Science.gov

Sample records for 11c fluence build-up

  1. Electron-Cloud Build-Up: Summary

    SciTech Connect

    Furman, M.A.

    2007-06-18

    I present a summary of topics relevant to the electron-cloud build-up and dissipation that were presented at the International Workshop on Electron-Cloud Effects 'ECLOUD 07' (Daegu, S. Korea, April 9-12, 2007). This summary is not meant to be a comprehensive review of the talks. Rather, I focus on those developments that I found, in my personal opinion, especially interesting. The contributions, all excellent, are posted in http://chep.knu.ac.kr/ecloud07/.

  2. Understanding nutrient build-up on urban road surfaces.

    PubMed

    Miguntanna, Nandika Prasadani; Goonetilleke, Ashantha; Egodowatta, Prasanna; Kokot, Serge

    2010-01-01

    This article discusses the outcomes of a research project on nutrients build-up on urban road surfaces. Nutrient build-up was investigated on road sites belonging to residential, industrial and commercial land use. Collected build-up samples were separated into five particle size ranges and were tested for total nitrogen (TN), total phosphorus (TP) and sub species of nutrients, namely, NO2-, NO3-, TKN and PO4(3-). Multivariate analytical techniques were used to analyse the data and to develop detailed understanding on buildup. Data analysis revealed that the solids loads on urban road surfaces are highly influenced by factors such as land use, antecedent dry period and traffic volume. However, the nutrient build-up process was found to be independent of the type of land use. It was solely dependent on the particle size of solids build-up. Most of the nutrients were associated with the particle size range < 150 microm. Therefore, the removal of particles below 150 microm from road surfaces is of importance for the removal of nitrogen and phosphorus from road surface solids build-up. It is also important to consider the difference in the composition of nitrogen and phosphorus build-up in the context of designing effective stormwater quality mitigation strategies.

  3. E-Cloud Build-up in Grooved Chambers

    SciTech Connect

    Venturini, Marco

    2007-05-01

    We simulate electron cloud build-up in a grooved vacuumchamber including the effect of space charge from the electrons. Weidentify conditions for e-cloud suppression and make contact withprevious estimates of an effective secondary electron yield for groovedsurfaces.

  4. Atomic Oxygen Fluence Monitor

    NASA Technical Reports Server (NTRS)

    Banks, Bruce A.

    2011-01-01

    This innovation enables a means for actively measuring atomic oxygen fluence (accumulated atoms of atomic oxygen per area) that has impinged upon spacecraft surfaces. Telemetered data from the device provides spacecraft designers, researchers, and mission managers with real-time measurement of atomic oxygen fluence, which is useful for prediction of the durability of spacecraft materials and components. The innovation is a compact fluence measuring device that allows in-space measurement and transmittance of measured atomic oxygen fluence as a function of time based on atomic oxygen erosion yields (the erosion yield of a material is the volume of material that is oxidized per incident oxygen atom) of materials that have been measured in low Earth orbit. It has a linear electrical response to atomic oxygen fluence, and is capable of measuring high atomic oxygen fluences (up to >10(exp 22) atoms/sq cm), which are representative of multi-year low-Earth orbital missions (such as the International Space Station). The durability or remaining structural lifetime of solar arrays that consist of polymer blankets on which the solar cells are attached can be predicted if one knows the atomic oxygen fluence that the solar array blanket has been exposed to. In addition, numerous organizations that launch space experiments into low-Earth orbit want to know the accumulated atomic oxygen fluence that their materials or components have been exposed to. The device is based on the erosion yield of pyrolytic graphite. It uses two 12deg inclined wedges of graphite that are over a grit-blasted fused silica window covering a photodiode. As the wedges erode, a greater area of solar illumination reaches the photodiode. A reference photodiode is also used that receives unobstructed solar illumination and is oriented in the same direction as the pyrolytic graphite covered photodiode. The short-circuit current from the photodiodes is measured and either sent to an onboard data logger, or

  5. Characterising metal build-up on urban road surfaces.

    PubMed

    Egodawatta, Prasanna; Ziyath, Abdul M; Goonetilleke, Ashantha

    2013-05-01

    Reliable approaches for predicting pollutant build-up are essential for accurate urban stormwater quality modelling. Based on the in-depth investigation of metal build-up on residential road surfaces, this paper presents empirical models for predicting metal loads on these surfaces. The study investigated metals commonly present in the urban environment. Analysis undertaken found that the build-up process for metals primarily originating from anthropogenic (copper and zinc) and geogenic (aluminium, calcium, iron and manganese) sources were different. Chromium and nickel were below detection limits. Lead was primarily associated with geogenic sources, but also exhibited a significant relationship with anthropogenic sources. The empirical prediction models developed were validated using an independent data set and found to have relative prediction errors of 12-50%, which is generally acceptable for complex systems such as urban road surfaces. Also, the predicted values were very close to the observed values and well within 95% prediction interval. PMID:23416742

  6. Wear and hardness of different core build-up materials.

    PubMed

    Schmage, Petra; Nergiz, Ibrahim; Sito, Fekry; Platzer, Ursula; Rosentritt, Martin

    2009-10-01

    Before crown preparation, teeth with extensive coronal destructions are built up with core materials. Sometimes, these build ups are exposed to the oral environment without the protection of crowns. Therefore, this in vitro investigation was aimed at evaluating the wear, surface roughness, Vickers hardness, and surface structure of 10 core composites, two glass ionomer cements (GICs), and four posterior restoration composites. The three-body wear was tested after water storage and 2,00,000 cycles. We measured both surface roughness and Vickers hardness (DIN 50133) and evaluated the surface structures by scanning electron microscopy. Results were statistically analyzed by use of the Mann-Whitney U test (alpha = 0.05). Lowest wear was found for the restorative composites (20 microm Grandio; others about 40 microm). A comparison of the composites Build-It, Chroma Core, Rebilda LC, and Rebilda DC to Quixfil showed similar wear values for each material (43-50 microm). Wear values of GICs and all others core composites ranged between 58 and 75 microm. Only Ti-Core showed significantly higher wear than all other materials (p < 0.05). All core materials except Ti-Core (35 HV) showed Vickers hardness values between 42 and 61 HV. Most core composites, particularly Build-It, Multicore Flow, Rebilda LC, Ecusit, and Tetric Evo Ceram, showed more homogenous surface structures compared to GICs and restorative composites. Therefore, wear values of core build-up materials not only differed widely but were higher than those of conventional restorative materials; yet, core build-up materials showed advantageous surface structures.

  7. Progressive Fracture of Fiber Composite Build-Up Structures

    NASA Technical Reports Server (NTRS)

    Gotsis, Pascal K.; Chamis, C. C.; Minnetyan, Levon

    1997-01-01

    Damage progression and fracture of built-up composite structures is evaluated by using computational simulation. The objective is to examine the behavior and response of a stiffened composite (0/ +/- 45/90)(sub s6) laminate panel by simulating the damage initiation, growth, accumulation, progression and propagation to structural collapse. An integrated computer code, CODSTRAN, was augmented for the simulation of the progressive damage and fracture of built-up composite structures under mechanical loading. Results show that damage initiation and progression have significant effect on the structural response. Influence of the type of loading is investigated on the damage initiation, propagation and final fracture of the build-up composite panel.

  8. Electron Cloud Build-up Study for DAFNE

    SciTech Connect

    Vaccarezza, C.; Cimino, R.; Drago, A.; Zobov, M.; Bellodi, G.; Schulte, D.; Zimmermann, F.; Rumolo, G.; Ohmi, K.; Pivi, M.; /SLAC

    2005-05-27

    After the first experimental observations compatible with the presence of the e-cloud effect in the DAFNE positron ring, a more systematic study has been performed regarding the e-cloud build-up. The measured field map of the magnetic field has been taken into account in the simulation for elements present in the four 10 m long bending sections, representing 40% of the whole positron ring. The obtained simulation results are presented together with the recent experimental observations performed on the vacuum behavior of the positron ring.

  9. Automated radiochemical synthesis and biodistribution of [11C]l-α-acetylmethadol ([11C]LAAM)

    PubMed Central

    Sai, Kiran Kumar Solingapuram; Fan, Jinda; Tu, Zhude; Zerkel, Patrick; Mach, Robert H.; Kharasch, Evan D.

    2015-01-01

    Long-acting opioid agonists methadone and l-α-acetylmethadol (LAAM) prevent withdrawal in opioid-dependent persons. Attempts to synthesize [11C]-methadone for PET evaluation of brain disposition were unsuccessful. Owing, however, to structural and pharmacologic similarities, we aimed to develop [11C]LAAM as a PET ligand to probe the brain exposure of long-lasting opioids in humans. This manuscript describes [11C]LAAM synthesis and its biodistribution in mice. The radiochemical synthetic strategy afforded high radiochemical yield, purity and specific activity, thereby making the synthesis adaptable to automated modules. PMID:24935116

  10. Flammable gas cloud build up in a ventilated enclosure.

    PubMed

    Ivings, M J; Gant, S E; Saunders, C J; Pocock, D J

    2010-12-15

    Ventilation is frequently used as a means for preventing the build up of flammable or toxic gases in enclosed spaces. The effectiveness of the ventilation often has to be considered as part of a safety case or risk assessment. In this paper methods for assessing ventilation effectiveness for hazardous area classification are examined. The analysis uses data produced from Computational Fluid Dynamics (CFD) simulations of low-pressure jet releases of flammable gas in a ventilated enclosure. The CFD model is validated against experimental measurements of gas releases in a ventilation-controlled test chamber. Good agreement is found between the model predictions and the experimental data. Analysis of the CFD results shows that the flammable gas cloud volume resulting from a leak is largely dependent on the mass release rate of flammable gas and the ventilation rate of the enclosure. The effectiveness of the ventilation for preventing the build up of flammable gas can therefore be assessed by considering the average gas concentration at the enclosure outlet(s). It is found that the ventilation rate of the enclosure provides a more useful measure of ventilation effectiveness than considering the enclosure air change rate.

  11. Flammable gas cloud build up in a ventilated enclosure.

    PubMed

    Ivings, M J; Gant, S E; Saunders, C J; Pocock, D J

    2010-12-15

    Ventilation is frequently used as a means for preventing the build up of flammable or toxic gases in enclosed spaces. The effectiveness of the ventilation often has to be considered as part of a safety case or risk assessment. In this paper methods for assessing ventilation effectiveness for hazardous area classification are examined. The analysis uses data produced from Computational Fluid Dynamics (CFD) simulations of low-pressure jet releases of flammable gas in a ventilated enclosure. The CFD model is validated against experimental measurements of gas releases in a ventilation-controlled test chamber. Good agreement is found between the model predictions and the experimental data. Analysis of the CFD results shows that the flammable gas cloud volume resulting from a leak is largely dependent on the mass release rate of flammable gas and the ventilation rate of the enclosure. The effectiveness of the ventilation for preventing the build up of flammable gas can therefore be assessed by considering the average gas concentration at the enclosure outlet(s). It is found that the ventilation rate of the enclosure provides a more useful measure of ventilation effectiveness than considering the enclosure air change rate. PMID:20855156

  12. Electron-Cloud Build-Up: Theory and Data

    SciTech Connect

    Furman, M. A.

    2010-10-08

    We present a broad-brush survey of the phenomenology, history and importance of the electron-cloud effect (ECE). We briefly discuss the simulation techniques used to quantify the electron-cloud (EC) dynamics. Finally, we present in more detail an effective theory to describe the EC density build-up in terms of a few effective parameters. For further details, the reader is encouraged to refer to the proceedings of many prior workshops, either dedicated to EC or with significant EC contents, including the entire 'ECLOUD' series. In addition, the proceedings of the various flavors of Particle Accelerator Conferences contain a large number of EC-related publications. The ICFA Beam Dynamics Newsletter series contains one dedicated issue, and several occasional articles, on EC. An extensive reference database is the LHC website on EC.

  13. Preflare energy build-up in a filament circuit

    NASA Technical Reports Server (NTRS)

    Martens, P. C. H.

    1987-01-01

    The May 16, 1981 flare observed at Debrecen is studied by extending to a fully three-dimensional model the two-dimensional Van Tend and Kuperus (1978) scenario for preflare energy build-up. It is shown that there are 10 to the 33rd ergs of free energy available to explain the subsequent large two-ribbon flare. As a result of the three-dimensional character of the present model, this estimate is an order of magnitude larger than that made by Van Tend. It is confirmed that the global form of the preflare circuit is highly important in determining the amount of energy stored in the preflare configuration. The present model gives correct predictions for the independently observed photospheric flow velocity and current strength in filaments.

  14. Progressive Fracture of Fiber Composite Build-Up Structures

    NASA Technical Reports Server (NTRS)

    Minnetyan, Levon; Gotsis, Pascal K.; Chamis, C. C.

    1997-01-01

    Damage progression and fracture of built-up composite structures is evaluated by using computational simulation. The objective is to examine the behavior and response of a stiffened composite (0 +/-45/90)(sub s6) laminate panel by simulating the damage initiation, growth, accumulation, progression and propagation to structural collapse. An integrated computer code CODSTRAN was augmented for the simulation of the progressive damage and fracture of built-up composite structures under mechanical loading. Results show that damage initiation and progression to have significant effect on the structural response. Influence of the type of loading is investigated on the damage initiation, propagation and final fracture of the build-up composite panel.

  15. Temperature rise and Heat build up inside a parked Car

    NASA Astrophysics Data System (ADS)

    Coady, Rose; Maheswaranathan, Ponn

    2001-11-01

    We have studied the heat build up inside a parked car under the hot summer Sun. Inside and outside temperatures were monitored every ten seconds from 9 AM to about 4 PM for a 2000 Toyota Camry parked in a Winthrop University parking lot without any shades or trees. Two PASCO temperature sensors, one inside the car and the other outside the car, are used along with PASCO-750 interface to collect the data. Data were collected under the following conditions while keeping track of the outside weather: fully closed windows, slightly open windows, half way open windows, fully open windows, and with window shades inside and outside. Inside temperatures reached as high as 150 degrees Fahrenheit on a sunny day with outside high temperature of about 100 degrees Fahrenheit. These results will be presented along with results from car cover and window tint manufacturers and suggestions to keep your car cool next time you park it under the Sun.

  16. 1-.sup.11 C-D-Glucose and related compounds

    DOEpatents

    Shiue, Chyng-Yann; Wolf, Alfred P.

    1984-03-27

    The novel compounds 1-.sup.11 C-D-glucose, 1-.sup.11 C-D-mannose, 1-.sup.11 C-D-galactose, 2-.sup.11 C-D-glucose, 2-.sup.11 C-D-mannose and 2-.sup.11 C-D-galactose which can be used in nuclear medicine to monitor the metabolism of glucose and galactose can be rapidly prepared by reaction of the appropriate aldose substrate with an alkali metal .sup.11 C-labeled cyanide followed by reduction with a Raney alloy in formic acid.

  17. 1-/sup 11/C-D-glucose and related compounds

    SciTech Connect

    Shiue, C.Y.; Wolf, A.P.

    1982-01-26

    The novel compounds 1-/sup 11/C-D-glucose, 1-/sup 11/C-D-mannose, 1-/sup 11/C-D-galactose, 2-/sup 11/C-D-glucose, 2-/sup 11/C-D-mannose and 2-/sup 11/C-D-galactose which can be used in nuclear medicine to monitor the metabolism of glucose and galactose can be rapidly prepared by reaction of the appropriate aldose substrate with an alkali metal /sup 11/C-labeled cyanide followed by reduction with a Raney alloy in formic acid.

  18. Inductive Flux Build-Up of RMF Formed FRCs

    NASA Astrophysics Data System (ADS)

    Hoffman, Alan; Milroy, Richard

    2004-11-01

    Slow formation of high beta plasmas, such as FRCs, is difficult due to the need to build up plasma pressure rapidly enough to balance the dominant poloidal field pressure. Slow formation was attempted in the Coaxial Slow Source (CSS) device where 4-turn inner and outer coils were used to explore slower formation options, but it was not possible to operate at low enough densities to avoid radiative collapse.^1 FRCs have also been formed slowly at relatively low pressures and magnetic fields using Rotating Magnetic Fields (RMF), but it has also been difficult to overcome radiation barriers and achieve high temperatures due to relatively low power inputs.^2 We have performed calculations that show FRCs could be formed using RMF, and then augmented in flux and energy using the inductive input from a CSS type internal coil. With correct tailoring of the coil current profiles, the FRC could then be translated off the central coil. This methodology should be capable of producing hot, high flux FRCs using slow, low voltage technology. ^1 Z.A. Pietrzyk, et. al., Nuclear Fusion 27, 1478 (1987). ^2 H.Y. Guo, et. al., Phys. Plasmas 9, 185 (2002).

  19. Understanding the build-up of SMBH and Galaxies

    NASA Astrophysics Data System (ADS)

    Carrera, Francisco; Georgakakis, Antonis; Ueda, Yoshihiro; Akylas, Thanassis; Lanzuisi, Giorgio; Castello, N.

    2015-09-01

    . The excellent survey capabilities of Athena/WFI (effective area, angular resolution, field of view) will allow to measure the incidence of feedback in the shape of warm absorbers and Ultra Fast Outflows among the general population of AGN, as well as to complete the census of black hole growth by detecting and characterising significant samples of the most heavily obscured (including Compton thick) AGN, to redshifts z~3-4. The outstanding spectral throughput and resolution of Athena/X-IFU will permit measuring the energetics of those outflows to assess their influence on their host galaxies. The demographics of the heavily obscured and outflowing populations relative to their hosts are fundamental for understanding how major black hole growth events relate to the build-up of galaxies.

