transcriptional subfamilies (Cdk7, Cdk8, Cdk9, Cdk11 and Cdk20). Unlike the prototypical Cdc28 kinase of budding yeast, most of these CDKs bind one or a few cyclins, consistent with functional specialization during evolution. This review summarizes how, although CDKs are traditionally separated into cell-cycle or transcriptional CDKs, these activities are frequently combined in many family members. Not surprisingly, deregulation of this family of proteins is a hallmark of several diseases, including cancer, and drug-targeted inhibition of specific members has generated very encouraging results in clinical trials. PMID:25180339

  5. Parenthood and opioid dependence.

    PubMed

    Pihkala, Heljä; Sandlund, Mikael

    2015-01-01

    Many patients in maintenance treatment programs for opioid dependence are parents to underage children. The aim of this study was to explore how parents who are regular patients in maintenance treatment perceive their parenthood. The study used a qualitative approach. The informants were recruited by staff at a substance abuse clinic in Sweden. Criteria for inclusion were participation in the local maintenance treatment program, having a child or children younger than 18 years, and being in contact with the child or children. Data were collected in 2012-2013 by in-depth interviews of seven fathers and five mothers and analyzed using concepts and procedures of qualitative content analysis. The central findings of the study were: 1) the parents' concerns about possible future discrimination against their children, ie, stigma by association; and 2) the patients' own parents' role as the most important support in parenthood. The issue of anticipated discrimination against the children of parents undergoing maintenance treatment might be an aspect to consider in the development of interventions and support. Considering the role of the patients' own parents also seems important.

  6. Deterioration + dependence = disaster

    SciTech Connect

    Halbouty, M.T.

    1987-05-01

    As a result of the impact of falling world oil prices, the worldwide oversupply of oil, the hostile raids and takeovers, and the retrenchment of the global petroleum industry, over a brief period of five years much of the US petroleum industry has slowly disintegrated. Exploration programs have been especially hard hit, and the losses incurred can be measured not only by balance-sheet assessments but by the decline in their national energy security and the devaluation of their greatest asset - the professionals who have been terminated or retired from their once world-premier manpower pool. In addition, major budgetary cutbacks in research and development programs have also necessitated reductions in people and projects. The deterioration that the petroleum industry has sustained in exploration programs and in other activities has had a ripple effect throughout all segments of the nation's industrial complex and its support structure. Their rising import levels, combined with their falling production, produce a devastating equation: Deterioration + Dependence = Disaster. Possible recommendations are made and solutions discusses to alleviate the conditions which exist in the industry.

  7. Context-dependent generalization

    PubMed Central

    Taylor, Jordan A.; Ivry, Richard B.

    2013-01-01

    The pattern of generalization following motor learning can provide a probe on the neural mechanisms underlying learning. For example, the breadth of generalization to untrained regions of space after visuomotor adaptation to targets in a restricted region of space has been attributed to the directional tuning properties of neurons in the motor system. Building on this idea, the effect of different types of perturbations on generalization (e.g., rotation vs. visual translation) have been attributed to the selection of differentially tuned populations. Overlooked in this discussion is consideration of how the context of the training environment may constrain generalization. Here, we explore the role of context by having participants learn a visuomotor rotation or a translational shift in two different contexts, one in which the array of targets were presented in a circular arrangement and the other in which they were presented in a rectilinear arrangement. The perturbation and environments were either consistent (e.g., rotation with circular arrangement) or inconsistent (e.g., rotation with rectilinear arrangement). The pattern of generalization across the workspace was much more dependent on the context of the environment than on the perturbation, with broad generalization for the rectilinear arrangement for both types of perturbations. Moreover, the generalization pattern for this context was evident, even when the perturbation was introduced in a gradual manner, precluding the use of an explicit strategy. We describe how current models of generalization might be modified to incorporate these results, building on the idea that context provides a strong bias for how the motor system infers the nature of the visuomotor perturbation and, in turn, how this information influences the pattern of generalization. PMID:23653603

  8. Pharmacotherapies for cannabis dependence

    PubMed Central

    Marshall, Kushani; Gowing, Linda; Ali, Robert; Le Foll, Bernard

    2015-01-01

    Background Cannabis is the most prevalent illicit drug in the world. Demand for treatment of cannabis use disorders is increasing. There are currently no pharmacotherapies approved for treatment of cannabis use disorders. Objectives To assess the effectiveness and safety of pharmacotherapies as compared with each other, placebo or supportive care for reducing symptoms of cannabis withdrawal and promoting cessation or reduction of cannabis use. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (to 4 March 2014), MEDLINE (to week 3 February 2014), EMBASE (to 3 March 2014) and PsycINFO (to week 4 February 2014). We also searched reference lists of articles, electronic sources of ongoing trials and conference proceedings, and contacted selected researchers active in the area. Selection criteria Randomised and quasi-randomised controlled trials involving the use of medications to reduce the symptoms and signs of cannabis withdrawal or to promote cessation or reduction of cannabis use, or both, in comparison with other medications, placebo or no medication (supportive care) in participants diagnosed as cannabis dependent or who were likely to be dependent. Data collection and analysis We used standard methodological procedures expected by The Cochrane Collaboration. Two review authors assessed studies for inclusion and extracted data. All review authors confirmed the inclusion decisions and the overall process. Main results We included 14 randomised controlled trials involving 958 participants. For 10 studies the average age was 33 years; two studies targeted young people; and age data were not available for two studies. Approximately 80% of study participants were male. The studies were at low risk of selection, performance, detection and selective outcome reporting bias. Three studies were at risk of attrition bias. All studies involved comparison of active medication and placebo. The medications included preparations containing

  9. Pharmacological Intervention of Nicotine Dependence

    PubMed Central

    Jain, Raka; Gupta, Tina

    2013-01-01

    Nicotine dependence is a major cause of mortality and morbidity all over the world. Various medications have been tried to treat nicotine dependence including nicotine replacement therapy, bupropion, and varenicline. A newer venture to nicotine dependence treatment is a nicotine vaccine which is yet to get footsteps in common practice. The present review assimilates various pharmacotherapeutic measures to address nicotine dependence. However, it is to be noted that psychological interventions, when combined with pharmacotherapy, offer the greatest benefits to the patients. PMID:24490153

  10. Field dependence and distraction revisited.

    PubMed

    Blowers, G H

    1976-02-01

    An attempt is made to replicate a former study of the relationship of field dependence as measured by rod-and-frame errors to distraction in an RT paradigm. For two groups of Ss (n = 14) who differed specifically in their dependence upon the tilted frame and were classified as frame-dependent and frame-independent, no relationship of frame (or field) dependence to susceptibility to distraction was found.

  11. Texting Dependence, iPod Dependence, and Delay Discounting.

    PubMed

    Ferraro, F Richard; Weatherly, Jeffrey N

    2016-01-01

    We gave 127 undergraduates questionnaires about their iPod and texting dependence and 2 hypothetical delay discounting scenarios related to free downloaded songs and free texting for life. Using regression analyses we found that when iPod dependence was the dependent variable, Text2-excessive use, Text4-psychological and behavioral symptoms, iPod2-excessive use, and iPod3-relationship disruption were significant predictors of discounting. When texting dependence was the dependent variable, Text4-psychological and behavioral symptoms and iPod3-relationship disruption were significant predictors of discounting. These are the first data to show that delay discounting relates to certain aspects of social media, namely iPod and texting dependence. These data also show that across these 2 dependencies, both psychological and behavioral symptoms and relationship disruptions are affected.

  12. Dependency Grammar: Classification and Exploration

    NASA Astrophysics Data System (ADS)

    Debusmann, Ralph; Kuhlmann, Marco

    Syntactic representations based on word-to-word dependencies have a long tradition in descriptive linguistics [29]. In recent years, they have also become increasingly used in computational tasks, such as information extraction [5], machine translation [43], and parsing [42]. Among the purported advantages of dependency over phrase structure representations are conciseness, intuitive appeal, and closeness to semantic representations such as predicate-argument structures. On the more practical side, dependency representations are attractive due to the increasing availability of large corpora of dependency analyses, such as the Prague Dependency Treebank [19].

  13. Dextropropoxyphene dependence: a cautionary note.

    PubMed

    Edwin, T; Nammalvar, N; Ramanujam, V

    2001-05-01

    Drug abuse and dependence is common in patients with chronic pain. Of concern are the opioid analgesics prescribed commonly, and its availability over the counter. Often the cause of dependence is iatrogenic. We report a case of a patient with chronic back pain and dextropropoxyphene dependence. With chronic pain being a significant risk factor for drug dependence, increased caution by the prescribing physicians is advisable while treating such patients using opioid analgesics. The dangers of opioid dependence, associated risk factors, and issues regarding the prescription of such medication are discussed to aid prevention of prescription drug abuse seen in general practice.

  14. A rare case modafinil dependence.

    PubMed

    Krishnan, Raman; Chary, Krishnan Vengadaragava

    2015-01-01

    Modafinil, a non-amphetamine psychostimulant, is indicated for narcolepsy, shift work sleep disorder and severe obstructive sleep apnea syndrome. Modafinil is prescribed at the dose of 100 mg once in a day or as two doses, 12 h apart in a day. It has also been found that it reduces cocaine dependence and withdrawal phenomenon. Modafinil is claimed to have very low liability for abuse and dependence. Here we report a rare case of modafinil dependence.

  15. Agitated Depression in Substance Dependence

    PubMed Central

    Leventhal, Adam M.; Gelernter, Joel; Oslin, David; Anton, Raymond F.; Farrer, Lindsay A.

    2011-01-01

    Background Depression with psychomotor agitation (PMA; “agitated depression”) is a putative psychiatric phenotype that appears to associate with some forms of substance dependence. However, it is unclear whether such relationships extend across different substances and independent (I-MDE) versus substance-induced (SI-MDE) subtypes of major depressive episodes. Method We examined whether lifetime depression with (vs. without) PMA was associated with lifetime substance dependence across individuals with lifetime: (1) I-MDE only (n = 575); and (2) SI-MDE only (n = 1683). Data were pooled from several family and genetic studies of substance dependence in which participants received identical structured interviews to diagnose DSM-IV mental disorders. Results In I-MDE, PMA was significantly associated with alcohol, cocaine, opioid, other drug (hallucinogen, inhalant, speed-ball), and sedative dependence. After controlling for demographic and clinical co-factors, PMA's relationship to dependence on opioids, other drugs, and sedatives remained significant, but not its relationship to alcohol or cocaine. In SI-MDE, PMA was significantly associated with alcohol, cocaine, opioid, and other drug dependence. After adjusting for co-factors, associations remained significant for dependence on cocaine and opioids, but not alcohol or other drugs. Relationships between PMA and opioid dependence were stronger in I-MDE than SI-MDE. Depression subtype (I-MDE vs. SI-MDE) did not moderate relations between PMA and non-opioid forms of substance dependence. Conclusions Agitated depression associates with certain forms of substance dependence, particularly opioid dependence. MDE subtype did not alter most PMA-dependence associations, which suggests that the mechanisms underlying this comorbidity are complex and potentially bidirectional. PMID:21277711

  16. Spike-timing-dependent synaptic plasticity depends on dendritic location

    NASA Astrophysics Data System (ADS)

    Froemke, Robert C.; Poo, Mu-ming; Dan, Yang

    2005-03-01

    In the neocortex, each neuron receives thousands of synaptic inputs distributed across an extensive dendritic tree. Although postsynaptic processing of each input is known to depend on its dendritic location, it is unclear whether activity-dependent synaptic modification is also location-dependent. Here we report that both the magnitude and the temporal specificity of spike-timing-dependent synaptic modification vary along the apical dendrite of rat cortical layer 2/3 pyramidal neurons. At the distal dendrite, the magnitude of long-term potentiation is smaller, and the window of pre-/postsynaptic spike interval for long-term depression (LTD) is broader. The spike-timing window for LTD correlates with the window of action potential-induced suppression of NMDA (N-methyl-D-aspartate) receptors; this correlation applies to both their dendritic location-dependence and pharmacological properties. Presynaptic stimulation with partial blockade of NMDA receptors induced LTD and occluded further induction of spike-timing-dependent LTD, suggesting that NMDA receptor suppression underlies LTD induction. Computer simulation studies showed that the dendritic inhomogeneity of spike-timing-dependent synaptic modification leads to differential input selection at distal and proximal dendrites according to the temporal characteristics of presynaptic spike trains. Such location-dependent tuning of inputs, together with the dendritic heterogeneity of postsynaptic processing, could enhance the computational capacity of cortical pyramidal neurons.

  17. The dependency paradox in close relationships: accepting dependence promotes independence.

    PubMed

    Feeney, Brooke C

    2007-02-01

    Using multiple methods, this investigation tested the hypothesis that a close relationship partner's acceptance of dependence when needed (e.g., sensitive responsiveness to distress cues) is associated with less dependence, more autonomous functioning, and more self-sufficiency (as opposed to more dependence) on the part of the supported individual. In two studies, measures of acceptance of dependency needs and independent functioning were obtained through couple member reports, by observing couple members' behaviors during laboratory interactions, by observing responses to experimentally manipulated partner assistance provided during an individual laboratory task, and by following couples over a period of 6 months to examine independent goal striving as a function of prior assessments of dependency acceptance. Results provided converging evidence in support of the proposed hypothesis. Implications of the importance of close relationships for optimal individual functioning are discussed.

  18. Some Concepts of Negative Dependence.

    DTIC Science & Technology

    1980-03-01

    The theory of positive dependence notions cannot yield useful results for some widely used distributions such as the multinomial, Dirichlet and the...multivariate hypergeometric. Some conditions of negative dependence that are satisfied by these distributions and which have practical meaning are

  19. Developing Knowledge of Nonadjacent Dependencies

    ERIC Educational Resources Information Center

    Culbertson, Jennifer; Koulaguina, Elena; Gonzalez-Gomez, Nayeli; Legendre, Géraldine; Nazzi, Thierry

    2016-01-01

    Characterizing the nature of linguistic representations and how they emerge during early development is a central goal in the cognitive science of language. One area in which this development plays out is in the acquisition of dependencies--relationships between co-occurring elements in a word, phrase, or sentence. These dependencies often involve…

  20. Sentence Dependency Structures in Abstracts.

    ERIC Educational Resources Information Center

    Craven, Timothy C.

    1988-01-01

    Describes the results of an analysis of 87 non-formulaic abstracts for structures of semantic dependency between sentences. An automatic structural simplification is presented which is based on an assumption about the use of the dependency structure, and the results of an evaluation of the method are discussed. (25 references) (CLB)

  1. Marijuana Dependence and Its Treatment

    PubMed Central

    Budney, Alan J.; Roffman, Roger; Stephens, Robert S.; Walker, Denise

    2007-01-01

    The prevalence of marijuana abuse and dependence disorders has been increasing among adults and adolescents in the United States. This paper reviews the problems associated with marijuana use, including unique characteristics of marijuana dependence, and the results of laboratory research and treatment trials to date. It also discusses limitations of current knowledge and potential areas for advancing research and clinical intervention. PMID:18292704

  2. Measuring Dependence on Imported Oil

    EIA Publications

    1995-01-01

    U.S. dependence on imported oil can be measured in at least two ways. The differences hinge largely on whether oil imports are defined as net imports (total imports minus exports) or as total imports. EIA introduces a revised table that expresses dependence on imports in terms of both measures.

  3. Dependability in E-Assessment

    ERIC Educational Resources Information Center

    Weippl, Edgar R.

    2007-01-01

    E-learning systems are used by many universities for both blended learning and distance education. In both cases the success of courses depends, among many other factors, on e-learning applications that work reliably. For e-assessments the expected level of reliability and dependability is even higher. By clearly analyzing technical and…

  4. Detecting Mood-Dependent Retrieval.

    ERIC Educational Resources Information Center

    Mayer, John D.; Bower, Gordon H.

    The mood-dependent retrieval hypothesis states that mood will enhance recall by acting as a recall cue if the stimuli have been learned initially in the same mood. Material learned in a happy mood will be best recalled when the person returns to a happy mood; the same holds for a sad mood. Mood-dependent retrieval effect has been regulary…

  5. Assessing dimensions of nicotine dependence

    PubMed Central

    Piper, Megan E.; McCarthy, Danielle E.; Bolt, Daniel M.; Smith, Stevens S.; Lerman, Caryn; Benowitz, Neal; Fiore, Michael C.; Baker, Timothy B.

    2008-01-01

    Considerable research, ranging from survey to clinical to genetic, has utilized traditional measures of tobacco dependence, such as the Fagerstrom Test of Nicotine Dependence (FTND) and the Diagnostic and Statistical Manual (DSM-IV) criteria, that focus on endpoint definitions of tobacco dependence such as heavy smoking, time to first cigarette in the morning, and smoking despite consequences. In an effort to better understand possible theories and mechanisms underlying tobacco dependence, which could be used to improve treatment and research, two multidimensional measures of tobacco dependence have been developed: the Nicotine Dependence Syndrome Scale (NDSS) and the Wisconsin Inventory of Smoking Dependence Motives (WISDM). This research used data from three randomized smoking cessation trials to examine the internal consistency and validity (convergent, concurrent and predictive) of these scales, relative to each other and the traditional measures. Results reveal that NDSS and WISDM subscales are related to important dependence criteria, but in a heterogeneous fashion. The data suggest that there are important underlying mechanisms or motives that are significantly related to different important outcomes, such as withdrawal and cessation. The FTND was most strongly related to abstinence at 1 week and 6 months post-quit, whereas the WISDM Tolerance subscale was most strongly related to abstinence at the end of treatment. The NDSS Priority subscale was consistently predictive of outcome at all three follow-up time points. There is also evidence that WISDM subscales are related to a biomarker of the rate of nicotine metabolism. PMID:18584464

  6. [Alcohol dependence, temper and personality].

    PubMed

    Lejoyeux, Michel

    2004-12-01

    This review focuses on classical and recent research work in the field of alcohol dependence. Data from psychopathological studies trying to determine a "pre-addictive" personality are exposed. More recent studies assess personality disorders and dimensions of temperament associated to alcohol dependence. Sensation seeking, antisocial personality and novelty seeking appear as the main psychological parameters involved in dependence. Sensation seeking is a dimension of personality often associated to behavioral dependence. Sensation seeking is assessed with a five-component scale including general factor, thrill and adventure seeking, experience-seeking, disinhibition, and boredom susceptibility. Patients presenting alcohol dependence have a higher level of sensation seeking. Neurophysiological and genetic studies try to correlate these personality features to biological parameters. Preliminary results of these works are presented and discussed.

  7. Psychostimulant Treatment of Cocaine Dependence

    PubMed Central

    Mariani, John J.; Levin, Frances R.

    2012-01-01

    Synopsis Cocaine dependence continues to be a significant public health problem and no clearly effective pharmacotherapy has yet been identified. Substitution pharmacotherapy is an effective approach for treating opioid and nicotine dependence, and accumulating evidence indicates that stimulant pharmacotherapy for cocaine dependence is a promising strategy. Broadly, stimulant medications that produce behavioral arousal, and medications across several therapeutic classes can be considered psychostimulants. To date, the available evidence is strongest for amphetamine analogs or dopaminergic agents combined with contingency management behavioral interventions as potential psychostimulant treatments for cocaine dependence. Most psychostimulants are controlled substances with inherent risks of misuse and diversion, and their use in patients with active substance use disorders is complex. As stimulant substitution treatment models for cocaine dependence are developed, particular attention to patient risk stratification is needed. PMID:22640764

  8. [Is the term "dependence" appropriate?].

    PubMed

    Pavlovský, P

    1996-05-01

    The term dependence is found in the International Classification of Diseases-10 only in conjunction with the diagnosis of a dependent personality disorder and the substance-related syndrome. Nowhere dependence not related to a substance is mentioned. At present we encounter in the press and professional literature frequently comments on dependence in relation to gambling, work, television, sports activities or some hobby. From the medical aspect it is a dominating idea, i.e. rather a phenomenon within the framework of an extended standard than a symptom from the field of psychopathology. The author recommends to avoid the use of the term "dependence not related to a substance" to prevent psychiatrization of common activities..

  9. Coexistence under positive frequency dependence.

    PubMed Central

    Molofsky, J.; Bever, J. D.; Antonovics, J.

    2001-01-01

    Negative frequency dependence resulting from interspecific interactions is considered a driving force in allowing the coexistence of competitors. While interactions between species and genotypes can also result in positive frequency dependence, positive frequency dependence has usually been credited with hastening the extinction of rare types and is not thought to contribute to coexistence. In the present paper, we develop a stochastic cellular automata model that allows us to vary the scale of frequency dependence and the scale of dispersal. The results of this model indicate that positive frequency dependence will allow the coexistence of two species at a greater rate than would be expected from chance. This coexistence arises from the generation of banding patterns that will be stable over long time-periods. As a result, we found that positive frequency-dependent interactions over local spatial scales promote coexistence over neutral interactions. This result was robust to variation in boundary conditions within the simulation and to variation in levels of disturbance. Under all conditions, coexistence is enhanced as the strength of positive frequency-dependent interactions is increased. PMID:11217898

  10. Drug dependence: some research issues*

    PubMed Central

    Cameron, D. C.

    1970-01-01

    This paper examines some problems of drug dependence, stressing the importance of a balanced approach. Consideration must be given to the demand for, as well as the supply of, drugs. Without a demand, there would be no continuing supply of man-made agents and no need to control the availability of naturally occurring agents. To achieve a balanced approach, increased research is needed into the effects on man of taking various dependence-producing drugs (particularly when these are used for long periods of time), the natural history of drug taking, the relative effectiveness of various preventive, therapeutic and restorative approaches and techniques, and means of identifying substances that, because of their dependence-producing properties, are apt to induce individual or public health problems. Attention is also called to some problems that may inhibit, but do not preclude, the initiation of studies in the field of drug dependence. PMID:5313071

  11. Time-dependent drift Hamiltonian

    SciTech Connect

    Boozer, A.H.

    1983-03-01

    The lowest-order drift equations are given in a canonical magnetic coordinate form for time-dependent magnetic and electric fields. The advantages of the canonical Hamiltonian form are also discussed.

  12. Dependent Types in Practical Programming

    DTIC Science & Technology

    1998-12-06

    to developing a type theory with dependent types and then designing upon it a functional programming language, we study practical methods for extending...developing a type theory with dependent types and then designing upon it a functional programming language, we study practical methods for extend- ing the...1 Introduction Types play a pivotal rôle in the design and implementation of programming languages. The use of types for catching program errors at

  13. Spatial dependence of extreme rainfall

    NASA Astrophysics Data System (ADS)

    Radi, Noor Fadhilah Ahmad; Zakaria, Roslinazairimah; Satari, Siti Zanariah; Azman, Muhammad Az-zuhri

    2017-05-01

    This study aims to model the spatial extreme daily rainfall process using the max-stable model. The max-stable model is used to capture the dependence structure of spatial properties of extreme rainfall. Three models from max-stable are considered namely Smith, Schlather and Brown-Resnick models. The methods are applied on 12 selected rainfall stations in Kelantan, Malaysia. Most of the extreme rainfall data occur during wet season from October to December of 1971 to 2012. This period is chosen to assure the available data is enough to satisfy the assumption of stationarity. The dependence parameters including the range and smoothness, are estimated using composite likelihood approach. Then, the bootstrap approach is applied to generate synthetic extreme rainfall data for all models using the estimated dependence parameters. The goodness of fit between the observed extreme rainfall and the synthetic data is assessed using the composite likelihood information criterion (CLIC). Results show that Schlather model is the best followed by Brown-Resnick and Smith models based on the smallest CLIC's value. Thus, the max-stable model is suitable to be used to model extreme rainfall in Kelantan. The study on spatial dependence in extreme rainfall modelling is important to reduce the uncertainties of the point estimates for the tail index. If the spatial dependency is estimated individually, the uncertainties will be large. Furthermore, in the case of joint return level is of interest, taking into accounts the spatial dependence properties will improve the estimation process.

  14. Scale-dependent halo bias from scale-dependent growth

    SciTech Connect

    Parfrey, Kyle; Hui, Lam; Sheth, Ravi K.

    2011-03-15

    We derive a general expression for the large-scale halo bias, in theories with a scale-dependent linear growth, using the excursion set formalism. Such theories include modified-gravity models, and models in which the dark energy clustering is non-negligible. A scale dependence is imprinted in both the formation and evolved biases by the scale-dependent growth. Mergers are accounted for in our derivation, which thus extends earlier work which focused on passive evolution. There is a simple analytic form for the bias for those theories in which the nonlinear collapse of perturbations is approximately the same as in general relativity. As an illustration, we apply our results to a simple Yukawa modification of gravity, and use Sloan Digital Sky Survey measurements of the clustering of luminous red galaxies to constrain the theory's parameters.

  15. Frequency-Dependent Changes in NMDAR-Dependent Synaptic Plasticity

    PubMed Central

    Kumar, Arvind; Mehta, Mayank R.

    2011-01-01

    The NMDAR-dependent synaptic plasticity is thought to mediate several forms of learning, and can be induced by spike trains containing a small number of spikes occurring with varying rates and timing, as well as with oscillations. We computed the influence of these variables on the plasticity induced at a single NMDAR containing synapse using a reduced model that was analytically tractable, and these findings were confirmed using detailed, multi-compartment model. In addition to explaining diverse experimental results about the rate and timing dependence of synaptic plasticity, the model made several novel and testable predictions. We found that there was a preferred frequency for inducing long-term potentiation (LTP) such that higher frequency stimuli induced lesser LTP, decreasing as 1/f when the number of spikes in the stimulus was kept fixed. Among other things, the preferred frequency for inducing LTP varied as a function of the distance of the synapse from the soma. In fact, same stimulation frequencies could induce LTP or long-term depression depending on the dendritic location of the synapse. Next, we found that rhythmic stimuli induced greater plasticity then irregular stimuli. Furthermore, brief bursts of spikes significantly expanded the timing dependence of plasticity. Finally, we found that in the ∼5–15-Hz frequency range both rate- and timing-dependent plasticity mechanisms work synergistically to render the synaptic plasticity most sensitive to spike timing. These findings provide computational evidence that oscillations can have a profound influence on the plasticity of an NMDAR-dependent synapse, and show a novel role for the dendritic morphology in this process. PMID:21994493

  16. Defining a Cancer Dependency Map.

    PubMed

    Tsherniak, Aviad; Vazquez, Francisca; Montgomery, Phil G; Weir, Barbara A; Kryukov, Gregory; Cowley, Glenn S; Gill, Stanley; Harrington, William F; Pantel, Sasha; Krill-Burger, John M; Meyers, Robin M; Ali, Levi; Goodale, Amy; Lee, Yenarae; Jiang, Guozhi; Hsiao, Jessica; Gerath, William F J; Howell, Sara; Merkel, Erin; Ghandi, Mahmoud; Garraway, Levi A; Root, David E; Golub, Todd R; Boehm, Jesse S; Hahn, William C

    2017-07-27

    Most human epithelial tumors harbor numerous alterations, making it difficult to predict which genes are required for tumor survival. To systematically identify cancer dependencies, we analyzed 501 genome-scale loss-of-function screens performed in diverse human cancer cell lines. We developed DEMETER, an analytical framework that segregates on- from off-target effects of RNAi. 769 genes were differentially required in subsets of these cell lines at a threshold of six SDs from the mean. We found predictive models for 426 dependencies (55%) by nonlinear regression modeling considering 66,646 molecular features. Many dependencies fall into a limited number of classes, and unexpectedly, in 82% of models, the top biomarkers were expression based. We demonstrated the basis behind one such predictive model linking hypermethylation of the UBB ubiquitin gene to a dependency on UBC. Together, these observations provide a foundation for a cancer dependency map that facilitates the prioritization of therapeutic targets. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Dependency Structures for Statistical Machine Translation

    ERIC Educational Resources Information Center

    Bach, Nguyen

    2012-01-01

    Dependency structures represent a sentence as a set of dependency relations. Normally the dependency structures from a tree connect all the words in a sentence. One of the most defining characters of dependency structures is the ability to bring long distance dependency between words to local dependency structures. Another the main attraction of…

  18. Dependency Structures for Statistical Machine Translation

    ERIC Educational Resources Information Center

    Bach, Nguyen

    2012-01-01

    Dependency structures represent a sentence as a set of dependency relations. Normally the dependency structures from a tree connect all the words in a sentence. One of the most defining characters of dependency structures is the ability to bring long distance dependency between words to local dependency structures. Another the main attraction of…

  19. Turkey's foreign dependence on energy

    SciTech Connect

    Uslu, T.

    2008-07-01

    Turkey becomes more dependent on the external countries in energy production every year. As an average of the period 1994-2002 the total primary energy production has been 27.9 Mtoe, and consumption has been 73.06 Mtoe, so Turkey is dependent on external countries in petroleum, natural gas, and hard coal consumption. The external dependency rate of these fuels has been at levels of 89.3%, 96.6%, and 82%, respectively. In the projections of Turkey for 2020, the primary energy consumption is estimated to be 298 Mtoe, production is estimated to be 70 Mtoe, the ratio of production to consumption will be reduced to 23.5%, and this situation will cause serious risks for sustainable development. In other words, Turkey will have to import 76.5% of the energy that it consumes in the 2020s.

  20. Anabolic steroid abuse and dependence.

    PubMed

    Brower, Kirk J

    2002-10-01

    Anabolic-androgenic steroids (AAS) are mainly used to treat androgen deficiency syndromes and, more recently, catabolic states such as AIDS-associated wasting. There is no evidence in the reviewed literature that AAS abuse or dependence develops from the therapeutic use of AAS. Conversely, 165 instances of AAS dependence have been reported among weightlifters and bodybuilders who, as part of their weight training regimens, chronically administered supraphysiologic doses, often including combinations of injected and oral AAS as well as other drugs of abuse. A new model is proposed in which both the "myoactive" and psychoactive effects of AAS contribute to the development of AAS dependence. The adverse consequences of AAS are reviewed, as well as their assessment by means of a history and physical, mental status examination, and laboratory testing. When patients with AAS use disorders are compared with patients with other substance use disorders, both similarities and differences become apparent and have implications for treatment.

  1. Developing Tests of Visual Dependency

    NASA Technical Reports Server (NTRS)

    Kindrat, Alexandra N.

    2011-01-01

    Astronauts develop neural adaptive responses to microgravity during space flight. Consequently these adaptive responses cause maladaptive disturbances in balance and gait function when astronauts return to Earth and are re-exposed to gravity. Current research in the Neuroscience Laboratories at NASA-JSC is focused on understanding how exposure to space flight produces post-flight disturbances in balance and gait control and developing training programs designed to facilitate the rapid recovery of functional mobility after space flight. In concert with these disturbances, astronauts also often report an increase in their visual dependency during space flight. To better understand this phenomenon, studies were conducted with specially designed training programs focusing on visual dependency with the aim to understand and enhance subjects ability to rapidly adapt to novel sensory situations. The Rod and Frame test (RFT) was used first to assess an individual s visual dependency, using a variety of testing techniques. Once assessed, subjects were asked to perform two novel tasks under transformation (both the Pegboard and Cube Construction tasks). Results indicate that head position cues and initial visual test conditions had no effect on an individual s visual dependency scores. Subjects were also able to adapt to the manual tasks after several trials. Individual visual dependency correlated with ability to adapt manual to a novel visual distortion only for the cube task. Subjects with higher visual dependency showed decreased ability to adapt to this task. Ultimately, it was revealed that the RFT may serve as an effective prediction tool to produce individualized adaptability training prescriptions that target the specific sensory profile of each crewmember.

  2. [Depression, tobacco dependence and nicotine].

    PubMed

    Fakhfakh, R; Lagrue, G

    2002-01-01

    The purpose of the study was to illustrate, through an observation, the association between depression and smoking dependence, as well as the considered anti-depressive properties of nicotine. Fageström Test for Nicotine Dependence was confirmed by the urinary cotinine dosage, and the expired Carbon Monoxide assessed the nicotine dependence. The anxio-depressive co-morbidity was determined through the cross-examination associated to the HAD test (Hospital Anxiety Depression Scale); then, in case of anomaly, by the depression inventory of Beck (13 items) and the structured interview: the Mini International Neuro Psychiatric Interview (MINI). Our patient, born in 1938, with the personal history of manic-depressive psychosis and alcoholic dependence severed in 1987, came to consult in 1995, after several smoking cessation attempts, followed every time by an extended and severe depression. He smoked 40 cigarettes per day, with a very high dependence (score of Fagerström = 10). The HAD and the Beck tests being normals; smoking cessation program has begun with nicotine patches. At the end of three months, he fell in a severe and resistant depression that continued during 2 years. Then, he stopped completely smoking. In 1997, a progressive treatment by nicotine-gum (NG) was proposed. Since the second week, while taking 2 to 3 NG per day, and without having modified his ADT, his psychological state improved, and in 3 months he recovered his previous psychological form. Confronted to literature data, this observation underlines the association between anxio-depressive states and the high level of smoking dependence. In the same way, the improving psychological effects of nicotine replacement, confirms the nicotine anti-depressive properties.

  3. Dopamine agonists for cocaine dependence.

    PubMed

    Soares, B G; Lima, M S; Reisser, A A; Farrell, M

    2001-01-01

    Cocaine is a major drug of abuse. Cocaine dependence is a common and serious condition, which has become nowadays a substantial public health problem. There is a wide and well documented range of consequences associated to chronic use of this drug, such as medical, psychological and social problems, including the spread of infectious diseases (e.g. AIDS, hepatitis and tuberculosis), crime, violence and neonatal drug exposure. Therapeutic management of the cocaine addicts includes an initial period of abstinence from the drug. During this phase the subjects may experience, besides the intense craving for cocaine, symptoms such as depression, fatigue, irritability, anorexia, and sleep disturbances. It was demonstrated that the acute use of cocaine may enhance dopamine transmission and chronically it decreases dopamine concentrations in the brain. Pharmacological treatment that affects dopamine could theoretically reduce these symptoms and contribute to a more successful therapeutic approach. To evaluate the efficacy and acceptability of dopamine agonists for treating cocaine dependence. We searched: The Cochrane Controlled Trials Register (Cochrane Library, issue 4, 2000), MEDLINE (from 1966 - 2000), EMBASE (from 1980 - 2000), LILACS (from 1982 - 2000), PsycLIT (from 1974 - 2000), Biological Abstracts (1982 to 2000). Reference searching; personal communication; conference abstracts; unpublished trials from pharmaceutical industry; book chapters on treatment of cocaine dependence. The inclusion criteria for all randomised controlled trials were that they should focus on the use of dopamine agonists on the treatment of cocaine dependence. Trials including patients with additional diagnosis such as opiate dependence were also eligible. The reviewers extracted the data independently and Relative Risks, weighted mean difference and number needed to treat were estimated. The reviewers assumed that people who died or dropped out had no improvement and tested the sensitivity

  4. Fault trees and sequence dependencies

    NASA Technical Reports Server (NTRS)

    Dugan, Joanne Bechta; Boyd, Mark A.; Bavuso, Salvatore J.

