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Sample records for 18f-labelled boronophenylalanine depending

  1. Cellular accumulation of 18F-labelled boronophenylalanine depending on DNA synthesis and melanin incorporation: a double-tracer microautoradiographic study of B16 melanomas in vivo.

    PubMed

    Kubota, R; Yamada, S; Ishiwata, K; Tada, M; Ido, T; Kubota, K

    1993-04-01

    The cellular distribution of 4-borono-2-[18F]fluoro-L-phenylalanine ([18F]FBPA, an analog of p-boronophenylaline), a potential agent for boron neutron capture therapy (BNCT), and [6-3H]thymidine ([3H]Thd, a DNA precursor) in murine two B16 melanoma sublines and FM3A mammary carcinoma was studied in vivo using double-tracer microautoradiography. Tumour volume, tumour age, cell density in the tissues and the proportion of S phase cells in the cell cycle were the same in the three tumour models. Volume doubling time, which represents tumour growth rate, was fastest in B16F10, followed by B16F1 (P < 0.05), the slowest being in FM3A (P < 0.001). The rate of DNA synthesis in S phase cells corresponded to the volume doubling time. The greatest amount of [18F]FBPA was observed in S phase melanocytes and the lowest amount was found in non-S phase non-melanocytes. The [18F]FBPA accumulation was primarily related to the activity of DNA synthesis and, secondarily, to the degree of pigmentation in melanocytes. The therapeutic efficacy of BNCT with p-boronophenylalanine may be greater in melanoma that exhibits greater DNA synthesis activity and higher melanin content.

  2. Cellular accumulation of 18F-labelled boronophenylalanine depending on DNA synthesis and melanin incorporation: a double-tracer microautoradiographic study of B16 melanomas in vivo.

    PubMed Central

    Kubota, R.; Yamada, S.; Ishiwata, K.; Tada, M.; Ido, T.; Kubota, K.

    1993-01-01

    The cellular distribution of 4-borono-2-[18F]fluoro-L-phenylalanine ([18F]FBPA, an analog of p-boronophenylaline), a potential agent for boron neutron capture therapy (BNCT), and [6-3H]thymidine ([3H]Thd, a DNA precursor) in murine two B16 melanoma sublines and FM3A mammary carcinoma was studied in vivo using double-tracer microautoradiography. Tumour volume, tumour age, cell density in the tissues and the proportion of S phase cells in the cell cycle were the same in the three tumour models. Volume doubling time, which represents tumour growth rate, was fastest in B16F10, followed by B16F1 (P < 0.05), the slowest being in FM3A (P < 0.001). The rate of DNA synthesis in S phase cells corresponded to the volume doubling time. The greatest amount of [18F]FBPA was observed in S phase melanocytes and the lowest amount was found in non-S phase non-melanocytes. The [18F]FBPA accumulation was primarily related to the activity of DNA synthesis and, secondarily, to the degree of pigmentation in melanocytes. The therapeutic efficacy of BNCT with p-boronophenylalanine may be greater in melanoma that exhibits greater DNA synthesis activity and higher melanin content. Images Figure 1 PMID:8471428

  3. 18F-labeling using click cycloadditions.

    PubMed

    Kettenbach, Kathrin; Schieferstein, Hanno; 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 (18)F in those molecules poses an exceeding challenge. Two major challenges during (18)F-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 (18)F-labeled prosthetic groups for click cycloadditions and will summarize recent trends in copper-catalyzed and copper-free click (18)F-cycloadditions. PMID:25003110

  4. One-step (18)F labeling of biomolecules using organotrifluoroborates.

    PubMed

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

    2015-09-01

    Herein we present a general protocol for the functionalization of biomolecules with an organotrifluoroborate moiety so that they can be radiolabeled with aqueous (18)F fluoride ((18)F(-)) and used for positron emission tomography (PET) imaging. Among the β(+)-emitting radionuclides, fluorine-18 ((18)F) is the isotope of choice for PET, and it is produced, on-demand, in many hospitals worldwide. Organotrifluoroborates can be (18)F-labeled in one step in aqueous conditions via (18)F-(19)F 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 (18)F-labeling method that obviates the need for HPLC purification. Within 30 min, (18)F-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 (18)F radiolabeling, takes 7-10 d. PMID:26313478

  5. (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

  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. Tetrazine-trans-cyclooctene ligation for the rapid construction of 18F labeled probes.

    PubMed

    Li, Zibo; Cai, Hancheng; Hassink, Matthew; Blackman, Melissa L; Brown, Richard C D; Conti, Peter S; Fox, Joseph M

    2010-11-14

    A radiolabeling method for bioconjugation based on the Diels-Alder reaction between 3,6-diaryl-s-tetrazines and an (18)F-labeled trans-cyclooctene is described. The reaction proceeds with exceptionally fast rates, making it an effective conjugation method within seconds at low micromolar concentrations.

  8. 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

  9. 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

  10. Efficient 18F labeling of cysteine-containing peptides and proteins using tetrazine-trans-cyclooctene ligation.

    PubMed

    Liu, Shuanglong; Hassink, Matthew; Selvaraj, Ramajeyam; Yap, Li-Peng; Park, Ryan; Wang, Hui; Chen, Xiaoyuan; Fox, Joseph M; Li, Zibo; Conti, Peter S

    2013-01-01

    18F positron emission tomography (PET) has a number of attributes that make it clinically attractive, including nearly 100% positron efficiency, very high specific radioactivity, and a short half-life of ≈ 110 minutes. However, the short half-life of 18F and the poor nucleophilicity of fluoride introduce challenges for the incorporation of 18F into complex molecules. Recently, the tetrazine-trans-cyclooctene ligation was introduced as a novel 18F labeling method that proceeds with fast reaction rates without catalysis. Herein we report an efficient method for 18F labeling of free cysteines of peptides and proteins based on sequential ligation with a bifunctional tetrazinyl-maleimide and an 18F-labeled trans-cyclooctene. The newly developed method was tested for site-specific labeling of both c(RGDyC) peptide and vascular endothelial growth factor (VEGF)-SH protein. Starting with 4 mCi of 18F-trans-cyclooctene and only 10 μg of tetrazine-RGD (80-100 μM) or 15 μg of tetrazine-VEGF (6.0 μM), 18F-labeled RGD peptide and VEGF protein could be obtained within 5 minutes in 95% yield and 75% yield, respectively. The obtained tracers were then evaluated in mice. In conclusion, a highly efficient method has been developed for site-specific 18F labeling of cysteine-containing peptides and proteins. The special characteristics of the tetrazine-trans-cyclooctene ligation provide unprecedented opportunities to synthesize 18F-labeled probes with high specific activity for PET applications.

  11. Radiosynthesis and preliminary biological evaluation of a new (18)F-labeled triethylene glycol derivative of triphenylphosphonium.

    PubMed

    Tominaga, Takahiro; Ito, Hiroaki; Ishikawa, Yoichi; Iwata, Ren; Ishiwata, Kiichi; Furumoto, Shozo

    2016-03-01

    Delocalized lipophilic cations such as [(18)F]fluorobenzyltriphenylphosphonium ([(18)F]FBnTP) can accumulate in mitochondria and have been used in myocardial perfusion imaging (MPI). In this study, we established a simplified method for [(18)F]FBnTP synthesis using triphenylphosphine hydrobromide (PPh3 •HBr) without preparing an intermediate that contains benzyl bromide structure. Applying this new method, we synthesized and evaluated a novel (18)F-labeled PEGylated BnTP derivative ([(18)F]FPEGBnTP). In vitro cellular uptake study demonstrated that [(18)F]FPEGBnTP accumulated in cells in proportion to the relative intensity of mitochondrial membrane potential. Biodistribution study revealed that the heart : liver uptake ratio of [(18)F]FPEGBnTP (4.00 at 60 min) was superior to that of [(18)F]FBnTP (1.50 at 60 min). However, [(18)F]FPEGBnTP showed slow blood clearance and high radioactivity uptake in bone at 120-min post-injection. These results imply the possibility of [(18)F]FPEGBnTP being used as a MPI agent. However, there is a need of further structural optimization and flow-dependent uptake study. PMID:26861736

  12. (18)F-Labeling of Mannan for Inflammation Research with Positron Emission Tomography.

    PubMed

    Li, Xiang-Guo; Hagert, Cecilia; Siitonen, Riikka; Virtanen, Helena; Sareila, Outi; Liljenbäck, Heidi; Tuisku, Jouni; Knuuti, Juhani; Bergman, Jörgen; Holmdahl, Rikard; Roivainen, Anne

    2016-09-01

    Recently mannan from Saccharomyces cerevisiae has been shown to be able to induce psoriasis and psoriatic arthritis in mice, and the phenotypes resemble the corresponding human diseases. To investigate the pathological processes, we set out to label mannan with fluorine-18 ((18)F) and study the (18)F-labeled mannan in vitro and in vivo with positron emission tomography (PET). Accordingly, mannan has been transformed into (18)F-fluoromannan with (18)F-bicyclo[6.1.0]nonyne. In mouse aorta, the binding of [(18)F]fluoromannan to the atherosclerotic lesions was clearly visualized and was significantly higher compared to blocking assays (P < 0.001) or healthy mouse aorta (P < 0.001). In healthy rats the [(18)F]fluoromannan radioactivity accumulated largely in the macrophage-rich organs such as liver, spleen, and bone marrow and the excess excreted in urine. Furthermore, the corresponding (19)F-labeled mannan has been used to induce psoriasis and psoriatic arthritis in mice, which indicates that the biological function of mannan is preserved after the chemical modifications. PMID:27660685

  13. (18)F-Labeling of Mannan for Inflammation Research with Positron Emission Tomography.

    PubMed

    Li, Xiang-Guo; Hagert, Cecilia; Siitonen, Riikka; Virtanen, Helena; Sareila, Outi; Liljenbäck, Heidi; Tuisku, Jouni; Knuuti, Juhani; Bergman, Jörgen; Holmdahl, Rikard; Roivainen, Anne

    2016-09-01

    Recently mannan from Saccharomyces cerevisiae has been shown to be able to induce psoriasis and psoriatic arthritis in mice, and the phenotypes resemble the corresponding human diseases. To investigate the pathological processes, we set out to label mannan with fluorine-18 ((18)F) and study the (18)F-labeled mannan in vitro and in vivo with positron emission tomography (PET). Accordingly, mannan has been transformed into (18)F-fluoromannan with (18)F-bicyclo[6.1.0]nonyne. In mouse aorta, the binding of [(18)F]fluoromannan to the atherosclerotic lesions was clearly visualized and was significantly higher compared to blocking assays (P < 0.001) or healthy mouse aorta (P < 0.001). In healthy rats the [(18)F]fluoromannan radioactivity accumulated largely in the macrophage-rich organs such as liver, spleen, and bone marrow and the excess excreted in urine. Furthermore, the corresponding (19)F-labeled mannan has been used to induce psoriasis and psoriatic arthritis in mice, which indicates that the biological function of mannan is preserved after the chemical modifications.

  14. Sultone opening with [18F]fluoride: an efficient 18F-labelling strategy for PET imaging.

    PubMed

    Schmitt, Sébastien; Bouteiller, Cédric; Barré, Louisa; Perrio, Cécile

    2011-11-01

    Sultones were subject to ring opening by nucleophilic attack with [(18)F]fluoride to afford easily purified (18)F-labelled hydrophilic sulfonated products in high yields. A two-step sequence including radiofluorination and coupling to lysine was then developed from a bis-sultone precursor as a model approach for the labelling of biopolymers.

  15. 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

  16. (18) F-labeled folic acid derivatives for imaging of the folate receptor via positron emission tomography.

    PubMed

    Schieferstein, Hanno; Ross, Tobias L

    2013-01-01

    The folate receptor (FR) is already known as a proven target in diagnostics and therapy of cancer. Furthermore, the FR is involved in inflammatory and autoimmune diseases. The major advantage as a valuable target is its strongly limited expression in healthy tissues. Over the past two decades, several folic acid-based radiopharmaceuticals addressing the FR have been developed, and some of them show great potential for applications in clinical routine. However, most of these radiofolates were developed for single photon emission computed tomography imaging, and only a few can be used for positron emission tomography (PET) imaging. The development of suitable (18) F-labeled derivatives for PET imaging of the FR has aroused great interest and recent studies revealed very promising candidates for further development and translation into human applications. In this review, we focus on the development of (18) F-labeled folic acid derivatives for PET imaging of the FR and discuss various radiochemical strategies and approaches towards (18) F-folates. Besides radiochemistry and (18) F-labeling, we briefly look into the crucial pharmacological parameters and the preclinical in vivo performance of those (18) F-folates.

  17. Comparison of two site-specifically (18)F-labeled affibodies for PET imaging of EGFR positive tumors.

    PubMed

    Su, Xinhui; Cheng, Kai; Jeon, Jongho; Shen, Bin; Venturin, Gianina Teribele; Hu, Xiang; Rao, Jianghong; Chin, Frederick T; Wu, Hua; Cheng, Zhen

    2014-11-01

    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 (64)Cu-DOTA-ZEGFR:1907 and (18)F-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 (64)Cu, (18)F may improve imaging of EGFR-expression and is more suitable for clinical application, but the labeling reaction of (18)F-FBEM-ZEGFR:1907 requires a long synthesis time. The aim of the present study is to develop a new generation of (18)F labeled affibody probes (Al(18)F-NOTA-ZEGFR:1907 and (18)F-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 Al(18)F to produce Al(18)F-NOTA-ZEGFR:1907. In a second approach the prosthetic group (18)F-labeled-2-cyanobenzothiazole ((18)F-CBT) was conjugated to Cys-ZEGFR:1907 to produce (18)F-CBT-ZEGFR:1907. Binding affinity and specificity of Al(18)F-NOTA-ZEGFR:1907 and (18)F-CBT-ZEGFR:1907 to EGFR were evaluated using A431 cells. Biodistribution and PET studies were conducted on mice bearing A431 xenografts after injection of Al(18)F-NOTA-ZEGFR:1907 or (18)F-CBT-ZEGFR:1907 with or without coinjection of unlabeled affibody proteins. The radiosyntheses of Al(18)F-NOTA-ZEGFR:1907 and (18)F-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 (18)F-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, Al(18)F-NOTA-ZEGFR:1907 demonstrated high in

  18. Site-specific (18)F-labeling of the protein hormone leptin using a general two-step ligation procedure.

    PubMed

    Flavell, Robert R; Kothari, Paresh; Bar-Dagan, Maya; Synan, Michael; Vallabhajosula, Shankar; Friedman, Jeffrey M; Muir, Tom W; Ceccarini, Giovanni

    2008-07-16

    The protein hormone leptin acts to regulate body fat and energy expenditure. Resistance to this hormone is implicated in human obesity and its pathophysiological consequences. In order to gain insight into the mechanism of leptin resistance, an (18)F-labeled derivative was developed to study the biodistribution of the hormone using positron emission tomography (PET). A two-step, site specific ligation approach was developed for this purpose, in which an aminooxy-reactive group was incorporated at the C-terminus of leptin using expressed protein ligation (EPL), which was subsequently derivatized with [ (18)F]fluorobenzaldehyde using an aniline-accelerated radiochemical oximation reaction. The modified hormone was shown to be biologically active in vitro and in vivo, and it was applied to PET imaging in ob/ ob mice. These protocols will allow for the routine production of site-specifically (18)F radiolabeled leptin, as well as other proteins, for use in PET imaging in systems from mouse to man.

  19. 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. PMID:27390067

  20. 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.

  1. A (18)F-labeled glucose analog: synthesis using a click labeling method and in vitro evaluation.

    PubMed

    Kim, Dong Hyun; Choe, Yearn Seong; Jung, Kyung-Ho; Lee, Kyung-Han; Choi, Joon Young; Choi, Yong; Kim, Byung-Tae

    2008-05-01

    A (18)F-labeled glucose analog, 4-[(2-[(18)F]fluoroethyl)-1-(beta-D: -glucopyranosyl)]-1H-1,2,3-triazole ([(18)F]1), was synthesized using a click labeling method and evaluated in vitro for its cellular transportation via glucose transporter (Glut-1) and its potential as a hexokinase substrate. The click labeling method was superior to conventional labeling method, due to a higher decay-corrected radiochemical yield (30% vs. 21%), higher specific activity (59.9 GBq/mumol vs. 23.5 GBq/mumol), and shorter synthesis time (75-80 min vs. 95-100 min). In vitro evaluation demonstrated that [(18)F]1 does not act as a hexokinase substrate and has low and non-specific uptake by SNU-C5 cells. These results suggest that click chemistry offers a rapid and efficient radiolabeling method which does not require the protection of functional groups, although a triazole moiety at C1 of [(18)F]1 is incompatible for hexokinase phosphorylation and facilitative diffusion via Glut-1. PMID:18481013

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

    PubMed

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

    2014-10-30

    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, (18)F-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. [(18)F]-18 and [(18)F]-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.

  3. 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

  4. 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.

  5. 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

  6. Synthesis of a Potent Aminopyridine-Based nNOS-Inhibitor by Two Recent No-Carrier-Added (18)F-Labelling Methods.

    PubMed

    Drerup, Christian; Ermert, Johannes; Coenen, Heinz H

    2016-01-01

    Nitric oxide (NO), an important multifunctional signaling molecule, is produced by three isoforms of NO-synthase (NOS) and has been associated with neurodegenerative disorders. Selective inhibitors of the subtypes iNOS (inducible) or nNOS (neuronal) are of great interest for decoding neurodestructive key factors, and (18)F-labelled analogues would allow investigating the NOS-function by molecular imaging with positron emission tomography. Especially, the highly selective nNOS inhibitor 6-((3-((3-fluorophenethylamino)methyl)phenoxy)methyl)-4-methylpyridin-2-amine (10) lends itself as suitable compound to be (18)F-labelled in no-carrier-added (n.c.a.) form. For preparation of the (18)F-labelled nNOS-Inhibitor [(18)F]10 a "build-up" radiosynthesis was developed based on a corresponding iodonium ylide as labelling precursor. The such activated phenethyl group of the compound was efficiently and regioselectively labelled with n.c.a. [(18)F]fluoride in 79% radiochemical yield (RCY). After conversion by reductive amination and microwave assisted displacement of the protecting groups, the desired nNOS-inhibitor was obtained in about 15% total RCY. Alternatively, for a simplified "late-stage" (18)F-labelling procedure a corresponding boronic ester precursor was synthesized and successfully used in a newer, copper(II) mediated n.c.a. (18)F-fluoro-deboroniation reaction, achieving the same total RCY. Thus, both methods proved comparatively suited to provide the highly selective NOS-inhibitor [(18)F]10 as probe for preclinical in vivo studies. PMID:27598109

  7. Synthesis of a Potent Aminopyridine-Based nNOS-Inhibitor by Two Recent No-Carrier-Added (18)F-Labelling Methods.

    PubMed

    Drerup, Christian; Ermert, Johannes; Coenen, Heinz H

    2016-09-01

    Nitric oxide (NO), an important multifunctional signaling molecule, is produced by three isoforms of NO-synthase (NOS) and has been associated with neurodegenerative disorders. Selective inhibitors of the subtypes iNOS (inducible) or nNOS (neuronal) are of great interest for decoding neurodestructive key factors, and (18)F-labelled analogues would allow investigating the NOS-function by molecular imaging with positron emission tomography. Especially, the highly selective nNOS inhibitor 6-((3-((3-fluorophenethylamino)methyl)phenoxy)methyl)-4-methylpyridin-2-amine (10) lends itself as suitable compound to be (18)F-labelled in no-carrier-added (n.c.a.) form. For preparation of the (18)F-labelled nNOS-Inhibitor [(18)F]10 a "build-up" radiosynthesis was developed based on a corresponding iodonium ylide as labelling precursor. The such activated phenethyl group of the compound was efficiently and regioselectively labelled with n.c.a. [(18)F]fluoride in 79% radiochemical yield (RCY). After conversion by reductive amination and microwave assisted displacement of the protecting groups, the desired nNOS-inhibitor was obtained in about 15% total RCY. Alternatively, for a simplified "late-stage" (18)F-labelling procedure a corresponding boronic ester precursor was synthesized and successfully used in a newer, copper(II) mediated n.c.a. (18)F-fluoro-deboroniation reaction, achieving the same total RCY. Thus, both methods proved comparatively suited to provide the highly selective NOS-inhibitor [(18)F]10 as probe for preclinical in vivo studies.

  8. 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

    2015-04-01

    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

  9. 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.

  10. Synthesis and Evaluation of 4-[18F]Fluoropropoxy-3-iodobenzylguanidine ([18F]FPOIBG): A Novel 18F-labeled Analogue of MIBG

    PubMed Central

    Vaidyanathan, Ganesan; McDougald, Darryl; Koumarianou, Eftychia; Choi, Jaeyeon; Hens, Marc; Zalutsky, Michael R.

    2015-01-01

    Introduction Radioiodinated meta-iodobenzylguanidine (MIBG), a norepinephrine transporter (NET) substrate, has been extensively used as an imaging agent to study the pathophysiology of the heart and for the diagnosis and treatment of neuroendocrine tumors. The goal of this study was to develop an 18F-labeled analogue of MIBG that like MIBG itself could be synthesized in a single radiochemical step. Towards this end, we designed 4-fluoropropoxy-3-iodobenzylguanidine (FPOIBG). Methods Standards of FPOIBG and 4-fluoropropoxy-3-bromobenzylguanidine (FPOBBG) as well as their tosylate precursors for labeling with 18F, and a tin precursor for the preparation of radioiodinated FPOIBG were synthesized. Radiolabeled derivatives were synthesized by nucleophilic substitution and electrophilic iododestannylation from the corresponding precursors. Labeled compounds were evaluated for NET transporter recognition in in vitro assays using three NET-expressing cell lines and in biodistribution experiments in normal mice, with all studies performed in a paired-label format. Competitive inhibition of [125I]MIBG uptake by unlabeled benzylguanidine compounds was performed in UVW-NAT cell line to determine IC50 values. Results [18F]FPOIBG was synthesized from the corresponding tosylate precursor in 5.2 ± 0.5% (n = 6) overall radiochemical yields starting with aqueous fluoride in about 105 min. In a paired-label in vitro assay, the uptake of [18F]FPOIBG at 2 h was 10.2 ± 1.5%, 39.6 ± 13.4%, and 13.3 ± 2.5%, in NET-expressing SK-N-SH, UVW-NAT, and SK-N-BE(2c) cells, respectively, while these values for [125I]MIBG were 57.3 ± 8.1%, 82.7 ± 8.9%, and 66.3 ± 3.6%. The specificity of uptake of both tracers was demonstrated by blocking with desipramine. The 125I-labeled congener of FPOIBG gave similar results. On the other hand, [18F]FPOBBG, a compound recently reported in the literature, demonstrated much higher uptake, albeit less than that of co-incubated [125I]MIBG. IC50 values for

  11. In vivo biodistribution of two [18F]-labelled muscarinic cholinergic receptor ligands: 2-[18F]- and 4-[18F]-fluorodexetimide.

    PubMed

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

    1991-01-01

    Two [18F]-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-[18F]- or 4-[18F]-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. PMID:2008155

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

    PubMed

    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 (18)F-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-[(18)F]fluorobenzoate ([(18)F]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 (18)F-labeled scFv-B43.13 ([(18)F]FBz-scFv-B43.13) was studied with PET. [(18)F]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

  13. 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

  14. 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

  15. 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.

  16. Improved radiosynthesis and preliminary in vivo evaluation of a (18)F-labeled glycopeptide-peptoid hybrid for PET imaging of neurotensin receptor 2.

    PubMed

    Maschauer, Simone; Greff, Cornelia; Einsiedel, Jürgen; Ott, Julian; Tripal, Philipp; Hübner, Harald; Gmeiner, Peter; Prante, Olaf

    2015-07-15

    The neurotensin receptor 2 (NTS2) is an attractive target for cancer imaging, as it is overexpressed in a variety of tumor types including prostate, pancreas and breast carcinoma. The aim of this study was the development of the first NTS2 subtype selective (18)F-labeled radioligand for imaging NTS2 expression in vivo by positron emission tomography (PET). The radiosynthesis of glycopeptoid (18)F-4 was realized by copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC), applying the prosthetic group 6-deoxy-6-[(18)F]fluoroglucosyl azide for (18)F-fluoroglycosylation of the alkyne-terminated NT(8-13) analog Pra-N-Me-Arg-Arg-Pro-N-homo-Tyr-Ile-Leu-OH. The binding affinity of the peptide-peptoid 4 for NTS2 was 7nM with excellent subtype selectivity over NTS1 (260-fold). In vitro autoradiography studies of rat brain slices confirmed the high selectivity of (18)F-4 for NTS2. Biodistribution experiments using HT29 and PC3 tumor-bearing nude mice revealed high renal and only moderate tumor uptake, while PET imaging experiments revealed specific binding of (18)F-4 in NTS2-positive tumors. As (18)F-4 displayed high stability in vitro but fast degradation in vivo, future work will focus on the development of metabolically more stable NT(8-13) analogs.

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

    PubMed

    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 (18)F-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 (18)F. 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, [(18)F]Fmpp2 produced heart images with good quality in both mice and rats. In the whole-body PET/CT images of mini-swine, [(18)F]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 [(18)F]Fmpp2 suggest that it is worth further investigation as a potential MPI agent. PMID:27646847

  18. 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

  19. 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

  20. 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

  1. 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.

  2. Synthesis and evaluation of new (18)F-labelled acetamidobenzoxazolone-based radioligands for imaging of the translocator protein (18 kDa, TSPO) in the brain.

    PubMed

    Tiwari, Anjani K; Fujinaga, Masayuki; Yui, Joji; Yamasaki, Tomoteru; Xie, Lin; Kumata, Katsushi; Mishra, Anil K; Shimoda, Yoko; Hatori, Akiko; Ji, Bin; Ogawa, Masanao; Kawamura, Kazunori; Wang, Feng; Zhang, Ming-Rong

    2014-12-21

    The visualization of the activated microglia/TSPO is one of the main aspects of neuroimaging. Here we describe two new (18)F-labelled molecules, 2-[5-(4-[(18)F]fluoroethoxyphenyl)- ([(18)F]2) and 2-[5-(4-[(18)F]fluoropropyloxyphenyl)- ([(18)F]3) -2-oxo-1,3-benzoxazol-3(2H)-yl]-N-methyl-N-phenylacetamide as novel PET ligands for imaging the translocator protein (18 kDa, TSPO) in the brain. The three-D pharmacophore evaluation and docking studies suggested their high affinity for the TSPO and in vitro binding assays of the TSPO showed binding affinities 6.6 ± 0.7 nM and 16.7 ± 2.5 nM for 2 and 3, respectively. The radiochemical yields for [(18)F]2 and [(18)F]3 were found to be 22 ± 4% (n = 8) and 5 ± 2% (n = 5), respectively at EOB. The radiochemical purity for both was found ≥98% and the specific activity was in the range of 98-364 GBq μmol(-1) at EOS. In vitro autoradiography with an ischemic rat brain showed significantly increased binding on the ipsilateral side compared to the contralateral side. The specificity of [(18)F]2 and [(18)F]3 for binding TSPO was confirmed using the TSPO ligands PK11195 and MBMP. The biodistribution patterns of both PET ligands were evaluated in normal mice by 1 h dynamic PET imaging. In the brain, regional radioactivity reached the maximum very rapidly within 0-4 min for both ligands, similar to (R)[(11)C]PK11195. The metabolite study of [(18)F]2 also favoured a more favourable profile for quantification in comparison to (R)[(11)C]PK11195. In summary, these data indicated that [(18)F]2 and [(18)F]3 have good potential to work as PET ligands, therefore there are merits to use these radioligands for the in vivo evaluation in animal models to see their efficacy in the living brain.

  3. 18F-Labeled NaF PET-CT in Detection of Bone Metastases in Patients With Preoperative Lung Cancer

    PubMed Central

    Rao, Liangjun; Zong, Zhen; Chen, Zhifeng; Wang, Xiaoyan; Shi, Xinchong; Yi, Chang; Zhang, Xiangsong

    2016-01-01

    Abstract We compared the diagnostic accuracy of 18F-labeled sodium fluoride (18F-NaF) PET-CT with 99m-technetium methylene diphosphonate (99mTc-MDP) single photon emission computed tomography (SPECT) to detect bone metastases (BMs) in patients with preoperative lung cancer. Patients with lung cancer (n = 181) were examined with 18F-NaF PET-CT, and another 167 patients with lung cancer were examined with 99mTc-MDP SPECT. 18F-NaF PET-CT and 99mTc-MDP SPECT were evaluated by 2 experienced readers. Lesions were graded on a scale of 0 (degenerative lesion) to 4 (definite BM), and equivocal lesions were determined as indifferent (grade 3). Based on patient-based analysis, there were only 4 equivocal patients in 18F-NaF PET-CT detection. However, in 99mTc-MDP SPECT detection, there were 19 equivocal patients, which indicated a significant difference in terms of occurrence ratio (χ2 = 9.005, P = 0.03). Sensitivity and specificity of PET-CT was significantly better than that of SPECT when equivocal reading was categorized as malignant or benign (P < 0.05). Based on lesions-based analysis, SPECT produced 26 equivocal lesions of 333 lesions, but PET-CT produced only 5 equivocal lesions of 991 lesions. PET-CT was significantly better than SPECT in the aspect of producing equivocal patients (χ2 = 58.141, P < 0.001). Sensitivity and specificity of PET-CT was significantly better than that of SPECT when equivocal reading was categorized as malignant or benign (P < 0.05). 18F-NaF PET-CT is a highly sensitive and specific modality for the detection of BM in patients with preoperative lung cancer. It is better than conventional 99mTc-MDP SPECT in detecting BM in patients with preoperative lung cancer. PMID:27100456

  4. 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. PMID:27546294

  5. 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.

  6. 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

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

    PubMed

    Demoin, Dustin Wayne; Wyatt, Linden C; Edwards, Kimberly J; Abdel-Atti, Dalya; Sarparanta, Mirkka; Pourat, Jacob; Longo, Valerie A; Carlin, Sean D; Engelman, Donald M; Andreev, Oleg A; Reshetnyak, Yana K; Viola-Villegas, Nerissa; Lewis, Jason S

    2016-09-21

    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 ((64)Cu and (18)F) 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 (64)Cu or [(18)F]-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 (18)F (4T1 uptake; 8.9 ± 1.7%ID/g at 4 h p.i.) or (64)Cu (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 (18)F- or (64)Cu-labeled NO2A-cysVar3. PMID:27396694

  8. 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

  9. 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

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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. PMID:12408309

  17. 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.

  18. 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.

  19. Delivery of (10)boron to oral squamous cell carcinoma using boronophenylalanine and borocaptate sodium for boron neutron capture therapy.

    PubMed

    Obayashi, Shigeki; Kato, Itsuro; Ono, Koji; Masunaga, Shin-Ichiro; Suzuki, Minoru; Nagata, Kenji; Sakurai, Yoshinori; Yura, Yoshiaki

    2004-05-01

    Boron neutron capture therapy (BNCT) is a unique radiation therapy in which boron compounds are trapped into tumor cells. To determine the biodistribution of boronophenylalanine (BPA) in nude mice carrying oral squamous cell carcinoma (SCC), BPA was administered at a dose of 250 mg/kg body weight intraperitoneally. Two hours later, (10)B concentration in the tumor was 15.96 ppm and tumor/blood, tumor/tongue, tumor/skin and tumor/bone (10)B concentration ratios were 6.44, 4.19, 4.68 and 4.56, respectively. Two hours after the administration of borocaptate sodium (BSH) at a dose of 75 mg/kg body weight, (10)B concentration in the tumor was 3.61 ppm, and tumor/blood, tumor/tongue, tumor/skin and tumor/bone (10)B concentration ratios were 0.77, 1.05, 0.60 and 0.59, respectively. When cultured oral SCC cells were incubated with BPA or BSH for 2 h and then exposed to thermal neutrons, the proportion of survival cells that were capable of forming cell colonies decreased exponentially, depending on (10)B concentration. BPA-mediated BNCT was more efficient than BSH-mediated BNCT. Addition of boron compounds in the cell suspension during neutron irradiation enhanced the cell-killing effect of the neutrons. These results indicate that BPA is more selectively incorporated into human oral SCC as compared with normal oral tissues, and that both extra- and intra-cellular BPA contribute to the cell-killing effect of BNCT. BPA may be a useful boron carrier for BNCT in the treatment of advanced oral SCC.

  20. 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.

  1. 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

  2. Efficient (18)F-Labeling of Synthetic Exendin-4 Analogues for Imaging Beta Cells.

    PubMed

    Keliher, Edmund J; Reiner, Thomas; Thurber, Greg M; Upadhyay, Rabi; Weissleder, Ralph

    2012-08-01

    A number of exendin derivatives have been developed to target glucagon-like peptide 1 (GLP-1) receptors on beta cells in vivo. Modifications of exendin analogues have been shown to have significant effects on pharmacokinetics and, as such, have been used to develop a variety of therapeutic compounds. Here, we show that an exendin-4, modified at position 12 with a cysteine conjugated to a tetrazine, can be labeled with (18)F-trans-cyclooctene and converted into a PET imaging agent at high yields and with good selectivity. The agent accumulates in beta cells in vivo and has sufficiently high accumulation in mouse models of insulinomas to enable in vivo imaging. PMID:23997998

  3. 18F Labeled Nanoparticles for in Vivo PET-CT Imaging

    PubMed Central

    Devaraj, Neal K.; Keliher, Edmund J.; Thurber, Greg M.; Nahrendorf, Matthias; Weissleder, Ralph

    2009-01-01

    We report the synthesis and in vivo characterization of an 18F modified trimodal nanoparticle (18F-CLIO). This particle consists of cross-linked dextran held together in core–shell formation by a superparamagnetic iron oxide core and functionalized with the radionuclide 18F in high yield via “click” chemistry. The particle can be detected with positron emission tomography, fluorescence molecular tomography, and magnetic resonance imaging. The presence of 18F dramatically lowers the detection threshold of the nanoparticles, while the facile conjugation chemistry provides a simple platform for rapid and efficient nanoparticle labeling. PMID:19138113

  4. Efficient 18F-Labeling of Synthetic Exendin-4 Analogues for Imaging Beta Cells

    PubMed Central

    Keliher, Edmund J; Reiner, Thomas; Thurber, Greg M; Upadhyay, Rabi; Weissleder, Ralph

    2012-01-01

    A number of exendin derivatives have been developed to target glucagon-like peptide 1 (GLP-1) receptors on beta cells in vivo. Modifications of exendin analogues have been shown to have significant effects on pharmacokinetics and, as such, have been used to develop a variety of therapeutic compounds. Here, we show that an exendin-4, modified at position 12 with a cysteine conjugated to a tetrazine, can be labeled with 18F-trans-cyclooctene and converted into a PET imaging agent at high yields and with good selectivity. The agent accumulates in beta cells in vivo and has sufficiently high accumulation in mouse models of insulinomas to enable in vivo imaging. PMID:23997998

  5. 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

  6. Synthesis and evaluation of 18F labeled FET prodrugs for tumor imaging

    PubMed Central

    Wang, Limin; Lieberman, Brian P.; Ploessl, Karl; Kung, Hank F.

    2013-01-01

    Introduction O-(2-[18F]fluoroethyl)-L-tyrosine (FET, [18F]1) is a useful amino-acid-based imaging agent for brain tumors. This paper reports the synthesis and evaluation of three FET prodrugs, O-(2-[18F]fluoroethyl)-L-tyrosyl-L-glycine (FET-Gly, [18F]2), O-(2-[18F]fluoroethyl)-L-tyrosyl-L-alanine (FET-Ala, [18F]3) and N-acetyl O-(2-[18F]fluoroethyl)-L-tyrosine (AcFET, [18F]4), which could be readily hydrolyzed to FET in vivo for tumor imaging. We investigated their metabolism in the blood and imaging properties in comparison to FET ([18F]1). Methods Three new [18F]FET derivatives, 2 – 4, were prepared from their corresponding tosylate-precursors through nucleophilic fluorination and subsequent deprotection reactions. In vitro uptake studies were carried out in 9L glioma cancer cell lines. In vitro and in vivo hydrolysis studies were conducted to evaluate the hydrolysis of FET prodrugs in blood and in Fisher 344 rats. Biodistribution and PET imaging studies were then performed in rats bearing 9L tumors. Results New FET prodrugs were prepared with 3 – 28 % decay corrected radiochemical yields, good enantiomeric purity (> 95 %) and high radiochemical purity (> 95 %). FET-Gly ([18F]2), FET-Ala ([18F]3), and AcFET ([18F]4) exhibited negligible uptake in comparison to the high uptake of FET ([18F]1) in 9L cells. Metabolism studies of FET-Gly ([18F]2), FET-Ala ([18F]3), and AcFET ([18F]4) in rat and human blood showed that FET-Ala ([18F]3) was hydrolyzed to FET ([18F]1) faster than FET-Gly ([18F]2) or AcFET ([18F]4). Most of the FET-Ala (79 %) was converted to FET ([18F]1) within 5 min in blood in vivo. Biodistribution studies demonstrated that FET-Ala ([18F]3) displayed the highest tumor uptake. The tumor-to-background ratios of FET-Ala ([18F]3) and FET ([18F]1) were comparable and appeared to be better than those of FET-Gly ([18F]2) and AcFET ([18F]4). PET imaging studies showed that both FET ([18F]1) and FET-Ala ([18F]3) could visualize tumors effectively, and that they share similar imaging characteristics. Conclusions FET-Ala ([18F]3) demonstrated promising properties as a prodrug of FET ([18F]1), which could be used in PET imaging of tumor amino acid metabolism. PMID:24183614

  7. 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

  8. 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

  9. Neither azeotropic drying, nor base nor other additives: a minimalist approach to (18)F-labeling.

    PubMed

    Richarz, R; Krapf, P; Zarrad, F; Urusova, E A; Neumaier, B; Zlatopolskiy, B D

    2014-10-28

    A novel, efficient, time-saving and reliable radiolabeling procedure via nucleophilic substitution with [(18)F]fluoride is described. Different radiolabeled aliphatic and aromatic compounds were prepared in high radiochemical yields simply by heating of quaternary anilinium, diaryliodonium and triarylsulfonium [(18)F]fluorides in suitable solvents. The latter were obtained via direct elution of (18)F(-) from an anion exchange resin with alcoholic solutions of onium precursors. Neither azeotropic evaporation of water, nor a base, nor any other additives like cryptands or crown ethers were necessary. Due to its simplicity this method should be highly suitable for automated radiosyntheses, especially in microfluidic devices. PMID:25190038

  10. Efficient (18)F-Labeling of Synthetic Exendin-4 Analogues for Imaging Beta Cells.

    PubMed

    Keliher, Edmund J; Reiner, Thomas; Thurber, Greg M; Upadhyay, Rabi; Weissleder, Ralph

    2012-08-01

    A number of exendin derivatives have been developed to target glucagon-like peptide 1 (GLP-1) receptors on beta cells in vivo. Modifications of exendin analogues have been shown to have significant effects on pharmacokinetics and, as such, have been used to develop a variety of therapeutic compounds. Here, we show that an exendin-4, modified at position 12 with a cysteine conjugated to a tetrazine, can be labeled with (18)F-trans-cyclooctene and converted into a PET imaging agent at high yields and with good selectivity. The agent accumulates in beta cells in vivo and has sufficiently high accumulation in mouse models of insulinomas to enable in vivo imaging.

  11. Boronophenylalanine uptake in C6 glioma model is dramatically increased by L-DOPA preloading.

    PubMed

    Capuani, S; Gili, T; Bozzali, M; Russo, S; Porcari, P; Cametti, C; Muolo, M; D'Amore, E; Maraviglia, B; Lazzarino, G; Pastore, F S

    2009-07-01

    One of the main limitations for BNCT effectiveness is the insufficient intake of (10)B nuclei within tumour cells. This work was aimed at investigating the use of L-DOPA as enhancer for boronophenylalanine (BPA) uptake in the C6 glioma model. The investigation was first performed in vitro, and then extended in vivo to the animal model. BPA accumulation in C6 glioma cells was assessed, using radiowave dielectric spectroscopy (RDS), with and without L-DOPA preloading. C6 glioma cells were also implanted in the brain of 25 rats, randomly assigned to two experimental branches: (1) intra-carotid BPA infusion; (2) intra-carotid BPA infusion after pre-treatment with L-DOPA, administrated 24 h before BPA infusion. All animals were sacrificed, and assessment of BPA concentrations in tumour tissue, normal brain, and blood samples was performed using high performance liquid chromatography (HPLC). L-DOPA preloading induced a massive increase of BPA concentration either in vitro on C6 glioma cells or in vivo in the animal model tumour. Moreover, no significant difference was found in the normal brain and blood samples between the two animal groups. This study suggests the potential use of L-DOPA as enhancer for BPA accumulation in malignant gliomas eligible for BNCT. PMID:19375337

  12. 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.

  13. (11)C- and (18)F-Labeled Radioligands for P-Glycoprotein Imaging by Positron Emission Tomography.