  20. Synthesis of Diverse (11)C-Labeled PET Radiotracers via Direct Incorporation of [(11)C]CO2.

    PubMed

    Mossine, Andrew V; Brooks, Allen F; Jackson, Isaac M; Quesada, Carole A; Sherman, Phillip; Cole, Erin L; Donnelly, David J; Scott, Peter J H; Shao, Xia

    2016-05-18

    Three new positron emission tomography (PET) radiotracers of interest to our functional neuroimaging and translational oncology programs have been prepared through new developments in [(11)C]CO2 fixation chemistry. [(11)C]QZ (glutaminyl cyclase) was prepared via a tandem trapping of [(11)C]CO2/intramolecular cyclization; [(11)C]tideglusib (glycogen synthase kinase-3) was synthesized through a tandem trapping of [(11)C]CO2 followed by an intermolecular cycloaddition between a [(11)C]isocyanate and an isothiocyanate to form the 1,2,4-thiadiazolidine-3,5-dione core; [(11)C]ibrutinib (Bruton's tyrosine kinase) was synthesized through a HATU peptide coupling of an amino precursor with [(11)C]acrylic acid (generated from [(11)C]CO2 fixation with vinylmagnesium bromide). All radiochemical syntheses are fully automated on commercial radiochemical synthesis modules and provide radiotracers in 1-5% radiochemical yield (noncorrected, based upon [(11)C]CO2). All three radiotracers have advanced to rodent imaging studies and preliminary PET imaging results are also reported. PMID:27043721

  1. Synthesis of Diverse (11)C-Labeled PET Radiotracers via Direct Incorporation of [(11)C]CO2.

    PubMed

    Mossine, Andrew V; Brooks, Allen F; Jackson, Isaac M; Quesada, Carole A; Sherman, Phillip; Cole, Erin L; Donnelly, David J; Scott, Peter J H; Shao, Xia

    2016-05-18

    Three new positron emission tomography (PET) radiotracers of interest to our functional neuroimaging and translational oncology programs have been prepared through new developments in [(11)C]CO2 fixation chemistry. [(11)C]QZ (glutaminyl cyclase) was prepared via a tandem trapping of [(11)C]CO2/intramolecular cyclization; [(11)C]tideglusib (glycogen synthase kinase-3) was synthesized through a tandem trapping of [(11)C]CO2 followed by an intermolecular cycloaddition between a [(11)C]isocyanate and an isothiocyanate to form the 1,2,4-thiadiazolidine-3,5-dione core; [(11)C]ibrutinib (Bruton's tyrosine kinase) was synthesized through a HATU peptide coupling of an amino precursor with [(11)C]acrylic acid (generated from [(11)C]CO2 fixation with vinylmagnesium bromide). All radiochemical syntheses are fully automated on commercial radiochemical synthesis modules and provide radiotracers in 1-5% radiochemical yield (noncorrected, based upon [(11)C]CO2). All three radiotracers have advanced to rodent imaging studies and preliminary PET imaging results are also reported.

  2. An efficient and practical radiosynthesis of [11C]temozolomide

    PubMed Central

    Moseley, Christian K.; Carlin, Stephen M.; Neelamegam, Ramesh

    2014-01-01

    Temozolomide (TMZ) is a prodrug for an alkylating agent used for the treatment of malignant brain tumors. A positron emitting version, [11C]TMZ, has been utilized to help elucidate the mechanism and biodistribution of TMZ. Challenges in [11C]TMZ synthesis and reformulation make it difficult for routine production. Herein we report a highly reproducible one-pot radiosynthesis of [11C]TMZ with a radiochemical yield of 17±5% and >97% radiochemical purity. PMID:23151019

  3. Taxonomy of factors which influence heavy metal build-up on urban road surfaces.

    PubMed

    Liu, An; Gunawardana, Chandima; Gunawardena, Janaka; Egodawatta, Prasanna; Ayoko, Godwin A; Goonetilleke, Ashantha

    2016-06-01

    Heavy metals build-up on urban road surfaces is a complex process and influenced by a diverse range of factors. Although numerous research studies have been conducted in the area of heavy metals build-up, limited research has been undertaken to rank these factors in terms of their influence on the build-up process. This results in limitations in the identification of the most critical factor/s for accurately estimating heavy metal loads and for designing effective stormwater treatment measures. The research study undertook an in-depth analysis of the factors which influence heavy metals build-up based on data generated from a number of different geographical locations around the world. Traffic volume was found to be the highest ranked factor in terms of influencing heavy metals build-up while land use was ranked the second. Proximity to arterial roads, antecedent dry days and road surface roughness has a relatively lower ranking. Furthermore, the study outcomes advances the conceptual understanding of heavy metals build-up based on the finding that with increasing traffic volume, total heavy metal build-up load increases while the variability decreases. The outcomes from this research study are expected to contribute to more accurate estimation of heavy metals build-up loads leading to more effective stormwater treatment design.

  4. Effect of avalanche build-up time on avalanche photodiode sensitivity

    SciTech Connect

    Ando, H.; Kanbe, H.

    1985-03-01

    A calculation method for the receiver sensitivity of an avalanche photodiode is considered, taking into account avalanche build-up time and carrier transit time, in addition to the CR time constant. Actual receiver performance is estimated in a high data rate region of up to 10 Gbits/s for germanium avalanche photodiodes, applying the measured avalanche build-up time.

  5. No-carrier-added [1.sup.11 c]putrescine

    DOEpatents

    McPherson, Daniel W.; Fowler, Joanna S.; Wolf, Alfred P.

    1989-01-01

    The invention relates to a new radiolabeled imaging agent, no-carrier-added [1-.sup.11 C]putrescine, and to the use of this very pure material as a radiotracer with positron emission tomography for imaging brain tumors. The invention further relates to the synthesis of no-carrier-added [1-.sup.11 C]putrescine based on the Michael addition of potassium .sup.11 C-labeled cyanide to acrylonitrile followed by reduction of the .sup.11 C-labeled dinitrile. The new method is rapid and efficient and provides radiotracer with a specific activity greater than 1.4 curies per millimol and in a purity greater than 95%.

  6. Characterizing polycyclic aromatic hydrocarbon build-up processes on urban road surfaces.

    PubMed

    Liu, Liang; Liu, An; Li, Dunzhu; Zhang, Lixun; Guan, Yuntao

    2016-07-01

    Reliable prediction models are essential for modeling pollutant build-up processes on urban road surfaces. Based on successive samplings of road deposited sediments (RDS), this study presents empirical models for mathematical replication of the polycyclic aromatic hydrocarbon (PAH) build-up processes on urban road surfaces. The contaminant build-up behavior was modeled using saturation functions, which are commonly applied in US EPA's Stormwater Management Model (SWMM). Accurate fitting results were achieved in three typical urban land use types, and the applicability of the models was confirmed based on their acceptable relative prediction errors. The fitting results showed high variability in PAH saturation value and build-up rate among different land use types. Results of multivariate data and temporal-based analyses suggested that the quantity and property of RDS significantly influenced PAH build-up. Furthermore, pollution sources, traffic parameters, road surface conditions, and sweeping frequency could synthetically impact the RDS build-up and RDS property change processes. Thus, changes in these parameters could be the main reason for variations in PAH build-up in different urban land use types. PMID:27086074

  7. Characterizing polycyclic aromatic hydrocarbon build-up processes on urban road surfaces.

    PubMed

    Liu, Liang; Liu, An; Li, Dunzhu; Zhang, Lixun; Guan, Yuntao

    2016-07-01

    Reliable prediction models are essential for modeling pollutant build-up processes on urban road surfaces. Based on successive samplings of road deposited sediments (RDS), this study presents empirical models for mathematical replication of the polycyclic aromatic hydrocarbon (PAH) build-up processes on urban road surfaces. The contaminant build-up behavior was modeled using saturation functions, which are commonly applied in US EPA's Stormwater Management Model (SWMM). Accurate fitting results were achieved in three typical urban land use types, and the applicability of the models was confirmed based on their acceptable relative prediction errors. The fitting results showed high variability in PAH saturation value and build-up rate among different land use types. Results of multivariate data and temporal-based analyses suggested that the quantity and property of RDS significantly influenced PAH build-up. Furthermore, pollution sources, traffic parameters, road surface conditions, and sweeping frequency could synthetically impact the RDS build-up and RDS property change processes. Thus, changes in these parameters could be the main reason for variations in PAH build-up in different urban land use types.

  8. New interplanetary proton fluence model

    NASA Technical Reports Server (NTRS)

    Feynman, Joan; Armstrong, T. P.; Dao-Gibner, L.; Silverman, S.

    1990-01-01

    A new predictive engineering model for the interplanetary fluence of protons with above 10 MeV and above 30 MeV is described. The data set used is a combination of observations made from the earth's surface and from above the atmosphere between 1956 and 1963 and observations made from spacecraft in the vicinity of earth between 1963 and 1985. The data cover a time period three times as long as the period used in earlier models. With the use of this data set the distinction between 'ordinary proton events' and 'anomalously large events' made in earlier work disappears. This permitted the use of statistical analysis methods developed for 'ordinary events' on the entire data set. The greater than 10 MeV fluences at 1 AU calculated with the new model are about twice those expected on the basis of models now in use. At energies above 30 MeV, the old and new models agree. In contrast to earlier models, the results do not depend critically on the fluence from any one event and are independent of sunspot number. Mission probability curves derived from the fluence distribution are presented.

  9. Rat brain acetylcholinesterase visualized with [11C]physostigmine.

    PubMed

    Planas, A M; Crouzel, C; Hinnen, F; Jobert, A; Né, F; DiGiamberardino, L; Tavitian, B

    1994-06-01

    Physostigmine, a powerful cholinesterase inhibitor, has recently been labelled with 11C in view of its potential application for in vivo imaging of cerebral acetylcholinesterase (AChE) using positron emission tomography. Here we carried out autoradiography of the rat brain using [11C]physostigmine in order to characterize the cerebral targets of this ligand. Autoradiograms were obtained using phosphor storage plates which, compared to autoradiographic films, greatly improved the quality of 11C images. Following autoradiography, brain sections were stained for AChE activity, allowing a direct comparison of autoradiographic and histoenzymatic localizations. The distributions of 11C label and of AChE activity were found to be essentially super-imposable, both after in vivo injection of and after in vitro incubation with [11C]physostigmine. Densitometric analysis showed that radioactivity and enzymatic activity distributions were regionally correlated. The fixation of [11C]physostigmine to cerebral tissue was abolished after incubation of the rat brain sections with BW 284C51, a specific AChE inhibitor, but not after incubation with iso-OMPA, a specific inhibitor of butyrylcholinesterase. Unilateral excitotoxic lesions of the striatum that eliminated local AChE expression concomitantly reduced the binding of the ligand in the lesioned area. These results indicate that autoradiographic images of the rat brain obtained with [11C]physostigmine reflect AChE distribution, thus supporting the use of this radioligand to trace cerebral AChE activity in humans with positron emission tomography.

  10. Influence of hydrogen fluence on surface blistering of H and He co-implanted Ge

    NASA Astrophysics Data System (ADS)

    Dai, Jiayun; Xue, Zhongying; Zhang, Miao; Wei, Xing; Wang, Gang; Di, Zengfeng

    2016-02-01

    The effect of hydrogen fluence on surface blistering of H and He co-implanted Ge is investigated using atom force microscope, X-ray diffraction and transmission electron microscopy. With a fixed He, we find that for 1 × 1016 cm-2 H implantation fluence, only a few small dome-shaped blisters appear, for 3 × 1016 cm-2 H implantation fluence, large blisters as well as craters are formed, while for 5 × 1016 cm-2 H implantation fluence, no blisters can be observed. The strain evolution and platelet forming tendency are found to be relevant for the different blistering phenomenon. The weak blistering phenomenon for 1 × 1016 cm-2 H implantation fluence may be attributed to less "free" H for the building up of internal pressure of platelets and the sustained growth of platelets. While the absence of blistering phenomenon for 5 × 1016 cm-2 H implantation fluence is likely due to the retarded relief of the decreased uniform compressive stress throughout the damage region.

  11. Analysis of the build-up of semi and non volatile organic compounds on urban roads.

    PubMed

    Mahbub, Parvez; Ayoko, Godwin A; Goonetilleke, Ashantha; Egodawatta, Prasanna

    2011-04-01

    Vehicular traffic in urban areas may adversely affect urban water quality through the build-up of traffic generated semi and non volatile organic compounds (SVOCs and NVOCs) on road surfaces. The characterisation of the build-up processes is the key to developing mitigation measures for the removal of such pollutants from urban stormwater. An in-depth analysis of the build-up of SVOCs and NVOCs was undertaken in the Gold Coast region in Australia. Principal Component Analysis (PCA) and Multicriteria Decision tools such as PROMETHEE and GAIA were employed to understand the SVOC and NVOC build-up under combined traffic scenarios of low, moderate, and high traffic in different land uses. It was found that congestion in the commercial areas and use of lubricants and motor oils in the industrial areas were the main sources of SVOCs and NVOCs on urban roads, respectively. The contribution from residential areas to the build-up of such pollutants was hardly noticeable. It was also revealed through this investigation that the target SVOCs and NVOCs were mainly attached to particulate fractions of 75-300 μm whilst the redistribution of coarse fractions due to vehicle activity mainly occurred in the >300 μm size range. Lastly, under combined traffic scenario, moderate traffic with average daily traffic ranging from 2300 to 5900 and average congestion of 0.47 were found to dominate SVOC and NVOC build-up on roads.

  12. Synthesis, isolation and purification of [11C]-choline

    PubMed Central

    Jadwiński, Michał; Chmura, Agnieszka; Gorczewski, Kamil; Sokół, Maria

    2016-01-01

    [11C]-choline is an effective PET tracer used for imaging of neoplastic lesions and metastases of the prostate cancer. However, its production can be a challenge for manufacturers, as it has not yet been described in Polish or European pharmacopoeia. In this study the technical aspects of [11C]-choline production are described and detailed process parameters are provided. The quality control procedures for releasing [11C]-choline as solutio iniectabilis are also presented. The purity and quality of the radiopharmaceutical obtained according to the proposed method were find to be high enough to safely administrate the radiopharmaceutical to patients. Application of an automated synthesizer makes it possible to carry out the entire process of [11C]-choline production, isolation and purification within 20 minutes. It is crucial to maintain all aspects of the process as short as possible, since the decay half-time of carbon-11 is 20.4 minutes. The resulting radiopharmaceutical is sterile and pyrogen-free and of a high chemical, radiochemical, and radionuclide purity proved by chromatographic techniques. The yield of the process is up to 20%. [11C]-choline PET scanning can be used as accurate and effective diagnostic tool in all centers equipped with [11C]-target containing cyclotron.

  13. Synthesis, isolation and purification of [(11)C]-choline.

    PubMed

    Szydło, Marcin; Jadwiński, Michał; Chmura, Agnieszka; Gorczewski, Kamil; Sokół, Maria

    2016-01-01

    [(11)C]-choline is an effective PET tracer used for imaging of neoplastic lesions and metastases of the prostate cancer. However, its production can be a challenge for manufacturers, as it has not yet been described in Polish or European pharmacopoeia. In this study the technical aspects of [(11)C]-choline production are described and detailed process parameters are provided. The quality control procedures for releasing [(11)C]-choline as solutio iniectabilis are also presented. The purity and quality of the radiopharmaceutical obtained according to the proposed method were find to be high enough to safely administrate the radiopharmaceutical to patients. Application of an automated synthesizer makes it possible to carry out the entire process of [(11)C]-choline production, isolation and purification within 20 minutes. It is crucial to maintain all aspects of the process as short as possible, since the decay half-time of carbon-11 is 20.4 minutes. The resulting radiopharmaceutical is sterile and pyrogen-free and of a high chemical, radiochemical, and radionuclide purity proved by chromatographic techniques. The yield of the process is up to 20%. [(11)C]-choline PET scanning can be used as accurate and effective diagnostic tool in all centers equipped with [(11)C]-target containing cyclotron. PMID:27660552

  14. Synthesis, isolation and purification of [(11)C]-choline.

    PubMed

    Szydło, Marcin; Jadwiński, Michał; Chmura, Agnieszka; Gorczewski, Kamil; Sokół, Maria

    2016-01-01

    [(11)C]-choline is an effective PET tracer used for imaging of neoplastic lesions and metastases of the prostate cancer. However, its production can be a challenge for manufacturers, as it has not yet been described in Polish or European pharmacopoeia. In this study the technical aspects of [(11)C]-choline production are described and detailed process parameters are provided. The quality control procedures for releasing [(11)C]-choline as solutio iniectabilis are also presented. The purity and quality of the radiopharmaceutical obtained according to the proposed method were find to be high enough to safely administrate the radiopharmaceutical to patients. Application of an automated synthesizer makes it possible to carry out the entire process of [(11)C]-choline production, isolation and purification within 20 minutes. It is crucial to maintain all aspects of the process as short as possible, since the decay half-time of carbon-11 is 20.4 minutes. The resulting radiopharmaceutical is sterile and pyrogen-free and of a high chemical, radiochemical, and radionuclide purity proved by chromatographic techniques. The yield of the process is up to 20%. [(11)C]-choline PET scanning can be used as accurate and effective diagnostic tool in all centers equipped with [(11)C]-target containing cyclotron.

  15. Synthesis, isolation and purification of [11C]-choline

    PubMed Central

    Jadwiński, Michał; Chmura, Agnieszka; Gorczewski, Kamil; Sokół, Maria

    2016-01-01

    [11C]-choline is an effective PET tracer used for imaging of neoplastic lesions and metastases of the prostate cancer. However, its production can be a challenge for manufacturers, as it has not yet been described in Polish or European pharmacopoeia. In this study the technical aspects of [11C]-choline production are described and detailed process parameters are provided. The quality control procedures for releasing [11C]-choline as solutio iniectabilis are also presented. The purity and quality of the radiopharmaceutical obtained according to the proposed method were find to be high enough to safely administrate the radiopharmaceutical to patients. Application of an automated synthesizer makes it possible to carry out the entire process of [11C]-choline production, isolation and purification within 20 minutes. It is crucial to maintain all aspects of the process as short as possible, since the decay half-time of carbon-11 is 20.4 minutes. The resulting radiopharmaceutical is sterile and pyrogen-free and of a high chemical, radiochemical, and radionuclide purity proved by chromatographic techniques. The yield of the process is up to 20%. [11C]-choline PET scanning can be used as accurate and effective diagnostic tool in all centers equipped with [11C]-target containing cyclotron. PMID:27660552

  16. Particle Test Fluence: What's the Right Number?

    NASA Technical Reports Server (NTRS)

    LaBel, Kenneth A.

    2016-01-01

    While we have been utilizing standard fluence levels such as those listed in the JESD57 document, we have begun revisiting what an appropriate test fluence is when it comes to qualifying a device for single events. Instead of a fixed fluence level or until a specific number of events occurs, a different thought process is required.