    1990-01-01

    One of the frequently cited shortcomings of fault-tree models, their inability to model so-called sequence dependencies, is discussed. Several sources of such sequence dependencies are discussed, and new fault-tree gates to capture this behavior are defined. These complex behaviors can be included in present fault-tree models because they utilize a Markov solution. The utility of the new gates is demonstrated by presenting several models of the fault-tolerant parallel processor, which include both hot and cold spares.

  5. Psychostimulant treatment of cocaine dependence.

    PubMed

    Mariani, John J; Levin, Frances R

    2012-06-01

    The use of stimulant medications for the treatment of cocaine dependence is an evolving scientific line of research. To date, the most promising results are with the higher-potency medications, the amphetamine analogues, or a combination of a dopaminergic medication with a contingency management behavioral intervention. The development of effective pharmacotherapies for opioid and nicotine dependence using an agonist replacement approach suggests that these promising findings needs to continue to be vigorously investigated. In clinical trial reports, there are very few instances of cardiovascular adverse events, which suggests that for well-selected patients with cocaine dependence, stimulant replacement therapy can be safe. However, clinical trial eligibility criteria excludes most high-risk patients from participating, and introducing stimulant substitution to the wider treatment community would likely expose more vulnerable patients to the medical risks associated with stimulant treatment while using cocaine. As treatment development research moves forward, attention must be paid to helping clinicians select patients who are most likely to benefit from stimulant substitution treatment and how to identify those at risk. An additional concern with the use of stimulant medication treatment of cocaine dependence is prescribing controlled substances for patients with active substance use disorders. Again, within a clinical trial, medication supplies are monitored and distributed carefully in small quantities. In a community setting, misuse or diversion will be risks associated with prescribing controlled substances to patients with addictive disorders, but therapeutic strategies for monitoring and limiting that risk can be implemented. Psychostimulant pharmacotherapy is a promising line of research for the treatment of cocaine dependence, a condition for which no effective pharmacotherapy has been identified. Further research is required to confirm positive results

  6. Isotopic dependence of nuclear temperatures

    SciTech Connect

    Su Jun; Zhang Fengshou

    2011-09-15

    A systematic study of isotope temperatures has been presented for heavy-ion collisions at 600 MeV/nucleon via the isospin-dependent quantum molecular dynamics model in the company of the statistical decay model (GEMINI). We find that the isospin dependence of the isotope temperatures in multifragmentation is weak; however, this effect is still visible over a wide isotopic range. The isotope temperatures for the neutron-rich projectiles are larger than those for the neutron-poor projectiles. We also find that the isotope temperatures calculated by the model decrease with increasing nuclear mass.

  7. [Dependent seniors: families and caregivers].

    PubMed

    Karsch, Ursula M

    2003-01-01

    This article focuses on health care for dependent seniors in relation to chronic illnesses. Expectations about family support for the dependent elderly are related to the role of family caregivers, but care requires support from the public and private sectors. Governments throughout the developed countries are examining their role in the provision of social welfare programs, especially in the public health sector. To recommend home care and family assistance, the context of changing family structures, the type of care needed, and professional follow-up must be taken into account.

  8. Experimental Studies of Boronophenylalanine ((10)BPA) Biodistribution for the Individual Application of Boron Neutron Capture Therapy (BNCT) for Malignant Melanoma Treatment.

    PubMed

    Carpano, Marina; Perona, Marina; Rodriguez, Carla; Nievas, Susana; Olivera, Maria; Santa Cruz, Gustavo A; Brandizzi, Daniel; Cabrini, Romulo; Pisarev, Mario; Juvenal, Guillermo Juan; Dagrosa, Maria Alejandra

    2015-10-01

    Patients with the same histopathologic diagnosis of cutaneous melanoma treated with identical protocols of boron neutron capture therapy (BNCT) have shown different clinical outcomes. The objective of the present studies was to evaluate the biodistribution of boronophenilalanina ((10)BPA) for the potential application of BNCT for the treatment of melanoma on an individual basis. The boronophenilalanine (BPA) uptake was evaluated in 3 human melanoma cell lines: MEL-J, A375, and M8. NIH nude mice were implanted with 4 10(6) MEL-J cells, and biodistribution studies of BPA (350 mg/kg intraperitoneally) were performed. Static infrared imaging using a specially modified infrared camera adapted to measure the body infrared radiance of small animals was used. Proliferation marker, Ki-67, and endothelial marker, CD31, were analyzed in tumor samples. The in vitro studies demonstrated different patterns of BPA uptake for each analyzed cell line (P<.001 for MEL-J and A375 vs M8 cells). The in vivo studies showed a maximum average boron concentration of 25.9 ± 2.6 μg/g in tumor, with individual values ranging between 11.7 and 52.0 μg/g of (10)B 2 hours after the injection of BPA. Tumor temperature always decreased as the tumors increased in size, with values ranging between 37 °C and 23 °C. A significant correlation between tumor temperature and tumor-to-blood boron concentration ratio was found (R(2) = 0.7, rational function fit). The immunohistochemical studies revealed, in tumors with extensive areas of viability, a high number of positive cells for Ki-67, blood vessels of large diameter evidenced by the marker CD31, and a direct logistic correlation between proliferative status and boron concentration difference between tumor and blood (R(2) = 0.81, logistic function fit). We propose that these methods could be suitable for designing new screening protocols applied before melanoma BNCT treatment for each individual patient and lesion. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Experimental Studies of Boronophenylalanine ({sup 10}BPA) Biodistribution for the Individual Application of Boron Neutron Capture Therapy (BNCT) for Malignant Melanoma Treatment

    SciTech Connect

    Carpano, Marina; Perona, Marina; Rodriguez, Carla; Nievas, Susana; Olivera, Maria; Santa Cruz, Gustavo A.; Brandizzi, Daniel; Cabrini, Romulo; Pisarev, Mario; Juvenal, Guillermo Juan; Dagrosa, Maria Alejandra

    2015-10-01

    Purpose: Patients with the same histopathologic diagnosis of cutaneous melanoma treated with identical protocols of boron neutron capture therapy (BNCT) have shown different clinical outcomes. The objective of the present studies was to evaluate the biodistribution of boronophenilalanina ({sup 10}BPA) for the potential application of BNCT for the treatment of melanoma on an individual basis. Methods and Materials: The boronophenilalanine (BPA) uptake was evaluated in 3 human melanoma cell lines: MEL-J, A375, and M8. NIH nude mice were implanted with 4 10{sup 6} MEL-J cells, and biodistribution studies of BPA (350 mg/kg intraperitoneally) were performed. Static infrared imaging using a specially modified infrared camera adapted to measure the body infrared radiance of small animals was used. Proliferation marker, Ki-67, and endothelial marker, CD31, were analyzed in tumor samples. Results: The in vitro studies demonstrated different patterns of BPA uptake for each analyzed cell line (P<.001 for MEL-J and A375 vs M8 cells). The in vivo studies showed a maximum average boron concentration of 25.9 ± 2.6 μg/g in tumor, with individual values ranging between 11.7 and 52.0 μg/g of {sup 10}B 2 hours after the injection of BPA. Tumor temperature always decreased as the tumors increased in size, with values ranging between 37°C and 23°C. A significant correlation between tumor temperature and tumor-to-blood boron concentration ratio was found (R{sup 2} = 0.7, rational function fit). The immunohistochemical studies revealed, in tumors with extensive areas of viability, a high number of positive cells for Ki-67, blood vessels of large diameter evidenced by the marker CD31, and a direct logistic correlation between proliferative status and boron concentration difference between tumor and blood (R{sup 2} = 0.81, logistic function fit). Conclusion: We propose that these methods could be suitable for designing new screening protocols applied before melanoma BNCT treatment for each individual patient and lesion.

  10. Biodistribution of the boron carriers boronophenylalanine (BPA) and/or decahydrodecaborate (GB-10) for Boron Neutron Capture Therapy (BNCT) in an experimental model of lung metastases

    SciTech Connect

    D.W. Nigg; Various Others

    2014-06-01

    BNCT was proposed for the treatment of diffuse, non-resectable tumors in the lung. We performed boron biodistribution studies with 5 administration protocols employing the boron carriers BPA and/or GB-10 in an experimental model of disseminated lung metastases in rats. All 5 protocols were non-toxic and showed preferential tumor boron uptake versus lung. Absolute tumor boron concentration values were therapeutically useful (25–76 ppm) for 3 protocols. Dosimetric calculations indicate that BNCT at RA-3 would be potentially therapeutic without exceeding radiotolerance in the lung.

  11. [Preventing dependency: the longevity challenge].

    PubMed

    Forette, Françoise

    2009-02-01

    Longevity can only be considered a privilege if the majority of the elderly population is active and in good health. In contrast to certain statistical interpretations, the HID study gives cause for optimism. It showed that only 7% of subjects aged 60 years and over suffer from dependency and, therefore, that 93% of the population remains independent. Of course, the rate of dependency increases with age, particularly in women and after 90 years of age. Dependency is mostly due to age-related diseases. The second cause is "frailty" and the third is inactivity, or more generally, lifestyle. All age-related diseases have modifiable risk factors and are thus accessible to prevention. Prevention must be started as soon as possible. It has been demonstrated that a mother's educational level influences her children's health in adulthood. It is never too late. The Hyvet study recently showed that the treatment of hypertension after 80 years of age is still able to significantly reduce the risk of death, stroke, heart failure and other cardiovascular complications. Inadequate disease management may also lead to avoidable dependency. This is the case of congestive heart failure and osteoporosis, which are not always treated in very old patients according to evidence-based principles. Another means of prevention is the detection and management of the frailty syndrome, which carries a measurable risk of loss of independence. In addition to these medical approaches, occupational activity involving strong cognitive stimulation has been shown to postpone the onset of cognitive impairment.

  12. The Study of Curricular Dependency

    ERIC Educational Resources Information Center

    Anastasiu, Dragos

    2006-01-01

    In the educational process, the disciplines D1, D2,...,Dn have a succession which is generated by the content and the final objective--the student formation. In this work, the disciplines are presented as structured text entities. The graph associated to the disciplines is established. A method for dependencies evaluation is proposed. The testing…

  13. Dependency Structures and Transformational Rules.

    ERIC Educational Resources Information Center

    Robinson, Jane J.

    In this paper the author shows that dependency grammars are not only equivalent to structure-free phrase-structure grammars (i.e., equally adequate), but are even more informative: they express both the "is a" relation which phrase-structure grammars express and the "governs" relation which phrase-structure grammars obscure. It…

  14. A User- Dependent SDI System

    ERIC Educational Resources Information Center

    Burton, Hilary D.

    1973-01-01

    A large-scale selective dissemination of information (SDI) system which is in operation at the Agricultural Research Service is described. The unique characteristic of this system is that the users develop and modify their own profiles. The implications of this user-dependent approach for information system planners are discussed. (2 references)…

  15. Network-timing-dependent plasticity

    PubMed Central

    Delattre, Vincent; Keller, Daniel; Perich, Matthew; Markram, Henry; Muller, Eilif B.

    2015-01-01

    Bursts of activity in networks of neurons are thought to convey salient information and drive synaptic plasticity. Here we report that network bursts also exert a profound effect on Spike-Timing-Dependent Plasticity (STDP). In acute slices of juvenile rat somatosensory cortex we paired a network burst, which alone induced long-term depression (LTD), with STDP-induced long-term potentiation (LTP) and LTD. We observed that STDP-induced LTP was either unaffected, blocked or flipped into LTD by the network burst, and that STDP-induced LTD was either saturated or flipped into LTP, depending on the relative timing of the network burst with respect to spike coincidences of the STDP event. We hypothesized that network bursts flip STDP-induced LTP to LTD by depleting resources needed for LTP and therefore developed a resource-dependent STDP learning rule. In a model neural network under the influence of the proposed resource-dependent STDP rule, we found that excitatory synaptic coupling was homeostatically regulated to produce power law distributed burst amplitudes reflecting self-organized criticality, a state that ensures optimal information coding. PMID:26106298

  16. Principal Components and Scale Dependence.

    ERIC Educational Resources Information Center

    Blankmeyer, Eric

    A limitation of the principal components method is its scale dependence. This note shows that the method is scale invariant if the normalization is modified in an obvious way. Then the effect of a change in units is as transparent as in linear regression, and principal components can be used without apology. Most researchers who use multivariate…

  17. Network-timing-dependent plasticity.

    PubMed

    Delattre, Vincent; Keller, Daniel; Perich, Matthew; Markram, Henry; Muller, Eilif B

    2015-01-01

    Bursts of activity in networks of neurons are thought to convey salient information and drive synaptic plasticity. Here we report that network bursts also exert a profound effect on Spike-Timing-Dependent Plasticity (STDP). In acute slices of juvenile rat somatosensory cortex we paired a network burst, which alone induced long-term depression (LTD), with STDP-induced long-term potentiation (LTP) and LTD. We observed that STDP-induced LTP was either unaffected, blocked or flipped into LTD by the network burst, and that STDP-induced LTD was either saturated or flipped into LTP, depending on the relative timing of the network burst with respect to spike coincidences of the STDP event. We hypothesized that network bursts flip STDP-induced LTP to LTD by depleting resources needed for LTP and therefore developed a resource-dependent STDP learning rule. In a model neural network under the influence of the proposed resource-dependent STDP rule, we found that excitatory synaptic coupling was homeostatically regulated to produce power law distributed burst amplitudes reflecting self-organized criticality, a state that ensures optimal information coding.

  18. Time dependent view factor methods

    SciTech Connect

    Kirkpatrick, R.C.

    1998-03-01

    View factors have been used for treating radiation transport between opaque surfaces bounding a transparent medium for several decades. However, in recent years they have been applied to problems involving intense bursts of radiation in enclosed volumes such as in the laser fusion hohlraums. In these problems, several aspects require treatment of time dependence.

  19. We Depend on Illinois' Environment.

    ERIC Educational Resources Information Center

    Illinois Environmental Protection Agency, Springfield.

    This teachers guide contains information and activities to provide 5th-grade students with a hands-on experience with air, land, and water pollution in Illinois. This booklet incorporates previous documents entitled: "Water the Liquid of Life,""The Land We Depend On," and "The Air We Breathe." The materials are…

  20. Developing knowledge of nonadjacent dependencies.

    PubMed

    Culbertson, Jennifer; Koulaguina, Elena; Gonzalez-Gomez, Nayeli; Legendre, Géraldine; Nazzi, Thierry

    2016-12-01

    Characterizing the nature of linguistic representations and how they emerge during early development is a central goal in the cognitive science of language. One area in which this development plays out is in the acquisition of dependencies-relationships between co-occurring elements in a word, phrase, or sentence. These dependencies often involve multiple levels of representation and abstraction, built up as infants gain experience with their native language. The authors used the Headturn Preference Procedure to systematically investigate the early acquisition of 1 such dependency, the agreement between a subject and verb in French, at 6 different ages between 14 and 24 months. The results reveal a complex developmental trajectory that provides the first evidence that infants might indeed progress through distinct stages in the acquisition of this nonadjacent dependency. The authors discuss how changes in general cognition and representational knowledge (from reflecting surface statistics to higher-level morphological features) might account for their findings. These findings highlight the importance of studying language acquisition at close time intervals over a substantial age range. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  1. Directional Dependence in Developmental Research

    ERIC Educational Resources Information Center

    von Eye, Alexander; DeShon, Richard P.

    2012-01-01

    In this article, we discuss and propose methods that may be of use to determine direction of dependence in non-normally distributed variables. First, it is shown that standard regression analysis is unable to distinguish between explanatory and response variables. Then, skewness and kurtosis are discussed as tools to assess deviation from…

  2. Dopamine agonists for cocaine dependence.

    PubMed

    Soares, B G O; Lima, M S; Reisser, A A P; Farrell, M

    2003-01-01

    Cocaine dependence is a common and serious condition, which has become nowadays a substantial public health problem. There is a wide and well documented range of consequences associated to chronic use of this drug, such as medical, psychological and social problems, including the spread of infectious diseases (e.g. AIDS, hepatitis and tuberculosis), crime, violence and neonatal drug exposure. Therapeutic management of the cocaine addicts includes an initial period of abstinence from the drug. During this phase the subjects may experience, besides the intense craving for cocaine, symptoms such as depression, fatigue, irritability, anorexia, and sleep disturbances. It was demonstrated that the acute use of cocaine may enhance dopamine transmission and chronically it decreases dopamine concentrations in the brain. Pharmacological treatment that affects dopamine could theoretically reduce these symptoms and contribute to a more successful therapeutic approach. To evaluate the efficacy and acceptability of dopamine agonists for treating cocaine dependence. Electronic searches of Cochrane Library, EMBASE, MEDLINE, PsycLIT, Biological Abstracts and LILACS; reference searching; personal communication; conference abstracts; unpublished trials from pharmaceutical industry; book chapters on treatment of cocaine dependence, was performed for the primary version of this review in 2001. Another search of the electronic databases was done in December of 2002 for this update. The specialised register of trials of the Cochrane Group on Drugs and Alcohol was searched until February 2003. The inclusion criteria for all randomised controlled trials were that they should focus on the use of dopamine agonists on the treatment of cocaine dependence. The reviewers extracted the data independently and Relative Risks, weighted mean difference and number needed to treat were estimated. The reviewers assumed that people who died or dropped out had no improvement and tested the sensitivity of

  3. Dependency Ordering of Atomic Observables

    NASA Astrophysics Data System (ADS)

    Cīrulis, Jānis

    2015-12-01

    The notion of atomic observable was introduced by S.Gudder for effect test spaces in 1997. In this paper an observable is a σ-homomorphism from the Borel algebra on a line to some logic. Roughly, an observable on a logic is atomic, if it is completely determined by its restriction to one-element subsets of its point spectrum. In particular, every discrete observable is atomic. We study some elementary properties of such observables, and discuss a possible notion of functional dependency between them. Algebraically, a dependency is a certain preorder relation on the set of all atomic observables, which induces an order relation on the set of all maximal orthogonal subsets of the logic. Several properties, as well as characteristics in terms of the underlying logic, of these relations are stated.

  4. Spike-timing-dependent construction.

    PubMed

    Lightheart, Toby; Grainger, Steven; Lu, Tien-Fu

    2013-10-01

    Spike-timing-dependent construction (STDC) is the production of new spiking neurons and connections in a simulated neural network in response to neuron activity. Following the discovery of spike-timing-dependent plasticity (STDP), significant effort has gone into the modeling and simulation of adaptation in spiking neural networks (SNNs). Limitations in computational power imposed by network topology, however, constrain learning capabilities through connection weight modification alone. Constructive algorithms produce new neurons and connections, allowing automatic structural responses for applications of unknown complexity and nonstationary solutions. A conceptual analogy is developed and extended to theoretical conditions for modeling synaptic plasticity as network construction. Generalizing past constructive algorithms, we propose a framework for the design of novel constructive SNNs and demonstrate its application in the development of simulations for the validation of developed theory. Potential directions of future research and applications of STDC for biological modeling and machine learning are also discussed.

  5. Time-dependent interstellar chemistry

    NASA Technical Reports Server (NTRS)

    Glassgold, A. E.

    1985-01-01

    Some current problems in interstellar chemistry are considered in the context of time-dependent calculations. The limitations of steady-state models of interstellar gas-phase chemistry are discussed, and attempts to chemically date interstellar clouds are reviewed. The importance of studying the physical and chemical properties of interstellar dust is emphasized. Finally, the results of a series of studies of collapsing clouds are described.

  6. Link Dependent Adaptive Radio Simulation

    DTIC Science & Technology

    2014-06-01

    14. ABSTRACT This paper shows the optimized Link Dependent Adaptive Radio (LDAR) using the variable QAM OFDM modulation size which adapts to channel...bit error rate (BER), Orthogonal Frequency Division Multiplexing ( OFDM ) 16. SECURITY CLASSIFICATION OF: Unclassified 17. LIMITATION OF ABSTRACT...using the variable QAM OFDM modulation size which adapts to channel conditions. The LDAR enhanced performance is illustrated by use of a flight path

  7. Genus dependence of superstring amplitudes

    SciTech Connect

    Davis, Simon

    2006-11-15

    The problem of the consistency of the finiteness of the supermoduli space integral in the limit of vanishing super-fixed point distance and the genus-dependence of the integral over the super-Schottky coordinates in the fundamental region containing a neighborhood of |K{sub n}|=0 is resolved. Given a choice of the categories of isometric circles representing the integration region, the exponential form of bounds for superstring amplitudes is derived.

  8. A Frequency Dependent Ray Theory

    DTIC Science & Technology

    1988-03-28

    4.2 The Korrnilitsin profile 30 4.3 Classical ray diagram for the Kormilitsin profile 32 4.4 Frequency dependent ray diagram for the Kormilitsin ...profile 36 4.5 Propagation loss curves for the Kormilitsin profile 37 4.6 The harmonic oscillator waveguide 41 4.7 Exact rays and classical rays in the...following criteria: (1) Each case should serve as a canonical example of some problem frequently encountered in acoustics. For example, the Kormilitsin

  9. Non-transfusion-dependent thalassemias

    PubMed Central

    Musallam, Khaled M.; Rivella, Stefano; Vichinsky, Elliott; Rachmilewitz, Eliezer A.

    2013-01-01

    Non-transfusion-dependent thalassemias include a variety of phenotypes that, unlike patients with beta (β)-thalassemia major, do not require regular transfusion therapy for survival. The most commonly investigated forms are β-thalassemia intermedia, hemoglobin E/β-thalassemia, and α-thalassemia intermedia (hemoglobin H disease). However, transfusion-independence in such patients is not without side effects. Ineffective erythropoiesis and peripheral hemolysis, the hallmarks of disease process, lead to a variety of subsequent pathophysiologies including iron overload and hypercoagulability that ultimately lead to a number of serious clinical morbidities. Thus, prompt and accurate diagnosis of non-transfusion-dependent thalassemia is essential to ensure early intervention. Although several management options are currently available, the need to develop more novel therapeutics is justified by recent advances in our understanding of the mechanisms of disease. Such efforts require wide international collaboration, especially since non-transfusion-dependent thalassemias are no longer bound to low- and middle-income countries but have spread to large multiethnic cities in Europe and the Americas due to continued migration. PMID:23729725

  10. Nicotine dependence and smoking cessation.

    PubMed

    Tan, Linxiang; Tang, Quansheng; Hao, Wei

    2009-11-01

    Tobacco use is the single most preventable cause of death, disability and disease in the world and is projected to be the leading cause of death and disability across all developed and developing countries by 2020. Nicotine, the primary active ingredient of cigarettes that contributes to physical dependence, acts on nicotine receptors in the central nervous system and leads to the release of neurotransmitters (such as dopamine). Like other drugs of abuse, nicotine is thought to produce reinforcing effect by activating the mesocorticolimbic dopamine system. A wide variety of cessation treatments of nicotine dependence is commercially available, yet only 2 general approaches have received empirical validation: behavioral intervention (including 5 As brief intervention) and pharmacotherapy. The evidences show that 5 As brief intervention is one of the most cost-effective treatments in clinical work for busy physicians. Three types of medications have been available in market for smoking cessation treatment: nicotine replacement treatment (NRT, i.e., transdermal patch, gum, inhaler, nasal spray, and lozenge), sustained release bupropion and varenicline. Varenicline, a novel alpha4beta2 nicotinic receptor partial agonist, is effective for tobacco dependence. Phase III trials suggest that it is more effective than NRT and bupropion SR. The safety profile of varenicline is excellent, with the most commonly occurring adverse events, nausea, typically mild and well tolerated. However, new safety warnings are added to the varenicline label because of post-marketing report including agitation, depression and suicidality. A causal connection between varenicline use and these symptoms has not been established.

  11. Non-transfusion-dependent thalassemias.

    PubMed

    Musallam, Khaled M; Rivella, Stefano; Vichinsky, Elliott; Rachmilewitz, Eliezer A

    2013-06-01

    Non-transfusion-dependent thalassemias include a variety of phenotypes that, unlike patients with beta (β)-thalassemia major, do not require regular transfusion therapy for survival. The most commonly investigated forms are β-thalassemia intermedia, hemoglobin E/β-thalassemia, and α-thalassemia intermedia (hemoglobin H disease). However, transfusion-independence in such patients is not without side effects. Ineffective erythropoiesis and peripheral hemolysis, the hallmarks of disease process, lead to a variety of subsequent pathophysiologies including iron overload and hypercoagulability that ultimately lead to a number of serious clinical morbidities. Thus, prompt and accurate diagnosis of non-transfusion-dependent thalassemia is essential to ensure early intervention. Although several management options are currently available, the need to develop more novel therapeutics is justified by recent advances in our understanding of the mechanisms of disease. Such efforts require wide international collaboration, especially since non-transfusion-dependent thalassemias are no longer bound to low- and middle-income countries but have spread to large multiethnic cities in Europe and the Americas due to continued migration.

  12. Dextromethorphan withdrawal and dependence syndrome.

    PubMed

    Mutschler, Jochen; Koopmann, Anne; Grosshans, Martin; Hermann, Derik; Mann, Karl; Kiefer, Falk

    2010-07-01

    The N-methyl-D-aspartate (NMDA) antagonist dextromethorphan has been available in pharmacies without a prescription since 1954 as an antitussive agent. There is an alarming increase in reports of its abuse. Dextromethorphan is avidly taken, mainly by young people, as a psychoactive drug. The currently available data yield incomplete information about the extent of the problem and its significance for addiction medicine in Germany. We report the case of a 44-year-old man who became dependent on dextromethorphan through years of abuse, buying the substance for himself without a prescription in German pharmacies. He told us he had taken it regularly for six years. He had become dependent on dextromethorphan, ultimately taking it in a dose of 1800 mg daily. This led him to overt neglect of his work and leisure activities. A urine sample taken on admission to the hospital was found to contain dextromethorphan. During inpatient detoxification, he developed an vegetative withdrawal syndrome consisting of craving, diaphoresis, nausea, hypertension, and tachycardia. He was treated on our ward for three weeks, and a stay in a residential detoxification facility was planned thereafter. Dextromethorphan is a psychotropic substance that carries a potential for abuse and dependence. On the basis of the currently available data, its reclassification as a prescription drug should be considered.

  13. [Secondary development of psychological dependence in a methamphetamine dependent].

    PubMed

    Edakubo, T; Kaneko, T; Kato, N

    1991-04-01

    A case of methamphetamine dependence was presented, who had used a large amount of the drug for a long time during both of the first and the second period of its prevalence. He led a socially and psychologically stable life with neither drug habits nor episodes of flash-back phenomenon in 20's and 30's of his age. While in the former period of the prevalence, visual illusion had occurred in him 3 months after the first injection of the drug, in the latter, auditory hallucination occurred in a month after the initiation of the reinjection. This hallucination was so invasive and persistent that he became insomniac and could not keep stable daily life. Recently the auditory hallucination has disappeared by the reinjection of the drug, resulting in releasing him from the sufferings like insomnia, and then promoting the drug use more frequently. Even at the law court to decide the penalty against his illegal drug use, he recurrently insisted that methamphetamine was his necessity in order to be freed from the hallucination and keep stable daily life. He declared his intention not to abandon his drug habit in spite of any punishments. On the central nervous system (CNS) depressants such as the morphine- and barbiturate-type drug, the psychological dependence is brought about secondarily by the mechanism to avoid the withdrawal symptoms. On the other hand, the secondary development of psychological dependence through avoidance of the chronic toxicity by the acute drug effect itself, should be considered as one of the characteristics of the CNS stimulants like methamphetamine.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Genetics Home Reference: pyridoxine-dependent epilepsy

    MedlinePlus

    ... Home Health Conditions pyridoxine-dependent epilepsy pyridoxine-dependent epilepsy Enable Javascript to view the expand/collapse boxes. ... PDF Open All Close All Description Pyridoxine-dependent epilepsy is a condition that involves seizures beginning in ...

  15. Time dependence of PEB effects

    NASA Astrophysics Data System (ADS)

    Yanagishita, Yuichiro; Shigematsu, Kazumasa; Yanagida, Kimio

    1990-06-01

    Though simulations of PEB (Post Exposure Bake) on the basis of PAC diffusion mode! have been carried out by a number of researchers '' (2) , it has never been confirmed that those could predict experimental data caused by PEB' s effects accurately . Because no details of chemical reactions thernlly induced by PEB are known, fundamental parameters which determine PEB' s effects must be obtained experimentally. We have acquired the volume of changes of development rate function, RATE(M) by PEB with DRM monitoring for some types of photoresist . The values of diffusion length have been obtained by means of compareing experimental B (exposure ener) vs T (development time to clear) curves with simulated ones which is based on RATEOA) data. Their dependence on the baking time has been investigated with fixed FEB temperature and it has been proved that a progress of the diffusion saturates only in less than a few seconds when the diffusion length is about lO'-l5ncn, which is much shorter than the standing wave length(= 66nm, for G-line). Profiles of low contrast resist patterns can be improved by the decrease in development rate of slightly exposed areas by PEB. The effects on these resists depend on the baking time because the volume of the decrease grows with increasing FEB time. On the other hands, for high contrast resists PEB' s diffusion enhances their resolution while the decreases in development rate have little effect on them. Time dependence cannot be observed for these resists because the diffusion length remains constant with increasing FEB time.

  16. Time-Dependent Photodissociation Regions

    NASA Technical Reports Server (NTRS)

    Hollenbach, David; Natta, Antonella

    1995-01-01

    We present theoretical models of the time-dependent thermal and chemical structure of molecular gas suddenly exposed to far-ultraviolet (FUV) (6 eV less than hv less than 13.6 eV) radiation fields and the consequent time- dependent infrared emission of the gas. We focus on the response of molecular hydrogen for cloud densities ranging from n = 10(exp 3) to 10(exp 6)/cu cm and FUV fluxes G(sub 0) = 10(exp 3)-10(exp 6) times the local FUV interstellar flux. For G(sub 0)/n greater than 10(exp -2) cu cm, the emergent H(sub 2) vibrational line intensities are initially larger than the final equilibrium values. The H(sub 2) lines are excited by FUV fluorescence and by collisional excitation in warm gas. Most of the H(sub 2) intensity is generated at a characteristic hydrogen column density of N approximately 10(exp 21)/sq cm, which corresponds to an FUV optical depth of unity caused by dust opacity. The time dependence of the H(sub 2) intensities arises because the initial abundances of H(sub 2) at these depths is much higher than the equilibrium values, so that H(sub 2) initially competes more effectively with dust in absorbing FUV photons. Considerable column densities of warm (T approximately 1000) K H(sub 2) gas can be produced by the FUV pumping of H(sub 2) vibrational levels followed by collisional de-excitation, which transfers the energy to heat. In dense (n greater than or approximately 10(exp 5)/cu cm) gas exposed to high (G(sub 0) greater than or approximately 10(exp 4)) fluxes, this warm gas produces a 2-1 S(1)/1-0 S(l) H(sub 2) line ratio of approximately 0.1, which mimics the ratio found in shocked gas. In lower density regions, the FUV pumping produces a pure-fluorescent ratio of approximately 0.5. We also present calculations of the time dependence of the atomic hydrogen column densities and of the intensities of 0 I 6300 A, S II 6730 A, Fe II 1.64 microns, and rotational OH and H20 emission. Potential applications include star-forming regions, clouds

  17. Nicotine dependence and psychiatric disorders.

    PubMed

    Salín-Pascual, Rafael J; Alcocer-Castillejos, Natasha V; Alejo-Galarza, Gabriel

    2003-01-01

    Nicotine addiction is the single largest preventable cause of morbidity and mortality in the Western World. Smoking is not any more just a bad habit, but a substance addiction problem. The pharmacological aspects of nicotine show that this substance has a broad distribution in the different body compartnents, due mainly to its lipophilic characteristic. There are nicotinic receptors as members of cholinergic receptors' family. They are located in neuromuscular junction and in the central nervous system (CNS). Although they are similar, pentameric structure with an ionic channel to sodium, there are some differences in the protein chains characteristics. Repeated administration of nicotine in rats, results in the sensitization phenomenon, which produces increase in the behavioral locomotor activity response. It has been found that most psychostimulants-induced behavioral sensitization through a nicotine receptor activation. Nicotine receptors in CNS are located mainly in presynaptic membrane and in that way they regulated the release of several neurotransmitters, among them acetylcholine, dopamine, serotonin, and norepinephrine. In some activities like sleep-wake cycle, nicotine receptors have a functional significance. Nicotine receptor stimulation promotes wake time, reduces both, total sleep time and rapid eye movement sleep (REMS). About nicotine dependence, this substance full fills all the criteria for dependence and withdrawal syndrome. There are some people that have more vulnerability for to become nicotine dependent, those are psychiatric patients. Among them schizophrenia, major depression, anxiety disorders and attention deficit disorder, represent the best example in this area. Nicotine may have some beneficial effects, among them are some neuroprotective effects in disorders like Parkinson's disease, and Gilles de la Tourette' syndrome. Also there are several evidences that support the role of nicotine in cognitive improvement functions like attention

  18. Amplitude-dependent station magnitude

    NASA Astrophysics Data System (ADS)

    Radzyner, Yael; Ben Horin, Yochai; Steinberg, David M.