    PubMed

    Cantore, Mariangela; Benadiba, Marcel; Elsinga, Philip H; Kwizera, Chantal; Dierckx, Rudi A J O; Colabufo, Nicola Antonio; Luurtsema, Gert

    2016-01-01

    P-Glycoprotein (P-gp) is an efflux transporter widely expressed at the human blood-brain barrier. It is involved in xenobiotics efflux and in onset and progression of neurodegenerative disorders. For these reasons, there is great interest in the assessment of P-gp expression and function by noninvasive techniques such as positron emission tomography (PET). Three radiolabeled aryloxazole derivatives: 2-[2-(2-methyl-((11)C)-5-methoxyphenyl)oxazol-4-ylmethyl]-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline ([(11)C]-5); 2-[2-(2-fluoromethyl-((18)F)-5-methoxyphenyl)oxazol-4-ylmethyl]-6,7-dimethoxy-1,2,3,4-tetra-hydroisoquinoline ([(18)F]-6); and 2-[2-(2-fluoroethyl-((18)F)-5-methoxyphenyl)oxazol-4-ylmethyl]-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline ([(18)F]-7), were tested in several in vitro biological assays to assess the effect of the aryl substituent in terms of potency and mechanism of action toward P-gp. Methyl derivative [(11)C]-5 is a potent P-gp substrate, whereas the corresponding fluoroethyl derivative [(18)F]-7 is a P-gp inhibitor. Fluoromethyl compound [(18)F]-6 is classified as a non-transported P-gp substrate, because its efflux increases after cyclosporine A modulation. These studies revealed a promising substrate and inhibitor, [(11)C]-5 and [(18)F]-7, respectively, for in vivo imaging of P-gp by using PET.

  14. Synthesis, uptake mechanism characterization and biological evaluation of 18F labeled fluoroalkyl phenylalanine analogs as potential PET imaging agents

    PubMed Central

    Wang, Limin; Qu, Wenchao; Lieberman, Brian P.; Plössl, Karl; Kung, Hank F.

    2010-01-01

    Introduction Amino acids based tracers represent a promising class of tumor metabolic imaging agents with successful clinical applications. Two new phenylalanine derivatives, p-(2-[18F]fluoroethyl)-L-phenylalanine (FEP, [18F]2) and p-(3-[18F]fluoropropyl)-L-phenylalanine (FPP, [18F]3) were synthesized and evaluated in comparison to clinically utilized O-(2-[18F]fluoroethyl)-L-tyrosine (FET, [18F]1). Methods FEP ([18F]2) and FPP ([18F]3) were successfully synthesized by a rapid and efficient two-step nucleophilic fluorination of tosylate precursors and deprotection reaction. In vitro cell uptake studies were carried out in 9L glioma cells. In vivo studies, 9L tumor xenografts were implanted in Fisher 344 rats. Results FEP ([18F]2) and FPP ([18F]3) could be efficiently labeled within 90 min with good enantiomeric purity (>95%), good yield (11–37%) and high specific activity (21–69 GBq/μmol). Cell uptake studies showed FEP had higher uptake than FPP as well as reference ligand FET ([18F]1). Uptake mechanism studies suggested that FEP is a selective substrate for system L and prefers its subtype LAT1. In vivo biodistribution studies demonstrated FEP had specific accumulation in tumor cells and tumor to background ratio reached 1.45 at 60 min. Small animal PET imaging studies showed FEP was comparable to FET for imaging rats bearing 9L tumor model. FEP had high uptake in 9L tumor compared to surrounding tissue and was quickly excreted through urinary tract. Conclusion Biological evaluations indicate that FEP ([18F]2) is a potential useful tracer for tumor imaging with PET. PMID:21220129

  15. 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

  16. Synthesis, In Vitro and In Vivo Evaluation of 18F-labeled PET Ligands for Imaging the Vesicular Acetylcholine Transporter

    PubMed Central

    Tu, Zhude; Efange, Simon M. N.; Xu, Jinbin; Li, Shihong; Jones, Lynne A.; Parsons, Stanley M.; Mach, Robert H.

    2009-01-01

    A new class of vesicular acetylcholine transporter inhibitor that incorporates a carbonyl group into the benzovesamicol structure was synthesized and analogs were evaluated in vitro. (±)-trans-2-Hydroxy-3-(4-(4-[18F]fluorobenzoyl)piperidino)tetralin (9e) has Ki values of 2.70 nM for VAChT, 191 nM for σ1 and 251 nM for σ2. The racemic precursor (9d) was resolved via chiral HPLC and (±)-[18F]9e, (-)-[18F]9e, and (+)-[18F]9e were respectively radiolabeled via microwave irradiation of the appropriate precursors with [18F]/F- and Kryptofix/K2CO3 in DMSO with radiochemical yields ∼50-60% and specific activities >2000 mCi/μmol. (-)-[18F]9e uptake in rat brain was consistent with in vivo selectivity for the VAChT with an initial uptake of 0.911 %ID/g in rat striatum and a striatum: cerebellum ratio of 1.88 by 30 min p.i.. MicroPET imaging of macaques demonstrated a 2.1 ratio of (-)-[18F]9e in putamen versus cerebellum at 2 h. p.i. (-)-[18F]9e has potential to be a PET tracer for clinical imaging of the VAChT. PMID:19203271

  17. Uptake and washout of borocaptate sodium and borono-phenylalanine in cultured melanoma cells: a multi-nuclear NMR study.

    PubMed

    Panov, V; Salomon, Y; Kabalka, G W; Bendel, P

    2000-07-01

    The cellular uptake and washout of the two principal boron neutron capture therapy (BNCT) agents, borocaptate sodium (BSH) and borono-phenylalanine (BPA), were monitored on-line, noninvasively, using nuclear magnetic resonance (NMR) spectroscopy. The uptake and washout of inorganic borate (B(i)) was also followed for comparison. M2R mouse melanoma cells grown on polystyrene microspheres were perfused inside the NMR sample tube. (11)B NMR was used to detect the presence of B(i), BSH and BPA, and (19)F NMR was applied to detect fluorinated BPA ((19)F-BPA). The results revealed chemical modifications of BSH due to spontaneous formation of the borocaptate dimer, BSSB, in the culture medium. BPA readily formed a complex with glucose contained in the culture medium but was also converted in the cells to a yet unidentified compound in a reaction that probably involves the hydrolysis of BPA and the release of B(i). The cellular accumulation ratio for BPA was significantly higher than 1 and was also significantly higher than that for BSH. On the other hand, the cellular retention time observed for BSH was much longer than for BPA, indicating a strong trapping of BSH in cells.

  18. Positron emission tomography-based boron neutron capture therapy using boronophenylalanine for high-grade gliomas: part II.

    PubMed

    Imahori, Y; Ueda, S; Ohmori, Y; Sakae, K; Kusuki, T; Kobayashi, T; Takagaki, M; Ono, K; Ido, T; Fujii, R

    1998-08-01

    Based on pharmacokinetic findings of fluorine-18-labeled L-fluoroboronophenylalanine by positron emission tomography (PET), methods for estimating tumor 10B concentration were devised. In clinical practice of boron neutron capture therapy (BNCT) for high-grade gliomas, a large amount of L-boronophenylalanine (L-10B-BPA)-fructose solution is used. Under these conditions, a slow i.v. infusion of L-10B-BPA-fructose solution should be performed for BNCT; therefore, the changes over time in 10B concentration in the target tissue were estimated by convoluting the actual time course of changes in plasma 10B concentration with a PET-based weight function including the proper rate constants [K1 (ml/g/min), k2 (min(-1)), k3 (min(-1)), and k4 (min(-1))]. With this method, the estimated values of 10B concentration in gliomas were very close to the 10B levels in surgical specimens. This demonstrated the similarity in pharmacokinetics between fluorine-18-labeled L-fluoroboronophenylalanine and L-10B-BPA. This method, using the appropriate rate constant, permits the determination of tumor 10B concentration and is widely suitable for clinical BNCT, because the averaged PET data are enough to use in future patients without individual PET study.

  19. Boron self-shielding effects on dose delivery of neutron capture therapy using epithermal beam and boronophenylalanine.

    PubMed

    Ye, S J

    1999-11-01

    Previous dosimetry studies for boron neutron capture therapy have often neglected the thermal neutron self-shielding effects caused by the 10B accumulation in the brain and the tumor. The neglect of thermal neutron flux depression, therefore, results in an overestimation of the actual dose delivery. The relevant errors are expected to be more pronounced when boronophenylalanine is used in conjunction with an epithermal neutron beam. In this paper, the boron self-shielding effects are calculated in terms of the thermal neutron flux depression across the brain and the dose delivered to the tumors. The degree of boron self-shielding is indicated by the difference between the thermal neutron fluxes calculated with and without considering a 10B concentration as part of the head phantom composition. The boron self-shielding effect is found to increase with increasing 10B concentrations and penetration depths from the skin. The calculated differences for 10B concentrations of 7.5-30 ppm are 2.3%-8.3% at 2.3 cm depth (depth of the maximum brain dose) and 4.6%-17% at 7.3 cm depth (the center of the brain). The additional self-shielding effects by the 10B concentration in a bulky tumor are investigated for a 3-cm-diam spherical tumor located either near the surface (3.3 cm depth) or at the center of the brain (7.3 cm depth) along the beam centerline. For 45 ppm of 10B in the tumor and 15 ppm of 10B in the brain, the dose delivered to the tumors is approximately 10% lower at 3.3 cm depth and 20% lower at the center of the brain, compared to the dose neglecting the boron self-shielding in transport calculations.

  20. Pharamacokinetic modeling for boronophenylalanine-fructose mediated neutron capture therapy: 10B concentration predictions and dosimetric consequences.

    PubMed

    Kiger, W S; Palmer, M R; Riley, K J; Zamenhof, R G; Busse, P M

    2003-01-01

    A two-compartment open model has been developed for predicting 10B concentrations in blood following intravenous infusion of the L-p-boronophenylalanine-fructose complex in humans and derived from pharmacokinetic studies of 24 patients in Phase I clinical trials of boron neutron capture therapy. The 10B concentration profile in blood exhibits a characteristic rise during the infusion to a peak of approximately 32 microg/g (for infusion of 350 mg/kg over 90 min) followed by a biexponential disposition profile with harmonic mean half-lives of 0.32 +/- 0.08 and 8.2 +/- 2.7 h, most likely due to redistribution and primarily renal elimination, respectively. The mean model rate constants k12, k21, and k10 are (mean +/- SD) 0.0227 +/- 0.0064 min(-1), 0.0099 +/- 0.0027 min(-1), 0.0052 +/- 0.0016 min(-1), respectively, and the central compartment volume of distribution V1 is 0.235 +/- 0.042 L/kg. In anticipation of the initiation of clinical trials using an intense neutron beam with concomitantly short irradiations, the ability of this model to predict, in advance, the average blood 10B concentration during brief irradiations was simulated in a retrospective analysis of the pharmacokinetic data from these patients. The prediction error for blood boron concentration and its effect on simulated dose delivered for each irradiation field are reported for three different prediction strategies. In this simulation, error in delivered dose (or, equivalently, neutron fluence) for a given single irradiation field resulting from error in predicted blood 10B concentration was limited to less than 10%. In practice, lower dose errors can be achieved by delivering each field in two fractions (on two separate days) and by adjusting the second fraction's dose to offset error in the first.

  1. 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.

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

    PubMed

    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.

  3. 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.

  4. 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.

  5. Fluorine-18-labeled boronophenylalanine positron emission tomography for oral cancers: Qualitative and quantitative analyses of malignant tumors and normal structures in oral and maxillofacial regions

    PubMed Central

    ARIYOSHI, YASUNORI; SHIMAHARA, MASASHI; KIMURA, YOSHIHIRO; ITO, YUICHI; SHIMAHARA, TAKESHI; MIYATAKE, SHIN-ICHI; KAWABATA, SHINJI

    2011-01-01

    The present study aimed to demonstrate the features of fluorine-18-labeled boronophenylalanine positron emission tomography (18F-BPA-PET) to reveal oral cancer, as well as normal structures in the oral and maxillofacial regions. We analyzed 18F-BPA-PET findings from 8 patients with histologically confirmed recurrent and/or advanced oral cancer scheduled for boron neutron capture therapy. The capacity of 18F-BPA-PET to delineate tumor and normal structures was assessed qualitatively and quantitatively. Tumors were easily identified as high uptake areas in all cases. Although the eyes, which were depicted as a low uptake area, and tongue musculature were readily identified, major vessels were not noted in any of the cases. Areas corresponding to the surface of the dorsum tongue to middle pharynx were expressed as high uptake areas in all of the cases. Quantitatively, tumors were expressed as the highest uptake area in 6 of the 8 cases, while the dorsum tongue had the highest uptake area in the remaining 2 cases. 18F-BPA-PET is useful in demonstrating the presence of a tumor. Thus, it is crucial to note the presence of a high uptake area corresponding to the dorsum area of the tongue when diagnosing a tumor using this technique. PMID:22866098

  6. 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

  7. Structure-Activity Relationship of (18)F-Labeled Phosphoramidate Peptidomimetic Prostate-Specific Membrane Antigen (PSMA)-Targeted Inhibitor Analogues for PET Imaging of Prostate Cancer.

    PubMed

    Dannoon, Shorouk; Ganguly, Tanushree; Cahaya, Hendry; Geruntho, Jonathan J; Galliher, Matthew S; Beyer, Sophia K; Choy, Cindy J; Hopkins, Mark R; Regan, Melanie; Blecha, Joseph E; Skultetyova, Lubica; Drake, Christopher R; Jivan, Salma; Barinka, Cyril; Jones, Ella F; Berkman, Clifford E; VanBrocklin, Henry F

    2016-06-23

    A series of phosphoramidate-based prostate specific membrane antigen (PSMA) inhibitors of increasing lipophilicity were synthesized (4, 5, and 6), and their fluorine-18 analogs were evaluated for use as positron emission tomography (PET) imaging agents for prostate cancer. To gain insight into their modes of binding, they were also cocrystallized with the extracellular domain of PSMA. All analogs exhibited irreversible binding to PSMA with IC50 values ranging from 0.4 to 1.3 nM. In vitro assays showed binding and rapid internalization (80-95%, 2 h) of the radiolabeled ligands in PSMA(+) cells. In vivo distribution demonstrated significant uptake in CWR22Rv1 (PSMA(+)) tumor, with tumor to blood ratios of 25.6:1, 63.6:1, and 69.6:1 for [(18)F]4, [(18)F]5, and [(18)F]6, respectively, at 2 h postinjection. Installation of aminohexanoic acid (AH) linkers in the phosphoramidate scaffold improved their PSMA binding and inhibition and was critical for achieving suitable in vivo imaging properties, positioning [(18)F]5 and [(18)F]6 as favorable candidates for future prostate cancer imaging clinical trials. PMID:27228467

  8. 18F-Labeled NaF PET-CT in Detection of Bone Metastases in Patients With Preoperative Lung Cancer.

    PubMed

    Rao, Liangjun; Zong, Zhen; Chen, Zhifeng; Wang, Xiaoyan; Shi, Xinchong; Yi, Chang; Zhang, Xiangsong

    2016-04-01

    We compared the diagnostic accuracy of F-labeled sodium fluoride (F-NaF) PET-CT with 99m-technetium methylene diphosphonate (Tc-MDP) single photon emission computed tomography (SPECT) to detect bone metastases (BMs) in patients with preoperative lung cancer. Patients with lung cancer (n = 181) were examined with F-NaF PET-CT, and another 167 patients with lung cancer were examined with Tc-MDP SPECT. F-NaF PET-CT and Tc-MDP SPECT were evaluated by 2 experienced readers. Lesions were graded on a scale of 0 (degenerative lesion) to 4 (definite BM), and equivocal lesions were determined as indifferent (grade 3). Based on patient-based analysis, there were only 4 equivocal patients in F-NaF PET-CT detection. However, in Tc-MDP SPECT detection, there were 19 equivocal patients, which indicated a significant difference in terms of occurrence ratio (χ = 9.005, P = 0.03). Sensitivity and specificity of PET-CT was significantly better than that of SPECT when equivocal reading was categorized as malignant or benign (P < 0.05). Based on lesions-based analysis, SPECT produced 26 equivocal lesions of 333 lesions, but PET-CT produced only 5 equivocal lesions of 991 lesions. PET-CT was significantly better than SPECT in the aspect of producing equivocal patients (χ = 58.141, P < 0.001). Sensitivity and specificity of PET-CT was significantly better than that of SPECT when equivocal reading was categorized as malignant or benign (P < 0.05). F-NaF PET-CT is a highly sensitive and specific modality for the detection of BM in patients with preoperative lung cancer. It is better than conventional Tc-MDP SPECT in detecting BM in patients with preoperative lung cancer.

  9. Synthesis and evaluation of (18)F-labeled bile acid compound: a potential PET imaging agent for FXR-related diseases.

    PubMed

    Jia, Lina; Jiang, Dawei; Hu, Pengcheng; Li, Xiao; Shi, Hongcheng; Cheng, Dengfeng; Zhang, Lan

    2014-07-01

    The farnesoid-X-receptor (FXR) is a member of the nuclear hormone receptor superfamily. The FXR has critical functions in maintaining bile acid synthesis and homeostasis, liver regeneration and tumorigenesis, intestinal diseases, intestinal tumorigenesis, cholesterol gallstone disease, cholestasis, and atherosclerosis. FXR expression is strongly downregulated in liver fibrosis, hepatocellular adenoma and hepatocellular carcinoma compared to expression levels in adjacent normal tissues. Chenodeoxycholic acid (CDCA) is the most potent physiological ligand for FXR. CDCA was radiolabeled with (18)F based on the efficiency click reaction of 1,3-dipolar cycloaddition of terminal alkynes and organic azides for noninvasively evaluating the relationship between FXR and FXR-related disease. The PET tracer [(18)F]8 was produced by 'click' labeling and showed a high non-decay corrected radiochemical yield (end of synthesis (EOS) yield=42±3% (n=5) from aqueous [(18)F]fluoride), high radiochemical purity ( >99%), and high specific activity (>320GBq/μmol). [(18)F]8 had a high metabolic stability in vitro and in vivo. PET imaging studies in nude mice indicated a rapid uptake of the tracer into liver tissue with uniform distribution of radioactivity in the liver. Significant accumulation of radioactivity was found in the liver, gallbladder, and intestine, while no obvious uptake was observed in other organs, such as the bladder, heart, and brain. Thus, this PET tracer represents a novel tool for early detection of abnormalities in the liver and staging of neoplasms.

  10. 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

  11. Radiosynthesis and evaluation of an 18F-labeled positron emission tomography (PET) radioligand for brain histamine subtype-3 receptors based on a nonimidazole 2-aminoethylbenzofuran chemotype

    PubMed Central

    Bao, Xiaofeng; Lu, Shuiyu; Liow, Jeih-San; Zoghbi, Sami S.; Jenko, Kimberly J.; Clark, David T.; Gladding, Robert L.; Innis, Robert B.; Pike, Victor W.

    2012-01-01

    A known chemotype of H3 receptor ligand was explored for development of a radioligand for imaging brain histamine subtype 3 (H3) receptors in vivo with positron emission tomography (PET), namely non-imidazole 2-aminoethylbenzofurans, represented by the compound (R)-(2-(2-(2-methylpyrrolidin-1-yl)ethyl)benzofuran-5-yl)(4-fluorophenyl)methanone (9). Compound 9 was labeled with fluorine-18 (t1/2= 109.7 min) in high specific activity by treating the prepared nitro analog (12) with cyclotron-produced [18F]fluoride ion. [18F]9 was studied with PET in mouse and in monkey after intravenous injection. [18F]9 showed favorable properties as a candidate PET radioligand, including moderately high brain uptake with a high proportion of H3 receptor-specific signal in the absence of radiodefluorination. The nitro compound 12 was found to have even higher H3 receptor affinity, indicating the potential of this chemotype for the development of further promising PET radioligands. PMID:22313227

  12. 18F-Labeled NaF PET-CT in Detection of Bone Metastases in Patients With Preoperative Lung Cancer.

    PubMed

    Rao, Liangjun; Zong, Zhen; Chen, Zhifeng; Wang, Xiaoyan; Shi, Xinchong; Yi, Chang; Zhang, Xiangsong

    2016-04-01

    We compared the diagnostic accuracy of F-labeled sodium fluoride (F-NaF) PET-CT with 99m-technetium methylene diphosphonate (Tc-MDP) single photon emission computed tomography (SPECT) to detect bone metastases (BMs) in patients with preoperative lung cancer. Patients with lung cancer (n = 181) were examined with F-NaF PET-CT, and another 167 patients with lung cancer were examined with Tc-MDP SPECT. F-NaF PET-CT and Tc-MDP SPECT were evaluated by 2 experienced readers. Lesions were graded on a scale of 0 (degenerative lesion) to 4 (definite BM), and equivocal lesions were determined as indifferent (grade 3). Based on patient-based analysis, there were only 4 equivocal patients in F-NaF PET-CT detection. However, in Tc-MDP SPECT detection, there were 19 equivocal patients, which indicated a significant difference in terms of occurrence ratio (χ = 9.005, P = 0.03). Sensitivity and specificity of PET-CT was significantly better than that of SPECT when equivocal reading was categorized as malignant or benign (P < 0.05). Based on lesions-based analysis, SPECT produced 26 equivocal lesions of 333 lesions, but PET-CT produced only 5 equivocal lesions of 991 lesions. PET-CT was significantly better than SPECT in the aspect of producing equivocal patients (χ = 58.141, P < 0.001). Sensitivity and specificity of PET-CT was significantly better than that of SPECT when equivocal reading was categorized as malignant or benign (P < 0.05). F-NaF PET-CT is a highly sensitive and specific modality for the detection of BM in patients with preoperative lung cancer. It is better than conventional Tc-MDP SPECT in detecting BM in patients with preoperative lung cancer. PMID:27100456

  13. (11) C-labeled and (18) F-labeled PET ligands for subtype-specific imaging of histamine receptors in the brain.

    PubMed

    Funke, Uta; Vugts, Danielle J; Janssen, Bieneke; Spaans, Arnold; Kruijer, Perry S; Lammertsma, Adriaan A; Perk, Lars R; Windhorst, Albert D

    2013-01-01

    The signaling molecule histamine plays a key role in the mediation of immune reactions, in gastric secretion, and in the sensory system. In addition, it has an important function as a neurotransmitter in the central nervous system, acting in pituitary hormone secretion, wakefulness, motor and cognitive functions, as well as in itch and nociception. This has raised interest in the role of the histaminergic system for the treatment and diagnosis of various pathologies such as allergy, sleeping and eating disorders, neurodegeneration, neuroinflammation, mood disorders, and pruritus. In the past 20 years, several ligands targeting the four different histamine receptor subtypes have been explored as potential radiotracers for positron emission tomography (PET). This contribution provides an overview of the developments of subtype-selective carbon-11-labeled and fluorine-18-labeled compounds for imaging in the brain. Using specific radioligands, the H1 R expression in human brain could be examined in diseases such as schizophrenia, depression, and anorexia nervosa. In addition, the sedative effects of antihistamines could be investigated in terms of H1 R occupancy. The H3 R is of special interest because of its regulatory role in the release of various other neurotransmitters, and initial H3 R PET imaging studies in humans have been reported. The H4 R is the youngest member of the histamine receptor family and is involved in neuroinflammation and various sensory pathways. To date, two H4 R-specific (11) C-labeled ligands have been synthesized, and the imaging of the H4 R in vivo is in the early stage.

  14. 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

  15. Synthesis of isomers of 18F-labelled amino acid radiopharmaceutical: position 2- and 3-L-18F-alpha-methyltyrosine using a separation and purification system.

    PubMed

    Tomiyoshi, K; Amed, K; Muhammad, S; Higuchi, T; Inoue, T; Endo, K; Yang, D

    1997-02-01

    To diagnose cancers with radiolabelled amino acid using positron emission tomography, we have constructed a separation and purification system for the production of L-18F-alpha-methyltyrosine (L-18FAmT). This system could provide radioprotection and consistent production of L-18FAmT. L-18FAmT was synthesized and purified and the efficiency of the system was examined. The radiochemical yield of L-18FAmT was 20.3 +/- 5.1% (n = 5) based on the radioactivity trapped in the reaction vessel. The radiochemical purity was greater than 99.4 +/- 0.3% (n = 5). The radiochemical stability in phosphate-buffered saline and human plasma was examined and little decomposition was observed by HPLC analysis. Our results indicate that the separation and purification system gave simple and quick synthesis of L-18FAmT with a large reduction in radiation exposure and consistent production of L-18FAmT.

  16. 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

  17. Multi-nuclear MRS and 19F MRI of 19F-labelled and 10B-enriched p-boronophenylalanine-fructose complex to optimize boron neutron capture therapy: phantom studies at high magnetic fields.

    PubMed

    Porcari, Paola; Capuani, Silvia; Campanella, Renzo; La Bella, Angela; Migneco, Luisa Maria; Maraviglia, Bruno

    2006-06-21

    Reaction yield optimization for the synthesis and the complexation of a boron neutron capture therapy agent (19)F-labelled, (10)B-enriched p-boronophenylalanine-fructose ((19)F-BPA-fr) complex was obtained. (1)H, (19)F, (13)C and (10)B magnetic resonance spectroscopy (MRS) of the (19)F-BPA-fr complex in aqueous and rat blood solution phantoms and its spatial distribution mapping using (19)F magnetic resonance imaging (MRI) results are reported. 7 T and 9.4 T magnetic fields were used to perform MRI and MRS respectively. Our in vitro results suggest that in vivo studies on (19)F-BPA through (19)F NMR will be feasible. PMID:16757868

  18. In vivo (19)F MRI and (19)F MRS of (19)F-labelled boronophenylalanine-fructose complex on a C6 rat glioma model to optimize boron neutron capture therapy (BNCT).

    PubMed

    Porcari, Paola; Capuani, Silvia; D'Amore, Emanuela; Lecce, Mario; La Bella, Angela; Fasano, Fabrizio; Campanella, Renzo; Migneco, Luisa Maria; Pastore, Francesco Saverio; Maraviglia, Bruno

    2008-12-01

    Boron neutron capture therapy (BNCT) is a promising binary modality used to treat malignant brain gliomas. To optimize BNCT effectiveness a non-invasive method is needed to monitor the spatial distribution of BNCT carriers in order to estimate the optimal timing for neutron irradiation. In this study, in vivo spatial distribution mapping and pharmacokinetics evaluation of the (19)F-labelled boronophenylalanine (BPA) were performed using (19)F magnetic resonance imaging ((19)F MRI) and (19)F magnetic resonance spectroscopy ((19)F MRS). Characteristic uptake of (19)F-BPA in C6 glioma showed a maximum at 2.5 h after compound infusion as confirmed by both (19)F images and (19)F spectra acquired on blood samples collected at different times after infusion. This study shows the ability of (19)F MRI to selectively map the bio-distribution of (19)F-BPA in a C6 rat glioma model, as well as providing a useful method to perform pharmacokinetics of BNCT carriers. PMID:19001698

  19. The enhancement of neutron irradiation of HeLa-S cervix carcinoma cells by cell-nucleus-addressed deca-p-boronophenylalanine.

    PubMed

    Braun, Klaus; Wolber, Gerd; Waldeck, Waldemar; Pipkorn, Rüdiger; Jenne, Jürgen; Rastert, Ralf; Ehemann, Volker; Eisenmenger, Andreas; Corban-Wilhelm, Heike; Braun, Isabell; Heckl, Stefan; Debus, Jürgen

    2003-06-01

    Boron neutron capture therapy (BNCT) is an experimental treatment modality which depends on a sufficient cellular uptake of Boron ((10)B) followed by an exposure to a thermal neutron beam from a nuclear reactor. High energetic particles (4He and 7Li) are created during the neutron capture reaction and produce DNA damages, which lead to cell killing. Regarding BNCT, the short radiation range of He- and Li-particles is decisive for the distribution of (10)B. Until now, BNCT has been lacking for therapeutically effective concentrations of (10)B. Twenty-four hours after the combined use of our 'Bioshuttle'-p-borono-phenylalanine(10)-constructs ('Bioshuttle'-p-BPA(10)) and neutron-irradiation, an obvious reduction of the radiation-resistant HeLa-S cells could be observed. No cells were alive 72 h after the incubation with 'Bioshuttle'-p-BPA(10) followed by neutron irradiation. A post-mitotic cell death could be assumed based on flow cytometrical data.

  20. [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.

  1. [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. PMID:23888587

  2. [Nicotine dependence].

    PubMed

    Kawazoe, Shingo; Shinkai, Takahiro

    2015-09-01

    Smoking is the most widespread addictive behavior in the world, and it causes physical and psychological dependence on nicotine. As for physical nicotine dependence, nicotine produces rewarding effects by interacting with nicotinic acetylcholine receptors on neurons in the brain's reward system. Psychological dependence on nicotine comes with a complex psychological procedure that is based on distorted cognition which justifies their smoking behavior. Clinicians should support smokers with willingness to quit smoking comprehensively with this knowledge, although the success rate of smoking cessation is no ideal in general. PMID:26394514

  3. 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

  4. Chemical dependence - resources

    MedlinePlus

    Drug abuse - resources; Resources - chemical dependence ... The following organizations are a good resource for information on drug dependence: National Council on Alcoholism and Drug Dependence -- ncadd.org National Institute on Drug Abuse -- www.drugabuse.gov ...

  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. Response of rat skin to boron neutron capture therapy with p-boronophenylalanine or borocaptate sodium.

    PubMed

    Morris, G M; Coderre, J A; Hopewell, J W; Micca, P L; Rezvani, M

    1994-08-01

    The effects of boron neutron capture irradiation employing either BPA or BSH as neutron capture agents has been assessed using the dorsal skin of Fischer 344 rats. Pharmacokinetic studies, using prompt gamma spectrometry, revealed comparable levels of boron-10 (10B) in blood and skin after the intravenous infusion of BSH (100 mg/kg body wt.). The 10B content of blood (12.0 +/- 0.5 micrograms/g) was slightly higher than that of skin (10.0 +/- 0.5 micrograms/g) after oral dosing with BPA. Biphasic skin reactions were observed after irradiation with the thermal neutron beam alone or in combination with BPA or BSH. The time of onset of the first phase of the skin reaction, moist desquamation, was approximately 2 weeks. The time at which the second-wave skin reaction, dermal necrosis, became evident was dose-related and occurred after a latent interval of > or = 24 weeks, well after the acute epithelial reaction had healed. The incidence of both phases of skin damage was also dose-related. The radiation doses required to produce skin damage in 50% of skin sites (ED50 values) were calculated from dose-effect curves and these values were used to determine relative biological effectiveness (RBE) and compound biological effectiveness (CBE) factors for both moist desquamation and dermal necrosis. It was concluded on the basis of these calculations that the microdistribution of the two neutron capture agents had a critical bearing on the overall biological effect after thermal neutron activation. BSH, which was possibly excluded from the cytoplasm of epidermal cells, had a low CBE factor value (0.56 +/- 0.06) while BPA, which may be selectively accumulated in epidermal cells had a very high CBE factor (3.74 +/- 0.7). For the dermal reaction, where vascular endothelial cells represent the likely target cell population, the CBE factor values were comparable, at 0.73 +/- 0.42 and 0.86 +/- 0.08 for BPA ad BSH, respectively.

  7. [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. PMID:23040955

  8. 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…

  9. 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,…

  10. 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. PMID:22712591

  11. 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.

  12. Mephentermine dependence with psychosis.

    PubMed

    Gehlawat, Pratibha; Singh, Priti; Gupta, Rajiv; Arya, Sidharth

    2013-01-01

    Mephentermine misuse or dependence has been rarely reported in the literature. This is surprising as mephentermine bears a close structural similarity to methamphetamine. Here we report a case of mephentermine dependence with induced psychosis. A 23-year-old professional weightlifter used to administer mephentermine (60 mg) for improving performance in tournaments. The patient became dependent on mephentermine in 2009, and his consumption increased to 100-150 mg every 2-3 days since August 2012 until his presentation in clinic in mid-October 2012. He developed psychosis and had persecutory delusions. Remission of psychosis was seen with stopping use of mephentermine and use of antipsychotic medication. PMID:23759255

  13. Dependent personality disorder

    MedlinePlus

    ... disapproval Becoming overly focused on fears of being abandoned Becoming very passive in relationships Feeling very upset ... a mental health professional if you or your child has symptoms of dependent personality disorder.

  14. Measurement of Tanning Dependence

    PubMed Central

    Heckman, C.J.; Darlow, S.; Kloss, J.D.; Cohen-Filipic, J.; Manne, S.L.; Munshi, T.; Yaroch, A.L.; Perlis, C.

    2014-01-01

    Background Indoor tanning has been found to be addictive. However, the most commonly-used tanning dependence measures have not been well-validated. Objective The study’s purpose was to explore the psychometric characteristics of and compare the mCAGE (modified Cut-down, Annoyed, Guilty, Eye-opener Scale), mDSM-IV-TR (modified Diagnostic and Statistical Manual of Mental Disorders – Fourth Edition - Text Revised), and TAPS (Tanning Pathology Scale) measures of tanning dependence and provide recommendations for research and practice. Methods This study was a cross-sectional online survey with 18–25 year old female university students. The main outcome variable was tanning dependence measured by the mCAGE, mDSM-IV-TR, and TAPS. Results Internal consistency of the TAPS subscales was good but was poor for the mCAGE and mDSM-IV-TR, except when their items were combined. Agreement between the mCAGE and mDSM-IV-TR was fair. Factor analysis of the TAPS confirmed the current four-factor structure. All of the tanning dependence scales were significantly correlated with one another. Likewise, most of the tanning dependence scales were significantly correlated with other measures of tanning attitudes and behaviors. However, the tolerance to tanning TAPS subscale was not significantly correlated with any measure of tanning attitudes or behaviors and had the lowest subscale internal reliability and eigenvalues. Conclusion Based on the data and existing literature, we make recommendations for the continued use of tanning dependence measures. Intervention may be needed for the approximately 5% of college women who tend to be classified as tanning dependent across measures. Monitoring of individuals reporting tanning dependence symptoms is warranted. PMID:23980870

  15. Medication dependence and anxiety

    PubMed Central

    von Moltke, Lisa L.; Greenblatt, David J.

    2003-01-01

    Anxiety disorders are common and costly psychiatric illnesses. Pharmacological treatment was enhanced with the introduction of benzodiazepines, which proved safer and more effective than older drugs. The risk of dependence, however, has made clinicians reluctant to use these medications. In fact, few patients appear to develop significant difficulties with these drugs, given how widely they are used. Careful planning for discontinuation of therapy is important. In addition, for some individuals, there appears to be a complex and as yet unelucidaied relationship between dependence on drugs or alcohol and anxiety. The newer antidepressants offer efficacy without abuse or dependence liability, but are expensive and have side effects that are intolerable for some patients. Pharmacological therapy for anxiety should be prescribed and managed so as to minimize any existing risk, while aiming to restore the patient to wellness in terms of symptoms and function. PMID:22033703

  16. Loperamide dependence and abuse.

    PubMed

    MacDonald, Ryan; Heiner, Jason; Villarreal, Joshua; Strote, Jared

    2015-05-02

    Loperamide is a common over-the-counter antidiarrheal considered safe in a broad range of dosages and thought devoid of abuse potential. We describe the first case of a patient with loperamide dependence due to misuse of its opiate-like effects achieved by chronic massive oral ingestions. A 26-year-old man who was taking 800 mg of loperamide per day presented requesting detoxification referral. Loperamide has potential for euphoric effects and information on how to facilitate such effects is easily available. It is important for physicians to be aware of the potential for misuse of and dependence on loperamide, with symptoms mimicking opiate use.

  17. 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.

  18. Gifted Military Dependents.

    ERIC Educational Resources Information Center

    Tittle, Bess M.; Walters, Debbie

    1985-01-01

    Two articles address problems and issues in serving gifted military dependents. The first offers suggestions for parents, including handcarrying records, involving themselves in schools, and maintaining a positive attitude toward service life. The second article describes TAG (talented and gifted) programs at the Department of Defense Dependents…

  19. Epilepsy and dependence.

    PubMed

    Martinove, Mária

    2010-03-01

    Epilepsy is relatively frequent neurological condition. Its prevalence is assumed to be about 1%, and it would be interesting to see how many of these people have comorbid substance dependence disorder. The manifestation of epilepsy exhibits a seizure-like condition with typical neurological and psychical symptoms, which are induced by pathological electric discharges in brain. The population of addicts is known to have higher prevalence of seizures, found not only in alcohol abusers, but also in illicit drug users. The aim of our paper is to give an overview of the prevalence rates of this serious health condition in patients with substance dependence treated at the OLUP NPO, Predná Hora. The author compares two groups of patients: with and without the epileptic seizures. Alcohol addicts prevailed in both groups. Each 8th treated dependent patient had at least one epileptic seizure. Nearly the same percent of dependent patients in both groups (43,6% vs. 40,9%) holds a driving license, thus they probably also drive a motor vehicle. Is there any person who would initiate withdrawal of driving license from such patients? Frequent somatic diseases in more than one half of the group with seizures (more than 62%) highlight the fact that this group of patients requires thorough and financially probably more demanding health care. PMID:20305305

  20. 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…

  1. 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)

  2. Measurement dependent locality

    NASA Astrophysics Data System (ADS)

    Pütz, Gilles; Gisin, Nicolas

    2016-05-01

    The demonstration and use of Bell-nonlocality, a concept that is fundamentally striking and is at the core of applications in device independent quantum information processing, relies heavily on the assumption of measurement independence, also called the assumption of free choice. The latter cannot be verified or guaranteed. In this paper, we consider a relaxation of the measurement independence assumption. We briefly review the results of Pütz et al (2014 Phys. Rev. Lett. 113 190402), which show that with our relaxation, the set of so-called measurement dependent local (MDL) correlations is a polytope, i.e. it can be fully described using a finite set of linear inequalities. Here we analyze this polytope, first in the simplest case of two parties with binary inputs and outputs, for which we give a full characterization. We show that partially entangled states are preferable to the maximally entangled state when dealing with measurement dependence in this scenario. We further present a method which transforms any Bell-inequality into an MDL inequality and give valid inequalities for the case of arbitrary number of parties as well as one for arbitrary number of inputs. We introduce the assumption of independent sources in the measurement dependence scenario and give a full analysis for the bipartite scenario with binary inputs and outputs. Finally, we establish a link between measurement dependence and another strong hindrance in certifying nonlocal correlations: nondetection events.

  3. 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.

  4. Clathrin-dependent endocytosis.

    PubMed Central

    Mousavi, Seyed Ali; Malerød, Lene; Berg, Trond; Kjeken, Rune

    2004-01-01

    The process by which clathrin-coated vesicles are produced involves interactions of multifunctional adaptor proteins with the plasma membrane, as well as with clathrin and several accessory proteins and phosphoinositides. Here we review recent findings highlighting new insights into mechanisms underlying clathrin-dependent endocytosis. PMID:14505490

  5. [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

  6. 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.

  7. [Tobacco dependence treatment guidelines].

    PubMed

    Králíková, Eva; Češka, Richard; Pánková, Alexandra; Štěpánková, Lenka; Zvolská, Kamila; Felbrová, Vladislava; Kulovaná, Stanislava; Zvolský, Miroslav

    2015-05-01

    Tobacco dependence causes every sixth death in the Czech Republic and is associated with diseases of the whole body. Treatment of tobacco dependence should be a standard part of clinical care to the extent of time available--from brief intervention at each clinical contact with patients up to intensive treatment. It includes psycho-socio-behavioural support and pharmacotherapy. It should apply to all professions in clinical medicine--as recommended by WHO mainly doctors, nurses, pharmacists and dentists, and should be covered within health care systems. Economically, it is one of the most cost-effective interventions in medicine. In our population over 15 years about 30% smokes (about 2.2 million people), diagnosis F17 relates to approximately 1.75 million people (about 80% of smokers). PMID:26955915

  8. Lokiarchaeon is hydrogen dependent.

    PubMed

    Sousa, Filipa L; Neukirchen, Sinje; Allen, John F; Lane, Nick; Martin, William F

    2016-01-01

    The nature of the host that acquired the mitochondrion at the eukaryote origin is an important microbial evolutionary issue. Modern phylogenetics indicates that the host was an archaeon. The metagenome sequence of Candidatus Lokiarchaeon has identified it as being the closest relative of the host yet known. Here, we report comparative genomic evidence indicating that Lokiarchaeon is hydrogen dependent, as one theory for the eukaryote origin-the hydrogen hypothesis-predicts for the host lineage. PMID:27572645

  9. 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).

  10. Tianeptine and alcohol dependence.

    PubMed

    Favre, J D; Guelfi-Sozzi, C; Delalleau, B; Lôo, H

    1997-10-01

    Several arguments are in favour of the use of antidepressant drugs in alcohol-dependent patients, especially those acting on the serotoninergic system: (1) neurochemical data indicate the interaction between alcohol and 5-HT metabolism, (2) pharmacological studies show an improvement in the behaviour of alcoholized animals treated with antidepressants, (3) depression is a frequent disease in alcoholic patients. Tianeptine has been shown to be active in the treatment of depression in patients with history of alcohol abuse or dependence. In a first double-blind study performed versus amitryptiline, depression after withdrawal was improved by tianeptine, and biological abnormalities usually related to chronic alcohol intake tended to decrease. Similar results were found in an open study carried out on 277 alcoholic patients treated for 1 year. As these patients were depressed, no definite conclusion could be drawn from these results in respect of a specific action of tianeptine on alcohol dependence. Thus, a multicentre double-blind study has been performed which compared tianeptine (12.5 mg t.i.d) and placebo in 342 non-depressed patients fulfilling DSM-III-R criteria for Psychoactive Substance Dependence (alcohol). Other inclusion criteria were: daily alcohol intake higher than 80 g, minimum score of 3 on the Short-Mast Questionnaire, mean corpuscular volume above 98 fl and/or gamma Gt more than twice the upper limit of normal. The patients were treated for 9 months. The intention-to-treat population and the per protocol population were made up of 327 patients and 111 patients, respectively. The main efficacy criterion was the absence of alcoholic relapse (abstinence) defined by the patient's statements, the investigators clinical judgement and some biological parameters: alcohol blood levels, gamma Gt levels. Secondary criteria were the evolution of the alcohol consumption in the patients who relapsed, cumulative abstinence duration, a visual analogue scale for the

  11. 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

  12. 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.