  17. Preclinical PET Neuroimaging of [11C]Bexarotene.

    PubMed

    Rotstein, Benjamin H; Placzek, Michael S; Krishnan, Hema S; Pekošak, Aleksandra; Collier, Thomas Lee; Wang, Changning; Liang, Steven H; Burstein, Ethan S; Hooker, Jacob M; Vasdev, Neil

    2016-01-01

    Activation of retinoid X receptors (RXRs) has been proposed as a therapeutic mechanism for the treatment of neurodegeneration, including Alzheimer's and Parkinson's diseases. We previously reported radiolabeling of a Food and Drug Administration-approved RXR agonist, bexarotene, by copper-mediated [(11)C]CO2 fixation and preliminary positron emission tomography (PET) neuroimaging that demonstrated brain permeability in nonhuman primate with regional binding distribution consistent with RXRs. In this study, the brain uptake and saturability of [(11)C]bexarotene were studied in rats and nonhuman primates by PET imaging under baseline and greater target occupancy conditions. [(11)C]Bexarotene displays a high proportion of nonsaturable uptake in the brain and is unsuitable for RXR occupancy measurements in the central nervous system. PMID:27553293

  18. Myocradial extraction of 1-[{sup 11}C] betamethylheptadecanoic acid

    SciTech Connect

    Elmaleh, D.R.; Livni, E.; Alpert, N.M.

    1994-03-01

    Betamethylheptadecanoic acid (BMHA) is a branched chain fatty acid analog that is transported into myocardial cells by the same long chain fatty acid carrier protein mechanism as natural fatty acids, but cannot be completely catabolzied and accumulates in the tissue. Thus, {sup 11}C-labeled BMHA is a useful tracer for the noninvasive evaluation of myocardial fatty acid utilization by positron emission tomography (PET). As a prelude to PET studies, the metabolism of BMHA was studied by classical techniques. The authors measured the net extraction fraction (E{sub n}) of 1-[{sup 11}C]-beta-R,S-methylheptadecanoic acid (1-[{sup 11}C]BMHA) and compared it to that of natural fatty acids in dogs, using arterial/venous measurements and a mathematical model. Two groups of conditioned dogs were studied. In the first group, measurements were made under fasting (normal control) conditions and in the second group, measurements were made during glucose and insulin infusion. Myocardial blood flow, and the extraction/utilization of other substrates (glucose, oxygen and lactate) were also measured. For natural fatty acids in the basal state, E{sub n}(FA) was 0.335. After glucose/insulin infusion, this value decreased to 0.195. The 1-[{sup 11}C]BMHA showed a similar decrease in E{sub n}(BMHA) from 0.220 in the control group to 0.100 in the group treated with glucose/insulin infusion. Preliminary PET studies with 1-[{sup 11}C]BMHA verified the validity of performing these measurements noninvasively. The results of these studies indicate that rates of fatty acid metabolism in the myocardium can be determined from steady-state concentrations of 1-[{sup 11}C]BMHA. 36 refs., 6 figs., 4 tabs.

  19. A comparison of the effects of different methods of impression build-up on earmoulds.

    PubMed

    Macrae, J H

    1991-06-01

    An investigation was carried out into effects of three types of impression build-up (patting down of impressions, special earmould-maker build-up and the multistage impression technique) on the dimensions, static pressure seal, degree of acoustic seal and the subjective tightness and comfort of earmoulds. Patting down the impression significantly improved the degree of acoustic seal provided by earmoulds without making them feel tighter or less comfortable. However, special build-up was much more effective than patting down and the multistage impression technique was slightly more effective than special build-up in improving the degree of acoustic seal. The improvement in acoustic seal provided by both multistage and specially built-up earmoulds can usually be obtained without an unacceptable level of discomfort. Patting down the impression did not improve the chance of obtaining a static pressure seal. Special build-up of the impression by the earmould-maker significantly increased the proportion of earmoulds which provided a static pressure seal but an even higher proportion of earmoulds made from multistage impressions provided a seal. Dimension results indicated that an increase in earmould-maker build-up of the minor axis at the beginning of the canal segment of the impression would improve the acoustic seal provided by specially built-up earmoulds and that earmoulds with rounder tips are more likely to provide a static pressure seal than earmoulds with more elliptical tips. The better the impression material fills the ear canal, the rounder the tip of the impression, and the rounder the tip of the earmould made from the impression.

  20. Dynamic Characteristics of Pressure Build Up Tank for HTS Power Cable Refrigeration System

    NASA Astrophysics Data System (ADS)

    Kim, Dongmin; Park, Heecheol; Kim, Seokho; Jang, Hyunman; Kim, Yanghun

    HTS power cables are cooled by the forced circulation of sub-cooled liquid nitrogen to remove heat loss and maintain a cryogenic temperature. The refrigeration systems used consist of cryocoolers, a pressure build-up tank, heat exchangers, and circulation pumps. Liquid nitrogen expands or shrinks according to the temperature variation inside the fixed volume of the refrigeration system and the cable cryostat. The system pressure also changes depending on the volume change of the liquid nitrogen. The pressure of the liquid nitrogen should be kept above a certain level to ensure its dielectric strength. In addition, the pressure should be kept below the allowable pressure level considering the mechanical strength of the refrigeration system. To enhance the pressure controllability, external heating and cooling should be possible in the pressure build-up tank. For the precise modeling of the pressure build-up tank, thermal stratification and axial thermal conduction are considered. An analysis of such a refrigeration system is performed using the commercial code 'Sinda/fluint', a comprehensive finite-difference, one-dimensional, lumped parameter tool. This paper presents the transient thermo-hydraulic characteristics and the design directions of an HTS cable refrigeration system according to a variable heat load including pressure build-up tank.

  1. Influence of pollutant build-up on variability in wash-off from urban road surfaces.

    PubMed

    Wijesiri, Buddhi; Egodawatta, Prasanna; McGree, James; Goonetilleke, Ashantha

    2015-09-15

    Variability in the pollutant wash-off process is a concept which needs to be understood in-depth in order to better assess the outcomes of stormwater quality models, and thereby strengthen stormwater pollution mitigation strategies. Current knowledge about the wash-off process does not extend to a clear understanding of the influence of the initially available pollutant build-up on the variability of the pollutant wash-off load and composition. Consequently, pollutant wash-off process variability is poorly characterised in stormwater quality models, which can result in inaccurate stormwater quality predictions. Mathematical simulation of particulate wash-off from three urban road surfaces confirmed that the wash-off load of particle size fractions < 150 μm and > 150 μm after a storm event vary with the build-up of the respective particle size fractions available at the beginning of the storm event. Furthermore, pollutant load and composition associated with the initially available build-up of < 150 μm particles predominantly influence the variability in washed-off pollutant load and composition. The influence of the build-up of pollutants associated with > 150 μm particles on wash-off process variability is significant only for relatively shorter duration storm events.

  2. (11)C-Methionine uptake in secondary brain epilepsy.

    PubMed

    Lopci, E; Bello, L; Chiti, A

    2014-01-01

    Carbon-11 methionine ((11)C-Methionine) is a radio-labeled amino acid currently utilized in Positron Emission Tomography (PET) for imaging primary and metastatic brain tumors. Its clinical use relies mostly on oncologic applications, but the tracer has the potential to investigate other non-malignant conditions. So far, very limited evidence concerns the use of (11)C-Methionine in patients suffering from seizure; however, the tracer can find a proper utilization in this setting especially as a diagnostic complement to (18)F-Fluorodeoxyglucose ((18)F-FDG). Herein we report the case of a 57-year-old patient presenting with epileptic crises secondary to a brain metastasis from bladder carcinoma, who was investigated in our institution with (11)C-Methionine PET. The scan documented the disease recurrence in the left parietal lobe associated with a diffused tracer uptake in the surrounding cerebral circumvolutions, derived from the comitial status. After surgical removal of the metastatic lesion, the patient experienced a complete recovery of symptoms and no further onset of secondary seizure.

  3. Analysis of build-up of heavy metals and volatile organics on urban roads in gold coast, Australia.

    PubMed

    Mahbub, Parvez; Goonetilleke, Ashantha; Ayoko, Godwin A; Egodawatta, Prasanna; Yigitcanlar, Tan

    2011-01-01

    Urban water quality can be significantly impaired by the build-up of pollutants such as heavy metals and volatile organics on urban road surfaces due to vehicular traffic. Any control strategy for the mitigation of traffic related build-up of heavy metals and volatile organic pollutants should be based on the knowledge of their build-up processes. In the study discussed in this paper, the outcomes of a detailed experimental investigation into build-up processes of heavy metals and volatile organics are presented. It was found that traffic parameters such as average daily traffic, volume over capacity ratio and surface texture depth had similar strong correlations with the build-up of heavy metals and volatile organics. Multicriteria decision analyses revealed that that the 1-74 microm particulate fraction of total suspended solids (TSS) could be regarded as a surrogate indicator for particulate heavy metals in build-up and this same fraction of total organic carbon could be regarded as a surrogate indicator for particulate volatile organics build-up. In terms of pollutants affinity, TSS was found to be the predominant parameter for particulate heavy metals build-up and total dissolved solids was found to be the predominant parameter for the potential dissolved particulate fraction in heavy metals buildup. It was also found that land use did not play a significant role in the build-up of traffic generated heavy metals and volatile organics.

  4. Experimental results of neutron fluence outside an iron shield in the forward direction

    SciTech Connect

    Torres, M.M.C.; Elwyn, A.J.; Fein, D.; James, E.; Johns, K.; Davis, W.; Ciampa, D.P.; Mierkiewicz, E.

    1996-09-01

    Analyses of both lateral shielding measurements and Monte Carlo calculations for beam stop geometry for incident hadrons at energies between 10 GeV and 10 TeV suggests that the dose equivalent can be represented by the expression H = H{sub 0}(E)e{sup -r/{lambda}}/r{sup 2} where H, is the source term, r is the radial distance to the point of interest in the shield, and {lambda} is the effective interaction length, or absorption mean free path. However, unlike the lateral shielding case, there is no similarly simple analytical expression that can be used to describe the on-axis longitudinal cascade development. In this study the results from the measurement in the forward direction of neutron fluence spectra (and the derived quantity dose equivalent) for 25 to 150 GeV pions incident on an iron beam stop as a function of thickness of iron are presented. The observed dependence of both fluence and dose equivalent on shield thickness and hadron energy was then quantified in terms of an expression in which a build up factor as well as an attenuation term was included. On the basis of this analysis the conversion factor from fluence to dose equivalent was also determined for these forward going neutrons. This work represents the first systematic study at an high energy accelerator of the depth dependence of neutron fluence in longitudinal shielding.

  5. Build-up material requirements in clinical dosimetry during total body irradiation treatments.

    PubMed

    Butson, Martin; Pope, Dane; Haque, Mamoon; Chen, Tom; Song, Guangli; Whitaker, May

    2016-01-01

    Total body irradiation (TBI) treatments are mainly used in a preparative regimen for hematopoietic stem cell (or bone marrow) transplantation. Our standard clinical regimen is a 12 Gy/6 fraction bi-daily technique using 6MV X-rays at a large extended source to surface distance (SSD). This work investigates and quantifies the dose build-up characteristics and thus the requirements for bolus used for in vivo dosimetry for TBI applications. Percentage dose build-up characteristics of photon beams have been investigated at large extended SSDs using ionization chambers and Gafchromic film. Open field measurements at different field sizes and with differing scatter conditions such as the introduction of standard Perspex scattering plates at different distances to the measurement point were made in an effort to determine the required bolus/build-up material required for accurate determination of applied dose. Percentage surface dose values measured for open fields at 300 cm SSD were found to range from 20% up to 65.5% for fields 5 cm × 5 cm to 40 cm × 40 cm, respectively. With the introduction of 1 cm Perspex scattering plates used in TBI treatments, the surface dose values increased up to 83-90% (93-97% at 1 mm depth), depending on the position of the Perspex scattering plate compared to the measurement point. Our work showed that at least 5 mm water equivalent bolus/scatter material should be placed over the EBT3 film for accurate dose assessment for TBI treatments. Results also show that a small but measurable decrease in measured dose occurred with 5 mm water equivalent thick bolus material of areas '3 cm(2). As such, we recommend that 3 cm × 3 cm × 5 mm bolus build-up is the smallest size that should be placed over EBT3 Gafchromic film when used for accurate in vivo dosimetry for TBI applications.

  6. Build-up material requirements in clinical dosimetry during total body irradiation treatments.

    PubMed

    Butson, Martin; Pope, Dane; Haque, Mamoon; Chen, Tom; Song, Guangli; Whitaker, May

    2016-01-01

    Total body irradiation (TBI) treatments are mainly used in a preparative regimen for hematopoietic stem cell (or bone marrow) transplantation. Our standard clinical regimen is a 12 Gy/6 fraction bi-daily technique using 6MV X-rays at a large extended source to surface distance (SSD). This work investigates and quantifies the dose build-up characteristics and thus the requirements for bolus used for in vivo dosimetry for TBI applications. Percentage dose build-up characteristics of photon beams have been investigated at large extended SSDs using ionization chambers and Gafchromic film. Open field measurements at different field sizes and with differing scatter conditions such as the introduction of standard Perspex scattering plates at different distances to the measurement point were made in an effort to determine the required bolus/build-up material required for accurate determination of applied dose. Percentage surface dose values measured for open fields at 300 cm SSD were found to range from 20% up to 65.5% for fields 5 cm × 5 cm to 40 cm × 40 cm, respectively. With the introduction of 1 cm Perspex scattering plates used in TBI treatments, the surface dose values increased up to 83-90% (93-97% at 1 mm depth), depending on the position of the Perspex scattering plate compared to the measurement point. Our work showed that at least 5 mm water equivalent bolus/scatter material should be placed over the EBT3 film for accurate dose assessment for TBI treatments. Results also show that a small but measurable decrease in measured dose occurred with 5 mm water equivalent thick bolus material of areas '3 cm(2). As such, we recommend that 3 cm × 3 cm × 5 mm bolus build-up is the smallest size that should be placed over EBT3 Gafchromic film when used for accurate in vivo dosimetry for TBI applications. PMID:27217628

  7. Build-up material requirements in clinical dosimetry during total body irradiation treatments

    PubMed Central

    Butson, Martin; Pope, Dane; Haque, Mamoon; Chen, Tom; Song, Guangli; Whitaker, May

    2016-01-01

    Total body irradiation (TBI) treatments are mainly used in a preparative regimen for hematopoietic stem cell (or bone marrow) transplantation. Our standard clinical regimen is a 12 Gy/6 fraction bi-daily technique using 6MV X-rays at a large extended source to surface distance (SSD). This work investigates and quantifies the dose build-up characteristics and thus the requirements for bolus used for in vivo dosimetry for TBI applications. Percentage dose build-up characteristics of photon beams have been investigated at large extended SSDs using ionization chambers and Gafchromic film. Open field measurements at different field sizes and with differing scatter conditions such as the introduction of standard Perspex scattering plates at different distances to the measurement point were made in an effort to determine the required bolus/build-up material required for accurate determination of applied dose. Percentage surface dose values measured for open fields at 300 cm SSD were found to range from 20% up to 65.5% for fields 5 cm × 5 cm to 40 cm × 40 cm, respectively. With the introduction of 1 cm Perspex scattering plates used in TBI treatments, the surface dose values increased up to 83–90% (93–97% at 1 mm depth), depending on the position of the Perspex scattering plate compared to the measurement point. Our work showed that at least 5 mm water equivalent bolus/scatter material should be placed over the EBT3 film for accurate dose assessment for TBI treatments. Results also show that a small but measurable decrease in measured dose occurred with 5 mm water equivalent thick bolus material of areas '3 cm2. As such, we recommend that 3 cm × 3 cm × 5 mm bolus build-up is the smallest size that should be placed over EBT3 Gafchromic film when used for accurate in vivo dosimetry for TBI applications. PMID:27217628

  8. Optimal Thermo-Structural Analysis for High Density Package Mounting on Build-up Board

    NASA Astrophysics Data System (ADS)

    Nakanishi, Tohru; Hase, Tomohiro

    The importance of the high density packaging technology and mounting technology on the printed wiring build-up board has been increased for the consumer electric products. On the other hand, the chance to use the build-up boards for mounting the high density packages has been increased. However, the understanding that the reliability of the solder connection depends on the structure of the package, the motherboard, and the material properties, is not very high. In this paper, the reliability for high density packaging, mounted on the build-up board, is assessed. The compact numerical analysis model for the reliability assessment is suggested and the most reliable packaging design with optimizing each of the parameters is reported. For introduction to the reliability assessment of the FCA attachment, ceramic and silicon are compared as the inter-poser with the parameter of the solder height. The verification of the numerical analysis results using tests on the actual hardware is also shown. And the established numerical analysis model is applied to the study of influence of the copper balance between the front side and the back side copper layers.

  9. Processing ultrasonic inspection data from multiple scan patterns for turbine rotor weld build-up evaluations

    SciTech Connect

    Guan, Xuefei; Zhou, S. Kevin; Rasselkorde, El Mahjoub; Abbasi, Waheed

    2015-03-31

    The study presents a data processing methodology for weld build-up using multiple scan patterns. To achieve an overall high probability of detection for flaws with different orientations, an inspection procedure with three different scan patterns is proposed. The three scan patterns are radial-tangential longitude wave pattern, axial-radial longitude wave pattern, and tangential shear wave pattern. Scientific fusion of the inspection data is implemented using volume reconstruction techniques. The idea is to perform spatial domain forward data mapping for all sampling points. A conservative scheme is employed to handle the case that multiple sampling points are mapped to one grid location. The scheme assigns the maximum value for the grid location to retain the largest equivalent reflector size for the location. The methodology is demonstrated and validated using a realistic ring of weld build-up. Tungsten balls and bars are embedded to the weld build-up during manufacturing process to represent natural flaws. Flat bottomed holes and side drilled holes are installed as artificial flaws. Automatic flaw identification and extraction are demonstrated. Results indicate the inspection procedure with multiple scan patterns can identify all the artificial and natural flaws.