    2016-04-01

    Magnitude, a concept first presented by Gutenberg and Richter, adjusts measurements of ground motion for epicentral distance and source depth. Following this principle, the IDC defines the j'th station body wave magnitude for event i as mb(stai,j) = log 10(Aj,i/Tj,i) + V C(Δj,i,hi) , where VC is the Veith-Clawson (VC) correction to compensate for the epicentral distance of the station and the depth of the source. The network magnitude is calculated as the average of station magnitudes. The IDC magnitude estimation is used for event characterization and discrimination and it should be as accurate as possible. Ideally, the network magnitude should be close in value to the station magnitudes. In reality, it is observed that the residuals range between -1 and 1 mu or ±25% of a given mb(neti) value. We show that the residual, mb(neti) -mb(staj,i), depends linearly on log 10(Aj,i/Tj,i), and we correct for this dependence using the following procedure: Calculate a "jackknifed" network magnitude, mbj,n(neti), i.e. an average over all participating stations except station n. Using all measurements at station n, calculate the parameters an, bn of the linear fit of the residual mbj,n(neti) - mb(stan,i to log 10(An,i/Tn,i). For each event i at station n calculate the new station magnitude mbnew(stan,i) = (an + 1)log(An,i/Tn,i) + V C(Δn,i,hi) + bn Calculate the new network magnitude: mbnew(neti) = 1N- ∑ n=1nmbnew(stan,i) The procedure was used on more than two million station-event pairs. Correcting for the station-specific dependence on log amplitude reduces the residuals by roughly a third. We have calculated the spread of the distributions, and compared the original values and those for the corrected magnitudes. The spread is the ratio between the variance of the network magnitudes, and the variance of the residual. Calculations show an increase in the ratio of the variance, meaning that the correction process presented in this document did not lead to loss of variance

  19. Frequency dependence of organic magnetoresistance

    NASA Astrophysics Data System (ADS)

    Wagemans, W.; Janssen, P.; van der Heijden, E. H. M.; Kemerink, M.; Koopmans, B.

    2010-09-01

    To identify the microscopic mechanisms of organic magnetoresistance (OMAR), the dependency on the frequency of the applied magnetic field is explored, which consists of a dc and ac component. The measured magnetoconductance decreases when the frequency is increased. The decrease is stronger for lower voltages, which is shown to be linked to the presence of a negative capacitance, as measured with admittance spectroscopy. The negative capacitance disappears when the frequency becomes comparable to the inverse transit time of the minority carriers. These results are in agreement with recent interpretations that magnetic field effects on minority carrier mobility dominate OMAR.

  20. SYSTEMATICALLY MISCLASSIFIED BINARY DEPENDENT VARIABLES

    PubMed Central

    TENNEKOON, VIDHURA; ROSENMAN, ROBERT

    2014-01-01

    When a binary dependent variable is misclassified, that is, recorded in the category other than where it really belongs, probit and logit estimates are biased and inconsistent. In some cases the probability of misclassification may vary systematically with covariates, and thus be endogenous. In this paper we develop an estimation approach that corrects for endogenous misclassification, validate our approach using a simulation study, and apply it to the analysis of a treatment program designed to improve family dynamics. Our results show that endogenous misclassification could lead to potentially incorrect conclusions unless corrected using an appropriate technique. PMID:27293307

  1. INTENSITY DEPENDENT EFFECTS IN RHIC

    SciTech Connect

    WEI,J.

    1999-09-02

    The Relativistic Heavy Ion Collider (RHIC) is currently under commissioning after a seven-year construction cycle. Unlike conventional hadron colliders, this machine accelerates, stores, and collides heavy ion beams of various combinations of species. The dominant intensity dependent effects are intra-beam scattering at both injection and storage, and complications caused by crossing transition at a slow ramp rate. In this paper, the authors present theoretical formalisms that have been used for the study, and discuss mechanisms, impacts, and compensation methods including beam cooling and transition jump schemes. Effects of space charge, beam-beam, and ring impedances are also summarized.

  2. PET imaging of leptin biodistribution and metabolism in rodents and primates.

    PubMed

    Ceccarini, Giovanni; Flavell, Robert R; Butelman, Eduardo R; Synan, Michael; Willnow, Thomas E; Bar-Dagan, Maya; Goldsmith, Stanley J; Kreek, Mary J; Kothari, Paresh; Vallabhajosula, Shankar; Muir, Tom W; Friedman, Jeffrey M

    2009-08-01

    We have determined the systemic biodistribution of the hormone leptin by PET imaging. PET imaging using (18)F- and (68)Ga-labeled leptin revealed that, in mouse, the hormone was rapidly taken up by megalin (gp330/LRP2), a multiligand endocytic receptor localized in renal tubules. In addition, in rhesus monkeys, 15% of labeled leptin localized to red bone marrow, which was consistent with hormone uptake in rodent tissues. These data confirm a megalin-dependent mechanism for renal uptake in vivo. The significant binding to immune cells and blood cell precursors in bone marrow is also consistent with prior evidence showing that leptin modulates immune function. These experiments set the stage for similar studies in humans to assess the extent to which alterations of leptin's biodistribution might contribute to obesity; they also provide a general chemical strategy for (18)F labeling of proteins for PET imaging of other polypeptide hormones.

  3. Dependent video coding using a tree representation of pixel dependencies

    NASA Astrophysics Data System (ADS)

    Amati, Luca; Valenzise, Giuseppe; Ortega, Antonio; Tubaro, Stefano

    2011-09-01

    Motion-compensated prediction induces a chain of coding dependencies between pixels in video. In principle, an optimal selection of encoding parameters (motion vectors, quantization parameters, coding modes) should take into account the whole temporal horizon of a GOP. However, in practical coding schemes, these choices are made on a frame-by-frame basis, thus with a possible loss of performance. In this paper we describe a tree-based model for pixelwise coding dependencies: each pixel in a frame is the child of a pixel in a previous reference frame. We show that some tree structures are more favorable than others from a rate-distortion perspective, e.g., because they entail a large descendance of pixels which are well predicted from a common ancestor. In those cases, a higher quality has to be assigned to pixels at the top of such trees. We promote the creation of these structures by adding a special discount term to the conventional Lagrangian cost adopted at the encoder. The proposed model can be implemented through a double-pass encoding procedure. Specifically, we devise heuristic cost functions to drive the selection of quantization parameters and of motion vectors, which can be readily implemented into a state-of-the-art H.264/AVC encoder. Our experiments demonstrate that coding efficiency is improved for video sequences with low motion, while there are no apparent gains for more complex motion. We argue that this is due to both the presence of complex encoder features not captured by the model, and to the complexity of the source to be encoded.

  4. Temperature dependency of quantitative ultrasound.

    PubMed

    Pocock, N A; Babichev, A; Culton, N; Graney, K; Rooney, J; Bell, D; Chu, J

    2000-01-01

    Quantitative ultrasound (QUS) parameters are temperature dependent. We examined the effect of temperature on QUS using Lunar Achilles+ and Hologic Sahara units. In vivo studies were performed in a cadaveric foot and in 5 volunteers. QUS scans were performed in the cadaveric foot, using both machines, at temperatures ranging from 15 to 40 degrees C. To assess the effect of change in water bath temperature in the Achilles+, independently of foot temperature, 5 volunteers were studied at water temperatures ranging from 10 to 42 degrees C. In the cadaveric foot there were strong negative correlations between temperature and speed of sound (SOS) but a moderately positive correlation between temperature and broadband ultrasound attenuation (BUA). Stiffness and the Quantitative Ultrasound Index (QUI) in the cadaveric foot showed strong negative correlations with temperature, reflecting their high dependence on SOS. In the 5 volunteers, in whom foot temperature was assumed to be constant, there was a small change in Stiffness in the Achilles+, with variation in water temperature. In conclusion, while there are opposite effects of temperature on SOS and BUA in vivo, there is still a significant effect of temperature variation on Stiffness and the QUI. This may have clinical significance in particular subjects. The precision of QUS may be affected by temperature variation of the environment or of the patient's limb. Instruments utilizing a water bath may be able partly to compensate for changes in environmental temperature, but standardization of water bath temperature is crucial to maximize precision.

  5. Time Dependent Nuclear Scattering Calculations

    NASA Astrophysics Data System (ADS)

    Weeks, David

    2005-04-01

    A new time dependent method for calculating scattering matrix elements of two and three body nuclear collisions below 50 Mev is being developed. The procedure closely follows the channel packet method (CPM) used to compute scattering matrix elements for non-adiabatic molecular reactions.ootnotetextT.A.Niday and D.E.Weeks, Chem. Phys. Letters 308 (1999) 106 Currently, one degree of freedom calculations using a simple square well have been completed and a two body scattering calculation using the Yukawa potential is anticipated. To perform nuclear scattering calculations with the CPM that will incorporate the nucleon-nucleon tensor force, we plan to position initial reactant and product channel packets in the asymptotic limit on single coupled potential energy surfaces labeled by the spin, isospin, and total angular momentum of the reactant nucleons. The wave packets will propagated numerically using the split operator method augmented by a coordinate dependant unitary transformation used to diagonalize the potential. Scattering matrix elements will be determined by the Fourier transform of the correlation function between the evolving reactant and product wave packets. A brief outline of the Argonne v18 nucleon-nucleon potentialootnotetextR.B.Wiringa, V.G.J.Stoks, and R.Schiavilla, Physical Review C 51(1995) 38 and the proposed wave packet calculations will be presented.

  6. State-Dependent Visual Processing

    PubMed Central

    Britz, Juliane; Michel, Christoph M.

    2011-01-01

    The temporal dynamics and anatomical correlates underlying human visual cognition are traditionally assessed as a function of stimulus properties and task demands. Any non-stimulus related activity is commonly dismissed as noise and eliminated to extract an evoked signal that is only a small fraction of the magnitude of the measured signal. We review studies that challenge this view by showing that non-stimulus related activity is not mere noise but that it has a well-structured organization which can largely determine the processing of upcoming stimuli. We review recent evidence from human electrophysiology that shows how different aspects of pre-stimulus activity such as pre-stimulus EEG frequency power and phase and pre-stimulus EEG microstates can determine qualitative and quantitative properties of both lower and higher-level visual processing. These studies show that low-level sensory processes depend on the momentary excitability of sensory cortices whereas perceptual processes leading to stimulus awareness depend on momentary pre-stimulus activity in higher-level non-visual brain areas. Also speed and accuracy of stimulus identification have likewise been shown to be modulated by pre-stimulus brain states. PMID:22203809

  7. Luminosity Dependence and Search Doppler

    NASA Technical Reports Server (NTRS)

    VanParadijs, Johannes A.

    1998-01-01

    The research supported by this grant covered two projects: (1) a study of the luminosity dependence of the properties of atoll sources; and (2) a search for Doppler shifts in the pulse arrival times of the anomalous pulsar 4U 0142+61. Following the discovery of kilohertz quasi-periodic oscillations (QPOS) in Sco X-1 studies of the X-ray properties of atoll sources have been dominated by searches for these QPOS, and the study of their dependence on other source properties, such as X-ray luminosity and spectral state. In the project supported by grant NAG5-3269 we have detected kHz QPOs for several atoll sources. The physical interpretation of these QPO is as yet unclear, but simple models (such as the Keplerian beat frequency model) can probably be excluded. The results of this research have been reported. We have studied the X-ray pulsations of the anomalous X-ray pulsar 4U 0142+61 using the Rossi XTE. A detailed search for Doppler shifts did not lead to a positive detection. The upper limits exclude almost all types of possible companion stars, except white dwarfs. However, the latter can be excluded since anomalous X-ray pulsars are very young objects. We therefore conclude that anomalous X-ray pulsars are single neutron stars.

  8. Viscosity-dependent protein dynamics.

    PubMed

    Finkelstein, Ilya J; Massari, Aaron M; Fayer, M D

    2007-05-15

    Spectrally resolved stimulated vibrational echo spectroscopy is used to investigate the dependence of fast protein dynamics on bulk solution viscosity at room temperature in four heme proteins: hemoglobin, myoglobin, a myoglobin mutant with the distal histidine replaced by a valine (H64V), and a cytochrome c552 mutant with the distal methionine replaced by an alanine (M61A). Fructose is added to increase the viscosity of the aqueous protein solutions over many orders of magnitude. The fast dynamics of the four globular proteins were found to be sensitive to solution viscosity and asymptotically approached the dynamical behavior that was previously observed in room temperature sugar glasses. The viscosity-dependent protein dynamics are analyzed in the context of a viscoelastic relaxation model that treats the protein as a deformable breathing sphere. The viscoelastic model is in qualitative agreement with the experimental data but does not capture sufficient system detail to offer a quantitative description of the underlying fluctuation amplitudes and relaxation rates. A calibration method based on the near-infrared spectrum of water overtones was constructed to accurately determine the viscosity of small volumes of protein solutions.

  9. Issues and Conflicts in Male Dependence.

    ERIC Educational Resources Information Center

    Ferguson, Roberta C.

    Dependence is a salient quality in both sexes, although it has been culturally more acceptable for women than for men to acknowledge and accept dependency. The conflict men experience with regard to dependency and the manifestations of such conflict in dependent adult behaviors were examined. Subjects were divided into a "most…

  10. Suicidal Behavior in Chemically Dependent Adolescents.

    ERIC Educational Resources Information Center

    Cavaiola, Alan A.; Lavender, Neil

    1999-01-01

    Study explores distinctions between chemically dependent suicide attempters, chemically dependent nonsuicidal adolescents, and high school students with no history of chemical dependency (N=250). Results reveal that there were significant differences between the chemically dependent groups. It was also found that the majority of suicidal gestures…

  11. Some Thoughts on Reformulating the Dependency Ratio.

    ERIC Educational Resources Information Center

    Crown, William H.

    1985-01-01

    Develops and applies methodology for systematically examining dependency of alternative demographic groups within the context of total dependency ratio using Bureau of Census and Bureau of Labor Statistics data. Although total dependency ratio increases as population ages, those under 16 will continue as the largest dependent group in future…

  12. [Abuse, dependence and intoxication of substances].

    PubMed

    Wada, Kiyoshi

    2015-09-01

    As for substance-related disorders, there were several differences between ICD-10 and DSM-IV, however, the concept of "dependence" had been essential for both criteria. DSM-5 published in 2013 had erased dependence. This confuses us. It is important to recognize dependence again. "Abuse" is the self-intake behavior of drug against the social norms. Repeated abuse results in dependence. Dependence is a state of loss of control against drug use due to craving. Abuse can produce "acute intoxication", and repeated abuse under dependence can produce "chronic intoxication". It is important to understand abuse, dependence and "intoxication" based on their relationship from the point of time course.

  13. Analysis of Critical Infrastructure Dependencies and Interdependencies

    SciTech Connect

    Petit, Frederic; Verner, Duane; Brannegan, David; Buehring, William; Dickinson, David; Guziel, Karen; Haffenden, Rebecca; Phillips, Julia; Peerenboom, James

    2015-06-01

    The report begins by defining dependencies and interdependencies and exploring basic concepts of dependencies in order to facilitate a common understanding and consistent analytical approaches. Key concepts covered include; Characteristics of dependencies: upstream dependencies, internal dependencies, and downstream dependencies; Classes of dependencies: physical, cyber, geographic, and logical; and Dimensions of dependencies: operating environment, coupling and response behavior, type of failure, infrastructure characteristics, and state of operations From there, the report proposes a multi-phase roadmap to support dependency and interdependency assessment activities nationwide, identifying a range of data inputs, analysis activities, and potential products for each phase, as well as key steps needed to progress from one phase to the next. The report concludes by outlining a comprehensive, iterative, and scalable framework for analyzing dependencies and interdependencies that stakeholders can integrate into existing risk and resilience assessment efforts.

  14. [Alcohol Dependence Syndrome: diagnostic criteria].

    PubMed

    Gigliotti, Analice; Bessa, Marco Antonio

    2004-05-01

    The Alcohol Dependence Syndrome (ADS) is a serious problem of public health. In spite of being deeply studied and having well-established diagnostic criteria, many times clinicians and even psychiatrists do not notice this disorder. The aim of this paper is to make a brief exposition on how men and society have developed their relationship with alcohol, emphasizing the development of the concept of alcoholism in medicine until the definition of ADS in ICD-10 and DSM-IV. The article explains the different ways of alcohol consume and how it influences different levels of risk and severity of its consequences, that evolves as a continuum. At last, it makes a comparison between ADS and alcohol harmful use, very important in the prevention and treatment of such disorders.

  15. Your Morals Depend on Language

    PubMed Central

    Costa, Albert; Foucart, Alice; Hayakawa, Sayuri; Aparici, Melina; Apesteguia, Jose; Heafner, Joy; Keysar, Boaz

    2014-01-01

    Should you sacrifice one man to save five? Whatever your answer, it should not depend on whether you were asked the question in your native language or a foreign tongue so long as you understood the problem. And yet here we report evidence that people using a foreign language make substantially more utilitarian decisions when faced with such moral dilemmas. We argue that this stems from the reduced emotional response elicited by the foreign language, consequently reducing the impact of intuitive emotional concerns. In general, we suggest that the increased psychological distance of using a foreign language induces utilitarianism. This shows that moral judgments can be heavily affected by an orthogonal property to moral principles, and importantly, one that is relevant to hundreds of millions of individuals on a daily basis. PMID:24760073

  16. Mass dependence of nitride sputtering

    NASA Astrophysics Data System (ADS)

    Elovikov, S. S.; Khrustachev, I. K.; Mosunov, A. S.; Yurasova, V. E.

    2003-08-01

    A molecular dynamics simulation was performed to study the sputtering yield Y for BN, AlN and GaN polycrystals of wurtzite structure as a function of the masses m 1 of bombarding ions with energies from 200 to 2000 eV. A nonmonotonic behavior of the Y ( m 1 ) curve was obtained for the irradiation by low-energy ions, the curve having a maximum with a position being dependent on m 2 / m 1 ( m 2 is the average mass of atoms in a compound). For AlN and GaN the maximum was observed at m 2 / m 1 = 2, and for BN at m 2 / m 1 = 1. The effect of the mass of bombarding ions on the mean energies and energy spectra of sputtered particles, the depth of sputtering origin, and the generation of emitted atoms for nitrides was also investigated and discussed.

  17. Reprogramming Roadblocks Are System Dependent

    PubMed Central

    Chantzoura, Eleni; Skylaki, Stavroula; Menendez, Sergio; Kim, Shin-Il; Johnsson, Anna; Linnarsson, Sten; Woltjen, Knut; Chambers, Ian; Kaji, Keisuke

    2015-01-01

    Summary Since the first generation of induced pluripotent stem cells (iPSCs), several reprogramming systems have been used to study its molecular mechanisms. However, the system of choice largely affects the reprogramming efficiency, influencing our view on the mechanisms. Here, we demonstrate that reprogramming triggered by less efficient polycistronic reprogramming cassettes not only highlights mesenchymal-to-epithelial transition (MET) as a roadblock but also faces more severe difficulties to attain a pluripotent state even post-MET. In contrast, more efficient cassettes can reprogram both wild-type and Nanog−/− fibroblasts with comparable efficiencies, routes, and kinetics, unlike the less efficient reprogramming systems. Moreover, we attribute a previously reported variation in the N terminus of KLF4 as a dominant factor underlying these critical differences. Our data establish that some reprogramming roadblocks are system dependent, highlighting the need to pursue mechanistic studies with close attention to the systems to better understand reprogramming. PMID:26278041

  18. A density dependent dispersion correction.

    PubMed

    Steinmann, Stephan N; Corminboeuf, Clémence

    2011-01-01

    Density functional approximations fail to provide an accurate treatment of weak interactions. More recent, but not readily available functionals can lead to significant improvements. A simple alternative to correct for the missing weak interactions is to add, a posteriori, an atom pair-wise dispersion correction. We here present a density dependent dispersion correction, dDXDM, which dramatically improves the performance of popular functionals (e.g., PBE-dDXDM or B3LYP-dDXDM) for a set of 145 systems featuring both inter- and intramolecular interactions. Whereas the highly parameterized M06-2X functional, the long-range corrected LC-BLYP and the fully non-local van der Waals density functional rPW86-W09 also lead to improved results as compared to standard DFT methods, the enhanced performance of dDXDM remains the most impressive.

  19. Psychostimulant drugs for cocaine dependence.

    PubMed

    Castells, Xavier; Cunill, Ruth; Pérez-Mañá, Clara; Vidal, Xavier; Capellà, Dolors

    2016-09-27

    Cocaine dependence is a severe disorder for which no medication has been approved. Like opioids for heroin dependence, replacement therapy with psychostimulants could be an effective therapy for treatment. To assess the effects of psychostimulants for cocaine abuse and dependence. Specific outcomes include sustained cocaine abstinence and retention in treatment. We also studied the influence of type of drug and comorbid disorders on psychostimulant efficacy. This is an update of the review previously published in 2010. For this updated review, we searched the Cochrane Drugs and Alcohol Group Trials Register, CENTRAL, MEDLINE, Embase and PsycINFO up to 15 February 2016. We handsearched references of obtained articles and consulted experts in the field. We included randomised parallel group controlled clinical trials comparing the efficacy of a psychostimulant drug versus placebo. We used standard methodological procedures expected by Cochrane. We included 26 studies involving 2366 participants. The included studies assessed nine drugs: bupropion, dexamphetamine, lisdexamfetamine, methylphenidate, modafinil, mazindol, methamphetamine, mixed amphetamine salts and selegiline. We did not consider any study to be at low risk of bias for all domains included in the Cochrane 'Risk of bias' tool. Attrition bias was the most frequently suspected potential source of bias of the included studies. We found very low quality evidence that psychostimulants improved sustained cocaine abstinence (risk ratio (RR) 1.36, 95% confidence interval (CI) 1.05 to 1.77, P = 0.02), but they did not reduce cocaine use (standardised mean difference (SMD) 0.16, 95% CI -0.02 to 0.33) among participants who continued to use it. Furthermore, we found moderate quality evidence that psychostimulants did not improve retention in treatment (RR 1.00, 95% CI 0.93 to 1.06). The proportion of adverse event-induced dropouts and cardiovascular adverse event-induced dropouts was similar for psychostimulants

  20. Geometry dependence of stellarator turbulence

    NASA Astrophysics Data System (ADS)

    Mynick, H. E.; Xanthopoulos, P.; Boozer, A. H.

    2009-11-01

    Using the nonlinear gyrokinetic code package GENE/GIST [F. Jenko, W. Dorland, M. Kotschenreuther, and B. N. Rogers, Phys. Plasmas 7, 1904 (2000); P. Xanthopoulos, W. A. Cooper, F. Jenko, Yu. Turkin, A. Runov, and J. Geiger, Phys. Plasmas 16, 082303 (2009)], we study the turbulent transport in a broad family of stellarator designs, to understand the geometry dependence of the microturbulence. By using a set of flux tubes on a given flux surface, we construct a picture of the two-dimensional structure of the microturbulence over that surface and relate this to relevant geometric quantities, such as the curvature, local shear, and effective potential in the Schrödinger-like equation governing linear drift modes.

  1. Your morals depend on language.

    PubMed

    Costa, Albert; Foucart, Alice; Hayakawa, Sayuri; Aparici, Melina; Apesteguia, Jose; Heafner, Joy; Keysar, Boaz

    2014-01-01

    Should you sacrifice one man to save five? Whatever your answer, it should not depend on whether you were asked the question in your native language or a foreign tongue so long as you understood the problem. And yet here we report evidence that people using a foreign language make substantially more utilitarian decisions when faced with such moral dilemmas. We argue that this stems from the reduced emotional response elicited by the foreign language, consequently reducing the impact of intuitive emotional concerns. In general, we suggest that the increased psychological distance of using a foreign language induces utilitarianism. This shows that moral judgments can be heavily affected by an orthogonal property to moral principles, and importantly, one that is relevant to hundreds of millions of individuals on a daily basis.

  2. Spatial dependency of action simulation.

    PubMed

    ter Horst, Arjan C; van Lier, Rob; Steenbergen, Bert

    2011-08-01

    In this study, we investigated the spatial dependency of action simulation. From previous research in the field of single-cell recordings, grasping studies and from crossmodal extinction tasks, it is known that our surrounding space can be divided into a peripersonal space and extrapersonal space. These two spaces are functionally different at both the behavioral and neuronal level. The peripersonal space can be seen as an action space which is limited to the area in which we can grasp objects without moving the object or ourselves. The extrapersonal space is the space beyond the peripersonal space. Objects situated within peripersonal space are mapped onto an egocentric reference frame. This mapping is thought to be accomplished by action simulation. To provide direct evidence of the embodied nature of this simulated motor act, we performed two experiments, in which we used two mental rotation tasks, one with stimuli of hands and one with stimuli of graspable objects. Stimuli were presented in both peri- and extrapersonal space. The results showed increased reaction times for biomechanically difficult to adopt postures compared to more easy to adopt postures for both hand and graspable object stimuli. Importantly, this difference was only present for stimuli presented in peripersonal space but not for the stimuli presented in extrapersonal space. These results extend previous behavioral findings on the functional distinction between peripersonal- and extrapersonal space by providing direct evidence for the spatial dependency of the use of action simulation. Furthermore, these results strengthen the hypothesis that objects situated within the peripersonal space are mapped onto an egocentric reference frame by action simulation.

  3. Waves, circulation and vertical dependence

    NASA Astrophysics Data System (ADS)

    Mellor, George

    2013-04-01

    Longuet-Higgins and Stewart (J Fluid Mech 13:481-504, 1962; Deep-Sea Res 11:529-562, 1964) and later Phillips (1977) introduced the problem of waves incident on a beach, from deep to shallow water. From the wave energy equation and the vertically integrated continuity equation, they inferred velocities to be Stokes drift plus a return current so that the vertical integral of the combined velocities was nil. As a consequence, it can be shown that velocities of the order of Stokes drift rendered the advective term in the momentum equation negligible resulting in a simple balance between the horizontal gradients of the vertically integrated elevation and wave radiation stress terms; the latter was first derived by Longuet-Higgins and Stewart. Mellor (J Phys Oceanogr 33:1978-1989, 2003a), noting that vertically integrated continuity and momentum equations were not able to deal with three-dimensional numerical or analytical ocean models, derived a vertically dependent theory of wave-circulation interaction. It has since been partially revised and the revisions are reviewed here. The theory is comprised of the conventional, three-dimensional, continuity and momentum equations plus a vertically distributed, wave radiation stress term. When applied to the problem of waves incident on a beach with essentially zero turbulence momentum mixing, velocities are very large and the simple balance between elevation and radiation stress gradients no longer prevails. However, when turbulence mixing is reinstated, the vertically dependent radiation stresses produce vertical velocity gradients which then produce turbulent mixing; as a consequence, velocities are reduced, but are still larger by an order of magnitude compared to Stokes drift. Nevertheless, the velocity reduction is sufficient so that elevation set-down obtained from a balance between elevation gradient and radiation stress gradients is nearly coincident with that obtained by the aforementioned papers. This paper

  4. Bioinspired orientation-dependent friction.

    PubMed

    Xue, Longjian; Iturri, Jagoba; Kappl, Michael; Butt, Hans-Jürgen; del Campo, Aránzazu

    2014-09-23

    Spatular terminals on the toe pads of a gecko play an important role in directional adhesion and friction required for reversible attachment. Inspired by the toe pad design of a gecko, we study friction of polydimethylsiloxane (PDMS) micropillars terminated with asymmetric (spatular-shaped) overhangs. Friction forces in the direction of and against the spatular end were evaluated and compared to friction forces on symmetric T-shaped pillars and pillars without overhangs. The shape of friction curves and the values of friction forces on spatula-terminated pillars were orientation-dependent. Kinetic friction forces were enhanced when shearing against the spatular end, while static friction was stronger in the direction toward the spatular end. The overall friction force was higher in the direction against the spatula end. The maximum value was limited by the mechanical stability of the overhangs during shear. The aspect ratio of the pillar had a strong influence on the magnitude of the friction force, and its contribution surpassed and masked that of the spatular tip for aspect ratios of >2.

  5. Coordinate Dependence of Variability Analysis

    PubMed Central

    Sternad, Dagmar; Park, Se-Woong; Müller, Hermann; Hogan, Neville

    2010-01-01

    Analysis of motor performance variability in tasks with redundancy affords insight about synergies underlying central nervous system (CNS) control. Preferential distribution of variability in ways that minimally affect task performance suggests sophisticated neural control. Unfortunately, in the analysis of variability the choice of coordinates used to represent multi-dimensional data may profoundly affect analysis, introducing an arbitrariness which compromises its conclusions. This paper assesses the influence of coordinates. Methods based on analyzing a covariance matrix are fundamentally dependent on an investigator's choices. Two reasons are identified: using anisotropy of a covariance matrix as evidence of preferential distribution of variability; and using orthogonality to quantify relevance of variability to task performance. Both are exquisitely sensitive to coordinates. Unless coordinates are known a priori, these methods do not support unambiguous inferences about CNS control. An alternative method uses a two-level approach where variability in task execution (expressed in one coordinate frame) is mapped by a function to its result (expressed in another coordinate frame). An analysis of variability in execution using this function to quantify performance at the level of results offers substantially less sensitivity to coordinates than analysis of a covariance matrix of execution variables. This is an initial step towards developing coordinate-invariant analysis methods for movement neuroscience. PMID:20421930

  6. Nuclear Dependence of Charm Production

    SciTech Connect

    Blanco-Covarrubias, A.; Engelfried, J.; Akgun, U.; Alkhazov, G.; Amaro-Reyes, J.; Atamantchouk, A.G.; Ayan, A.S.; Balatz, M.Y.; Bondar, N.F.; Cooper, P.S.; Dauwe, Loretta J.; /Michigan U., Flint /Moscow, ITEP

    2009-02-01

    With data taken by SELEX, which accumulated data during the 1996-1997 fixed target run at Fermilab, we study the production of charmed hadrons on copper and carbon targets with {Sigma}{sup -}, p, {pi}{sup -}, and {pi}{sup +} beams. Parameterizing the production cross section {infinity} A{sup {alpha}}, A being the atomic number, we determine {alpha} for D{sup +}, D{sup 0}, D{sub s}{sup +}, D{sup +}(2010), {Lambda}{sub c}{sup +}, and their respective anti-particles, as a function of their transverse momentum p{sub t} and scaled longitudinal momentum x{sub F}. Within our statistics there is no dependence of {alpha} on x{sub F} for any charm species for the interval 0.1 < x{sub F} < 1.0. The average value of {alpha} for charm production by pion beams is {alpha}{sub meson} = 0.850 {+-} 0.028. This is somewhat larger than the corresponding average {alpha}{sub baryon} = 0.755 {+-} 0.016 for charm production by baryon beams ({Sigma}{sup -}, p).

  7. Sequence-dependent nucleosome positioning.

    PubMed

    Chung, Ho-Ryun; Vingron, Martin

    2009-03-13

    Eukaryotic DNA is organized into a macromolecular structure called chromatin. The basic repeating unit of chromatin is the nucleosome, which consists of two copies of each of the four core histones and DNA. The nucleosomal organization and the positions of nucleosomes have profound effects on all DNA-dependent processes. Understanding the factors that influence nucleosome positioning is therefore of general interest. Among the many determinants of nucleosome positioning, the DNA sequence has been proposed to have a major role. Here, we analyzed more than 860,000 nucleosomal DNA sequences to identify sequence features that guide the formation of nucleosomes in vivo. We found that both a periodic enrichment of AT base pairs and an out-of-phase oscillating enrichment of GC base pairs as well as the overall preference for GC base pairs are determinants of nucleosome positioning. The preference for GC pairs can be related to a lower energetic cost required for deformation of the DNA to wrap around the histones. In line with this idea, we found that only incorporation of both signal components into a sequence model for nucleosome formation results in maximal predictive performance on a genome-wide scale. In this manner, one achieves greater predictive power than published approaches. Our results confirm the hypothesis that the DNA sequence has a major role in nucleosome positioning in vivo.

  8. [A case of ketamine dependence].

    PubMed

    Błachut, Michał; Sołowiów, Katarzyna; Janus, Aleksandra; Ruman, Jerzy; Cekus, Agnieszka; Matysiakiewicz, Jerzy; Hese, Robert Teodor

    2009-01-01

    Ketamine is a rapid-acting anaesthetic agent which has been used for over 40 years. It is an antagonist of N-methyl-D-aspartate (NMDA) receptors and agonist of mu and sigma opiate receptors. Ketamine acts through inhibition of sensory parts in the brain and stimulation of the limbic system and optic thalamus. The most common psychiatric disorders observed after the use of ketamine are: psychomotor agitation, hallucinations, status of stupor, consciousness disorders. There are observed cases of non-medical use of ketamine since the sixties of the 20th century. The authors describe the case of a 52 year old man who has been addicted to ketamine for 15 years. The patient was admitted to hospital to observe and treat the withdrawal syndrome as an effect of abrupt discontinuation of a chronically abused substance. On the ground of medical examinations, standard tests, anamnesis and hospital observation, ketamine dependence syndrome of a person with personality disorders was recognized. There was no somatic symptoms of withdrawal syndrome observed. The patient complained of sleep disorders and anxiety. Diazepam, carbamazepine and vitamins was used during treatment. The patient was motivated to stop using ketamine. This case and the described symptoms were compared with others articles.

  9. Irradiance-dependent UVB Photocarcinogenesis

    PubMed Central

    Lan, Cheng-Che E.; Wu, Ching-Shuang; Huang, Shu-Mei; Wu, Chin-Han; Lai, Hsiao-Chi; Peng, Yu-Ting; Hou, Pao-Sheng; Yang, Hui-Jun; Chen, Gwo-Shing

    2016-01-01

    Ultraviolet B (UVB) radiation from the sun may lead to photocarcinogenesis of the skin. Sunscreens were used to protect the skin by reducing UVB irradiance, but sunscreen use did not reduce sunburn episodes. It was shown that UVB-induced erythema depends on surface exposure but not irradiance of UVB. We previously showed that irradiance plays a critical role in UVB-induced cell differentiation. This study investigated the impact of irradiance on UVB-induced photocarcinogenesis. For hairless mice receiving equivalent exposure of UVB radiation, the low irradiance (LI) UVB treated mice showed more rapid tumor development, larger tumor burden, and more keratinocytes harboring mutant p53 in the epidermis as compared to their high irradiance (HI) UVB treated counterpart. Mechanistically, using cell models, we demonstrated that LI UVB radiation allowed more keratinocytes harboring DNA damages to enter cell cycle via ERK-related signaling as compared to its HI UVB counterpart. These results indicated that at equivalent exposure, UVB radiation at LI has higher photocarcinogenic potential as compared to its HI counterpart. Since erythema is the observed sunburn at moderate doses and use of sunscreen was not found to associate with reduced sunburn episodes, the biological significance of sunburn with or without sunscreen use warrants further investigation. PMID:27869214

  10. Energy dependence of hadronic activity

    NASA Astrophysics Data System (ADS)

    Gabriel, T. A.; Groom, D. E.; Job, P. K.; Mokhov, N. V.; Stevenson, G. R.