  13. 4-[18F]Fluorophenylpiperazines by improved Hartwig-Buchwald N-arylation of 4-[18F]fluoroiodobenzene, formed via hypervalent λ3-iodane precursors: application to build-up of the dopamine D4 ligand [18F]FAUC 316.

    PubMed

    Kügler, Fabian; Ermert, Johannes; Kaufholz, Peter; Coenen, Heinz H

    2015-01-01

    Substituted phenylpiperazines are often neuropharmacologically active compounds and in many cases are essential pharmacophores of neuroligands for different receptors such as D2-like dopaminergic, serotoninergic and other receptors. Nucleophilic, no-carrier-added (n.c.a.) 18F-labelling of these ligands in an aromatic position is desirable for studying receptors with in vivo molecular imaging. 1-(4-[18F]Fluorophenyl)piperazine was synthesized in two reaction steps starting by 18F-labelling of a iodobenzene-iodonium precursor, followed by Pd-catalyzed N-arylation of the intermediate 4-[18F]fluoro-iodobenzene. Different palladium catalysts and solvents were tested with particular attention to the polar solvents dimethylformamide (DMF) and dimethylsulfoxide (DMSO). Weak inorganic bases like potassium phosphate or cesium carbonate seem to be essential for the arylation step and lead to conversation rates above 70% in DMF which is comparable to those in typically used toluene. In DMSO even quantitative conversation was observed. Overall radiochemical yields of up to 40% and 60% in DMF and DMSO, respectively, were reached depending on the labelling yield of the first step. The fluorophenylpiperazine obtained was coupled in a third reaction step with 2-formyl-1H-indole-5-carbonitrile to yield the highly selective dopamine D4 ligand [18F]FAUC 316. PMID:25558857

  14. 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.

  15. Parenthood and opioid dependence

    PubMed Central

    Pihkala, Heljä; Sandlund, Mikael

    2015-01-01

    Introduction Many patients in maintenance treatment programs for opioid dependence are parents to underage children. Objective The aim of this study was to explore how parents who are regular patients in maintenance treatment perceive their parenthood. Methods 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. Results 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. Conclusion 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. PMID:25709518

  16. Cyclin-dependent kinases.

    PubMed

    Malumbres, Marcos

    2014-01-01

    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

  17. Cholesterol-dependent cytolysins.

    PubMed

    Gilbert, Robert J C

    2010-01-01

    The cholesterol-dependent cytolysins (CDCs) are part of a large family of pore-forming proteins that include the human proteins perforin and the complement membrane attack complex. The activity of all family members is focused on membranes, but the proteins are themselves involved in a diverse range of phenomena. An overview of some of these phenomena is provided here, along with an historical perspective of CDCs themselves and how our understanding of their mechanism of action has developed over the years. The way in which pore formation depends on specific characteristics of the membrane under attack as well as of the protein doing the attacking is emphasised. The cholesterol-dependent cytolysins (CDCs) have been the focus of a renewed keen research interest for over ten years now. Their importance has been even further enhanced by the homology now identified between them and the membrane attack complex/perforin (MACPF) family of proteins, which includes several components of the complement cascade as well as perforin itself. In this chapter I aim to provide an overview of our understanding of the interaction between CDCs and other members of what is now called the MACPF/CDC superfamily, with their target membranes. CDCs (also in the past known as thiol-activated toxins or cholesterol-binding toxins) were originally identified from four Gram-positive bacterial genera (Clostridium, Listeria, Bacillus and Streptococcus). Well-known examples include listeriolysin, perfringolysin, streptolysin and pneumoysin. Listeriolysin from L. monocytogenes is responsible for the escape of bacteria from the phagosome to colonise the cytoplasm and has been applied as a protein adjuvant in the development of vaccines against cancer and tuberculosis, for example. Perfringolysin from C. perfringens (Fig. 1A) has become perhaps the most studied CDC4 and has an important role in pathology associated with infection (gangrene). Streptolysin from S. pyogenes is another intensely studied

  18. 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

  19. 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

  20. 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

  1. 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. PMID:27424418

  2. 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.

  3. Tobacco Dependence Among Intermittent Smokers

    PubMed Central

    Ferguson, Stuart G.; Dunbar, Michael S.; Scholl, Sarah M.

    2012-01-01

    Introduction: Intermittent smokers (ITS) are an increasingly prevalent segment of smokers, yet it is unknown whether or how dependence severity may vary across ITS. Methods: Participants were 217 ITS (70 never daily ITS [NITS], 138 converted ITS [CITS], and 9 unknown), who smoked 4–27 days per month, and 197 daily smokers (DS), recruited for a study on smoking patterns. Participants completed questionnaires on dependence (time to first cigarette after waking, Fagerström Test of Nicotine Dependence [FTND], Nicotine Dependence Syndrome Scale [NDSS], Wisconsin Inventory of Smoking Dependence Motives [WISDM], and Hooked on Nicotine Checklist [HONC]) and recorded each cigarette in real time over 3 weeks using Ecological Momentary Assessment. Logistic regression assessed differences in dependence between groups (DS vs. ITS; CITS vs. NITS), and least squares regression examined associations between dependence and smoking behavior (mean, maximum cigarettes per day; proportion of days smoked; longest period of abstinence) within ITS. Results: As expected, DS were significantly more dependent than ITS: FTND, NDSS, and WISDM discriminated between ITS and DS with greater than 90% accuracy. Similarly, among ITS, NITS demonstrated lower dependence than CITS. Within ITS, dependence measures also correlated with observed smoking rate and duration of abstinence. Conclusions: The study confirmed that DS are more dependent than ITS and that CITS are more dependent than NITS. Importantly, ITS exhibit features of dependence, and there is meaningful variation in dependence within ITS, suggesting that some aspects of dependence may appear with very infrequent smoking. Future work should examine implications for ITS’ potential progression to daily smoking and cessation outcome. PMID:22529224

  4. Study designs for dependent happenings.

    PubMed

    Halloran, M E; Struchiner, C J

    1991-09-01

    In 1916, Sir Ronald Ross defined "dependent happenings" as events where the number affected in a unit of time depends on the number already affected. That is, the incidence depends on the prevalence, a characteristic of many infectious diseases. Because of this dependence, interventions against infectious diseases can have not only direct protective effects for the person receiving an intervention, but also indirect effects resulting from changes in the intensity of transmission in the population. This paper develops the conceptual framework for four types of study designs that differentiate and account for direct and indirect effects of intervention programs in dependent happenings.

  5. Mexican oil and dependent development

    SciTech Connect

    Gentleman, J.A.

    1982-01-01

    The developmet of Mexico's enormous hydrocarbon resources during the latter part of the 1970's provides an opportunity to examine the impact of Mexico's dependent-state status upon the use of the resource. Specifically, this study examines the hypothesis, drawn from the dependency literature, that the development of this resource within the context of dependency would lead to a greater internationalization of the Mexican economy and, in general, a deepening of Mexico's dependence rather than a lessening of that dependence as Mexico's political leaders suggest. The study also examines the impact of hydrocarbon development upon the growth of the Mexican state and state capitalism. Finally, the study examines the extent to which Mexico has sought to and has been able to modify the conditions of its dependence at the level of international exchange in the specific areas of trade, labor, and energy. Has the ''oil weapon'' been sufficiently powerful to modify substantially and fundamentally the terms of Mexico's dependence as some would argue should be able to do and as Mexico's leaders believed it would. Essentially, the study finds that Mexico's dependence has been exacerbated by the program of hydrocarbon development. Not only has the specific profile of oil, gas, and petrochemicals development been substantially impacted upon by Mexico's dependence, but the program for general economic development based upon the utilization of new oil revenues initiated a new era of dependent development for Mexico.

  6. 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…

  7. 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.

  8. Evaluating Dependence Criteria for Caffeine.

    PubMed

    Striley, Catherine L W; Griffiths, Roland R; Cottler, Linda B

    2011-12-01

    Background: Although caffeine is the most widely used mood-altering drug in the world, few studies have operationalized and characterized Diagnostic and Statistical Manual IV (DSM-IV) substance dependence criteria applied to caffeine. Methods: As a part of a nosological study of substance use disorders funded by the National Institute on Drug Abuse, we assessed caffeine use and dependence symptoms among high school and college students, drug treatment patients, and pain clinic patients who reported caffeine use in the last 7 days and also reported use of alcohol, nicotine, or illicit drugs within the past year (n=167). Results: Thirty-five percent met the criteria for dependence when all seven of the adopted DSM dependence criteria were used. Rates of endorsement of several of the most applicable diagnostic criteria were as follows: 26% withdrawal, 23% desire to cut down or control use, and 44% continued use despite harm. In addition, 34% endorsed craving, 26% said they needed caffeine to function, and 10% indicated that they talked to a physician or counselor about problems experienced with caffeine. There was a trend towards increased caffeine dependence among those dependent on nicotine or alcohol. Within a subgroup that had used caffeine, alcohol, and nicotine in the past year, 28% fulfilled criteria for caffeine dependence compared to 50% for alcohol and 80% for nicotine. Conclusion: The present study adds to a growing literature suggesting the reliability, validity, and clinical utility of the caffeine dependence diagnosis. Recognition of caffeine dependence in the DSM-V may be clinically useful. PMID:24761264

  9. Alcohol dependence--classificatory considerations.

    PubMed

    Lesch, O M; Ades, J; Badawy, A; Pelc, I; Sasz, H

    1993-01-01

    The term alcoholism or alcohol dependence has acquired a broad range of meanings. The Plinius Maior Society herewith presents new classificatory considerations and suggests additional recording of special dimensions according to the individual hypothesis and design of a study.

  10. The Cost of Technological Dependence

    ERIC Educational Resources Information Center

    Patel, Surendra J.

    1973-01-01

    Technological transfer often exacts a definite price, with the developing countries in an obvious situation of dependency. But today it is possible to appraise the economic and social cost of transference. (BL)

  11. Dependence of maxima in space

    NASA Astrophysics Data System (ADS)

    Ferreira, H.; Pereira, L.

    2015-01-01

    We evaluate the dependence among large values of a spatial process of maxima trough a coefficient that can be applied in natural, technical and societal extreme phenomena. Its main properties are: a) k locations can be taken into account; b) it takes values in [0,1] and higher values indicate stronger dependence; c) it is independent of the univariate marginal distributions of the random field; d) it can be related with other coefficients in the literature such as the tail dependence and the extremal coefficients; e) it agrees with the concordance property for multivariate distributions; f) it has as a particular case the variogram from geostatistics; g) it can be easily estimated. We illustrate the application of the introduced coefficient with the estimation of the degree of dependence among large values of the amount of tritium in drinking water for tree cities.

  12. 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.

  13. 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…

  14. [Drug dependence and psychotropic drugs].

    PubMed

    Giraud, M J; Lemonnier, E; Bigot, T

    1994-11-01

    Although the utility of psychotropic drugs has been well demonstrated, caution must still be exercised in their use. Among their potential risks, drug dependency must be kept in mind. This risk is well accepted with regard to benzodiazepines, and it appeared useful to study the potential risk for antidepressants, neuroleptics and thymoregulatory agents. Whatever the drug, the predominant factor appears to be psychological dependency. Prevention of drug dependency is most often achieved by informing the patient, limiting the length of use of the drug, making regular reevaluation of symptoms and of drug indication, and frequently be establishing a "treatment contract". The importance of the patient-physician relationship in the prescription of such treatment must be underlined. PMID:7984941

  15. 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.

  16. ROS-dependent signal transduction

    PubMed Central

    Reczek, Colleen R; Chandel, Navdeep S

    2014-01-01

    Reactive oxygen species (ROS) are no longer viewed as just a toxic by-product of mitochondrial respiration, but are now appreciated for their role in regulating a myriad of cellular signaling pathways. H2O2, a type of ROS, is a signaling molecule that confers target specificity through thiol oxidation. Although redox-dependent signaling has been implicated in numerous cellular processes, the mechanism by which the ROS signal is transmitted to its target protein in the face of highly reactive and abundant antioxidants is not fully understood. In this review of redox-signaling biology, we discuss the possible mechanisms for H2O2-dependent signal transduction. PMID:25305438

  17. Waveform-Dependent Absorbing Metasurfaces

    NASA Astrophysics Data System (ADS)

    Wakatsuchi, Hiroki; Kim, Sanghoon; Rushton, Jeremiah J.; Sievenpiper, Daniel F.

    2013-12-01

    We present the first use of a waveform-dependent absorbing metasurface for high-power pulsed surface currents. The new type of nonlinear metasurface, composed of circuit elements including diodes, is capable of storing high-power pulse energy to dissipate it between pulses, while allowing propagation of small signals. Interestingly, the absorbing performance varies for high-power pulses but not for high-power continuous waves (CW’s), since the capacitors used are fully charged up. Thus, the waveform dependence enables us to distinguish various signal types (i.e., CW or pulse) even at the same frequency, which potentially creates new kinds of microwave technologies and applications.

  18. 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 designed to develop research,…

  19. 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

  20. 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…

  1. Time-Dependent Reliability Analysis

    1999-10-27

    FRANTIC-3 was developed to evaluate system unreliability using time-dependent techniques. The code provides two major options: to evaluate standby system unavailability or, in addition to the unavailability to calculate the total system failure probability by including both the unavailability of the system on demand as well as the probability that it will operate for an arbitrary time period following the demand. The FRANTIC-3 time dependent reliability models provide a large selection of repair and testingmore » policies applicable to standby or continously operating systems consisting of periodically tested, monitored, and non-repairable (non-testable) components. Time-dependent and test frequency dependent failures, as well as demand stress related failure, test-caused degradation and wear-out, test associated human errors, test deficiencies, test override, unscheduled and scheduled maintenance, component renewal and replacement policies, and test strategies can be prescribed. The conditional system unavailabilities associated with the downtimes of the user specified failed component are also evaluated. Optionally, the code can perform a sensitivity study for system unavailability or total failure probability to the failure characteristics of the standby components.« less

  2. 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.

  3. Time-Dependent Reliability Analysis

    SciTech Connect

    Sartori, Enrico

    1999-10-27

    FRANTIC-3 was developed to evaluate system unreliability using time-dependent techniques. The code provides two major options: to evaluate standby system unavailability or, in addition to the unavailability to calculate the total system failure probability by including both the unavailability of the system on demand as well as the probability that it will operate for an arbitrary time period following the demand. The FRANTIC-3 time dependent reliability models provide a large selection of repair and testing policies applicable to standby or continously operating systems consisting of periodically tested, monitored, and non-repairable (non-testable) components. Time-dependent and test frequency dependent failures, as well as demand stress related failure, test-caused degradation and wear-out, test associated human errors, test deficiencies, test override, unscheduled and scheduled maintenance, component renewal and replacement policies, and test strategies can be prescribed. The conditional system unavailabilities associated with the downtimes of the user specified failed component are also evaluated. Optionally, the code can perform a sensitivity study for system unavailability or total failure probability to the failure characteristics of the standby components.

  4. Nalmefene. Alcohol dependence: no advance.

    PubMed

    2014-06-01

    Alcohol dependence is a chronic, severe and sometimes fatal disease. Psychological and social support is a crucial element of patient management. Acamprosate and naltrexone are the drugs of choice to help patients remain abstinent, but they are only moderately effective. Nalmefene, an opioid receptor antagonist related to naltrexone, has been authorised in the European Union to help alcohol-dependent patients reduce their alcohol consumption. Nalmefene has not been compared with naltrexone or acamprosate in clinical trials. Clinical evaluation is mainly based on two double-blind, randomised, placebo-controlled trials in which nalmefene was taken "on demand" at a dose of one tablet per day. The trials lasted 6 months and included a total of 1322 patients. During an initial two-week period in which all patients received medical and psychosocial support, about one-third of patients in both trials reduced their alcohol consumption without medication. Depending on the subgroup and the trial, about one-third to one-half of patients discontinued medical treatment before the end of the study period. In both trials, patients taking nalmefene had two fewer "heavy drinking days" per month than patients in the placebo groups. However, at the end of the study, they continued to drink heavily at least one week per month on average. Daily alcohol consumption was 5 to 9 grams lower with nalmefene than with placebo. The most frequent adverse effects observed in clinical trials were insomnia, dizziness, headache and nausea, which were severe in more than 10% of patients. Other serious but less frequent adverse effects included confusion, hallucinations and dissociation, usually at the beginning of treatment. These adverse effects affected about 3% of patients treated with nalmefene, a proportion three times higher than in the placebo groups. The consequences of mixing nalmefene with large amounts of alcohol are not known. In practice, the effects of nalmefene in alcohol-dependent

  5. State-dependent molecular dynamics.

    PubMed

    Yang, Ciann-Dong; Weng, Hung-Jen

    2014-01-01

    This paper proposes a new mixed quantum mechanics (QM)-molecular mechanics (MM) approach, where MM is replaced by quantum Hamilton mechanics (QHM), which inherits the modeling capability of MM, while preserving the state-dependent nature of QM. QHM, a single mechanics playing the roles of QM and MM simultaneously, will be employed here to derive the three-dimensional quantum dynamics of diatomic molecules. The resulting state-dependent molecular dynamics including vibration, rotation and spin are shown to completely agree with the QM description and well match the experimental vibration-rotation spectrum. QHM can be incorporated into the framework of a mixed quantum-classical Bohmian method to enable a trajectory interpretation of orbital-spin interaction and spin entanglement in molecular dynamics.

  6. Serial dependence in visual perception.

    PubMed

    Fischer, Jason; Whitney, David

    2014-05-01

    Visual input often arrives in a noisy and discontinuous stream, owing to head and eye movements, occlusion, lighting changes, and many other factors. Yet the physical world is generally stable; objects and physical characteristics rarely change spontaneously. How then does the human visual system capitalize on continuity in the physical environment over time? We found that visual perception in humans is serially dependent, using both prior and present input to inform perception at the present moment. Using an orientation judgment task, we found that, even when visual input changed randomly over time, perceived orientation was strongly and systematically biased toward recently seen stimuli. Furthermore, the strength of this bias was modulated by attention and tuned to the spatial and temporal proximity of successive stimuli. These results reveal a serial dependence in perception characterized by a spatiotemporally tuned, orientation-selective operator-which we call a continuity field-that may promote visual stability over time.

  7. 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.

  8. Nuclear dependence of charm production

    NASA Astrophysics Data System (ADS)

    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, L. J.; Davidenko, G. V.; Dersch, U.; Dolgolenko, A. G.; Dzyubenko, G. B.; Edelstein, R.; Emediato, L.; Endler, A. M. F.; Eschrich, I.; Escobar, C. O.; Estrada, N.; Evdokimov, A. V.; Filimonov, I. S.; Flores-Castillo, A.; Garcia, F. G.; Golovtsov, V. L.; Gouffon, P.; Gülmez, E.; Iori, M.; Jun, S. Y.; Kaya, M.; Kilmer, J.; Kim, V. T.; Kochenda, L. M.; Konorov, I.; Kozhevnikov, A. P.; Krivshich, A. G.; Krüger, H.; Kubantsev, M. A.; Kubarovsky, V. P.; Kulyavtsev, A. I.; Kuropatkin, N. P.; Kurshetsov, V. F.; Kushnirenko, A.; Lach, J.; Landsberg, L. G.; Larin, I.; Leikin, E. M.; López-Hinojosa, G.; Lungov, T.; Maleev, V. P.; Mao, D.; Mathew, P.; Mattson, M.; Matveev, V.; McCliment, E.; Moinester, M. A.; Molchanov, V. V.; Morelos, A.; Nemitkin, A. V.; Neoustroev, P. V.; Newsom, C.; Nilov, A. P.; Nurushev, S. B.; Ocherashvili, A.; Onel, Y.; Ozkorucuklu, S.; Penzo, A.; Petrenko, S. V.; Procario, M.; Prutskoi, V. A.; Razmyslovich, B. V.; Rud, V. I.; Russ, J.; Sánchez-López, J. L.; Simon, J.; Sitnikov, A. I.; Smith, V. J.; Srivastava, M.; Steiner, V.; Stepanov, V.; Stutte, L.; Svoiski, M.; Terentyev, N. K.; Torres, I.; Uvarov, L. N.; Vasiliev, A. N.; Vavilov, D. V.; Vázquez-Jáuregui, E.; Verebryusov, V. S.; Victorov, V. A.; Vishnyakov, V. E.; Vorobyov, A. A.; Vorwalter, K.; You, J.; Zukanovich-Funchal, R.

    2009-12-01

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

  9. Mexican oil and dependent development

    SciTech Connect

    Gentlemen, J.

    1984-01-01

    This study was conceived as an opportunity to examine the impact that the condition of dependency would have upon Mexico's effort to develop its huge petroleum resources in the mid 1970s. It is hardly a pleasant tale and one that provides little encouragement for those searching for solutions to underdevelopment within the contemporary Mexican political setting. Despite the fact that the study details a failed development project, the alternative to the model in place is far from obvious, as painful as that observation may be. Indeed, the failure of the development project and the analysis presented here of that failure is not directly suggestive of a preferable development alternative. While a ''socialist'' model is usually implied by dependence analysis, the socialist alternative frankly provides little guarantee of a prospect of long term viability, self-directed development and essential political and human rights to oppressed people.

  10. Genetic factors influencing alcohol dependence

    PubMed Central

    Mayfield, R D; Harris, R A; Schuckit, M A

    2008-01-01

    Plentiful data from both animal and human studies support the importance of genetic influences in substance abuse and dependence (Bierut et al., 1998; Tsuang et al., 1998; Kendler et al., 2003). This review summarizes the evidence supporting such genetic influences, places them into perspective regarding animal and human studies, discusses the importance of both genes and environment, and highlights some specific genes of interest regarding the vulnerabilities for problems associated with alcohol use disorders. A long history of repetitive heavy use of alcohol exists across generations as well as the high prevalence of alcohol-related problems in Western societies. Moreover, the information offered here addresses the importance of more general issues regarding genetics and gene expression related to alcohol abuse and dependence. PMID:18362899

  11. Geometry Dependence of Stellarator Turbulence

    SciTech Connect

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

    2009-08-10

    Using the nonlinear gyrokinetic code package GENE/GIST, 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 2D 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 Schrodinger-like equation governing linear drift modes.

  12. 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.

  13. Dopamine-dependent responses to morphine depend on glucocorticoid receptors

    PubMed Central

    Marinelli, Michela; Aouizerate, Bruno; Barrot, Michel; Le Moal, Michel; Piazza, Pier Vincenzo

    1998-01-01

    Previous work has shown that glucocorticoid hormones facilitate the behavioral and dopaminergic effects of morphine. In this study we examined the possible role in these effects of the two central corticosteroid receptor types: mineralocorticoid receptor (MR), and glucocorticoid receptor (GR). To accomplish this, specific antagonists of these receptors were infused intracerebroventricularly and 2 hr later we measured: (i) locomotor activity induced by a systemic injection of morphine (2 mg/kg); (ii) locomotor activity induced by an infusion of morphine (1 μg per side) into the ventral tegmental area, which is a dopamine-dependent behavioral response to morphine; (iii) morphine-induced dopamine release in the nucleus accumbens, a dopaminergic projection site mediating the locomotor and reinforcing effects of drugs of abuse. Blockade of MRs by spironolactone had no significant effects on locomotion induced by systemic morphine. In contrast, blockade of GRs by either RU38486 or RU39305, which is devoid of antiprogesterone effects, reduced the locomotor response to morphine, and this effect was dose dependent. GR antagonists also reduced the locomotor response to intraventral tegmental area morphine as well as the basal and morphine-induced increase in accumbens dopamine, as measured by microdialysis in freely moving rats. In contrast, spironolactone did not modify dopamine release. In conclusion, glucocorticoids, via GRs, facilitate the dopamine-dependent behavioral effects of morphine, probably by facilitating dopamine release. The possibility of decreasing the behavioral and dopaminergic effects of opioids by an acute administration of GR antagonists may open new therapeutic strategies for treatment of drug addiction. PMID:9636221

  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. Scale-Dependent Dispersivity Explained Without Scale-Dependent Heterogeneity

    NASA Astrophysics Data System (ADS)

    Dhaliwal, P.; Engdahl, N. B.; Fogg, G. E.

    2011-12-01

    The observed scale-dependence of dispersivity has often been attributed to the scale-dependence of porous media heterogeneity. However, mass transfer between areas of high and low hydraulic conductivity and preferential solute migration may provide an alternative explanation for this phenomenon. To illustrate this point, we used geostatistical models representing the heterogeneity and interconnectedness of a typical aquifer system and plume modeling via a highly accurate random walk particle tracking method. The apparent dispersivity values were calculated using the statistical moments of the plumes. Apparent dispersivity was seen to grow from 0.01(m)to 100(m) over length scales of 0.06(m) to 500(m) even though heterogeneity scales and facies proportions were stationary and invariant with scale in the simulations. The results suggest that the increase in dispersivity was due solely to a stretching of the plume by two mechanisms. The first mechanism results from the diffusion of solute into areas of low conductivity and the second comes from the movement of solute through well-connected high K zone channels. Under such conditions, an "asymptotic dispersivity" may never be reached.

  16. PET Imaging of Leptin Biodistribution and Metabolism in Rodents and Primates

    PubMed Central

    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

    2010-01-01

    Summary Here we report the first PET imaging studies of leptin's systemic biodistribution in vivo. PET imaging using 18F and 68Ga 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 and also provide a novel and general chemical strategy for 18F labeling of proteins for PET imaging of other polypeptide hormones. PMID:19656493

  17. 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.

  18. 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. PMID:19952392

  19. 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

  20. Helper-Dependent Adenoviral Vectors

    PubMed Central

    Rosewell, Amanda; Vetrini, Francesco; Ng, Philip

    2012-01-01

    Helper-dependent adenoviral vectors are devoid of all viral coding sequences, possess a large cloning capacity, and can efficiently transduce a wide variety of cell types from various species independent of the cell cycle to mediate long-term transgene expression without chronic toxicity. These non-integrating vectors hold tremendous potential for a variety of gene transfer and gene therapy applications. Here, we review the production technologies, applications, obstacles to clinical translation and their potential resolutions, and the future challenges and unanswered questions regarding this promising gene transfer technology. PMID:24533227

  1. 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

  2. Complement-dependent cytotoxicity crossmatch.

    PubMed

    Peña, Jeremy Ryan; Fitzpatrick, Donna; Saidman, Susan L

    2013-01-01

    The complement-dependent cytotoxic crossmatch is an informative test that detects alloantibodies in pre- and post-transplant patients, which may dictate clinical management of transplant patients. While challenging to perform, the cytotoxic crossmatch represents the only assay that provides direct evidence for the presence of potentially pathologic (i.e., cytotoxic) alloantibodies. The cytotoxic crossmatch combines patient (recipient) serum and donor cells. If donor-reactive alloantibodies are present in patient serum, these antibodies can bind donor cells. Antibody-antigen complexes, in turn, can activate the complement cascade, leading to complement-mediated cytotoxicity. Two commonly performed cytotoxic crossmatches, using donor lymphocytes as target cells, are described.

  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. The genetics of nicotine dependence.

    PubMed

    Li, Ming D

    2006-04-01

    Despite almost two decades of intensive tobacco-control efforts, approximately 23% of American adults continue to smoke, and 13% are nicotine-dependent. Cigarette smoking is the greatest preventable cause of cancer, accounting for at least 30% of all cancer deaths and 87% of lung cancer deaths. Smoking behavior is influenced by both genetic and environmental factors. Many years of twin and adoption studies have demonstrated that the heritability of liability for nicotine dependence (ND) is at least 50%. During the past several years, significant efforts have been made to identify susceptibility genes for ND using both genome-wide linkage and association analysis approaches. It is expected that identification of susceptibility genes for ND will allow the development and tailoring of both prevention strategies for individuals at risk and effective treatment programs and medicines for individuals who use tobacco products. This review summarizes the recent progress in genetic studies of ND. As genotyping technology is being improved and well-characterized clinical samples on smoking behavior become available, more and more genes and genetic variants responsible for ND will be identified in the near future. PMID:16539894

  5. Selfsimilar time dependent shock structures

    NASA Technical Reports Server (NTRS)

    Beck, R.; Drury, L. O.

    1985-01-01

    Diffusive shock acceleration as an astrophysical mechanism for accelerating charged particles has the advantage of being highly efficient. This means however that the theory is of necessity nonlinear; the reaction of the accelerated particles on the shock structure and the acceleration process must be self-consistently included in any attempt to develop a complete theory of diffusive shock acceleration. Considerable effort has been invested in attempting, at least partially, to do this and it has become clear that in general either the maximum particle energy must be restricted by introducing additional loss processes into the problem or the acceleration must be treated as a time dependent problem (Drury, 1984). It is concluded that stationary modified shock structures can only exist for strong shocks if additional loss processes limit the maximum energy a particle can attain. This is certainly possible and if it occurs the energy loss from the shock will lead to much greater shock compressions. It is however equally possible that no such processes exist and we must then ask what sort of nonstationary shock structure develops. The ame argument which excludes stationary structures also rules out periodic solutions and indeed any solution where the width of the shock remains bounded. It follows that the width of the shock must increase secularly with time and it is natural to examine the possibility of selfsimilar time dependent solutions.

  6. Dependence receptors and colorectal cancer.

    PubMed

    Mehlen, Patrick; Tauszig-Delamasure, Servane

    2014-11-01

    The research on colorectal cancer (CRC) biology has been leading the oncology field since the early 1990s. The search for genetic alterations has allowed the identification of the main tumour suppressors or oncogenes. Recent work obtained in CRC has unexpectedly proposed the existence of novel category of tumour suppressors, the so-called 'dependence receptors'. These transmembrane receptors behave as Dr Jekyll and Mr Hyde with two opposite sides: they induce a positive signalling (survival, proliferation, differentiation) in presence of their ligand, but are not inactive in the absence of their ligand and rather trigger apoptosis when unbound. This trait confers them a conditional tumour suppressor activity: they eliminate cells that grow abnormally in an environment offering a limited quantity of ligand. This review will describe how receptors such as deleted in colorectal carcinoma (DCC), uncoordinated 5 (UNC5), rearranged during transfection (RET) or TrkC constrain CRC progression and how this dependence receptor paradigm may open up therapeutical perspectives. PMID:25163468

  7. 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…

  8. [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. PMID:26394503

  9. [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.

  10. 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.

  11. 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. PMID:24760073

  12. 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

  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. Interpersonal dependency in alcoholic and obese men.

    PubMed

    Mills, J K

    1995-06-01

    While psychological conflict about dependency needs of alcoholic and obese persons has been widely observed, few studies have examined differences in dependency characteristics between these clinical groups. The Interpersonal Dependency Inventory was administered to 22 alcoholic and 8 morbidly obese men in intensive treatment for alcohol and obesity. The original hypothesis that alcoholic and obese men would show similar dependency needs was supported. Dependency correlates of personality may serve as useful predictor variables in the clinical treatment of alcoholic and obese persons.

  15. Temperature Dependence of Cesium Iodine

    NASA Astrophysics Data System (ADS)

    Valentine, John David

    The gamma-ray excited, temperature dependent scintillation characteristics of CsI(T1) are reported over the temperature range of -100 to +50^circ C. The modified Bollinger-Thomas and shaped square wave methods were used to measure the rise and decay times. Emission spectra were measured using a monochromator and corrected for monochromator and photocathode spectral efficiencies. The shaped square wave method was also used to determine the scintillation yield as was a current mode method. The thermoluminescence emission of CsI(T1) were measured using the same current mode method. At room temperature, CsI(T1) was found to have two primary decay components with decay time constants of tau_1 = 679 +/- 9 ns (63.7%) and tau_2 = 3.34 +/- 0.10 mus (36.1%), an absolute scintillation yield of 65,500 +/- 4,100 photons/MeV, and emission bands at about 400 and 560 nm. The tau_1 luminescent state was observed to be populated by an exponential process with a resulting rise time constant of 19.6 +/- 1.9 ns at room temperature. An ultra-fast decay component with a <0.5 ns decay time was found to emit about 0.2% of the total scintillation light (about 100 photons/MeV). Except for the ultra-fast decay time, the rise and decay time constants were observed to increase exponentially with inverse temperature. At -80 ^circC, tau_1 and tau_2 were determined to be 2.22 +/- 0.31 mu s and 18.0 +/- 1.44 mus, respectively, while the 400 nm emission band was not observed below -50 ^circC. At +50^circ C, the decay constants were found to be 628 +/- 3 ns (70.5%) and 2.63 +/- 0.03 mus (29.3%) and both emission bands are present. The scintillation yield of CsI(T1) was observed to be only slightly temperature dependent between -40 and +50^circ C, peaking at about -30 ^circC (about 6% above the room temperature yield). Four different commercially-available CsI(T1) crystals were used. Minimal variations in the measured scintillation characteristics were observed among these four crystals

  16. 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.

  17. Depth dependent multiple logging system

    SciTech Connect

    Howells, A. P. S.; Angehrn, J. A.; Dienglewicz, A. M.; Viswanathan, R.

    1985-12-03

    An improved well logging technique is provided for more accurately deriving and correlating a plurality of measurements made during a single traversal of a logging instrument through subsurface formations. In one exemplary embodiment, methods and apparatus are provided for deriving a more accurate and precise measurement of depth at which real-time logging measurements are made, and in particular for correcting anomalies occurring in the depth indication from cable stretch, yo-yo of the sonde in the borehole and the like. The more accurate and precise depth measurement is then utilized for generating well logging measurements on a depth-dependent basis, deriving at least some of such measurements in digital form and alternately transmitting to the surface digital and analog representations of such measurements. Furthermore, methods and apparatus are provided for deriving measurements of subsurface earth formation from a plurality of logging instruments combined in a single tool, wherein such measurements are made during a single pass through a borehole with the resultant measurement data correlatively merged, recorded and displayed.

  18. 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).

  19. Psychobiological mechanisms of exercise dependence.

    PubMed

    Hamer, Mark; Karageorghis, Costas I

    2007-01-01

    Exercise dependence (ED) is characterised by an obsessive and unhealthy preoccupation with exercise. Previous research has focused largely on identifying behavioural aspects of ED, although the biological mechanisms remain unknown and are under researched. We review various ED hypotheses including affect regulation, anorexia analogue, sympathetic arousal and beta-endorphin. We also present a novel hypothesis pertaining to ED and interleukin (IL)-6, which combines previous hypotheses with literature from the field of psycho-neuroimmunology. We explore the notion that IL-6 provides a link from the periphery to the brain, which may mediate the underlying features of ED. We propose a conceptual model indicating that, in individuals prone to ED, exercise results in a transient reduction in negative affect, but concurrently results in excessive production of IL-6 and the activation of neuroendocrine pathways, which are associated with behavioural and psychological disturbances of exercise withdrawal. Our intention is for this model to serve as a basis for further research in the area of ED, which may eventually lead to the development of successful treatment strategies. Recent developments in methods to reliably assess these biological markers from blood and saliva samples should encourage such research to be undertaken in exercise settings. PMID:17503874

  20. 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.

  1. Common Surgeries Raise Risk for Opioid Dependence

    MedlinePlus

    ... fullstory_159815.html Common Surgeries Raise Risk for Opioid Dependence: Study Doctors should explore alternatives for pain ... have an elevated risk of growing dependent on opioid painkillers, a new study finds. These prescription painkillers ...

  2. 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'…

  3. Dependency and Education: Reproduction or Conspiracy?

    ERIC Educational Resources Information Center

    Velloso, Jacques

    1985-01-01

    The origins and meaning of dependency are examined, how the dependency approach as an analytical tool can be used to advance research in comparative education is illustrated, and two issues raised by the critics of dependency--the issues of reproduction and of conspiracy--are discussed. (RM)

  4. 25 CFR 700.57 - Dependent.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 2 2010-04-01 2010-04-01 false Dependent. 700.57 Section 700.57 Indians THE OFFICE OF NAVAJO AND HOPI INDIAN RELOCATION COMMISSION OPERATIONS AND RELOCATION PROCEDURES General Policies and Instructions Definitions § 700.57 Dependent. A dependent is a person who either derives more than one-half...

  5. 25 CFR 700.57 - Dependent.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 25 Indians 2 2011-04-01 2011-04-01 false Dependent. 700.57 Section 700.57 Indians THE OFFICE OF NAVAJO AND HOPI INDIAN RELOCATION COMMISSION OPERATIONS AND RELOCATION PROCEDURES General Policies and Instructions Definitions § 700.57 Dependent. A dependent is a person who either derives more than one-half...

  6. 25 CFR 700.57 - Dependent.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 25 Indians 2 2012-04-01 2012-04-01 false Dependent. 700.57 Section 700.57 Indians THE OFFICE OF NAVAJO AND HOPI INDIAN RELOCATION COMMISSION OPERATIONS AND RELOCATION PROCEDURES General Policies and Instructions Definitions § 700.57 Dependent. A dependent is a person who either derives more than one-half...

  7. 25 CFR 700.57 - Dependent.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 25 Indians 2 2013-04-01 2013-04-01 false Dependent. 700.57 Section 700.57 Indians THE OFFICE OF NAVAJO AND HOPI INDIAN RELOCATION COMMISSION OPERATIONS AND RELOCATION PROCEDURES General Policies and Instructions Definitions § 700.57 Dependent. A dependent is a person who either derives more than one-half...

  8. 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,…

  9. Community Stability and Timber-Dependent Communities.

    ERIC Educational Resources Information Center

    Machlis, Gary E.; Force, Jo Ellen

    1988-01-01

    Critically evaluates the literature on timber-dependent communities. Examines methodological and theoretical concerns with concepts of community and resource-based economies. Suggests timber dependency may represent a special case of resource dependency and that study of forest-based communities can contribute to sociological knowledge of rural…

  10. 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, Language, Brain" (pp. 95-126). Cambridge, MA:…

  11. 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

  12. The pathological status of exercise dependence

    PubMed Central

    Bamber, D.; Cockerill, I.; Carroll, D.

    2000-01-01

    Objectives—This study was concerned with the concept of exercise dependence. Levels of psychological morbidity, personality profiles, and exercise beliefs were compared among subjects screened for exercise dependence and eating disorders. Method—Adult female exercisers were allocated on the basis of questionnaire screening to one of the following groups: primary exercise dependence (n = 43); secondary exercise dependence, where there was the coincidence of exercise dependence and an eating disorder (n = 27); eating disorder (n =14); control, where there was no evidence of either exercise dependence or eating disorder (n = 110). Questionnaire assessment was undertaken of psychological morbidity, self esteem, weight and body shape dissatisfaction, personality, and exercise beliefs. Results—Aside from a higher incidence of reported menstrual abnormalities, the primary exercise dependence group was largely indistinguishable from the controls. In stark contrast, the secondary exercise dependence group reported higher levels of psychological morbidity, neuroticism, dispositional addictiveness, and impulsiveness, lower self esteem, greater concern with body shape and weight, as well as with the social, psychological, and aesthetic costs of not exercising than the controls, but differed little from the eating disorder group. Conclusions—In the absence of an eating disorder, women identified as being exercise dependent do not exhibit the sorts of personality characteristics and levels of psychological distress that warrant the construction of primary exercise dependence as a widespread pathology. Key Words: exercise dependence; eating disorders; personality; self esteem; neuroticism; psychological morbidity PMID:10786869

  13. 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

  14. 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…

  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. PMID:17474850

  16. 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.

  17. [Vitamin D dependency and its treatment].

    PubMed

    Kitanaka, Sachiko

    2016-02-01

    Vitamin D dependency is classified to vitamin D-dependent rickets type 1 which shows defective 1,25(OH)(2)D production, and vitamin D-dependent rickets type 2 which shows end-organ unresponsiveness to 1,25(OH)(2)D. Recent advance in the molecular analysis of these diseases revealed variety in the presentation and in the inheritance patterns. Molecular diagnosis would be preferable for adequate therapy especially in type 2.

  18. [Vitamin D dependency and its treatment].

    PubMed

    Kitanaka, Sachiko

    2016-02-01

    Vitamin D dependency is classified to vitamin D-dependent rickets type 1 which shows defective 1,25(OH)(2)D production, and vitamin D-dependent rickets type 2 which shows end-organ unresponsiveness to 1,25(OH)(2)D. Recent advance in the molecular analysis of these diseases revealed variety in the presentation and in the inheritance patterns. Molecular diagnosis would be preferable for adequate therapy especially in type 2. PMID:26813508

  19. 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

  20. Incorporating spatial dependence in regional frequency analysis

    PubMed Central

    Wang, Zhuo; Yan, Jun; Zhang, Xuebin

    2014-01-01

    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. PMID:25745273

  1. 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

  2. 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)

  3. Alcoholism, Field Dependency and Organic Impairment.

    ERIC Educational Resources Information Center

    Lafferty, Patricia; Kahn, Marvin W.