  10. Characterizing heavy metal build-up on urban road surfaces: implication for stormwater reuse.

    PubMed

    Liu, An; Liu, Liang; Li, Dunzhu; Guan, Yuntao

    2015-05-15

    Stormwater reuse is increasingly popular in the worldwide. In terms of urban road stormwater, it commonly contains toxic pollutants such as heavy metals, which could undermine the reuse safety. The research study investigated heavy metal build-up characteristics on urban roads in a typical megacity of South China. The research outcomes show the high variability in heavy metal build-up loads among different urban road sites. The degree of traffic congestion and road surface roughness was found to exert a more significant influence on heavy metal build-up rather than traffic volume. Due to relatively higher heavy metal loads, stormwater from roads with more congested traffic conditions or rougher surfaces might be suitable for low-water-quality required activities while the stormwater from by-pass road sections could be appropriate for relatively high-water-quality required purposes since the stormwater could be relatively less polluted. Based on the research outcomes, a decision-making process for heavy metals based urban road stormwater reuse was proposed. The new finding highlights the importance to undertaking a "fit-for-purpose" road stormwater reuse strategy. Additionally, the research results can also contribute to enhancing stormwater reuse safety. PMID:25687783

  11. On spatial stabilization of dielectric barrier discharge microfilaments by residual heat build-up in air

    NASA Astrophysics Data System (ADS)

    Ráhel, Jozef; Szalay, Zsolt; Čech, Jan; Morávek, Tomás

    2016-04-01

    Microfilaments of dielectric barrier discharge are known for their multiple re-appearance at the same spot on dielectrics. This effect of localized re-appearance is driven by residual excited species and ions, surface charge deposited on the dielectric and the local temperature build-up resulting in the local increase of reduced electric field E/ΔN. To assess the magnitude of the latter, the breakdown voltage vs. temperature up to 180 °C was carefully measured at coplanar DBD and used as an input into the numerical simulation of heat build-up by the train of discharge pulses. An average reduction of breakdown voltage was found to be 20 V/K. The model predicted a quasi-stable microfilament temperature into which the thermal build-up rapidly converges. Its magnitude agreed well with the reported rotational temperature of similar electrode configuration. The impact of quasi-stable temperature on microfilament formation dynamics is further discussed. Contribution to the Topical Issue "Recent Breakthroughs in Microplasma Science and Technology", edited by Kurt Becker, Jose Lopez, David Staack, Klaus-Dieter Weltmann and Wei Dong Zhu.

  12. Characterizing heavy metal build-up on urban road surfaces: implication for stormwater reuse.

    PubMed

    Liu, An; Liu, Liang; Li, Dunzhu; Guan, Yuntao

    2015-05-15

    Stormwater reuse is increasingly popular in the worldwide. In terms of urban road stormwater, it commonly contains toxic pollutants such as heavy metals, which could undermine the reuse safety. The research study investigated heavy metal build-up characteristics on urban roads in a typical megacity of South China. The research outcomes show the high variability in heavy metal build-up loads among different urban road sites. The degree of traffic congestion and road surface roughness was found to exert a more significant influence on heavy metal build-up rather than traffic volume. Due to relatively higher heavy metal loads, stormwater from roads with more congested traffic conditions or rougher surfaces might be suitable for low-water-quality required activities while the stormwater from by-pass road sections could be appropriate for relatively high-water-quality required purposes since the stormwater could be relatively less polluted. Based on the research outcomes, a decision-making process for heavy metals based urban road stormwater reuse was proposed. The new finding highlights the importance to undertaking a "fit-for-purpose" road stormwater reuse strategy. Additionally, the research results can also contribute to enhancing stormwater reuse safety.

  13. Study of the 11C(p,gamma) reaction via the indirect d(11C,12N)ntransfer reaction

    SciTech Connect

    Lee, Dongwon; Powell, James; Perajarvi, Kari; Guo, Fanqing; Moltz, Dennis; Cerny, Joseph

    2008-01-07

    The {sup 11}C(p,{gamma}){sup 12}N reaction is expected to be an important branch point in supermassive low-metallicity stars because it could produce CNO seed nuclei before the traditional triple-alpha process turns on. In the present work, the d({sup 11}C, {sup 12}N)n transfer reaction was employed to evaluate this reaction using a radioactive ion beam of 150 MeV {sup 11}C with 6 x 10{sup 5} ions/s on target from the BEARS project at the 88-inch cyclotron at Lawrence Berkeley National Laboratory. Excellent agreement was obtained between the experimental cross sections ({theta}{sub c.m.} = 10.9{sup o} to 71.5{sup o}) and DWBA calculations. The asymptotic normalization coefficient was deduced to be (C{sub eff}{sup 12N}){sup 2} = (C{sub p1/2}{sup 12N}){sup 2} + (C{sub p3/2}{sup 12N}){sup 2} = 1.83 {+-} 0.27 fm{sup -1}.

  14. Cu(I)-catalyzed (11)C carboxylation of boronic acid esters: a rapid and convenient entry to (11)C-labeled carboxylic acids, esters, and amides.

    PubMed

    Riss, Patrick J; Lu, Shuiyu; Telu, Sanjay; Aigbirhio, Franklin I; Pike, Victor W

    2012-03-12

    Rapid and direct: the carboxylation of boronic acid esters with (11)CO(2) provides [(11)C]carboxylic acids as a convenient entry into [(11)C]esters and [(11)C]amides. This conversion of boronates is tolerant to diverse functional groups (e.g., halo, nitro, or carbonyl). PMID:22308017

  15. Cryogenic molecular separation system for radioactive 11C ion acceleration

    NASA Astrophysics Data System (ADS)

    Katagiri, K.; Noda, A.; Suzuki, K.; Nagatsu, K.; Boytsov, A. Yu.; Donets, D. E.; Donets, E. D.; Donets, E. E.; Ramzdorf, A. Yu.; Nakao, M.; Hojo, S.; Wakui, T.; Noda, K.

    2015-12-01

    A 11C molecular production/separation system (CMPS) has been developed as part of an isotope separation on line system for simultaneous positron emission tomography imaging and heavy-ion cancer therapy using radioactive 11C ion beams. In the ISOL system, 11CH4 molecules will be produced by proton irradiation and separated from residual air impurities and impurities produced during the irradiation. The CMPS includes two cryogenic traps to separate specific molecules selectively from impurities by using vapor pressure differences among the molecular species. To investigate the fundamental performance of the CMPS, we performed separation experiments with non-radioactive 12CH4 gases, which can simulate the chemical characteristics of 11CH4 gases. We investigated the separation of CH4 molecules from impurities, which will be present as residual gases and are expected to be difficult to separate because the vapor pressure of air molecules is close to that of CH4. We determined the collection/separation efficiencies of the CMPS for various amounts of air impurities and found desirable operating conditions for the CMPS to be used as a molecular separation device in our ISOL system.

  16. [11C]phenytoin revisited: synthesis by [11C]CO carbonylation and first evaluation as a P-gp tracer in rats

    PubMed Central

    2012-01-01

    Background At present, several positron emission tomography (PET) tracers are in use for imaging P-glycoprotein (P-gp) function in man. At baseline, substrate tracers such as R-[11C]verapamil display low brain concentrations with a distribution volume of around 1. [11C]phenytoin is supposed to be a weaker P-gp substrate, which may lead to higher brain concentrations at baseline. This could facilitate assessment of P-gp function when P-gp is upregulated. The purpose of this study was to synthesize [11C]phenytoin and to characterize its properties as a P-gp tracer. Methods [11C]CO was used to synthesize [11C]phenytoin by rhodium-mediated carbonylation. Metabolism and, using PET, brain pharmacokinetics of [11C]phenytoin were studied in rats. Effects of P-gp function on [11C]phenytoin uptake were assessed using predosing with tariquidar. Results [11C]phenytoin was synthesized via [11C]CO in an overall decay-corrected yield of 22 ± 4%. At 45 min after administration, 19% and 83% of radioactivity represented intact [11C]phenytoin in the plasma and brain, respectively. Compared with baseline, tariquidar predosing resulted in a 45% increase in the cerebral distribution volume of [11C]phenytoin. Conclusions Using [11C]CO, the radiosynthesis of [11C]phenytoin could be improved. [11C]phenytoin appeared to be a rather weak P-gp substrate. PMID:22747744

  17. 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

  18. Simulations of electron cloud build-up and saturation in the APS

    SciTech Connect

    Harkay, K.C.; Rosenberg, R.A.; Furman, M.A.; Pivi, M.

    2002-06-19

    In studies with positron beams in the Advanced Photon Source, a dramatic amplification was observed in the electron cloud for certain bunch current and bunch spacings. In modeling presented previously, we found qualitative agreement with the observed beam-induced multipacting condition, provided reasonable values were chosen for the secondary electron yield parameters, including the energy distribution. In this paper, we model and discuss the build-up and saturation process observed over long bunch trains at the resonance condition. Understanding this saturation mechanism in more detail may have implications for predicting electron cloud amplification, multipacting, and instabilities in future rings.

  19. The use of tetrabutylammonium fluoride to promote N- and O-(11) C-methylation reactions with iodo[(11) C]methane in dimethyl sulfoxide.

    PubMed

    Kikuchi, Tatsuya; Minegishi, Katsuyuki; Hashimoto, Hiroki; Zhang, Ming-Rong; Kato, Koichi

    2013-11-01

    The N- or O-methylation reactions of compounds bearing amide, aniline, or phenol moieties using iodo[(11) C]methane (1) with the aid of a base are frequently applied to the preparation of (11) C-labeled radiopharmaceuticals. Although sodium hydride and alkaline metal hydroxides are commonly employed as bases in these reactions, their poor solubility properties in organic solvents and hydrolytic activities have sometimes limited their application and made the associated (11) C-methylation reactions difficult. In contrast to these bases, tetrabutylammonium fluoride (TBAF) is moderately basic, highly soluble in organic solvents, and weakly nucleophilic. Although it was envisaged that TBAF could be used as the preferred base for (11) C-methylation reactions using 1, studies concerning the use of TBAF to promote (11) C-methylation reactions are scarce. Herein, we have evaluated the efficiency of the (11) C-methylation reactions of 13 model compounds using TBAF and 1. In most cases, the N-(11) C-methylations were efficiently promoted by TBAF in dimethyl sulfoxide at ambient temperature, whereas the O-(11) C-methylations required heating in some cases. Comparison studies revealed that the efficiencies of the (11) C-methylation reactions with TBAF were comparable or sometimes greater than those conducted with sodium hydride. Based on these results, TBAF should be considered as the preferred base for (11) C-methylation reactions using 1. PMID:25196029

  20. Build-up of toxic metals on the impervious surfaces of a commercial seaport.

    PubMed

    Ziyath, Abdul M; Egodawatta, Prasanna; Goonetilleke, Ashantha

    2016-05-01

    In the context of increasing threats to the sensitive marine ecosystem by toxic metals, this study investigated the metal build-up on impervious surfaces specific to commercial seaports. The knowledge generated from this study will contribute to managing toxic metal pollution of the marine ecosystem. The study found that inter-modal operations and main access roadway had the highest loads followed by container storage and vehicle marshalling sites, while the quay line and short term storage areas had the lowest. Additionally, it was found that Cr, Al, Pb, Cu and Zn were predominantly attached to solids, while significant amount of Cu, Pb and Zn were found as nutrient complexes. As such, treatment options based on solids retention can be effective for some metal species, while ineffective for other species. Furthermore, Cu and Zn are more likely to become bioavailable in seawater due to their strong association with nutrients. Mathematical models to replicate the metal build-up process were also developed using experimental design approach and partial least squares regression. The models for Cr and Pb were found to be reliable, while those for Al, Zn and Cu were relatively less reliable, but could be employed for preliminary investigations.

  1. Investigation of Pectin/Chitosan Multilayers Build-up on Corona Charged Polylactide Substrates

    NASA Astrophysics Data System (ADS)

    Yovcheva, T. A.; Marudova, M. G.; Viraneva, A. P.; Gencheva, E. A.; Mekishev, G. A.; Sainov, S. H.

    2010-01-01

    The aim of the present research is to investigate the formation and stability of pectin/chitosan multilayer films on preliminary corona charged polylactide substrate with different polarity. For this purpose two different multilayer structures with alternative ordering of polycation and polyanion layers were prepared. Layer-by-layer (LbL) deposition technique was used for multilayer build-up. The FT-IR transmittance spectra of the substrates with multilayers indicated of the presence of pectin and chitosan. The intensity of the typical bands was found to increase with increasing of the number of the deposited layers. The stability and physico-chemical properties of the multilayer structures were investigated by determination of surface refractive index and swelling behaviour. Multilayers are stable enough in distilled water and their equilibrium degree of swelling increases with the increase of build-up layers. This relation is correlated with the increased amount of hydrophilic biopolymers. It was found out that chitosan/pectin multilayers buil-up on negatively charged substrate consist of higher amount of polyelectrolytes and are more stable in distilled water.

  2. Understanding the physical processes of pollutant build-up and wash-off on roof surfaces.

    PubMed

    Egodawatta, Prasanna; Thomas, Evan; Goonetilleke, Ashantha

    2009-03-01

    Pollutants originating with roof runoff can have a significant impact on urban stormwater quality. This signifies the importance of understanding pollutant processes on roof surfaces. Additionally, knowledge of pollutant processes on roof surfaces is important as roofs are used as the primary catchment surface for domestic rainwater harvesting. In recent years, rainwater harvesting has become one of the primary sustainable water management techniques to counteract the growing demand for potable water. This paper presents the outcomes of an in-depth research study into particulate matter build-up and wash-off for roof surfaces. In this research, particulate matter was considered as the indicator pollutant where the processes related to other pollutants can be predicted based on the understanding generated for particulate matter. The study outcomes confirm that the build-up process on roof surfaces is comparatively similar to road surfaces. However, particle loads collected from roofs were significantly less compared to road surfaces and much finer in texture. Wash-off from roofs also showed significant similarities to wash-off from roads. A relatively high concentration of particulate matter was noted during the initial part of storm events. Furthermore, the amount of particulate matter remaining on the roof surfaces was significantly high for less intense rain events. PMID:19157516

  3. Optical fiber sensors and their application in monitoring stress build-up in dental resin cements

    NASA Astrophysics Data System (ADS)

    Ottevaere, H.; Tabak, M.; Fernandez Fernandez, A.; Berghmans, F.; Thienpont, H.

    2005-09-01

    The field of optical fiber sensing is highly diverse and this diversity is perceived as a great advantage over more conventional sensors in that an optical sensor can be tailored to measure any of a myriad of physical parameters. In this paper we present a niche application for optical fiber sensors in the domain of biophotonics, namely the monitoring of stress build-up during the curing process of dental resin cements. We discuss the origin of this stress build-up and the problems it can cause when treating patients. Optical fiber sensors aim at excelling in two kind of applications: firstly to perform quality control on batch produced dental cements and measure their total material shrinkage, secondly to monitor the hardening of the cement during in-vivo measurements resulting in the dynamic measurement of the shrinkage and to control the stress in a facing based restoration. We therefore investigated two types of optical fiber sensors as alternatives to conventional measurement techniques; namely polarimetric optical fiber sensors and fiber Bragg gratings written in polarization maintaining fibers. After discussing the results obtained with both optical fiber sensors, we will conclude with a critical assessment of the suitability of the two proposed sensing configurations for multi-parameter stress monitoring.

  4. Impact of eccentricity build-up and graveyard disposal Strategies on MEO navigation constellations

    NASA Astrophysics Data System (ADS)

    Radtke, Jonas; Domínguez-González, Raúl; Flegel, Sven K.; Sánchez-Ortiz, Noelia; Merz, Klaus

    2015-12-01

    With currently two constellations being in or close to the build-up phase, in a few years the Medium Earth Orbit (MEO) region will be populated with four complete navigation systems in relatively close orbital altitudes: The American GPS, Russian GLONASS, European Galileo, and Chinese BeiDou. To guarantee an appropriate visibility of constellation satellites from Earth, these constellations rely on certain defined orbits. For this, both the repeat pattern, which is basically defined by the semimajor axis and inclination, as well as the orbital planes, which are defined by the right ascension of ascending node, are determining values. To avoid an overcrowding of the region of interest, the disposal of satellites after their end-of-life is recommended. However, for the MEO region, no internationally agreed mitigation guidelines exist. Because of their distances to Earth, ordinary disposal manoeuvres leading to a direct or delayed re-entry due to atmospheric drag are not feasible: The needed fuel masses for such manoeuvres are by far above the reasonable limits and available fuel budgets. Thus, additional approaches have to be applied. For this, in general two options exist: disposal to graveyard orbits or the disposal to eccentricity build-up orbits. In the study performed, the key criterion for the graveyard strategy is that the disposed spacecraft must keep a safe minimum distance to the altitude of the active constellation on a long-term time scale of up to 200 years. This constraint imposes stringent requirements on the stability of the graveyard orbit. Similar disposals are also performed for high LEO satellites and disposed GEO payloads. The eccentricity build-up strategy on the other hand uses resonant effects between the Earth's geopotential, the Sun and the Moon. Depending on the initial conditions, these can cause a large eccentricity build-up, which finally can lead to a re-entry of the satellite. In this paper, the effects of applying either the first or

  5. Pharmacokinetic Analysis of 11C-PBR28 in the Rat Model of Herpes Encephalitis: Comparison with (R)-11C-PK11195.

    PubMed

    Parente, Andrea; Feltes, Paula Kopschina; Vállez García, David; Sijbesma, Jurgen W A; Moriguchi Jeckel, Cristina M; Dierckx, Rudi A J O; de Vries, Erik F J; Doorduin, Janine

    2016-05-01

    (11)C-PBR28 is a second-generation translocator protein (TSPO) tracer with characteristics supposedly superior to the most commonly used tracer for neuroinflammation, (R)-(11)C-PK11195. Despite its use in clinical research, no studies on the imaging properties and pharmacokinetic analysis of (11)C-PBR28 in rodent models of neuroinflammation have been published yet. Therefore, this study aimed to evaluate (11)C-PBR28 as a tool for detection and quantification of neuroinflammation in preclinical research and to compare its imaging properties with (R)-(11)C-PK11195. The herpes simplex encephalitis (HSE) model was used for induction of neuroinflammation in male Wistar rats. Six or 7 d after virus inoculation, a dynamic (11)C-PBR28 or (R)-(11)C-PK11195 PET scan with arterial blood sampling was obtained. Pharmacokinetic modeling was performed on the PET data and analyzed using volumes of interest and a voxel-based approach. Volume-of-interest- and voxel-based analysis of (11)C-PBR28 images showed overexpression of TSPO in brain regions known to be affected in the HSE rat model. (11)C-PBR28 was metabolized faster than (R)-(11)C-PK11195, with a metabolic half-life in plasma of 5 and 21 min, respectively. Overall, (11)C-PBR28 was more sensitive than (R)-(11)C-PK11195 in detecting neuroinflammation. The binding potential (BPND) of (11)C-PBR28 was significantly higher (P < 0.05) in the medulla (176%), pons (146%), midbrain (101%), hippocampus (85%), thalamus (73%), cerebellum (54%), and hypothalamus (49%) in HSE rats than in control rats, whereas (R)-(11)C-PK11195 showed a higher BPND only in the medulla (32%). The BPND in control animals was not significantly different between tracers, suggesting that the nonspecific binding of both tracers is similar. (11)C-PBR28 was more sensitive than (R)-(11)C-PK11195 in the detection of TSPO overexpression in the HSE rat model, because more brain regions with significantly increased tracer uptake could be found, irrespective of the data

  6. Algorithms for optimizing CT fluence control

    NASA Astrophysics Data System (ADS)

    Hsieh, Scott S.; Pelc, Norbert J.