    1994-01-01

    Two features of high-energy hadronic cascades have long been known to shielding specialists: a) in a high-energy hadronic cascade in a given material (incident E ≳ 10 GeV), the relative abundance and spectrum of each hadronic species responsible for most of the energy deposition is independent of the energy or species of the incident hadron, and b) because π0 production bleeds off more and more energy into the electromagnetic sector as the energy of the incident hadron increases, the absolute level of this low-energy hadronic activity ( E ≲ 1 GeV) rises less rapidly than the incident energy, and in fact rises very nearly as a power of the incident energy. Both features are of great importance in hadron calorimetry, where it is the "universal spectrum" which makes possible the definition of an intrinsic {e}/{h}, and the increasing fraction of the energy going into π0's which leads to the energy dependence of {e}/{π}. We present evidence for the "universal spectrum," and use an induction argument and simulation results to demonstrate that the low-energy activity ss Em, with 0.80 ≲ m ≲ 0.85. The hadronic activity produced by incident pions is 15-20% less than that initiated by protons.

  11. Frequency dependence of organic magnetoresistance

    NASA Astrophysics Data System (ADS)

    Wang, Fujian; Rybicki, James; Lin, Ran; Hutchinson, Kent; Hou, Jia; Wohlgenannt, Markus

    2011-03-01

    Organic magnetoresistive (OMAR) devices show a large enough magnetoresistive response (typically 10%) for potential applications as magnetic field sensors. However, applications often require sensing high frequency magnetic fields, and the examination of the frequency-dependent magnetoresistive response is therefore required. Analysis of time constants that limit the frequency response may also shed light on the mechanism behind the OMAR effect, because different OMAR mechanisms occur at different time scales In our experiments, the AC magnetic field is supplied by a coil with a ferrite core which is driven by a function generator The AC magnet shows a frequency response that is almost flat up to 1MHz. We found that the OMAR frequency limit is about 10 kHz for a typical organic semiconductor device and at least 100 kHz for devices made from a doped polymer film. We also performed capacitance and conductance vs. frequency measurements to understand the origin of the observed limit frequencies. This work was supported by Army MURI under GrantNo. W911NF-08-1-0317 and NSF under Grant No. ECS 0725280.

  12. Density Gradient Dependent Helicon Modes

    NASA Astrophysics Data System (ADS)

    Panevsky, Martin; Bengtson, Roger

    2002-11-01

    Radially localized helicon modes have been proposed to provide a fuller description of helicon discharges over a wide span of operating conditions and gas types [1]. These plasma modes could be of vital importance to the VASIMR engine. They depend on a radial density gradient and appear to operate over a range of frequencies inaccessible to traditional helicon discharges. Our work focuses on confirming experimentally the existence and properties of these helicon modes in Argon, Helium, and Hydrogen. We investigate the density profile, power deposition, wavefields, and dispersion relation of the new helicon modes which differ substantially from the properties of the traditional helicon plasma. We are using a set of dual half-turn helical antennas driven at 13.56 MHz. Our diagnostics includes a system for monitoring the plasma impedance, a set of Langmuir probes, a set of magnetic probes, as well as sensors for monitoring the pressure and DC magnetic field. *Work supported in part by Advanced Space Propulsion Lab, Johnson Space Center, NASA [1] B. N. Breizman and A. V. Arefiev, Phys. Rev. 84, 3863 (2000)

  13. Temperature dependence of basalt weathering

    NASA Astrophysics Data System (ADS)

    Li, Gaojun; Hartmann, Jens; Derry, Louis A.; West, A. Joshua; You, Chen-Feng; Long, Xiaoyong; Zhan, Tao; Li, Laifeng; Li, Gen; Qiu, Wenhong; Li, Tao; Liu, Lianwen; Chen, Yang; Ji, Junfeng; Zhao, Liang; Chen, Jun

    2016-06-01

    The homeostatic balance of Earth's long-term carbon cycle and the equable state of Earth's climate are maintained by negative feedbacks between the levels of atmospheric CO2 and the chemical weathering rate of silicate rocks. Though clearly demonstrated by well-controlled laboratory dissolution experiments, the temperature dependence of silicate weathering rates, hypothesized to play a central role in these weathering feedbacks, has been difficult to quantify clearly in natural settings at landscape scale. By compiling data from basaltic catchments worldwide and considering only inactive volcanic fields (IVFs), here we show that the rate of CO2 consumption associated with the weathering of basaltic rocks is strongly correlated with mean annual temperature (MAT) as predicted by chemical kinetics. Relations between temperature and CO2 consumption rate for active volcanic fields (AVFs) are complicated by other factors such as eruption age, hydrothermal activity, and hydrological complexities. On the basis of this updated data compilation we are not able to distinguish whether or not there is a significant runoff control on basalt weathering rates. Nonetheless, the simple temperature control as observed in this global dataset implies that basalt weathering could be an effective mechanism for Earth to modulate long-term carbon cycle perturbations.

  14. Nicotine Dependence Measures for Perinatal Women.

    PubMed

    Yang, Irene; Hall, Lynne A

    2016-03-02

    This integrative review provides an overview of nicotine dependence measures used with perinatal women and an evaluation of their psychometric properties. Fifty-five articles that met inclusion and exclusion criteria were identified from five different databases. Most of the studies used the Fagerström Test for Nicotine Dependence (FTND). Other approaches included diagnostic tests, the Wisconsin Inventory of Smoking Dependence Motives (WISDM), the Tobacco Dependence Screener, and single-item measures. This review indicated that the FTND may not be the best option for measuring nicotine dependence in this population. The WISDM is a newer instrument that has excellent psychometric properties and captures nonnicotinic dimensions of nicotine dependence relevant to women. Future research is needed to assess its reliability in the perinatal population. Other recommendations from this review include the use of biomarker validation, thorough psychometric reporting on nicotine dependence instruments, and the use of multiple instruments to maximize comparability between nicotine dependence instruments.

  15. Temperature Dependence of Optical Phonon Lifetimes,

    DTIC Science & Technology

    This reprint reports an application of a picosecond laser system to the measurement of the temperature dependence of the relaxation time of LO...Raman linewidths, and to the theoretically predicted temperature dependence of the relaxation time. (Author).

  16. Jealousy, Gender, Sex Roles, and Dependency.

    ERIC Educational Resources Information Center

    Madden, Margaret E.; And Others

    One hundred adults ages 18 to 42 completed measures of jealousy and dependency in romantic relationships and of sex role traditionalism. Traditionalism and jealousy were correlated, as predicted, but dependency and jealousy were not. For men, but not for women, traditionalism and jealousy were positively correlated. Dependency and traditionalism…

  17. Temperature Dependence of Laser Induced Breakdown

    DTIC Science & Technology

    1994-01-01

    consistent dependence on the temperature of the medium. The theory of the temperature dependence of LIB and experimental observations for all pulse...durations and their implications for retinal damage are discussed. Laser Induced Breakdown, Temperature dependence , Threshold valve, Nanosecond, Picosecond, Femtosecond, laser pulses.

  18. Indicators of Dependency in Participatory Extension Education.

    ERIC Educational Resources Information Center

    Grudens-Schuck, Nancy; Hargrove, Tasha M.

    Participatory adult education programs assist individuals to substitute interdependent, mutually beneficial relationships for unrewarding, dependent relationships. Indicators of changes in dependency, however, are absent or imprecise in evaluations of participatory projects. A study explored facets of dependency by relating practitioners'…

  19. Generalized Categorial Grammar for Unbounded Dependencies Recovery

    ERIC Educational Resources Information Center

    Nguyen, Luan Viet

    2014-01-01

    Accurate recovery of predicate-argument dependencies is vital for interpretation tasks like information extraction and question answering, and unbounded dependencies may account for a significant portion of the dependencies in any given text. This thesis describes a Generalized Categorial Grammar (GCG) which, like other categorial grammars,…

  20. Generalized Categorial Grammar for Unbounded Dependencies Recovery

    ERIC Educational Resources Information Center

    Nguyen, Luan Viet

    2014-01-01

    Accurate recovery of predicate-argument dependencies is vital for interpretation tasks like information extraction and question answering, and unbounded dependencies may account for a significant portion of the dependencies in any given text. This thesis describes a Generalized Categorial Grammar (GCG) which, like other categorial grammars,…

  1. Minimization of Dependency Length in Written English

    ERIC Educational Resources Information Center

    Temperley, David

    2007-01-01

    Gibson's Dependency Locality Theory (DLT) [Gibson, E. 1998. "Linguistic complexity: locality of syntactic dependencies." "Cognition," 68, 1-76; Gibson, E. 2000. "The dependency locality theory: A distance-based theory of linguistic complexity." In A. Marantz, Y. Miyashita, & W. O'Neil (Eds.), "Image,…

  2. Minimization of Dependency Length in Written English

    ERIC Educational Resources Information Center

    Temperley, David

    2007-01-01

    Gibson's Dependency Locality Theory (DLT) [Gibson, E. 1998. "Linguistic complexity: locality of syntactic dependencies." "Cognition," 68, 1-76; Gibson, E. 2000. "The dependency locality theory: A distance-based theory of linguistic complexity." In A. Marantz, Y. Miyashita, & W. O'Neil (Eds.), "Image,…

  3. Comparison of the pharmacokinetics between L-BPA and L-FBPA using the same administration dose and protocol: a validation study for the theranostic approach using [(18)F]-L-FBPA positron emission tomography in boron neutron capture therapy.

    PubMed

    Watanabe, Tsubasa; Hattori, Yoshihide; Ohta, Youichiro; Ishimura, Miki; Nakagawa, Yosuke; Sanada, Yu; Tanaka, Hiroki; Fukutani, Satoshi; Masunaga, Shin-Ichiro; Hiraoka, Masahiro; Ono, Koji; Suzuki, Minoru; Kirihata, Mitsunori

    2016-11-08

    Boron neutron capture therapy (BNCT) is a cellular-level particle radiation therapy that combines the selective delivery of boron compounds to tumour tissue with neutron irradiation. L-p-Boronophenylalanine (L-BPA) is a boron compound now widely used in clinical situations. Determination of the boron distribution is required for successful BNCT prior to neutron irradiation. Thus, positron emission tomography with [(18)F]-L-FBPA, an (18)F-labelled radiopharmaceutical analogue of L-BPA, was developed. However, several differences between L-BPA and [(18)F]-L-FBPA have been highlighted, including the different injection doses and administration protocols. The purpose of this study was to clarify the equivalence between L-BPA and [(19)F]-L-FBPA as alternatives to [(18)F]-L-FBPA. SCC-VII was subcutaneously inoculated into the legs of C3H/He mice. The same dose of L-BPA or [(19)F]-L-FBPA was subcutaneously injected. The time courses of the boron concentrations in blood, tumour tissue, and normal tissue were compared between the groups. Next, we administered the therapeutic dose of L-BPA or the same dose of [(19)F]-L-FBPA by continuous infusion and compared the effects of the administration protocol on boron accumulation in tissues. There were no differences between L-BPA and [(19)F]-L-FBPA in the transition of boron concentrations in blood, tumour tissue, and normal tissue using the same administration protocol. However, the normal tissue to blood ratio of the boron concentrations in the continuous-infusion group was lower than that in the subcutaneous injection group. No difference was noted in the time course of the boron concentrations in tumour tissue and normal tissues between L-BPA and [(19)F]-L-FBPA. However, the administration protocol had effects on the normal tissue to blood ratio of the boron concentration. In estimating the BNCT dose in normal tissue by positron emission tomography (PET), we should consider the possible overestimation of the normal tissue to

  4. Motivational and psychological correlates of bodybuilding dependence

    PubMed Central

    EMINI, NEIM N.; BOND, MALCOLM J.

    2014-01-01

    Abstract Background and aims: Exercise may become physically and psychologically maladaptive if taken to extremes. One example is the dependence reported by some individuals who engage in weight training. The current study explored potential psychological, motivational, emotional and behavioural concomitants of bodybuilding dependence, with a particular focus on motives for weight training. Using a path analysis paradigm, putative causal models sought to explain associations among key study variables. Methods: A convenience sample of 101 men aged between 18 and 67 years was assembled from gymnasia in Adelaide, South Australia. Active weight trainers voluntarily completed a questionnaire that included measures of bodybuilding dependence (social dependency, training dependency, and mastery), anger, hostility and aggression, stress and motivations for weight training. Results: Three motives for weight training were identified: mood control, physique anxiety and personal challenge. Of these, personal challenge and mood control were the most directly salient to dependence. Social dependency was particularly relevant to personal challenge, whereas training dependency was associated with both personal challenge and mood control. Mastery demonstrated a direct link with physique anxiety, thus reflecting a unique component of exercise dependence. Conclusions: While it was not possible to determine causality with the available data, the joint roles of variables that influence, or are influenced by, bodybuilding dependence are identified. Results highlight unique motivations for bodybuilding and suggest that dependence could be a result of, and way of coping with, stress manifesting as aggression. A potential framework for future research is provided through the demonstration of plausible causal linkages among these variables. PMID:25317342

  5. Motivational and psychological correlates of bodybuilding dependence.

    PubMed

    Emini, Neim N; Bond, Malcolm J

    2014-09-01

    Exercise may become physically and psychologically maladaptive if taken to extremes. One example is the dependence reported by some individuals who engage in weight training. The current study explored potential psychological, motivational, emotional and behavioural concomitants of bodybuilding dependence, with a particular focus on motives for weight training. Using a path analysis paradigm, putative causal models sought to explain associations among key study variables. A convenience sample of 101 men aged between 18 and 67 years was assembled from gymnasia in Adelaide, South Australia. Active weight trainers voluntarily completed a questionnaire that included measures of bodybuilding dependence (social dependency, training dependency, and mastery), anger, hostility and aggression, stress and motivations for weight training. Three motives for weight training were identified: mood control, physique anxiety and personal challenge. Of these, personal challenge and mood control were the most directly salient to dependence. Social dependency was particularly relevant to personal challenge, whereas training dependency was associated with both personal challenge and mood control. Mastery demonstrated a direct link with physique anxiety, thus reflecting a unique component of exercise dependence. While it was not possible to determine causality with the available data, the joint roles of variables that influence, or are influenced by, bodybuilding dependence are identified. RESULTS highlight unique motivations for bodybuilding and suggest that dependence could be a result of, and way of coping with, stress manifesting as aggression. A potential framework for future research is provided through the demonstration of plausible causal linkages among these variables.

  6. Adult Patients' Experiences of Nursing Care Dependence.

    PubMed

    Piredda, Michela; Matarese, Maria; Mastroianni, Chiara; D'Angelo, Daniela; Hammer, Marilyn J; De Marinis, Maria Grazia

    2015-09-01

    Care dependence can be associated with suffering and humiliation. Nurses' awareness of patients' perception of care dependence is crucial to enable them in helping the dependent persons. This study aimed to describe adult patients' experience of nursing care dependence. A metasynthesis was conducted to integrate qualitative findings from 18 studies published through December 2014 on adult patients' experiences of care dependency. Procedures included the Johanna Briggs Institute approach for data extraction, quality appraisal, and integration of findings. The experience of dependence revealed the concept of the embodied person, particularly in relation to care of the physical body. The relationship between the individual and nurses within the context of care had a major impact for dependent patients. When the care relation was perceived as positive, the experience led to the development of the person in finding new balances in life, but when it was perceived as negative, it increased patient' suffering. Care dependence is manifested mostly as bodily dependence and is consistent with its relational nature. The nurse-patient relationship is important to the dependent patients' experience. A greater understanding of patients' experiences of dependence is crucial to enable nurses in improving care and decreasing patient suffering. © 2015 Sigma Theta Tau International.

  7. Genetics of Nicotine Dependence and Pharmacotherapy

    PubMed Central

    Lessov-Schlaggar, Christina N.; Pergadia, Michele L.; Khroyan, Taline V.; Swan, Gary E.

    2008-01-01

    Nicotine dependence is substantially heritable. Several regions across the genome have been implicated in containing genes that confer liability to nicotine dependence and variation in individual genes has been associated with nicotine dependence. Smoking cessation measures are also heritable, and measured genetic variation is associated with nicotine dependence treatment efficacy. Despite significant strides in the understanding of the relative contribution of genetic and environmental factors to nicotine dependence and treatment, emergent challenges necessitate interdisciplinary coordinated effort for effective problem solving. These challenges include refinement of the nicotine dependence phenotype, better understanding of the dynamic interplay between genes and environment in nicotine dependence etiology, application and development of molecular and statistical methodology that can adequately address vast amounts of data, and continuous translational cross-talk. PMID:17888884

  8. Supporting elderly dependent people at home.

    PubMed Central

    Vetter, N. J.; Lewis, P. A.; Llewellyn, L.

    1992-01-01

    OBJECTIVE--To clarify the relation between the dependency of elderly people and the assistance they receive from others by using a detailed but simple measure of dependency. DESIGN--Secondary analysis of data from a survey of people aged 70 and over. SETTING--Two general practices in south Wales. SUBJECTS--1280 people aged 70 and over. MAIN OUTCOME MEASURES--Dependency on others to perform essential functions; detailed data on who assists with those functions. RESULTS--Increasing dependency was associated with increased use of more than one member of the family or friends and an increase in the provision of statutory services. CONCLUSION--The complexity of the relation between dependency and those who care for dependent people has previously been underestimated. The presence of providers of statutory services at the household of elderly dependent people suggests that these services can be developed further to help those caring for elderly people at home. Images FIG 1 FIG 3 PMID:1606435

  9. A Multiple Motives Approach to Tobacco Dependence: The Wisconsin Inventory of Smoking Dependence Motives (WISDM-68)

    ERIC Educational Resources Information Center

    Piper, Megan E.; Piasecki, Thomas M.; Federman, E. Belle; Bolt, Daniel M.; Smith, Stevens S.; Fiore, Michael C.; Baker, Timothy C.

    2004-01-01

    The dependence construct fills an important explanatory role in motivational accounts of smoking and relapse. Frequently used measures of dependence are either atheoretical or grounded in a unidimensional model of physical dependence. This research creates a multidimensional measure of dependence that is based on theoretically grounded motives for…

  10. Co-dependency in the workplace.

    PubMed

    Davidhizar, R; Eshleman, J

    1992-01-01

    Co-dependency has become a familiar term in recent years. No only do mental health professionals encounter the phenomenon, but with the bestseller status of Co-Dependent No More (Beattie 1987), more and more laypersons have begun to identify co-dependent individuals among family members and friends. Community health nurse managers may encounter this problem in clients as well as in other nurses. Of particular concern to the community health nurse manager is co-dependency among nurses on the staff. Co-dependency exhibited by nurses can have a negative effect on group morale and team spirit in a community health setting. This article defines co-dependency and presents guidelines for responding to it in community health nurses.

  11. Assessment of dependency, agreeableness, and their relationship.

    PubMed

    Lowe, Jennifer Ruth; Edmundson, Maryanne; Widiger, Thomas A

    2009-12-01

    Agreeableness is central to the 5-factor model conceptualization of dependency. However, 4 meta-analyses of the relationship of agreeableness with dependency have failed to identify a consistent relationship. It was the hypothesis of the current study that these findings might be due in part to an emphasis on the assessment of adaptive, rather than maladaptive, variants of agreeableness. This hypothesis was tested by using experimentally altered NEO Personality Inventory-Revised (Costa & McCrae, 1992) items that were reversed with respect to their implications for maladaptiveness. The predicted correlations were confirmed with the experimentally altered version with measures of dependent personality disorder, measures of trait dependency (including 2 measures of adaptive dependency), and measures of dependency from alternative dimensional models of personality disorder. The theoretical implications of the findings and suggestions for future research are discussed.

  12. Development Factors and Field Dependence-Independence.

    DTIC Science & Technology

    1984-11-01

    The use of field dependence -field independence measures has been suggested for both the selection and classification of naval aviators. If measures...of field dependence -field independence are predictive of pilot proficiency, the utility of the construct for selection and classification could be...moderated by the influence of intraindividual changes in field dependence -field independence (FD-FI) over time. This report reviews (1) particulars of the

  13. Temperature Dependence of Large Polaron Superconductivity.

    DTIC Science & Technology

    1995-07-18

    to explain the variation of critical temperature Tc with chemical composition and the temperature dependence of high-Tc superconductor properties is...One result of this refinement is a clearer picture of the dependence of electron hopping activation energy on crystal-field parameters. A... dependence is more typically exponential. With these improvements, precise fits to penetration depth versus temperature measurements for high-purity YBCO

  14. Dependence Graphs for Information Assurance of Systems

    DTIC Science & Technology

    2003-06-01

    in sequential programs using dependence analysis, which provides a sound basis for understanding such information flows. The goal was to develop...the design of extensions to the dependence analysis to support concurrency and asynchronous transfer of control. To improve accuracy, it was necessary...achieving results in the area of dependence -graph representations, and queries for software assurance. The results of the research are described in the appendices.

  15. Passion and dependency in online shopping activities.

    PubMed

    Wang, Chih-Chien; Yang, Hui-Wen

    2007-04-01

    This study examines the influence of harmonious passion (HP) and obsessive passion (OP) to online shopping dependency. The results show that both HP and OP might lead to online shopping dependency and online shoppers with OP are more dependent on online shopping activities. In addition, this study also found out that HP and OP could be denoted as a sequence of different intensities of passion, where HP might be a necessity of OP.

  16. Temperature-dependent susceptibility in ALON

    NASA Astrophysics Data System (ADS)

    West, Bruce J.

    2001-02-01

    Herein, we propose a stochastic model of the complex susceptibility in aluminum nitride (ALON), a polycrystalline transparent ceramic. The proposed model yields an inverse power-law dependence of the dielectric loss tangent on frequency, in remarkably close agreement with data. In addition, the phenomenological parameters are found to be strongly temperature-dependent. This temperature dependence is determined, in the theoretical model, to be a consequence of the thermodynamic properties of the molecular dipoles in the material.

  17. NON-PARAMETRIC ESTIMATION UNDER STRONG DEPENDENCE

    PubMed Central

    Zhao, Zhibiao; Zhang, Yiyun; Li, Runze

    2014-01-01

    We study non-parametric regression function estimation for models with strong dependence. Compared with short-range dependent models, long-range dependent models often result in slower convergence rates. We propose a simple differencing-sequence based non-parametric estimator that achieves the same convergence rate as if the data were independent. Simulation studies show that the proposed method has good finite sample performance. PMID:25018572

  18. NON-PARAMETRIC ESTIMATION UNDER STRONG DEPENDENCE.

    PubMed

    Zhao, Zhibiao; Zhang, Yiyun; Li, Runze

    2014-01-01

    We study non-parametric regression function estimation for models with strong dependence. Compared with short-range dependent models, long-range dependent models often result in slower convergence rates. We propose a simple differencing-sequence based non-parametric estimator that achieves the same convergence rate as if the data were independent. Simulation studies show that the proposed method has good finite sample performance.

  19. Spectral methods for time dependent problems

    NASA Technical Reports Server (NTRS)

    Tadmor, Eitan

    1990-01-01

    Spectral approximations are reviewed for time dependent problems. Some basic ingredients from the spectral Fourier and Chebyshev approximations theory are discussed. A brief survey was made of hyperbolic and parabolic time dependent problems which are dealt with by both the energy method and the related Fourier analysis. The ideas presented above are combined in the study of accuracy stability and convergence of the spectral Fourier approximation to time dependent problems.

  20. Patient Dependency Knowledge-Based Systems.

    PubMed

    Soliman, F

    1998-10-01

    The ability of Patient Dependency Systems to provide information for staffing decisions and budgetary development has been demonstrated. In addition, they have become powerful tools in modern hospital management. This growing interest in Patient Dependency Systems has renewed calls for their automation. As advances in Information Technology and in particular Knowledge-Based Engineering reach new heights, hospitals can no longer afford to ignore the potential benefits obtainable from developing and implementing Patient Dependency Knowledge-Based Systems. Experience has shown that the vast majority of decisions and rules used in the Patient Dependency method are too complex to capture in the form of a traditional programming language. Furthermore, the conventional Patient Dependency Information System automates the simple and rigid bookkeeping functions. On the other hand Knowledge-Based Systems automate complex decision making and judgmental processes and therefore are the appropriate technology for automating the Patient Dependency method. In this paper a new technique to automate Patient Dependency Systems using knowledge processing is presented. In this approach all Patient Dependency factors have been translated into a set of Decision Rules suitable for use in a Knowledge-Based System. The system is capable of providing the decision-maker with a number of scenarios and their possible outcomes. This paper also presents the development of Patient Dependency Knowledge-Based Systems, which can be used in allocating and evaluating resources and nursing staff in hospitals on the basis of patients' needs.

  1. Concentration-Dependent Carbon Diffusivity in Austenite

    NASA Astrophysics Data System (ADS)

    Gu, Xiaoting; Michal, Gary M.; Ernst, Frank; Kahn, Harold; Heuer, Arthur H.

    2014-08-01

    The diffusion coefficient of carbon in austenite depends on the local carbon concentration. This concentration dependence is particularly noticeable during low-temperature "paraequilibrium" carburization. A critical review of the extensive literature on this topic reveals that an early paper by Asimow provides an excellent description of this substantial concentration dependence. The present analysis suggests that the marked concentration dependence of carbon diffusivity is most likely due to interstitial carbon decreasing the activation energy for carbon jumps from one interstitial site to its neighbor.

  2. Incorporating spatial dependence in regional frequency analysis

    NASA Astrophysics Data System (ADS)

    Wang, Zhuo; Yan, Jun; Zhang, Xuebin

    2014-12-01

    The efficiency of regional frequency analysis (RFA) is undermined by intersite dependence, which is usually ignored in parameter estimation. We propose a spatial index flood model where marginal generalized extreme value distributions are joined by an extreme-value copula characterized by a max-stable process for the spatial dependence. The parameters are estimated with a pairwise likelihood constructed from bivariate marginal generalized extreme value distributions. The estimators of model parameters and return levels can be more efficient than those from the traditional index flood model when the max-stable process fits the intersite dependence well. Through simulation, we compared the pairwise likelihood method with an L-moment method and an independence likelihood method under various spatial dependence models and dependence levels. The pairwise likelihood method was found to be the most efficient in mean squared error if the dependence model was correctly specified. When the dependence model was misspecified within the max-stable models, the pairwise likelihood method was still competitive relative to the other two methods. When the dependence model was not a max-stable model, the pairwise likelihood method led to serious bias in estimating the shape parameter and return levels, especially when the dependence was strong. In an illustration with annual maximum precipitation data from Switzerland, the pairwise likelihood method yielded remarkable reduction in the standard errors of return level estimates in comparison to the L-moment method.

  3. Incorporating spatial dependence in regional frequency analysis.

    PubMed

    Wang, Zhuo; Yan, Jun; Zhang, Xuebin

    2014-12-01

    The efficiency of regional frequency analysis (RFA) is undermined by intersite dependence, which is usually ignored in parameter estimation. We propose a spatial index flood model where marginal generalized extreme value distributions are joined by an extreme-value copula characterized by a max-stable process for the spatial dependence. The parameters are estimated with a pairwise likelihood constructed from bivariate marginal generalized extreme value distributions. The estimators of model parameters and return levels can be more efficient than those from the traditional index flood model when the max-stable process fits the intersite dependence well. Through simulation, we compared the pairwise likelihood method with an L-moment method and an independence likelihood method under various spatial dependence models and dependence levels. The pairwise likelihood method was found to be the most efficient in mean squared error if the dependence model was correctly specified. When the dependence model was misspecified within the max-stable models, the pairwise likelihood method was still competitive relative to the other two methods. When the dependence model was not a max-stable model, the pairwise likelihood method led to serious bias in estimating the shape parameter and return levels, especially when the dependence was strong. In an illustration with annual maximum precipitation data from Switzerland, the pairwise likelihood method yielded remarkable reduction in the standard errors of return level estimates in comparison to the L-moment method.

  4. Diagnostic criteria for exercise dependence in women

    PubMed Central

    Bamber, D; Cockerill, I; Rodgers, S; Carroll, D

    2003-01-01

    Objective: To formulate diagnostic criteria for exercise dependence. Method: Fifty six adult female exercisers were interviewed about their exercise behaviour and attitudes. The eating disorders examination, a semistructured clinical interview, was used to diagnose eating disorders. Interviews were taped, transcribed verbatim, and analysed from a social constructionist perspective using QSR NUD*IST. Participants also completed the exercise dependence questionnaire. Results: Two diagnostic criteria emerged from analysis of the interview data: impaired functioning and withdrawal. Impaired functioning was manifest in four areas: psychological, social and occupational, physical, and behavioural. Impairment in at least two areas was considered necessary for diagnosis. Withdrawal was evident as either an adverse reaction to the interruption of exercise or unsuccessful attempts at exercise control. Either sufficed for diagnosis. The absence or presence of an eating disorder was used to distinguish between primary and secondary exercise dependence. Ten women met these criteria for exercise dependence. All 10 also exhibited eating disorders and, accordingly, should be regarded as showing secondary, rather than primary, exercise dependence. Exercise dependent women had significantly higher scores on the exercise dependence questionnaire than non-dependent women. Conclusion: These new diagnostic criteria should now be adopted and explored further, particularly among men and individuals with possible primary exercise dependence. PMID:14514528

  5. Warming: mechanism and latitude dependence

    NASA Astrophysics Data System (ADS)

    Barkin, Yury

    2010-05-01

    flows distribution with respect the Earth's hemispheres in first caused by eccentric position of the Earth core with respect to the mantle (displaced in present geological epoch in direction to Brasil). Of course the asymmetric distribution of heat loss is a long-term phenomenon in the geological history. But in present epoch due to drift of the core to the North we must observe some increasing of the heat flow of the Northern hemisphere and decreasing of the heat flow of the Southern hemisphere. In reality mentioned changes of heat flows are contrast (asymmetrical) and can have general tendency of increasing heat flows in both hemispheres (due to activization of relative oscillations of the core and mantle relatively polar axis). Contrast secular warming of Northern and Southern hemispheres of the Earth in present epoch. Dependence of warming from latitude. And warm flows are asymmetrically, more intensively warm is redistributed in northern hemisphere of the Earth and less intensively in a southern hemisphere. From here it follows, that the phenomenon of more intensive warming up of northern hemisphere, rather than southern in present period should be observed. Data of climatic observations (in first temperature trends for various latitude belts). More detailed analysis shows, that the phenomenon of warming in different form is shown in various latitudinal belts of the Earth. This phenomenon is more clearly shown in latitudinal belts further situated on latitude from South Pole, i.e. in high northern latitudes. Really, the trend of increase of temperature in northern hemisphere is characterized by greater rate, than a trend of temperature in a southern hemisphere. And not only trend components of temperatures increase with increasing of latitudes from southern pole to northern pole, but also amplitudes of decade fluctuations of temperature in high northern breadthes are more bigger than in southern hemisphere. Thus again it is necessary to expect a contrast and

  6. Opioid dependence during pregnancy. Effects and management.

    PubMed

    Kaltenbach, K; Berghella, V; Finnegan, L

    1998-03-01

    This article describes the complex problems associated with opioid dependence during pregnancy. Medical, obstetric, and psychosocial problems are presented. Methadone maintenance for the treatment of opioid dependence is described in this article. Specific issues of appropriate methadone dose during pregnancy, medical withdrawal, and the relationship of methadone dose and the severity of neonatal abstinence also are discussed.

  7. The Restorative Recovery School: Countering Chemical Dependency

    ERIC Educational Resources Information Center

    Riestenberg, Nancy

    2007-01-01

    In a recovery school, the students commit to working on recovery from chemical dependency and addiction while becoming successful students. Since all of the students attending the school have been in chemical dependency treatment, the safety of the environment is the first concern of students, their families and staff. Applying restorative…

  8. E. coli survival in waters: temperature dependence

    USDA-ARS?s Scientific Manuscript database

    Knowing the survival rates of water-borne Escherichia coli is important for evaluating microbial contamination and in making appropriate management decisions. E. coli survival rates are dependent on temperature; this dependency is routinely expressed using an analog of the Q10 model. This suggestion...

  9. PRESSURE DEPENDENCE OF PHONON ASSISTED INTERBAND TUNNELING,

    DTIC Science & Technology

    Since very much is known about the band structure of germanium and of its dependence on stress, one can expect to obtain detailed information about... dependence of the relative change of tunneling current with hydrostatic pressure, in Sb-doped germanium tunnel junctions at 4.2 K. This effect is re

  10. The Viscosity-Temperature-Dependence of Liquids,

    DTIC Science & Technology

    The viscosity-temperature- dependence of liquids of different types can be represented by the formula lg kinematic viscosity = A/T to the x power + B...if A has a constant value, only one viscosity measurement at one temperature is necessary for the characterization of the viscosity-temperature- dependence . Examples for each different case are given. (Author)

  11. Empirical Evaluation of Directional-Dependence Tests

    ERIC Educational Resources Information Center

    Thoemmes, Felix

    2015-01-01

    Testing of directional dependence is a method to infer causal direction that recently has attracted some attention. Previous examples by e.g. von Eye and DeShon (2012a) and extensive simulation studies by Pornprasertmanit and Little (2012) have demonstrated that under specific assumptions, directional-dependence tests can recover the true causal…

  12. Alcohol dependence in the Naval Service.

    PubMed

    Dickie, A K; Coetzee, R H

    2014-01-01

    Alcohol misuse is a significant occupational health issue in the United Kingdom Armed Forces. Dependence associated with alcohol misuse represents the severe end of the clinical and occupational consequences of sustained alcohol misuse. This article aims to explore the diagnosis, management and occupational considerations of alcohol dependence in the Naval Service environment.

  13. A Time-Dependent Anharmonic Oscillator

    NASA Astrophysics Data System (ADS)

    Contreras-Astorga, A.

    2017-05-01

    Supersymmetric Quantum Mechanics is commonly used to generate time independent Hamiltonians with a desired spectrum. This technique can be generalized to construct time dependent potentials. In this work, the harmonic oscillator and a coherent state are taken to perform a generalized SUSY transformation in order to obtain a time dependent anharmonic oscillator.

  14. Empirical Evaluation of Directional-Dependence Tests

    ERIC Educational Resources Information Center

    Thoemmes, Felix

    2015-01-01

    Testing of directional dependence is a method to infer causal direction that recently has attracted some attention. Previous examples by e.g. von Eye and DeShon (2012a) and extensive simulation studies by Pornprasertmanit and Little (2012) have demonstrated that under specific assumptions, directional-dependence tests can recover the true causal…

  15. Dependent Children and Suicide of Married Parents.

    ERIC Educational Resources Information Center

    Kozak, Conrad M.; Gibbs, James O.