    Although research has suggested that field dependency is a relatively stable characteristic of alcoholics, the results have been confounded by the use of different measures and different time intervals. To investigate the degree of organic brain impairment and its association with measured field dependency amongst alcoholics, 41 male alcoholics,…

  4. 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.

  5. 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…

  6. 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…

  7. TIME DELAY SYSTEMS WITH DISTRIBUTION DEPENDENT DYNAMICS

    PubMed Central

    Banks, H. T.; Dediu, Sava; Nguyen, Hoan K.

    2009-01-01

    General delay dynamical systems in which uncertainty is present in the form of probability measure dependent dynamics are considered. Several motivating examples arising in biology are discussed. A functional analytic framework for investigating well–posedness (existence, uniqueness and continuous dependence of solutions), inverse problems, sensitivity analysis and approximations of the measures for computational purposes is surveyed. PMID:19865602

  8. TIME DELAY SYSTEMS WITH DISTRIBUTION DEPENDENT DYNAMICS.

    PubMed

    Banks, H T; Dediu, Sava; Nguyen, Hoan K

    2007-01-01

    General delay dynamical systems in which uncertainty is present in the form of probability measure dependent dynamics are considered. Several motivating examples arising in biology are discussed. A functional analytic framework for investigating well-posedness (existence, uniqueness and continuous dependence of solutions), inverse problems, sensitivity analysis and approximations of the measures for computational purposes is surveyed.

  9. 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)

  10. 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...

  11. 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.

  12. Enhancing Dependent Sample Analyses with Graphics

    ERIC Educational Resources Information Center

    Pruzek, Robert M.; Helmreich, James E.

    2009-01-01

    A standard topic in many Introductory Statistics courses is the analysis of dependent samples. A simple graphical approach that is particularly relevant to dependent sample comparisons is presented, illustrated and discussed in the context of analyzing five real data sets. Each data set to be presented has been published in a textbook, usually…

  13. 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…

  14. 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.

  15. Model dependence of elliptic flow differences

    NASA Astrophysics Data System (ADS)

    Cozma, M. D.

    2013-02-01

    An isospin dependent version of the QMD transport model is used to study the influence of the isovector part of the equation of state of nuclear matter on observables that can be measured in heavy-ion collisions at intermediate energy. The model dependence of neutron-proton elliptic flow difference is studied for AuAu collisions at an incident energy of 400 MeV per nucleon. It is found that the sensitivity to microscopical nucleon-nucleon cross-sections, momentum dependence of the optical potential, compressibility modulus of nuclear matter and width of nucleon wave function are moderate compared to the dependence on the stiffness of the isospin asymmetric part of the equation of state. It is concluded that neutron-proton elliptic flow difference is a suitable observable for setting constraints on the supra-saturation density dependence of symmetry energy.

  16. 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.

  17. 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.

  18. 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.

  19. Cigarette smoking, nicotine dependence, and treatment.

    PubMed Central

    Sees, K L

    1990-01-01

    Since the 1988 Surgeon General's report on nicotine addiction, more attention is being given to nicotine dependence as a substantial contributing factor in cigarette smokers' inability to quit. Many new medications are being investigated for treating nicotine withdrawal and for assisting in long-term smoking abstinence. Medications alone probably will not be helpful; they should be used as adjuncts in comprehensive smoking abstinence programs that address not only the physical dependence on nicotine but also the psychological dependence on cigarette smoking. PMID:2190425

  20. Process dependent nuclear k⊥ broadening effect

    NASA Astrophysics Data System (ADS)

    Schäfer, Andreas; Zhou, Jian

    2013-10-01

    We study the process dependent nuclear k⊥ broadening effect by employing the transverse momentum dependent (TMD) factorization approach in combination with the Mclerran-Venugopalan model. More specifically, we investigate how the parton transverse momentum distributions are affected by the process dependent gauge links in cold nuclear matter. In particular, our analysis also applies to the polarized cases including the nuclear quark Boer-Mulders function and the linearly polarized gluon distribution. Our main focus is on the nuclear TMDs at intermediate or large x.

  1. 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.

  2. 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.

  3. Bounds for state-dependent quantum cloning

    SciTech Connect

    Han Yongjian; Zhang Yongsheng; Guo Guangcan

    2002-11-01

    Due to the no-cloning theorem, the unknown quantum state can only be cloned approximately or exactly with some probability. There are two types of cloners: universal and state-dependent cloner. The optimal universal cloner has been found and can be viewed as a special state-dependent quantum cloner that has no information about the states. In this paper, we investigate the state-dependent cloning when the state set contains more than two states. We get some bounds of the global fidelity for these processes. This method is not dependent on the number of the states contained in the state set. It is also independent of the numbers of copying.

  4. National Council on Alcoholism and Drug Dependence

    MedlinePlus

    ... 2016 A new study finds the number of young children and teens hospitalized … NCADD Joins the Global #GIVINGTUESDAY Mo… 3 November, 2016 The National Council on Alcoholism and Drug Dependence (NCADD) has joi… State Votes ...

  5. Polarization Dependent Optical Responses of Graphene Nanoribbons

    NASA Astrophysics Data System (ADS)

    Cao, Ting; Choi, Sangkook; Louie, Steven

    2014-03-01

    The optical response of an anisotropic system depends on light's polarization direction. In this study, we perform first-principle calculations on polarization dependent optical absorption spectra of graphene nanoribbons at the RPA and GW-BSE level. We observe significant polarization dependent features. We demonstrate the many-body origins of these features. We also discuss the polarization dependent optical responses of other carbon nanostructures, and connect our work to experimental measurements. This work was supported by National Science Foundation Grant No. DMR10-1006184, the U.S. Department of Energy under Contract No. DE-AC02-05CH11231. Computational resources have been provided by DOE at Lawrence Berkeley National Laboratory's NERSC facility

  6. ▼Nalmefene for alcohol dependence.

    PubMed

    2014-05-01

    The burden of morbidity and mortality resulting from alcohol dependence is high. World Health Organization (WHO) figures suggest that in the UK the prevalence of alcohol use disorders in those aged 15 years and older is around 6.4% for men and 1.5% for women.1 Reduction of harm resulting from alcohol dependence remains a high priority in all four devolved health services in the UK.2-5 Several medicines are licensed for the maintenance of abstinence in alcohol-dependent patients. However, until recently no drug was licensed for the management of alcohol dependence in people who are still drinking. ▼Nalmefene (Selincro, Lundbeck), an opioid modulator licensed for the reduction of alcohol consumption, was launched in the UK in May 2013.6,7 Here we discuss the evidence for its effectiveness and safety and consider its place in therapy.

  7. 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.

  8. 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)

  9. 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. PMID:20530050

  10. Treating drug-dependent patients in hospitals.

    PubMed

    Skene, Loane; Keays, David; Gardner, Bruce

    2002-08-01

    Are hospital staff legally permitted to test drug-dependent patients for drugs or infectious disease without the patient's consent in order to treat the patient or to protect themselves or other patients? What should staff do with "suspicious" items in the patient's possession (drugs, credit cards in different names, firearms)? Can drug-dependent patients lawfully use illicit drugs in hospital? Who should supply and administer them? PMID:12242876

  11. The Developmental Trajectory of Nonadjacent Dependency Learning

    ERIC Educational Resources Information Center

    Gomez, Rebecca; Maye, Jessica

    2005-01-01

    We investigated the developmental trajectory of nonadjacent dependency learning in an artificial language. Infants were exposed to 1 of 2 artificial languages with utterances of the form [aXc or bXd] (Grammar 1) or [aXd or bXc] (Grammar 2). In both languages, the grammaticality of an utterance depended on the relation between the 1st and 3rd…

  12. Time dependent breakdown in silicon dioxide films

    NASA Technical Reports Server (NTRS)

    Svensson, C.; Shumka, A.

    1975-01-01

    An investigation was conducted regarding the possible existence of a time-dependent breakdown mechanism in thermal oxides of the type used as gate oxide in MOS circuits. Questions of device fabrication are discussed along with details concerning breakdown measurements and the determination of C-V characteristics. A relatively large prebreakdown current observed in one of the cases is related to the time-dependent breakdown.

  13. PROFILE OF LIVER DYSFUNCTION IN ALCHOHOL DEPENDENCE

    PubMed Central

    Desai, N.G.; Vaswani, M.; Chavan, B.S.; Tripathi, B.M.; Kaw, N.

    1996-01-01

    Ninety two patients of alcohol dependence were studied for liver function at a specialised drug dependence treatment centre. Biochemical laboratory evidence of liver dysfunction was found in a very large number of patients, including the patients who had no clinical signs or symptoms. The findings from this retrospective study are discussed in the context of the earlier studies from other settings in India. PMID:21584115

  14. Molecular and genetic determinants of alcohol dependence.

    PubMed

    Awofala, Awoyemi A

    2013-01-01

    Alcohol dependence is a complex disorder affecting all social and ethnic groups. Although the scientific understanding of the mechanism governing this multifactorial disease is still in its infancy, understanding its biological bases, including the potential contribution of genetic factors, is key to characterizing individual's risk and developing efficacious therapeutic target to combat the disease. This review provides an overview of different approaches that are being increasingly integrated to extend our knowledge of the genetic underpinnings of alcohol dependence.

  15. 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.

  16. [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.

  17. Lucigenin-dependent chemiluminescence in articular chondrocytes.

    PubMed

    Rathakrishnan, C; Tiku, M L

    1993-08-01

    We were recently able to measure intracellular levels of hydrogen peroxide within normal articular chondrocytes using the trapped indicator 2',7'-dichlorofluorescein diacetate. Further studies have shown that stimulated chondrocytes produce luminol-dependent chemiluminescence, suggesting that these cells produce hydrogen peroxide and singlet oxygen. In the present study, we have investigated the lucigenin-dependent chemiluminescence response in normal articular chondrocytes. Chondrocytes either in suspension or adhered to cover slips showed lucigenin-dependent chemiluminescence. There was a dose-dependent increase in chemiluminescence response when chondrocytes were incubated with soluble stimuli like phorbol-myristate-acetate, concanavalin A, and f-met-leu-phe. Catalase and the metabolic inhibitor, sodium azide, which inhibits the enzyme myeloperoxidase, had no inhibitory effect on lucigenin-dependent chemiluminescence production. Only the antioxidant, superoxide dismutase, prevented lucigenin-dependent chemiluminescence, indicating that this assay measures the production of superoxide anions by chondrocytes. We confirmed that chondrocytes release superoxide radicals using the biochemical assay of ferricytochrome c reduction. Since cartilage tissue is semi-transparent, we were able to measure chemiluminescence response in live cartilage tissue, showing that chondrocytes which are embedded within the matrix can also generate superoxide anion radicals. Reactive oxygen intermediates have been shown to play a significant role in the degradation of matrix in arthritis. Our previous and present studies suggest that oxygen radicals produced by chondrocytes may be an important mechanism by which chondrocytes induce cartilage matrix degradation.

  18. 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.

  19. 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

  20. Minimization of dependency length in written English.

    PubMed

    Temperley, David

    2007-11-01

    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, Language, Brain (pp. 95-126). Cambridge, MA: MIT Press.] proposes that the processing complexity of a sentence is related to the length of its syntactic dependencies: longer dependencies are more difficult to process. The DLT is supported by a variety of phenomena in language comprehension. This raises the question: Does language production reflect a preference for shorter dependencies as well? I examine this question in a corpus study of written English, using the Wall Street Journal portion of the Penn Treebank. The DLT makes a number of predictions regarding the length of constituents in different contexts; these predictions were tested in a series of statistical tests. A number of findings support the theory: the greater length of subject noun phrases in inverted versus uninverted quotation constructions, the greater length of direct-object versus subject NPs, the greater length of postmodifying versus premodifying adverbial clauses, the greater length of relative-clause subjects within direct-object NPs versus subject NPs, the tendency towards "short-long" ordering of postmodifying adjuncts and coordinated conjuncts, and the shorter length of subject NPs (but not direct-object NPs) in clauses with premodifying adjuncts versus those without.

  1. Is frictional healing slip-dependent?

    NASA Astrophysics Data System (ADS)

    Bhattacharya, P.; Rubin, A. M.; Ryan, K. L.; Riviere, J. V.; Marone, C.

    2015-12-01

    Frictional re-strengthening of bare rock surfaces at very low stresses and near zero slip rate, as observed in the laboratory, is traditionally interpreted as showing support for purely time-dependent healing as embodied in the Aging law. However, while slide-hold-slide experiments on bare surfaces do show an apparent (purely) time-dependent increase in the static friction upon reslide, we show that the stress minima attained during the preceding holds show a strong slip-dependence which contradict the Aging law. A velocity strengthening Slip law explains such data much better. We also show that, large velocity step decreases, which drive the system far below steady state just like long holds, clearly support the slip-dependent response of the Slip law over the time-dependent healing contained in the Aging law. But, while time-dependent healing has an intuitive physical picture in terms of growth of the 'real contact area' with time, it is more difficult to ascribe one to slip-dependent healing. Here, we explore the possibility that the slip-dependence arises out of an interplay between contact `quality' and `quantity' at the scale of the asperity contacts. First, to further study the slip-dependence of healing, we carry out large velocity step decreases and sequences of long slide-hold-slides on both bare rock and gouge. Secondly, to probe the micro-mechanical origins of healing, we complement our mechanical data with amplitudes and travel time data of ultrasonic P- and S- waves transmitted across the sliding interface. While ultrasonic P-wave transmissivity has been used as a proxy for 'real contact area' in friction experiments by Nagata et al. (2012, 2014) before, the simultaneous use of P- and S-phases in our experiments is designed specifically to probe contact rheology. Initial results show strong correlations between changes in friction, transmitted wave amplitudes and travel times in response to changes in slip rate. We also observe important differences

  2. 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

  3. Eating pattern of morphine dependent rats.

    PubMed

    Yanaura, S; Suzuki, T

    1979-10-01

    To analyze the drug ingestion patterns of rats in the course of dependence development while on the drug-admixed food (DAF) method, an automatic food intake measuring apparatus was developed. Rats were put on morphine-admixed food, and the food ingestion patterns were recorded with the apparatus in the course of dependence development, during drug withdrawal and at the time of challenge with levallorphan. The naive rats ate the regular diet intermittently at night, and the eating time of morphine-treated rats was longer than that of naive rats. The treated rats also exhibited a frequent eating behavior after 4--5 days on the morphine treatment. During morphine withdrawal, the animal gradually ate the regular diet at about 1-hour intervals, even after evolvement of abstinence signs. When the morphine-dependent rats were given levallorphan, they neither ate nor approached to the food for the first 2--3 hours, but after this time, showed abrupt increases in these activities. Thus, the drug intake pattern of rats in the course of morphine dependence development suggests a correlation between the stage of development of physical dependence and the stage when the animals frequently eat the drug-admixed food.

  4. 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

  5. Spatial dependences among precipitation maxima over Belgium

    NASA Astrophysics Data System (ADS)

    Vannitsem, S.; Naveau, P.

    2007-09-01

    For a wide range of applications in hydrology, the probability distribution of precipitation maxima represents a fundamental quantity to build dykes, propose flood planning policies, or more generally, to mitigate the impact of precipitation extremes. Classical Extreme Value Theory (EVT) has been applied in this context by usually assuming that precipitation maxima can be considered as Independent and Identically Distributed (IID) events, which approximately follow a Generalized Extreme Value distribution (GEV) at each recording site. In practice, weather stations records can not be considered as independent in space. Assessing the spatial dependences among precipitation maxima provided by two Belgium measurement networks is the main goal of this work. The pairwise dependences are estimated by a variogram of order one, also called madogram, that is specially tailored to be in compliance with spatial EVT and to capture EVT bivariate structures. Our analysis of Belgium precipitation maxima indicates that the degree of dependence varies greatly according to three factors: the distance between two stations, the season (summer or winter) and the precipitation accumulation duration (hourly, daily, monthly, etc.). Increasing the duration (from one hour to 20 days) strengthens the spatial dependence. The full independence is reached after about 50 km (100 km) for summer (winter) for a duration of one hour, while for long durations only after a few hundred kilometers. In addition this dependence is always larger in winter than in summer whatever is the duration. An explanation of these properties in terms of the dynamical processes dominating during the two seasons is advanced.

  6. Alcohol dependence as a chronic pain disorder

    PubMed Central

    Egli, Mark; Koob, George F.; Edwards, Scott

    2013-01-01

    Dysregulation of pain neurocircuitry and neurochemistry has been increasingly recognized as playing a critical role in a diverse spectrum of diseases including migraine, fibromyalgia, depression, and PTSD. Evidence presented here supports the hypothesis that alcohol dependence is among the pathologies arising from aberrant neurobiological substrates of pain. In this review, we explore the possible influence of alcohol analgesia and hyperalgesia in promoting alcohol misuse and dependence. We examine evidence that neuroanatomical sites involved in the negative emotional states of alcohol dependence also play an important role in pain transmission and may be functionally altered under chronic pain conditions. We also consider possible genetic links between pain transmission and alcohol dependence. We propose an allostatic load model in which episodes of alcohol intoxication and withdrawal, traumatic stressors, and injury are each capable of dysregulating an overlapping set of neural substrates to engender sensory and affective pain states that are integral to alcohol dependence and comorbid conditions such as anxiety, depression, and chronic pain. PMID:22975446

  7. 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

  8. Time dependence of adiabatic particle number

    NASA Astrophysics Data System (ADS)

    Dabrowski, Robert; Dunne, Gerald V.

    2016-09-01

    We consider quantum field theoretic systems subject to a time-dependent perturbation, and discuss the question of defining a time-dependent particle number not just at asymptotic early and late times, but also during the perturbation. Naïvely, this is not a well-defined notion for such a nonequilibrium process, as the particle number at intermediate times depends on a basis choice of reference states with respect to which particles and antiparticles are defined, even though the final late-time particle number is independent of this basis choice. The basis choice is associated with a particular truncation of the adiabatic expansion. The adiabatic expansion is divergent, and we show that if this divergent expansion is truncated at its optimal order, a universal time dependence is obtained, confirming a general result of Dingle and Berry. This optimally truncated particle number provides a clear picture of quantum interference effects for perturbations with nontrivial temporal substructure. We illustrate these results using several equivalent definitions of adiabatic particle number: the Bogoliubov, Riccati, spectral function and Schrödinger picture approaches. In each approach, the particle number may be expressed in terms of the tiny deviations between the exact and adiabatic solutions of the Ermakov-Milne equation for the associated time-dependent oscillators.

  9. 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

  10. Representing higher-order dependencies in networks.

    PubMed

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

    2016-05-01

    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

  11. Incident Angle Dependence of Organic Solar Cells

    NASA Astrophysics Data System (ADS)

    Degeorge, Vincent; Valle, Brent; Singer, Kenneth

    2010-10-01

    We have been recently studying the use of interference effects to enhance optical absorption in polymer photovoltaic cells. These interference effects are expected to be angle dependent. We measure here the angle dependent absorption and compare with numerical simulations. The cells used were P3HT/PCBM active layer, organic photovoltaic cells. The angular dependence of the cells' reflection was measured using an Ocean Optics light source and spectrophotometer and a precision rotary stage apparatus. The experimental results were compared to a Matlab simulation of the characteristic matrix problem. Analysis showed that the reflection/absorption peaks predicted by the simulation largely coincided in wavelength to those observed in experiment. Moreover, no additional cavity resonance can be attributed to incidence angle.

  12. 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.

  13. 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.

  14. Field dependence in the institutionalized elderly.

    PubMed

    Mosley, J; Guyot, G

    1987-01-01

    The institutional-inducement hypothesis of field dependence regression in the elderly was assessed by administering the Children's Embedded Figures Test (CEFT) to a group of elderly upon admission to a nursing home and to a group of community-living elderly. Both groups were retested four months later. The institutionalized group exhibited significantly lower CEFT scores on initial testing than the community-living group. In addition, the CEFT scores for the institutionalized group declined significantly from pretest to posttest. The results suggested that greater field dependence in the institutionalized elderly may be due to pre-institutional dependence regression that continues after institutionalization. Additional measures of mental status and activity levels were also lower in the institutionalized group upon admission supporting a pre-institutional generalized regression effect.

  15. Landauer Approach to Time-Dependent Transport

    NASA Astrophysics Data System (ADS)

    Chen, L. Y.; Nash, P. L.

    Based upon the nonequilibrium Green's function formalism, we present a time-dependent Landauer approach to transport through a mesoscopic system under an ac bias voltage. The system is modeled as an elastic scatterer coupled to large electron reservoirs through perfect conducting wires (leads). The chemical potentials of the reservoirs are driven apart by the bias and, consequently, current flows through the leads from one reservoir to another. We examine the nonequilibrium statistical processes of electrons in the leads. The electronic waves are quantized on the basis of orthonormal wave packets moving along the leads, scattered by the scatterer, and coupled to the reservoirs. The time for an electron to traverse the leads between the source and the drain reservoirs plus the phase delay time caused by the scatterer is found to be the relevant time scale in the time-dependent transport. The frequency dependence of the admittance is fully investigated.

  16. Predictive a priori pressure-dependent kinetics.

    PubMed

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

    2014-12-01

    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. PMID:25477457

  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

    2014-12-01

    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. Rats exhibit reference-dependent choice behavior.

    PubMed

    Bhatti, Mehwish; Jang, Hyeran; Kralik, Jerald D; Jeong, Jaeseung

    2014-07-01

    Human preferences depend on whether a chosen outcome appears to be a loss or a gain compared with what had been expected, i.e., in comparison to a reference point. Because reference dependence has such a strong influence on human decision-making, it is important to uncover its origins, which will in turn help delineate the underlying mechanisms. It remains unknown whether rats use reference points in decision-making, and yet, the study of rats could help address the question of whether reference dependence is evolutionarily conserved among mammals and could provide a nonhuman animal model to investigate the neural mechanisms underlying this important cognitive process. The aim of the current study was to determine whether rats show reference-dependent choice behavior. We developed a novel paradigm by modifying the "T" maze by installing "pockets" to the left and right of the "T" stem that held reward pellets so rats would potentially develop reference values for each option prior to choice. We found that the rats were indeed sensitive to the way alternatives were presented. That is, they exhibited reference-dependent choice behavior by avoiding the choice option framed as a loss (e.g., having four reward pellets in the pocket, but receiving only one), at least under conditions with certain outcomes and clear differences between the reference and outcome quantities. Despite the small number of rats in this study, this species-level capacity suggests that reference dependence in general and loss aversion in particular may be conserved traits that evolved at or before the emergence of mammals.

  19. Temperature Dependence of Radiative and Nonradiative Rates from Time-Dependent Correlation Function Methods.

    PubMed

    Banerjee, Shiladitya; Baiardi, Alberto; Bloino, Julien; Barone, Vincenzo

    2016-02-01

    The temperature dependence of the rate constants in radiative and nonradiative decays from excited electronic states has been studied using a time-dependent correlation function approach in the framework of the adiabatic representation and the harmonic oscillator approximation. The present work analyzes the vibrational aspect of the processes, which gives rise to the temperature dependence, with the inclusion of mode-mixing, as well as of frequency change effects. The temperature dependence of the rate constants shows a contrasting nature, depending on whether the process has been addressed within the Franck-Condon approximation or beyond it. The calculation of the Duschinsky matrix and the shift vector between the normal modes of the two states can be done in Cartesian and/or internal coordinates, depending on the flexibility of the investigated molecule. A new computational code has been developed to calculate the rates of intersystem crossing, internal conversion, and fluorescence for selected molecules as functions of temperature. PMID:26683207

  20. 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.

  1. 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.

  2. 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.

  3. [Problems of pain medication and dependence].

    PubMed

    Hocker, K M

    1994-05-01

    Based on the experience in a psychosomatic clinic, drug dependency problems among chronic pain patients are reported. The following three theses have evolved: 1. By far most important of all is the problem of tranquilizer abuse, which entails serious, and sometimes dramatic, withdrawal syndromes. An indication for continuous tranquilizer medication does not exist. 2. Compound preparations are problematical, in particular if they contain codeine. We frequently see abuse and even dependence. 3. Opium derivatives continue to be rarely prescribed in non-cancer chronic pain. Several instances of incorrect pain management have been found, such as prescription to substance abusers, on insufficient indication, or prescription on request instead of time-schedule therapy.

  4. 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. PMID:24810390

  5. 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.

  6. [Substitution therapy tested against amphetamine dependence].

    PubMed

    Bloniecki Kallio, Victor; Guterstam, Joar; Franck, Johan

    2016-01-01

    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. PMID:26756343

  7. Time-dependent corona models - Scaling laws

    NASA Technical Reports Server (NTRS)

    Korevaar, P.; Martens, P. C. H.

    1989-01-01

    Scaling laws are derived for the one-dimensional time-dependent Euler equations that describe the evolution of a spherically symmetric stellar atmosphere. With these scaling laws the results of the time-dependent calculations by Korevaar (1989) obtained for one star are applicable over the whole Hertzsprung-Russell diagram and even to elliptic galaxies. The scaling is exact for stars with the same M/R-ratio and a good approximation for stars with a different M/R-ratio. The global relaxation oscillation found by Korevaar (1989) is scaled to main sequence stars, a solar coronal hole, cool giants and elliptic galaxies.

  8. Maximum likelihood clustering with dependent feature trees

    NASA Technical Reports Server (NTRS)

    Chittineni, C. B. (Principal Investigator)

    1981-01-01

    The decomposition of mixture density of the data into its normal component densities is considered. The densities are approximated with first order dependent feature trees using criteria of mutual information and distance measures. Expressions are presented for the criteria when the densities are Gaussian. By defining different typs of nodes in a general dependent feature tree, maximum likelihood equations are developed for the estimation of parameters using fixed point iterations. The field structure of the data is also taken into account in developing maximum likelihood equations. Experimental results from the processing of remotely sensed multispectral scanner imagery data are included.

  9. 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.

  10. Conductivity dependent surface plasmon polariton propagation

    NASA Astrophysics Data System (ADS)

    Ali, Arshad; Bacha, Bakht Amin; Jabar, M. S. Abdul; Khan, Anwar Ali; Uddin, Rafi; Ahmad, Iftikhar

    2016-09-01

    Conductivity-dependent surface plasmon polariton (SPP) propagation is investigated at the interface between a metal and a tripod-type atomic medium. Our theoretical investigations show that the SPP propagation depends on the conductivity of the metallic medium and the coherent driving fields applied in the atomic medium up to a saturation limit. Further, the SPPs drag and rotate with collective spinning of the proposed structure. The rotation is modified with the spin angular velocity of the whole structure. A maximum rotation of  ±4 microradians is observed. Our results may find applications in plasmonster technology.

  11. 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

  12. Mode-dependent characterization of photonic lanterns.

    PubMed

    Yu, Dawei; Fu, Songnian; Cao, Zizheng; Tang, Ming; Liu, Deming; Giles, Ian; Koonen, Ton; Okonkwo, Chigo

    2016-05-15

    We propose and experimentally demonstrate a simple method for characterizing the power transfer matrix of photonic lanterns (PLs) used for mode division multiplexing (MDM) transmission. Due to the optical reflection arising at output facet of the few-mode fiber (FMF), we are able to detect the power at the individual single-mode fiber (SMF) input port and exploit a series of equations based on the theory of energy conservation to obtain mode-dependent characteristics of the PL, including the property of mode selectivity, insertion loss (IL), and channel-dependent loss (CDL). The proposed method is experimentally verified for both the mode selective and the nonmode selective photonic lanterns.

  13. 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.

  14. Differential equations of time dependent order

    NASA Astrophysics Data System (ADS)

    Ludu, A.

    2016-10-01

    We introduce a special type of ordinary differential equations dx x/dtx = f (t, x) whose order of differentiation is a continuous variable depending on the dependent x or independent t variables. We show that such variable order of differentiation equations (VODE) can be solved as Volterra integral equations of second kind with singular integrable kernel. We find the conditions for existence and uniqueness of solutions of such VODE, and present some numeric solutions for particular cases exhibiting bifurcations and blow-up.

  15. A Risk Allele for Nicotine Dependence in CHRNA5 Is a Protective Allele for Cocaine Dependence

    PubMed Central

    Grucza, Richard A; Wang, Jen C.; Stitzel, Jerry A.; Hinrichs, Anthony L.; Saccone, Scott F.; Saccone, Nancy L.; Bucholz, Kathleen K.; Cloninger, C. Robert; Neuman, Rosalind J.; Budde, John P.; Fox, Louis; Bertelsen, Sarah; Kramer, John; Hesselbrock, Victor; Tischfield, Jay; Nurnberger, John. I.; Almasy, Laura; Porjesz, Bernice; Kuperman, Samuel; Schuckit, Marc A.; Edenberg, Howard J.; Rice, John P.; Goate, Alison M.; Bierut, Laura J.

    2008-01-01

    Background A non-synonymous coding polymorphism, rs16969968, of the CHRNA5 gene which encodes the alpha-5 subunit of the nicotinic acetylcholine receptor (nAChR) has been found to be associated with nicotine dependence (20). The goal of the present study is to examine the association of this variant with cocaine dependence. Methods Genetic association analysis in two, independent samples of unrelated cases and controls; 1.) 504 European-American participating in the Family Study on Cocaine Dependence (FSCD); 2.) 814 European Americans participating in the Collaborative Study on the Genetics of Alcoholsim (COGA). Results In the FSCD, there was a significant association between the CHRNA5 variant and cocaine dependence (OR = 0.67 per allele, p = 0.0045, assuming an additive genetic model), but in the reverse direction compared to that previously observed for nicotine dependence. In multivariate analyses that controlled for the effects of nicotine dependence, both the protective effect for cocaine dependence and the previously documented risk effect for nicotine dependence were statistically significant. The protective effect for cocaine dependence was replicated in the COGA sample. In COGA, effect sizes for habitual smoking, a proxy phenotype for nicotine dependence, were consistent with those observed in FSCD. Conclusion The minor (A) allele of rs16969968, relative to the major G allele, appears to be both a risk factor for nicotine dependence and a protective factor for cocaine dependence. The biological plausibility of such a bidirectional association stems from the involvement of nAChRs with both excitatory and inhibitory modulation of dopamine-mediated reward pathways. PMID:18519132

  16. Wave function for time-dependent harmonically confined electrons in a time-dependent electric field.

    PubMed

    Li, Yu-Qi; Pan, Xiao-Yin; Sahni, Viraht

    2013-09-21

    The many-body wave function of a system of interacting particles confined by a time-dependent harmonic potential and perturbed by a time-dependent spatially homogeneous electric field is derived via the Feynman path-integral method. The wave function is comprised of a phase factor times the solution to the unperturbed time-dependent Schrödinger equation with the latter being translated by a time-dependent value that satisfies the classical driven equation of motion. The wave function reduces to that of the Harmonic Potential Theorem wave function for the case of the time-independent harmonic confining potential. PMID:24070284

  17. Regulation of hippocampus-dependent memory by cyclic AMP-dependent protein kinase

    PubMed Central

    Abel, Ted; Nguyen, Peter V.

    2010-01-01

    The hippocampus is crucial for the consolidation of new declarative long-term memories. Genetic and behavioral experimentation have revealed that several protein kinases are critical for the formation of hippocampus-dependent long-term memories. Cyclic-AMP dependent protein kinase (PKA) is a serine–threonine kinase that has been strongly implicated in the expression of specific forms of hippocampus-dependent memory. We review evidence that PKA is required for hippocampus-dependent memory in mammals, and we highlight some of the proteins that have been implicated as targets of PKA. Future directions and open questions regarding the role of PKA in memory storage are also described. PMID:18394470

  18. 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 priorities.…

  19. 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…

  20. Financial Aid Applicants: Dependent Students. Research Report.

    ERIC Educational Resources Information Center

    Northern Virginia Community Coll., Annandale. Office of Institutional Research.

    The Office of Institutional Research (OIR) at Northern Virginia Community College (NVCC) conducts analytical studies and provides information in support of institutional planning, policy formation, and decision making. This OIR report, prepared in conjunction with the Financial Aid Office, analyzes dependent students who applied for financial aid…

  1. The path dependence of deformation texture development

    SciTech Connect

    Takeshita, T.; Kocks, U.F.; Wenk, H.R.

    1987-01-01

    It is demonstrated for the case of three different strain paths, all of which end up with the same, elongated specimen shape, that the texture developed during straining is path dependent. This is true both for experiments on aluminum polycrystals and for simulations using the LApp code.

  2. 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

  3. Text Dependent Questions and the CCSS

    ERIC Educational Resources Information Center

    Aspen Institute, 2012

    2012-01-01

    An effective text dependent question first and foremost embraces the key principle of close reading embedded in the Common Core State Standards (CCSS) Anchor Reading Standards by asking students to provide evidence from complex text and draw inferences based on what the text explicitly says (Standards 1 and 10). A close look at the intervening…

  4. 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…

  5. 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…

  6. Shedding "UV" light on endogenous opioid dependence.

    PubMed

    Tejeda, Hugo A; Bonci, Antonello

    2014-06-19

    Excessive sun tanning can result in addictive behavior. In this issue of Cell, Fell et al. utilize a combination of behavioral pharmacology and transgenic mice to demonstrate that chronic UV light exposure recruits p53 signaling in keratinocytes, subsequently increasing β-endorphin signaling at opioid receptors, and produces an endogenous opioid-dependent state.

  7. 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…

  8. Shedding "UV" light on endogenous opioid dependence.

    PubMed

    Tejeda, Hugo A; Bonci, Antonello

    2014-06-19

    Excessive sun tanning can result in addictive behavior. In this issue of Cell, Fell et al. utilize a combination of behavioral pharmacology and transgenic mice to demonstrate that chronic UV light exposure recruits p53 signaling in keratinocytes, subsequently increasing β-endorphin signaling at opioid receptors, and produces an endogenous opioid-dependent state. PMID:24949960

  9. Satisfaction with life and opioid dependence

    PubMed Central

    Luty, Jason; Arokiadass, Sujaa Mary Rajagopal

    2008-01-01

    Background Serious substance misuse and dependence is widely seen as damaging to an individual and to society in general. Whereas the medical and society effects of substance misuse are widely described, some commentators suggest substance misuse may be an "alternative lifestyle". Aim To assess general life satisfaction amongst treatment-seeking people with substance dependence. Methods The Satisfaction With Life Scale (SWLS) was administered to a sample of opioid-dependent people receiving substitute medication. Results 105 subjects and 105 age-sex matched subjects in a comparison group completed the questionnaire. The mean SWLS score was 7.12 (SD = 10.6; median = 6) for patients compared to 22.6 (SD = 6.8) in the comparison group. (Two sided p < 0.0001; Median difference = -13.5; Wilcoxon signed rank test.) Conclusion The study used a validated instrument and objective reports to confirm significantly higher rates of dissatisfaction with life among opioid dependent people in treatment when compared to members of the general population. PMID:18226241

  10. Prevention of Welfare Dependency--An Overview.

    ERIC Educational Resources Information Center

    Kaplan, Jan

    2001-01-01

    This document examines strategies for preventing working families and disadvantaged youth from needing cash assistance and becoming dependent on welfare. The document begins with a brief discussion of the tenuous nature of the boundary between families who need public assistance and families who don't and factors contributing to welfare…

  11. 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…

  12. 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.

  13. 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)

  14. Evaluation Framework for Dependable Mobile Learning Scenarios

    ERIC Educational Resources Information Center

    Bensassi, Manel; Laroussi, Mona

    2014-01-01

    The goal of the dependability analysis is to predict inconsistencies and to reveal ambiguities and incompleteness in the designed learning scenario. Evaluation, in traditional learning design, is generally planned after the execution of the scenario. In mobile learning, this stage becomes too difficult and expensive to apply due to the complexity…

  15. 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,…

  16. Mycobacterium paratuberculosis. Factors that influence mycobactin dependence.

    PubMed

    Lambrecht, R S; Collins, M T

    1992-01-01

    Mycobacterium paratuberculosis does not produce any detectable mycobactin, an iron-binding compound that is synthesized by most Mycobacterium spp. and necessary for the growth of all mycobacteria. This study examined the influence of various culture conditions on mycobactin dependence in M. paratuberculosis. Using a radiometric growth assay, we found the minimal concentration of mycobactin J necessary for growth of M. paratuberculosis to be 0.006 microM, whereas 1.2 microM (1 microgram/ml) was required for optimal growth. In media without mycobactin at iron concentrations less than or equal to 100 microM, growth of M. paratuberculosis occurred at pH 5.0, but not pH 6.8. Iron concentrations greater than 100 microM did not significantly increase growth at pH 5.0, but at pH 6.8 the growth rate increased with increasing amounts of iron reaching a rate equal to control cultures containing mycobactin. Mycobacterium paratuberculosis appeared to lose mycobactin dependence when subcultured; however, this was subsequently shown to be a result of mycobactin carried over from primary medium. Removal of this contaminating cell-wall-associated mycobactin reestablished mycobactin dependence. We conclude that mycobactin dependence must be carefully determined because it is a key test used in identification of M. paratuberculosis and may be easily influenced by media pH, iron concentration, and mycobactin carryover from primary media. PMID:1582168

  17. 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

  18. Perceiving sequential dependencies in auditory streamsa

    PubMed Central

    Kidd, Gerald; Mason, Christine R.; Streeter, Timothy; Thompson, Eric R.; Best, Virginia; Wakefield, Gregory H.

    2013-01-01

    This study examined the ability of human listeners to detect the presence and judge the strength of a statistical dependency among the elements comprising sequences of sounds. The statistical dependency was imposed by specifying transition matrices that determined the likelihood of occurrence of the sound elements. Markov chains were constructed from these transition matrices having states that were pure tones/noise bursts that varied along the stimulus dimensions of frequency and/or interaural time difference. Listeners reliably detected the presence of a statistical dependency in sequences of sounds varying along these stimulus dimensions. Furthermore, listeners were able to discriminate the relative strength of the dependency in pairs of successive sound sequences. Random variation along an irrelevant stimulus dimension had small but significant adverse effects on performance. A much greater decrement in performance was found when the sound sequences were concurrent. Likelihood ratios were computed based on the transition matrices to specify Ideal Observer performance for the experimental conditions. Preliminary modeling efforts were made based on degradations of Ideal Observer performance intended to represent human observer limitations. This experimental approach appears to be useful for examining auditory “stream” formation and maintenance over time based on the predictability of the constituent sound elements. PMID:23927120

  19. [Cure of amineptine dependence with clonidine?].

    PubMed

    Bourin, M; Gest, D; Baudot, S

    1990-01-01

    Two patients with dependence to amineptine were treated with clonidine which is used in morphine withdrawals. After some days, the two patients stopped amineptine intake. The only way of action seems to be the potentialization of amineptine by clonidine, as probed in mice, or the increase of sensibilization of alpha 2 adrenoreceptors.

  20. 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.

  1. L-D dependence for supernova remnants

    NASA Astrophysics Data System (ADS)

    Stanković, M.; Tešić, Lj.; Urošević, D.

    2003-10-01

    We discuss here the L-D relation (the possible dependence of the radio luminosity on linear diameter) for the supernova remnants (SNRs) in order to see wether determination of SNR distances on the basis of Σ-D relation is possible.

  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. 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.

  4. 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…

  5. 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…

  6. 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.

  7. 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 private sector…

  8. Including Children Dependent on Ventilators in School.

    ERIC Educational Resources Information Center

    Levine, Jack M.

    1996-01-01

    Guidelines for including ventilator-dependent children in school are offered, based on experience with six such students at a New York State school. Guidelines stress adherence to the medical management plan, the school-family partnership, roles of the social worker and psychologist, orientation, transportation, classroom issues, and steps toward…

  9. The Price of Welfare Dependency: Children Pay.

    ERIC Educational Resources Information Center

    Jones, Rebecca M.

    1995-01-01

    Discusses child poverty, the causes of high poverty rates among children, and proposals and programs aimed at reforming Aid to Families with Dependent Children (AFDC). Proposes another approach to providing cash benefits to children in the form of a children's allowance or refundable tax credit similar to programs in other industrialized nations.…

  10. 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.…

  11. 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.