    2014-03-01

    The ability to customize the incident x-ray fluence in CT via beam-shaping filters or mA modulation is known to improve image quality and/or reduce radiation dose. Previous work has shown that complete control of x-ray fluence (ray-by-ray fluence modulation) would further improve dose efficiency. While complete control of fluence is not currently possible, emerging concepts such as dynamic attenuators and inverse-geometry CT allow nearly complete control to be realized. Optimally using ray-by-ray fluence modulation requires solving a very high-dimensional optimization problem. Most optimization techniques fail or only provide approximate solutions. We present efficient algorithms for minimizing mean or peak variance given a fixed dose limit. The reductions in variance can easily be translated to reduction in dose, if the original variance met image quality requirements. For mean variance, a closed form solution is derived. The peak variance problem is recast as iterated, weighted mean variance minimization, and at each iteration it is possible to bound the distance to the optimal solution. We apply our algorithms in simulations of scans of the thorax and abdomen. Peak variance reductions of 45% and 65% are demonstrated in the abdomen and thorax, respectively, compared to a bowtie filter alone. Mean variance shows smaller gains (about 15%).

  7. A comparative small-animal PET evaluation of [11C]tariquidar, [11C]elacridar and (R)-[11C]verapamil for detection of P-glycoprotein expressing murine breast cancer

    PubMed Central

    Wanek, Thomas; Kuntner, Claudia; Bankstahl, Jens P.; Bankstahl, Marion; Stanek, Johann; Sauberer, Michael; Mairinger, Severin; Strommer, Sabine; Wacheck, Volker; Löscher, Wolfgang; Erker, Thomas; Müller, Markus; Langer, Oliver

    2013-01-01

    Purpose One important mechanism for chemoresistance of tumours is overexpression of the adenosine triphosphate-binding cassette transporter P-glycoprotein (Pgp). Pgp reduces intracellular concentrations of chemotherapeutic drugs. Aim of this study was to compare the suitability of the radiolabelled Pgp inhibitors [11C]tariquidar and [11C]elacridar with the Pgp substrate radiotracer (R)-[11C]verapamil to discriminate tumours expressing low and high levels of Pgp using small-animal PET imaging in a murine breast cancer model. Methods Murine mammary carcinoma cells (EMT6) were continuously exposed to doxorubicin to generate a Pgp overexpressing, doxorubicin-resistant cell line (EMT6AR1.0 cells). Both cell lines were subcutaneously injected in female athymic nude mice. One week after implantation, animals underwent PET scans with [11C]tariquidar (n=7), [11C]elacridar (n=6) and (R)-[11C]verapamil (n=7), before and after administration of unlabelled tariquidar (15 mg/kg). Pgp expression in tumour grafts was studied by Western blotting. Results [11C]Tariquidar showed significantly higher retention in Pgp overexpressing EMT6AR1.0 compared with EMT6 tumours (mean area under the time-activity curve in scan 1 from time 0 to 60 min, AUC0-60±SD: 38.8±2.2 min vs. 25.0±5.3 min, p=0.016, Wilcoxon matched pairs test). [11C]Elacridar and (R)-[11C]verapamil were not able to discriminate Pgp expression in tumour models. Following administration of unlabelled tariquidar, both EMT6Ar1.0 and EMT6 tumours showed increases in tumoural uptake of [11C]tariquidar, [11C]elacridar and (R)-[11C]verapamil. Conclusions Among the tested radiotracers, [11C]tariquidar performed best in discriminating high from low Pgp expressing tumours. Therefore [11C]tariquidar merits further investigation as a PET tracer to assess Pgp expression levels of solid tumours. PMID:21983837

  8. Importance of salinity stratification in the build up of El Nino

    NASA Astrophysics Data System (ADS)

    Maes, C.; Picaut, J.; Belamari, S.

    2003-04-01

    An increase of mass and heat content in the equatorial band of the Pacific Ocean, and in particular in the western part of the basin, appears necessary for the initiation of El Nino. This build up has led to the recharge theory of El Nino. The western Pacific warm pool is also characterized by the presence of specific salinity stratification known as the barrier layer. This barrier isolates the warm surface water from entrainment cooling and potentially preserves the heat content prior to El Nino. The importance of salinity stratification in the build up of El Nino is investigated using a general circulation coupled model of the tropical Pacific. The Meteo-France/ARPEGE global atmospheric model coupled to the LODYC/OPA ocean model is able to reproduce self-sustained El Nino events. In particular, this coupled model displays an increase of heat content in the western equatorial Pacific the year prior to each El Nino event. The methodology consists of removing the stratification effect of salinity in the vertical mixing parameterization the year prior to El Nino, and then plugs it back. The cutoff is restricted to the western side of the equatorial band where sea surface temperature (SST) is greater than 28C. By removing the barrier layer the year prior to El Nino, the main effect is to reduce the ocean heat content in the western part of the equatorial band and increase it in the east. When the stratification effect of salinity is plug back, El Nino is greatly reduced or even aborted. This has tested over three El Nino events of different intensities and through 5 additional member ensemble. The failure for El Nino to start is statistically significant and proves that salinity stratification plays a crucial role in the build up of El Nino. Detailed analyses indicate that vertical diffusion in the warm pool and SST-wind coupling in the central Pacific are essential to set up the favorable condition for the initiation of El Nino.

  9. Analytical expressions for the gate utilization factors of passive multiplicity counters including signal build-up

    SciTech Connect

    Croft, Stephen; Evans, Louise G; Schear, Melissa A

    2010-01-01

    In the realm of nuclear safeguards, passive neutron multiplicity counting using shift register pulse train analysis to nondestructively quantify Pu in product materials is a familiar and widely applied technique. The approach most commonly taken is to construct a neutron detector consisting of {sup 3}He filled cylindrical proportional counters embedded in a high density polyethylene moderator. Fast neutrons from the item enter the moderator and are quickly slowed down, on timescales of the order of 1-2 {micro}s, creating a thermal population which then persists typically for several 10's {micro}s and is sampled by the {sup 3}He detectors. Because the initial transient is of comparatively short duration it has been traditional to treat it as instantaneous and furthermore to approximate the subsequent capture time distribution as exponential in shape. With these approximations simple expressions for the various Gate Utilization Factors (GUFs) can be obtained. These factors represent the proportion of time correlated events i.e. Doubles and Triples signal present in the pulse train that is detected by the coincidence gate structure chosen (predelay and gate width settings of the multiplicity shift register). More complicated expressions can be derived by generalizing the capture time distribution to multiple time components or harmonics typically present in real systems. When it comes to applying passive neutron multiplicity methods to extremely intense (i.e. high emission rate and highly multiplying) neutron sources there is a drive to use detector types with very fast response characteristics in order to cope with the high rates. In addition to short pulse width, detectors with a short capture time profile are also desirable so that a short coincidence gate width can be set in order to reduce the chance or Accidental coincidence signal. In extreme cases, such as might be realized using boron loaded scintillators, the dieaway time may be so short that the build-up

  10. Acoustic build-up in on-chip stimulated Brillouin scattering

    PubMed Central

    Wolff, C.; Steel, M. J.; Eggleton, B. J.; Poulton, C. G.

    2015-01-01

    We investigate the role of the spatial evolution of the acoustic field in stimulated Brillouin scattering processes in short high-gain structures. When the gain is strong enough that the gain length becomes comparable to the acoustic wave decay length of order 100 microns, standard approximations treating the acoustic field as a local response no longer apply. Treating the acoustic evolution more accurately, we find that the backward SBS gain of sub-millimetre long waveguides is significantly reduced from the value obtained by the conventional treatment because the acoustic mode requires several decay lengths to build up to its nominal value. In addition, the corresponding resonance line is broadened with the development of side bands. In contrast, we argue that intra-mode forward SBS is not expected to show these effects. Our results have implications for several recent proposals and experiments on high-gain stimulated Brillouin scattering in short semiconductor waveguides. PMID:26338720

  11. Twin ruptures grew to build up the giant 2011 Tohoku, Japan, earthquake

    PubMed Central

    Maercklin, Nils; Festa, Gaetano; Colombelli, Simona; Zollo, Aldo

    2012-01-01

    The 2011 Tohoku megathrust earthquake had an unexpected size for the region. To image the earthquake rupture in detail, we applied a novel backprojection technique to waveforms from local accelerometer networks. The earthquake began as a small-size twin rupture, slowly propagating mainly updip and triggering the break of a larger-size asperity at shallower depths, resulting in up to 50 m slip and causing high-amplitude tsunami waves. For a long time the rupture remained in a 100–150 km wide slab segment delimited by oceanic fractures, before propagating further to the southwest. The occurrence of large slip at shallow depths likely favored the propagation across contiguous slab segments and contributed to build up a giant earthquake. The lateral variations in the slab geometry may act as geometrical or mechanical barriers finally controlling the earthquake rupture nucleation, evolution and arrest. PMID:23050093

  12. Building-up a Smile in a 5-Year-Old Child: A Case Report.

    PubMed

    Marwaha, Mohita; Bhat, Manohar; Singh Nanda, Kanwar Deep

    2012-05-01

    A variety of therapeutic modalities, from removable partial dentures to conventional fixed space maintainer can be used for the replacement of traumatically missing or carious lost primary anterior teeth. Dentistry has advanced to a point where it is undesirable for children to be partially edentulous or to have unattractive anterior teeth. The introduction of new materials and adhesive systems in dentistry, offers a new reconstructive alternative for severely destroyed or lost primary anterior teeth. The purpose of this article was to present a clinical case of four primary anterior teeth replacement by means of fiber-reinforced composite bridge. This technique offers a conservative, esthetic and noninvasive treatment. It can be considered, as a long- lasting reversible provisional treatment. How to cite this article: Marwaha M, Bhat M, Nanda KDS. Building-up a Smile in a 5-Year-Old Child: A Case Report. Int J Clin Pediatr Dent 2012;5(2):151-154.

  13. Building-up a Smile in a 5-Year-Old Child: A Case Report

    PubMed Central

    Bhat, Manohar; Singh Nanda, Kanwar Deep

    2012-01-01

    ABSTRACT A variety of therapeutic modalities, from removable partial dentures to conventional fixed space maintainer can be used for the replacement of traumatically missing or carious lost primary anterior teeth. Dentistry has advanced to a point where it is undesirable for children to be partially edentulous or to have unattractive anterior teeth. The introduction of new materials and adhesive systems in dentistry, offers a new reconstructive alternative for severely destroyed or lost primary anterior teeth. The purpose of this article was to present a clinical case of four primary anterior teeth replacement by means of fiber-reinforced composite bridge. This technique offers a conservative, esthetic and noninvasive treatment. It can be considered, as a long- lasting reversible provisional treatment. How to cite this article: Marwaha M, Bhat M, Nanda KDS. Building-up a Smile in a 5-Year-Old Child: A Case Report. Int J Clin Pediatr Dent 2012;5(2):151-154. PMID:25206158

  14. Can captive orangutans (Pongo pygmaeus abelii) be coaxed into cumulative build-up of techniques?

    PubMed

    Lehner, Stephan R; Burkart, Judith M; Schaik, Carel P van

    2011-11-01

    While striking cultural variation in behavior from one site to another has been described in chimpanzees and orangutans, cumulative culture might be unique to humans. Captive chimpanzees were recently found to be rather conservative, sticking to the technique they had mastered, even after more effective alternatives were demonstrated. Behavioral flexibility in problem solving, in the sense of acquiring new solutions after having learned another one earlier, is a vital prerequisite for cumulative build-up of techniques. Here, we experimentally investigate whether captive orangutans show such flexibility, and if so, whether they show techniques that cumulatively build up (ratchet) on previous ones after conditions of the task are changed. We provided nine Sumatran orangutans (Pongo pygmaeus abelii) with two types of transparent tubes partly filled with syrup, along with potential tools such as sticks, twigs, wood wool and paper. In the first phase, the orangutans could reach inside the tubes with their hands (Regular Condition), but in the following phase, tubes had been made too narrow for their hands to fit in (Restricted Condition 1), or in addition the setup lacked their favorite materials (Restricted Condition 2). The orangutans showed high behavioral flexibility, applying nine different techniques under the regular condition in total. Individuals abandoned preferred techniques and switched to different techniques under restricted conditions when this was advantageous. We show for two of these techniques how they cumulatively built up on earlier ones. This suggests that the near-absence of cumulative culture in wild orangutans is not due to a lack of flexibility when existing solutions to tasks are made impossible.

  15. Inhibition of radical reactions for an improved potassium tert-butoxide-promoted (11) C-methylation strategy for the synthesis of α-(11) C-methyl amino acids.

    PubMed

    Suzuki, Chie; Kato, Koichi; Tsuji, Atsushi B; Zhang, Ming-Rong; Arano, Yasushi; Saga, Tsuneo

    2015-03-01

    α-(11) C-Methyl amino acids are useful tools for biological imaging studies. However, a robust procedure for the labeling of amino acids has not yet been established. In this study, the (11) C-methylation of Schiff-base-activated α-amino acid derivatives has been optimized for the radiosynthesis of various α-(11) C-methyl amino acids. The benzophenone imine analog of methyl 2-amino butyrate was (11) C-methylated with [(11) C]methyl iodide following its initial deprotonation with potassium tert-butoxide (KOtBu). The use of an alternative base such as tetrabutylammonium fluoride, triethylamine, and 1,8-diazabicyclo[5.4.0]undec-7-ene did not result in the (11) C-methylated product. Furthermore, the KOtBu-promoted (11) C-methylation of the Schiff-base-activated amino acid analog was enhanced by the addition of 1,2,4,5-tetramethoxybenzene or 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) and inhibited by the addition of 1,10-phenanthroline. These results suggest that inhibition of radical generation induced by KOtBu improves the α-(11) C-methylation of the Schiff-base-activated amino acids. The addition of a mixture of KOtBu and TEMPO to a solution of Schiff-base-activated amino acid ester and [(11) C]methyl iodide provided optimal results, and the tert-butyl ester and benzophenone imine groups could be readily hydrolyzed to give the desired α-(11) C-methyl amino acids with a high radiochemical conversion. This strategy could be readily applied to the synthesis of other α-(11) C-methyl amino acids.

  16. Synthesis and evaluation of inhaled [11C]butane and intravenously injected [11C]acetone as potential radiotracers for studying inhalant abuse.

    PubMed

    Gerasimov, Madina R; Ferrieri, Richard A; Pareto, Deborah; Logan, Jean; Alexoff, David; Ding, Yu-Shin

    2005-02-01

    The phenomenon of inhalant abuse is a growing problem in the US and many countries around the world. Yet, relatively little is known about the pharmacokinetic properties of inhalants that underlie their abuse potential. While the synthesis of 11C-labeled toluene, acetone and butane has been proposed in the literature, none of these compounds has been developed as radiotracers for PET studies. In the present report we extend our previous studies with [11C]toluene to include [11C]acetone and [11C]butane with the goal of comparing the pharmacokinetic profiles of these three volatile abused substances. Both [11C]toluene and [11C]acetone were administered intravenously and [11C]butane was administered via inhalation to anesthesized baboons. Rapid and efficient uptake of radiolabeled toluene and acetone into the brain was followed by fast clearance in the case of toluene and slower kinetics in the case of acetone. [11C]Butane was detected in the blood and brain following inhalation, but the levels of radioactivity in both tissues dropped to half of the maximal values over the period of less than a minute. To our knowledge, this is the first reported study of the in vivo brain pharmacokinetics of labeled acetone and butane in nonhuman primates. These data provide insight into the pharmacokinetic features possibly associated with the abuse liability of toluene, acetone and butane.

  17. Interplanetary proton fluence model - JPL 1991

    NASA Technical Reports Server (NTRS)

    Feynman, J.; Spitale, G.; Wang, J.; Gabriel, S.

    1993-01-01

    We describe an updated predictive engineering model for the interplanetary fluence of protons with energies respectively greater than 1, 4, 10, 30, and 60 MeV. This has been the first opportunity to derive a model from a data set that has been collected in space over a long enough period of time to produce a valid sample of solar proton events. The model provides a quantitative basis for estimating the exposures to solar protons of spacecraft during missions of varying length and of surfaces and atmospheres of solar system objects. The data sets contain several major proton events comparable to the 1972 event. For the cases of the over 10 and over 30 MeV particles, the fluences are somewhat lower than in our earlier model No over 1, over 4, and over 60 MeV proton fluence models have been published in the literature previously. We present our results in a convenient graphical form which may be used to calculate the 1 AU fluence expected at a given confidence level as a function of the length of the exposure. A method of extending this estimate to other heliocentric distances is described.

  18. Studies with differentially labeled [11C]cocaine, [11C]norcocaine, [11C]benzoylecgonine, and [11C]- and 4'-[18F]fluorococaine to probe the extent to which [11C]cocaine metabolites contribute to PET images of the baboon brain.