    1979-01-01

    Single suicides and married suicides with dependent children were compared to similar groups in the general population. Married people with dependent children experienced the lowest average suicide rate, but had a larger mean number of children than the population as a whole. (Author)

  16. Fuzzy Functional Dependencies and Redundancy Elimination.

    ERIC Educational Resources Information Center

    Bosc, Patrick; Dubois, Didier; Prade, Henri

    1998-01-01

    For about 10 years, several proposals to deal with ill-known information in database management systems have been made, and extensions of the relational data model have been proposed. An overview of functional dependencies is provided, and the connection between fuzzy functional dependencies and database design is discussed. (AEF)

  17. The Restorative Recovery School: Countering Chemical Dependency

    ERIC Educational Resources Information Center

    Riestenberg, Nancy

    2007-01-01

    In a recovery school, the students commit to working on recovery from chemical dependency and addiction while becoming successful students. Since all of the students attending the school have been in chemical dependency treatment, the safety of the environment is the first concern of students, their families and staff. Applying restorative…

  18. [The Mayo Clinic Nicotine Dependence Center].

    PubMed

    Hurt, Richard D; Hays, Taylor J; Croghan, Ivana T

    2017-01-01

    Since 1988, this world leading center provided treatment of tobacco dependence to tens of thousands of tobacco-dependent patients, educated thousands of health professionals and has rich research activities. Its system was a model for such similar centers including those in the Czech Republic.

  19. Chemical Dependence and Clinical Depression in Pregnancy.

    ERIC Educational Resources Information Center

    Burns, Kayreen; And Others

    1985-01-01

    Assessed the extent and depth of depression in 54 chemically dependent pregnant women, divided into three groups by age. Results indicated that the older chemically dependent women scored significantly higher on the depression index than did either of the two younger groups, while the teenagers obtained a mean score comparable to that of the…

  20. Escherichia coli survival in waters: Temperature dependence

    EPA Science Inventory

    Knowing the survival rates of water-borne Escherichia coli is important in evaluating microbial contamination and making appropriate management decisions. E. coli survival rates are dependent on temperature, a dependency that is routinely expressed using an analogue of the Q10 mo...

  1. Psychological Distress in Abused, Chemically Dependent Adolescents.

    ERIC Educational Resources Information Center

    Cavaiola, Alan A.; Schiff, Matthew M.

    2000-01-01

    Study assessed whether differences exist in levels of psychological distress in abused, chemically dependent adolescents when compared to non-abused counterparts, and non-abused, non-chemically dependent adolescents. Results indicated abused adolescents demonstrated more severe levels of distress, and earlier onset of alcohol and drug use.…

  2. Assessment of Dependency, Agreeableness, and Their Relationship

    ERIC Educational Resources Information Center

    Lowe, Jennifer Ruth; Edmundson, Maryanne; Widiger, Thomas A.

    2009-01-01

    Agreeableness is central to the 5-factor model conceptualization of dependency. However, 4 meta-analyses of the relationship of agreeableness with dependency have failed to identify a consistent relationship. It was the hypothesis of the current study that these findings might be due in part to an emphasis on the assessment of adaptive, rather…

  3. Chemical Dependency Regional Needs Assessment: Northeastern Minnesota.

    ERIC Educational Resources Information Center

    Stone, Marylee

    The Minnesota Model of Chemical Dependency Treatment, which evolved from a combination of the grassroots Alcoholics Anonymous movement and the State Mental Health Services in the 1960s has made Minnesota an international leader in chemical dependency treatment efforts. Northeastern Minnesota has shared this reputation with the state. In spite of…

  4. Assessment of Dependency, Agreeableness, and Their Relationship

    ERIC Educational Resources Information Center

    Lowe, Jennifer Ruth; Edmundson, Maryanne; Widiger, Thomas A.

    2009-01-01

    Agreeableness is central to the 5-factor model conceptualization of dependency. However, 4 meta-analyses of the relationship of agreeableness with dependency have failed to identify a consistent relationship. It was the hypothesis of the current study that these findings might be due in part to an emphasis on the assessment of adaptive, rather…

  5. Determining Directional Dependency in Causal Associations

    ERIC Educational Resources Information Center

    Pornprasertmanit, Sunthud; Little, Todd D.

    2012-01-01

    Directional dependency is a method to determine the likely causal direction of effect between two variables. This article aims to critique and improve upon the use of directional dependency as a technique to infer causal associations. We comment on several issues raised by von Eye and DeShon (2012), including: encouraging the use of the signs of…

  6. 5 CFR 843.405 - Dependency.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... EMPLOYEES RETIREMENT SYSTEM-DEATH BENEFITS AND EMPLOYEE REFUNDS Child Annuities § 843.405 Dependency. To be eligible for survivor annuity benefits, a child must have been dependent on the employee or retiree at the time of the employee's or retiree's death....

  7. 5 CFR 843.405 - Dependency.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... EMPLOYEES RETIREMENT SYSTEM-DEATH BENEFITS AND EMPLOYEE REFUNDS Child Annuities § 843.405 Dependency. To be eligible for survivor annuity benefits, a child must have been dependent on the employee or retiree at the time of the employee's or retiree's death....

  8. 5 CFR 843.405 - Dependency.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... EMPLOYEES RETIREMENT SYSTEM-DEATH BENEFITS AND EMPLOYEE REFUNDS Child Annuities § 843.405 Dependency. To be eligible for survivor annuity benefits, a child must have been dependent on the employee or retiree at the time of the employee's or retiree's death....

  9. 5 CFR 843.405 - Dependency.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... EMPLOYEES RETIREMENT SYSTEM-DEATH BENEFITS AND EMPLOYEE REFUNDS Child Annuities § 843.405 Dependency. To be eligible for survivor annuity benefits, a child must have been dependent on the employee or retiree at the time of the employee's or retiree's death....

  10. 5 CFR 843.405 - Dependency.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... EMPLOYEES RETIREMENT SYSTEM-DEATH BENEFITS AND EMPLOYEE REFUNDS Child Annuities § 843.405 Dependency. To be eligible for survivor annuity benefits, a child must have been dependent on the employee or retiree at the time of the employee's or retiree's death....

  11. Bohr Hamiltonian with time-dependent potential

    NASA Astrophysics Data System (ADS)

    Naderi, L.; Hassanabadi, H.; Sobhani, H.

    2016-04-01

    In this paper, Bohr Hamiltonian has been studied with the time-dependent potential. Using the Lewis-Riesenfeld dynamical invariant method appropriate dynamical invariant for this Hamiltonian has been constructed and the exact time-dependent wave functions of such a system have been derived due to this dynamical invariant.

  12. Escherichia coli survival in waters: Temperature dependence

    EPA Science Inventory

    Knowing the survival rates of water-borne Escherichia coli is important in evaluating microbial contamination and making appropriate management decisions. E. coli survival rates are dependent on temperature, a dependency that is routinely expressed using an analogue of the Q10 mo...

  13. Quantifying Item Dependency by Fisher's Z.

    ERIC Educational Resources Information Center

    Shen, Linjun

    Three aspects of the usual approach to assessing local item dependency, Yen's "Q" (H. Huynh, H. Michaels, and S. Ferrara, 1995), deserve further investigation. Pearson correlation coefficients do not distribute normally when the coefficients are large, and thus cannot quantify the dependency well. In the second place, the accuracy of…

  14. Risk Management using Dependency Stucture Matrix

    NASA Astrophysics Data System (ADS)

    Petković, Ivan

    2011-09-01

    An efficient method based on dependency structure matrix (DSM) analysis is given for ranking risks in a complex system or process whose entities are mutually dependent. This rank is determined according to the element's values of the unique positive eigenvector which corresponds to the matrix spectral radius modeling the considered engineering system. For demonstration, the risk problem of NASA's robotic spacecraft is analyzed.

  15. Chemogenomics of pyridoxal 5'-phosphate dependent enzymes.

    PubMed

    Singh, Ratna; Spyrakis, Francesca; Cozzini, Pietro; Paiardini, Alessandro; Pascarella, Stefano; Mozzarelli, Andrea

    2013-02-01

    Pyridoxal 5'-phosphate (PLP) dependent enzymes comprise a large family that plays key roles in amino acid metabolism and are acquiring an increasing interest as drug targets. For the identification of compounds inhibiting PLP-dependent enzymes, a chemogenomics-based approach has been adopted in this work. Chemogenomics exploits the information coded in sequences and three-dimensional structures to define pharmacophore models. The analysis was carried out on a dataset of 65 high-resolution PLP-dependent enzyme structures, including representative members of four-fold types. Evolutionarily conserved residues relevant to coenzyme or substrate binding were identified on the basis of sequence-structure comparisons. A dataset was obtained containing the information on conserved residues at substrate and coenzyme binding site for each representative PLP-dependent enzyme. By linking coenzyme and substrate pharmacophores, bifunctional pharmacophores were generated that will constitute the basis for future development of small inhibitors targeting specific PLP-dependent enzymes.

  16. Dependence effects in unique signal transmission

    SciTech Connect

    Cooper, J.A.

    1988-04-01

    ''Unique Signals'' are communicated from a source to a ''strong link'' safety device in a weapon by means of one or more digital communication channels. The probability that the expected unique signal pattern could be generated accidentally (e.g., due to an abnormal environment) would be an important measure. A probabilistic assessment of this likelihood is deceptive, because it depends on characteristics of the other traffic on the communication channel. One such characteristic that is frequently neglected in analysis is dependence. This report gives a mathematical model for dependence; cites some of the ways in which dependence can increase the likelihood of inadvertent unique signal pattern generation; and suggests that communicating each unique signal ''event'' at the highest level of protocol in the communication system minimizes dependence effects. 3 refs., 4 figs.

  17. Applying supersymmetry to energy dependent potentials

    SciTech Connect

    Yekken, R.; Lassaut, M.; Lombard, R.J.

    2013-11-15

    We investigate the supersymmetry properties of energy dependent potentials in the D=1 dimensional space. We show the main aspects of supersymmetry to be preserved, namely the factorization of the Hamiltonian, the connections between eigenvalues and wave functions of the partner Hamiltonians. Two methods are proposed. The first one requires the extension of the usual rules via the concept of local equivalent potential. In this case, the superpotential becomes depending on the state. The second method, applicable when the potential depends linearly on the energy, is similar to what has been already achieved by means of the Darboux transform. -- Highlights: •Supersymmetry extended to energy dependent potentials. •Generalization of the concept of superpotential. •An alternative method used for linear E-dependence leads to the same results as Darboux transform.

  18. Invariants for time-dependent Hamiltonian systems.

    PubMed

    Struckmeier, J; Riedel, C

    2001-08-01

    An exact invariant is derived for n-degree-of-freedom Hamiltonian systems with general time-dependent potentials. The invariant is worked out in two equivalent ways. In the first approach, we define a special Ansatz for the invariant and determine its time-dependent coefficients. In the second approach, we perform a two-step canonical transformation of the initially time-dependent Hamiltonian to a time-independent one. The invariant is found to contain a function of time f(2)(t), defined as a solution of a linear third-order differential equation whose coefficients depend in general on the explicitly known configuration space trajectory that follows from the system's time evolution. It is shown that the invariant can be interpreted as the time integral of an energy balance equation. Our result is applied to a one-dimensional, time-dependent, damped non-linear oscillator, and to a three-dimensional system of Coulomb-interacting particles that are confined in a time-dependent quadratic external potential. We finally show that our results can be used to assess the accuracy of numerical simulations of time-dependent Hamiltonian systems.

  19. Time-dependent photoelectron angular distributions

    NASA Astrophysics Data System (ADS)

    Wang, Xiangyang

    1999-09-01

    I show that the angular distribution of electrons photoionized from gas phase targets by short light pulses is time-dependent, when the orbital momentum composition of the photocurrent changes with excitation energy so evolves with the time of detection. A theory of time- dependent photoionization is outlined and general formulas of time-dependent photoelectron flux and angular distribution are given. Two general propagator methods suitable to describe the time-dependent photoionization and scattering processes are developed. The photoionization process is viewed as a local excitation followed by a half scattering. The local excitation process is solved theoretically in a small region around the target core. This approach has been generalized to describe the evolution of a wavepacket in an unbound system. An asymptotic propagator theorem is discovered and used to derive analytic expressions for asymptotic propagators. The origin of the time dependence is explored by parameterizing the time delay and orbital momentum coupling in a two channel model. K-shell photoionization of N2 and CO are calculated with this time- dependent photoionization theory, implemented using a multiple scattering model. Numerical results demonstrate that the time dependence of photoelectron angular distributions is a realistic effect.

  20. Time-dependent rates of molecular evolution.

    PubMed

    Ho, Simon Y W; Lanfear, Robert; Bromham, Lindell; Phillips, Matthew J; Soubrier, Julien; Rodrigo, Allen G; Cooper, Alan

    2011-08-01

    For over half a century, it has been known that the rate of morphological evolution appears to vary with the time frame of measurement. Rates of microevolutionary change, measured between successive generations, were found to be far higher than rates of macroevolutionary change inferred from the fossil record. More recently, it has been suggested that rates of molecular evolution are also time dependent, with the estimated rate depending on the timescale of measurement. This followed surprising observations that estimates of mutation rates, obtained in studies of pedigrees and laboratory mutation-accumulation lines, exceeded long-term substitution rates by an order of magnitude or more. Although a range of studies have provided evidence for such a pattern, the hypothesis remains relatively contentious. Furthermore, there is ongoing discussion about the factors that can cause molecular rate estimates to be dependent on time. Here we present an overview of our current understanding of time-dependent rates. We provide a summary of the evidence for time-dependent rates in animals, bacteria and viruses. We review the various biological and methodological factors that can cause rates to be time dependent, including the effects of natural selection, calibration errors, model misspecification and other artefacts. We also describe the challenges in calibrating estimates of molecular rates, particularly on the intermediate timescales that are critical for an accurate characterization of time-dependent rates. This has important consequences for the use of molecular-clock methods to estimate timescales of recent evolutionary events. © 2011 Blackwell Publishing Ltd.

  1. Stability on Time-Dependent Domains

    NASA Astrophysics Data System (ADS)

    Knobloch, E.; Krechetnikov, R.

    2014-06-01

    We explore the key differences in the stability picture between extended systems on time-fixed and time-dependent spatial domains. As a paradigm, we take the complex Swift-Hohenberg equation, which is the simplest nonlinear model with a finite critical wavenumber, and use it to study dynamic pattern formation and evolution on time-dependent spatial domains in translationally invariant systems, i.e., when dilution effects are absent. In particular, we discuss the effects of a time-dependent domain on the stability of spatially homogeneous and spatially periodic base states, and explore its effects on the Eckhaus instability of periodic states. New equations describing the nonlinear evolution of the pattern wavenumber on time-dependent domains are derived, and the results compared with those on fixed domains. Pattern coarsening on time-dependent domains is contrasted with that on fixed domains with the help of the Cahn-Hilliard equation extended here to time-dependent domains. Parallel results for the evolution of the Benjamin-Feir instability on time-dependent domains are also given.

  2. Bimodal lipid substrate dependence of phosphatidylinositol kinase.

    PubMed

    Ganong, B R

    1990-07-24

    Phosphatidylinositol (PI) kinase activity was solubilized from rat liver microsomes and partially purified by chromatography on hydroxyapatite and Reactive Green 19-Superose. Examination of the ATP dependence using a mixed micellar assay gave a Km of 120 microM. The dependence of reaction rate on PI was more complicated. PI kinase bound a large amount of Triton X-100, and as expected for a micelle-associated enzyme utilizing a micelle-associated lipid substrate, the reaction rate was dependent on the micellar mole fraction, PI/(PI + Triton X-100), with a Km of 0.02 (unitless). Activity showed an additional dependence on bulk PI concentration at high micelle dilution. These results demonstrated two kinetically distinguishable steps leading to formation of a productive PI/enzyme(/ATP) complex. The rate of the first step, which probably represents exchange of PI from the bulk micellar pool into enzyme-containing micelles, depends on bulk PI concentration. The rate of the second step, association of PI with enzyme within a single micelle, depends on the micellar mole fraction of PI. Depression of the apparent Vmax at low ionic strength suggested that electrostatic repulsion between negatively charged PI/Triton X-100 mixed micelles inhibits PI exchange, consistent with a model in which intermicellar PI exchange depends on micellar collisions.

  3. Implicit and self-attributed dependency needs in dependent and histrionic personality disorders.

    PubMed

    Bornstein, R F

    1998-08-01

    Theorists speculate that dependent personality disorder (DPD) and histrionic personality disorder (HPD) are both associated with high levels of implicit (i.e., unconscious) dependency needs but speculate that only DPD is associated with high levels of self-attributed (i.e., conscious) dependency needs. To test this hypothesis, 444 undergraduates (236 women and 208 men) completed the Personality Diagnostic Questionnaire-Revised (PDQ-R), along with widely used measures of implicit dependency needs (the Rorschach Oral Dependency Scale; ROD), and self-attributed dependency needs (the Interpersonal Dependency Inventory; IDI). Correlational analyses and comparisons of IDI and ROD scores in participants scoring above and below the PDQ-R DPD and HPD thresholds supported theorists' speculations regarding implicit and self-attributed dependency needs in DPD and HPD. Implications of these results are discussed, and suggestions for future studies are offered.

  4. Frequency Dependence of APATS Antenna Gain

    DTIC Science & Technology

    1982-03-01

    ESD-TR-82-120 HTR-8354 3FREQUENCY DEPENDENCE OF APATS ANTENNA GAIN 0 By G. A. ROBERTSHAW MARCH 1982 Prepared for DEPUTY FOR SURVEILLANCE AND CONTROL...FREQUENCY DEPENDENCE OF APATS ANTENNA GAIN 6. PERFORMING ORG. REPORT NUMBER MTR-8354 7. AUTHOR(*) S. CONTRACT OR GRANT NUMBER(s) G. A. ROBERTSHAW F19628-81-C...employed, each channel will lose 1.76 dB of gain. * E.g., if "a" is aperture length in array azimuth plane, frequency dependence begins for 0 > srFl

  5. Birefringence in time-dependent moving media

    NASA Astrophysics Data System (ADS)

    Lin, Shirong; Zhang, Ruoyang; Zhai, Yanwang; Wei, Jianye; Zhao, Qing

    2016-08-01

    Electromagnetic wave propagation in one- and two-dimensional time-dependent moving media is investigated in this paper. We identify another origin of linear birefringence caused by the component of the flow perpendicular to the wave vector. Previously, birefringence is induced by applying external electric and magnetic fields to non-crystalline material. Here it is shown that the time-varying velocity field also contributes to such a phenomenon. Our results indicate that the parallel component, time-dependent or not, will not yield birefringence. Furthermore, the time-dependent flow also results in a frequency shift. One-dimensional simulation is conducted to demonstrate these effects.

  6. Field dependency, brain asymmetry and psychophysiological differences.

    PubMed

    Silverman, A J

    1979-01-01

    Field dependent individuals differ psychologically from field independent subjects. They use more primitive defense mechanisms, and are more responsive to social forces around them than field independent subjects. Psychophysiological differences exist between these groups which will be reviewed. Obesity and alcoholism are also related to field dependency, as well as other psychosomatic disorders. Our series of experiments show that field dependent subjects are less left cerebrally dominant, and show most elements (in subclinical form) of a left cerebral lobe (Gerstmann's) syndrome. Implications for psychosomatic medicine are noted in the psychophysiological differences seen.

  7. Alcohol dependency prevention and early intervention.

    PubMed Central

    Nathan, P E

    1988-01-01

    Current data on efforts to prevent alcoholism indicate that we are better able to prevent some of the consequences of alcohol misuse, such as alcohol-related car crashes and fetal alcohol syndrome, than chronic alcohol dependence itself. A review of data on outcomes of treatment for long-term alcohol dependence indicates that 9 of 10 alcohol dependent persons receive no treatment for the disorder in any given year. When treatment is provided for long-term alcohol dependent persons, it has only slightly positive results. As a result, many clinicians and researchers have concluded that rather than exclusive preoccupation with long-term alcoholics, early intervention with persons who are just beginning to abuse alcohol may be a more effective use of resources. PMID:3141965

  8. ALGEBRAIC DEPENDENCE THEOREMS ON COMPLEX PSEUDOCONCAVE SPACES

    DTIC Science & Technology

    The notion of pseudoconcave space is introduced and classical theorems on algebraic dependence of meromorphic functions are extended for this new class of spaces and for sections in a coherent sheaf. (Author)

  9. Work Disability Benefits? Depends on the Doc

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_163275.html Work Disability Benefits? Depends on the Doc International study ... give widely varying opinions about whether claimants for work disability benefits should get those benefits, researchers report. ...

  10. Codependency: a disorder separate from chemical dependency.

    PubMed

    O'Brien, P E; Gaborit, M

    1992-01-01

    This study examined the relationship between codependency (an excessive preoccupation with the lives, feelings, and problems of others), chemical dependency of a significant other, and depression. The Significant Others' Drug Use Survey (SODS) determined whether the subject was in a relationship with a significant other at risk of being chemically dependent. Beck's Depression Inventory (BDI) was used to assess depression. Two hypotheses were tested: first, that codependency exists independently of chemical dependency and, second, that codependent people tend to be more depressed than non-codependents. Results supported the first hypothesis, but not the second. A significant correlation between depression and having a significant other likely to be chemically dependent was observed. The usefulness of the concept of codependency is discussed with proposals for subsequent research.

  11. Extracting Dependence Relations from Unstructured Medical Text.

    PubMed

    Jochim, Charles; Lassoued, Yassine; Sacaleanu, Bogdan; Deleris, Léa A

    2015-01-01

    Dependence relations among disease and risk factors are a key ingredient in risk modeling and decision support models. Currently such information is either provided by experts (costly and time consuming) or extracted from data (if available). The published medical literature represents a promising source of such knowledge; however its manual processing is practically infeasible. While a number of solutions have been introduced to add structure to biomedical literature, none adequately recover dependence relations. The objective of our research is to build such an automatic dependence extraction solution, based on a sequence of natural language processing steps, which take as input a set of MEDLINE abstracts and provide as output a list of structured dependence statements. This paper presents a hybrid pipeline approach, a combination of rule-based and machine learning algorithms. We found that this approach outperforms a strictly rule-based approach.

  12. Topic 5: Time-Dependent Behavior

    SciTech Connect

    Pfeiffer, P.A.; Tanabe, Tada-aki

    1991-12-31

    This chapter is a report of the material presented at the International Workshop on Finite Element Analysis of Reinforced Concrete, Session 4 -- Time Dependent Behavior, held at Columbia University, New York on June 3--6, 1991. Dr. P.A. Pfeiffer presented recent developments in time-dependent behavior of concrete and Professor T. Tanabe presented a review of research in Japan on time-dependent behavior of concrete. The chapter discusses the recent research of time-dependent behavior of concrete in the past few years in both the USA-European and Japanese communities. The author appreciates the valuable information provided by Zdenek P. Bazant in preparing the USA-European Research section.

  13. Field Independence-Dependence and Verbal Restructuring.

    ERIC Educational Resources Information Center

    Noble, Julie P.; Frank, Bernard M.

    1985-01-01

    Using 80 female undergraduate students, this study investigated the hypothesis that field-independent individuals are more efficient in verbal restructuring tasks than field-dependent individuals. Results of an analysis did not support the hypothesis. (Author/LMO)

  14. Free Beauty, Dependent Beauty, and Art.

    ERIC Educational Resources Information Center

    Stecker, Robert

    1987-01-01

    Explains the difference between free and dependent beauty. States that these distinctions, formed by Immanuel Kant, have important implications for aesthetic education. Concludes with a defense of Kant's aesthetics. (JDH)

  15. POME-copula for hydrological dependence analysis

    NASA Astrophysics Data System (ADS)

    Liu, D.; Wang, D.; Wang, L.; Chen, Y.; Chen, X.; Gu, S.

    2015-05-01

    Hydrological multivariate analysis has been widely studied using copula-based modelling, in which marginal distribution inference is one of the key issues. The main object of this study is to discuss the applicability of the principle of maximum entropy (POME) in marginal distribution inference, thus to develop a POME-copula framework to analyse the dependence of hydrological variables. Marginal distributions are derived with the POME approach before bivariate copulas constructed with corresponding parameters estimated by the dependence of the derived margins. The proposed POME-copula has been employed in hydrological dependence analyses, with the annual maximum streamflow and water level collected from the Yangtze River, and the monthly streamflow from the Yellow River. Results show that the POME-copula method performs well in capturing dependence patterns of various hydrological variables.

  16. Free Beauty, Dependent Beauty, and Art.

    ERIC Educational Resources Information Center

    Stecker, Robert

    1987-01-01

    Explains the difference between free and dependent beauty. States that these distinctions, formed by Immanuel Kant, have important implications for aesthetic education. Concludes with a defense of Kant's aesthetics. (JDH)

  17. EDTA-dependent pseudothrombocytopenia in a child.

    PubMed

    Akbayram, Sinan; Dogan, Murat; Akgun, Cihangir; Caksen, Hüseyin; Oner, Ahmet Faik

    2011-10-01

    Ethylenediaminetetraacetic acid (EDTA)-dependent pseudothrombocytopenia (PTCP) is the phenomenon of a spurious low platelet count due to antiplatelet antibodies that cause platelet clumping in blood anticoagulated with EDTA. The aggregation of platelets in EDTA-dependent PTCP is usually prevented by other anticoagulants, such as sodium citrate or heparin. EDTA-dependent PTCP has never been associated with hemorrhagic diathesis or platelet dysfunction. In this article, a 10-year-old boy with EDTA- and heparin-dependent PTCP is presented because of rare presentation. We report that EDTA and heparin can induce platelet clumping, and thus spuriously low platelet counts. However, aggregation of platelets was not detected in blood samples with sodium citrate, and platelet count was normal.

  18. Temperature dependence of nucleation in Yukawa fluids

    NASA Astrophysics Data System (ADS)

    Li, J.-S.; Wilemski, G.

    2002-03-01

    We have studied the temperature dependence of gas-liquid nucleation in Yukawa fluids with gradient theory (GT) and density functional theory (DFT). Each of these nonclassical theories exhibits a weaker (i.e. better) temperature dependence than classical nucleation theory. At a given temperature, the difference between GT and DFT for the reversible work to form a critical nucleus gets smaller with increasing superaturation. For the temperature dependence, the reversible work for GT is very close to that for DFT at high temperatures. The difference between the two theories increases with decreasing temperature and supersaturation. Thus, in contrast to the behavior of a Peng-Robinson fluid, we find that GT can improve the temperature dependence over that of classical nucleation theory, although not always to the same degree as DFT.

  19. ALCHEMIC: Advanced time-dependent chemical kinetics

    NASA Astrophysics Data System (ADS)

    Semenov, Dmitry A.

    2017-08-01

    ALCHEMIC solves chemical kinetics problems, including gas-grain interactions, surface reactions, deuterium fractionization, and transport phenomena and can model the time-dependent chemical evolution of molecular clouds, hot cores, corinos, and protoplanetary disks.

  20. Emotional awareness in substance-dependent patients.

    PubMed

    Carton, Solange; Bayard, Sophie; Paget, Virginie; Jouanne, Céline; Varescon, Isabelle; Edel, Yves; Detilleux, Michel

    2010-06-01

    We explored emotional awareness in substance-dependent patients and its relationships to self-reported alexithymia. Sixty-four outpatients with drug dependence or alcohol dependence were evaluated before the beginning of treatment with the Hamilton Depressive Scale and the Covi Anxiety Scale, and they completed the Toronto Alexithymia Scale (TAS-20) and the Levels of Emotional Awareness Scale (LEAS). Subjects exhibited low levels of emotional awareness and TAS-20 scores were high. Both measures were not related to depressive and anxious symptomatology. This research is the first to provide LEAS results with substance-dependent patients and highlights their deficits in emotions' differentiation and complexity. The lack of a relationship between LEAS and TAS-20 is discussed from the methodological and theoretical points of view. (c) 2010 Wiley Periodicals, Inc.

  1. Theoretical temperature dependence of solar cell parameters

    NASA Technical Reports Server (NTRS)

    Fan, John C. C.

    1986-01-01

    A simple formulation has been derived for the temperature dependence of cell parameters for any solar cell material. Detailed calculations have been performed for high-quality monocrystalline GaAs, Si and Ge cells. Preliminary experimental data for GaAs and Si cells are close to the calculated values. In general, the higher the energy gap of a material, the small is the temperature dependence of its solar cell parameters.

  2. Linezolid Dependence in Staphylococcus epidermidis Bloodstream Isolates

    PubMed Central

    Ntokou, Eleni; Zarkotou, Olympia; Ranellou, Kyriaki; Themeli-Digalaki, Katerina; Stathopoulos, Constantinos; Tsakris, Athanassios

    2013-01-01

    We document linezolid dependence among 5 highly linezolid-resistant (LRSE) Staphylococcus epidermidis bloodstream isolates that grew substantially faster at 32 µg/mL linezolid presence. These isolates carried the mutations T2504A and C2534T in multiple 23S rRNA copies and 2 mutations leading to relevant amino acid substitutions in L3 protein. Linezolid dependence could account for increasing LRSE emergence. PMID:23260390

  3. Mephentermine dependence with psychosis. A case report.

    PubMed

    Uday, G J; Josh, U G; Bhat, S M

    1988-01-01

    Dependence on mephentermine, a widely used sympathomimetic pressor agent, is so far unreported, although misuse of inhalers is recognised. A case of mephentermine dependence associated with chronic psychosis is reported here. Psychosis initially surfaced with chronic dexamphetamine abuse, but was sustained for 3 years by mephentermine. After a period of remission lasting for 4 years, the patient again developed psychosis on restarting abuse of mephentermine, which lasted for 5 years.

  4. Dependability analysis of WRT54GL router

    NASA Astrophysics Data System (ADS)

    Gawkowski, Piotr; DzieŻyc, Marcin

    2016-09-01

    The paper presents the methodology, techniques and achieved results of dependability analysis of popular WRT54GL router using complex Software Implemented Fault Injection (SWIFI) system. Several problems and their solutions are discussed and presented, for instance, the SWIFI in embedded system, high controllability over the injected faults and observability of their effects, and the automation of the experiments. They are presented on the background of the achieved dependability results.

  5. Density dependence of nuclear symmetry energy

    NASA Astrophysics Data System (ADS)

    Behera, B.; Routray, T. R.; Tripathy, S. K.

    2016-10-01

    High density behavior of nuclear symmetry energy is studied on the basis of the stiffest density dependence of asymmetric contribution to energy per nucleon in charge neutral n + p + e + μ matter under beta equilibrium. The density dependence of nuclear symmetry energy obtained in this way is neither very stiff nor soft at high densities and is found to be in conformity with recent observations of neutron stars.

  6. [Prevalence and Therapy of Crystal Methamphetamine Dependence].

    PubMed

    Soyka, Michael; Koller, Gabi; Proebstl, Lisa; Kamp, Felicia; Franke, Andreas; Schmidt, Peggy; Baumgärtner, Gerd; Schacht-Jablonowsky, Maik; Sievert, Annegret; Straif, Maximilian; Hamdorf, Willem

    2017-02-01

    Following a short overview on the epidemiology and clinical correlates of amphetamine abuse and dependence, with special emphasis on metamphetamine ("crystal"), current treatment concepts and recent results of therapy research are discussed. The efficacy of two inpatient treatment models for methamphetamine dependence are currently studied in a study funded by the German Ministry of health. The study concept is given and possible implications are discussed. © Georg Thieme Verlag KG Stuttgart · New York.

  7. Liquid-filled ionization chamber temperature dependence

    NASA Astrophysics Data System (ADS)

    Franco, L.; Gómez, F.; Iglesias, A.; Pardo, J.; Pazos, A.; Pena, J.; Zapata, M.

    2006-05-01

    Temperature and pressure corrections of the read-out signal of ionization chambers have a crucial importance in order to perform high-precision absolute dose measurements. In the present work the temperature and pressure dependences of a sealed liquid isooctane filled ionization chamber (previously developed by the authors) for radiotherapy applications have been studied. We have analyzed the thermal response of the liquid ionization chamber in a ˜20C interval around room temperature. The temperature dependence of the signal can be considered linear, with a slope that depends on the chamber collection electric field. For example, a relative signal slope of 0.27×10-2 K-1 for an operation electric field of 1.67×106 V m-1 has been measured in our detector. On the other hand, ambient pressure dependence has been found negligible, as expected for liquid-filled chambers. The thermal dependence of the liquid ionization chamber signal can be parametrized within the Onsager theory on initial recombination. Considering that changes with temperature of the detector response are due to variations in the free ion yield, a parametrization of this dependence has been obtained. There is a good agreement between the experimental data and the theoretical model from the Onsager framework.

  8. Experimental analysis of computer system dependability

    NASA Technical Reports Server (NTRS)

    Iyer, Ravishankar, K.; Tang, Dong

    1993-01-01

    This paper reviews an area which has evolved over the past 15 years: experimental analysis of computer system dependability. Methodologies and advances are discussed for three basic approaches used in the area: simulated fault injection, physical fault injection, and measurement-based analysis. The three approaches are suited, respectively, to dependability evaluation in the three phases of a system's life: design phase, prototype phase, and operational phase. Before the discussion of these phases, several statistical techniques used in the area are introduced. For each phase, a classification of research methods or study topics is outlined, followed by discussion of these methods or topics as well as representative studies. The statistical techniques introduced include the estimation of parameters and confidence intervals, probability distribution characterization, and several multivariate analysis methods. Importance sampling, a statistical technique used to accelerate Monte Carlo simulation, is also introduced. The discussion of simulated fault injection covers electrical-level, logic-level, and function-level fault injection methods as well as representative simulation environments such as FOCUS and DEPEND. The discussion of physical fault injection covers hardware, software, and radiation fault injection methods as well as several software and hybrid tools including FIAT, FERARI, HYBRID, and FINE. The discussion of measurement-based analysis covers measurement and data processing techniques, basic error characterization, dependency analysis, Markov reward modeling, software-dependability, and fault diagnosis. The discussion involves several important issues studies in the area, including fault models, fast simulation techniques, workload/failure dependency, correlated failures, and software fault tolerance.