  12. Cultural Dependency in Canada's Feature Film Industry.

    ERIC Educational Resources Information Center

    Pendakur, Manjunath

    1981-01-01

    Examines the ownership and policies of the dominant firms in the Canadian film market to explain Canada's dependence on imported films. Demonstrates how the economic relations existing between Canadian and U.S. film industries limit the profitability of films made in Canada. (JMF)

  13. 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.…

  14. Temperature dependence of polymer photovoltaic devices

    NASA Astrophysics Data System (ADS)

    Nakazawa, Yuko

    One of many steps to develop a sustainable society is to reduce the use of fossil fuels by replacing them with renewable energy sources, such as solar energy. This dissertation concerns one of the most contemporary methods to harvest solar radiation and covert it to electricity, using thin polymer films. The photovoltaic devices in this study consisted of a thin layer of p-phenylenevinylene (PPV) based semiconducting polymer sandwiched between two metals (semi-transparent ITO and evaporated metal electrode). Two modified device structures were studied, an interfacial heterojunction device, which includes an additional layer of inorganic n-type semiconductor (Ti-oxides) and a bulk heterojunction device, which is formed by blending electron-attracting materials. Both modifications resulted in higher device performances under ambient conditions due to an increased number of dissociation sites. From studies of inorganic solar cells, it is well known that temperature has a large effect on device performance. However, there are only a few studies on organic Solar cells, concerning the temperature dependence. This thesis focuses on understanding the temperature dependent behaviors of polymer photovoltaic devices. Temperature dependence study allows us to examine how the device parameters such as short circuit current (Isc) and open circuit voltage (Voc) are affected by the material properties and the device architectures. The current-voltage relationships were measured in a temperature controlled OXFORD cryostat operating between 150K and 404K. From the dark current-voltage measurements, the field-independent hole mobility (mu0) was extracted, using a space charge limited current analysis. From the photocurrent-voltage measurements, the temperature dependence on Isc, Voc, and fill factor were studied. The temperature characteristics of Isc (T) were compared to that of mu0(T), and two different dependencies were obtained for different device architectures. The temperature

  15. Evolution in population parameters: density-dependent selection or density-dependent fitness?

    PubMed

    Travis, Joseph; Leips, Jeff; Rodd, F Helen

    2013-05-01

    Density-dependent selection is one of earliest topics of joint interest to both ecologists and evolutionary biologists and thus occupies an important position in the histories of these disciplines. This joint interest is driven by the fact that density-dependent selection is the simplest form of feedback between an ecological effect of an organism's own making (crowding due to sustained population growth) and the selective response to the resulting conditions. This makes density-dependent selection perhaps the simplest process through which we see the full reciprocity between ecology and evolution. In this article, we begin by tracing the history of studying the reciprocity between ecology and evolution, which we see as combining the questions of evolutionary ecology with the assumptions and approaches of ecological genetics. In particular, density-dependent fitness and density-dependent selection were critical concepts underlying ideas about adaptation to biotic selection pressures and the coadaptation of interacting species. However, theory points to a critical distinction between density-dependent fitness and density-dependent selection in their influences on complex evolutionary and ecological interactions among coexisting species. Although density-dependent fitness is manifestly evident in empirical studies, evidence of density-dependent selection is much less common. This leads to the larger question of how prevalent and important density-dependent selection might really be. Life-history variation in the least killifish Heterandria formosa appears to reflect the action of density-dependent selection, and yet compelling evidence is elusive, even in this well-studied system, which suggests some important challenges for understanding density-driven feedbacks between ecology and evolution.

  16. Condition-dependent, phenotype-dependent and genetic-dependent factors in the natal dispersal of a solitary rodent.

    PubMed

    Selonen, Vesa; Hanski, Ilpo K

    2010-09-01

    1. Dispersal can be condition- and phenotype-dependent and related to individual genetic differences. Few studies have addressed the relative importance of these factors on dispersal. We studied the factors behind philopatry and dispersal in juvenile Siberian flying squirrels, Pteromys volans L. 2. The dispersal distance and the distances explored before abandoning the natal nest were not related to any of the condition-dependent factors studied such as the area of high-quality habitat or the number of conspecifics near the natal area. In addition, the body mass (a phenotypic trait) of individuals was not related to philopatry and dispersal in flying squirrels. 3. Genetic variability, measured by microsatellite heterozygosity, was positively correlated with dispersal. The correlation was mainly driven by one locus related to the distances explored before abandoning the natal nest. 4. We conclude that condition- and phenotype-dependent factors did not have detectable effects on philopatry and dispersal, but individual heterozygosity was related to dispersal in flying squirrels. Our results suggest that genetic variability is important behind the dispersal of the species. PMID:20561101

  17. Age of Alcohol-Dependence Onset: Associations with Severity of Dependence and Seeking Treatment

    ERIC Educational Resources Information Center

    Hingson, Ralph W.; Heeren, Timothy; Winter, Michael R.

    2007-01-01

    Objective: We explored whether people who become alcohol dependent at younger ages are more likely to seek alcohol-related help or treatment or experience chronic relapsing dependence. Methods: In 2001-2002 the National Institute on Alcohol Abuse and Alcoholism completed a face-to-face interview survey with a multistage probability sample of 43…

  18. Time-Dependent Behaviors of Granite: Loading-Rate Dependence, Creep, and Relaxation

    NASA Astrophysics Data System (ADS)

    Hashiba, K.; Fukui, K.

    2016-07-01

    To assess the long-term stability of underground structures, it is important to understand the time-dependent behaviors of rocks, such as their loading-rate dependence, creep, and relaxation. However, there have been fewer studies on crystalline rocks than on tuff, mudstone, and rock salt, because the high strength of crystalline rocks makes the detection of their time-dependent behaviors much more difficult. Moreover, studies on the relaxation, temporal change of stress and strain (TCSS) conditions, and relations between various time-dependent behaviors are scarce for not only granites, but also other rocks. In this study, previous reports on the time-dependent behaviors of granites were reviewed and various laboratory tests were conducted using Toki granite. These tests included an alternating-loading-rate test, creep test, relaxation test, and TCSS test. The results showed that the degree of time dependence of Toki granite is similar to other granites, and that the TCSS resembles the stress-relaxation curve and creep-strain curve. A viscoelastic constitutive model, proposed in a previous study, was modified to investigate the relations between the time-dependent behaviors in the pre- and post-peak regions. The modified model reproduced the stress-strain curve, creep, relaxation, and the results of the TCSS test. Based on a comparison of the results of the laboratory tests and numerical simulations, close relations between the time-dependent behaviors were revealed quantitatively.

  19. Cascading failures in coupled networks with both inner-dependency and inter-dependency links

    PubMed Central

    Liu, Run-Ran; Li, Ming; Jia, Chun-Xiao; Wang, Bing-Hong

    2016-01-01

    We study the percolation in coupled networks with both inner-dependency and inter-dependency links, where the inner- and inter-dependency links represent the dependencies between nodes in the same or different networks, respectively. We find that when most of dependency links are inner- or inter-ones, the coupled networks system is fragile and makes a discontinuous percolation transition. However, when the numbers of two types of dependency links are close to each other, the system is robust and makes a continuous percolation transition. This indicates that the high density of dependency links could not always lead to a discontinuous percolation transition as the previous studies. More interestingly, although the robustness of the system can be optimized by adjusting the ratio of the two types of dependency links, there exists a critical average degree of the networks for coupled random networks, below which the crossover of the two types of percolation transitions disappears, and the system will always demonstrate a discontinuous percolation transition. We also develop an approach to analyze this model, which is agreement with the simulation results well. PMID:27142883

  20. Distinguishing between state-dependent and non-state-dependent depression-related psychosocial variables.

    PubMed

    Rosenbaum, M; Lewinsohn, P M; Gotlib, I H

    1996-09-01

    The goals of this study were: (a) to determine which among a set of depression-related psychosocial variables are state-dependent; (b) to examine whether state-trait distinctions among psychosocial variables are a function of gender; and (c) to test the hypothesis that state-dependence of psychosocial variables is mostly evident in people with a history of clinical depression. Altogether, 562 participants residing in two communities completed a battery of psychosocial measures at point of entry into the study (T1) and after an average interval of 8.3 months (T2). The state-dependence of psychosocial variables was examined in two groups of participants: (a) low-high (LH: those who were low on the Center for Epidemiologic Studies Depression Scale at T1 and high at T2; N = 45); and (b) high-low (HL: those who were high at T1 and low at T2; N = 64). The following variables were found to be state-dependent: engagement in pleasant and unpleasant events; frequency of social contacts; dissatisfaction with oneself, one's neighborhood dwelling and one's friends; irrational beliefs, and positive and negative expectancies. In contrast, the following variables were not state-dependent: dissatisfaction with family and job, perception of control, and external attributions for positive and negative events. State-dependence was not moderated by age, gender or a history of depression. Possible explanations for why some variables are state-dependent and others are not state-dependent are offered.

  1. 32 CFR 48.302 - Substantiating evidence regarding dependency and age of dependents.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 1 2014-07-01 2014-07-01 false Substantiating evidence regarding dependency and age of dependents. 48.302 Section 48.302 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE PERSONNEL, MILITARY AND CIVILIAN RETIRED SERVICEMAN'S FAMILY PROTECTION...

  2. 32 CFR 48.302 - Substantiating evidence regarding dependency and age of dependents.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 1 2012-07-01 2012-07-01 false Substantiating evidence regarding dependency and age of dependents. 48.302 Section 48.302 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE PERSONNEL, MILITARY AND CIVILIAN RETIRED SERVICEMAN'S FAMILY PROTECTION...

  3. Cascading failures in coupled networks with both inner-dependency and inter-dependency links.

    PubMed

    Liu, Run-Ran; Li, Ming; Jia, Chun-Xiao; Wang, Bing-Hong

    2016-05-04

    We study the percolation in coupled networks with both inner-dependency and inter-dependency links, where the inner- and inter-dependency links represent the dependencies between nodes in the same or different networks, respectively. We find that when most of dependency links are inner- or inter-ones, the coupled networks system is fragile and makes a discontinuous percolation transition. However, when the numbers of two types of dependency links are close to each other, the system is robust and makes a continuous percolation transition. This indicates that the high density of dependency links could not always lead to a discontinuous percolation transition as the previous studies. More interestingly, although the robustness of the system can be optimized by adjusting the ratio of the two types of dependency links, there exists a critical average degree of the networks for coupled random networks, below which the crossover of the two types of percolation transitions disappears, and the system will always demonstrate a discontinuous percolation transition. We also develop an approach to analyze this model, which is agreement with the simulation results well.

  4. A Comparative Study of Self-Regulation in Substance Dependent and Non-Dependent Individuals

    PubMed Central

    Bakhshani, Nour Mohammad; Hossienbor, Mohsen

    2013-01-01

    Background: Several factors influence the beginning and maintenance of substance use. The purpose of this study was to examine as well as to compare ‘self-regulation’ in both substance dependent and non-substance dependent individuals. Method: In a cross-sectional study 228 (118 substance dependent and 110 with no history of using substance) participants aged 16-55 were recruited. All of the participants were asked to complete the Self-Regulation Inventory (SRI-25) and a demographic characteristics data checklist. Data was analyzed using descriptive statistics (frequency, mean and standard deviation) and the t-test. Results: The results showed significant differences between substance dependent and non- substance dependent groups in all the scales of the self-regulation inventory including positive actions, controllability, expression of feelings and needs, assertiveness, and well-being seeking (p<0.01). Conclusion: Self-regulation and self-control skills in drug dependent individuals are lower than those without substance dependence individuals. It is concluded that substance use may related to a deficiency in self-control and regulation of feelings. Therefore, for prevention and treatment of substance dependence disorder, it is necessary to work out and exploit strategies that include the improvement of self-regulation. PMID:24171872

  5. Sleep-dependent motor memory consolidation in older adults depends on task demands.

    PubMed

    Gudberg, Christel; Wulff, Katharina; Johansen-Berg, Heidi

    2015-03-01

    It is often suggested that sleep-dependent consolidation of motor learning is impaired in older adults. The current study challenges this view and suggests that the degree of motor consolidation seen with sleep in older age groups depends on the kinematic demands of the task. We show that, when tested with a classic sequence learning task, requiring individuated finger movements, older adults did not show sleep-dependent consolidation. By contrast, when tested with an adapted sequence learning task, in which movements were performed with the whole hand, sleep-dependent motor improvement was observed in older adults. We suggest that age-related decline in fine motor dexterity may in part be responsible for the previously described deficit in sleep-dependent motor consolidation with aging. PMID:25618616

  6. Genetics of Opioid Dependence: A Review of the Genetic Contribution to Opioid Dependence

    PubMed Central

    Mistry, Chetna J; Bawor, Monica; Desai, Dipika; Marsh, David C; Samaan, Zainab

    2014-01-01

    This narrative review aims to provide an overview of the impact of opioid dependence and the contribution of genetics to opioid dependence. Epidemiological data demonstrate that opioid dependence is a global trend with far-reaching effects on the social, economic, and health care systems. A review of classical genetic studies of opioid use suggests significant heritability of drug use behavior, however the evidence from molecular genetic studies is inconclusive. Nonetheless, certain genetic variants are important to consider given their role in the pathophysiology of addictive behavior. We undertook a literature review to identify the current state of knowledge regarding the role of genes in opioid dependence. Determining the association of genetic markers could change the current understanding of the various factors contributing to opioid dependence and therefore may improve recognition of individuals at risk for the disorder and prevention and treatment strategies. PMID:25242908

  7. Epidemiology of tobacco use and dependence.

    PubMed

    Giovino, G A; Henningfield, J E; Tomar, S L; Escobedo, L G; Slade, J

    1995-01-01

    Knowledge of the epidemiology of tobacco use and dependence can be used to guide research initiatives, intervention programs, and policy decisions. Both the reduction in the prevalence of smoking among US adults and black adolescents and the decline in per capita consumption are encouraging. These changes have probably been influenced by factors operating at the individual (e.g., school-based prevention programs and cessation programs) and environmental (e.g., mass media educational strategies, the presence of smoke-free laws and policies, and the price of tobacco products) levels (for a discussion of these factors, see, e.g., refs. 2, 48, 52, 183, and 184). The lack of progress among adolescents, especially whites and males, and the high risk for experimenters of developing tobacco dependence present cause for great concern (48, 183-186). In addition to those discussed above, several areas of research can be recommended. 1. Better understanding of the clustering of tobacco use with the use of other drugs, other risk behaviors, and other psychiatric disorders could better illuminate the causal processes involved, as well as the special features of the interventions needed to prevent and treat tobacco dependence. 2. To better understand population needs, trend analyses of prevalence, initiation, and cessation should, whenever possible, incorporate standardized measures of these other risk factors. Future research should compare the effect of socioeconomic status variables on measures of smoking behavior among racial/ethnic groups in the United States. 3. For reasons that may be genetic, environmental, or both, some persons do not progress beyond initial experimentation with tobacco use (2, 48, 183, 187-192), but about one-third to one-half of those who experiment with cigarettes become regular users (48, 193, 194). Factors, both individual and environmental, that can influence the susceptibility of individuals to tobacco dependence need further attention. 4. To

  8. Protocol dependence of the jamming transition

    NASA Astrophysics Data System (ADS)

    Bertrand, Thibault; Behringer, Robert P.; Chakraborty, Bulbul; O'Hern, Corey S.; Shattuck, Mark D.

    2016-01-01

    We propose a theoretical framework for predicting the protocol dependence of the jamming transition for frictionless spherical particles that interact via repulsive contact forces. We study isostatic jammed disk packings obtained via two protocols: isotropic compression and simple shear. We show that for frictionless systems, all jammed packings can be obtained via either protocol. However, the probability to obtain a particular jammed packing depends on the packing-generation protocol. We predict the average shear strain required to jam initially unjammed isotropically compressed packings from the density of jammed packings, shape of their basins of attraction, and path traversed in configuration space. We compare our predictions to simulations of shear strain-induced jamming and find quantitative agreement. We also show that the packing fraction range, over which shear strain-induced jamming occurs, tends to zero in the large system limit for frictionless packings with overdamped dynamics.

  9. Size-Dependent Raman Shifts for nanocrystals

    PubMed Central

    Gao, Yukun; Zhao, Xinmei; Yin, Penggang; Gao, Faming

    2016-01-01

    Raman spectroscopy is a very sensitive tool for probing semiconductor nanocrystals. The underlying mechanism behind the size-dependent Raman shifts is still quite controversial. Here we offer a new theoretical method for the quantum confinement effects on the Raman spectra of semiconductor nanocrystals. We propose that the shift of Raman spectra in nanocrystals can result from two overlapping effects: the quantum effect shift and surface effect shift. The quantum effect shift is extracted from an extended Kubo formula, the surface effect shift is determined via the first principles calculations. Fairly good prediction of Raman shifts can be obtained without the use of any adjustable parameter. Closer analysis shows that the size-dependent Raman shifts in Si nanocrystals mainly result from the quantum effect shifts. For nanodiamond, the proportion of surface effect shift in Raman shift is up to about 40%. Such model can also provide a good baseline for using Raman spectroscopy as a tool to measure size. PMID:27102066

  10. Size-dependent melting of Bi nanoparticles

    NASA Astrophysics Data System (ADS)

    Olson, E. A.; Efremov, M. Yu.; Zhang, M.; Zhang, Z.; Allen, L. H.

    2005-02-01

    Nanocalorimetry was used to investigate the melting of Bi nanoparticles. The particles were formed by evaporating Bi onto a silicon nitride substrate, which was then heated. The particles self-assemble into truncated spherical particles. Below 5-nm average film thickness, mean particle sizes increased linearly with deposition thickness but increased rapidly for 10-nm-thick films. As expected, small particles were found to exhibit size-dependent melting temperatures less than the bulk melting temperature (e.g., ΔT =67K for a 3-nm radius particle). The measured melting temperatures for particles below ˜7nm in radius, however, were ˜50K above the value predicted by the homogeneous melting model. We discuss this discrepancy in terms of a possible size-dependent crystal structure change and the superheating of the solid phase.

  11. Syntactic dependency parsers for biomedical-NLP.

    PubMed

    Cohen, Raphael; Elhadad, Michael

    2012-01-01

    Syntactic parsers have made a leap in accuracy and speed in recent years. The high order structural information provided by dependency parsers is useful for a variety of NLP applications. We present a biomedical model for the EasyFirst parser, a fast and accurate parser for creating Stanford Dependencies. We evaluate the models trained in the biomedical domains of EasyFirst and Clear-Parser in a number of task oriented metrics. Both parsers provide stat of the art speed and accuracy in the Genia of over 89%. We show that Clear-Parser excels at tasks relating to negation identification while EasyFirst excels at tasks relating to Named Entities and is more robust to changes in domain.

  12. Integral dependent spin couplings in CI calculations

    NASA Technical Reports Server (NTRS)

    Iberle, K.; Davidson, E. R.

    1982-01-01

    Although the number of ways to combine Slater determinants to form spin eigenfunctions increases rapidly with the number of open shells, most of these spin couplings will make only a small contribution to a given state, provided the spin coupling is chosen judiciously. The technique of limiting calculations to the interacting subspace pioneered by Bunge (1970) was employed by Munch and Davidson (1975) to the vanadium atom. The use of an interacting space looses its advantage in more complex cases. However, the problem can always be reduced to only one interacting spin coupling by making the coefficients integral dependent. The present investigation is concerned with the performance of integral dependent interacting couplings, taking into account the results of three test calculations.

  13. Time-dependent species sensitivity distributions.

    PubMed

    Fox, David R; Billoir, Elise

    2013-02-01

    Time is a central component of toxicity assessments. However, current ecotoxicological practice marginalizes time in concentration-response (C-R) modeling and species sensitivity distribution (SSD) analyses. For C-R models, time is invariably fixed, and toxicity measures are estimated from a function fitted to the data at that time. The estimated toxicity measures are used as inputs to the SSD modeling phase, which similarly avoids explicit recognition of the temporal component. The present study extends some commonly employed probability models for SSDs to derive theoretical results that characterize the time-dependent nature of hazardous concentration (HCx) values. The authors' results show that even from very simple assumptions, more complex patterns in the SSD time dependency can be revealed.

  14. Time-Dependent Erosion of Ion Optics

    NASA Technical Reports Server (NTRS)

    Wirz, Richard E.; Anderson, John R.; Katz, Ira; Goebel, Dan M.

    2008-01-01

    The accurate prediction of thruster life requires time-dependent erosion estimates for the ion optics assembly. Such information is critical to end-of-life mechanisms such as electron backstreaming. CEX2D was recently modified to handle time-dependent erosion, double ions, and multiple throttle conditions in a single run. The modified code is called "CEX2D-t". Comparisons of CEX2D-t results with LDT and ELT post-tests results show good agreement for both screen and accel grid erosion including important erosion features such as chamfering of the downstream end of the accel grid and reduced rate of accel grid aperture enlargement with time.

  15. Photochemotherapy: Light Dependent Therapies in Medicine

    NASA Astrophysics Data System (ADS)

    Zovinka, Edward P.; Sunseri, Danielle R.

    2002-11-01

    Light-dependent therapies, such as photodynamic therapy and extracorporeal photopheresis, are not new, but have remained of interest to chemists and health care professionals since the middle of the twentieth century. While most people link light-dependent therapies only to the treatment of cancer, these therapies may be of use for a diverse set of medical conditions, from acne to AIDS. The techniques arise directly from the application of chemical concepts, such as spectroscopy, MO theory, and organic chemical reactions. Because of its application to health care, the field of photochemistry provides a tool to demonstrate the significance of chemistry to a socially important issue.

    See Featured Molecules.

  16. Size-Dependent Raman Shifts for nanocrystals.

    PubMed

    Gao, Yukun; Zhao, Xinmei; Yin, Penggang; Gao, Faming

    2016-04-22

    Raman spectroscopy is a very sensitive tool for probing semiconductor nanocrystals. The underlying mechanism behind the size-dependent Raman shifts is still quite controversial. Here we offer a new theoretical method for the quantum confinement effects on the Raman spectra of semiconductor nanocrystals. We propose that the shift of Raman spectra in nanocrystals can result from two overlapping effects: the quantum effect shift and surface effect shift. The quantum effect shift is extracted from an extended Kubo formula, the surface effect shift is determined via the first principles calculations. Fairly good prediction of Raman shifts can be obtained without the use of any adjustable parameter. Closer analysis shows that the size-dependent Raman shifts in Si nanocrystals mainly result from the quantum effect shifts. For nanodiamond, the proportion of surface effect shift in Raman shift is up to about 40%. Such model can also provide a good baseline for using Raman spectroscopy as a tool to measure size.

  17. Kinship as a frequency dependent strategy

    PubMed Central

    Ji, Ting; Zheng, Xiu-Deng; He, Qiao-Qiao; Wu, Jia-Jia; Tao, Yi

    2016-01-01

    Humans divide themselves up into separate cultures, which is a unique and ubiquitous characteristic of our species. Kinship norms are one of the defining features of such societies. Here we show how norms of marital residence can evolve as a frequency-dependent strategy, using real-world cases from southwestern China and an evolutionary game model. The process of kinship change has occurred in the past and is also occurring now in southwestern China. Our data and models show how transitions between residence types can occur both as response to changing costs and benefits of co-residence with kin, and also due to the initial frequency of the strategies adopted by others in the population: patrilocal societies can become matrilocal, and neolocal societies can become duolocal. This illustrates how frequency-dependent selection plays a role both in the maintenance of group-level cultural diversity and in cultural extinction. PMID:26998333

  18. Scale Dependence of Spatiotemporal Intermittence of Rain

    NASA Technical Reports Server (NTRS)

    Kundu, Prasun K.; Siddani, Ravi K.

    2011-01-01

    It is a common experience that rainfall is intermittent in space and time. This is reflected by the fact that the statistics of area- and/or time-averaged rain rate is described by a mixed distribution with a nonzero probability of having a sharp value zero. In this paper we have explored the dependence of the probability of zero rain on the averaging space and time scales in large multiyear data sets based on radar and rain gauge observations. A stretched exponential fannula fits the observed scale dependence of the zero-rain probability. The proposed formula makes it apparent that the space-time support of the rain field is not quite a set of measure zero as is sometimes supposed. We also give an ex.planation of the observed behavior in tenus of a simple probabilistic model based on the premise that rainfall process has an intrinsic memory.

  19. Reducing US Oil Dependence Using Simulation

    NASA Technical Reports Server (NTRS)

    Ayoub, Fadi; Arnaout, Georges M.

    2011-01-01

    People across the world are addicted to oil; as a result, the instability of oil prices and the shortage of oil reserves have influenced human behaviors and global businesses. Today, the United States makes up only 5% of the global population but consumes 25% of the. world total energy. Most of this energy is generated from fossil fuels in the form of electricity. The contribution of this paper is to examine the possibilities of replacing fossil fuel with renewable energies to generate electricity as well as to examine other methods to reduce oil and gas consumption. We propose a system dynamics model in an attempt to predict the future US dependence on fossil fuels by using renewable energy resources such as, nuclear, wind, solar, and hydro powers. Based on the findings of our model, the study expects to provide insights towards promising solutions of the oil dependency problem.

  20. Frequency-dependent selection by predators.

    PubMed

    Allen, J A

    1988-07-01

    Sometimes predators tend to concentrate on common varieties of prey and overlook rare ones. Within prey species, this could result in the fitness of each variety being inversely related to its frequency in the population. Such frequency-dependent or 'apostatic' selection by predators hunting by sight could maintain polymorphism for colour pattern, and much of the supporting evidence for this idea has come from work on birds and artificial prey. These and other studies have shown that the strength of the observed selection is affected by prey density, palatability, coloration and conspicuousness. When the prey density is very high, selection becomes 'anti-apostatic': predators preferentially remove rare prey. There is still much to be learned about frequency-dependent selection by predators on artificial prey: work on natural polymorphic prey has hardly begun. PMID:2905488

  1. Energy dependent 4-dimensional multiple scattering distributions

    NASA Astrophysics Data System (ADS)

    Tschalär, C.

    1984-12-01

    A complete analytic solution in Fourier space is presented of the four dimensional small angle, multiple scattering distribution MSD in angle and space, produced by an energy dependent single scattering cross section from an initial pencil beam of heavy particles. Independently, simple integrals are derived for the central moments of the energy dependent MSD in the continuous-slowing-down approximation. The distributions of the projections t and x of the scattering angle and displacement into a plane through the axis of propagation are evaluated numerically for a truncated Rutherford scattering cross section using a fast Fourier transform. The resulting MSDs for a wide range of particles, initial and final momenta, and scattering materials are found to be approximately represented by one-dimensional set of standard distributions symmetrized by a linear transformation in t- x-space.

  2. Decomposing climate dependency of forest dynamics

    NASA Astrophysics Data System (ADS)

    Lines, Emily

    2016-04-01

    Forest simulation models have proved extremely useful in understanding forest dynamics by scaling from tree-level processes to landscape scales, but typically contain no climate dependency in their subprocesses. Forest inventory databases may be used to investigate the role of climate on tree-level processes, and the climate drivers of geographical ranges of different species, by making a space-for-time substitution. We demonstrate the value of inventory data for determining the climate drivers of forest processes. By scaling up from individual demographic rates using a forest simulation model, parameterised for mainland Spain, we determine the key climate dependencies driving emergent forest properties, allowing defensible predictions of the impacts of climate change.

  3. Protocol dependence of the jamming transition.

    PubMed

    Bertrand, Thibault; Behringer, Robert P; Chakraborty, Bulbul; O'Hern, Corey S; Shattuck, Mark D

    2016-01-01

    We propose a theoretical framework for predicting the protocol dependence of the jamming transition for frictionless spherical particles that interact via repulsive contact forces. We study isostatic jammed disk packings obtained via two protocols: isotropic compression and simple shear. We show that for frictionless systems, all jammed packings can be obtained via either protocol. However, the probability to obtain a particular jammed packing depends on the packing-generation protocol. We predict the average shear strain required to jam initially unjammed isotropically compressed packings from the density of jammed packings, shape of their basins of attraction, and path traversed in configuration space. We compare our predictions to simulations of shear strain-induced jamming and find quantitative agreement. We also show that the packing fraction range, over which shear strain-induced jamming occurs, tends to zero in the large system limit for frictionless packings with overdamped dynamics. PMID:26871137

  4. Brain Pathways to Recovery from Alcohol Dependence

    PubMed Central

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

    2015-01-01

    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. PMID:26074423

  5. Kinship as a frequency dependent strategy.

    PubMed

    Ji, Ting; Zheng, Xiu-Deng; He, Qiao-Qiao; Wu, Jia-Jia; Mace, Ruth; Tao, Yi

    2016-02-01

    Humans divide themselves up into separate cultures, which is a unique and ubiquitous characteristic of our species. Kinship norms are one of the defining features of such societies. Here we show how norms of marital residence can evolve as a frequency-dependent strategy, using real-world cases from southwestern China and an evolutionary game model. The process of kinship change has occurred in the past and is also occurring now in southwestern China. Our data and models show how transitions between residence types can occur both as response to changing costs and benefits of co-residence with kin, and also due to the initial frequency of the strategies adopted by others in the population: patrilocal societies can become matrilocal, and neolocal societies can become duolocal. This illustrates how frequency-dependent selection plays a role both in the maintenance of group-level cultural diversity and in cultural extinction. PMID:26998333

  6. Anchorage Dependent Cells Attached to a Polymer

    NASA Technical Reports Server (NTRS)

    2004-01-01

    Biomedical research offers hope for a variety of medical problems, from diabetes to the replacement of damaged bone and tissues. Bioreactors, which are used to grow cells and tissue cultures, play a major role in such research and production efforts. Anchorage dependent cells on STS-95 will be grown on beads similar to these cells produced during previous investigations. Recombinant proteins may offer the possibility of reducing or eliminating transplant rejections. Research by Synthecon, Inc. using the BioDyn Bioreactor will focus on the preliminary process for growing a proprietary recombinant protein that can decrease rejection of transplanted tissue. The cells producing this protein are anchorage dependent, meaning that they must attach to something to grow. These cells will be cultured in the bioreactor in a medium containing polymer microbeads. Synthecon hopes that the data from this mission will lead to the development of a commercial protein that will aid in prevention of transplant rejection.

  7. Anchorage Dependent Cells Attached to a Polymer

    NASA Technical Reports Server (NTRS)

    2004-01-01

    Biomedical research offers hope for a variety of medical problems, from diabetes to the replacement of damaged bone and tissues. Bioreactors, which are used to grow cells and tissue cultures, play a major role in such research and production efforts. Anchorage dependent cells on STS-95 will be grown on beads, similar to these cells produced during previous investigations. Recombinant proteins may offer the possibility of reducing or eliminating transplant rejections. Research by Synthecon, Inc. using the BioDyn Bioreactor will focus on the preliminary process for growing a proprietary recombinant protein that can decrease rejection of transplanted tissue. The cells producing this protein are anchorage dependent, meaning that they must attach to something to grow. These cells will be cultured in the bioreactor in a medium containing polymer microbeads. Synthecon hopes that the data from this mission will lead to the development of a commercial protein that will aid in prevention of transplant rejection.

  8. Robust frame-dependent video watermarking

    NASA Astrophysics Data System (ADS)

    Holliman, Matthew J.; Macy, William W.; Yeung, Minerva M.

    2000-05-01

    In this paper, we describe some of the problems associated with watermarking key management, with particular attention to the case of video. We also describe a possible solution to the problem, which is that of image-dependent watermarking, and briefly discuss some of the possible advantages to be gained from adopting such an approach. The paper also presents a simple, efficient means of robustly extracting bits from a video sequence. The algorithm has applications to secure, oblivious video watermark detection.

  9. Transformation of time dependence to linear algebra

    NASA Astrophysics Data System (ADS)

    Menšík, Miroslav

    2005-10-01

    Reduced density matrix and memory function in the Nakajima-Zwanzig equation are expanded in properly chosen basis of special functions. This trick completely transforms time dependence to linear algebra. Then, the master equation for memory function is constructed and expanded in the same basis functions. For the model of a simple harmonic oscillator it is shown that this trick introduces infinite partial summation of the memory function in the system-bath interaction.

  10. Time-dependent oral absorption models

    NASA Technical Reports Server (NTRS)

    Higaki, K.; Yamashita, S.; Amidon, G. L.

    2001-01-01

    The plasma concentration-time profiles following oral administration of drugs are often irregular and cannot be interpreted easily with conventional models based on first- or zero-order absorption kinetics and lag time. Six new models were developed using a time-dependent absorption rate coefficient, ka(t), wherein the time dependency was varied to account for the dynamic processes such as changes in fluid absorption or secretion, in absorption surface area, and in motility with time, in the gastrointestinal tract. In the present study, the plasma concentration profiles of propranolol obtained in human subjects following oral dosing were analyzed using the newly derived models based on mass balance and compared with the conventional models. Nonlinear regression analysis indicated that the conventional compartment model including lag time (CLAG model) could not predict the rapid initial increase in plasma concentration after dosing and the predicted Cmax values were much lower than that observed. On the other hand, all models with the time-dependent absorption rate coefficient, ka(t), were superior to the CLAG model in predicting plasma concentration profiles. Based on Akaike's Information Criterion (AIC), the fluid absorption model without lag time (FA model) exhibited the best overall fit to the data. The two-phase model including lag time, TPLAG model was also found to be a good model judging from the values of sum of squares. This model also described the irregular profiles of plasma concentration with time and frequently predicted Cmax values satisfactorily. A comparison of the absorption rate profiles also suggested that the TPLAG model is better at prediction of irregular absorption kinetics than the FA model. In conclusion, the incorporation of a time-dependent absorption rate coefficient ka(t) allows the prediction of nonlinear absorption characteristics in a more reliable manner.

  11. Renewable Energy Can Help Reduce Oil Dependency

    ScienceCinema

    Arvizu, Dan

    2016-07-12

    In a speech to the Economic Club of Kansas City on June 23, 2010, NREL Director Dan Arvizu takes a realistic look at how renewable energy can help reduce America's dependence on oil, pointing out that the country gets as much energy from renewable sources now as it does from offshore oil production. For a transcript, visit http://www.nrel.gov/director/pdfs/energy_overview_06_10.pdf

  12. The epidemiology of tobacco use and dependence.

    PubMed

    Hudmon, Karen Suchanek; Kilfoy, Briseis A; Prokhorov, Alexander V

    2006-03-01

    Tobacco use continues to be a public health issue of great importance. Acute and critical care nurses in particular have a unique opportunity to become a cornerstone for the nation's tobacco control efforts through integration of prevention and cessation interventions as part of patient care. This article provides readers with a working knowledge of tobacco use and dependence as background reading for the subsequent articles presented in this special issue addressing tobacco cessation in acute and critical care settings. PMID:16546003

  13. Time-dependent nucleation in partitioning systems

    SciTech Connect

    Kelton, K.F.; Narayan, K.L.

    1998-12-31

    Nucleation in multi-component systems is poorly understood, particularly when the rates of long-range diffusion are comparable with the rates of attachment at the cluster interface. For illustration, measurements of the time-dependent nucleation rates in silicate and metallic glasses are discussed. A new model for nucleation in partitioning systems, which explains many of devitrification microstructural features in bulk metallic glasses, is presented.

  14. Correlation dependences of electromagnetic and deformation parameters

    NASA Astrophysics Data System (ADS)

    Bataleva, E. A.

    2016-05-01

    In-situ monitoring observations are carried out, and correlation analysis aimed at estimating the dependences between the electromagnetic parameters (variations of apparent resistivity, the impedance phase, components of the impedance tensor, and deformations of the daylight surface on the territory of the Bishkek geodynamic polygon) is performed. A new approach to the explanation of the physical mechanism forming variations in electrical conductivity of the medium is proposed on this basis.

  15. Biperiden dependence: case report and literature review.

    PubMed

    Espi Martinez, Fernando; Espi Forcen, Fernando; Shapov, Arlenne; Martinez Moya, Amparo

    2012-01-01

    Anticholinergic drugs are frequently used in psychiatry for the prophylaxis and treatment of extrapiramidal symptoms caused by neuroleptics. Abuse of anticholinergic agents has been reported in patients with psychotic disorders, on treatment with neuroleptics, and polysubstance use disorders. We are reporting the case of a patient who presented with hypoactive delirium as a consequence of biperiden dependence. The clinician must pay special attention to detect anticholinergic misuse in patients presenting with delirium of unknown cause.

  16. Transverse Momentum Dependent Hadron Multiplicities at COMPASS

    NASA Astrophysics Data System (ADS)

    Makke, Nour

    2016-02-01

    Unpolarised semi-inclusive deep inelastic scattering is receiving a growing interest as a powerful tool to access poorly known transverse momentum dependent parton distributions and fragmentation functions that play a key role in many processes, in particular in the study of the spin structure of the nucleon. These functions can be investigated through experimental observables. New results on these observables by the COMPASS experiment at CERN will be shown and discussed.

  17. Biperiden Dependence: Case Report and Literature Review

    PubMed Central

    Espi Martinez, Fernando; Espi Forcen, Fernando; Shapov, Arlenne; Martinez Moya, Amparo

    2012-01-01

    Anticholinergic drugs are frequently used in psychiatry for the prophylaxis and treatment of extrapiramidal symptoms caused by neuroleptics. Abuse of anticholinergic agents has been reported in patients with psychotic disorders, on treatment with neuroleptics, and polysubstance use disorders. We are reporting the case of a patient who presented with hypoactive delirium as a consequence of biperiden dependence. The clinician must pay special attention to detect anticholinergic misuse in patients presenting with delirium of unknown cause. PMID:22937420

  18. Strongly scale-dependent non-Gaussianity

    SciTech Connect

    Riotto, Antonio; Sloth, Martin S.

    2011-02-15

    We discuss models of primordial density perturbations where the non-Gaussianity is strongly scale dependent. In particular, the non-Gaussianity may have a sharp cutoff and be very suppressed on large cosmological scales, but sizable on small scales. This may have an impact on probes of non-Gaussianity in the large-scale structure and in the cosmic microwave background radiation anisotropies.

  19. Transverse-momentum-dependent parton distributions (TMDs)

    NASA Astrophysics Data System (ADS)

    Bacchetta, Alessandro

    2011-10-01

    Transverse-momentum-dependent parton distributions (TMDs) provide three-dimensional images of the partonic structure of the nucleon in momentum space. We made impressive progress in understanding TMDs, both from the theoretical and experimental point of view. This brief overview on TMDs is divided in two parts: in the first, an essential list of achievements is presented. In the second, a selection of open questions is discussed.

  20. Chronic Heroin Dependence Leading to Adrenal Insufficiency

    PubMed Central

    2014-01-01

    Opioids have been the mainstay for pain relief and palliation over a long period of time. They are commonly abused by drug addicts and such dependence usually imparts severe physiologic effects on multiple organ systems. The negative impact of opioids on the endocrine system is poorly understood and often underestimated. We describe a patient who developed severe suppression of the hypothalamic-pituitary adrenal (HPA) axis leading to secondary adrenal insufficiency due to long standing abuse of opioids. PMID:25221675

  1. Renewable Energy Can Help Reduce Oil Dependency

    SciTech Connect

    Arvizu, Dan

    2010-01-01

    In a speech to the Economic Club of Kansas City on June 23, 2010, NREL Director Dan Arvizu takes a realistic look at how renewable energy can help reduce America's dependence on oil, pointing out that the country gets as much energy from renewable sources now as it does from offshore oil production. For a transcript, visit http://www.nrel.gov/director/pdfs/energy_overview_06_10.pdf

  2. Field dependence-independence of basketball referees.

    PubMed

    Tabernero, B; Márquez, S

    1999-06-01

    This study examined the field dependence-independence of basketball referees. A total of 205 subjects (nonathletes, athletes active in individual or team sports, and referees) completed the Group Embedded Figures Test. Analysis indicated no significant differences among referees due to age, group, or number of years officiating. Statistically significant lower scores were obtained by team-sport players and referees than by nonathletes. Mean scores of team-sport players and referees did not differ significantly.

  3. Time-dependent projected Hartree-Fock

    SciTech Connect

    Tsuchimochi, Takashi; Van Voorhis, Troy

    2015-03-28

    Projected Hartree-Fock (PHF) has recently emerged as an alternative approach to describing degenerate systems where static correlation is abundant, when the spin-symmetry is projected. Here, we derive a set of linearized time-dependent equations for PHF in order to be able to access excited states. The close connection of such linear-response time-dependent PHF (TDPHF) to the stability condition of a PHF wave function is discussed. Expanding this analysis also makes it possible to give analytical expressions for the projected coupling terms of Hamiltonian and overlaps between excited Slater determinants. TDPHF with spin-projection (TDSUHF) and its Tamm-Dancoff approximation are benchmarked for several electronically degenerate molecules including the dissociating H{sub 2}, F{sub 2} and O{sub 3} at equilibrium, and the distorted ethylene. It is shown that they give consistently better descriptions of excited states than does time-dependent HF (TDHF). Furthermore, we demonstrate that they offer not only singly but also doubly excited states, which naturally arise upon spin-projection. We also address the thermodynamic limit of TDSUHF, using non-interacting He gas. While TDPHF singly excited states tend to converge to those of HF with the size of the system due to the lack of size-extensivity of PHF, doubly excited states remain reasonable even at the thermodynamic limit. We find that the overall performance of our method is systematically better than the regular TDHF in many cases at the same computational scaling.

  4. The biodiversity-dependent ecosystem service debt.

    PubMed

    Isbell, Forest; Tilman, David; Polasky, Stephen; Loreau, Michel

    2015-02-01

    Habitat destruction is driving biodiversity loss in remaining ecosystems, and ecosystem functioning and services often directly depend on biodiversity. Thus, biodiversity loss is likely creating an ecosystem service debt: a gradual loss of biodiversity-dependent benefits that people obtain from remaining fragments of natural ecosystems. Here, we develop an approach for quantifying ecosystem service debts, and illustrate its use to estimate how one anthropogenic driver, habitat destruction, could indirectly diminish one ecosystem service, carbon storage, by creating an extinction debt. We estimate that c. 2-21 Pg C could be gradually emitted globally in remaining ecosystem fragments because of plant species loss caused by nearby habitat destruction. The wide range for this estimate reflects substantial uncertainties in how many plant species will be lost, how much species loss will impact ecosystem functioning and whether plant species loss will decrease soil carbon. Our exploratory analysis suggests that biodiversity-dependent ecosystem service debts can be globally substantial, even when locally small, if they occur diffusely across vast areas of remaining ecosystems. There is substantial value in conserving not only the quantity (area), but also the quality (biodiversity) of natural ecosystems for the sustainable provision of ecosystem services.