    PubMed

    Gatley, S J; Yu, D W; Fowler, J S; MacGregor, R R; Schlyer, D J; Dewey, S L; Wolf, A P; Martin, T; Shea, C E; Volkow, N D

    1994-03-01

    The psychostimulant drug of abuse, cocaine (benzoylecgonine methyl ester), is rapidly metabolized by cleavage of its two ester groups, to give benzoylecgonine (BE) and ecgonine methyl ester, and by N-demethylation, to give N-norcocaine (NC). The recent use of [N-methyl-11CH3]cocaine to image brain cocaine binding sites with positron emission tomography (PET) raises the question of whether PET images partially reflect the distribution and kinetics of labeled cocaine metabolites. We prepared [O-methyl-11CH3]cocaine by methylation of the sodium salt of BE with [11C]CH3I, and showed that PET baboon brain scans, as well as regional brain kinetics and plasma time-activity curves corrected for the presence of labeled metabolites, are nearly identical to those seen with [N-methyl-11CH3]cocaine. This strongly suggests that 11C metabolites do not significantly affect PET images, because the metabolite pattern is different for the two labeled forms of cocaine. In particular, nearly half the 11C in blood plasma at 30 min was [11C]CO2 when [N-methyl-11CH3]cocaine was administered, whereas [11C]CO2 was not formed from [O-methyl-11CH3]cocaine. Only a trace of [11C]NC was detected in plasma after [O-methyl-11CH3]cocaine administration. Nearly identical brain PET data were also obtained when 4'-[N-methyl-11CH3]fluorococaine and 4'-[18F]fluorococaine (prepared by nucleophilic aromatic substitution from [18F]fluoride- and 4'-nitrococaine) were compared with [N-methyl-11CH3]cocaine. In vitro assays with rat brain membranes showed that cocaine and 4'-fluorococaine were equipotent at the dopamine reuptake site, but that 4'-fluorococaine was about 100 times more potent at the 5-hydroxytryptamine reuptake site.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. Cenozoic topographic build-up of the Iranien plateau: first constraints from low-temperature thermochronology

    NASA Astrophysics Data System (ADS)

    François, Thomas; Agard, Philippe; Meyer, Bertrand; Zarrinkoub, Mohammad; Chung, Sun-Lin; Bernet, Matthias; Burov, Evgueni

    2013-04-01

    The Iranian plateau is a smooth topographic high at the rear of the Zagros mountains, with average elevation of c. 1.5 km. Its formation is thought to result from the collision between the Arabian and Eurasian plates since ~35 Myrs, following a long-standing subduction, and represents an interesting analogue to the so far better documented Tibetan plateau. Yet, while the Zagros orogeny was reappraised by numerous authors over the past few years, the topographic build-up of both the Zagros and the Iranian plateau remains ill-constrained. We herein present (U-Th)/He and fission track (FT) thermochronology results to reconstruct the Cenozoic tectonic evolution of the Iranien plateau and quantify the age and amount of vertical movements. Apatite and zircon single grain cooling age data were collected on plutonic rocks (for which crystallization ages were already available: Chiu et al., 2010) from the internal domains of Sanandaj-Sirjan Zone (SSZ), Urumieh-Doktar magmatic arc (UDMA), Central Iran and, for comparison, Kopet Dagh. We stress that an important milestone for topographic build-up is the presence of the marine Qom formation (coeval with the external Asmari formation) in the UDMA and part of the SSZ, indicating that the plateau was at or near sea level at 20 Ma. Temperature time paths inferred from low temperature thermochronology suggest a spatial and temporal separation of exhumation processes. The results show that the SSZ was exhumed very early in the collision process (essentially before 20 Ma), with a likely acceleration around the Oligocene (i.e., at the onset of continental collision) from 0.05 to 0.3 mm/yr. Post-collision cooling along the UDMA is marked by an average, constant exhumation rate of 0.3-0.4 mm/yr, which suggests that no significant increase or decrease of erosion occurred since continental collision. In Central Iran, the overlap (within error) of ZrFT, AFT and AHe ages from gneissic samples points to their rapid cooling during the upper

  20. Target design considerations for high specific activity [{sup 11}C]O{sub 2}

    SciTech Connect

    Ferrieri, R.A.; Alexoff, D.L.; Schlyer, D.J.; McDonald, K.; Wolf, A.P.

    1993-12-31

    In the routine preparation of {sup 11}C-labeled compounds through N-[{sup 11}C]-methylation using [{sup 11}C]H{sub 3}I, total masses are always higher than synthesis mass contribution, suggesting that the target system contributes carrier carbon to the final product mass. This conclusion prompted this evaluation of target materials and target design for [{sup 11}C]O{sub 2} production. Ultimately, one is faced with the sprospect of compromising between [{sup 11}C]O{sub 2} specific activity and the amount that can be extracted from the target after a reasonable irradiation time.

  1. Build-up Approach to Updating the Mock Quiet Spike(TM)Beam Model

    NASA Technical Reports Server (NTRS)

    Herrera, Claudia Y.; Pak, Chan-gi

    2007-01-01

    A crucial part of aircraft design is ensuring that the required margin for flutter is satisfied. A trustworthy flutter analysis, which begins by possessing an accurate dynamics model, is necessary for this task. Traditionally, a model was updated manually by fine tuning specific stiffness parameters until the analytical results matched test data. This is a time consuming iterative process. The NASA Dryden Flight Research Center has developed a mode matching code to execute this process in a more efficient manner. Recently, this code was implemented in the F-15B/Quiet Spike (Gulfstream Aerospace Corporation, Savannah, Georgia) model update. A build-up approach requiring several ground vibration test configurations and a series of model updates was implemented to determine the connection stiffness between aircraft and test article. The mode matching code successfully updated various models for the F-15B/Quiet Spike project to within 1 percent error in frequency and the modal assurance criteria values ranged from 88.51-99.42 percent.

  2. Build-up Approach to Updating the Mock Quiet Spike(TradeMark) Beam Model

    NASA Technical Reports Server (NTRS)

    Herrera, Claudia Y.; Pak, Chan-gi

    2007-01-01

    A crucial part of aircraft design is ensuring that the required margin for flutter is satisfied. A trustworthy flutter analysis, which begins by possessing an accurate dynamics model, is necessary for this task. Traditionally, a model was updated manually by fine tuning specific stiffness parameters until the analytical results matched test data. This is a time consuming iterative process. NASA Dryden Flight Research Center has developed a mode matching code to execute this process in a more efficient manner. Recently, this code was implemented in the F-15B/Quiet Spike(TradeMark) (Gulfstream Aerospace Corporation, Savannah, Georgia) model update. A build-up approach requiring several ground vibration test configurations and a series of model updates was implemented in order to determine the connection stiffness between aircraft and test article. The mode matching code successfully updated various models for the F-15B/Quiet Spike(TradeMark) project to within 1 percent error in frequency and the modal assurance criteria values ranged from 88.51-99.42 percent.

  3. Comparative study of mechanical properties of direct core build-up materials

    PubMed Central

    Kumar, Girish; Shivrayan, Amit

    2015-01-01

    Background and Objectives: The strength greatly influences the selection of core material because core must withstand forces due to mastication and para-function for many years. This study was conducted to evaluate certain mechanical properties of commonly used materials for direct core build-up, including visible light cured composite, polyacid modified composite, resin modified glass ionomer, high copper amalgam, and silver cermet cement. Materials and Methods: All the materials were manipulated according to the manufacturer's recommendations and standard test specimens were prepared. A universal testing machine at different cross-head speed was used to determine all the four mechanical properties. Mean compressive strength, diametral tensile strength, flexural strength, and elastic modulus with standard deviations were calculated. Multiple comparisons of the materials were also done. Results: Considerable differences in compressive strength, diametral tensile strength, and flexural strength were observed. Visible light cured composite showed relatively high compressive strength, diametral tensile strength, and flexural strength compared with the other tested materials. Amalgam showed the highest value for elastic modulus. Silver cermet showed less value for all the properties except for elastic modulus. Conclusions: Strength is one of the most important criteria for selection of a core material. Stronger materials better resist deformation and fracture provide more equitable stress distribution, greater stability, and greater probability of clinical success. PMID:25684905

  4. Building up low-complexity spectrally-efficient Terabit superchannels by receiver-side duobinary shaping.

    PubMed

    Li, Jianqiang; Sjödin, Martin; Karlsson, Magnus; Andrekson, Peter A

    2012-04-23

    Recently, an increasing interest has been put on spectrally-efficient multi-carrier superchannels for beyond 100G. Apart from orthogonal frequency-division multiplexing (OFDM) and Nyquist wavelength-division multiplexing (WDM), another low-complexity WDM approach based on transmitter-side pre-filtering and receiver-side duobinary shaping is proposed to build up multi-carrier superchannels. This approach is referred to as receiver-side duobinary-shaped WDM (RS-DBS-WDM). Generation and transmission of a 1.232-Tbit/s 11-carrier superchannel is experimentally demonstrated. The superchannel signal can be well fit inside the passband of multiple 300-GHz reconfigurable optical add and drop multiplexers (ROADMs). In the superchannel scenario, the proposed RS-DBS-WDM is qualitatively compared with OFDM and Nyquist-WDM in terms of implementation complexity. In sum, the proposed RS-DBS-WDM approach features high transceiver analog-bandwidth efficiency, high spectral-efficiency, the absence of specific spectral manipulation, compatibility with conventional WDM technologies and coherent detection algorithms, and comparable implementation penalty.

  5. Integration of micro-filtration into osmotic membrane bioreactors to prevent salinity build-up.

    PubMed

    Wang, Xinhua; Yuan, Bo; Chen, Yao; Li, Xiufen; Ren, Yueping

    2014-09-01

    The high salinity remains as one of major obstacles of the osmotic membrane bioreactor (OMBR). In this study, a new pathway was explored to prevent the salinity build-up by integrating the micro-filtration (MF) membrane to the OMBR (MF-OMBR). The results indicated that the salinity characterized by conductivity in the MF-OMBR was effectively alleviated and controlled at a lower value of about 5 mS/cm, and the stable flux of forward osmosis (FO) membrane correspondingly increased to approximately 5.5L/(m(2)h). Besides, the addition of MF membrane in the OMBR could increase the total organic carbon (TOC) and ammonium nitrogen (NH3-N) removals due to the activated sludge by improving the microbial activity. The membrane fouling especially the reversible fouling in the MF-OMBR was severer compared to that in the conventional OMBR, which resulted in a lower water flux than the expectation due to the increase of filtration resistance and external concentration polarization.

  6. An efficient and practical synthesis of [2-11C]indole via superfast nucleophilic [11C]cyanation and RANEY® Nickel catalyzed reductive cyclization

    DOE PAGES

    So Jeong Lee; Fowler, Joanna S.; Alexoff, David; Schueller, Michael; Kim, Dohyun; Nauth, Alexander; Weber, Carina; Kim, Sung Won; Hooker, Jacob M.; Ma, Ling; et al

    2015-09-21

    We developed a rapid method for the synthesis of carbon-11 radiolabeled indole using a sub-nanomolar quantity of no-carrier-added [11C]cyanide as radio-precursor. Based upon a reported synthesis of 2-(2-nitrophenyl)acetonitrile (2), a highly reactive substrate 2-nitrobenzyl bromide (1) was evaluated for nucleophilic [11C]cyanation. Additionally, related reaction conditions were explored with the goal of obtaining of highly reactive 2-(2-nitrophenyl)-[1-11C]acetonitrile ([11C]-2) while inhibiting its rapid conversion to 2,3-bis(2-nitrophenyl)-[1-11C]propanenitrile ([11C]-3). Next, a Raney Nickel catalyzed reductive cyclization method was utilized for synthesizing the desired [2-11C]indole with hydrazinium monoformate as the active reducing agent. Extensive and iterative screening of basicity, temperature and stoichiometry was required tomore » overcome the large stoichiometry bias that favored 2-nitrobenzylbromide (1) over [11C]cyanide, which both caused further alkylation of the desired nitrile and poisoned the Raney Nickel catalyst. The result is an efficient two-step, streamlined method to reliably synthesize [2-11C]indole with an entire radiochemical yield of 21 ± 2.2% (n = 5, ranging from 18 – 24%). The radiochemical purity of the final product was > 98% and specific activity was 176 ± 24.8 GBq/μmol (n = 5, ranging from 141 – 204 GBq/μmol). The total radiosynthesis time including product purification by semi-preparative HPLC was 50 – 55 min from end of cyclotron bombardment.« less

  7. Influence of uncertainty inherent to heavy metal build-up and wash-off on stormwater quality.

    PubMed

    Wijesiri, Buddhi; Egodawatta, Prasanna; McGree, James; Goonetilleke, Ashantha

    2016-03-15

    Uncertainty inherent to heavy metal build-up and wash-off stems from process variability. This results in inaccurate interpretation of stormwater quality model predictions. The research study has characterised the variability in heavy metal build-up and wash-off processes based on the temporal variations in particle-bound heavy metals commonly found on urban roads. The study outcomes found that the distribution of Al, Cr, Mn, Fe, Ni, Cu, Zn, Cd and Pb were consistent over particle size fractions <150 μm and >150 μm, with most metals concentrated in the particle size fraction <150 μm. When build-up and wash-off are considered as independent processes, the temporal variations in these processes in relation to the heavy metals load are consistent with variations in the particulate load. However, the temporal variations in the load in build-up and wash-off of heavy metals and particulates are not consistent for consecutive build-up and wash-off events that occur on a continuous timeline. These inconsistencies are attributed to interactions between heavy metals and particulates <150 μm and >150 μm, which are influenced by particle characteristics such as organic matter content. The behavioural variability of particles determines the variations in the heavy metals load entrained in stormwater runoff. Accordingly, the variability in build-up and wash-off of particle-bound pollutants needs to be characterised in the description of pollutant attachment to particulates in stormwater quality modelling. This will ensure the accounting of process uncertainty, and thereby enhancing the interpretation of the outcomes derived from modelling studies.

  8. Effect of the calibration in water and the build-up cap on the Mg(Ar) ionization chamber measurements.

    PubMed

    Koivunoro, H; Hyvönen, H; Uusi-Simola, J; Jokelainen, I; Kosunen, A; Kortesniemi, M; Seppälä, T; Auterinen, I; Savolainen, S

    2011-12-01

    Magnesium-walled argon gas flow ionization chamber (Mg(Ar)) is used for photon dose measurements in the epithermal neutron beam of FiR 1 reactor in Finland. In this study, the photon dose measurements were re-evaluated against calculations applying a new chamber calibration factor defined in water instead of in air. Also, effect of the build-up cap on the measurements was investigated. The new calibration factor provides improved agreement between measured and calculated photon dose. Use of the build-up cap does not affect the measured signal in water in neutron beam.

  9. [11C]PR04.MZ, a promising DAT ligand for low concentration imaging: synthesis, efficient 11C-0-methylation and initial small animal PET studies

    SciTech Connect

    Riss, P.J.; Hooker, J.; Alexoff, D.; Kim, Sung-Won; Fowler, J.S.; Roesch, F.

    2009-05-01

    PR04.MZ was designed as a highly selective dopamine transporter inhibitor, derived from natural cocaine. Its binding profile indicates that [{sup 11}C]PR04.MZ may be suited as a PET radioligand for the non-invasive exploration of striatal and extrastriatal DAT populations. As a key feature, its structural design facilitates both, labelling with fluorine-18 at its terminally fluorinated butynyl moiety and carbon-11 at its methyl ester function. The present report concerns the efficient [{sup 11}C]MeI mediated synthesis of [{sup 11}C]PR04.MZ from an O-desmethyl precursor trifluoroacetic acid salt with Rb{sub 2}CO{sub 3} in DMF in up to 95 {+-} 5% labelling yield. A preliminary {mu}PET-experiment demonstrates the reversible, highly specific binding of [{sup 11}C]PR04.MZ in the brain of a male Sprague-Dawley rat.

  10. Synthesis optimization of 2-(4-N-[11C]methylaminophenyl)-6-hydroxybenzothiazole ([11C]PIB), β-amyloid PET imaging tracer for Alzheimer's disease diagnosis.

    PubMed

    Coliva, A; Monterisi, C; Apollaro, A; Gatti, D; Penso, M; Gianolli, L; Perani, D; Gilardi, M C; Carpinelli, A

    2015-11-01

    [11C]PIB is the most used amyloid plaques-specific positron-emitting radiotracers. The radiosynthesis of this compound, carried out by methylation of its precursor with [11C]methyl triflate in 2-butanone, has been improved optimizing the initial concentration and the purification method. Two HPLC methods were compared: good radiochemical yields, specific activities, and chemical purity above 98% were achieved by using as eluant acetonitrile/citrate and formulation in 10% ethanol.

  11. Synthesis of radiotracers for studying muscarinic cholinergic receptors in the living human brain using positron emission tomography: [11C]dexetimide and [11C]levetimide.

    PubMed

    Dannals, R F; Långström, B; Ravert, H T; Wilson, A A; Wagner, H N

    1988-01-01

    Dexetimide (Fig. 1a), a potent muscarinic cholinergic receptor antagonist, and levetimide (Fig. 1b), its pharmacologically inactive enantiomer, were labeled with 11C for non-invasive in vivo studies of muscarinic cholinergic receptors in the human brain using positron emission tomography. The syntheses were completed in approximately 32 min using [alpha-11C]benzyl iodide as the precursor. The synthesis, purification, characterization and determination of specific activity are presented and discussed. PMID:2838435

  12. Assessment of potential nutrient build-up around beef cattle production areas using electromagnetic induction.

    PubMed

    Cordeiro, Marcos R C; Ranjan, Ramanathan Sri; Cicek, Nazim

    2011-12-01

    Electromagnetic induction (EMI) has been used to map soil properties such as salinity and water content. The objective of this research is to use EMI to map the potential distribution of nutrients around beef cattle pens and to relate this distribution to major physiographic field features. Beef cattle farms in different physiographic locations were surveyed in Manitoba, Canada, using an EM-38 conductivity meter georeferenced with a GPS receiver. Samples were collected using a response surface design and analysed for electrical conductivity (ECe), which was used as a proxy for determining potential build-up of nutrients. Multiple linear regression models (MLR) were used for calibration of the EM readings. The results showed that areas 1 through 4 had ECe < or = 3.5 dSm(-1), but areas 5 and 6 exceeded this concentration and reached maximum values of 5.5 and 7.0 dS m(-1), respectively. Higher values in area 6 were probably due to the presence of a rocky layer at 0.3 m depth, leaving a thin soil layer to accumulate the nutrients. Micro-depressions played a major role in salt accumulation, with the depressions corresponding to higher values of ECe. The presence of features such as drainage ditches and compacted soils beneath roads strongly affected the direction of the plumes. Based on these results, the location of the pens on high elevations and the provision to collect the run-off from the pens were identified as good design criteria. Highly permeable soils may require a low permeability liner to capture the deep percolation and redirect it towards a collection area.

  13. Young and embedded clusters in Cygnus-X: evidence for building up the initial mass function?

    NASA Astrophysics Data System (ADS)

    Maia, F. F. S.; Moraux, E.; Joncour, I.