  9. Affective Dependence and Aggression: An Exploratory Study

    PubMed Central

    Petruccelli, Filippo; Diotaiuti, Pierluigi; Verrastro, Valeria; Petruccelli, Irene; Federico, Roberta; Martinotti, Giovanni; Fossati, Andrea; Di Giannantonio, Massimo; Janiri, Luigi

    2014-01-01

    Introduction. Emotionally dependent subjects may engage in controlling, restrictive, and aggressive behaviours, which limit their partner's autonomy. The underlying causes of such behaviours are not solely based on levels of aggression, but act as a mean of maintaining the subject's own sense of self-worth, identity, and general functioning. Objective. The aim of the paper is to explore the correlation between affective dependency and reactive/proactive aggression and to evaluate individual differences as predisposing factors for aggressive behaviour and emotional dependency. Methods. The Spouse-Specific Dependency Scale (SSDS) and the Reactive Proactive Questionnaire (RPQ) were administered to a sample of 3375 subjects. Results. In the whole sample, a positive correlation between emotional dependency and proactive aggression was identified. Differences with regard to sex, age group, and geographical distribution were evidenced for the scores of the different scales. Conclusion. A fundamental distinction between reactive and proactive aggression was observed, anchoring proactive aggression more strictly to emotional dependency. Sociocultural and demographical variables, together with the previous structuring of attachment styles, help to determine the scope, frequency, and intensity of the demands made to the partner, as well as to feed the fears of loss, abandonment, or betrayal. PMID:25054147

  10. Use of drugs with dependence liability

    PubMed Central

    Jacob, Moire S.; Sellers, Edward M.

    1979-01-01

    The term addictive as used by the popular press frequently confuses the more precise concepts of acute and chronic tolerance, physical dependence and withdrawal, and psychologic dependence. Serious physical dependence on psychoactive drugs is rare and is easily managed. In contrast, psychologic dependence, the most important reason for persistent drug use, is much more common and is difficult to treat. Some tactics are available — for example, confrontation and discussion with the patient about how a drug is not going to be effective over long periods. Treating the symptom of a complex problem should, of course, not be expected to solve the problem. The most important tactic is to prescribe dependence-associated drugs only when clearly indicated, when the problem is responsive to drug therapy and for the shortest period necessary, without the option for renewing the prescription. Many problems related to drug use long after the period of expected benefit is past can be avoided by far more restrictive drug prescribing. Barbiturates and nonbarbiturate sedative hypnotics (e.g., ethchlorvynol, glutethimide, meprobamate, methaqualone and methyprylon) should not be prescribed for insomnia, acute reactive anxiety, chronic anxiety neurosis or depressive illnesses, since the safer and equally effective benzodiazepines, which are less associated with dependence, are available. PMID:42479

  11. Activity dependent CAM cleavage and neurotransmission

    PubMed Central

    Conant, Katherine; Allen, Megan; Lim, Seung T.

    2015-01-01

    Spatially localized proteolysis represents an elegant means by which neuronal activity dependent changes in synaptic structure, and thus experience dependent learning and memory, can be achieved. In vitro and in vivo studies suggest that matrix metalloproteinase and adamalysin activity is concentrated at the cell surface, and emerging evidence suggests that increased peri-synaptic expression, release and/or activation of these proteinases occurs with enhanced excitatory neurotransmission. Synaptically expressed cell adhesion molecules (CAMs) could therefore represent important targets for neuronal activity-dependent proteolysis. Several CAM subtypes are expressed at the synapse, and their cleavage can influence the efficacy of synaptic transmission through a variety of non-mutually exclusive mechanisms. In the following review, we discuss mechanisms that regulate neuronal activity-dependent synaptic CAM shedding, including those that may be calcium dependent. We also highlight CAM targets of activity-dependent proteolysis including neuroligin and intercellular adhesion molecule-5 (ICAM-5). We include discussion focused on potential consequences of synaptic CAM shedding, with an emphasis on interactions between soluble CAM cleavage products and specific pre- and post-synaptic receptors. PMID:26321910

  12. Maintainence Treatment of Opioid Dependence with Tramadol

    PubMed Central

    Sarkar, Siddharth; Varshney, Mohit; Patil, Vaibhav; Lal, Rakesh

    2017-01-01

    Background: Although tramadol has been used in the management of acute withdrawal in patients with opioid dependence, its use for maintenance treatment as a harm reduction approach has not been assessed systematically. This case series describes patients with opioid dependence who were treated with tramadol for long-term maintenance. Methods: Patients with opioid dependence who received treatment at the National Drug Dependence Treatment Centre of All India Institute of Medical Sciences, New Delhi, were included in the study. Patients who received at least 6 months of tramadol and had follow-up adherence of more than 80% were included in the case series. Results: A total of 25 cases were included, all of whom were males. The types of opioids being taken at the time of initiation of tramadol were natural opiates (poppy husk and raw opium), followed by heroin. The median dose of tramadol at initiation and maintenance was 300 mg/day. Nineteen patients were able to achieve complete abstinence to other opiates on tramadol. Conclusion: Tramadol may be an effective option in the long-term management of patients with opioid dependence. Further studies are required for establishing the efficacy of tramadol for agonist management of patients with opioid dependence. PMID:28936080

  13. Maintainence Treatment of Opioid Dependence with Tramadol.

    PubMed

    Sarkar, Siddharth; Varshney, Mohit; Patil, Vaibhav; Lal, Rakesh

    2017-08-01

    Although tramadol has been used in the management of acute withdrawal in patients with opioid dependence, its use for maintenance treatment as a harm reduction approach has not been assessed systematically. This case series describes patients with opioid dependence who were treated with tramadol for long-term maintenance. Patients with opioid dependence who received treatment at the National Drug Dependence Treatment Centre of All India Institute of Medical Sciences, New Delhi, were included in the study. Patients who received at least 6 months of tramadol and had follow-up adherence of more than 80% were included in the case series. A total of 25 cases were included, all of whom were males. The types of opioids being taken at the time of initiation of tramadol were natural opiates (poppy husk and raw opium), followed by heroin. The median dose of tramadol at initiation and maintenance was 300 mg/day. Nineteen patients were able to achieve complete abstinence to other opiates on tramadol. Tramadol may be an effective option in the long-term management of patients with opioid dependence. Further studies are required for establishing the efficacy of tramadol for agonist management of patients with opioid dependence.

  14. Neonatal behavior after drug dependent pregnancy.

    PubMed Central

    van Baar, A L; Fleury, P; Soepatmi, S; Ultee, C A; Wesselman, P J

    1989-01-01

    Neurobehavioural development of 35 infants of drug dependent mothers was compared with the development of 37 reference infants as part of a prospective longitudinal research project. Infants of drug dependent mothers had more poor responses than the other children on neurological examination. This difference is significant only when data of infants of drug dependent mothers born at full term are analysed. Two tailed testing indicated that significantly more infants of drug dependent mothers than reference children had electro-encephalograms rated as suspect or abnormal. By the end of the first month the infants of drug dependent mothers tended to be more active, and they had worse scores than the reference children on the neonatal behavioural assessment scale. Analysing data only of infants born at full term, the groups differ significantly on the interactive items. The results of this study show that even after treatment for the neonatal abstinence syndrome, infants of drug dependent mothers seem to differ from comparison children, which could indicate later developmental problems. PMID:2467626

  15. [Health Technology Dependency: A Concept Analysis].

    PubMed

    Chen, Miao-Yi; Chen, Ting-Yu; Kao, Chi-Wen

    2016-02-01

    Health technology dependence is a widely recognized concept that refers to the utilization of technology, including drugs, equipment, instruments, and related devices, to compensate for a physical disability or to prevent the progression of a disability. Although technology may significantly prolong the life of a patient, technology may also increase the psychological pressure of these patients and the burdens of their caregivers. There is a current dearth of related research and discussions related to the concept of "health technology dependency". Therefore, the present paper uses the strategies of concept analysis described by Walker & Avant (2010) to analyze this concept. The characteristic definition of health technology dependence addresses individuals who: (1) currently live with health technology, (2) may perceive physical or psychological burdens due to health technology, and (3) feel physical and psychological well-being when coping positively with their health technology dependency and, further, regard health technology as a part of their body. Further, the present paper uses case examples to help analyze the general concept. It is hoped that nurses may better understand the concept of "health technology dependency", consider the concerns of health-technology-dependent patients and their families, and develop relevant interventions to promote the well-being of these patients and their families.

  16. Increased visual dependence in Parkinson's disease.

    PubMed

    Azulay, Jean Philippe; Mesure, Serge; Amblard, Bernard; Pouget, Jean

    2002-12-01

    The present study tested the hypothesis that there is increased visual dependence perceptually in patients with Parkinson's disease. We also evaluated whether the visual control of posture and locomotion was related to perceptual visual field dependence. 21 patients with idiopathic Parkinson's disease and 22 age-matched normal subjects were compared on judgment of the visual vertical using the Rod-and-Frame test with visual perturbations in the frontal plane with a tilted frame. Patients had significantly larger errors than controls in the estimation of the subjective vertical. In the same experiment, we performed a posture and a gait analysis in both groups. Posturographic evaluation did not indicate significant differences in unsteadiness between patients and controls. Gait analysis indicated a typical pattern of reduced velocity, shortened stride length, and normal step width. A significant correlation of .89 was found only in the Parkinsonian group between their errors in estimating subjective visual vertical and the Romberg quotient evaluating visual contribution to postural control. No specific locomotor pattern was correlated with visual dependence. Considering our results and previous reports on the visual control of posture, we conclude that patients with Parkinson's disease showed a significantly increased dependence upon visual information both perceptually and motorically, with an increased perceptual visual dependence in the patients being predictive of an equivalent visual dependence or visual control of posture and equilibrium.

  17. Sex differences amongst dependent heroin users: histories, clinical characteristics and predictors of other substance dependence

    PubMed Central

    Shand, Fiona L; Degenhardt, Louisa; Slade, Tim; Nelson, Elliot C

    2010-01-01

    Introduction and aims To examine differences in the characteristics and histories of male and female dependent heroin users, and in the clinical characteristics associated with multiple substance dependence diagnoses. Design and methods 1513 heroin dependent participants underwent an interview covering substance use and dependence, psychiatric history, child maltreatment, family background, adult violence and criminal history. Family background, demographic and clinical characteristics were analysed by sex. Ordinal regression was used to test for a relationship between number of substance dependence diagnoses and other clinical variables. Results Women were more likely to experience most forms of child maltreatment, to first use heroin with a boyfriend or partner, to experience ongoing adult violence at the hands of a partner, and to have a poorer psychiatric history than men. Males had more prevalent lifetime substance dependence diagnoses and criminal histories and were more likely to meet criteria for ASPD. Predictors of multiple substance dependence diagnoses for both sexes were mental health variables, antisocial behaviour, childhood sexual abuse, victim of adult violence, younger age at first cannabis use and overdose. As the number of dependence diagnoses increased, clinical and behavioural problems increased. Childhood emotional neglect was related to increasing dependence diagnoses for females but not males, whereas PTSD was a significant predictor for males but not females. Discussion and conclusions Mental health problems, other substance dependence, childhood and adult trauma were common in this sample, with sex differences indicating different treatment needs and possible different pathways to heroin dependence for men and women. PMID:20833480

  18. Are Tobacco Dependence and Withdrawal Related Amongst Heavy Smokers? Relevance to Conceptualizations of Dependence

    PubMed Central

    Baker, Timothy B.; Piper, Megan E.; Schlam, Tanya R.; Cook, Jessica W.; Smith, Stevens S.; Loh, Wei-Yin; Bolt, Daniel

    2013-01-01

    Measured tobacco dependence is typically only modestly related to tobacco withdrawal severity amongst regular smokers making a quit attempt. The weak association between dependence and withdrawal is notable because it conflicts with core theories of dependence and because both measures predict cessation outcomes, suggesting they both index a common dependence construct. This study used data from a smoking cessation comparative effectiveness trial (N = 1504) to characterize relations of tobacco dependence with craving and negative affect withdrawal symptoms using multiple dependence measures and analytic methods to detect both additive and interactive effects and to determine whether withdrawal meaningfully mediates the influence of dependence on smoking cessation. We conclude: (1) while univariate analyses suggest dependence and withdrawal measures are only modestly interrelated, more powerful analytic techniques show they are, in fact, meaningfully related and their shared variance is associated with cessation likelihood; (2) there are clear differences between craving and negative affective withdrawal symptoms, with the former more related to smoking heaviness and the latter related to trait measures of negative affect; moreover, craving more strongly mediates dependence effects on cessation; (3) both craving and negative affect withdrawal symptoms are strongly related to a pattern of regular smoking that is sensitive to the passage of time and powerfully affected by smoking cues. These findings support models that accord an important role for associative processes and withdrawal symptoms, especially craving, in drug dependence. The findings also support the use of withdrawal variables as criteria for the evaluation of dependence measures. PMID:22642839

  19. Alcoholic neurobiology: changes in dependence and recovery.

    PubMed

    Crews, Fulton T; Buckley, Tracey; Dodd, Peter R; Ende, Gabriele; Foley, Nina; Harper, Clive; He, Jun; Innes, David; Loh, El-Wui; Pfefferbaum, Adolph; Zou, Jian; Sullivan, Edith V

    2005-08-01

    This article presents the proceedings of a symposium held at the meeting of the International Society for Biomedical Research on Alcoholism (ISBRA) in Mannheim, Germany, in October, 2004. Chronic alcoholism follows a fluctuating course, which provides a naturalistic experiment in vulnerability, resilience, and recovery of human neural systems in response to presence, absence, and history of the neurotoxic effects of alcoholism. Alcohol dependence is a progressive chronic disease that is associated with changes in neuroanatomy, neurophysiology, neural gene expression, psychology, and behavior. Specifically, alcohol dependence is characterized by a neuropsychological profile of mild to moderate impairment in executive functions, visuospatial abilities, and postural stability, together with relative sparing of declarative memory, language skills, and primary motor and perceptual abilities. Recovery from alcoholism is associated with a partial reversal of CNS deficits that occur in alcoholism. The reversal of deficits during recovery from alcoholism indicates that brain structure is capable of repair and restructuring in response to insult in adulthood. Indirect support of this repair model derives from studies of selective neuropsychological processes, structural and functional neuroimaging studies, and preclinical studies on degeneration and regeneration during the development of alcohol dependence and recovery form dependence. Genetics and brain regional specificity contribute to unique changes in neuropsychology and neuroanatomy in alcoholism and recovery. This symposium includes state-of-the-art presentations on changes that occur during active alcoholism as well as those that may occur during recovery-abstinence from alcohol dependence. Included are human neuroimaging and neuropsychological assessments, changes in human brain gene expression, allelic combinations of genes associated with alcohol dependence and preclinical studies investigating mechanisms of

  20. Mapping Groundwater Dependent Ecosystems in California

    PubMed Central

    Howard, Jeanette; Merrifield, Matt

    2010-01-01

    Background Most groundwater conservation and management efforts focus on protecting groundwater for drinking water and for other human uses with little understanding or focus on the ecosystems that depend on groundwater. However, groundwater plays an integral role in sustaining certain types of aquatic, terrestrial and coastal ecosystems, and their associated landscapes. Our aim was to illuminate the connection between groundwater and surface ecosystems by identifying and mapping the distribution of groundwater dependent ecosystems (GDEs) in California. Methodology/Principal Findings To locate where groundwater flow sustains ecosystems we identified and mapped groundwater dependent ecosystems using a GIS. We developed an index of groundwater dependency by analyzing geospatial data for three ecosystem types that depend on groundwater: (1) springs and seeps; (2) wetlands and associated vegetation alliances; and (3) stream discharge from groundwater sources (baseflow index). Each variable was summarized at the scale of a small watershed (Hydrologic Unit Code-12; mean size = 9,570 ha; n = 4,621), and then stratified and summarized to 10 regions of relative homogeneity in terms of hydrologic, ecologic and climatic conditions. We found that groundwater dependent ecosystems are widely, although unevenly, distributed across California. Although different types of GDEs are clustered more densely in certain areas of the state, watersheds with multiple types of GDEs are found in both humid (e.g. coastal) and more arid regions. Springs are most densely concentrated in the North Coast and North Lahontan, whereas groundwater dependent wetlands and associated vegetation alliances are concentrated in the North and South Lahontan and Sacramento River hydrologic regions. The percentage of land area where stream discharge is most dependent on groundwater is found in the North Coast, Sacramento River and Tulare Lake regions. GDE clusters are located at the highest percentage

  1. Integrating models that depend on variable data

    NASA Astrophysics Data System (ADS)

    Banks, A. T.; Hill, M. C.

    2016-12-01

    Models of human-Earth systems are often developed with the goal of predicting the behavior of one or more dependent variables from multiple independent variables, processes, and parameters. Often dependent variable values range over many orders of magnitude, which complicates evaluation of the fit of the dependent variable values to observations. Many metrics and optimization methods have been proposed to address dependent variable variability, with little consensus being achieved. In this work, we evaluate two such methods: log transformation (based on the dependent variable being log-normally distributed with a constant variance) and error-based weighting (based on a multi-normal distribution with variances that tend to increase as the dependent variable value increases). Error-based weighting has the advantage of encouraging model users to carefully consider data errors, such as measurement and epistemic errors, while log-transformations can be a black box for typical users. Placing the log-transformation into the statistical perspective of error-based weighting has not formerly been considered, to the best of our knowledge. To make the evaluation as clear and reproducible as possible, we use multiple linear regression (MLR). Simulations are conducted with MatLab. The example represents stream transport of nitrogen with up to eight independent variables. The single dependent variable in our example has values that range over 4 orders of magnitude. Results are applicable to any problem for which individual or multiple data types produce a large range of dependent variable values. For this problem, the log transformation produced good model fit, while some formulations of error-based weighting worked poorly. Results support previous suggestions fthat error-based weighting derived from a constant coefficient of variation overemphasizes low values and degrades model fit to high values. Applying larger weights to the high values is inconsistent with the log

  2. Mapping groundwater dependent ecosystems in California.

    PubMed

    Howard, Jeanette; Merrifield, Matt

    2010-06-23

    Most groundwater conservation and management efforts focus on protecting groundwater for drinking water and for other human uses with little understanding or focus on the ecosystems that depend on groundwater. However, groundwater plays an integral role in sustaining certain types of aquatic, terrestrial and coastal ecosystems, and their associated landscapes. Our aim was to illuminate the connection between groundwater and surface ecosystems by identifying and mapping the distribution of groundwater dependent ecosystems (GDEs) in California. To locate where groundwater flow sustains ecosystems we identified and mapped groundwater dependent ecosystems using a GIS. We developed an index of groundwater dependency by analyzing geospatial data for three ecosystem types that depend on groundwater: (1) springs and seeps; (2) wetlands and associated vegetation alliances; and (3) stream discharge from groundwater sources (baseflow index). Each variable was summarized at the scale of a small watershed (Hydrologic Unit Code-12; mean size = 9,570 ha; n = 4,621), and then stratified and summarized to 10 regions of relative homogeneity in terms of hydrologic, ecologic and climatic conditions. We found that groundwater dependent ecosystems are widely, although unevenly, distributed across California. Although different types of GDEs are clustered more densely in certain areas of the state, watersheds with multiple types of GDEs are found in both humid (e.g. coastal) and more arid regions. Springs are most densely concentrated in the North Coast and North Lahontan, whereas groundwater dependent wetlands and associated vegetation alliances are concentrated in the North and South Lahontan and Sacramento River hydrologic regions. The percentage of land area where stream discharge is most dependent on groundwater is found in the North Coast, Sacramento River and Tulare Lake regions. GDE clusters are located at the highest percentage in the North Coast (an area of the highest annual

  3. Microdomain organization and frequency-dependence of CREB-dependent transcriptional signaling in heart cells

    PubMed Central

    Kobrinsky, Evgeny; Duong, Son Q.; Sheydina, Anna; Soldatov, Nikolai M.

    2011-01-01

    Voltage-gated Cav1.2 calcium channels couple membrane depolarization to cAMP response-element-binding protein (CREB)-dependent transcriptional activation. To investigate the spatial and temporal organization of CREB-dependent transcriptional nuclear microdomains, we combined perforated patch-clamp technique and FRET microscopy for monitoring CREB and CREB-binding protein interaction in the nuclei of live cells. The experimental approach to the quantitative assessment of CREB-dependent transcriptional signaling evoked by cAMP- and Cav1.2-dependent mechanisms was devised in COS1 cells expressing recombinant Cav1.2 calcium channels. Using continuous 2-dimensional wavelet transform and time series analyses, we found that nuclear CREB-dependent transcriptional signaling is organized differentially in spatially and temporally separated microdomains of 4 distinct types. In rat neonatal cardiomyocytes, CREB-dependent transcription is mediated by the cAMP-initiated CaMKII-sensitive and Cav1.2-initiated CaMKII-insensitive mechanisms. The latter microdomains show a tendency to exhibit periodic behavior correlated with spontaneous contraction of myocytes suggestive of frequency-dependent CREB-dependent transcriptional regulation in the heart.—Kobrinsky, E., Duong, S.Q., Sheydina, A., Soldatov, N. M. Microdomain organization and frequency-dependence of CREB-dependent transcriptional signaling in heart cells. PMID:21248242

  4. How context dependent are species interactions?

    PubMed

    Chamberlain, Scott A; Bronstein, Judith L; Rudgers, Jennifer A

    2014-07-01

    The net effects of interspecific species interactions on individuals and populations vary in both sign (-, 0, +) and magnitude (strong to weak). Interaction outcomes are context-dependent when the sign and/or magnitude change as a function of the biotic or abiotic context. While context dependency appears to be common, its distribution in nature is poorly described. Here, we used meta-analysis to quantify variation in species interaction outcomes (competition, mutualism, or predation) for 247 published articles. Contrary to our expectations, variation in the magnitude of effect sizes did not differ among species interactions, and while mutualism was most likely to change sign across contexts (and predation least likely), mutualism did not strongly differ from competition. Both the magnitude and sign of species interactions varied the most along spatial and abiotic gradients, and least as a function of the presence/absence of a third species. However, the degree of context dependency across these context types was not consistent among mutualism, competition and predation studies. Surprisingly, study location and ecosystem type varied in the degree of context dependency, with laboratory studies showing the highest variation in outcomes. We urge that studying context dependency per se, rather than focusing only on mean outcomes, can provide a general method for describing patterns of variation in nature.

  5. Percolation on networks with conditional dependence group.

    PubMed

    Wang, Hui; Li, Ming; Deng, Lin; Wang, Bing-Hong

    2015-01-01

    Recently, the dependence group has been proposed to study the robustness of networks with interdependent nodes. A dependence group means that a failed node in the group can lead to the failures of the whole group. Considering the situation of real networks that one failed node may not always break the functionality of a dependence group, we study a cascading failure model that a dependence group fails only when more than a fraction β of nodes of the group fail. We find that the network becomes more robust with the increasing of the parameter β. However, the type of percolation transition is always first order unless the model reduces to the classical network percolation model, which is independent of the degree distribution of the network. Furthermore, we find that a larger dependence group size does not always make the networks more fragile. We also present exact solutions to the size of the giant component and the critical point, which are in agreement with the simulations well.

  6. Percolation on Networks with Conditional Dependence Group

    PubMed Central

    Wang, Hui; Li, Ming; Deng, Lin; Wang, Bing-Hong

    2015-01-01

    Recently, the dependence group has been proposed to study the robustness of networks with interdependent nodes. A dependence group means that a failed node in the group can lead to the failures of the whole group. Considering the situation of real networks that one failed node may not always break the functionality of a dependence group, we study a cascading failure model that a dependence group fails only when more than a fraction β of nodes of the group fail. We find that the network becomes more robust with the increasing of the parameter β. However, the type of percolation transition is always first order unless the model reduces to the classical network percolation model, which is independent of the degree distribution of the network. Furthermore, we find that a larger dependence group size does not always make the networks more fragile. We also present exact solutions to the size of the giant component and the critical point, which are in agreement with the simulations well. PMID:25978634

  7. Skeletal muscle tensile strain dependence: hyperviscoelastic nonlinearity

    PubMed Central

    Wheatley, Benjamin B; Morrow, Duane A; Odegard, Gregory M; Kaufman, Kenton R; Donahue, Tammy L Haut

    2015-01-01

    Introduction Computational modeling of skeletal muscle requires characterization at the tissue level. While most skeletal muscle studies focus on hyperelasticity, the goal of this study was to examine and model the nonlinear behavior of both time-independent and time-dependent properties of skeletal muscle as a function of strain. Materials and Methods Nine tibialis anterior muscles from New Zealand White rabbits were subject to five consecutive stress relaxation cycles of roughly 3% strain. Individual relaxation steps were fit with a three-term linear Prony series. Prony series coefficients and relaxation ratio were assessed for strain dependence using a general linear statistical model. A fully nonlinear constitutive model was employed to capture the strain dependence of both the viscoelastic and instantaneous components. Results Instantaneous modulus (p<0.0005) and mid-range relaxation (p<0.0005) increased significantly with strain level, while relaxation at longer time periods decreased with strain (p<0.0005). Time constants and overall relaxation ratio did not change with strain level (p>0.1). Additionally, the fully nonlinear hyperviscoelastic constitutive model provided an excellent fit to experimental data, while other models which included linear components failed to capture muscle function as accurately. Conclusions Material properties of skeletal muscle are strain-dependent at the tissue level. This strain dependence can be included in computational models of skeletal muscle performance with a fully nonlinear hyperviscoelastic model. PMID:26409235

  8. Dependent Happenings: A Recent Methodological Review.

    PubMed

    Halloran, M Elizabeth; Hudgens, Michael G

    2016-12-01

    One hundred years ago Sir Ronald Ross published his treatise on a general Theory of Happenings. Dependent happenings are those in which the frequency depends on the number already affected. When there is dependency of events, interventions can have different types of effects. Interventions such as vaccination can have direct protective effects for the person receiving the treatment, as well as indirect/spillover effects for others in the population. Causal inference is a framework for carefully defining the causal effect of a treatment, exposure, or policy, and then determining conditions under which such effects can be estimated from the observed data. We consider here scenarios in which the potential outcomes of an individual can depend on the treatment of other individuals in the population, known as causal inference with interference. Much of the research so far has assumed the population is divided into groups or clusters, and individuals can interfere with others within their clusters but not across clusters. Recent developments have assumed more general forms of interference. We review some of the different types of effects that have been defined for dependent happenings, particularly using the methods of causal inference with interference. Many of the methods are applicable across disciplines, such as infectious diseases, social sciences, and economics.

  9. Visual dependency and dizziness after vestibular neuritis.

    PubMed

    Cousins, Sian; Cutfield, Nicholas J; Kaski, Diego; Palla, Antonella; Seemungal, Barry M; Golding, John F; Staab, Jeffrey P; Bronstein, Adolfo M

    2014-01-01

    Symptomatic recovery after acute vestibular neuritis (VN) is variable, with around 50% of patients reporting long term vestibular symptoms; hence, it is essential to identify factors related to poor clinical outcome. Here we investigated whether excessive reliance on visual input for spatial orientation (visual dependence) was associated with long term vestibular symptoms following acute VN. Twenty-eight patients with VN and 25 normal control subjects were included. Patients were enrolled at least 6 months after acute illness. Recovery status was not a criterion for study entry, allowing recruitment of patients with a full range of persistent symptoms. We measured visual dependence with a laptop-based Rod-and-Disk Test and severity of symptoms with the Dizziness Handicap Inventory (DHI). The third of patients showing the worst clinical outcomes (mean DHI score 36-80) had significantly greater visual dependence than normal subjects (6.35° error vs. 3.39° respectively, p = 0.03). Asymptomatic patients and those with minor residual symptoms did not differ from controls. Visual dependence was associated with high levels of persistent vestibular symptoms after acute VN. Over-reliance on visual information for spatial orientation is one characteristic of poorly recovered vestibular neuritis patients. The finding may be clinically useful given that visual dependence may be modified through rehabilitation desensitization techniques.

  10. Visual Dependency and Dizziness after Vestibular Neuritis

    PubMed Central

    Cousins, Sian; Cutfield, Nicholas J.; Kaski, Diego; Palla, Antonella; Seemungal, Barry M.; Golding, John F.; Staab, Jeffrey P.; Bronstein, Adolfo M.

    2014-01-01

    Symptomatic recovery after acute vestibular neuritis (VN) is variable, with around 50% of patients reporting long term vestibular symptoms; hence, it is essential to identify factors related to poor clinical outcome. Here we investigated whether excessive reliance on visual input for spatial orientation (visual dependence) was associated with long term vestibular symptoms following acute VN. Twenty-eight patients with VN and 25 normal control subjects were included. Patients were enrolled at least 6 months after acute illness. Recovery status was not a criterion for study entry, allowing recruitment of patients with a full range of persistent symptoms. We measured visual dependence with a laptop-based Rod-and-Disk Test and severity of symptoms with the Dizziness Handicap Inventory (DHI). The third of patients showing the worst clinical outcomes (mean DHI score 36–80) had significantly greater visual dependence than normal subjects (6.35° error vs. 3.39° respectively, p = 0.03). Asymptomatic patients and those with minor residual symptoms did not differ from controls. Visual dependence was associated with high levels of persistent vestibular symptoms after acute VN. Over-reliance on visual information for spatial orientation is one characteristic of poorly recovered vestibular neuritis patients. The finding may be clinically useful given that visual dependence may be modified through rehabilitation desensitization techniques. PMID:25233234

  11. Emotion recognition (sometimes) depends on horizontal orientations

    PubMed Central

    Huynh, Carol M; Balas, Benjamin

    2014-01-01

    Face recognition depends critically on horizontal orientations (Goffaux & Dakin, 2010). Face images that lack horizontal features are harder to recognize than those that have that information preserved. Presently, we asked if facial emotional recognition also exhibits this dependency by asking observers to categorize orientation-filtered happy and sad expressions. Furthermore, we aimed to dissociate image-based orientation energy from object-based orientation by rotating images 90-degrees in the picture-plane. In our first experiment, we showed that the perception of emotional expression does depend on horizontal orientations and that object-based orientation constrained performance more than image-based orientation. In Experiment 2 we showed that mouth openness (i.e. open versus closed-mouths) also influenced the emotion-dependent reliance on horizontal information. Lastly, we describe a simple computational analysis that demonstrates that the impact of mouth openness was not predicted by variation in the distribution of orientation energy across horizontal and vertical orientation bands. Overall, our results suggest that emotion recognition does largely depend on horizontal information defined relative to the face, but that this bias is modulated by multiple factors that introduce variation in appearance across and within distinct emotions. PMID:24664854

  12. Adverse childhood events and lifetime alcohol dependence.

    PubMed

    Pilowsky, Daniel J; Keyes, Katherine M; Hasin, Deborah S

    2009-02-01

    We sought to study the association between adverse events occurring in childhood and adolescence and lifetime alcohol dependence in a representative sample of American adults. With data from the National Epidemiologic Survey on Alcohol and Related Conditions, we conducted logistic regression multivariate analyses to examine the impact of adverse events occurring in childhood (aged < 18 years) on the lifetime prevalence of alcohol dependence. We controlled for age at drinking onset, binge drinking, alcoholism in parents and grandparents of respondents, and demographic characteristics. Adverse childhood events were associated with familial alcoholism and with early and binge drinking, and therefore, we controlled for these potential confounders. Experiencing 2 or more adverse childhood events, compared with none, significantly increased the risk for alcohol dependence, even after we controlled for sociodemographic variables and disorder-specific potential confounders not considered in the extant literature (adjusted odds ratio = 1.37; 95% confidence interval = 1.06, 1.77). Individuals who experienced 2 or more adverse childhood events are at increased risk for lifetime alcohol dependence. A better understanding of the factors underlying the risk for alcohol dependence is important for developing better prevention and early intervention measures.

  13. Representing higher-order dependencies in networks

    PubMed Central

    Xu, Jian; Wickramarathne, Thanuka L.; Chawla, Nitesh V.

    2016-01-01

    To ensure the correctness of network analysis methods, the network (as the input) has to be a sufficiently accurate representation of the underlying data. However, when representing sequential data from complex systems, such as global shipping traffic or Web clickstream traffic as networks, conventional network representations that implicitly assume the Markov property (first-order dependency) can quickly become limiting. This assumption holds that, when movements are simulated on the network, the next movement depends only on the current node, discounting the fact that the movement may depend on several previous steps. However, we show that data derived from many complex systems can show up to fifth-order dependencies. In these cases, the oversimplifying assumption of the first-order network representation can lead to inaccurate network analysis results. To address this problem, we propose the higher-order network (HON) representation that can discover and embed variable orders of dependencies in a network representation. Through a comprehensive empirical evaluation and analysis, we establish several desirable characteristics of HON, including accuracy, scalability, and direct compatibility with the existing suite of network analysis methods. We illustrate how HON can be applied to a broad variety of tasks, such as random walking, clustering, and ranking, and we demonstrate that, by using it as input, HON yields more accurate results without any modification to these tasks. PMID:27386539

  14. Flavin-Dependent Enzymes in Cancer Prevention

    PubMed Central

    Wojcieszyńska, Danuta; Hupert-Kocurek, Katarzyna; Guzik, Urszula

    2012-01-01

    Statistical studies have demonstrated that various agents may reduce the risk of cancer’s development. One of them is activity of flavin-dependent enzymes such as flavin-containing monooxygenase (FMO)GS-OX1, FAD-dependent 5,10-methylenetetrahydrofolate reductase and flavin-dependent monoamine oxidase. In the last decade, many papers concerning their structure, reaction mechanism and role in the cancer prevention were published. In our work, we provide a more in-depth analysis of flavin-dependent enzymes and their contribution to the cancer prevention. We present the actual knowledge about the glucosinolate synthesized by flavin-containing monooxygenase (FMO)GS-OX1 and its role in cancer prevention, discuss the influence of mutations in FAD-dependent 5,10-methylenetetrahydrofolate reductase on the cancer risk, and describe FAD as an important cofactor for the demethylation of histons. We also present our views on the role of riboflavin supplements in the prevention against cancer. PMID:23222680

  15. [Dependency policies. Consequences for affected families].

    PubMed

    Escuredo Rodríguez, Bibiana

    2008-05-01

    Dependency creates a social problem whose burden falls upon the affected family and which causes problems in the lives and health of caretakers. A solution to these problems depends on the policies enacted. Nurses should know these policies and their consequences and act accordingly. For nurses to do so, the author has carried out a qualitative documented research project which analyzes the main Spanish dependency policies including the Geriatrics Plan and the following laws: regarding situations requiring living together and mutual aid, conciliation of working and personal lives, family caretaking for elderly and dependent relatives. This project's results indicate the aid provided consists in monetary loans and social services. The coverage provided by these aid programs is minimal or scarce. These programs promote keeping patients in need of dependency care in their homes under the care of relatives. There is little aid directed at caretakers and frequently such aid implies high personal costs. Nurses can and should contribute to bring awareness of these situations, to alleviate them and to modify some of these problems.