  5. Reticulocyte RNA-Dependent RNA Polymerase

    PubMed Central

    Downey, Kathleen M.; Byrnes, John J.; Jurmark, Bonnie S.; So, Antero G.

    1973-01-01

    A cytoplasmic, microsomal bound RNA-dependent RNA polymerase has been purified 2500-fold from rabbit reticulocyte lysates. The synthesis of RNA with the purified enzyme is absolutely dependent on the addition of an RNA template. The best template is hemoglobin messenger RNA, while bacteriophage RNA and poly(A,G) are less active, and DNA is completely inactive as a template. With poly(A,G) as a template, only UTP and CTP are incorporated into polynucleotide chains, indicating that the RNA polymerase is an RNA replicase and not a terminal transferase. With messenger RNA as a template, all four ribonucleoside triphosphates are required for maximal activity. The RNA-dependent RNA polymerase reaction is extremely sensitive to low concentrations of heme, rifamycin AF/013, and ribonuclease and resistant to actinomycin D and DNase. The discovery of RNA-directed RNA synthesis in reticulocytes offers an additional site for control of gene expression in mammalian cells and provides a possible mechanism for amplification of the expression of specific genes. PMID:4519633

  6. Structure of weakly 2-dependent siphons

    NASA Astrophysics Data System (ADS)

    Chao, Daniel Yuh; Chen, Jiun-Ting

    2013-09-01

    Deadlocks arising from insufficiently marked siphons in flexible manufacturing systems can be controlled by adding monitors to each siphon - too many for large systems. Li and Zhou add monitors to elementary siphons only while controlling the rest of (called dependent) siphons by adjusting control depth variables of elementary siphons. Only a linear number of monitors are required. The control of weakly dependent siphons (WDSs) is rather conservative since only positive terms were considered. The structure for strongly dependent siphons (SDSs) has been studied earlier. Based on this structure, the optimal sequence of adding monitors has been discovered earlier. Better controllability has been discovered to achieve faster and more permissive control. The results have been extended earlier to S3PGR2 (systems of simple sequential processes with general resource requirements). This paper explores the structures for WDSs, which, as found in this paper, involve elementary resource circuits interconnecting at more than (for SDSs, exactly) one resource place. This saves the time to compute compound siphons, their complementary sets and T-characteristic vectors. Also it allows us (1) to improve the controllability of WDSs and control siphons and (2) to avoid the time to find independent vectors for elementary siphons. We propose a sufficient and necessary test for adjusting control depth variables in S3PR (systems of simple sequential processes with resources) to avoid the sufficient-only time-consuming linear integer programming test (LIP) (Nondeterministic Polynomial (NP) time complete problem) required previously for some cases.

  7. Influence of Sensory Dependence on Postural Control

    NASA Technical Reports Server (NTRS)

    Santana, Patricia A.; Mulavara, Ajitkumar P.; Fiedler, Matthew J.

    2011-01-01

    The current project is part of an NSBRI funded project, "Development of Countermeasures to Aid Functional Egress from the Crew Exploration Vehicle Following Long-Duration Spaceflight." The development of this countermeasure is based on the use of imperceptible levels of electrical stimulation to the balance organs of the inner ear to assist and enhance the response of a person s sensorimotor function. These countermeasures could be used to increase an astronaut s re-adaptation rate to Earth s gravity following long-duration space flight. The focus of my project is to evaluate and examine the correlation of sensory preferences for vision and vestibular systems. Disruption of the sensorimotor functions following space flight affects posture, locomotion and spatial orientation tasks in astronauts. The Group Embedded Figures Test (GEFT), the Rod and Frame Test (RFT) and the Computerized Dynamic Posturography Test (CDP) are measurements used to examine subjects visual and vestibular sensory preferences. The analysis of data from these tasks will assist in relating the visual dependence measures recognized in the GEFT and RFT with vestibular dependence measures recognized in the stability measures obtained during CDP. Studying the impact of sensory dependence on the performance in varied tasks will help in the development of targeted countermeasures to help astronauts readapt to gravitational changes after long duration space flight.

  8. Interactive dependency curves for resilience management.

    PubMed

    Petit, Frédéric; Wallace, Kelly; Phillip, Julia

    Physical dependencies are a fundamental consideration when assessing the resilience of an organisation and, ultimately, the resilience of a region. Every organisation needs specific resources for supporting its operations. A disruption in the supply of these resources can severely impact business continuity. It is important to characterise dependencies thoroughly when seeking to reduce the extent an organisation is directly affected by the missions, functions and operations of other organisations. The general protocol when addressing each critical resource is to determine the use for the resource, whether there are redundant services providing the resource, and what protections, backup equipment and arrangements are in place to maintain service. Finally, the criticality of the resource is determined by estimating the time it will take for the facility to experience a severe impact once primary service is lost and what percentage of facility operations can be maintained without backup service in place, as well as identifying whether any external regulations/policies are in place that require shutdown of the facility because of service disruption owing to lack of a critical resource. All of this information can be presented in the form of interactive dependency curves that help anticipate and manage the effect(s) of a disruption on critical resources supply.

  9. Interactive dependency curves for resilience management.

    PubMed

    Petit, Frédéric; Wallace, Kelly; Phillip, Julia

    Physical dependencies are a fundamental consideration when assessing the resilience of an organisation and, ultimately, the resilience of a region. Every organisation needs specific resources for supporting its operations. A disruption in the supply of these resources can severely impact business continuity. It is important to characterise dependencies thoroughly when seeking to reduce the extent an organisation is directly affected by the missions, functions and operations of other organisations. The general protocol when addressing each critical resource is to determine the use for the resource, whether there are redundant services providing the resource, and what protections, backup equipment and arrangements are in place to maintain service. Finally, the criticality of the resource is determined by estimating the time it will take for the facility to experience a severe impact once primary service is lost and what percentage of facility operations can be maintained without backup service in place, as well as identifying whether any external regulations/policies are in place that require shutdown of the facility because of service disruption owing to lack of a critical resource. All of this information can be presented in the form of interactive dependency curves that help anticipate and manage the effect(s) of a disruption on critical resources supply. PMID:25416376

  10. Socio-Emotional Factors in Alcohol Dependence

    PubMed Central

    Tikka, Deyashini Lahiri; Ram, Daya; Dubey, Indu; Tikka, Sai Krishna

    2014-01-01

    Background: Alcohol-dependent patients are traditionally believed to have insecure attachment styles, higher anger expression, and lower self-esteem. There is a need to study them together. Aim: To understand the relationships amongst various of the socio-emotional factors. Materials and Methods: Forty male patients with Alcohol dependence syndrome and 40 matched healthy controls (General Health Questionnaire-12 score <3) were compared on attachment styles (on Relationship Scale Questionnaire), anger domains (on State Trait Anger Expression Inventory), and self-esteem (on Rosenberg Self-esteem Scale). Statistics and Analysis: Comparison using independent samples t test and chi square test; correlation using Pearson's correlation coefficient. Results: Patients had significantly higher anger expression, ‘anger in’ and ‘anger out,’ and lower self-esteem than healthy controls. Severity of alcohol dependence had significant correlation with ‘anger out,’ and self-esteem had significant negative correlation with anger expression. Conclusion: The present study suggests that the socio-emotional factors studied are developmentally linked to each other. PMID:24860216

  11. Depth dependence of vascular fluorescence imaging

    PubMed Central

    Davis, Mitchell A.; Shams Kazmi, S. M.; Ponticorvo, Adrien; Dunn, Andrew K.

    2011-01-01

    In vivo surface imaging of fluorescently labeled vasculature has become a widely used tool for functional brain imaging studies. Techniques such as phosphorescence quenching for oxygen tension measurements and indocyanine green fluorescence for vessel perfusion monitoring rely on surface measurements of vascular fluorescence. However, the depth dependence of the measured fluorescence signals has not been modeled in great detail. In this paper, we investigate the depth dependence of the measured signals using a three-dimensional Monte Carlo model combined with high resolution vascular anatomy. We found that a bulk-vascularization assumption to modeling the depth dependence of the signal does not provide an accurate picture of penetration depth of the collected fluorescence signal in most cases. Instead the physical distribution of microvasculature, the degree of absorption difference between extravascular and intravascular space, and the overall difference in absorption at the excitation and emission wavelengths must be taken into account to determine the depth penetration of the fluorescence signal. Additionally, we found that using targeted illumination can provide for superior surface vessel sensitivity over wide-field illumination, with small area detection offering an even greater amount of sensitivity to surface vasculature. Depth sensitivity can be enhanced by either increasing the detector area or increasing the illumination area. Finally, we see that excitation wavelength and vessel size can affect intra-vessel sampling distribution, as well as the amount of signal that originates from inside the vessel under targeted illumination conditions. PMID:22162824

  12. Phase dependencies of the human baroreceptor reflex

    NASA Technical Reports Server (NTRS)

    Seidel, H.; Herzel, H.; Eckberg, D. L.

    1997-01-01

    We studied the influence of respiratory and cardiac phase on responses of the cardiac pacemaker to brief (0.35-s) increases of carotid baroreceptor afferent traffic provoked by neck suction in seven healthy young adult subjects. Cardiac responses to neck suction were measured indirectly from electrocardiographic changes of heart period. Our results show that it is possible to separate the influences of respiratory and cardiac phases at the onset of a neck suction impulse by a product of two factors: one depending only on the respiratory phase and one depending only on the cardiac phase. This result is consistent with the hypothesis that efferent vagal activity is a function of afferent baroreceptor activity, whereas respiratory neurons modulate that medullary throughput independent of the cardiac phase. Furthermore, we have shown that stimulus broadening and stimulus cropping influence the outcome of neck suction experiments in a way that makes it virtually impossible to obtain information on the phase dependency of the cardiac pacemaker's sensitivity to vagal stimulation without accurate knowledge of the functional shape of stimulus broadening.

  13. Communication imperialism and dependency: a conceptual clarification.

    PubMed

    Lee, P S

    1988-01-01

    Communications imperialism has to do with the domination of a country's media activities by another. The ownership, structure, distribution or content of the media in 1 country are affected by pressures from media interests of another country or group out of proportion with those of that country. To determine if this is happening we should consider the country's policies, the private sector;s efforts to export communications elements, and actions of the dominant country against the dominated. The 4 aspects of international media in this situation are television program exportation, foreign ownership and control of media distribution, the infringement of capital opinions on other societies, and the transfer of commercialism and broadcasting norms. In addition to the software and hardware and the other forms of communication such as satellites, computers, and transportation of the mass media, there are the cultural effects on the developing countries. In the case of involuntary of voluntary dependency of the recipient country, the effect of the unbalanced international communication can be harmful or beneficial. Communication dependency may not be harmful to the culture of the recipient country. In determining the theory of unbalanced international communications 3 factors should be considered. There are: the role of the interacting countries, the nature of the dependency of the recipient country, and the beneficial or harmful effect of unbalanced communication pattern on that country. PMID:12283101

  14. Dissipative time-dependent quantum transport theory.

    PubMed

    Zhang, Yu; Yam, Chi Yung; Chen, GuanHua

    2013-04-28

    A dissipative time-dependent quantum transport theory is developed to treat the transient current through molecular or nanoscopic devices in presence of electron-phonon interaction. The dissipation via phonon is taken into account by introducing a self-energy for the electron-phonon coupling in addition to the self-energy caused by the electrodes. Based on this, a numerical method is proposed. For practical implementation, the lowest order expansion is employed for the weak electron-phonon coupling case and the wide-band limit approximation is adopted for device and electrodes coupling. The corresponding hierarchical equation of motion is derived, which leads to an efficient and accurate time-dependent treatment of inelastic effect on transport for the weak electron-phonon interaction. The resulting method is applied to a one-level model system and a gold wire described by tight-binding model to demonstrate its validity and the importance of electron-phonon interaction for the quantum transport. As it is based on the effective single-electron model, the method can be readily extended to time-dependent density functional theory.

  15. Addiction and dependence in DSM-V.

    PubMed

    O'Brien, Charles

    2011-05-01

    As preparations for the fifth revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM) are under way, this paper focuses upon changes proposed for the substance use disorders section. It briefly outlines the history behind the current nomenclature, and the selection of the term 'dependence' over 'addiction' in earlier versions of the DSM. The term 'dependence', while used in past decades to refer to uncontrolled drug-seeking behavior, has an alternative meaning--the physiological adaptation that occurs when medications acting on the central nervous system are ingested with rebound when the medication is abruptly discontinued. These dual meanings have led to confusion and may have propagated current clinical practices related to under-treatment of pain, as physicians fear creating an 'addiction' by prescribing opioids. In part to address this problem, a change proposed for DSM-V is to alter the chapter name to 'Addiction and Related Disorders', which will include disordered gambling. The specific substance use disorders may be referred to as 'alcohol use' or 'opioid use' disorders. The criteria for the disorders are likely to remain similar, with the exception of removal of the 'committing illegal acts' criterion and addition of a 'craving' criterion. The other major change relates to the elimination of the abuse/dependence dichotomy, given the lack of data supporting an intermediate stage. These changes are anticipated to improve clarification and diagnosis and treatment of substance use and related disorders.

  16. Time Dependent Behavior in the Weissenberg Effect

    NASA Astrophysics Data System (ADS)

    Degen, Michael M.; Andereck, C. David

    1997-03-01

    The Weissenberg effect is the climb of a non-Newtonian fluid up a rotating rod. We have found novel transitional effects in the behavior of a particular climbing fluid, STP(STP Oil Treatment distributed by First Brands Corporation.). The first state is a time-independent axisymmetric concave climb. As the rotation rate of the rod is increased, the first transition is to an axisymmetric climb with an ``onion dome'' shape. At higher rotation rates, the flow undergoes a symmetry breaking bifurcation to a time-dependent state. This time-dependent state exhibits an oscillation with a single frequency. Upon further increase of the rod rotation rate, the oscillation becomes modulated by a second frequency. The nature of each transition will be characterized, including the measurement of oscillation amplitudes and the frequency (or frequencies) of the time dependent states. These results will be compared with previous work.(G.S. Beavers, D.D. Joseph, J. Fluid Mech. 69), 475 (1975).(D.D. Joseph, R.L. Fosdick, Arch. Rational Mech. 49), 321 (1973).

  17. Reward-Dependent Modulation of Movement Variability

    PubMed Central

    Izawa, Jun; Shadmehr, Reza

    2015-01-01

    Movement variability is often considered an unwanted byproduct of a noisy nervous system. However, variability can signal a form of implicit exploration, indicating that the nervous system is intentionally varying the motor commands in search of actions that yield the greatest success. Here, we investigated the role of the human basal ganglia in controlling reward-dependent motor variability as measured by trial-to-trial changes in performance during a reaching task. We designed an experiment in which the only performance feedback was success or failure and quantified how reach variability was modulated as a function of the probability of reward. In healthy controls, reach variability increased as the probability of reward decreased. Control of variability depended on the history of past rewards, with the largest trial-to-trial changes occurring immediately after an unrewarded trial. In contrast, in participants with Parkinson's disease, a known example of basal ganglia dysfunction, reward was a poor modulator of variability; that is, the patients showed an impaired ability to increase variability in response to decreases in the probability of reward. This was despite the fact that, after rewarded trials, reach variability in the patients was comparable to healthy controls. In summary, we found that movement variability is partially a form of exploration driven by the recent history of rewards. When the function of the human basal ganglia is compromised, the reward-dependent control of movement variability is impaired, particularly affecting the ability to increase variability after unsuccessful outcomes. PMID:25740529

  18. Software dependability in the Tandem GUARDIAN system

    NASA Technical Reports Server (NTRS)

    Lee, Inhwan; Iyer, Ravishankar K.

    1995-01-01

    Based on extensive field failure data for Tandem's GUARDIAN operating system this paper discusses evaluation of the dependability of operational software. Software faults considered are major defects that result in processor failures and invoke backup processes to take over. The paper categorizes the underlying causes of software failures and evaluates the effectiveness of the process pair technique in tolerating software faults. A model to describe the impact of software faults on the reliability of an overall system is proposed. The model is used to evaluate the significance of key factors that determine software dependability and to identify areas for improvement. An analysis of the data shows that about 77% of processor failures that are initially considered due to software are confirmed as software problems. The analysis shows that the use of process pairs to provide checkpointing and restart (originally intended for tolerating hardware faults) allows the system to tolerate about 75% of reported software faults that result in processor failures. The loose coupling between processors, which results in the backup execution (the processor state and the sequence of events) being different from the original execution, is a major reason for the measured software fault tolerance. Over two-thirds (72%) of measured software failures are recurrences of previously reported faults. Modeling, based on the data, shows that, in addition to reducing the number of software faults, software dependability can be enhanced by reducing the recurrence rate.

  19. The diagnosis of marijuana (cannabis) dependence.

    PubMed

    Miller, N S; Gold, M S

    1989-01-01

    The definition of marijuana (Cannabis) dependence (addiction) contains three critical elements. These are (a) preoccupation with the acquisition of marijuana, (b) compulsive use of marijuana, (c) relapse to or recurrent use of the marijuana. The manifestations of abnormal marijuana use may assume many forms. Medical, psychiatric, neurological, traumatic, and sociological sequelae occur commonly in acute and chronic marijuana use. Marijuana dependence must be diagnosed primarily as the etiological or precipitating agent to adequately prevent and treat these conditions. The central role of marijuana addiction can be identified. The consequences of the marijuana addiction should be separated from the marijuana addict's actual motivation or craving to use marijuana. Marijuana addicts use abnormally because of what marijuana does to them and not for them. Marijuana reinforces its own use. Psychosocial stressors are not required to produce a marijuana addiction in biologically susceptible individuals. Consequences that result from an addiction to marijuana do not produce the abnormal use. A presumptive diagnosis of marijuana dependence (addiction) can be established by detecting significant consequences associated with marijuana use. A definitive diagnosis entails confirming the presence of addictive behavior by identifying a preoccupation, compulsivity and relapse relative to the drug, marijuana. PMID:2677398

  20. Dependent personality disorder and physical abuse.

    PubMed

    Loas, Gwenolé; Cormier, Julie; Perez-Diaz, Fernando

    2011-01-30

    The aim of this study was to test the hypothesis that the likelihood of physical spousal abuse is increased in dependent personality disorder (DPD) compared to other personality disorders. The sample consisted of 305 subjects consecutively admitted to an outpatient department of legal medicine for physical abuse. Using the Structured Clinical Interview for Disorders, screen questionnaire (SCID-II-SQ), the subjects were divided into three groups: without personality disorders (WPD, N=108), with non-dependent personality disorders (NDPD, N=179) and with DPDs (DPD, N=18). First,, the three groups were compared to the rate of spouses among the perpetrators. The rate of spouses among the perpetrators was significantly different between the three groups: 44.4% of the perpetrators were the spouse for DPD subjects versus 11.2% for WPD and 20.1% for NDPD. Second, logistic regressions using the status of perpetrators (spouse or others) as dependent variable and socio-demographical variables as well as the rates of DPD, avoidant, obsessive-compulsive and borderline personality disorders as independent variables reported that these four disorders of personality were significant predictors. Moreover, the co-morbidities of DPD with avoidant, obsessive-compulsive or borderline personality disorders were higher than 50%. These results suggest first that DPD subjects are at high risk of physical abuse by their spouses and second that this relationship was found also for the two other cluster C personality disorders as well as for borderline personality disorder.

  1. DEPEND: A simulation-based environment for system level dependability analysis

    NASA Technical Reports Server (NTRS)

    Goswami, Kumar; Iyer, Ravishankar K.

    1992-01-01

    The design and evaluation of highly reliable computer systems is a complex issue. Designers mostly develop such systems based on prior knowledge and experience and occasionally from analytical evaluations of simplified designs. A simulation-based environment called DEPEND which is especially geared for the design and evaluation of fault-tolerant architectures is presented. DEPEND is unique in that it exploits the properties of object-oriented programming to provide a flexible framework with which a user can rapidly model and evaluate various fault-tolerant systems. The key features of the DEPEND environment are described, and its capabilities are illustrated with a detailed analysis of a real design. In particular, DEPEND is used to simulate the Unix based Tandem Integrity fault-tolerance and evaluate how well it handles near-coincident errors caused by correlated and latent faults. Issues such as memory scrubbing, re-integration policies, and workload dependent repair times which affect how the system handles near-coincident errors are also evaluated. Issues such as the method used by DEPEND to simulate error latency and the time acceleration technique that provides enormous simulation speed up are also discussed. Unlike any other simulation-based dependability studies, the use of these approaches and the accuracy of the simulation model are validated by comparing the results of the simulations, with measurements obtained from fault injection experiments conducted on a production Tandem Integrity machine.

  2. Pyridoxal-5'-phosphate-dependent catalytic antibodies.

    PubMed

    Gramatikova, Svetlana; Mouratou, Barbara; Stetefeld, Jörg; Mehta, Perdeep K; Christen, Philipp

    2002-11-01

    Strategies for expanding the catalytic scope of antibodies include the incorporation of inorganic or organic cofactors into their binding sites. An obvious choice is pyridoxal-5'-phosphate (PLP), which is probably the most versatile organic cofactor of enzymes. Monoclonal antibodies against the hapten N(alpha)-(5'-phosphopyridoxyl)-L-lysine, a stable analog of the covalent coenzyme-substrate adducts were screened by a competition ELISA for binding of the PLP-amino acid Schiff base adduct. The Schiff base with its C4'-N alpha double bond is, in contrast to the hapten, a planar compound and is an obligatory intermediate in all PLP-dependent reactions of amino acids. This highly discriminating screening step eliminated all but 5 of 24 hapten-binding antibodies. The five remaining antibodies were tested for catalysis of the PLP-dependent alpha,beta-elimination reaction of beta-chloroalanine. Antibody 15A9 complied with this selection criterion and catalyzed in addition the cofactor-dependent transamination reaction of hydrophobic D-amino acids and oxo acids (k(cat)'=0.42 min(-1) with D-alanine at 25 degrees C). Homology modeling together with alanine scanning yielded a 3D model of Fab 15A9. The striking analogy between antibody 15A9 and PLP-dependent enzymes includes the following features: (1) The binding sites accommodate the planar coenzyme-amino acid adduct. (2) The bond at C alpha to be broken lies together with the C alpha-N bond in a plane orthogonal to the plane of coenzyme and imine bond. (3) The alpha-carboxylate group of the substrate is bound by an arginine residue. (4) The coenzyme-substrate adduct assumes a cisoid conformation. (5) PLP markedly contributes to catalytic efficiency, being a 10(4) times more efficient amino group acceptor than pyruvate. The protein moiety, however, ensures reaction as well as substrate specificity, and further accelerates the reaction (in 15A9 k(cat (Ab x PLP))'/k(cat (PLP))'=5 x 10(3)). The analogies of antibody 15A9 with

  3. Genetics Home Reference: vitamin D-dependent rickets

    MedlinePlus

    ... Home Health Conditions vitamin D-dependent rickets vitamin D-dependent rickets Enable Javascript to view the expand/ ... Download PDF Open All Close All Description Vitamin D-dependent rickets is a disorder of bone development ...

  4. 20 CFR 725.207 - Determination of dependency; divorced spouse.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ..., and Duration of Entitlement Conditions and Duration of Entitlement: Miner's Dependents (augmented Benefits) § 725.207 Determination of dependency; divorced spouse. For the purpose of augmenting...

  5. Chronic methamphetamine exposure induces cardiac fas-dependent and mitochondria-dependent apoptosis.

    PubMed

    Liou, Cher-Ming; Tsai, Shiow-Chwen; Kuo, Chia-Hua; Williams, Timothy; Ting, Hua; Lee, Shin-Da

    2014-06-01

    Very limited information regarding the influence of chronic methamphetamine exposure on cardiac apoptosis is available. In this study, we evaluate whether chronic methamphetamine exposure will increase cardiac Fas-dependent (type I) and mitochondria-dependent (type II) apoptotic pathways. Thirty-two male Wistar rats at 3-4 months of age were randomly divided into a vehicle-treated group [phosphate-buffered saline (PBS) 0.5 ml SQ per day] and a methamphetamine-treated group (MA 10 mg/kg SQ per day) for 3 months. We report that after 3 months of exposure, abnormal myocardial architecture, more minor cardiac fibrosis and cardiac TUNEL-positive apoptotic cells were observed at greater frequency in the MA group than in the PBS group. Protein levels of TNF-α, Fas ligand, Fas receptor, Fas-associated death domain, activated caspase-8, and activated caspase-3 (Fas-dependent apoptosis) extracted from excised hearts were significantly increased in the MA group, compared to the PBS group. Protein levels of cardiac Bak, t-Bid, Bak to Bcl-xL ratio, activated caspase-9, and activated caspase-3 (mitochondria-dependent apoptosis) were significantly increased in the MA group, compared with the PBS group. The results from this study reveal that chronic methamphetamine exposure will activate cardiac Fas-dependent and mitochondria-dependent apoptotic pathways, which may indicate a possible mechanism for developing cardiac abnormalities in humans with chronic methamphetamine abuse.

  6. Study of charge-dependent azimuthal correlations using reaction-plane-dependent balance functions

    NASA Astrophysics Data System (ADS)

    Wang, Hui; STAR Collaboration

    2011-12-01

    STAR has recently reported charge-dependent azimuthal correlations that are sensitive to the charge separation effect in Au+Au collisions at \\sqrt{s_NN} = 200 GeV. Qualitatively, these results agree with some of the theoretical predictions for local parity violation in heavy-ion collisions. However, a study using reaction-plane-dependent balance functions shows an alternative origin of this signal. The balance function, which measures the correlation between oppositely charged pairs, is sensitive to the mechanisms of charge formation and the subsequent relative diffusion of the balancing charges. The reaction-plane-dependent balance function measurements can be related to STAR's charge-dependent azimuthal correlations. We report reaction-plane-dependent balance functions for Au+Au collisions at \\sqrt{s_NN} = 200, 62.4, 39, 11.5 and 7.7 GeV using the STAR detector. The model of Schlichting and Pratt incorporating local charge conservation and elliptic flow reproduces most of the three-particle azimuthal correlation results at 200 GeV. The experimental charge-dependent azimuthal charge correlations observed at 200 GeV can be explained in terms of local charge conservation and elliptic flow.

  7. Cardiac Fas-Dependent and Mitochondria-Dependent Apoptosis after Chronic Cocaine Abuse

    PubMed Central

    Liou, Cher-Ming; Tsai, Shiow-Chwen; Kuo, Chia-Hua; Ting, Hua; Lee, Shin-Da

    2014-01-01

    To evaluate whether chronic cocaine abuse will increase cardiac Fas-dependent and mitochondria-dependent apoptotic pathways, thirty-two male Wistar rats at 3–4 months of age were randomly divided into a vehicle-treated group (phosphate-buffered saline, PBS, 0.5 mL, SQ per day) and a cocaine-treated group (Cocaine, 10 mg/kg, SQ per day). After 3 months of treatment, the excised left ventricles were measured by H&E staining, Western blotting, DAPI staining and TUNEL assays. More cardiac TUNEL-positive apoptotic cells were observed in the Cocaine group than the PBS group. Protein levels of TNF-alpha, Fas ligand, Fas death receptor, FADD, activated caspase-8, and activated caspase-3 (Fas-dependent apoptosis) extracted from excised hearts in the Cocaine group were significantly increased, compared to the PBS group. Protein levels of cardiac Bax, cytosolic cytochrome c, t-Bid-to-Bid, Bak-to-Bcl-xL, Bax-to-Bcl-2 ratio, activated caspase-9, and activated caspase-3 (mitochondria-dependent apoptosis) were significantly increased in the Cocaine group, compared to the PBS group. Chronic cocaine exposure appeared to activate the cardiac Fas-dependent and mitochondria-dependent apoptosis, which may indicate a possible mechanism for the development of cardiac abnormalities in humans with chronic cocaine abuse. PMID:24722570

  8. Ionic dependence of sulphur mustard cytotoxicity

    SciTech Connect

    Sawyer, Thomas W. Nelson, Peggy; Bjarnason, Stephen; Vair, Cory; Shei Yimin; Tenn, Catherine; Lecavalier, Pierre; Burczyk, Andrew

    2010-09-15

    The effect of ionic environment on sulphur mustard (bis 2-chloroethyl sulphide; HD) toxicity was examined in CHO-K1 cells. Cultures were treated with HD in different ionic environments at constant osmolar conditions (320 mOsM, pH 7.4). The cultures were refed with fresh culture medium 1 h after HD exposure, and viability was assessed. Little toxicity was apparent when HD exposures were carried out in ion-free sucrose buffer compared to LC{sub 50} values of {approx} 100-150 {mu}M when the cultures were treated with HD in culture medium. Addition of NaCl to the buffer increased HD toxicity in a salt concentration-dependent manner to values similar to those obtained in culture medium. HD toxicity was dependent on both cationic and anionic species with anionic environment playing a much larger role in determining toxicity. Substitution of NaI for NaCl in the treatment buffers increased HD toxicity by over 1000%. The activity of the sodium hydrogen exchanger (NHE) in recovering from cytosolic acidification in salt-free and in different chloride salts did not correlate with the HD-induced toxicity in these buffers. However, the inhibition by HD of intracellular pH regulation correlated with its toxicity in NaCl, NaI and sucrose buffers. Analytical chemical studies and the toxicity of the iodine mustard derivative ruled out the role of chemical reactions yielding differentially toxic species as being responsible for the differences in HD toxicity observed. This work demonstrates that the early events that HD sets into motion to cause toxicity are dependent on ionic environment, possibly due to intracellular pH deregulation.

  9. Time-dependent Dyson orbital theory.

    PubMed

    Gritsenko, O V; Baerends, E J

    2016-08-21

    Although time-dependent density functional theory (TDDFT) has become the tool of choice for real-time propagation of the electron density ρ(N)(t) of N-electron systems, it also encounters problems in this application. The first problem is the neglect of memory effects stemming from the, in TDDFT virtually unavoidable, adiabatic approximation, the second problem is the reliable evaluation of the probabilities P(n)(t) of multiple photoinduced ionization, while the third problem (which TDDFT shares with other approaches) is the reliable description of continuum states of the electrons ejected in the process of ionization. In this paper time-dependent Dyson orbital theory (TDDOT) is proposed. Exact TDDOT equations of motion (EOMs) for time-dependent Dyson orbitals are derived, which are linear differential equations with just static, feasible potentials of the electron-electron interaction. No adiabatic approximation is used, which formally resolves the first TDDFT problem. TDDOT offers formally exact expressions for the complete evolution in time of the wavefunction of the outgoing electron. This leads to the correlated probability of single ionization P(1)(t) as well as the probabilities of no ionization (P(0)(t)) and multiple ionization of n electrons, P(n)(t), which formally solves the second problem of TDDFT. For two-electron systems a proper description of the required continuum states appears to be rather straightforward, and both P(1)(t) and P(2)(t) can be calculated. Because of the exact formulation, TDDOT is expected to reproduce a notorious memory effect, the "knee structure" of the non-sequential double ionization of the He atom. PMID:26987972

  10. Outboard Motor Maximizes Power and Dependability

    NASA Technical Reports Server (NTRS)

    2008-01-01

    Developed by Jonathan Lee, a structural materials engineer at Marshall Space Flight Center, and PoShou Chen, a scientist with Huntsville, Alabama-based Morgan Research Corporation, MSFC-398 is a high-strength aluminum alloy able to operate at high temperatures. MSFC-398 was licensed for marine applications by Bombardier Recreational Products Inc., and is now found in the complete line of Evinrude E-TEC outboard motors, a line of two-stroke motors that maintain the power and dependability of a two-stroke with the refinement of a four-stroke.

  11. Sequence dependent hole evolution in DNA.

    PubMed

    Lakhno, V D

    2004-06-01

    The paper examines thedynamical behavior of a radical cation(G(+*)) generated in adouble stranded DNA for differentoligonucleotide sequences. The resonancehole tunneling through an oligonucleotidesequence is studied by the method ofnumerical integration of self-consistentquantum-mechanical equations. The holemotion is considered quantum mechanicallyand nucleotide base oscillations aretreated classically. The results obtaineddemonstrate a strong dependence of chargetransfer on the type of nucleotidesequence. The rates of the hole transferare calculated for different nucleotidesequences and compared with experimentaldata on the transfer from (G(+*))to a GGG unit.

  12. Alcohol use dependence in fragile X syndrome

    PubMed Central

    Salcedo-Arellano, María J; Lozano, Reymundo; Tassone, Flora; Hagerman, Randi J; Saldarriaga, Wilmar

    2016-01-01

    Summary Alcohol use disorders (AUDs) have been reported in a limited number of individuals with cognitive impairment but rarely in those with fragile X syndrome (FXS). However, in Colombia, culturally, alcohol consumption is very common. Here, we report eight cases of patients with FXS who have frequent alcohol consumption in Ricaurte, Colombia. Some of these patients have also used tobacco and illegal substances, including cocaine, which use has not been previously reported in those with FXS. Alcohol and substance use dependence is associated with exacerbation of their behavioral problems, such as increased impulsivity and aggression, as well as of medical problems such as an increased frequency of seizures. PMID:27672544

  13. Alcohol use dependence in fragile X syndrome.

    PubMed

    Salcedo-Arellano, María J; Lozano, Reymundo; Tassone, Flora; Hagerman, Randi J; Saldarriaga, Wilmar

    2016-08-01

    Alcohol use disorders (AUDs) have been reported in a limited number of individuals with cognitive impairment but rarely in those with fragile X syndrome (FXS). However, in Colombia, culturally, alcohol consumption is very common. Here, we report eight cases of patients with FXS who have frequent alcohol consumption in Ricaurte, Colombia. Some of these patients have also used tobacco and illegal substances, including cocaine, which use has not been previously reported in those with FXS. Alcohol and substance use dependence is associated with exacerbation of their behavioral problems, such as increased impulsivity and aggression, as well as of medical problems such as an increased frequency of seizures. PMID:27672544

  14. Calcium-dependent regulation of photosynthesis.

    PubMed

    Hochmal, Ana Karina; Schulze, Stefan; Trompelt, Kerstin; Hippler, Michael

    2015-09-01

    The understanding of calcium as a second messenger in plants has been growing intensively over the last decades. Recently, attention has been drawn to the organelles, especially the chloroplast but focused on the stromal Ca2+ transients in response to environmental stresses. Herein we will expand this view and discuss the role of Ca2+ in photosynthesis. Moreover we address of how Ca2+ is delivered to chloroplast stroma and thylakoids. Thereby, new light is shed on the regulation of photosynthetic electron flow and light-dependent metabolism by the interplay of Ca2+, thylakoid acidification and redox status. This article is part of a Special Issue entitled: Chloroplast biogenesis.

  15. An altitude-dependent spacecraft charging model

    NASA Technical Reports Server (NTRS)

    Haffner, J. W.

    1977-01-01

    A model for the altitude dependence of the hot plasma parameters responsible for the electrostatic charging of spacecraft was developed. Based upon plasma orbit theory, the directed velocity is a function of the ambient magnetic field flux density. A consequence of this approach is that while the thermal velocity distributions (assumed to be Maxwellian) of the plasma particles are independent of the magnetic field strength (and hence altitude), the particle densities increase with magnetic field strength. Thus, according to this model, while the equilibrium voltage is independent of altitude, the charging current density increases with decreasing altitude. However, the probability of such spacecraft charging decreases with decreasing altitude.

  16. Parrondo Games with Spatial Dependence, III

    NASA Astrophysics Data System (ADS)

    Ethier, S. N.; Lee, Jiyeon

    2015-10-01

    We study Toral’s Parrondo games with N players and one-dimensional spatial dependence as modified by Xie et al. Specifically, we use computer graphics to sketch the Parrondo and anti-Parrondo regions for 3 ≤ N ≤ 9. Our work was motivated by a recent paper of Li et al., who applied a state space reduction method to this model, reducing the number of states from 2N to N + 1. We show that their reduced Markov chains are inconsistent with the model of Xie et al.

  17. Kernel score statistic for dependent data.

    PubMed

    Malzahn, Dörthe; Friedrichs, Stefanie; Rosenberger, Albert; Bickeböller, Heike

    2014-01-01

    The kernel score statistic is a global covariance component test over a set of genetic markers. It provides a flexible modeling framework and does not collapse marker information. We generalize the kernel score statistic to allow for familial dependencies and to adjust for random confounder effects. With this extension, we adjust our analysis of real and simulated baseline systolic blood pressure for polygenic familial background. We find that the kernel score test gains appreciably in power through the use of sequencing compared to tag-single-nucleotide polymorphisms for very rare single nucleotide polymorphisms with <1% minor allele frequency.

  18. Temperature dependence of sapphire fiber Raman scattering

    DOE PAGES

    Liu, Bo; Yu, Zhihao; Tian, Zhipeng; Homa, Daniel; Hill, Cary; Wang, Anbo; Pickrell, Gary

    2015-04-27

    Anti-Stokes Raman scattering in sapphire fiber has been observed for the first time. Temperature dependence of Raman peaks’ intensity, frequency shift, and linewidth were also measured. Three anti-Stokes Raman peaks were observed at temperatures higher than 300°C in a 0.72-m-long sapphire fiber excited by a second-harmonic Nd YAG laser. The intensity of anti-Stokes peaks are comparable to that of Stokes peaks when the temperature increases to 1033°C. We foresee the combination of sapphire fiber Stokes and anti-Stokes measurement in use as a mechanism for ultrahigh temperature sensing.

  19. Dependable control systems with Internet of Things.

    PubMed

    Tran, Tri; Ha, Q P

    2015-11-01

    This paper presents an Internet of Things (IoT)-enabled dependable control system (DepCS) for continuous processes. In a DepCS, an actuator and a transmitter form a regulatory control loop. Each processor inside such actuator and transmitter is designed as a computational platform implementing the feedback control algorithm. The connections between actuators and transmitters via IoT create a reliable backbone for a DepCS. The centralized input-output marshaling system is not required in DepCSs. A state feedback control synthesis method for DepCS applying the self-recovery constraint is presented in the second part of the paper.

  20. Psychoactive Substance Dependence: A Dentist's Challenge.

    PubMed

    Millar, Lynsey

    2015-05-01

    Given the number of individuals who are dependent on alcohol and/or drugs, it is inevitable that they will present for dental treatment. They are at an increased risk of dental disease for multiple reasons. This paper aims to provide an overview for general dental practitioners (GDPs) of the challenges that can arise in treating such patients, alongside some suggestions for meeting these challenges. General issues are taken into consideration first, then a focus is made on each of the most common substances, together with their implications in dentistry. PMID:26556258

  1. HIV infection in females dependent on drugs.

    PubMed

    Wai, B H; Singh, S; Varma, S L

    1996-03-01

    One hundred and seventy-one drug-dependent females in a drug rehabilitation centre were studied to estimate the prevalence of HIV infection among them. Twenty-four (14%) were positive on the Western Blot test. The presence of HIV infection was significantly correlated with syphilis (p < 0.03) and age (p < 0.001); 83% of those who were HIV positive were intravenous drug users. The need for harm reduction programmes to prevent spread of HIV infection among injecting drug users is stressed. PMID:8867206

  2. Escherichia coli survival in waters: temperature dependence.

    PubMed

    Blaustein, R A; Pachepsky, Y; Hill, R L; Shelton, D R; Whelan, G

    2013-02-01

    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 model. This suggestion was made 34 years ago based on 20 survival curves taken from published literature, but has not been revisited since then. The objective of this study was to re-evaluate the accuracy of the Q₁₀ equation, utilizing data accumulated since 1978. We assembled a database of 450 E. coli survival datasets from 70 peer-reviewed papers. We then focused on the 170 curves taken from experiments that were performed in the laboratory under dark conditions to exclude the effects of sunlight and other field factors that could cause additional variability in results. All datasets were tabulated dependencies "log concentration vs. time." There were three major patterns of inactivation: about half of the datasets had a section of fast log-linear inactivation followed by a section of slow log-linear inactivation; about a quarter of the datasets had a lag period followed by log-linear inactivation; and the remaining quarter were approximately linear throughout. First-order inactivation rate constants were calculated from the linear sections of all survival curves and the data grouped by water sources, including waters of agricultural origin, pristine water sources, groundwater and wells, lakes and reservoirs, rivers and streams, estuaries and seawater, and wastewater. Dependency of E. coli inactivation rates on temperature varied among the water sources. There was a significant difference in inactivation rate values at the reference temperature between rivers and agricultural waters, wastewaters and agricultural waters, rivers and lakes, and wastewater and lakes. At specific sites, the Q₁₀ equation was more accurate in rivers and coastal waters than in lakes making the value of

  3. Alcohol use dependence in fragile X syndrome

    PubMed Central

    Salcedo-Arellano, María J; Lozano, Reymundo; Tassone, Flora; Hagerman, Randi J; Saldarriaga, Wilmar

    2016-01-01

    Summary Alcohol use disorders (AUDs) have been reported in a limited number of individuals with cognitive impairment but rarely in those with fragile X syndrome (FXS). However, in Colombia, culturally, alcohol consumption is very common. Here, we report eight cases of patients with FXS who have frequent alcohol consumption in Ricaurte, Colombia. Some of these patients have also used tobacco and illegal substances, including cocaine, which use has not been previously reported in those with FXS. Alcohol and substance use dependence is associated with exacerbation of their behavioral problems, such as increased impulsivity and aggression, as well as of medical problems such as an increased frequency of seizures.

  4. Size-dependent thermopower of nickel nanoparticles

    SciTech Connect

    Singh, Jaiveer; Kaurav, N.; Okram, Gunadhor S.