    2016-05-01

    We provide a new view on the Cygnus-X north complex by accessing for the first time the low mass content of young stellar populations in the region. Canada-France-Hawaii Telescope/Wide-Field Infrared Camera was used to perform a deep near-infrared survey of this complex, sampling stellar masses down to ˜0.1 M⊙. Several analysis tools, including a extinction treatment developed in this work, were employed to identify and uniformly characterize a dozen unstudied young star clusters in the area. Investigation of their mass distributions in low-mass domain revealed a relatively uniform log-normal initial mass function (IMF) with a characteristic mass of 0.32 ± 0.08 M⊙ and mass dispersion of 0.40 ± 0.06. In the high-mass regime, their derived slopes showed that while the youngest clusters (age < 4 Myr) presented slightly shallower values with respect to the Salpeter's, our older clusters (4 Myr < age < 18 Myr) showed IMF compliant values and a slightly denser stellar population. Although possibly evidencing a deviation from an `universal' IMF, these results also supports a scenario where these gas-dominated young clusters gradually `build up' their IMF by accreting low-mass stars formed in their vicinity during their first ˜3 Myr, before the gas expulsion phase, emerging at the age of ˜4 Myr with a fully fledged IMF. Finally, the derived distances to these clusters confirmed the existence of at least three different star-forming regions throughout Cygnus-X north complex, at distances of 500-900 pc, 1.4-1.7 and 3.0 kpc, and revealed evidence of a possible interaction between some of these stellar populations and the Cygnus OB2 association.

  14. A comprehensive interpretation of the NEEM basal ice build-up using a multi parametric approach

    NASA Astrophysics Data System (ADS)

    Goossens, Thomas; Sapart, Celia Julia; Popp, Trevor; El Amri, Saïda; Tison, Jean-louis

    2015-04-01

    Basal ice is a common expression to describe debris-laden ice layers found close to the ice-bedrock interface under glaciers and ice sheets. The study of basal ice properties provides us with the unique opportunity of improving our understanding of subglacial environments and processes and refine ice sheet behaviour modelling. Here, we present and discuss the results of water stable isotopes (δ18O and δD), ice fabrics, debris weight and gas content of the basal part of the NEEM (North Eemian Ice Drilling Program) ice core. Below 2533.85 m deep, almost 10 m of basal debris-rich material were retrieved from the borehole. The situation at NEEM is different from the previously well-documented GRIP core where the basal ice corresponds to pre ice sheet ice overridden by the growing ice sheet. At NEEM, the basal debris-rich material presents δ18O values from -39.89 to -34.36 permil within the range of the above last 300 m of meteoric ice from -44.86 to -30.59 permil. The sequence is however composed of an alternation of three visually contrasting types of ice : clear ice with specks of particulate inclusions, stratified debris-rich layers, and ice containing dispersed debris. Using water stable isotopes (δ18O and δ D) signatures, each of these ice types are discriminated and clues are given for their conditions of formation and transformation processes. The proposed interpretation is then refined in the light of the other available parameters. While clear basal ice with specks corresponds to altered meteoric glacial ice, stratified debris-rich layer and ice containing dispersed debris present a melting/refreezing signature, somewhat blurred by mixing processes. Based on the identified origins of the different ice types, the present study proposes a first interpretative framework for the build-up of the NEEM basal ice sequence.

  15. Binding of nitrided type 410 stainless steel valve stems caused by corrosion product build-up

    SciTech Connect

    Coffin, S.M.; Hardies, R.O.

    1996-10-01

    Nitrided type 410 stainless steel governor valve stems are used in safety-related reactor core isolation cooling (RCIC) and auxiliary feedwater (AFW) pumps at Boiling Water Reactors and Pressurized Water Reactors, respectively. Corrosion of the governor valve stems in the packing assembly area has been noted in at least seventeen nuclear power plants. Corrosion product build-up between the valve stem and packing assembly has resulted in binding of the valve stem in at least nine of these plants. Nitriding is known to degrade the corrosion resistance of, stainless steels. This is due to the formation of chromium nitrides in the diffusion layer of the hardened case which leave the surrounding matrix depleted in chromium. The rate of corrosion is substantially affected by the presence or absence of a continuous, adherent compound layer. The compound layer is less susceptible to corrosion than the diffusion layer and acts to protect the underlying diffusion layer from being exposed to moisture. At Calvert Cliffs, the original nitrided stem had a continuous, adherent compound layer and a hardened case of approximately 60 microns in depth. This stem performed acceptably for years. In contrast, the replacement nitrided stems did not have a continuous, adherent compound layer and had a hardened case of approximately 10 microns in depth. These stems performed acceptably for three or four months. This difference in performance is attributed primarily to the absence of an adherent, continuous compound layer in the recently-supplied nitrided stems. Since nitrided type 410 stainless steel valve stems will corrode in the presence of moisture (although at substantially different rates), the replacement valve stems will be fabricated from Inconel 718.

  16. How does the interaction between spelling and motor processes build up during writing acquisition?

    PubMed

    Kandel, Sonia; Perret, Cyril

    2015-03-01

    How do we recall a word's spelling? How do we produce the movements to form the letters of a word? Writing involves several processing levels. Surprisingly, researchers have focused either on spelling or motor production. However, these processes interact and cannot be studied separately. Spelling processes cascade into movement production. For example, in French, producing letters PAR in the orthographically irregular word PARFUM (perfume) delays motor production with respect to the same letters in the regular word PARDON (pardon). Orthographic regularity refers to the possibility of spelling a word correctly by applying the most frequent sound-letter conversion rules. The present study examined how the interaction between spelling and motor processing builds up during writing acquisition. French 8-10 year old children participated in the experiment. This is the age handwriting skills start to become automatic. The children wrote regular and irregular words that could be frequent or infrequent. They wrote on a digitizer so we could collect data on latency, movement duration and fluency. The results revealed that the interaction between spelling and motor processing was present already at age 8. It became more adult-like at ages 9 and 10. Before starting to write, processing irregular words took longer than regular words. This processing load spread into movement production. It increased writing duration and rendered the movements more dysfluent. Word frequency affected latencies and cascaded into production. It modulated writing duration but not movement fluency. Writing infrequent words took longer than frequent words. The data suggests that orthographic regularity has a stronger impact on writing than word frequency. They do not cascade in the same extent.

  17. Proton Particle Test Fluence: What's the Right Number?

    NASA Technical Reports Server (NTRS)

    LaBel, Kenneth A.; Ladbury, Raymond

    2015-01-01

    While we have been utilizing standard fluence levels such as those listed in the JESD57 document, we have begun revisiting what an appropriate test fluence is when it comes to qualifying a device for single events. Instead of a fixed fluence level or until a specific number of events occurs, a different thought process is required.

  18. The solar physics shuttle/Spacelab program and its relationship to studies of the flare build-up

    NASA Technical Reports Server (NTRS)

    Neupert, W. M.

    1975-01-01

    The definition of the NASA program to support astronomical observations from shuttle/Spacelab is discussed. Steps are described which were taken to insure that instruments to be used in specific scientific efforts such as a flare build-up study have flight opportunities.

  19. A comprehensive interpretation of the NEEM basal ice build-up using a multi parametric approach

    NASA Astrophysics Data System (ADS)

    Goossens, T.; Sapart, C. J.; Dahl-Jensen, D.; Popp, T.; El Amri, S.; Tison, J. L.

    2015-10-01

    interpretative framework for the build-up of the NEEM basal ice sequence, based on the origin of the various ice types.

  20. Clinical comparison of various esthetic restorative options for coronal build-up of primary anterior teeth

    PubMed Central

    Duhan, Himanshu; Pandit, Inder Kumar; Srivastava, Nikhil; Gugnani, Neeraj; Gupta, Monika; Kochhar, Gulsheen Kaur

    2015-01-01

    Background: This study was designed to compare the clinical performance of composite, strip crowns, biological restoration, and composite with stainless steel band when used for the coronal build-up of anterior teeth. Materials and Methods: A total of 20 patients aged 3-6 years presenting with mutilated primary anterior teeth due to caries or trauma were selected for the study using randomized simple sampling. A total of 52 primary anterior teeth were randomly divided into four equal groups having 13 teeth in each group. Teeth in Group I were restored with composite, in Group II with strip crowns, in Group III with biologic restoration and with stainless steel band reinforced composite in group IV. The restorations were evaluated for color match, retention, surface texture, and anatomic form according to Ryge's Direct (US Public Health Service) evaluation criteria at baseline (immediate postoperative), after 48 h, 3, 6, and 9 months. The data obtained were statistically analyzed using Chi-square test, and level of significance, that is, P value was determined. Results: At baseline, none of the groups showed any color changes. Other than Group III all other groups showed highly significant changes (P < 0.05) in color after 3 months. Loss of retention was seen in both Groups I and IV after 3 months. After 6 months, retention loss was seen in all the groups except Group II, in which loss was seen after 9 months (P > 0.05). Deterioration in surface texture was exhibited maximum by restorations in Group IV followed by Group I at 3 months. Whereas, no surface changes were seen in Group II and III. Only Group I and IV showed discontinuity in anatomic form after 3 months. After 6 months, except in Group II, discontinuity in anatomic form was observed in all the groups. Discontinuity in anatomic form was seen in all the 4 groups after 9 months although the difference was not significant (P > 0.05). Conclusion: Biological restoration was found to be most satisfying

  1. Public health policy and the building up of a Brazilian medical identity.

    PubMed

    de Castro-Santos, L A

    2005-12-01

    Since George Herbert Mead studied "the social self" and the interactionists went further in distinguishing "images of self", a lecture on the building up of a Brazilian medical identity should try to focus on the patterns of self-images, presented images, and aspired-to images among the Brazilian medical elites during the First Republic (1889-1930). In no other period of Brazilian history were those "images" of professional identity so close--in contrast, later periods of Brazilian history witnessed an almost permanent "collision" or the clashing of such images among public health specialists. Oswaldo Cruz, Carlos Chagas, Artur Neiva and Belisário Pena are perhaps the best examples of successful careers as "sanitarians" (to recall John Duffy's historical work on luminaries before and after the "New Public Health" in the United States), and as important political actors during Brazil's First Republic. In light of the prominent political, policy-oriented, and scientific roles public health professionals played in Brazil, it is interesting to suggest that in large part such prominence resulted from the symbolic impact of the ideologies of sanitary reform on the political agenda of that period of Brazilian history. Where many studies look for personal rivalries and disputes around Chagas and Neiva as public figures, we may also see the importance of finding identity-building processes among public health specialists as an integrated group (e.g., trying to appear as "significant others" for the new generations of medical graduates in the country), regardless of existing rivalries. Cruz and Chagas, especially, were names with great impact in the Brazilian press (pro and con), a circumstance made possible largely by their easy and direct access to the Brazilian presidents Rodrigues Alves and Epitácio Pessoa, and, most clearly, by public health being one of Brazil's political priorities to find a place among the "civilized nations" of the world. A task that further

  2. Synthesis and positron emission tomographic (PET) baboon studies of [{sup 11}C]methadone and R-(-)-[{sup 11}C]methandone

    SciTech Connect

    Ding, Y.S.; Fowler, J.S.; Volkow, N.D.

    1996-05-01

    Methadone (MET) maintenance has been used successfully for many years in the rehabilitation of heroin addicts. MET, a typical m{mu}-opioid receptor agonist, exists as two enantiomers and is used clinically as the racemic mixture. However, R-(-)-MET has a 10-fold higher affinity for m{mu} receptors than S-(+)-MET (IC{sub 50}: 3.0 nM and 26.4 nM, respectively) and R-(-)-MET is almost entirely responsible for the therapeutic actions of the racemate. In order to examine the pharmacokinetics and stereoselectivity of the drug, we have synthesized both [{sup 11}C]MET and R-(-)-[{sup 11}C]MET. Preparing the precursor by one-step approach to the N-demethylated methadone was precluded as other investigators cited problems with intramolecular cyclization. Therefore, a four-step synthesis using MET (or R-(-)-MET) as starting material was required to obtain the precursor, followed by a two-step radiolabeling synthesis (N-methylation followed by oxidation) to obtain [{sup 11}C]MET (or R-(-)-[{sup 11}C]MET). Comparative PET studies in the same baboon showed peak striatal uptake was 0.022%/cc at 5 minutes with a half time of clearance from peak of 100 minutes for R-(-)-[{sup 11}C]MET and a peak uptake of 0.013%/cc with a half time of 90 min for [{sup 11}C]MET. R-(-)-[{sup 11}C]MET also showed a slower disappearance in plasma. Both tracers showed higher C-11 in basal ganglia (BG), thalamus and midbrain relative to the cerebellum (CB) and occipital cortex (OC) but the BG/OC ratio was higher for R-(-)-[{sup 11}C]MET (1.3 vs 1.1). Pretreatment with naloxone (1 mg/kg, iv) increased R-(-)-[{sup 11}C]MET uptake in all brain regions whereas unlabeled MET slightly increased C-11 clearance in BG, OC and CB. These initial results show higher brain concentration and specificity of the pharmacologically active enantiomer of methadone along with significant non-specific binding.

  3. Development of additive [11C]CO2 target system in the KOTRON-13 cyclotron and its application for [11C]radiopharmaceutical production

    NASA Astrophysics Data System (ADS)

    Moon, Byung Seok; Lee, Hong Jin; Lee, Won Kyung; Hur, Min Goo; Yang, Seung Dae; Lee, Byung Chul; Kim, Sang Eun

    2015-08-01

    The KOTRON-13 cyclotron, which was developed in South Korea for the production of medical radioisotopes, has the structural limitation of only one beam-output port, restricting the production of the carbon-11 isotope. In the present study, we investigate the design of a switchable target system and develop an effective carbon-11 target in the KOTRON-13 cyclotron, for combination with the fluorine-18 target. The target system was designed by introducing a sliding-type element between the fluorine-18 and carbon-11 targets, a tailor-made C-11 target and its cooling system. For the efficient production of [11C]CO2, the desirable target shape and internal volume were determined by a Stopping and Range of Ions in Matter (SRIM) simulation program, and the target grid was modified to resist the cavity pressure during beam irradiation. We evaluated the [11C]CO2 production while varying the material and thickness of the target foil, oxygen content of the nitrogen gas, and target loading pressure. Using sliding-type equipment including an additional gate valve and a high vacuum in a beam line, the bi-directional conversion between the fluorine-18 and carbon-11 targets was efficient regarding the accurate beam irradiation on both targets. The optimal [11C]CO2 production for 30 min irradiation at 60 μA (86.6 ± 1.7 GBq in the target at EOB) was observed at a thickness of 19 μm with HAVAR® material as a target foil and a target loading pressure of 24 bar with nitrogen plus 300 ppb of oxygen gas. Additionally, the coolant cavity system in the target grid and target chamber is useful to remove the heat transferred to the target body by the internal convection of water and thereby ensure the stability of the [11C]CO2 production under a high beam current. In the application of C-11 labeled radiopharmaceuticals such as [11C]PIB, [11C]DASB, [11C]PBR28, [11C]Methionine and [11C]Clozapine, the radiochemical yields were shown to be 25-38% (decay corrected) with over 166 GBq/μmol of

  4. An asymmetric approach to the radiosynthesis of both enantiomers of α-[11C]methyldopa and α-[11C]methyltyrosine for positron emission tomography

    NASA Astrophysics Data System (ADS)

    Popkov, A.; Nádvorník, M.; Jirman, J.; Kružberská, P.; Lyčka, A.; Weidlich, T.; Kožíšek, J.; Breza, M.; Lehel, S.; Gillings, N. M.

    2006-01-01

    In PET, α-methyl amino acids can play a dual role: a) precursors of neurotransmitters analogues for the study of neurodegenerative diseases; b) non-metabolised analogues of proteinogenic amino acids for the study of amino acids uptake into normal and cancer cells. The difference in the uptake rates during a PET scan could visualise cancer cells in a human body. Clinical applications of such amino acids are strongly limited due to their poor availability. For the synthesis of α-[11C]methyl-tryptohan, an industrial procedure was adopted. All attempts to prepare enantiomerically pure α-[11C]methylated tyrosine failed. We carried out [11C]methylation of metalocomplex synthons derived from protected DOPA or tyrosine. Individual diastereomers were successfully separated by preparative HPLC, diluted with excess of water and extracted on C18 cartridges. Optimisation of the procedure followed by hydrolysis of the complexes and purification of the enantiomers of α-[11C]methylDOPA and α-[11C]methyltyrosine is underway.

  5. 1-/sup 11/C-2-deoxy-D-glucose and process for the preparation thereof

    DOEpatents

    MacGregor, R.R.; Wolf, A.P.; Shiue, C.Y.; Wan, C.N.

    1980-02-08

    The novel labelled compound 1-/sup 11/C-2-deoxy-D-glucose, and a process for its preparation from 2,3:4,5-di-O-isopropylidene-D-arabinitol derivatives of relatively high reactivity are disclosed. 1-/sup 11/C-2-deoxy-D-glucose is useful for measuring regional brain glucose metabolism in vivo.

  6. Isotopic Dependence of GCR Fluence behind Shielding

    NASA Technical Reports Server (NTRS)

    Cucinotta, Francis A.; Wilson, John W.; Saganti, Premkumar; Kim, Myung-Hee Y.; Cleghorn, Timothy; Zeitlin, Cary; Tripathi, Ram K.

    2006-01-01

    In this paper we consider the effects of the isotopic composition of the primary galactic cosmic rays (GCR), nuclear fragmentation cross-sections, and isotopic-grid on the solution to transport models used for shielding studies. Satellite measurements are used to describe the isotopic composition of the GCR. For the nuclear interaction data-base and transport solution, we use the quantum multiple-scattering theory of nuclear fragmentation (QMSFRG) and high-charge and energy (HZETRN) transport code, respectively. The QMSFRG model is shown to accurately describe existing fragmentation data including proper description of the odd-even effects as function of the iso-spin dependence on the projectile nucleus. The principle finding of this study is that large errors (+/-100%) will occur in the mass-fluence spectra when comparing transport models that use a complete isotopic-grid (approx.170 ions) to ones that use a reduced isotopic-grid, for example the 59 ion-grid used in the HZETRN code in the past, however less significant errors (<+/-20%) occur in the elemental-fluence spectra. Because a complete isotopic-grid is readily handled on small computer workstations and is needed for several applications studying GCR propagation and scattering, it is recommended that they be used for future GCR studies.

  7. Understanding the build-up of supermassive black holes and galaxies

    NASA Astrophysics Data System (ADS)

    Carrera, Francisco; Ueda, Yoshihiro; Georgakakis, Antonis

    2016-07-01

    . The excellent survey capabilities of Athena/WFI (effective area, angular resolution, field of view) will allow to measure the incidence of feedback in the shape of warm absorbers and Ultra Fast Outflows among the general population of AGN, as well as to complete the census of black hole growth by detecting and characterising significant samples of the most heavily obscured (including Compton thick) AGN, to redshifts z~3-4. The outstanding spectral throughput and resolution of Athena/X-IFU will permit measuring the energetics of those outflows to assess their influence on their host galaxies. The demographics of the heavily obscured and outflowing populations relative to their hosts are fundamental for understanding how major black hole growth events relate to the build-up of galaxies.