  16. Linear dependencies in Weyl-Heisenberg orbits

    NASA Astrophysics Data System (ADS)

    Dang, Hoan Bui; Blanchfield, Kate; Bengtsson, Ingemar; Appleby, D. M.

    2013-11-01

    Five years ago, Lane Hughston showed that some of the symmetric informationally complete positive operator valued measures (SICs) in dimension 3 coincide with the Hesse configuration (a structure well known to algebraic geometers, which arises from the torsion points of a certain elliptic curve). This connection with elliptic curves is signalled by the presence of linear dependencies among the SIC vectors. Here we look for analogous connections between SICs and algebraic geometry by performing computer searches for linear dependencies in higher dimensional SICs. We prove that linear dependencies will always emerge in Weyl-Heisenberg orbits when the fiducial vector lies in a certain subspace of an order 3 unitary matrix. This includes SICs when the dimension is divisible by 3 or equal to 8 mod 9. We examine the linear dependencies in dimension 6 in detail and show that smaller dimensional SICs are contained within this structure, potentially impacting the SIC existence problem. We extend our results to look for linear dependencies in orbits when the fiducial vector lies in an eigenspace of other elements of the Clifford group that are not order 3. Finally, we align our work with recent studies on representations of the Clifford group.

  17. Predictive a priori pressure-dependent kinetics.

    PubMed

    Jasper, Ahren W; Pelzer, Kenley M; Miller, James A; Kamarchik, Eugene; Harding, Lawrence B; Klippenstein, Stephen J

    2014-12-05

    The ability to predict the pressure dependence of chemical reaction rates would be a great boon to kinetic modeling of processes such as combustion and atmospheric chemistry. This pressure dependence is intimately related to the rate of collision-induced transitions in energy E and angular momentum J. We present a scheme for predicting this pressure dependence based on coupling trajectory-based determinations of moments of the E,J-resolved collisional transfer rates with the two-dimensional master equation. This completely a priori procedure provides a means for proceeding beyond the empiricism of prior work. The requisite microcanonical dissociation rates are obtained from ab initio transition state theory. Predictions for the CH4 = CH3 + H and C2H3 = C2H2 + H reaction systems are in excellent agreement with experiment.

  18. Management of methamphetamine abuse and dependence.

    PubMed

    Ling, Walter; Rawson, Richard; Shoptaw, Steve; Ling, Walter

    2006-10-01

    Preliminary implications for evidence-based treatments and future practice may be drawn from new research findings that inspire a fresh view of methamphetamine dependence and associated medical consequences. Current user populations include increasingly impacted subgroups (ie, youths, women, men who have sex with men, and rural residents); complex consequences of methamphetamine abuse among these subgroups require additional efforts involving contextual understanding of characteristics and needs to develop effective treatments. The neurobiological data on cellular activity of methamphetamine taken with findings from neuroimaging studies indicate potential targets for pharmacologic interventions. In early trials, several candidate medications--bupropion, modafinil, and, to a lesser extent, baclofen--have shown promise in treating aspects of methamphetamine dependence, including aiding memory function necessary to more effectively participate in and benefit from behavioral therapies. Clinicians and researchers must interact to efficiently address the problems of methamphetamine dependence, a major drug problem in the United States and the world.

  19. Dependence of fusion on isospin dynamics

    NASA Astrophysics Data System (ADS)

    Godbey, K.; Umar, A. S.; Simenel, C.

    2017-01-01

    We introduce a new microscopic approach to calculate the dependence of fusion barriers and cross sections on isospin dynamics. The method is based on the time-dependent Hartree-Fock theory and the isoscalar and isovector properties of the energy density functional (EDF). The contribution to the fusion barriers originating from the isoscalar and isovector parts of the EDF is calculated. It is shown that, for nonsymmetric systems, the isovector dynamics influence the subbarrier fusion cross sections. For most systems this results in an enhancement of the subbarrier cross sections, while for others we observe differing degrees of hindrance. We use this approach to provide an explanation of recently measured fusion cross sections which show a enhancement at low Ec .m . energies for the system 40Ca+132Sn as compared with the more neutron-rich system 48Ca+132Sn and discuss the dependence of subbarrier fusion cross sections on transfer.

  20. Flavour-dependent leptogenesis with reheating

    SciTech Connect

    Antusch, Stefan

    2007-11-20

    Upper bounds on the reheat temperature of the early universe, as they appear for example in classes of supergravity models, impose severe constraints on the thermal leptogenesis mechanism. To analyse these constraints, we extend the flavour-dependent treatment of leptogenesis to include reheating. We solve the flavour-dependent Boltzmann equations to obtain the leptogenesis efficiency as a function of the flavour dependent washout parameter m-tilde{sub 1,{alpha}} and of m{sub N{sub 1}}/T{sub RH}, the ratio of the mass of the lightest right-handed neutrino over the reheat temperature, and calculate the minimal values of the reheat temperature compatible with thermal leptogenesis in type I and type II seesaw scenarios.

  1. Endothelium-dependent relaxation of blood vessels

    SciTech Connect

    Hynes, M.R.

    1987-01-01

    Dilation of blood vessels in response to a large number of agents has been shown to be dependent on an intact vascular endothelium. The present studies examine some aspects of endothelium-dependent vasodilation in blood vessels of the rabbit and rat. Using the rabbit ear artery and the subtype-selective muscarinic antagonist pirenzepine, muscarinic receptors of the endothelium and smooth muscle cells were shown to be of the low affinity M/sub 2/ subtype. Inhibition of (/sup 3/H)(-)quinuclidinyl benzilate was used to determine affinity for the smooth muscle receptors while antagonism of methacholine induced vasodilation yielded the endothelial cell receptor affinity. The effect of increasing age (1-27 months) on endothelium-dependent relaxation was studied in aortic rings, perfused tail artery and perfused mesenteric bed of the Fisher 344 rat. The influence of endothelium on contractile responses was examined using the perfused caudal artery.

  2. Brain pathways to recovery from alcohol dependence.

    PubMed

    Cui, Changhai; Noronha, Antonio; Warren, Kenneth R; Koob, George F; Sinha, Rajita; Thakkar, Mahesh; Matochik, John; Crews, Fulton T; Chandler, L Judson; Pfefferbaum, Adolf; Becker, Howard C; Lovinger, David; Everitt, Barry J; Egli, Mark; Mandyam, Chitra D; Fein, George; Potenza, Marc N; Harris, R Adron; Grant, Kathleen A; Roberto, Marisa; Meyerhoff, Dieter J; Sullivan, Edith V

    2015-08-01

    This article highlights the research presentations at the satellite symposium on "Brain Pathways to Recovery from Alcohol Dependence" held at the 2013 Society for Neuroscience Annual Meeting. The purpose of this symposium was to provide an up to date overview of research efforts focusing on understanding brain mechanisms that contribute to recovery from alcohol dependence. A panel of scientists from the alcohol and addiction research field presented their insights and perspectives on brain mechanisms that may underlie both recovery and lack of recovery from alcohol dependence. The four sessions of the symposium encompassed multilevel studies exploring mechanisms underlying relapse and craving associated with sustained alcohol abstinence, cognitive function deficit and recovery, and translational studies on preventing relapse and promoting recovery. Gaps in our knowledge and research opportunities were also discussed. Published by Elsevier Inc.

  3. Treating Tobacco Dependence in a Medical Setting

    PubMed Central

    Hurt, Richard D.; Ebbert, Jon O.; Hays, J. Taylor; McFadden, David D.

    2014-01-01

    The US Public Health Service Guideline for Treating Tobacco Use and Dependence 2008 Update emphasizes tobacco use as a chronic medical disorder; highlights both behavioral counseling and the use of 1 or more of the 7 approved medications; and points out the utility, efficacy, and reach of telephone quitlines. The treatment of users of smokeless tobacco continues to be less than optimal. Although providing evidence-based treatment for tobacco-dependent patients is a challenge for busy physicians, a team approach including trained and certified tobacco treatment specialists (TTS) provides an efficient treatment model. TTS represent a new and growing part of the health care team and hold great potential for expanding the collective tobacco treatment expertise in the medical setting. The effective treatment of tobacco dependence frequently requires tailoring, and often intensifying, interventions (both counseling and pharmacotherapy) to meet the needs of the individual patient. PMID:19706827

  4. Pulsar braking: Time dependent moment of inertia?

    NASA Astrophysics Data System (ADS)

    Urbanec, Martin

    2017-08-01

    Pulsars rotate with extremely stable rotational frequency enabling one to measure its first and second time derivatives. These observed values can be combined to the so-called braking index. However observed values of braking index differ from the theoretical value of 3 corresponding to braking by magnetic dipole radiation being the dominant theoretical model. Such a difference can be explained by contribution of other mechanism like pulsar wind or quadrupole radiation, or by time dependency of magnetic field or moment of inertia. In this presentation we focus on influence of time dependent moment of inertia on the braking index. We will also discuss possible physical models for time-dependence of moment of inertia.

  5. Canopy bidirectional reflectance dependence on leaf orientation

    NASA Technical Reports Server (NTRS)

    Brakke, Thomas W.; Otterman, Joseph

    1990-01-01

    The dependence of the bidirectional reflectance (BR) on the inclination and azimuthal orientation of a leaf is analyzed, with the primary assumption that, in terms of both obscuration and shadowing, the entire canopy consists of the same leaves. The BR patterns of a dense canopy are examined as a function of canopy architecture. It is assumed that the leaves are opaque Lambertian reflectors, having identical orientation and relfecting properties throughout the canopy, and distributed randomly with respect to the the irradiation field and the viewing direction. Analytical expressions are presented and analyzed for the BR factor. It is noted that maximal BR occurs at large viewing zenith angles. A complex and often steep dependence of the BR on azimuthal location is reported, noting that the BR thus depends on the leaf azimuth as well as the zenith angle. It is concluded that the question of azimuthal distribution has to be addressed when conducting model inversions to infer canopy characteristics and architecture.

  6. Temperature Dependence of Factors Controlling Isoprene Emissions

    NASA Technical Reports Server (NTRS)

    Duncan, Bryan N.; Yoshida, Yasuko; Damon, Megan R.; Douglass, Anne R.; Witte, Jacquelyn C.

    2009-01-01

    We investigated the relationship of variability in the formaldehyde (HCHO) columns measured by the Aura Ozone Monitoring Instrument (OMI) to isoprene emissions in the southeastern United States for 2005-2007. The data show that the inferred, regional-average isoprene emissions varied by about 22% during summer and are well correlated with temperature, which is known to influence emissions. Part of the correlation with temperature is likely associated with other causal factors that are temperature-dependent. We show that the variations in HCHO are convolved with the temperature dependence of surface ozone, which influences isoprene emissions, and the dependence of the HCHO column to mixed layer height as OMI's sensitivity to HCHO increases with altitude. Furthermore, we show that while there is an association of drought with the variation in HCHO, drought in the southeastern U.S. is convolved with temperature.

  7. [Affective dependency and psychiatry: a discord].

    PubMed

    Versaevel, C

    2011-02-01

    The term "loving dependence" is increasingly used by professionals of the relation of help and the patients themselves. It joins in the wider spectre of the interpersonal dependency. More and more patients suffering from this disorder are coming for psychiatric consultation. However, this notion remains vague and absent in the vocabulary of the psychiatrists. Globally, this term describes the functioning of certain patients who present a fear of not being loved and a dependency on another person. The fear of not being loved provokes a fear of abandonment or incites development of strategies to be loved (seduce, help). Dependency on another person is a consequence of the lack of confidence in the capabilities of the individual. The other person reassures them because this person does what the patient is afraid of doing, because he/she does not feel capable. The lack of confidence in own's capabilities can also incite the individual to become a perfectionist and successful. The fear of not being loved and of not being competent is determined partly in the person's childhood. These impressions are real and/or the individuals are hypersensitive. The article describes the emotional, cognitive and behavioural levels, the various types of interpersonal dependency: dependences of type "umbilical cord", "rescuer", "stereotype" and "against dependence". The objective is to specify the concept better on clinical level, with the aim of defining criteria and pathological limits. This is the first stage before beginning rigorous scientific research. The stakes are high. There are relationships with anxiety, depressive disorders, alcoholism, food behaviour disorders, suicide and somatic pathologies. Dependency seems to be the consequence of a pathological expression of the normal dimensions of the personality: the need to be loved and valued (admired). The onset of dependency occurs in stages, when the person is weakened by events of life or by depression. The impression not to

  8. Temperature Dependence of Factors Controlling Isoprene Emissions

    NASA Technical Reports Server (NTRS)

    Duncan, Bryan N.; Yoshida, Yasuko; Damon, Megan R.; Douglass, Anne R.; Witte, Jacquelyn C.

    2009-01-01

    We investigated the relationship of variability in the formaldehyde (HCHO) columns measured by the Aura Ozone Monitoring Instrument (OMI) to isoprene emissions in the southeastern United States for 2005-2007. The data show that the inferred, regional-average isoprene emissions varied by about 22% during summer and are well correlated with temperature, which is known to influence emissions. Part of the correlation with temperature is likely associated with other causal factors that are temperature-dependent. We show that the variations in HCHO are convolved with the temperature dependence of surface ozone, which influences isoprene emissions, and the dependence of the HCHO column to mixed layer height as OMI's sensitivity to HCHO increases with altitude. Furthermore, we show that while there is an association of drought with the variation in HCHO, drought in the southeastern U.S. is convolved with temperature.

  9. Drug dependence: its significance and characteristics

    PubMed Central

    Eddy, Nathan B.; Halbach, H.; Isbell, Harris; Seevers, Maurice H.

    1965-01-01

    It has become impossible in practice, and is scientifically unsound, to maintain a single definition for all forms of drug addiction and/or habituation. A feature common to these conditions as well as to drug abuse in general is dependence, psychic or physical or both, of the individual on a chemical agent. Therefore, better understanding should be attained by substitution of the term drug dependence of this or that type, according to the agent or class of agents involved, in discussions of these conditions, especially inter-disciplinary. Short descriptions, followed by concise listings of their characteristics, are formulated for the various types of dependence on at present widely abused major groups of substances. PMID:5294186

  10. Treating tobacco dependence in a medical setting.

    PubMed

    Hurt, Richard D; Ebbert, Jon O; Hays, J Taylor; McFadden, David D

    2009-01-01

    The US Public Health Service Guideline for Treating Tobacco Use and Dependence 2008 Update emphasizes tobacco use as a chronic medical disorder; highlights both behavioral counseling and the use of 1 or more of the 7 approved medications; and points out the utility, efficacy, and reach of telephone quitlines. The treatment of users of smokeless tobacco continues to be less than optimal. Although providing evidence-based treatment for tobacco- dependent patients is a challenge for busy physicians, a team approach including trained and certified tobacco treatment specialists (TTS) provides an efficient treatment model. TTS represent a new and growing part of the health care team and hold great potential for expanding the collective tobacco treatment expertise in the medical setting. The effective treatment of tobacco dependence frequently requires tailoring, and often intensifying, interventions (both counseling and pharmacotherapy) to meet the needs of the individual patient.

  11. Peripartum pain management in opioid dependent women

    PubMed Central

    Höflich, Anna S.; Langer, Martin; Jagsch, Reinhold; Bäwert, Andjela; Winklbaur, Bernadette; Fischer, Gabriele; Unger, Annemarie

    2011-01-01

    Increased pain sensitivity and the development of opioid tolerance complicate the treatment of pain experienced by opioid maintained pregnant women during delivery and the perinatal period. The aim of the present study was to investigate differences in pain management of opioid maintained compared to non-dependent pregnant women during delivery and the postpartum period. 40 deliveries of 37 opioid dependent women enrolled in a double-blind, double-dummy randomized controlled trial (RCT) examining the safety and efficacy of methadone (mean dose at the time of delivery = 63.89 mg) and buprenorphine (mean dose at the time of delivery = 14.05 mg) during pregnancy were analyzed and participants were matched to a non-dependent comparison group of 80 pregnant women. Differences in pain management (opioid and non-opioid analgesic medication) during delivery and perinatal period were analyzed. Following cesarean delivery opioid maintained women received significantly less opioid analgesics (day of delivery p = 0.038; day 1: p = 0.02), NSAIDs were administered more frequently to opioid dependent patients than to the comparison group during cesarean section and on the third day postpartum. Significantly higher nicotine consumption in the group of opioid dependent women had a strong influence on the retrieved results, and might be considered as an independent factor of altered pain experience. Differences in pain treatment became evident when comparing opioid maintained women to healthy controls. These differences might be based on psychosocial consequences of opioid addiction along with the lack of an interdisciplinary consensus on pain treatment protocols for opioid dependent patients. PMID:22396085

  12. Subtypes of major depression in substance dependence.

    PubMed

    Niciu, Mark J; Chan, Grace; Gelernter, Joel; Arias, Albert J; Douglas, Kara; Weiss, Roger; Anton, Raymond F; Farrer, Lindsay; Cubells, Joseph F; Kranzler, Henry R

    2009-10-01

    This study evaluated features that differentiate subtypes of major depressive episode (MDE) in the context of substance dependence (SD). Design  Secondary data analysis using pooled data from family-based and case-control genetic studies of SD. Community recruitment through academic medical centers. A total of 1929 unrelated subjects with alcohol and/or drug dependence. Demographics, diagnostic criteria for psychiatric and substance use disorders and related clinical features were obtained using the Semi-Structured Assessment for Drug Dependence and Alcoholism. We compared four groups: no life-time MDE (no MDE), independent MDE only (I-MDE), substance-induced MDE only (SI-MDE) and both types of MDE. Psychiatric measures were better predictors of MDE subtype than substance-related or socio-demographic ones. Subjects with both types of MDE reported more life-time depressive symptoms and comorbid anxiety disorders and were more likely to have attempted suicide than subjects with I-MDE or SI-MDE. Subjects with both types of MDE, like those with I-MDE, were also more likely than subjects with SI-MDE to be alcohol-dependent only than either drug-dependent only or both alcohol- and drug-dependent. SD individuals with both types of MDE have greater psychiatric severity than those with I-MDE only or SI-MDE only. These and other features that distinguish among the MDE subtypes have important diagnostic and potential therapeutic implications. © 2009 The Authors. Journal compilation © 2009 Society for the Study of Addiction.

  13. [Genetic factors of alcohol-dependence].

    PubMed

    Pinto, E; Ansseau, M

    2009-10-01

    Alcohol dependence is a complex and multifactorial disease resulting both from neurobiological mechanisms and environmental factors. It is frequently associated with comorbid psychiatric disorders or with specific personality or behavioral features. Although action can be taken on the environment in order to decrease the risk of the illness, current methods used to prevent or to treat this pathology show moderate efficacy: problematic consumption of ethanol in the general population as well as relapse rates under treatment in dependent patients remain indeed very high. It is therefore of major importance to broaden our knowledge of alcohol dependence and its comorbidities so as to improve both their prevention and treatment. In this perspective, recent progress in the field of neurosciences may contribute to achieve this goal. Precisely, genetics is a promising way benefiting from many advances in genetic epidemiology, cellular and molecular biology, neuroimaging and pharmacology. In parallel with a better understanding of the neurobiology of addictions and associated behaviors, these techniques led to the identification of brain mechanisms in which a genetic variation may influence the individual vulnerability towards alcohol dependence. Moreover, there is growing evidence that alcoholism results from the interaction of genetic and environmental factors influencing both its expression and its course. Given the fact that alcohol-dependence seems highly heritable (50 to 60% of the variance in both men and women), this review assesses the role of some of the genomic regions linked with the disease, as well as the principal variants of candidate genes identified as specifically involved in the predisposition. Polymorphisms of genes influencing alcohol metabolism, GABAergic, dopaminergic and serotonergic neurotransmission seem, indeed, at stake in the development of alcohol-dependence and its related features such as personality, behavior, impulse control or craving

  14. Neurocognitive Characteristics of Individuals with Schizophrenia and Cocaine Dependence: Comparison of Currently Dependent and Remitted Groups

    PubMed Central

    Peer, Jason; Bennett, Melanie E.; Bellack, Alan S.

    2009-01-01

    Several investigations of cognitive functioning in indivduals with schizophrenia and co-occurring cocaine use have yielded mixed results when compared to samples with schizophrenia only. However, no studies have specifically compared remitted and current cocaine dependence in schizophrenia. Such an analyis could help clarify the degree and type of cognitive impairment associated with cocaine dependence in schizophrenia. Two samples of individuals with schizophrenia – those with current cocaine dependence (SZ-D; n = 72) and those with cocaine dependence in remission (SZ-R; n = 48) were compared on a brief neuropsychological test battery. Parallel current dependent and remitted samples with affective disorder (AD-D; n = 65 and AD-R; n = 55) were also included in the analyses. Results yielded few neuropsychological differences between remitted and current dependent states across the SZ and AD groups. These findings suggest that cognitive impairment may be relatively static in these populations. PMID:19684503

  15. Size-Dependent Accuracy of Nanoscale Thermometers.

    PubMed

    Alicki, Robert; Leitner, David M

    2015-07-23

    The accuracy of two classes of nanoscale thermometers is estimated in terms of size and system-dependent properties using the spin-boson model. We consider solid state thermometers, where the energy splitting is tuned by thermal properties of the material, and fluorescent organic thermometers, in which the fluorescence intensity depends on the thermal population of conformational states of the thermometer. The results of the theoretical model compare well with the accuracy reported for several nanothermometers that have been used to measure local temperature inside living cells.

  16. [Substitution therapy tested against amphetamine dependence].

    PubMed

    Bloniecki Kallio, Victor; Guterstam, Joar; Franck, Johan

    2016-01-06

    Amphetamine dependence is relatively common in Sweden and it is the most frequently used substance among patients with intravenous drug abuse. Current treatment options are limited but recently substitution therapy with psychostimulant medication has been evaluated in several clinical trials. Such treatment is controversial in Sweden, perhaps due to the failure of experimental prescription of psychostimulants in the 1960s. Recent clinical trials however indicate that structured treatment programs with psychostimulants might have positive effects, although the results are inconsistent and the evidence base is still limited. Future research is needed in order to determine the potential role of substitution therapy for amphetamine dependence in clinical practice.

  17. Benzodiazepines consumption: does dependence vary with age?

    PubMed

    Gérardin, Marie; Victorri-Vigneau, Caroline; Guerlais, Marylène; Guillou-Landreat, Morgane; Grall-Bronnec, Marie; Jolliet, Pascale

    2014-09-01

    We have compared two groups of chronic benzodiazepines (or zolpidem/zopiclone) users: "Seniors," aged 65 years or more, and "Adults," aged less than 65 years. The study took place in the Pays de Loire region. The questionnaire assesses dependence based on items from the DSM-IV. The analysis was based on 176 Senior questionnaires and 212 Adult questionnaires. Whereas Senior patients take benzodiazepines routinely with little negative consequences, Adults suffer from underlying psychological trouble, mention a higher consumption than planned, which causes negative consequences. 35.2% of Seniors are dependent on benzodiazepines versus 49.8% of Adults.

  18. Temperature dependence of thermopower in molecular junctions

    NASA Astrophysics Data System (ADS)

    Kim, Youngsang; Lenert, Andrej; Meyhofer, Edgar; Reddy, Pramod

    2016-07-01

    The thermoelectric properties of molecular junctions are of considerable interest due to their promise for efficient energy conversion. While the dependence of thermoelectric properties of junctions on molecular structure has been recently studied, their temperature dependence remains unexplored. Using a custom built variable temperature scanning tunneling microscope, we measured the thermopower and electrical conductance of individual benzenedithiol junctions over a range of temperatures (100 K-300 K). We find that while the electrical conductance is independent of temperature, the thermopower increases linearly with temperature, confirming the predictions of the Landauer theory.

  19. Time-Dependent Molecular Reaction Dynamics

    NASA Astrophysics Data System (ADS)

    Öhrn, Yngve

    2007-11-01

    This paper is a brief review of a time-dependent, direct, nonadiabatic theory of molecular processes called Electron Nuclear Dynamics (END). This approach to the study of molecular reaction dynamics is a hierarchical theory that can be applied at various levels of approximation. The simplest level of END uses classical nuclei and represents all electrons by a single, complex, determinantal wave function. The wave function parameters such as average nuclear positions and momenta, and molecular orbital coefcients carry the time dependence and serve as dynamical variables. Examples of application are given of the simplest level of END to ion-atom and ion-molecule reactions.

  20. Investigations of Low Temperature Time Dependent Cracking

    SciTech Connect

    Van der Sluys, W A; Robitz, E S; Young, B A; Bloom, J

    2002-09-30

    The objective of this project was to investigate metallurgical and mechanical phenomena associated with time dependent cracking of cold bent carbon steel piping at temperatures between 327 C and 360 C. Boiler piping failures have demonstrated that understanding the fundamental metallurgical and mechanical parameters controlling these failures is insufficient to eliminate it from the field. The results of the project consisted of the development of a testing methodology to reproduce low temperature time dependent cracking in laboratory specimens. This methodology was used to evaluate the cracking resistance of candidate heats in order to identify the factors that enhance cracking sensitivity. The resultant data was integrated into current available life prediction tools.

  1. Pharmacotherapy of dual substance abuse and dependence.

    PubMed

    Kenna, George A; Nielsen, Darci M; Mello, Patricia; Schiesl, Alison; Swift, Robert M

    2007-01-01

    The US FDA has approved a limited number of treatments for alcohol, nicotine and opioid dependence; however, no treatments for other abused drugs such as marijuana, cocaine or methamphetamine are approved. This review focuses on research into drug pharmacotherapies, particularly single-drug therapies, for substance abuse and dependence contributing to the most important dual substance use disorders (SUDs). Given the implications of poly-substance abuse, it is essential that clinicians and researchers be aware of potential pharmacotherapies for the treatment of dual SUDs.A substantial number of patients abuse more than one drug concurrently, complicating the treatment of SUD and leaving clinicians with few FDA-approved drug options for their patients. In this era of evidence-based medicine, such patients are typically treated with therapeutically proven medications, but in ways that are outside the scope of a drug's original indication by the FDA. Such 'off-label' prescribing has become an important therapeutic strategy for practitioners seeking treatments for other diseases in subpopulations such as paediatrics and gerontology or for medical conditions such as oncology or mental illness. Similarly, the information that most clinicians use to make their decisions for treating patients abusing multiple drugs stems from trials treating a single SUD, anecdotal experiences from their own practice or that of their colleagues, or single-case studies reported in the literature. The existing evidence suggests there are few treatments for SUDs that confer significant reductions in substance use across a broad patient population. Moreover, even fewer clinical efficacy trials have been conducted that provide evidence of therapeutic benefit for these drugs. Recognising the difficulty in making the proper drug choice for facilitating maximum treatment success, this review highlights the single drugs or drug combinations that show some potential for treating dual SUDs. This

  2. Testing for nonlinear dependence in financial markets.

    PubMed

    Dore, Mohammed; Matilla-Garcia, Mariano; Marin, Manuel Ruiz

    2011-07-01

    This article addresses the question of improving the detection of nonlinear dependence by means of recently developed nonparametric tests. To this end a generalized version of BDS test and a new test based on symbolic dynamics are used on realizations from a well-known artificial market for which the dynamic equation governing the market is known. Comparisons with other tests for detecting nonlinearity are also provided. We show that the test based on symbolic dynamics outperforms other tests with the advantage that it depends only on one free parameter, namely the embedding dimension. This does not hold for other tests for nonlinearity.

  3. Gate dependent electronic Raman scattering in graphene

    NASA Astrophysics Data System (ADS)

    Riccardi, E.; Méasson, M.-A.; Kazayous, M.; Sacuto, A.; Gallais, Y.; Spectroscopy Of Quasi-Particles (Squap) Team

    We report the direct observation of polarization resolved electronic Raman scattering in a gated monolayer graphene device. The evolution of the electronic Raman scattering spectra with gate voltage and its polarization dependence are in full agreement with theoretical expectations for non-resonant Raman processes involving interband electron-hole excitations across the Dirac cone. We further show that the spectral dependence of the electronic Raman scattering signal can be simply described by the dynamical polarizability of graphene in the long wavelength limit. The possibility to directly observe Dirac fermion excitations in graphene opens the way to promising Raman investigations of electronic properties of graphene and other 2D materials.

  4. Gate dependent electronic Raman scattering in graphene

    NASA Astrophysics Data System (ADS)

    Riccardi, E.; Méasson, M.-A.; Kazayous, M.; Sacuto, A.; Gallais, Y.; Spectroscopy Of Quasi-Particles (Squap) Team

    We report the direct observation of polarization resolved electronic Raman scattering in a gated monolayer graphene device. The evolution of the electronic Raman scattering spectra with gate voltage and its polarization dependence are in full agreement with theoretical expectations for non-resonant Raman processes involving interband electron-hole excitations across the Dirac cone [1]. We further show that the spectral dependence of the electronic Raman scattering signal can be simply described by the dynamical polarizability of graphene in the long wavelength limit [2]. The possibility to directly observe Dirac fermion excitations in graphene opens the way to promising Raman investigations of electronic properties of graphene and other 2D materials.

  5. Age differences in field dependence/independence.

    PubMed

    Panek, P E

    1985-01-01

    The present study investigated age and sex differences in field-dependence/independence controlling statistically for IQ. The Group Embedded Figures Test and Quick Test were administered to 46 young adults, 22 male and 24 female (M age = 18.65 years) and 45 old adults, 22 male and 23 female (M age = 73.96 years). Results indicated significant age differences in field dependence/independence existed even after controlling statistically for intelligence. No significant sex differences were found in either age group; for young adults this is inconsistent with extensive research. Implications of results were discussed.

  6. Time-dependent Flare Models with MALI

    NASA Astrophysics Data System (ADS)

    Kašparová, J.; Heinzel, P.; Varady, M.; Karlický, M.

    2003-01-01

    Temporal variations of Hα line profile intensities related to electron beams are presented. We show first results of time dependent simulations of a chromospheric response to a 1 sec monoenergetic electron beam. 1-D hydrodynamic code together with particle representation of the beam have been used to calculate atmospheric evolution. Time dependent radiative transfer problem has been solved for the resulting atmosphere in the MALI approach, using the Crank-Nicholson implicit scheme. Non-thermal collisional rates were included in linearised equations of statistical equilibrium.

  7. Dependence in Classification of Aluminium Waste

    NASA Astrophysics Data System (ADS)

    Resti, Y.

    2015-06-01

    Based on the dependence between edge and colour intensity of aluminium waste image, the aim of this paper is to classify the aluminium waste into three types; pure aluminium, not pure aluminium type-1 (mixed iron/lead) and not pure aluminium type 2 (unrecycle). Principal Component Analysis (PCA) was employed to reduction the dimension of image data, while Bayes’ theorem with the Gaussian copula was applied to classification. The copula was employed to handle dependence between edge and colour intensity of aluminium waste image. The results showed that the classifier has been correctly classifiable by 88.33%.

  8. Temperature dependence in atom-surface scattering

    NASA Astrophysics Data System (ADS)

    Pollak, Eli; Manson, J. R.

    2012-03-01

    It is shown that a straightforward measure of the temperature dependence of energy resolved atom-surface scattering spectra measured under classical conditions can be related to the strength of the surface corrugation. Using classical perturbation theory combined with a Langevin bath formalism for describing energy transfer, explicit expressions for the scattering probabilities are obtained for both two-dimensional, in-plane scattering and full three-dimensional scattering. For strong surface corrugations results expressed as analytic closed-form equations for the scattering probability are derived which demonstrate that the temperature dependence of the scattering probability weakens with increasing corrugation strength. The relationship to the inelastic rainbow is briefly discussed.

  9. Sustained-release naltrexone for opioid dependence.

    PubMed

    Lobmaier, P; Kornør, H; Kunøe, N; Bjørndal, A

    2008-04-16

    Naltrexone is an opioid antagonist which effectively blocks heroin effects. Since opioid dependence treatment with naltrexone tablets suffers from high dropout rates, several depot injections and implants are under investigation. Sustained-release formulations are claimed to be effective, but a systematic review of the literature is lacking. To evaluate the effectiveness of sustained-release naltrexone for opioid dependence and its adverse effects in different study populations. The following databases were searched from their inception to November 2007: Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, LILACS, PsycINFO, ISI Web of Science, trial database at http://clinicaltrials.gov, available NIDA monographs, CPDD and AAAP conference proceedings. The reference lists of identified studies, published reviews and relevant web sides were searched manually. Study authors and drug companies were contacted to obtain any unpublished material or missing data. To evaluate effectiveness only RCTs were included. To evaluate safety, any clinical trial reporting adverse effects was assessed. Treatment condition was extended to include alcohol dependent subjects and healthy volunteers. Reviewers independently evaluated the reports, rated methodological quality and extracted data. Analyses were performed separately for opioid dependent, alcohol dependent and healthy participants. Foe effectiveness, one report met inclusion criteria. Two dosages of naltrexone depot injections (192 and 384 mg) were compared to placebo. High-dose significantly increased days in treatment compared to placebo (WMD 21.00, 95% CI 10.68 to 31.32, p<0.0001). High-dose compared to low-dose significantly increased days in treatment (WMD 12.00, 95% CI 1.69 to 22.31, p=0.02). Number of patients retained in treatment did not show significant differences between groups. For adverse effects, seventeen reports met inclusion criteria analyses, six were RCTs. Side effects were significantly

  10. Water Temperature Dependence of Single Bubble Sonoluminescence

    SciTech Connect

    Hilgenfeldt, S.; Lohse, D.; Moss, W.C.

    1998-02-01

    The strong dependence of the intensity of single bubble sonoluminescence (SBSL) on water temperature observed in experiment can be accounted for by the temperature dependence of the material constants of water, most essentially of the viscosity, of the argon solubility in water, and of the vapor pressure. The strong increase of light emission at low water temperatures is due to the possibility of applying higher driving pressures, caused by increased bubble stability. The presented calculations combine the Rayleigh-Plesset equation based hydrodynamical/chemical approach to SBSL and full gas dynamical calculations of the bubble{close_quote}s interior. {copyright} {ital 1998} {ital The American Physical Society}

  11. On spectral dependence of polarization of asteroids

    NASA Astrophysics Data System (ADS)

    Lupishko, D. F.; Shkuratov, Yu. G.

    2016-09-01

    From the analysis of all of the data available on the spectral dependence of polarization of light reflected by asteroids, it has been shown that the slope of the spectral dependence of polarization of asteroids changes its sign, when moving from the negative branch of the phase curve of polarization to the positive one. This effect also manifests itself in the spectral behavior of polarization of the Moon and, probably, in the polarization of the other atmosphereless bodies. From the analysis of a population of asteroids of different types, a weak correlation between the spectral slopes of the polarization degree and the albedo has been found.