    2014-04-24

    Nickel nanoparticles (Ni-NPs) were prepared by thermal decomposition method using Trioctylphosphine (TOP) and Oleylamine (OA). The average particle size (D) estimated from X-ray diffraction (XRD) using Scherrer equation, to be 1-10nm, systematically decreases with increasing concentration of TOP at constant OA concentration. The observed thermopower strongly depends on particle size particularly at low temperatures reaching a very high value of ∼ 10{sup 5} μV/K (at 20 K), and is attributed to the enhanced grain-boundary scattering combined with quantum confinement.

  5. Transverse Momentum Dependent Distributions in Hard Scattering

    SciTech Connect

    Alexie Prokudin

    2011-05-01

    Transverse Momentum Dependent Distributions (TMDs) describe the spin structure of the proton. At leading twist spin structure of spin-1/2 hadron can be described by 8 TMDs. TMDs reveal three-dimensional distribution of partons inside polarised nucleon. Experimentally these functions can be studied in polarised experiments using Spin Asymmetries in particular Single Spin Asymmetries (SSAs). We discuss transversity that measures distribution of transversely polarised quarks in a transversely polarised nucleon and Sivers distribution function that describes distribution of unpolarised quarks in a transversely polarised nucleon.

  6. Environmental dependence of masses and coupling constants

    SciTech Connect

    Olive, Keith A.; Pospelov, Maxim

    2008-02-15

    We construct a class of scalar field models coupled to matter that lead to the dependence of masses and coupling constants on the ambient matter density. Such models predict a deviation of couplings measured on the Earth from values determined in low-density astrophysical environments, but do not necessarily require the evolution of coupling constants with the redshift in the recent cosmological past. Additional laboratory and astrophysical tests of {delta}{alpha} and {delta}(m{sub p}/m{sub e}) as functions of the ambient matter density are warranted.

  7. Rickets–vitamin D deficiency and dependency

    PubMed Central

    Sahay, Manisha; Sahay, Rakesh

    2012-01-01

    Rickets is an important problem even in countries with adequate sun exposure. The causes of rickets/osteomalacia are varied and include nutritional deficiency, especially poor dietary intake of vitamin D and calcium. Non-nutritional causes include hypophosphatemic rickets primarily due to renal phosphate losses and rickets due to renal tubular acidosis. In addition, some varieties are due to inherited defects in vitamin D metabolism and are called vitamin D dependent rickets. This chapter highlights rickets/osteomalacia related to vitamin D deficiency or to inherited defects in vitamin D metabolism. Hypophosphatemic rickets and rickets due to renal tubular acidosis are discussed in other sections of the journal. PMID:22470851

  8. Pulsar Electrodynamics: a Time-dependent View

    SciTech Connect

    Spitkovsky, Anatoly; /KIPAC, Menlo Park

    2006-04-10

    Pulsar spindown forms a reliable yet enigmatic prototype for the energy loss processes in many astrophysical objects including accretion disks and back holes. In this paper we review the physics of pulsar magnetospheres, concentrating on recent developments in force-free modeling of the magnetospheric structure. In particular, we discuss a new method for solving the equations of time-dependent force-free relativistic MHD in application to pulsars. This method allows to dynamically study the formation of the magnetosphere and its response to perturbations, opening a qualitatively new window on pulsar phenomena. Applications of the method to other magnetized rotators, such as magnetars and accretion disks, are also discussed.

  9. [The Amygdala in mechanisms of alcohol dependence].

    PubMed

    Akhmadeev, A V; Kalimullina, L B

    2016-01-01

    In the present review for the first time systematized literature data about reactive changes, of neurons in the basolateral and medial nuclei of the Amygdala which occur in response to acute and chronic exposure of ethanol. Summarized information about the mechanisms of disturbances in glutamatergic-and GABAergic systems of the basolateral nucleus that determining an increased level of anxiety, which is seen as a main motivating factor of desire for alcohol, thus involved to the manifestation of alcohol dependence. Reviewed molecular and genetic aspects of rsearchs involvement of medial nucleus in the mechanisms of alcoholism. PMID:27530042

  10. Mercury - Wavelength and longitude dependence of polarization

    NASA Technical Reports Server (NTRS)

    Gehrels, T.; Landau, R.; Coyne, G. V.

    1987-01-01

    The polarization-time variations noted in the present linear polarization observations of the integrated Mercury disk, with filters covering the 0.3-1.0 micron bandpass and between 53-130 deg of phase angle, may be accounted for in terms of longitude dependence through the variation of brightness or other properties over the surface. Kepler's equation for the eccentric anomaly was solved for each observation, and the true anomaly was used to find the subsolar longitude. The difference found in the polarization-albedo relations of Mercury and the moon indicates a difference in surface texture and/or composition.

  11. Gravity-Dependent Transport in Industrial Processes

    NASA Technical Reports Server (NTRS)

    Ostrach, Simon; Kamotani, Yasuhiro

    1996-01-01

    Gravity dependent transport phenomena in various industrial processes are investigated in order to indicate new directions for micro-gravity research that enhance the commercial success of the space program. The present article describes the commercialization possibilities of such topics associated with physicochemical transport phenomena. The topics are: coating flow, rotating electrochemical system, and convection in low Plandtl number fluids. The present study is directed to understand these phenomena, and to develop a knowledge base for their applications with emphasis to a micro-gravity environment.

  12. HEROIN DEPENDENCE : THE NEW DELHI EXPERIENCE

    PubMed Central

    Adityanjee; Mohan, D.; Saxena, S.

    1984-01-01

    SUMMARY Socio-demographic and clinical profile of the first one hundred and five patients attending a de-addiction clinic of New Delhi for heroin dependence is presented. It reveals a sudden rise of Heroin use in young educated males, probably because of its easy availability and its decreasing prices in the last few years. This trend is likely to be observed in the other metropolitan cities of India as well. Need for strengthening of preventive, curative and rehabilitative services is emphasized. PMID:21966005

  13. ALCOHOL DEPENDENCE--NEUROBIOLOGY AND TREATMENT.

    PubMed

    Michalak, Agnieszka; Biała, Grazyna

    2016-01-01

    The consequences of alcohol dependence concern serious health care, social and economic problems. The scope of many studies is to better understand mechanisms underlying alcohol addiction in order to work out new, more effective treatment strategies. Alcohol affects many neurotransmission systems within the brain. In general, acute alcohol enhances inhibitory transmission, up-regulating the GABAergic system and impairing glutamatergic function, therefore interfering the balance between excitatory and inhibitory synaptic inputs. Chronic alcohol consumption, meanwhile, in order to restore equilibrium leads to neuroadaptive changes caus- ing both decreased GABAergic and increased glutamatergic activity. Also function of other neurotransmitters and modulators is modified by the presence of alcohol, including glycine, adenosine, serotonin and dopamine. Moreover, a significant impact of alcohol on the endogenous opioid system, nicotinic cholinergic transmission and the endocannabinoids system has been also established. At present, only four medications are approved for the treatment of alcohol dependence in Europe, that is naltrexone, acamprosate, disulfiram and the most recent nalmefene. Among other promising strategies the following drugs are mentioned: baclofen, topiramate, ondansetron, aripiprazole, rimonabant and varenicline. Additionally, the role of appetite-regulating hormones, neuroimmune modulators or the body's stress-response system modulators in reducing alcohol consumption is currently of great interest, however, further investigations are needed. PMID:27008795

  14. Diameter-dependent hydrophobicity in carbon nanotubes

    NASA Astrophysics Data System (ADS)

    Kyakuno, Haruka; Fukasawa, Mamoru; Ichimura, Ryota; Matsuda, Kazuyuki; Nakai, Yusuke; Miyata, Yasumitsu; Saito, Takeshi; Maniwa, Yutaka

    2016-08-01

    Single-wall carbon nanotubes (SWCNTs) are a good model system that provides atomically smooth nanocavities. It has been reported that water-SWCNTs exhibit hydrophobicity depending on the temperature T and the SWCNT diameter D. SWCNTs adsorb water molecules spontaneously in their cylindrical pores around room temperature, whereas they exhibit a hydrophilic-hydrophobic transition or wet-dry transition (WDT) at a critical temperature Twd ≈ 220-230 K and above a critical diameter Dc ≈ 1.4-1.6 nm. However, details of the WDT phenomenon and its mechanism remain unknown. Here, we report a systematic experimental study involving X-ray diffraction, optical microscopy, and differential scanning calorimetry. It is found that water molecules inside thick SWCNTs (D > Dc) evaporate and condense into ice Ih outside the SWCNTs at Twd upon cooling, and the ice Ih evaporates and condenses inside the SWCNTs upon heating. On the other hand, residual water trapped inside the SWCNTs below Twd freezes. Molecular dynamics simulations indicate that upon lowering T, the hydrophobicity of thick SWCNTs increases without any structural transition, while the water inside thin SWCNTs (D < Dc) exhibits a structural transition, forming an ordered ice. This ice has a well-developed hydrogen bonding network adapting to the cylindrical pores of the SWCNTs. Thus, the unusual diameter dependence of the WDT is attributed to the adaptability of the structure of water to the pore dimension and shape.

  15. The tobacco dependence dimension in Colombia.

    PubMed

    Posada-Villa, Jose; Cheng, Hui G; Martins, Silvia S; Storr, Carla L; Aguilar-Gaxiola, Sergio A; Anthony, James C

    2011-01-01

    This epidemiological study of a sample of smokers from the general population of Colombia examined the population distribution and dimensionality of eight hypothesized inter-correlated clinical features (CFs) associated with tobacco dependence syndrome (TDS). Data were drawn from interviews of 4 426 smokers conducted in a national survey in Colombia as part of the World Mental Health Survey Initiative. Daily smokers completed a Spanish-language TDS module, and the 237 smokers who had begun smoking during the five years prior to the assessment were selected. Confirmatory factor analysis (CFA) for a unidimensional TDS provided discrimination and difficulty parameter estimates. Two CFs that were reported very infrequently among the study sample were dropped from the CFA. Among the six remaining CFs, discrimination (D1) estimates ranged from 1.1 to 6.0 and difficulty (D2) estimates ranged from 1.1 to 2.2, providing evidentiary support for a unidimensional tobacco dependence construct. The Spanish-language TDS module used in this study could serve as a valuable tool in future studies for evaluating public health outreach and early intervention programs directed toward community residents who have begun smoking tobacco.

  16. The discovery of ubiquitin-dependent proteolysis

    PubMed Central

    Wilkinson, Keith D.

    2005-01-01

    In early 1980, Irwin A. Rose, Avram Hershko, and Aaron Ciechanover published two papers in PNAS that reported the astounding observation that energy-dependent intracellular proteolysis was far more complicated than the previously accepted models of lysosomal proteolysis or the action of ATP-dependent proteases such as bacterial lon. In fact, it has turned out to be even more complicated than they could have suspected. The general model of covalently attaching a small protein as a targeting signal has proved to be every bit as important to eukaryotic cells as the better understood modifications such as phosphorylation or acetylation. The key player in this modification, a small protein called ubiquitin (APF-1 in these papers), is the founding member of a large family of proteins containing the β-grasp fold and is used as a posttranslational targeting signal to modify the structure, function, and/or localization of other proteins. The story of this discovery is a textbook example of the confluence of intellectual curiosity, unselfish collaboration, chance, luck, and preparation. PMID:16230621

  17. Solvent dependent photophysical properties of dimethoxy curcumin

    NASA Astrophysics Data System (ADS)

    Barik, Atanu; Indira Priyadarsini, K.

    2013-03-01

    Dimethoxy curcumin (DMC) is a methylated derivative of curcumin. In order to know the effect of ring substitution on photophysical properties of curcumin, steady state absorption and fluorescence spectra of DMC were recorded in organic solvents with different polarity and compared with those of curcumin. The absorption and fluorescence spectra of DMC, like curcumin, are strongly dependent on solvent polarity and the maxima of DMC showed red shift with increase in solvent polarity function (Δf), but the above effect is prominently observed in case of fluorescence maxima. From the dependence of Stokes' shift on solvent polarity function the difference between the excited state and ground state dipole moment was estimated as 4.9 D. Fluorescence quantum yield (ϕf) and fluorescence lifetime (τf) of DMC were also measured in different solvents at room temperature. The results indicated that with increasing solvent polarity, ϕf increased linearly, which has been accounted for the decrease in non-radiative rate by intersystem crossing (ISC) processes.

  18. Temperature dependence of optically induced cell deformations

    NASA Astrophysics Data System (ADS)

    Fritsch, Anatol; Kiessling, Tobias R.; Stange, Roland; Kaes, Josef A.

    2012-02-01

    The mechanical properties of any material change with temperature, hence this must be true for cellular material. In biology many functions are known to undergo modulations with temperature, like myosin motor activity, mechanical properties of actin filament solutions, CO2 uptake of cultured cells or sex determination of several species. As mechanical properties of living cells are considered to play an important role in many cell functions it is surprising that only little is known on how the rheology of single cells is affected by temperature. We report the systematic temperature dependence of single cell deformations in Optical Stretcher (OS) measurements. The temperature is changed on a scale of about 20 minutes up to hours and compared to defined temperature shocks in the range of milliseconds. Thereby, a strong temperature dependence of the mechanics of single suspended cells is revealed. We conclude that the observable differences arise rather from viscosity changes of the cytosol than from structural changes of the cytoskeleton. These findings have implications for the interpretation of many rheological measurements, especially for laser based approaches in biological studies.

  19. Rate-dependent incompleteness of earthquake catalogs

    NASA Astrophysics Data System (ADS)

    Hainzl, Sebastian

    2016-04-01

    Important information about the earthquake generation process can be gained from instrumental earthquake catalogs, but this requires complete recordings to avoid biased results. The local completeness magnitude Mc is known to depend on general conditions such as the seismographic network and the environmental noise, which generally limit the possibility to detect small events. The detectability can be additionally reduced by an earthquake-induced increase of the noise-level leading to short-term variations of Mc, which cannot be resolved by traditional methods relying on the analysis of the frequency-magnitude distribution. Based on simple assumptions, I propose a new method to estimate such temporal excursions of Mc solely based on the estimation of the earthquake rate resulting in a high temporal resolution of Mc. The approach is shown to be in agreement with the apparent decrease of the estimated Gutenberg-Richter b-value in high-activity phases of recorded data sets and the observed incompleteness periods after mainshocks. Furthermore, an algorithm to estimate temporal changes of Mc is introduced and applied to empirical aftershock and swarm sequences from California and central Europe, indicating that observed b-value fluctuations are often related to rate-dependent incompleteness of the earthquake catalogs.

  20. Anomalous frequency dependent diamagnetism in metal silicide

    NASA Astrophysics Data System (ADS)

    Dahal, Ashutosh; Gunasekera, Jagat; Harriger, Leland; Singh, David J.; Singh, Deepak K.; Leland Harriger Collaboration

    Discovery of superconductivity in PbO-type FeSe has generated a lot of interest. Among the samples we synthesize with similar structure, NiSi has showed anomalous but very interesting results. Nickel silicides are important electronic materials that have been used as contacts for field effect transistors, as interconnects and in nanoelectronic devices. The magnetic properties of NiSi are not well known, however. In this presentation, we report a highly unusual magnetic phenomenon in NiSi. The ac susceptibility measurements on NiSi reveal strong frequency dependence of static and dynamic susceptibilities that are primarily diamagnetic at room temperature. The static susceptibility is found to exhibit a strong frequency dependence of the diamagnetic response below 100K, while dynamic susceptibility showed peak type feature at 10KHz frequency around 50K. Detailed neutron scattering measurements on high quality powder sample of NiSi on SPINS cold spectrometer further revealed an inelastic peak around 1.5meV, even though no magnetic order is detected. The inelastic peak dissipates above 100K, which is where the static susceptibility starts to diverge with frequency. Research is supported by U.S. Department of Energy, Office of Basic Energy Sciences under Grant No. DE-SC0014461.

  1. Size-dependent properties of semiconductor nanostructures

    NASA Astrophysics Data System (ADS)

    Kwak, Hyun Wook

    Doping is crucial to many potential applications of nanometer-sized semiconductors. Since their properties are strongly affected by both doping and quantum size effect, it is important to understand how dopants will influence its media under strong quantum confinement. In this dissertation, we will discuss the role of quantum confinement in the properties of nanometer-sized semiconductors doped with impurities. It is well-known that electronic and optical properties of nanometer-sized semiconductors can vary with size. We present size-dependent properties of lithium doped silicon and zinc oxide nanocrystals as examples. With the help of first-principles methods based on real space approach, we find that not only the size itself but also the chemical nature of the impurity is important to determine the properties of nanometer-sized semiconductors. We will also discuss size-induced magnetism in semiconductor nanostructures doped with non-magnetic impurities. From recent studies, it has been proposed that magnetic semiconductors can be designed by using non-magnetic defects, e.g., through the introduction of an extrinsic impurity atom that does not exhibit magnetism by itself. We examine this idea with silicon and zinc oxide nanostructures doped with impurities. We find that quantum size effect may induce magnetism in doped nanostructures. The evidence of the size-dependent magnetic properties offers a new perspective for the design of semiconductor-based spintronic materials.

  2. Coupled temperature dependences of volume and compressibility

    NASA Astrophysics Data System (ADS)

    Lawson, A. C.; Ledbetter, H.

    2011-04-01

    We present a new method for understanding the changes with temperature of the volume and compressibility of solids. These changes depend on five parameters: V 0, B 0, Θ, γ G and δ T. V 0 and B 0 are the atomic volume and bulk modulus at T = 0 K, Θ is the Debye temperature, γ G is the Grüneisen parameter, and δ T is the Anderson-Grüneisen parameter. Equations for the temperature-dependent volume, bulk modulus and thermal expansion are given, and examples of the use of these equations are provided, with particular emphasis on the light actinides. For the elements, we examine the relationship between experimental values of γ G and δ T, and find no clear correlation. In particular, Swenson's rule, which states that the bulk modulus does not change with temperature if the volume is held constant, is a poor approximation to the data. We reveal a new useful approximate relationship between dB/dP and γ G. We find that the thermodynamic quantity q, which describes the variation in γ G with volume, distributes around 2, not around 1, as often assumed. We show that the thermal- expansion behavior of Si and Ge (including negative thermal expansion at low temperatures) are well described with the use of a two-level invar model.

  3. KK molecules with momentum-dependent interactions

    SciTech Connect

    Lemmer, R. H.

    2009-10-15

    It is shown that the momentum-dependent kaon-antikaon interactions generated via vector-meson exchange from the standard SU{sub V}(3)xSU{sub A}(3) interaction Lagrangian lead to a nonlocal potential in coordinate space that can be incorporated without approximation into a nonrelativistic version of the Bethe-Salpeter wave equation containing a radial-dependent effective kaon mass appearing in a fully symmetrized kinetic energy operator, in addition to a local potential. Estimates of the mass and decay widths of f{sub 0}(980) and a{sub 0}(980), considered as KK molecules of isospin 0 and 1, as well as for K{sup +}K{sup -} atomic bound states (kaonium) are presented and compared with previous studies of a similar nature. It is argued that without a better knowledge of hadronic form factors it is not possible to distinguish between the molecular versus elementary particle models for the structure of the light scalar mesons.

  4. [Opioid tolerance and dependence--pharmacological aspects].

    PubMed

    Jaba, I M; Luncanu, I; Mungiu, O C

    2001-01-01

    Prolonged opioids administration leads inevitably to tolerance and dependence, a phenomenon we meet more often in healthy people than in ill patients. Tolerance means a hypersensibility of neuronal membranes as well as changes in the number and affinity of opioid receptors, which implies intake of larger doses to obtain the initial effect. Physical dependence, quite different of the psychological one, is the appearance of abstinence syndrome on sudden interruption of opioid administration or on administration of an antagonist. There is usually cross-tolerance in opioids, but it can also be incomplete, when the initial opioid can be replaced with another one that produces a milder abstinence syndrome. Classically, metadone is used in long time therapy, after detoxification with an antagonist is performed (naloxon, naltrexon). Modern pharmacological alternatives are levo-alpha-acetyl-methadol (LAAM) and agonists-antagonists (butorphanol, buprenorphine, pentazocine, nalbuphine). An antagonist can also be used if associated with an alpha--stimulant (clonidine), in order to remove noradrenergic manifestations of abstinence syndrome. Now other therapeutical principles are being studied: enkephalinaze inhibitors to reduce the abstinence syndrome, NMDA receptor antagonists, NO sintetasis inhibitors, that facilitates opioid analgesia and hinders tolerance development; colecystokinin-receptors agonists or antagonists to reduce tolerance on morphine. A recent study showed that the concomitant administration of an opioid agonist (sufentanil) and a calcium channels blocker (nimodipine) not only prevents from tolerance development but also triggers hypersensibility to analgesic effects of the opioid. PMID:12092171

  5. [Cereal-dependent exercise-induced anaphylaxis].

    PubMed

    Seoane-Rodríguez, Marta; Caralli, María Elisa; Morales-Cabeza, Cristina; Micozzi, Sarah; De Barrio-Fernández, Manuel; Rojas Pérez-Ezquerra, Patricia

    2016-01-01

    Wheat-dependent exercise-induced anaphylaxis (WDEIA) is increasing. In vitro test such as omega-5-gliadin levels are useful in the diagnosis, while oral single blind challenge tests (OCT) with wheat plus exercise continuous being the gold standard diagnostic method. This paper reports the case of a 38-year-old woman, with several episodes of anaphylaxis after eating different foods and doing exercise after ingestion. An allergy study was performed with positive skin prick tests for wheat, barley and rye. Total IgE 238.0KU/L, positive specific IgE (>100KU/L) to wheat, barley and rye, and negative to rTri-a-19 omega-5 gliadin. OCT with bread and exercise was positive. In this case of wheat-dependent exerciseinduced anaphylaxis (WDEIA) with negative serum specific IgE to omega-5-gliadin, negative results with gamma, alpha, bheta y omega-gliadin doesn't exclude the diagnosis of WDEIA. PMID:26943835

  6. A Case of Insulin-dependent Diabetes.

    PubMed

    Gonzalez, Nicholas

    2016-07-01

    Background • There is a paucity of information on alternative, nutrition-based treatments for insulin-dependent diabetes. Primary Study Objective • This case report provides detailed information on the nutrition-based treatment of a man with insulin-dependent diabetes. Methods/Design • This is a single case report taken from the author's private practice. Setting • The treatment was provided at a private office in New York, NY, USA. Participants • A single patient in the author's practice is reported. Intervention • The patient was treated with a combination of pancreatic enzymes, supplements and nutrients, and cleansing and detoxification procedures, plus amber lenses for severe insomnia. Primary Outcome Measures • The outcome measures were patient self-report of symptoms, overall well-being, and function at work and in leisure time; observation of the patient by the physician; and blood work. Results • The patient described dramatic, sustained improvement in terms of symptoms, function, well-being, and life satisfaction. Improvement in blood sugar control was documented by blood work. Conclusion • The complex, tailored nutritional protocol combined with detoxification procedures, resulted in marked improvement in a patient who had been treated by numerous different physicians without benefit prior to his consulting with the author. PMID:27548490

  7. The time-dependent Gutzwiller approximation

    NASA Astrophysics Data System (ADS)

    Fabrizio, Michele

    2015-03-01

    The time-dependent Gutzwiller Approximation (t-GA) is shown to be capable of tracking the off-equilibrium evolution both of coherent quasiparticles and of incoherent Hubbard bands. The method is used to demonstrate that the sharp dynamical crossover observed by time-dependent DMFT in the quench-dynamics of a half-filled Hubbard model can be identified within the t-GA as a genuine dynamical transition separating two distinct physical phases. This result, strictly variational for lattices of infinite coordination number, is intriguing as it actually questions the occurrence of thermalization. Next, we shall present how t-GA works in a multi-band model for V2O3 that displays a first-order Mott transition. We shall show that a physically accessible excitation pathway is able to collapse the Mott gap down and drive off-equilibrium the insulator into a metastable metal phase. Work supported by the European Union, Seventh Framework Programme, under the project GO FAST, Grant Agreement No. 280555.

  8. Solvent dependent photophysical properties of dimethoxy curcumin.

    PubMed

    Barik, Atanu; Indira Priyadarsini, K

    2013-03-15

    Dimethoxy curcumin (DMC) is a methylated derivative of curcumin. In order to know the effect of ring substitution on photophysical properties of curcumin, steady state absorption and fluorescence spectra of DMC were recorded in organic solvents with different polarity and compared with those of curcumin. The absorption and fluorescence spectra of DMC, like curcumin, are strongly dependent on solvent polarity and the maxima of DMC showed red shift with increase in solvent polarity function (Δf), but the above effect is prominently observed in case of fluorescence maxima. From the dependence of Stokes' shift on solvent polarity function the difference between the excited state and ground state dipole moment was estimated as 4.9 D. Fluorescence quantum yield (φ(f)) and fluorescence lifetime (τ(f)) of DMC were also measured in different solvents at room temperature. The results indicated that with increasing solvent polarity, φ(f) increased linearly, which has been accounted for the decrease in non-radiative rate by intersystem crossing (ISC) processes. PMID:23314392

  9. Authority dependence and judgments of utilitarian harm.

    PubMed

    Piazza, Jared; Sousa, Paulo; Holbrook, Colin

    2013-09-01

    Three studies tested the conditions under which people judge utilitarian harm to be authority dependent (i.e., whether its right or wrongness depends on the ruling of an authority). In Study 1, participants judged the right or wrongness of physical abuse when used as an interrogation method anticipated to yield useful information for preventing future terrorist attacks. The ruling of the military authority towards the harm was manipulated (prohibited vs. prescribed) and found to significantly influence judgments of the right or wrongness of inflicting harm. Study 2 established a boundary condition with regards to the influence of authority, which was eliminated when the utility of the harm was definitely obtained rather than forecasted. Finally, Study 3 replicated the findings of Studies 1-2 in a completely different context-an expert committee's ruling about the harming of chimpanzees for biomedical research. These results are discussed as they inform ongoing debates regarding the role of authority in moderating judgments of complex and simple harm. PMID:23747648

  10. Density-dependent adjustment of inducible defenses

    PubMed Central

    Tollrian, Ralph; Duggen, Sonja; Weiss, Linda C.; Laforsch, Christian; Kopp, Michael

    2015-01-01

    Predation is a major factor driving evolution, and organisms have evolved adaptations increasing their survival chances. However, most defenses incur trade-offs between benefits and costs. Many organisms save costs by employing inducible defenses as responses to fluctuating predation risk. The level of defense often increases with predator densities. However, individual predation risk should not only depend on predator density but also on the density of conspecifics. If the predator has a saturating functional response one would predict a negative correlation between prey density and individual predation risk and hence defense expression. Here, we tested this hypothesis using six model systems, covering a taxonomic range from protozoa to rotifers and crustaceans. In all six systems, we found that the level of defense expression increased with predator density but decreased with prey density. In one of our systems, i.e. in Daphnia, we further show that the response to prey density is triggered by a chemical cue released by conspecifics and congeners. Our results indicate that organisms adjust the degree of defense to the acute predation risk, rather than merely to predators’ densities. Our study suggests that density-dependent defense expression reflects accurate predation-risk assessment and is a general principle in many inducible-defense systems. PMID:26235428

  11. Nalmefene and its use in alcohol dependence.

    PubMed

    Gual, A; Bruguera, P; López-Pelayo, H

    2014-05-01

    Nalmefene is the first available drug approved in the E.U. to reduce alcohol use in alcohol-dependent patients. Reduction in alcohol use in heavy drinkers diminishes mortality risk and socio-economic burden. Nalmefene has shown efficacy at 6 months in alcohol-dependent patients with high or very high drinking risk levels in reducing total alcohol consumption (-7.6 g/day [95% confidence interval (CI): -11.6 to -3.5]; P = 0.0003), heavy drinking days (-2.00 days/month [95% CI: -3.00 to -1.00]; P ⟨ 0.00001) and other secondary outcome measures such as γ-glutamyl transferase, alanine aminotransferase, drinking risk level and Clinical Global Impression. It is generally well tolerated and has limited contraindications and interactions. As-needed dosage is a novel concept in the addictions field, which may overcome limitations of traditional regimens. In the pivotal trials, nalmefene was taken 52% of the days and compliance with the as-needed treatment regimen was good (above 80% of the days) in 68% of the nalmefene-treated patients. A new pharmacological approach combined with a brief psychosocial intervention for alcoholism is available and appears to be feasible, safe and efficacious.

  12. Frequency dependent thermal expansion in binary viscoelasticcomposites

    SciTech Connect

    Berryman, James G.

    2007-12-01

    The effective thermal expansion coefficient beta* of abinary viscoelastic composite is shown to be frequency dependent even ifthe thermal expansion coefficients beta A and beta B of both constituentsare themselves frequency independent. Exact calculations for binaryviscoelastic systems show that beta* is related to constituent valuesbeta A, beta B, volume fractions, and bulk moduli KA, KB, as well as tothe overall bulk modulus K* of the composite system. Then, beta* isdetermined for isotropic systems by first bounding (or measuring) K* andtherefore beta*. For anisotropic systems with hexagonal symmetry, theprincipal values of the thermal expansion beta*perp and beta*para can bedetermined exactly when the constituents form a layered system. In allthe examples studied, it is shown explicitly that the eigenvectors of thethermoviscoelastic system possess non-negative dissipation -- despite thecomplicated analytical behavior of the frequency dependent thermalexpansivities themselves. Methods presented have a variety ofapplications from fluid-fluid mixtures to fluid-solid suspensions, andfrom fluid-saturated porous media to viscoelastic solid-solidcomposites.

  13. Unconscious relational encoding depends on hippocampus

    PubMed Central

    Duss, Simone B.; Reber, Thomas P.; Hänggi, Jürgen; Schwab, Simon; Wiest, Roland; Müri, René M.; Brugger, Peter; Gutbrod, Klemens

    2014-01-01

    Textbooks divide between human memory systems based on consciousness. Hippocampus is thought to support only conscious encoding, while neocortex supports both conscious and unconscious encoding. We tested whether processing modes, not consciousness, divide between memory systems in three neuroimaging experiments with 11 amnesic patients (mean age = 45.55 years, standard deviation = 8.74, range = 23–60) and 11 matched healthy control subjects. Examined processing modes were single item versus relational encoding with only relational encoding hypothesized to depend on hippocampus. Participants encoded and later retrieved either single words or new relations between words. Consciousness of encoding was excluded by subliminal (invisible) word presentation. Amnesic patients and controls performed equally well on the single item task activating prefrontal cortex. But only the controls succeeded on the relational task activating the hippocampus, while amnesic patients failed as a group. Hence, unconscious relational encoding, but not unconscious single item encoding, depended on hippocampus. Yet, three patients performed normally on unconscious relational encoding in spite of amnesia capitalizing on spared hippocampal tissue and connections to language cortex. This pattern of results suggests that processing modes divide between memory systems, while consciousness divides between levels of function within a memory system. PMID:25273998

  14. DSSC anchoring groups: a surface dependent decision.

    PubMed

    O'Rourke, C; Bowler, D R

    2014-05-14

    Electrodes in dye sensitised solar cells are typically nanocrystalline anatase TiO2 with a majority (1 0 1) surface exposed. Generally the sensitising dye employs a carboxylic anchoring moiety through which it adheres to the TiO₂ surface. Recent interest in exploiting the properties of differing TiO₂ electrode morphologies, such as rutile nanorods exposing the (1 1 0) surface and anatase electrodes with high percentages of the (0 0 1) surface exposed, begs the question of whether this anchoring strategy is best, irrespective of the majority surface exposed. Here we address this question by presenting density functional theory calculations contrasting the binding properties of two promising anchoring groups, phosphonic acid and boronic acid, to that of carboxylic acid. Anchor-electrode interactions are studied for the prototypical anatase (1 0 1) surface, along with the anatase (0 0 1) and rutile (1 1 0) surfaces. Finally the effect of using these alternative anchoring groups to bind a typical coumarin dye (NKX-2311) to these TiO₂ substrates is examined. Significant differences in the binding properties are found depending on both the anchor and surface, illustrating that the choice of anchor is necessarily dependent upon the surface exposed in the electrode. In particular the boronic acid is found to show the potential to be an excellent anchor choice for electrodes exposing the anatase (0 0 1) surface.

  15. Sequence-dependent Internalization of Aggregating Peptides*

    PubMed Central

    Couceiro, José R.; Gallardo, Rodrigo; De Smet, Frederik; De Baets, Greet; Baatsen, Pieter; Annaert, Wim; Roose, Kenny; Saelens, Xavier; Schymkowitz, Joost; Rousseau, Frederic

    2015-01-01

    Recently, a number of aggregation disease polypeptides have been shown to spread from cell to cell, thereby displaying prionoid behavior. Studying aggregate internalization, however, is often hampered by the complex kinetics of the aggregation process, resulting in the concomitant uptake of aggregates of different sizes by competing mechanisms, which makes it difficult to isolate pathway-specific responses to aggregates. We designed synthetic aggregating peptides bearing different aggregation propensities with the aim of producing modes of uptake that are sufficiently distinct to differentially analyze the cellular response to internalization. We found that small acidic aggregates (≤500 nm in diameter) were taken up by nonspecific endocytosis as part of the fluid phase and traveled through the endosomal compartment to lysosomes. By contrast, bigger basic aggregates (>1 μm) were taken up through a mechanism dependent on cytoskeletal reorganization and membrane remodeling with the morphological hallmarks of phagocytosis. Importantly, the properties of these aggregates determined not only the mechanism of internalization but also the involvement of the proteostatic machinery (the assembly of interconnected networks that control the biogenesis, folding, trafficking, and degradation of proteins) in the process; whereas the internalization of small acidic aggregates is HSF1-independent, the uptake of larger basic aggregates was HSF1-dependent, requiring Hsp70. Our results show that the biophysical properties of aggregates determine both their mechanism of internalization and proteostatic response. It remains to be seen whether these differences in cellular response contribute to the particular role of specific aggregated proteins in disease. PMID:25391649

  16. State-dependent choice and ecological rationality.

    PubMed

    Nevai, Andrew L; Waite, Thomas A; Passino, Kevin M

    2007-08-01

    Decision makers who minimize costly errors should flexibly adjust the way they trade off competing demands, depending on their current state. We explore how state (amount of hoarded food) affects willingness to take extra predation risk to obtain larger food rewards, particularly in animals that may overemphasize safety. Assuming a sigmoid fitness function, we explore how a supplement in state influences this willingness trade danger for food energy. Above a threshold, the model predicts the supplement will weaken this willingness. Incremental increases in state in the deceleratory phase yield smaller fitness gains, so it pays to increase emphasis on safety after receiving a supplement. Below this threshold, the model makes the opposite prediction because incremental increases in state yield bigger fitness gains and so it pays to decrease emphasis on safety. We use the model to explain why hoarding gray jays (Perisoreus canadensis) were induced by an experimental subsidy to accept greater danger. This formerly puzzling finding makes sense if the jays' effective hoard was relatively small, due to theft and decomposition. We discuss adaptive state-dependent choice as a general explanation for apparently irrational behavior.

  17. Insulin-dependent diabetes and HLA.

    PubMed

    Dausset, J; Hors, J; Contu, L; Busson, M; Schmid, M; Cathelineau, G; Lestradet, H; Baron, D

    1979-12-01

    The study of a hundred and fifteen unrelated insulin-dependent diabetes and eight families with at least two insulin-dependent diabetes members made it possible to confirm the higher frequency of HLA-B8 and B18 (p less than 0.001) among patients, producing a RR of 2.24 and 2.47 respectively. The increased B15 frequency did not achieve statistical significance. B18 whose gametic association (delta = 0.0438) was significant only in diabetic patients was often related to Aw19-2 (Aw30 + Aw31). The B8/B18 genotype gave a relative risk (RR = 4.98) which was significantly higher than that of B8, B18 and B15 heterozygotes (1.50, 1.24 and 1.39 respectively). Pairs of diabetic siblings were more frequently HLA identical than would be expected by chance, and distribution of the pairs of affected sibs into the three categories, identical, semi-identical and different, was closer to the recessive model than to the dominant one. The fact that the B8/B18 individuals had a RR slightly higher than the B8 and B18 homozygotes and distinctly higher than the heterozygotes for only one of these genes, favours the hypothesis of two dominant genes, giving the appearance of recessivity. The gene associated with B18 in Southern Europe seems to play the same part as that of the gene associated with B15 in Northern Europe. PMID:398300

  18. [Cereal-dependent exercise-induced anaphylaxis].

    PubMed

    Seoane-Rodríguez, Marta; Caralli, María Elisa; Morales-Cabeza, Cristina; Micozzi, Sarah; De Barrio-Fernández, Manuel; Rojas Pérez-Ezquerra, Patricia

    2016-01-01

    Wheat-dependent exercise-induced anaphylaxis (WDEIA) is increasing. In vitro test such as omega-5-gliadin levels are useful in the diagnosis, while oral single blind challenge tests (OCT) with wheat plus exercise continuous being the gold standard diagnostic method. This paper reports the case of a 38-year-old woman, with several episodes of anaphylaxis after eating different foods and doing exercise after ingestion. An allergy study was performed with positive skin prick tests for wheat, barley and rye. Total IgE 238.0KU/L, positive specific IgE (>100KU/L) to wheat, barley and rye, and negative to rTri-a-19 omega-5 gliadin. OCT with bread and exercise was positive. In this case of wheat-dependent exerciseinduced anaphylaxis (WDEIA) with negative serum specific IgE to omega-5-gliadin, negative results with gamma, alpha, bheta y omega-gliadin doesn't exclude the diagnosis of WDEIA.

  19. Evolution of density-dependent cooperation.

    PubMed

    Seppänen, Anne; Parvinen, Kalle

    2014-12-01

    Cooperation is surprisingly common in life despite of its vulnerability to selfish cheating, i.e. defecting. Defectors do not contribute to common resources but take the advantage of cooperators' investments. Therefore, the emergence and maintenance of cooperation have been considered irrational phenomena. In this study, we focus on plastic, quantitative cooperation behaviour, especially on its evolution. We assume that individuals are capable to sense the population density in their neighbourhood and adjust their real-valued investments on public goods based on that information. The ecological setting is described with stochastic demographic events, e.g. birth and death, occurring at individual level. Individuals form small populations, which further constitute a structured metapopulation. For evolutionary investigations, we apply the adaptive dynamics framework. The cost of cooperative investment is incorporated into the model in two ways, by decreasing the birth rate or by increasing the death rate. In the first case, density-dependent cooperation evolves to be a decreasing function of population size as expected. In the latter case, however, the density-dependent cooperative investment can have a qualitatively different form as it may evolve to be highest in intermediate-sized populations. Indeed, we emphasize that some details in modelling may have a significant impact on the results obtained.

  20. Perturbative Critical Behavior from Spacetime Dependent Couplings

    SciTech Connect

    Dong, Xi; Horn, Bart; Silverstein, Eva; Torroba, Gonzalo

    2012-08-03

    We find novel perturbative fixed points by introducing mildly spacetime-dependent couplings into otherwise marginal terms. In four-dimensional QFT, these are physical analogues of the small-{epsilon} Wilson-Fisher fixed point. Rather than considering 4-{epsilon} dimensions, we stay in four dimensions but introduce couplings whose leading spacetime dependence is of the form {lambda}x{sup {kappa}}{mu}{sup {kappa}}, with a small parameter {kappa} playing a role analogous to {epsilon}. We show, in {phi}{sup 4} theory and in QED and QCD with massless flavors, that this leads to a critical theory under perturbative control over an exponentially wide window of spacetime positions x. The exact fixed point coupling {lambda}{sub *}(x) in our theory is identical to the running coupling of the translationally invariant theory, with the scale replaced by 1/x. Similar statements hold for three-dimensional {phi}{sup 6} theories and two-dimensional sigma models with curved target spaces. We also describe strongly coupled examples using conformal perturbation theory.

  1. Age-dependent decay in the landscape

    SciTech Connect

    Winitzki, Sergei

    2008-03-15

    The picture of the 'multiverse' arising in diverse cosmological scenarios involves transitions between metastable vacuum states. It was pointed out by Krauss and Dent that the transition rates decrease at very late times, leading to a dependence of the transition probability between vacua on the age of each vacuum region. I investigate the implications of this non-Markovian, age-dependent decay on the global structure of the spacetime in landscape scenarios. I show that the fractal dimension of the eternally inflating domain is precisely equal to 3, instead of being slightly below 3, which is the case in scenarios with purely Markovian, age-independent decay. I develop a complete description of a non-Markovian landscape in terms of a nonlocal master equation. Using this description I demonstrate by an explicit calculation that, under some technical assumptions about the landscape, the probabilistic predictions of our position in the landscape are essentially unchanged, regardless of the measure used to extract these predictions. I briefly discuss the physical plausibility of realizing non-Markovian vacuum decay in cosmology in view of the possible decoherence of the metastable quantum state.

  2. Nalbuphine hydrochloride dependence in anabolic steroid users.

    PubMed

    Wines, J D; Gruber, A J; Pope, H G; Lukas, S E

    1999-01-01

    Nalbuphine hydrochloride, a nonscheduled opioid agonist/antagonist analgesic, is currently approved for the treatment of pain. Recently, nalbuphine dependence was reported in three anabolic steroid users in Britain. To further document this phenomenon, we conducted interviews on eleven subjects who reported nalbuphine use. Eight subjects were clinically dependent on nalbuphine, and seven of the subjects who were asked about tolerance and withdrawal with nalbuphine acknowledged these symptoms. Eight subjects, who had never used drugs intravenously before, reported using nalbuphine by this route. Nalbuphine-related morbidity was extensive and included medical complications and psychiatric symptoms. Nalbuphine users also exhibited a high rate of comorbid Axis I disorders, including other substance misuse. Virtually all subjects described widespread nalbuphine use in the gymnasiums they frequented. These observations, together with the recent increase in nalbuphine-related articles in the lay press, suggest that nalbuphine may represent a new drug of abuse among athletes, especially those using anabolic steroids, and that nalbuphine's scheduling status may need to be re-evaluated.

  3. Epigenetic regulation of estrogen-dependent memory

    PubMed Central

    Fortress, Ashley M.; Frick, Karyn M.

    2014-01-01

    Hippocampal memory formation is highly regulated by post-translational histone modifications and DNA methylation. Accordingly, these epigenetic processes play a major role in the effects of modulatory factors, such as sex steroid hormones, on hippocampal memory. Our laboratory recently demonstrated that the ability of the potent estrogen 17β-estradiol (E2) to enhance hippocampal-dependent novel object recognition memory in ovariectomized female mice requires ERK-dependent histone H3 acetylation and DNA methylation in the dorsal hippocampus. Although these data provide valuable insight into the chromatin modifications that mediate the memory-enhancing effects of E2, epigenetic regulation of gene expression is enormously complex. Therefore, more research is needed to fully understand how E2 and other hormones employ epigenetic alterations to shape behavior. This review discusses the epigenetic alterations shown thus far to regulate hippocampal memory, briefly reviews the effects of E2 on hippocampal function, and describes in detail our work on epigenetic regulation of estrogenic memory enhancement. PMID:24878494

  4. Heating liquid dielectrics by time dependent fields

    NASA Astrophysics Data System (ADS)

    Khalife, A.; Pathak, U.; Richert, R.

    2011-10-01

    Steady state and time-resolved dielectric relaxation experiments are performed at high fields on viscous glycerol and the effects of energy absorption from the electric field are studied. Time resolution is obtained by a sinusoidal field whose amplitude is switched from a low to a high level and by recording voltage and current traces with an oscilloscope during this transition. Based on their distinct time and frequency dependences, three sources of modifying the dynamics and dielectric loss via an increase in the effective temperature can be distinguished: electrode temperature, real sample temperature, and configurational temperatures of the modes that absorbed the energy. Isothermal conditions that are desired for focusing on the configurational temperature changes (as in dielectric hole burning and related techniques) are maintained only for very thin samples and for moderate power levels. For high frequencies, say ν > 1 MHz, changes of the real temperature will exceed the effects of configurational temperatures in the case of macroscopic samples. Regarding microwave chemistry, heating via cell phone use, and related situations in which materials are subject to fields involving frequencies beyond the MHz regime, we conclude that changes in the configurational (or fictive) temperatures remain negligible compared with the increase of the real temperature. This simplifies the assessment of how time dependent electric fields modify the properties of materials.

  5. Nalmefene and its use in alcohol dependence.

    PubMed

    Gual, A; Bruguera, P; López-Pelayo, H

    2014-05-01

    Nalmefene is the first available drug approved in the E.U. to reduce alcohol use in alcohol-dependent patients. Reduction in alcohol use in heavy drinkers diminishes mortality risk and socio-economic burden. Nalmefene has shown efficacy at 6 months in alcohol-dependent patients with high or very high drinking risk levels in reducing total alcohol consumption (-7.6 g/day [95% confidence interval (CI): -11.6 to -3.5]; P = 0.0003), heavy drinking days (-2.00 days/month [95% CI: -3.00 to -1.00]; P ⟨ 0.00001) and other secondary outcome measures such as γ-glutamyl transferase, alanine aminotransferase, drinking risk level and Clinical Global Impression. It is generally well tolerated and has limited contraindications and interactions. As-needed dosage is a novel concept in the addictions field, which may overcome limitations of traditional regimens. In the pivotal trials, nalmefene was taken 52% of the days and compliance with the as-needed treatment regimen was good (above 80% of the days) in 68% of the nalmefene-treated patients. A new pharmacological approach combined with a brief psychosocial intervention for alcoholism is available and appears to be feasible, safe and efficacious. PMID:24918835

  6. Temperature dependence of BCF plastic scintillation detectors

    PubMed Central

    Wootton, Landon; Beddar, Sam

    2013-01-01

    We examined temperature dependence in plastic scintillation detectors (PSDs) made of BCF-60 or BCF-12 scintillating fiber coupled to optical fiber with cyanoacrylate. PSDs were subjected to a range of temperatures using a temperature-controlled water bath and irradiated at each temperature while either the dose was measured using a CCD camera or the spectral output was measured using a spectrometer. The spectrometer was used to examine the intensity and spectral distribution of scintillation light emitted by the PSDs, Cerenkov light generated within the PSD, and light transmitted through an isolated optical coupling. BCF-60 PSDs exhibited a 0.50% decrease and BCF-12 PSDs a 0.09% decrease in measured dose per °C increase, relative to dose measured at 22°C. Spectrometry revealed that the total intensity of the light generated by BCF-60 and BCF-12 PSDs decreased by 0.32% and 0.13%, respectively, per °C increase. The spectral distribution of the light changed slightly with temperature for both PSDs, accounting for the disparity between the change in measured dose and total light output. The generation of Cerenkov light was temperature independent. However, light transmitted through optical coupling between the scintillator and the optical fiber also exhibited temperature dependence. PMID:23574889

  7. Orientation-Dependent Handedness and Chiral Design

    NASA Astrophysics Data System (ADS)

    Efrati, Efi; Irvine, William T. M.

    2014-01-01

    Chirality occupies a central role in fields ranging from biological self-assembly to the design of optical metamaterials. The definition of chirality, as given by Lord Kelvin, associates chirality with the lack of mirror symmetry: the inability to superpose an object on its mirror image. While this definition has guided the classification of chiral objects for over a century, the quantification of handed phenomena based on this definition has proven elusive, if not impossible, as manifest in the paradox of chiral connectedness. In this work, we put forward a quantification scheme in which the handedness of an object depends on the direction in which it is viewed. While consistent with familiar chiral notions, such as the right-hand rule, this framework allows objects to be simultaneously right and left handed. We demonstrate this orientation dependence in three different systems—a biomimetic elastic bilayer, a chiral propeller, and optical metamaterial—and find quantitative agreement with chirality pseudotensors whose form we explicitly compute. The use of this approach resolves the existing paradoxes and naturally enables the design of handed metamaterials from symmetry principles.

  8. Theory of sequence-dependent DNA elasticity

    NASA Astrophysics Data System (ADS)

    Coleman, Bernard D.; Olson, Wilma K.; Swigon, David

    2003-04-01

    The elastic properties of a molecule of duplex DNA are strongly dependent on nucleotide sequence. In the theory developed here the contribution ψn of the nth base-pair step to the elastic energy is assumed to be given by a function ψ˜n of six kinematical variables, called tilt, roll, twist, shift, slide, and rise, that describe the relative orientation and displacement of the nth and (n+1)th base pairs. The sequence dependence of elastic properties is determined when one specifies the way ψ˜n depends on the nucleotides of the two base pairs of the nth step. Among the items discussed are the symmetry relations imposed on ψ˜n by the complementarity of bases, i.e., of A to T and C to G, the antiparallel nature of the DNA sugar-phosphate chains, and the requirement that ψ˜n be independent of the choice of the direction of increasing n. Variational equations of mechanical equilibrium are here derived without special assumptions about the form of the functions ψ˜n, and numerical solutions of those equations are shown for illustrative cases in which ψ˜n is, for each n, a quadratic form and the DNA forms a closed, 150 base-pair, minicircle that can be called a DNA o-ring because it has a nearly circular stress-free configuration. Examples are given of noncircular equilibrium configurations of naked DNA o-rings and of cases in which the interaction with ligands induces changes in configuration that are markedly different from those undergone by a minicircle of intrinsically straight DNA. When a minicircle of intrinsically straight DNA interacts with an intercalating agent that upon binding to DNA causes a local reduction of intrinsic twist, the configuration that minimizes elastic energy depends on the number of intercalated molecules, but is independent of the spatial distribution of those molecules along the minicircle. In contrast, it is shown here that the configuration and elastic energy of a DNA o-ring can depend strongly on the spatial distribution of

  9. Contaminant transport in soil with depth-dependent reaction coefficients and time-dependent boundary conditions.

    PubMed

    Gao, Guangyao; Fu, Bojie; Zhan, Hongbin; Ma, Ying

    2013-05-01

    Predicting the fate and movement of contaminant in soils and groundwater is essential to assess and reduce the risk of soil contamination and groundwater pollution. Reaction processes of contaminant often decreased monotonously with depth. Time-dependent input sources usually occurred at the inlet of natural or human-made system such as radioactive waste disposal site. This study presented a one-dimensional convection-dispersion equation (CDE) for contaminant transport in soils with depth-dependent reaction coefficients and time-dependent inlet boundary conditions, and derived its analytical solution. The adsorption coefficient and degradation rate were represented as sigmoidal functions of soil depth. Solute breakthrough curves (BTCs) and concentration profiles obtained from CDE with depth-dependent and constant reaction coefficients were compared, and a constant effective reaction coefficient, which was calculated by arithmetically averaging the depth-dependent reaction coefficient, was proposed to reflect the lumped depth-dependent reaction effect. With the effective adsorption coefficient and degradation rate, CDE could produce similar BTCs and concentration profiles as those from CDE with depth-dependent reactions in soils with moderate chemical heterogeneity. In contrast, the predicted concentrations of CDE with fitted reaction coefficients at a certain depth departed significantly from those of CDE with depth-dependent reactions. Parametric analysis was performed to illustrate the effects of sinusoidally and exponentially decaying input functions on solute BTCs. The BTCs and concentration profiles obtained from the solutions for finite and semi-infinite domain were compared to investigate the effects of effluent boundary condition. The finite solution produced higher concentrations at the increasing limb of the BTCs and possessed a higher peak concentration than the semi-infinite solution which had a slightly long tail. Furthermore, the finite solution gave

  10. Contaminant transport in soil with depth-dependent reaction coefficients and time-dependent boundary conditions.

    PubMed

    Gao, Guangyao; Fu, Bojie; Zhan, Hongbin; Ma, Ying

    2013-05-01

    Predicting the fate and movement of contaminant in soils and groundwater is essential to assess and reduce the risk of soil contamination and groundwater pollution. Reaction processes of contaminant often decreased monotonously with depth. Time-dependent input sources usually occurred at the inlet of natural or human-made system such as radioactive waste disposal site. This study presented a one-dimensional convection-dispersion equation (CDE) for contaminant transport in soils with depth-dependent reaction coefficients and time-dependent inlet boundary conditions, and derived its analytical solution. The adsorption coefficient and degradation rate were represented as sigmoidal functions of soil depth. Solute breakthrough curves (BTCs) and concentration profiles obtained from CDE with depth-dependent and constant reaction coefficients were compared, and a constant effective reaction coefficient, which was calculated by arithmetically averaging the depth-dependent reaction coefficient, was proposed to reflect the lumped depth-dependent reaction effect. With the effective adsorption coefficient and degradation rate, CDE could produce similar BTCs and concentration profiles as those from CDE with depth-dependent reactions in soils with moderate chemical heterogeneity. In contrast, the predicted concentrations of CDE with fitted reaction coefficients at a certain depth departed significantly from those of CDE with depth-dependent reactions. Parametric analysis was performed to illustrate the effects of sinusoidally and exponentially decaying input functions on solute BTCs. The BTCs and concentration profiles obtained from the solutions for finite and semi-infinite domain were compared to investigate the effects of effluent boundary condition. The finite solution produced higher concentrations at the increasing limb of the BTCs and possessed a higher peak concentration than the semi-infinite solution which had a slightly long tail. Furthermore, the finite solution gave

  11. The shape dependency of two-dimensional magnetic field dependence of a Josephson junction

    NASA Astrophysics Data System (ADS)

    Watanabe, Norimichi; Nakayama, Akiyoshi; Abe, Susumu; Kawai, Sho; Nishi, Yohei; Masuda, Koji

    2008-04-01

    Modulation characteristics of a Josephson current are usually measured by applying the external magnetic field parallel to the junction plane from one direction, and uniformity in tunnel barrier is discussed. So far, we have measured two-dimensional magnetic field dependence of a square Josephson junction by independently scanning the magnetic field (Hx,Hy) parallel to the junction plane from two directions. We can get a lot of information about spatial critical current distribution in a Josephson junction by observing the magnetic field dependence of a Josephson junction in two dimensions. This time, we have fabricated the different-shaped Josephson junctions and investigated the shape dependency of two-dimensional magnetic field dependence of a Josephson junction. We observed the Ic-(Hx,Hy) characteristics of triangular, hexagonal, and circular Josephson junctions quite different from the Ic-(Hx,Hy), characteristics of a square Josephson junction. Furthermore, we simulated two-dimensional magnetic field dependence of a Josephson junction by calculating the superconducting current density distribution in each magnetic field. The simulation results agreed well with experimental results.

  12. Energy dependence of the freeze out eccentricity from azimuthally-dependent HBT analyses at STAR

    NASA Astrophysics Data System (ADS)

    Anson, Christopher; STAR Collaboration

    2011-10-01

    Non-central heavy ion collisions at RHIC create an anisotropic participant zone of QCD matter under extreme conditions of energy and matter density. While this zone is initially out-of- plane-extended, pressure gradients cause the hot, dense medium to expand preferentially in plane. Over time, this expansion makes the shape more spherical, perhaps even becoming extended in the in-plane direction. The change in shape is determined by the expansion and freeze-out time scales which depend, in part, on the early pressure gradients. As a result, the freeze-out shape may provide a sensitive probe of the Equation of State of hot QCD matter. The recent RHIC Beam Energy Scan, which covered energies from √{sNN} of 7.7 to 39 GeV provides an opportunity to explore the energy dependence of the freeze out eccentricity. The new low energy data from STAR complements high statistics data sets at √{sNN} of 62.4 and 200 GeV. The dependence of the HBT radius parameters on azimuthal angle relative to the reaction plane have been extracted. These dependences can be related to the freeze out eccentricity within the context of a blast wave model. We will present STAR's most recent results from azimuthally-dependent HBT analyses across a wide range of energies.

  13. Cross-physical dependence of several drugs in methaqualone-dependent rats.

    PubMed

    Suzuki, T; Koike, Y; Chida, Y; Misawa, M

    1988-04-01

    We investigated the characteristics of physical dependence on methaqualone. Rats were made physically dependent on methaqualone by the use of the drug-admixed food (DAF) method for 33 days. Pentobarbital, barbital, ethanol and diazepam were cross-administered against methaqualone to evaluate the degree of suppression of methaqualone withdrawal signs as an index for the cross-physical dependence liability of these drugs to methaqualone. To evaluate the cross-physical dependence liability, we used AUC of body weight loss and withdrawal scores between the first cross-administration (9 hr after the withdrawal) and 27 hr after the withdrawal. AUC of weight loss was significantly suppressed by the four test drugs as compared to each control. Withdrawal scores were also significantly inhibited by the cross-administration of barbital, ethanol and diazepam. Considering that the rats given barbital or ethanol fell asleep after the cross-administration, diazepam seems to cause the strongest suppression of methaqualone withdrawal signs among the four test drugs. Thus, physical dependence on methaqualone may be similar by nature to that on benzodiazepines rather than barbiturates and alcohol.

  14. Kinetic analysis of AUC-dependent saturable clearance of liposomes: mathematical description of AUC dependency.

    PubMed

    Harashima, H; Yamane, C; Kume, Y; Kiwada, H

    1993-06-01

    The objective of this study was to examine the AUC dependency of saturable hepatic clearance (CLh) of liposomes and to postulate a mathematical model to describe the characteristics. The AUC dependency of saturable CLh was examined under intravenous rapid administration at various doses. The CLh increased with increasing blood concentration but decreased with the increase of AUC at each dose. In addition, the relationship between AUC and CLh was consistent with that observed in previously reported infusion studies. These experimental data confirm the AUC dependency of saturable CLh of liposomes. A mathematical model was developed for this AUC dependency. The decrease of CLh was described by the uptake amount (X) as follows: CLh = CLm(1-X/Xm), where CLm and Xm represent the maximum uptake clearance and the maximum uptake amount, respectively. The rate equation for uptake was analytically solved as CLh = X/AUC = Xm/AUC(1-exp(CLm/XmAUC)). Uptake clearance can be described by CLm, Xm, and AUC, and so uptake clearance is constant if AUC is constant. These experimental analyses and theoretical considerations show the validity of the AUC-dependent saturable CLh of liposomes.

  15. The cosmological dependence of cluster density profiles

    NASA Astrophysics Data System (ADS)

    Crone, Mary M.; Evrard, August E.; Richstone, Douglas O.

    1994-10-01

    We use N-body simulations to study the shape of mean cluster density and velocity profiles in the nonlinear regime formed via gravitational instability. The dependence of the final structure on both cosmology and initial density field is examined, using a grid of cosmologies and scale-free initial power spectra P(k) varies as kn. Einstein-de Sitter, open (Omega0 = 0.2 and 0.1) and flat, low density (Omega0 = 0.2 lambda0 = 0.8) models are examined, with initial spectral indices n = -2, -1 and 0. For each model, we stack clusters in an appropriately scaled manner to define an average density profile in the nonlinear regime. The profiles are well fit by a power law rho(r) varies as r-alpha for radii whereat the local density contrast is between 100 and 3000. This covers 99% of the cluster volume. We find a clear trend toward steeper slopes (larger alphas) with both increasing n and decreasing Omega0. The Omega0 dependence is partially masked by the n dependence; there is degeneracy in the values of alpha between the Einstein-de Sitter and flat, low-density cosmologies. However, the profile slopes in the open models are consistently higher than the Omega = 1 values for the range of n examined. Cluster density profiles are thus potentially useful cosmological diagnostics. We find no evidence for a constant density core in any of the models, although the density profiles do tend to flatten at small radii. Much of the flattening is due to the force softening required by the simulations. An attempt is made to recover the unsoftened profiles assuming angular momentum invariance. The recovered profiles in Einstein-de Sitter cosmologies are consistent with a pure power law up to the highest density contrasts (106) accessible with our resolution. The low-density models show significant deviation from a power law above density contrasts approximately 105. We interpret this curvature as reflecting the non-scale-invariant nature of the background cosmology in these models. These

  16. Renormalization scheme dependence with renormalization group summation

    NASA Astrophysics Data System (ADS)

    McKeon, D. G. C.

    2015-08-01

    We consider all perturbative radiative corrections to the total e+e- annihilation cross section Re+e- showing how the renormalization group (RG) equation associated with the radiatively induced mass scale μ can be used to sum the logarithmic contributions in two ways. First of all, one can sum leading-log, next-to-leading-log, etc., contributions to Re+e- using in turn the one-loop, two-loop, etc., contributions to the RG function β . A second summation shows how all logarithmic corrections to Re+e- can be expressed entirely in terms of the log-independent contributions when one employs the full β -function. Next, using Stevenson's characterization of any choice of renormalization scheme by the use of the contributions to the β -function arising beyond two-loop order, we examine the RG scheme dependence in Re+e- when using the second way of summing logarithms. The renormalization scheme invariants that arise are then related to the renormalization scheme invariants found by Stevenson. We next consider two choices of the renormalization scheme, one which can be used to express Re+e- solely in terms of two powers of a running coupling, and the second which can be used to express Re+e- as an infinite series in the two-loop running coupling (i.e., a Lambert W -function). In both cases, Re+e- is expressed solely in terms of renormalization scheme invariant parameters that are to be computed by a perturbative evaluation of Re+e-. We then establish how in general the coupling constant arising in one renormalization scheme can be expressed as a power series of the coupling arising in any other scheme. We then establish how, by using a different renormalization mass scale at each order of perturbation theory, all renormalization scheme dependence can be absorbed into these mass scales when one uses the second way of summing logarithmic corrections to Re+e-. We then employ the approach to renormalization scheme dependency that we have applied to Re+e- to a RG summed

  17. The cosmological dependence of cluster density profiles

    NASA Technical Reports Server (NTRS)

    Crone, Mary M.; Evrard, August E.; Richstone, Douglas O.

    1994-01-01

    We use N-body simulations to study the shape of mean cluster density and velocity profiles in the nonlinear regime formed via gravitational instability. The dependence of the final structure on both cosmology and initial density field is examined, using a grid of cosmologies and scale-free initial power spectra P(k) varies as k(exp n). Einstein-de Sitter, open (Omega(sub 0) = 0.2 and 0.1) and flat, low density (Omega(sub 0) = 0.2 lambda(sub 0) = 0.8) models are examined, with initial spectral indices n = -2, -1 and 0. For each model, we stack clusters in an appropriately scaled manner to define an average density profile in the nonlinear regime. The profiles are well fit by a power law rho(r) varies as r(exp -alpha) for radii whereat the local density contrast is between 100 and 3000. This covers 99% of the cluster volume. We find a clear trend toward steeper slopes (larger alphas) with both increasing n and decreasing Omega(sub 0). The Omega(sub 0) dependence is partially masked by the n dependence; there is degeneracy in the values of alpha between the Einstein-de Sitter and flat, low-density cosmologies. However, the profile slopes in the open models are consistently higher than the Omega = 1 values for the range of n examined. Cluster density profiles are thus potentially useful cosmological diagnostics. We find no evidence for a constant density core in any of the models, although the density profiles do tend to flatten at small radii. Much of the flattening is due to the force softening required by the simulations. An attempt is made to recover the unsoftened profiles assuming angular momentum invariance. The recovered profiles in Einstein-de Sitter cosmologies are consistent with a pure power law up to the highest density contrasts (10(exp 6)) accessible with our resolution. The low-density models show significant deviation from a power law above density contrasts approximately 10(exp 5). We interpret this curvature as reflecting the non

  18. Grizzly bear habitat selection is scale dependent.

    PubMed

    Ciarniello, Lana M; Boyce, Mark S; Seip, Dale R; Heard, Douglas C

    2007-07-01

    The purpose of our study is to show how ecologists' interpretation of habitat selection by grizzly bears (Ursus arctos) is altered by the scale of observation and also how management questions would be best addressed using predetermined scales of analysis. Using resource selection functions (RSF) we examined how variation in the spatial extent of availability affected our interpretation of habitat selection by grizzly bears inhabiting mountain and plateau landscapes. We estimated separate models for females and males using three spatial extents: within the study area, within the home range, and within predetermined movement buffers. We employed two methods for evaluating the effects of scale on our RSF designs. First, we chose a priori six candidate models, estimated at each scale, and ranked them using Akaike Information Criteria. Using this method, results changed among scales for males but not for females. For female bears, models that included the full suite of covariates predicted habitat use best at each scale. For male bears that resided in the mountains, models based on forest successional stages ranked highest at the study-wide and home range extents, whereas models containing covariates based on terrain features ranked highest at the buffer extent. For male bears on the plateau, each scale estimated a different highest-ranked model. Second, we examined differences among model coefficients across the three scales for one candidate model. We found that both the magnitude and direction of coefficients were dependent upon the scale examined; results varied between landscapes, scales, and sexes. Greenness, reflecting lush green vegetation, was a strong predictor of the presence of female bears in both landscapes and males that resided in the mountains. Male bears on the plateau were the only animals to select areas that exposed them to a high risk of mortality by humans. Our results show that grizzly bear habitat selection is scale dependent. Further, the

  19. Grizzly bear habitat selection is scale dependent.

    PubMed

    Ciarniello, Lana M; Boyce, Mark S; Seip, Dale R; Heard, Douglas C

    2007-07-01

    The purpose of our study is to show how ecologists' interpretation of habitat selection by grizzly bears (Ursus arctos) is altered by the scale of observation and also how management questions would be best addressed using predetermined scales of analysis. Using resource selection functions (RSF) we examined how variation in the spatial extent of availability affected our interpretation of habitat selection by grizzly bears inhabiting mountain and plateau landscapes. We estimated separate models for females and males using three spatial extents: within the study area, within the home range, and within predetermined movement buffers. We employed two methods for evaluating the effects of scale on our RSF designs. First, we chose a priori six candidate models, estimated at each scale, and ranked them using Akaike Information Criteria. Using this method, results changed among scales for males but not for females. For female bears, models that included the full suite of covariates predicted habitat use best at each scale. For male bears that resided in the mountains, models based on forest successional stages ranked highest at the study-wide and home range extents, whereas models containing covariates based on terrain features ranked highest at the buffer extent. For male bears on the plateau, each scale estimated a different highest-ranked model. Second, we examined differences among model coefficients across the three scales for one candidate model. We found that both the magnitude and direction of coefficients were dependent upon the scale examined; results varied between landscapes, scales, and sexes. Greenness, reflecting lush green vegetation, was a strong predictor of the presence of female bears in both landscapes and males that resided in the mountains. Male bears on the plateau were the only animals to select areas that exposed them to a high risk of mortality by humans. Our results show that grizzly bear habitat selection is scale dependent. Further, the

  20. Neonatal Narcotic Dependence. Report Series 29, No. 1.

    ERIC Educational Resources Information Center

    National Inst. on Drug Abuse (DHEW/PHS), Rockville, MD. National Clearinghouse for Drug Abuse Information.

    This brief report suggests that it is evident that many uncertainties still remain with regard to neonatal narcotic dependence. Discussion centers on the precise causes and symptoms of neonatal narcotic dependence, the most efficacious treatment procedures, the relative severity of heroin dependence as compared with methadone dependence in the…

  1. Local Dependence in an Operational CAT: Diagnosis and Implications

    ERIC Educational Resources Information Center

    Pommerich, Mary; Segall, Daniel O.

    2008-01-01

    The accuracy of CAT scores can be negatively affected by local dependence if the CAT utilizes parameters that are misspecified due to the presence of local dependence and/or fails to control for local dependence in responses during the administration stage. This article evaluates the existence and effect of local dependence in a test of…

  2. 38 CFR 3.250 - Dependency of parents; compensation.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Dependency of parents....250 Dependency of parents; compensation. (a) Income—(1) Conclusive dependency. Dependency of a parent... not exceed: (i) $400 for a mother or father not living together; (ii) $660 for a mother and father,...

  3. Bayesian Network Models for Local Dependence among Observable Outcome Variables

    ERIC Educational Resources Information Center

    Almond, Russell G.; Mulder, Joris; Hemat, Lisa A.; Yan, Duanli

    2009-01-01

    Bayesian network models offer a large degree of flexibility for modeling dependence among observables (item outcome variables) from the same task, which may be dependent. This article explores four design patterns for modeling locally dependent observations: (a) no context--ignores dependence among observables; (b) compensatory context--introduces…

  4. Sleep-Dependent Memory Consolidation in Children.

    PubMed

    Maski, Kiran P

    2015-06-01

    In the past 30 years, much research has been conducted elucidating the role of sleep in memory and learning; however, the interaction between sleep and cognitive functioning may be unknown in clinical realms. This article serves to provide a primer on sleep-dependent memory consolidation, a process in which memory is stabilized or even enhanced over a period of sleep. Given the increased amounts of sleep needed in infancy and childhood, the link between sleep and neuronal plasticity is highlighted in this article. Furthermore, sleep disruptions are common to children with neurodevelopmental disorders such as attention-deficit hyperactivity disorder; thus, recent studies showing direct relationships between sleep and memory functioning in such vulnerable groups are discussed. PMID:26072343

  5. Energy-dependent cell cohesion in myxobacteria.

    PubMed

    Gilmore, D F; White, D

    1985-01-01

    Cohesion in the myxobacterium Stigmatella aurantiaca was characterized. Two classes of cohesion were revealed, termed class A and class B. Class A cohesion is a characteristic of vegetative cells grown in tryptone or casitone (Difco Laboratories, Detroit, Mich.), whereas class B cohesion requires the addition of calcium ion for induction. Class A cohesion occurs in the presence of any cation and is temperature independent. Class B cohesion requires the presence of a cation in the calcium group and is energy dependent. We conclude that S. aurantiaca responds to calcium ion by synthesizing the molecular components of a system of cell cohesion (class B) and that the functioning of this system requires the expenditure of metabolic energy.

  6. Source distribution dependent scatter correction for PVI

    SciTech Connect

    Barney, J.S.; Harrop, R.; Dykstra, C.J. . School of Computing Science TRIUMF, Vancouver, British Columbia )

    1993-08-01

    Source distribution dependent scatter correction methods which incorporate different amounts of information about the source position and material distribution have been developed and tested. The techniques use image to projection integral transformation incorporating varying degrees of information on the distribution of scattering material, or convolution subtraction methods, with some information about the scattering material included in one of the convolution methods. To test the techniques, the authors apply them to data generated by Monte Carlo simulations which use geometric shapes or a voxelized density map to model the scattering material. Source position and material distribution have been found to have some effect on scatter correction. An image to projection method which incorporates a density map produces accurate scatter correction but is computationally expensive. Simpler methods, both image to projection and convolution, can also provide effective scatter correction.

  7. Supernumerary teeth vary depending on gender.

    PubMed

    Küchler, Erika Calvano; Costa, Adriana Gomes da; Costa, Marcelo de Castro; Vieira, Alexandre Rezende; Granjeiro, José Mauro

    2011-01-01

    The presence of supernumerary teeth (ST) is a dental developmental anomaly of patterning and morphogenesis. Its variability of morphology, location and developmental timing can shed light on its etiology. In this work we report ST patterns. Orthopantomograms of 1,166 pediatric subjects were examined and the morphology, location and timing of the formation of ST were determined. The frequency of supernumerary teeth in the studied population was 2.3% (n = 27). Twenty-five subjects presented one ST. Maxilla midline was the most commonly affected region (nine cases). We noted high incidence of conical morphology in the midline region. Only teeth with tuberculate morphology presented delayed formation. ST in the midline region occurred more often in males whereas ST in the incisor region were more common in females. In conclusion, ST patterns vary depending on gender. PMID:21359454

  8. Patterns of density dependence in measles dynamics.

    PubMed Central

    Finkenstädt, B; Keeling, M; Grenfell, B

    1998-01-01

    An important question in metapopulation dynamics is the influence of external perturbations on the population's long-term dynamic behaviour. In this paper we address the question of how spatiotemporal variations in demographic parameters affect the dynamics of measles populations in England and Wales. Specifically, we use nonparametric statistical methods to analyse how birth rate and population size modulate the negative density dependence between successive epidemics as well as their periodicity. For the observed spatiotemporal data from 60 cities, and for simulated model data, the demographic variables act as bifurcation parameters on the joint density of the trade-off between successive epidemics. For increasing population size, a transition occurs from an irregular unpredictable pattern in small communities towards a regular, predictable endemic pattern in large places. Variations in the birth rate parameter lead to a bifurcation from annual towards biennial cyclicity in both observed data and model data. PMID:9628034

  9. Pseudospectral time-dependent density functional theory

    NASA Astrophysics Data System (ADS)

    Ko, Chaehyuk; Malick, David K.; Braden, Dale A.; Friesner, Richard A.; Martínez, Todd J.

    2008-03-01

    Time-dependent density functional theory (TDDFT) is implemented within the Tamm-Dancoff approximation (TDA) using a pseudospectral approach to evaluate two-electron repulsion integrals. The pseudospectral approximation uses a split representation with both spectral basis functions and a physical space grid to achieve a reduction in the scaling behavior of electronic structure methods. We demonstrate here that exceptionally sparse grids may be used in the excitation energy calculation, following earlier work employing the pseudospectral approximation for determining correlation energies in wavefunction-based methods with similar conclusions. The pseudospectral TDA-TDDFT method is shown to be up to ten times faster than a conventional algorithm for hybrid functionals without sacrificing chemical accuracy.

  10. Concentration Dependent Structure of Block Copolymer Solutions

    NASA Astrophysics Data System (ADS)

    Choi, Soohyung; Bates, Frank S.; Lodge, Timothy P.

    2015-03-01

    Addition of solvent molecules into block copolymer can induce additional interactions between the solvent and both blocks, and therefore expands the range of accessible self-assembled morphologies. In particular, the distribution of solvent molecules plays a key role in determining the microstructure and its characteristic domain spacing. In this study, concentration dependent structures formed by poly(styrene-b-ethylene-alt-propylene) (PS-PEP) solution in squalane are investigated using small-angle X-ray scattering. This reveals that squalane is essentially completely segregated into the PEP domains. In addition, the conformation of the PS block changes from stretched to nearly fully relaxed (i.e., Gaussian conformation) as amounts of squalane increases. NRF

  11. Time-dependent landslide probability mapping

    USGS Publications Warehouse

    Campbell, Russell H.; Bernknopf, Richard L.; ,

    1993-01-01

    Case studies where time of failure is known for rainfall-triggered debris flows can be used to estimate the parameters of a hazard model in which the probability of failure is a function of time. As an example, a time-dependent function for the conditional probability of a soil slip is estimated from independent variables representing hillside morphology, approximations of material properties, and the duration and rate of rainfall. If probabilities are calculated in a GIS (geomorphic information system ) environment, the spatial distribution of the result for any given hour can be displayed on a map. Although the probability levels in this example are uncalibrated, the method offers a potential for evaluating different physical models and different earth-science variables by comparing the map distribution of predicted probabilities with inventory maps for different areas and different storms. If linked with spatial and temporal socio-economic variables, this method could be used for short-term risk assessment.

  12. Stimuli dependent impedance of conductive magnetorheological elastomers

    NASA Astrophysics Data System (ADS)

    Wang, Yu; Xuan, Shouhu; Dong, Bo; Xu, Feng; Gong, Xinglong

    2016-02-01

    The structure dependent impedance of conductive magnetorheological elastomers (MREs) under different loads and magnetic fields has been studied in this work. By increasing the weight fraction of iron particles, the conductivity of the MREs increased. Dynamic mechanical measurements and synchrotron radiation x-ray computed tomography (SR-CT) were used and they provided reasons for the electrical properties changing significantly under pressure and magnetic field stimulation. The high sensitivity of MREs to external stimuli renders them suitable for application in force or magnetic field sensors. The equivalent circuit model was proposed to analyze the impedance response of MREs and it fits the experimental results very well. Each circuit component reflected the change of the inner interface under different conditions, thus relative changes in the microstructure could be distinguished. This method could be used not only to detect the structural changes in the MRE but also to provide a great deal of valuable information for the further understanding of the MR mechanism.

  13. Rate dependency, behavioral mechanisms, and behavioral pharmacology.

    PubMed

    Branch, M N

    1984-11-01

    Behavioral pharmacology has become increasingly independent of the experimental analysis of behavior. At its beginning, behavioral pharmacology was closely related to the experimental analysis of behavior, with developments in each field aiding the other. Early attempts to systematize data in behavioral pharmacology culminated with the development of the rate-dependency concept, but as this principle was found to have more limited generality than originally was hoped, a theoretical void developed. This circumstance was followed by increased reliance on pharmacological theory as a basis for experimentation and interpretation, with an attendant decrease in emphasis on environmental variables and behavioral interpretations. Lack of interplay between behavioral pharmacology and the experimental analysis of behavior is detrimental to both disciplines because each could contribute significantly to the other. The current trend might be reversed if more research were directed at elucidating behavioral mechanisms of drug action.

  14. Frequency-dependent numerical dynamics in mosquitofish.

    PubMed Central

    Horth, Lisa; Travis, Joseph

    2002-01-01

    Altering the genetic composition of a population can alter several aspects of its numerical dynamics. Whether natural populations routinely contain the genetic variation capable of affecting the stability of those dynamics is less clear. Here we report a study of experimental populations of mosquitofish (Gambusia holbrooki), designed to examine this issue. The experiment examined the numerical effects of varying the initial relative frequency of a rare male genotype. A higher relative frequency of the rare, melanic genotype produced higher mortality rates in melanic males, higher mortality rates in females, higher juvenile abundance, and fewer fluctuations in the numbers of females across time. This work demonstrates that a natural population can harbour genetic variants in a single gender that are capable of inducing qualitative differences in the numerical dynamics of the opposite gender, through the effects of negative frequency-dependent selection. PMID:12427317

  15. NAD + -dependent Formate Dehydrogenase from Plants

    PubMed Central

    Alekseeva, A.A.; Savin, S.S.; Tishkov, V.I.

    2011-01-01

    NAD+-dependent formate dehydrogenase (FDH, EC 1.2.1.2) widely occurs in nature. FDH consists of two identical subunits and contains neither prosthetic groups nor metal ions. This type of FDH was found in different microorganisms (including pathogenic ones), such as bacteria, yeasts, fungi, and plants. As opposed to microbiological FDHs functioning in cytoplasm, plant FDHs localize in mitochondria. Formate dehydrogenase activity was first discovered as early as in 1921 in plant; however, until the past decade FDHs from plants had been considerably less studied than the enzymes from microorganisms. This review summarizes the recent results on studying the physiological role, properties, structure, and protein engineering of plant formate dehydrogenases. PMID:22649703

  16. View-Dependent Streamline Deformation and Exploration

    PubMed Central

    Tong, Xin; Edwards, John; Chen, Chun-Ming; Shen, Han-Wei; Johnson, Chris R.; Wong, Pak Chung

    2016-01-01

    Occlusion presents a major challenge in visualizing 3D flow and tensor fields using streamlines. Displaying too many streamlines creates a dense visualization filled with occluded structures, but displaying too few streams risks losing important features. We propose a new streamline exploration approach by visually manipulating the cluttered streamlines by pulling visible layers apart and revealing the hidden structures underneath. This paper presents a customized view-dependent deformation algorithm and an interactive visualization tool to minimize visual clutter in 3D vector and tensor fields. The algorithm is able to maintain the overall integrity of the fields and expose previously hidden structures. Our system supports both mouse and direct-touch interactions to manipulate the viewing perspectives and visualize the streamlines in depth. By using a lens metaphor of different shapes to select the transition zone of the targeted area interactively, the users can move their focus and examine the vector or tensor field freely. PMID:26600061

  17. Substance dependency among homeless American Indians.

    PubMed

    Lobo, Susan; Vaughan, Margaret Mortensen

    2003-01-01

    Extensive qualitative research in the San Francisco Bay Area in California and in Tucson, Arizona, indicates strong associations between substance abuse and homelessness among American Indians. This article takes a comparative approach to describe and analyze precipitating factors and survival patterns of those who are both homeless and who suffer from substance dependency. Possible precipitating factors presented through case studies consider the complex interaction of childhood fostering or adoption into non-Native families, different types of involuntary institutionalization during youth, and the personal impact of accident, trauma and loss. Coping strategies and keys to survival are examined, including the role of the extended family and close friendships, American Indian and mainstream organizations that offer formal and informal services, the existence of anchor or key households, the helping relationships and sobriety groups among homeless individuals, spirituality, and cultural resiliency.

  18. The contact area dependent interfacial thermal conductance

    SciTech Connect

    Liu, Chenhan; Wei, Zhiyong; Bi, Kedong; Yang, Juekuan; Chen, Yunfei; Wang, Jian

    2015-12-15

    The effects of the contact area on the interfacial thermal conductance σ are investigated using the atomic Green’s function method. Different from the prediction of the heat diffusion transport model, we obtain an interesting result that the interfacial thermal conductance per unit area Λ is positively dependent on the contact area as the area varies from a few atoms to several square nanometers. Through calculating the phonon transmission function, it is uncovered that the phonon transmission per unit area increases with the increased contact area. This is attributed to that each atom has more neighboring atoms in the counterpart of the interface with the increased contact area, which provides more channels for phonon transport.

  19. Driving and insulin-dependent diabetes.

    PubMed

    Frier, B M; Matthews, D M; Steel, J M; Duncan, L J

    1980-06-01

    A survey of 250 patients with insulin-dependent diabetes (IDD) holding a full motor vehicle driving licence revealed that 107 (42.8%) had not declared IDD on their application for a driving licence. 70 of these (28% of entire group) claimed that they were unaware of the statutory requirements. There was no difference in the declaration-rate between men and women. 159 patients (66%) declared IDD for their motor insurance. 86 patients (34.4%) had had severe or frequent hypoglycaemia in the preceding six months, during which they had been driving regularly. 34 patients (13.6%) admitted involvement in a driving accident since commencing treatment with insulin, and 13 of these patients were aware that hypoglycaemia had been an important causal factor. The prevalence of diabetic retinopathy and cataracts was considerable, but few patients (2.4%) had severe impairment of vision in both eyes. PMID:6104046

  20. SPOTing Acetyl-Lysine Dependent Interactions.

    PubMed

    Picaud, Sarah; Filippakopoulos, Panagis

    2015-08-17

    Post translational modifications have been recognized as chemical signals that create docking sites for evolutionary conserved effector modules, allowing for signal integration within large networks of interactions. Lysine acetylation in particular has attracted attention as a regulatory modification, affecting chromatin structure and linking to transcriptional activation. Advances in peptide array technologies have facilitated the study of acetyl-lysine-containing linear motifs interacting with the evolutionary conserved bromodomain module, which specifically recognizes and binds to acetylated sequences in histones and other proteins. Here we summarize recent work employing SPOT peptide technology to identify acetyl-lysine dependent interactions and document the protocols adapted in our lab, as well as our efforts to characterize such bromodomain-histone interactions. Our results highlight the versatility of SPOT methods and establish an affordable tool for rapid access to potential protein/modified-peptide interactions involving lysine acetylation.