  12. Temperature dependent dissipation in magnetic nanoparticles

    NASA Astrophysics Data System (ADS)

    Regmi, R.; Naik, A.; Thakur, J. S.; Vaishnava, P. P.; Lawes, G.

    2014-05-01

    We parameterized the temperature dependent magnetic dissipation of iron oxide nanoparticles fixed in a frozen aqueous solution in an ac magnetic field. The magnetic power dissipated can be modeled by considering only Neel relaxation. This dissipation increased monotonically with temperature, increasing by approximately 50% between -40 °C and -10 °C. These experimental results provide quantitative confirmation for the Neel model of magnetic dissipative heating for nanoparticles rigidly confined in a solid matrix. We also find substantial temperature dependence in the magnetic dissipation of nanoparticles suspended in a liquid, which has important consequences for potential applications of magnetic nanoparticles for hyperthermia.

  13. Does Melissa Officinalis Cause Withdrawal or Dependence?

    PubMed Central

    Demirci, Kadir; Akgönül, Mehmet; Demirdaş, Arif; Akpınar, Abdullah

    2015-01-01

    Introduction: Melissa officinalis is a medical and aromatic plant that is used for its hypnotic, sedative, and spasmolytic effects. This report presents a case study of30-year-old patient who was admitted to an emergency department with restlessness, tremor, distractibility, and sweating following a discontinuation of Melissa officinalis consumption. Case report: In this case, withdrawal symptoms may be related to the dependence effect caused by long-term use of Melissa officinalis. Although Melissa officinalis, a plant, is preferred by many patients as an alternative to pharmaceutical drugs, patients should be made aware that it may have a risk of dependency and can lead to withdrawal symptoms. PMID:25870482

  14. What can dependence theories tell us about assessing the emergence of tobacco dependence?

    PubMed

    Tiffany, Stephen T; Conklin, Cynthia A; Shiffman, Saul; Clayton, Richard R

    2004-06-01

    Little is known about the processes that underlie changes in smoking that occur between the first use of a cigarette, subsequent regular use and eventual addictive use. At present, assessments of those critical processes are poorly developed and not strongly informed by contemporary models of drug dependence. The preceding three papers in this special issue address explicitly how modern drug-dependence theories describe the emergence of drug dependence and the implications of those theories for assessment. The papers covered three domains of theories: negative reinforcement, positive reinforcement, and cognitive and social learning. In this paper, we summarize these reviews and extract general themes and issues that emerge across all the articles. These include: (1) the importance of learning processes; (2) limitations of self-report measures; (3) the view of dependence as a process and not a state; (4) the conception of dependence on a continuum in contrast to the conventional perspective of tobacco dependence as a natural category; (5) the ontological status of the dependence concept; (6) limitations of backward extrapolations from adult assessments; (7) the possibility of multiple dimensions or forms of dependence; and (8) the value of a transdisciplinary approach when studying the emergence of tobacco dependence.

  15. Some pharmacological aspects of drug dependence.

    PubMed

    Chesher, G B

    1975-12-06

    The self-administration of drugs to achieve altered states of consciousness is recognized as normal human behaviour. Community attitudes towards drug use vary according to the drug and often bear little relationship to the known pharmacological and toxicological effects of the drug. For an objective assessment of the potential dangers associated with drug use, a distinction is made between drug use and drug abuse. It is stressed that the progression from drug use to drug abuse involves social and psychological factors in addition to the pharmacological factors which are outlined in this paper. The sequential development of drug dependency is described under the headings: Induction; continued consumption; compulsive consumption; withdrawal; abstinence; reinduction. Man uses psychotropic drugs because he finds the effects rewarding. Some experimental models to explore the neurophysiological basis of the reward are described. Experiments employing inhibitors of protein synthesis suggest that the phenomena of tolerance and physical dependence involve the synthesis of new protein. It has been suggested that the new protein might be new receptor molecules for the drug or neurotransmitter substances. These new receptors might constitute a "drug memory" and provide a possible explanation for high relapse rate of drug dependent subjects. A pharmacological basis for the methadone maintenance programme of management of narcotic dependent subjects is briefly outlined.

  16. Problems Identifying Independent and Dependent Variables

    ERIC Educational Resources Information Center

    Leatham, Keith R.

    2012-01-01

    This paper discusses one step from the scientific method--that of identifying independent and dependent variables--from both scientific and mathematical perspectives. It begins by analyzing an episode from a middle school mathematics classroom that illustrates the need for students and teachers alike to develop a robust understanding of…

  17. Context dependent anti-aliasing image reconstruction

    NASA Technical Reports Server (NTRS)

    Beaudet, Paul R.; Hunt, A.; Arlia, N.

    1989-01-01

    Image Reconstruction has been mostly confined to context free linear processes; the traditional continuum interpretation of digital array data uses a linear interpolator with or without an enhancement filter. Here, anti-aliasing context dependent interpretation techniques are investigated for image reconstruction. Pattern classification is applied to each neighborhood to assign it a context class; a different interpolation/filter is applied to neighborhoods of differing context. It is shown how the context dependent interpolation is computed through ensemble average statistics using high resolution training imagery from which the lower resolution image array data is obtained (simulation). A quadratic least squares (LS) context-free image quality model is described from which the context dependent interpolation coefficients are derived. It is shown how ensembles of high-resolution images can be used to capture the a priori special character of different context classes. As a consequence, a priori information such as the translational invariance of edges along the edge direction, edge discontinuity, and the character of corners is captured and can be used to interpret image array data with greater spatial resolution than would be expected by the Nyquist limit. A Gibb-like artifact associated with this super-resolution is discussed. More realistic context dependent image quality models are needed and a suggestion is made for using a quality model which now is finding application in data compression.

  18. Chewing Maintains Hippocampus-Dependent Cognitive Function.

    PubMed

    Chen, Huayue; Iinuma, Mitsuo; Onozuka, Minoru; Kubo, Kin-Ya

    2015-01-01

    Mastication (chewing) is important not only for food intake, but also for preserving and promoting the general health. Recent studies have showed that mastication helps to maintain cognitive functions in the hippocampus, a central nervous system region vital for spatial memory and learning. The purpose of this paper is to review the recent progress of the association between mastication and the hippocampus-dependent cognitive function. There are multiple neural circuits connecting the masticatory organs and the hippocampus. Both animal and human studies indicated that cognitive functioning is influenced by mastication. Masticatory dysfunction is associated with the hippocampal morphological impairments and the hippocampus-dependent spatial memory deficits, especially in elderly. Mastication is an effective behavior for maintaining the hippocampus-dependent cognitive performance, which deteriorates with aging. Therefore, chewing may represent a useful approach in preserving and promoting the hippocampus-dependent cognitive function in older people. We also discussed several possible mechanisms involved in the interaction between mastication and the hippocampal neurogenesis and the future directions for this unique fascinating research.

  19. Context-Dependent Control over Attentional Capture

    ERIC Educational Resources Information Center

    Cosman, Joshua D.; Vecera, Shaun P.

    2013-01-01

    A number of studies have demonstrated that the likelihood of a salient item capturing attention is dependent on the "attentional set" an individual employs in a given situation. The instantiation of an attentional set is often viewed as a strategic, voluntary process, relying on working memory systems that represent immediate task…

  20. Comparing Theories of Reference-Dependent Choice

    ERIC Educational Resources Information Center

    Bhatia, Sudeep

    2017-01-01

    Preferences are influenced by the presence or absence of salient choice options, known as reference points. This behavioral tendency is traditionally attributed to the loss aversion and diminishing sensitivity assumptions of prospect theory. In contrast, some psychological research suggests that reference dependence is caused by attentional biases…

  1. Organizational Change, Absenteeism, and Welfare Dependency

    ERIC Educational Resources Information Center

    Roed, Knut; Fevang, Elisabeth

    2007-01-01

    Based on Norwegian register data, we set up a multivariate mixed proportional hazard model (MMPH) to analyze nurses' pattern of work, sickness absence, nonemployment, and social insurance dependency from 1992 to 2000, and how that pattern was affected by workplace characteristics. The model is estimated by means of the nonparametric…

  2. Gravity-dependent transport in industrial processes

    NASA Technical Reports Server (NTRS)

    Ostrach, Simon; Kamotani, Yasuhiro

    1994-01-01

    Gravity-dependent transport phenomena in various industrial processes are investigated in order to address a broader range of microgravity phenomena and to develop new applications of microgravity. A number of important topics are identified and analyzed in detail. The present article describes results on coating flow, zeolite growth, and rotating electrochemical system.

  3. Colloidal solitary waves with temperature dependent compressibility

    NASA Astrophysics Data System (ADS)

    Azmi, A.; Marchant, T. R.

    2014-05-01

    Spatial solitary waves which form in colloidal suspensions of dielectric nanoparticles are considered. The interactions, or compressibility, of the colloidal particles, is modelled using a series in the particle density, or packing fraction, where the virial, or series, coefficients depend on the type of particle interaction model. Both the theoretical hard disk and sphere repulsive models, and a model with temperature dependent compressibility, are considered. Experimental results show that particle interactions can be temperature dependent and either repulsive or attractive in nature, so we model the second virial coefficient using a physically realistic temperature power law. One- and two-dimensional semi-analytical colloidal solitary wave solutions are found. Trial functions, based on the form of the nonlinear Schrödinger equation soliton, are used, together with averaging, to develop the semi-analytical solutions. When the background packing fraction is low, the one-dimensional solitary waves have three solutions branches (with a bistable regime) while the two-dimensional solitary waves have two solution branches, with a single stable branch. The temperature dependent second virial coefficient results in changes to the solitary wave properties and the parameter space, in which multiple solutions branches occur. An excellent comparison is found between the semi-analytical and numerical solutions.

  4. Pearson and Pedagogy: Countering Co-Dependency

    ERIC Educational Resources Information Center

    Fielder, John

    2008-01-01

    Noel Pearson and Marcia Langton have both used the terms "co-dependency" and "rescuing" as part of their challenge to the rights-based focus informing Indigenous policies in Australia since the 1960s. Their premise is that the liberal/Left welfare-based agenda, for decades, has largely overlooked Indigenous responsibility. At…

  5. Temperature-dependent Study of Isobutanol Decomposition

    DTIC Science & Technology

    2012-11-01

    conventional petrol becomes increasingly more fervent. New legislations and pressure is being forced on the fuel industry to reduce America’s dependence on...A. R.; Sakai, S.; Devasher, R. B. Time Resolved FTIR Analysis of Combustion of Ethanol, E85, and Gasoline in an Internal Combustion Engine . Rose

  6. Pearson and Pedagogy: Countering Co-Dependency

    ERIC Educational Resources Information Center

    Fielder, John

    2008-01-01

    Noel Pearson and Marcia Langton have both used the terms "co-dependency" and "rescuing" as part of their challenge to the rights-based focus informing Indigenous policies in Australia since the 1960s. Their premise is that the liberal/Left welfare-based agenda, for decades, has largely overlooked Indigenous responsibility. At…

  7. Dependency and Marginality in Kingston, Jamaica.

    ERIC Educational Resources Information Center

    Clarke, Colin G.

    1983-01-01

    Kingston, capital of Jamaica, has been molded by three institutions: colonialism, the sugar plantation, and slavery. It has an enormous marginal population living in permanent poverty and not absorbable into the labor force. This marginality, fundamentally related to dependent capitalism, sustains itself by keeping wages low. (CS)

  8. Spin multiplicity dependence of nonlinear optical properties.

    PubMed

    Jha, Prakash Chandra; Rinkevicius, Zilvinas; Agren, Hans

    2009-03-23

    Open-shell spin-restricted time-dependent density functional theory is applied to explore the spin multiplicity dependence of linear and nonlinear optical properties. An open-shell neutral conjugated system, the C(4)H(4)N radical in the doublet X(2)A(2), quartet X(4)A(2), and sextet X(6)A(1) states, is chosen as a model system to illustrate various aspects of the theory. It is found that irrespective of the exchange-correlation functional employed, the components of the polarizability alpha(-omega,omega) and first hyperpolarizability beta(-2 omega,omega,omega) show very different dependency with respect to the multiplicity, with an increasing trend for higher spin states. This is rationalized by the decrease in conjugation and stability of the system with increasing multiplicity, and by the way the interaction between unpaired electrons and the external field is shielded by remaining electrons of the molecule. The study suggests the applicability of open-shell systems for frequency-dependent nonlinear optical properties and for the possibility of spin control for such properties.

  9. Curvature Dependent Reactivity of Fullerenes and Nanotubes

    NASA Technical Reports Server (NTRS)

    Park, Seongjun; Cho, Kyeongjae; Srivastava, Deepak

    2000-01-01

    Dependence of pyramidalization angle, examples of nanotube surfaces, internal and external reactivity, and binding energies are some of the topics discussed in this conference presentation preprint. Final conclusions include the relationship between the pyramidal angle of the surface and its associated external reaction energy.

  10. Problems Identifying Independent and Dependent Variables

    ERIC Educational Resources Information Center

    Leatham, Keith R.

    2012-01-01

    This paper discusses one step from the scientific method--that of identifying independent and dependent variables--from both scientific and mathematical perspectives. It begins by analyzing an episode from a middle school mathematics classroom that illustrates the need for students and teachers alike to develop a robust understanding of…

  11. It All Depends on Your Attitude.

    ERIC Educational Resources Information Center

    Kastner, Bernice

    1992-01-01

    Presents six learning exercises that introduce students to the mathematics used to control and track spacecraft attitude. Describes the geocentric system used for Earthbound location and navigation, the celestial sphere, the spacecraft-based celestial system, time-dependent angles, observer-fixed coordinate axes, and spacecraft rotational axes.…

  12. It All Depends on Your Attitude.

    ERIC Educational Resources Information Center

    Kastner, Bernice

    1992-01-01

    Presents six learning exercises that introduce students to the mathematics used to control and track spacecraft attitude. Describes the geocentric system used for Earthbound location and navigation, the celestial sphere, the spacecraft-based celestial system, time-dependent angles, observer-fixed coordinate axes, and spacecraft rotational axes.…

  13. Linear dependencies between composite fermion states

    NASA Astrophysics Data System (ADS)

    Meyer, M. L.; Liabøtrø, O.; Viefers, S.

    2016-09-01

    The formalism of composite fermions (CFs) has been one of the most prominent and successful approaches to describing the fractional quantum Hall effect, in terms of trial many-body wave functions. Testing the accuracy of the latter typically involves rather heavy numerical comparison to exact diagonalization results. Thus, optimizing computational efficiency has been an important technical issue in this field. One generic (and not yet fully understood) property of the CF approach is that it tends to overcount the number of linearly independent candidate states for fixed sets of quantum numbers. Technically speaking, CF Slater determinants that are orthogonal before projection to the lowest Landau level, may lead to wave functions that are identical, or possess linear dependencies, after projection. This leads to unnecessary computations, and has been pointed out in the literature both for fermionic and bosonic systems. We here present a systematic approach that enables us to reveal all linear dependencies between bosonic compact states in the lowest CF ‘cyclotron energy’ sub-band, and almost all dependencies in higher sub-bands, at the level of the CF Slater determinants, i.e. before projection, which implies a major computational simplification. Our approach is introduced for so-called simple states of two-species rotating bosons, and then generalized to generic compact bosonic states, both one- and two-species. Some perspectives also apply to fermionic systems. The identities and linear dependencies we find, are analytically exact for ‘brute force’ projection in the disk geometry.

  14. Costs of Oil Dependence: A 2000 Update

    SciTech Connect

    Greene, D.L.

    2000-05-17

    Oil dependence remains a potentially serious economic and strategic problem for the United States. This report updates previous estimates of the costs of oil dependence to the U.S. economy and introduces several methodological enhancements. Estimates of the costs to the U.S. economy of the oil market upheavals of the last 30 years are in the vicinity of $7 trillion, present value 1998 dollars, about as large as the sum total of payments on the national debt over the same period. Simply adding up historical costs in 1998 dollars without converting to present value results in a Base Case cost estimate of $3.4 trillion. Sensitivity analysis indicates that cost estimates are sensitive to key parameters. A lower bound estimate of $1.7 trillion and an upper bound of $7.1 trillion (not present value) indicate that the costs of oil dependence have been large under almost any plausible set of assumptions. These cost estimates do not include military, strategic or political costs associated with U.S. and world dependence on oil imports.

  15. Cost of Oil Dependence: A 2000 Update

    SciTech Connect

    Greene, D.L.; Tishchishyna, N.I.

    2000-05-01

    Oil dependence remains a potentially serious economic and strategic problem for the United States. This report updates previous estimates of the costs of oil dependence to the U.S. economy and introduces several methodological enhancements. Estimates of the costs to the U.S. economy of the oil market upheavals of the last 30 years are in the vicinity of $7 trillion, present value 1998 dollars, about as large as the sum total of payments on the national debt over the same period. Simply adding up historical costs in 1998 dollars without converting to present value results in a Base Case cost estimate of $3.4 trillion. Sensitivity analysis indicates that cost estimates are sensitive to key parameters. A lower bound estimate of $1.7 trillion and an upper bound of $7.1 trillion (not present value) indicate that the costs of oil dependence have been large under almost any plausible set of assumptions. These cost estimates do not include military, strategic or political costs associated with U.S. and world dependence on oil imports.

  16. Pharmacotherapeutic Treatment of Alcohol Dependence: An Overview

    ERIC Educational Resources Information Center

    Graves, Erin; Goodwin, Lloyd R., Jr.

    2008-01-01

    Pharmacotherapy medications can reduce the likelihood of relapse, decrease craving intensity and severity of withdrawal symptoms, and bolster the likelihood of achieving and maintaining recovery goals for many individuals seeking recovery from alcohol dependence. An overview of the benefits and concerns of integrating pharmacotherapeutic…

  17. Instructional Media, Attitude Change and Field Dependence.

    ERIC Educational Resources Information Center

    Kloock, Terryl R.; And Others

    The effectiveness of two media types (sound film and still slides with audiotape) in changing student attitudes, and their impact on students varying in field dependency levels was examined. Subjects, 82 college students scoring at the high and low extremes of the Group Embedded Figures Test (GEFT), were randomly assigned to either a (1) multi-cue…

  18. Time-dependent freezing rate parcel model

    NASA Astrophysics Data System (ADS)

    Vali, G.; Snider, J. R.

    2015-02-01

    The time-dependent freezing rate (TDFR) model here described represents the formation of ice particles by immersion freezing within an air parcel. The air parcel trajectory follows an adiabatic ascent and includes a period in time when the parcel remains stationary at the top of its ascent. The description of the ice nucleating particles (INPs) in the air parcel is taken from laboratory experiments with cloud and precipitation samples and is assumed to represent the INP content of the cloud droplets in the parcel. Time dependence is included to account for variations in updraft velocity and for the continued formation of ice particles under isothermal conditions. The magnitudes of these factors are assessed on the basis of laboratory measurements. Results show that both factors give rise to three-fold variations in ice concentration for a realistic range of the input parameters. Refinements of the parameters specifying time dependence and INP concentrations are needed to make the results more specific to different atmospheric aerosol types. The simple model framework described in this paper can be adapted to more elaborate cloud models. The results here presented can help guide decisions on whether to include a time-dependent ice nucleation scheme or a simpler singular description in models.

  19. Time-dependent freezing rate parcel model

    NASA Astrophysics Data System (ADS)

    Vali, G.; Snider, J. R.

    2014-11-01

    The Time-Dependent Freezing Rate (TDFR) model here described represents the formation of ice particles by immersion freezing within an air parcel. The air parcel trajectory follows an adiabatic ascent and includes a period at time with the parcel remaining stationary at the top of its ascent. The description of the ice nucleating particles (INPs) in the air parcel is taken from laboratory experiments with cloud and precipitation samples and is assumed to represent the INP content of the cloud droplets in the parcel. Time-dependence is included to account for variations in updraft velocity and for the continued formation of ice particles at isothermal conditions. The magnitudes of these factors are assessed on the basis of laboratory measurements. Results show that both factors give rise to factors of about 3 variations in ice concentration for a realistic range of the input parameters. Refinements of the parameters specifying time-dependence and INP concentrations are needed to make the results more specific to different atmospheric aerosol types. The simple model framework described in this paper can be adapted to more elaborate cloud models. The results here presented can help guide decisions on whether to include a time-dependent ice nucleation scheme or a simpler singular description in models.

  20. Socioeconomic Heterogeneity of Mining-Dependent Counties.

    ERIC Educational Resources Information Center

    Nord, Mark; Luloff, A. E.

    1993-01-01

    Although the socioeconomic well-being of all U.S. mining-dependent counties was slightly above the national average in 1990, disaggregation reveals substantial effects of region and mining subsector. In particular, southern and Great Lakes coal-mining counties had significantly lower high school graduation rates and higher poverty and unemployment…

  1. Chewing Maintains Hippocampus-Dependent Cognitive Function

    PubMed Central

    Chen, Huayue; Iinuma, Mitsuo; Onozuka, Minoru; Kubo, Kin-Ya

    2015-01-01

    Mastication (chewing) is important not only for food intake, but also for preserving and promoting the general health. Recent studies have showed that mastication helps to maintain cognitive functions in the hippocampus, a central nervous system region vital for spatial memory and learning. The purpose of this paper is to review the recent progress of the association between mastication and the hippocampus-dependent cognitive function. There are multiple neural circuits connecting the masticatory organs and the hippocampus. Both animal and human studies indicated that cognitive functioning is influenced by mastication. Masticatory dysfunction is associated with the hippocampal morphological impairments and the hippocampus-dependent spatial memory deficits, especially in elderly. Mastication is an effective behavior for maintaining the hippocampus-dependent cognitive performance, which deteriorates with aging. Therefore, chewing may represent a useful approach in preserving and promoting the hippocampus-dependent cognitive function in older people. We also discussed several possible mechanisms involved in the interaction between mastication and the hippocampal neurogenesis and the future directions for this unique fascinating research. PMID:26078711

  2. Serial dependence in the perception of attractiveness

    PubMed Central

    Xia, Ye; Leib, Allison Yamanashi; Whitney, David

    2016-01-01

    The perception of attractiveness is essential for choices of food, object, and mate preference. Like perception of other visual features, perception of attractiveness is stable despite constant changes of image properties due to factors like occlusion, visual noise, and eye movements. Recent results demonstrate that perception of low-level stimulus features and even more complex attributes like human identity are biased towards recent percepts. This effect is often called serial dependence. Some recent studies have suggested that serial dependence also exists for perceived facial attractiveness, though there is also concern that the reported effects are due to response bias. Here we used an attractiveness-rating task to test the existence of serial dependence in perceived facial attractiveness. Our results demonstrate that perceived face attractiveness was pulled by the attractiveness level of facial images encountered up to 6 s prior. This effect was not due to response bias and did not rely on the previous motor response. This perceptual pull increased as the difference in attractiveness between previous and current stimuli increased. Our results reconcile previously conflicting findings and extend previous work, demonstrating that sequential dependence in perception operates across different levels of visual analysis, even at the highest levels of perceptual interpretation. PMID:28006077

  3. Ion-dependent gating of kainate receptors.

    PubMed

    Bowie, Derek

    2010-01-01

    Ligand-gated ion channels are an important class of signalling protein that depend on small chemical neurotransmitters such as acetylcholine, l-glutamate, glycine and gamma-aminobutyrate for activation. Although numerous in number, neurotransmitter substances have always been thought to drive the receptor complex into the open state in much the same way and not rely substantially on other factors. However, recent work on kainate-type (KAR) ionotropic glutamate receptors (iGluRs) has identified an exception to this rule. Here, the activation process fails to occur unless external monovalent anions and cations are present. This absolute requirement of ions singles out KARs from all other ligand-gated ion channels, including closely related AMPA- and NMDA-type iGluR family members. The uniqueness of ion-dependent gating has earmarked this feature of KARs as a putative target for the development of selective ligands; a prospect all the more compelling with the recent elucidation of distinct anion and cation binding pockets. Despite these advances, much remains to be resolved. For example, it is still not clear how ion effects on KARs impacts glutamatergic transmission. I conclude by speculating that further analysis of ion-dependent gating may provide clues into how functionally diverse iGluRs families emerged by evolution. Consequently, ion-dependent gating of KARs looks set to continue to be a subject of topical inquiry well into the future.

  4. Perceived Lightness Depends on Perceived Spatial Arrangement

    ERIC Educational Resources Information Center

    Gilchrist, Alan L.

    1977-01-01

    Shows that the perceived shade of gray depends on the luminance relationship between surfaces perceived to be in the same plane and not between surfaces that are merely adjacent in the retinal image. This implies that lateral inhibition cannot explain lightness constancy. (MLH)

  5. Autofellatio: a power and dependency conflict.

    PubMed

    Cavenar, J O; Spaulding, J G; Butts, N T

    1977-11-01

    The literature concerning autofellatio is reviewed, and two additional cases are reported. A third case of a neurotic patient in whom there was a reversal of an autofellatio fantasy is presented. These cases seem to involve narcissism, dependency, and power conflicts as have those cases previously reported in the literature.

  6. Conflict Adaptation Depends on Task Structure

    ERIC Educational Resources Information Center

    Akcay, Caglar; Hazeltine, Eliot

    2008-01-01

    The dependence of the Simon effect on the correspondence of the previous trial can be explained by the conflict-monitoring theory, which holds that a control system adjusts automatic activation from irrelevant stimulus information (conflict adaptation) on the basis of the congruency of the previous trial. The authors report on 4 experiments…

  7. Stress Disrupts Context-Dependent Memory

    ERIC Educational Resources Information Center

    Schwabe, Lars; Bohringer, Andreas; Wolf, Oliver T.

    2009-01-01

    Memory is facilitated when the retrieval context resembles the learning context. The brain structures underlying contextual influences on memory are susceptible to stress. Whether stress interferes with context-dependent memory is still unknown. We exposed healthy adults to stress or a control procedure before they learned an object-location task…

  8. Pharmacotherapeutic Treatment of Alcohol Dependence: An Overview

    ERIC Educational Resources Information Center

    Graves, Erin; Goodwin, Lloyd R., Jr.

    2008-01-01

    Pharmacotherapy medications can reduce the likelihood of relapse, decrease craving intensity and severity of withdrawal symptoms, and bolster the likelihood of achieving and maintaining recovery goals for many individuals seeking recovery from alcohol dependence. An overview of the benefits and concerns of integrating pharmacotherapeutic…

  9. Transverse impedance localization using intensity dependent optics

    SciTech Connect

    Calaga,R.; Arduini, G.; Metral, E.; Papotti, G.; Quatraro, D.; Rumolo, G.; Salvant, B.; Tomas, R.

    2009-05-04

    Measurements of transverse impedance in the SPS to track the evolution over the last few years show discrepancies compared to the analytical estimates of the major contributors. Recent measurements to localize the major sources of the transverse impedance using intensity dependent optics are presented. Some simulations using HEADTAIL to understand the limitations of the reconstruction and related numerical aspects are also discussed.

  10. Correlates of Baclofen Effectiveness in Alcohol Dependence

    PubMed Central

    Shukla, Lekhansh; Shukla, Tulika; Bokka, Spandana; Kandasamy, Arun; Benegal, Vivek; Murthy, Pratima; Chand, Prabhat

    2015-01-01

    Alcohol dependence is a global concern. Baclofen has shown promise as an anti-craving agent but its efficiency remains to be settled. We reviewed 549 male cases diagnosed with alcohol dependence who received Acamprosate (201) or Baclofen (348). ‘Time to first drink’ was compared between two groups and multiple regression analysis was done in baclofen group to identify correlates of effectiveness. There was a significant difference in outcome measure between Baclofen (M = 4.44, SD = 3.75) and Acamprosate group (M = 3.73, SD = 2.19); t (547) = 2.45, P = 0.01. Initial regression analysis with six predictor variables (average daily alcohol units, current age, age at onset of dependence, family history, duration of dependence and dose of baclofen in mg/day) showed significant correlation of outcome variable with only two predictor variables — dose of baclofen and average daily intake. Using the hierarchical method it was found that ‘dose of baclofen’ and ‘average alcohol intake’ explain a significant amount of variance in ‘time to first drink’. [F (1, 345) = 182.8, P < 0.001, R2 = 0.52, R2adjusted = 0.51]. This information can be used to select patients in long term longitudinal studies and may explain variable results seen in clinical trials of baclofen done earlier. PMID:26664095

  11. Engineering Design for a Technological Dependent Society

    ERIC Educational Resources Information Center

    Parden, Robert J.

    1974-01-01

    Discusses a Sloan Foundation undergraduate project conducted at the University of California at Santa Clara, with emphases upon interdisciplinary design. Indicates that engineering should be seen as a broad education for a technology dependent society, rather than education leading to a specialized, dead-end career. (CC)

  12. Organizational Change, Absenteeism, and Welfare Dependency

    ERIC Educational Resources Information Center

    Roed, Knut; Fevang, Elisabeth

    2007-01-01

    Based on Norwegian register data, we set up a multivariate mixed proportional hazard model (MMPH) to analyze nurses' pattern of work, sickness absence, nonemployment, and social insurance dependency from 1992 to 2000, and how that pattern was affected by workplace characteristics. The model is estimated by means of the nonparametric…

  13. Term Dependence: Truncating the Bahadur Lazarsfeld Expansion.

    ERIC Educational Resources Information Center

    Losee, Robert M., Jr.

    1994-01-01

    Studies the performance of probabilistic information retrieval systems using differing statistical dependence assumptions when estimating the probabilities inherent in the retrieval model. Experimental results using the Bahadur Lazarsfeld expansion on the Cystic Fibrosis database are discussed that suggest that incorporating term dependence…

  14. Term Dependence: Truncating the Bahadur Lazarsfeld Expansion.

    ERIC Educational Resources Information Center

    Losee, Robert M., Jr.

    1994-01-01

    Studies the performance of probabilistic information retrieval systems using differing statistical dependence assumptions when estimating the probabilities inherent in the retrieval model. Experimental results using the Bahadur Lazarsfeld expansion on the Cystic Fibrosis database are discussed that suggest that incorporating term dependence…

  15. Assessment of seismic loss dependence using copula.

    PubMed

    Goda, Katsuichiro; Ren, Jiandong

    2010-07-01

    The catastrophic nature of seismic risk is attributed to spatiotemporal correlation of seismic losses of buildings and infrastructure. For seismic risk management, such correlated seismic effects must be adequately taken into account, since they affect the probability distribution of aggregate seismic losses of spatially distributed structures significantly, and its upper tail behavior can be of particular importance. To investigate seismic loss dependence for two closely located portfolios of buildings, simulated seismic loss samples, which are obtained from a seismic risk model of spatially distributed buildings by taking spatiotemporally correlated ground motions into account, are employed. The characterization considers a loss frequency model that incorporates one dependent random component acting as a common shock to all buildings, and a copula-based loss severity model, which facilitates the separate construction of marginal loss distribution functions and nonlinear copula function with upper tail dependence. The proposed method is applied to groups of wood-frame buildings located in southwestern British Columbia. Analysis results indicate that the dependence structure of aggregate seismic losses can be adequately modeled by the right heavy tail copula or Gumbel copula, and that for the considered example, overall accuracy of the proposed method is satisfactory at probability levels of practical interest (at most 10% estimation error of fractiles of aggregate seismic loss). The developed statistical seismic loss model may be adopted in dynamic financial analysis for achieving faster evaluation with reasonable accuracy.

  16. Smartphone dependence classification using tensor factorization

    PubMed Central

    Kim, Yejin; Yook, In Hye; Yu, Hwanjo; Kim, Dai-Jin

    2017-01-01

    Excessive smartphone use causes personal and social problems. To address this issue, we sought to derive usage patterns that were directly correlated with smartphone dependence based on usage data. This study attempted to classify smartphone dependence using a data-driven prediction algorithm. We developed a mobile application to collect smartphone usage data. A total of 41,683 logs of 48 smartphone users were collected from March 8, 2015, to January 8, 2016. The participants were classified into the control group (SUC) or the addiction group (SUD) using the Korean Smartphone Addiction Proneness Scale for Adults (S-Scale) and a face-to-face offline interview by a psychiatrist and a clinical psychologist (SUC = 23 and SUD = 25). We derived usage patterns using tensor factorization and found the following six optimal usage patterns: 1) social networking services (SNS) during daytime, 2) web surfing, 3) SNS at night, 4) mobile shopping, 5) entertainment, and 6) gaming at night. The membership vectors of the six patterns obtained a significantly better prediction performance than the raw data. For all patterns, the usage times of the SUD were much longer than those of the SUC. From our findings, we concluded that usage patterns and membership vectors were effective tools to assess and predict smartphone dependence and could provide an intervention guideline to predict and treat smartphone dependence based on usage data. PMID:28636614

  17. Instructional Media, Attitude Change and Field Dependence.

    ERIC Educational Resources Information Center

    Kloock, Terryl R.; And Others

    The effectiveness of two media types (sound film and still slides with audiotape) in changing student attitudes, and their impact on students varying in field dependency levels was examined. Subjects, 82 college students scoring at the high and low extremes of the Group Embedded Figures Test (GEFT), were randomly assigned to either a (1) multi-cue…

  18. Youth At-Risk of Welfare Dependency.

    ERIC Educational Resources Information Center

    Kaplan, April

    1999-01-01

    This issue of WIN (Welfare Information Network) Issue Notes focuses on the tendency of children from low-income families to drop out of high school, become teen parents, become involved in drug-related activities, and become involved in other activities that place them at high risk of long-term welfare dependency. Section 1 offers the background.…

  19. Texas Employer 1996 Dependent Care Survey.

    ERIC Educational Resources Information Center

    Ruggiere, Paul; Glass, James

    Many employers have enacted "family-friendly benefits" in response to demands placed on their employees by the stress of caring for children or aging parents. The Employer Dependent Care Survey measured the prevalence of flexible work arrangements and child care and elder care benefits in Texas. Participating were 1,331 out of 6,500…

  20. Dependency Traits Among Parents of Drug Abusers

    ERIC Educational Resources Information Center

    Tennant, Forest S., Jr.

    1976-01-01

    Studies question whether there is a significant association between parents' dependency traits and drug habits in their offspring. Reported here is a survey of 1,091 young males. The reported occurrence of parents' alcohol consumption, smoking, use of stimulants and sedatives, and overeating were compared among abusers and non-users of hashish,…