  8. Probing the Build-Up of Quiescent Galaxies at z>3

    NASA Astrophysics Data System (ADS)

    Finkelstein, Steven

    We propose to perform the most robust investigation to date into the evolution of massive quiescent and star-forming galaxies at z > 3, at a time when the universe was less than two billion years old. The build-up of quiescent galaxies in particular is poorly understood, primarily due to large Poisson and cosmic variance issues that have plagued previous studies that probed small volumes, leading to a disagreement on the quiescent fraction by a factor of >3 in the literature. Our proposed work is only now possible due to a new legacy survey led by our team: the Spitzer-HETDEX Exploratory Large Area Survey (SHELA), which is imaging a 23 deg^2 area of the sky at optical, and near, mid and far-infrared, and X-ray wavelengths. In particular, the wide area coverage of the Spitzer/IRAC data allows us to be sensitive to massive galaxies at very high redshifts, the Herschel data allows us to rule out lower-redshift counterparts, and the XMM-Newton data allows us to remove quasar contaminants from our sample. This survey covers a volume >14X that of the largest previous survey for quiescent galaxies at z=3.5, and ~6X larger than that of the largest previous survey for star-forming galaxies at z=4. All of these data exist in the region soon to be observed by the Hobby Eberly Telescope Dark Energy Experiment (HETDEX), which will provide high-precision measures of halo masses and local density at z~3. Using this exquisite multi-wavelength dataset, we will measure the abundance of massive quiescent galaxies at z ~ 3-5, and, combining with measures of the halo masses and environment, compare properties of quiescent galaxies to star-forming galaxies to investigate the physical cause behind the quenching. We will also investigate the onset of quenching in star-forming galaxies in two ways, first by studying the relation between star formation rate and stellar mass, to search for a break in the typically-linear relation at high masses, and second by constraining the feedback

  9. Role for 11C-choline PET in active surveillance of prostate cancer

    PubMed Central

    Boychak, Oleksandr; Vos, Larissa; Makis, William; Buteau, Francois-Alexandre; Pervez, Nadeem; Parliament, Matthew; McEwan, Alexander J.B.; Usmani, Nawaid

    2015-01-01

    Introduction: Active surveillance (AS) is an increasingly popular management strategy for men diagnosed with low-risk indolent prostate cancer. Current tests (prostate-specific antigen [PSA], clinical staging, and prostate biopsies) to monitor indolent disease lack accuracy. 11C-choline positron emission tomography (PET) has excellent detection rates in local and distant recurrence of prostate cancer. We examine 11C-choline PET for identifying aggressive prostate cancer warranting treatment in the AS setting. Methods: In total, 24 patients on AS had clinical assessment and PSA testing every 6 months and 11C-choline PET and prostate biopsies annually. The sensitivity and specificity to identify prostate cancer and progressive disease (PD) were calculated for each 11C-choline PET scan. Results: In total, 62 biopsy-paired, serial 11C-choline PET scans were analyzed using a series of standard uptake value-maximum (SUVmax) cut-off thresholds. During follow-up (mean 25.3 months), 11 of the 24 low-risk prostate cancer patients developed PD and received definitive treatment. The prostate cancer detection rate with 11C-choline PET had moderate sensitivity (72.1%), but low specificity (45.0%). PD prediction from baseline 11C-choline PET had satisfactory sensitivity (81.8%), but low specificity (38.5%). The addition of clinical parameters to the baseline 11C-choline PET improved specificity (69.2%), with a slight reduction in sensitivity (72.7%) for PD prediction. Conclusions: Addition of 11C-choline PET imaging during AS may help to identify aggressive disease earlier than traditional methods. However, 11C-choline PET alone has low specificity due to overlap of SUV values with benign pathologies. Triaging low-risk prostate cancer patients into AS versus therapy will require further optimization of PET protocols or consideration of alternative strategies (i.e., magnetic resonance imaging, biomarkers). PMID:25844108

  10. Effects of Incident Electron Fluence and Energy on the Election Yield Curves and Emission Spectra of Dielectrics

    NASA Technical Reports Server (NTRS)

    Sim, Alec; Dennison, J. R.; Thomson, Clint

    2005-01-01

    We present an experimental study of evolution of electron emission yields and spectra as a result of internal charge build up due to electron dose. Reliable total, backscattered and secondary yield curves and electron emission spectra for un-charged insulators using a low fluence, pulsed electron beam (= or < 5 microsec at = or < 3 nA/sq mm or = or < 10(exp 5) e/sq mm per pulse) with low energy electron and UV flooding to neutralize the charging between pulses. Quantifiable changes in yield curves are observed due to < 100 fC/sq mm fluences for several excellent dielectric thin film materials. We find good agreement with a phenomenological argument based on insulator charging predicted by the yield curve; this includes an approximately linear decrease in the magnitude of the yield as incident energies approach the crossover energies and an exponential decrease in yield as accumulated internal charge reduces the landing energy to asymptotically approach a steady state surface charge and unity yield. We also find that the exponential decay of yield curves with fluence exhibit an energy dependent decay constant, alpha(E), over a broad range of incident energies below, between and above the crossover energies. Finally, we present some preliminary physics-based models for this energy dependence and attempt to relate our charging measurements to knowledge of how charge is deposited within the insulator, the mechanisms for charge trapping and transport, and how the profile of trapped charge affects the transport and emission of charges from insulators.

  11. Effect of curing mode on the hardness of dual-cured composite resin core build-up materials.

    PubMed

    Arrais, César Augusto Galvão; Kasaz, Aline de Cerqueira; Albino, Luís Gustavo Barrote; Rodrigues, José Augusto; Reis, Andre Figueiredo

    2010-01-01

    This study evaluated the Knoop Hardness (KHN) values of two dual-cured composite resin core build-up materials and one resin cement exposed to different curing conditions. Two dual-cured core build-up composite resins (LuxaCore-Dual, DMG; and FluoroCore2, Dentsply Caulk), and one dual-cured resin cement (Rely X ARC, 3M ESPE) were used in the present study. The composite materials were placed into a cylindrical matrix (2 mm in height and 3 mm in diameter), and the specimens thus produced were either light-activated for 40 s (Optilux 501, Demetron Kerr) or were allowed to self-cure for 10 min in the dark (n = 5). All specimens were then stored in humidity at 37 degrees C for 24 h in the dark and were subjected to KHN analysis. The results were submitted to 2-way ANOVA and Tukey's post-hoc test at a pre-set alpha of 5%. All the light-activated groups exhibited higher KHN values than the self-cured ones (p = 0.00001), regardless of product. Among the self-cured groups, both composite resin core build-up materials showed higher KHN values than the dual-cured resin cement (p = 0.00001). LuxaCore-Dual exhibited higher KHN values than FluoroCore2 (p = 0.00001) when they were allowed to self-cure, while no significant differences in KHN values were observed among the light-activated products. The results suggest that dual-cured composite resin core build-up materials may be more reliable than dual-cured resin cements when curing light is not available.

  12. Experimental method of in-vivo dosimetry without build-up device on the skin for external beam radiotherapy

    NASA Astrophysics Data System (ADS)

    Jeon, Hosang; Nam, Jiho; Lee, Jayoung; Park, Dahl; Baek, Cheol-Ha; Kim, Wontaek; Ki, Yongkan; Kim, Dongwon

    2015-06-01

    Accurate dose delivery is crucial to the success of modern radiotherapy. To evaluate the dose actually delivered to patients, in-vivo dosimetry (IVD) is generally performed during radiotherapy to measure the entrance doses. In IVD, a build-up device should be placed on top of an in-vivo dosimeter to satisfy the electron equilibrium condition. However, a build-up device made of tissue-equivalent material or metal may perturb dose delivery to a patient, and requires an additional laborious and time-consuming process. We developed a novel IVD method using a look-up table of conversion ratios instead of a build-up device. We validated this method through a monte-carlo simulation and 31 clinical trials. The mean error of clinical IVD is 3.17% (standard deviation: 2.58%), which is comparable to that of conventional IVD methods. Moreover, the required time was greatly reduced so that the efficiency of IVD could be improved for both patients and therapists.

  13. Source term evaluation model for high-level radioactive waste repository with decay chain build-up.

    PubMed

    Chopra, Manish; Sunny, Faby; Oza, R B

    2016-09-18

    A source term model based on two-component leach flux concept is developed for a high-level radioactive waste repository. The long-lived radionuclides associated with high-level waste may give rise to the build-up of activity because of radioactive decay chains. The ingrowths of progeny are incorporated in the model using Bateman decay chain build-up equations. The model is applied to different radionuclides present in the high-level radioactive waste, which form a part of decay chains (4n to 4n + 3 series), and the activity of the parent and daughter radionuclides leaching out of the waste matrix is estimated. Two cases are considered: one when only parent is present initially in the waste and another where daughters are also initially present in the waste matrix. The incorporation of in situ production of daughter radionuclides in the source is important to carry out realistic estimates. It is shown that the inclusion of decay chain build-up is essential to avoid underestimation of the radiological impact assessment of the repository. The model can be a useful tool for evaluating the source term of the radionuclide transport models used for the radiological impact assessment of high-level radioactive waste repositories. PMID:27337157

  14. Source term evaluation model for high-level radioactive waste repository with decay chain build-up.

    PubMed

    Chopra, Manish; Sunny, Faby; Oza, R B

    2016-09-18

    A source term model based on two-component leach flux concept is developed for a high-level radioactive waste repository. The long-lived radionuclides associated with high-level waste may give rise to the build-up of activity because of radioactive decay chains. The ingrowths of progeny are incorporated in the model using Bateman decay chain build-up equations. The model is applied to different radionuclides present in the high-level radioactive waste, which form a part of decay chains (4n to 4n + 3 series), and the activity of the parent and daughter radionuclides leaching out of the waste matrix is estimated. Two cases are considered: one when only parent is present initially in the waste and another where daughters are also initially present in the waste matrix. The incorporation of in situ production of daughter radionuclides in the source is important to carry out realistic estimates. It is shown that the inclusion of decay chain build-up is essential to avoid underestimation of the radiological impact assessment of the repository. The model can be a useful tool for evaluating the source term of the radionuclide transport models used for the radiological impact assessment of high-level radioactive waste repositories.

  15. Understanding the uncertainty associated with particle-bound pollutant build-up and wash-off: A critical review.

    PubMed

    Wijesiri, Buddhi; Egodawatta, Prasanna; McGree, James; Goonetilleke, Ashantha

    2016-09-15

    Accurate prediction of stormwater quality is essential for developing effective pollution mitigation strategies. The use of models incorporating simplified mathematical replications of pollutant processes is the common practice for determining stormwater quality. However, an inherent process uncertainty arises due to the intrinsic variability associated with pollutant processes, which has neither been comprehensively understood, nor well accounted for in uncertainty assessment of stormwater quality modelling. This review provides the context for defining and quantifying the uncertainty associated with pollutant build-up and wash-off on urban impervious surfaces based on the hypothesis that particle size is predominant in influencing process variability. Critical analysis of published research literature brings scientific evidence together in order to establish the fact that particle size changes with time, and different sized particles exhibit distinct behaviour during build-up and wash-off, resulting in process variability. Analysis of the different adsorption behaviour of particles confirmed that the variations in pollutant load and composition are influenced by particle size. Particle behaviour and variations in pollutant load and composition are related due to the strong affinity of pollutants such as heavy metals and hydrocarbons for specific particle size ranges. As such, the temporal variation in particle size is identified as the key to establishing a basis for assessing build-up and wash-off process uncertainty. Therefore, accounting for pollutant build-up and wash-off process variability, which is influenced by particle size, would facilitate the assessment of the uncertainty associated with modelling outcomes. Furthermore, the review identified fundamental knowledge gaps where further research is needed in relation to: (1) the aggregation of particles suspended in the atmosphere during build-up; (2) particle re-suspension during wash-off; (3) pollutant

  16. Concurrent Monte Carlo transport and fluence optimization with fluence adjusting scalable transport Monte Carlo

    PubMed Central

    Svatos, M.; Zankowski, C.; Bednarz, B.

    2016-01-01

    Purpose: The future of radiation therapy will require advanced inverse planning solutions to support single-arc, multiple-arc, and “4π” delivery modes, which present unique challenges in finding an optimal treatment plan over a vast search space, while still preserving dosimetric accuracy. The successful clinical implementation of such methods would benefit from Monte Carlo (MC) based dose calculation methods, which can offer improvements in dosimetric accuracy when compared to deterministic methods. The standard method for MC based treatment planning optimization leverages the accuracy of the MC dose calculation and efficiency of well-developed optimization methods, by precalculating the fluence to dose relationship within a patient with MC methods and subsequently optimizing the fluence weights. However, the sequential nature of this implementation is computationally time consuming and memory intensive. Methods to reduce the overhead of the MC precalculation have been explored in the past, demonstrating promising reductions of computational time overhead, but with limited impact on the memory overhead due to the sequential nature of the dose calculation and fluence optimization. The authors propose an entirely new form of “concurrent” Monte Carlo treat plan optimization: a platform which optimizes the fluence during the dose calculation, reduces wasted computation time being spent on beamlets that weakly contribute to the final dose distribution, and requires only a low memory footprint to function. In this initial investigation, the authors explore the key theoretical and practical considerations of optimizing fluence in such a manner. Methods: The authors present a novel derivation and implementation of a gradient descent algorithm that allows for optimization during MC particle transport, based on highly stochastic information generated through particle transport of very few histories. A gradient rescaling and renormalization algorithm, and the

  17. Production and suppression of {sup 11}C in the solar neutrino experiment Borexino

    SciTech Connect

    Meindl, Quirin; Bellini, G.; Benziger, J.; Bonetti, S.; Avanzini, M. Buizza; Caccianiga, B.; Cadonati, L.; Calaprice, F.; Carraro, C.; Chavarria, A.; Chepurnov, A.; Dalnoki-Veress, F.; D'Angelo, D.; Davini, S.; Kerret, H. de; Derbin, A.; Etenko, A.; Feilitzsch, F. von; Fomenko, K.; Franco, D.

    2011-04-27

    Cosmogenic {sup 11}C is produced in-situ by atmospheric muons and forms the main background for the measurement of solar pep- and CNO-neutrinos. However, FLUKA simulations show that the majority of {sup 11}C is accompanied by a free neutron in the final state, thus allowing for an efficient tagging method, the so-called Three-Fold Coincidence technique. The technique and its first applications on Borexino data are presented.

  18. Production and suppression of 11C in the solar neutrino experiment Borexino

    NASA Astrophysics Data System (ADS)

    Meindl, Quirin; Bellini, G.; Benziger, J.; Bonetti, S.; Avanzini, M. Buizza; Caccianiga, B.; Cadonati, L.; Calaprice, F.; Carraro, C.; Chavarria, A.; Chepurnov, A.; Dalnoki-Veress, F.; D'Angelo, D.; Davini, S.; de Kerret, H.; Derbin, A.; Etenko, A.; von Feilitzsch, F.; Fomenko, K.; Franco, D.; Galbiati, C.; Gazzana, S.; Ghiano, C.; Giammarchi, M.; Goeger-Neff, M.; Goretti, A.; Guardincerri, E.; Hardy, S.; Ianni, Aldo; Ianni, Andrea; Joyce, M.; Kobychev, V.; Korga, G.; Kryn, D.; Laubenstein, M.; Leung, M.; Lewke, T.; Litvinovich, E.; Loer, B.; Lombardi, P.; Ludhova, L.; Machulin, I.; Manecki, S.; Maneschg, W.; Manuzio, G.; Meindl, Q.; Meroni, E.; Miramonti, L.; Misiaszek, M.; Montanari, D.; Muratova, V.; Oberauer, L.; Obolensky, M.; Ortica, F.; Pallavicini, M.; Papp, L.; Perasso, L.; Perasso, S.; Pocar, A.; Raghavan, R. S.; Ranucci, G.; Razeto, A.; Re, A.; Risso, P.; Romani, A.; Rountree, D.; Sabelnikov, A.; Saldanha, R.; Salvo, C.; Schönert, S.; Simgen, H.; Skorokhvatov, M.; Smirnov, O.; Sotnikov, A.; Sukhotin, S.; Suvorov, Y.; Tartaglia, R.; Testera, G.; Vignaud, D.; Vogelaar, R. B.; Winter, J.; Wojcik, M.; Wright, A.; Wurm, M.; Xu, J.; Zaimidoroga, O.; Zavatarelli, S.; Zuzel, G.

    2011-04-01

    Cosmogenic 11C is produced in-situ by atmospheric muons and forms the main background for the measurement of solar pep- and CNO-neutrinos. However, FLUKA simulations show that the majority of 11C is accompanied by a free neutron in the final state, thus allowing for an efficient tagging method, the so-called Three-Fold Coincidence technique. The technique and its first applications on Borexino data are presented.

  19. Serotonin 2A receptor agonist binding in the human brain with [11C]Cimbi-36

    PubMed Central

    Ettrup, Anders; da Cunha-Bang, Sophie; McMahon, Brenda; Lehel, Szabolcs; Dyssegaard, Agnete; Skibsted, Anine W; Jørgensen, Louise M; Hansen, Martin; Baandrup, Anders O; Bache, Søren; Svarer, Claus; Kristensen, Jesper L; Gillings, Nic; Madsen, Jacob; Knudsen, Gitte M

    2014-01-01

    [11C]Cimbi-36 was recently developed as a selective serotonin 2A (5-HT2A) receptor agonist radioligand for positron emission tomography (PET) brain imaging. Such an agonist PET radioligand may provide a novel, and more functional, measure of the serotonergic system and agonist binding is more likely than antagonist binding to reflect 5-HT levels in vivo. Here, we show data from a first-in-human clinical trial with [11C]Cimbi-36. In 29 healthy volunteers, we found high brain uptake and distribution according to 5-HT2A receptors with [11C]Cimbi-36 PET. The two-tissue compartment model using arterial input measurements provided the most optimal quantification of cerebral [11C]Cimbi-36 binding. Reference tissue modeling was feasible as it induced a negative but predictable bias in [11C]Cimbi-36 PET outcome measures. In five subjects, pretreatment with the 5-HT2A receptor antagonist ketanserin before a second PET scan significantly decreased [11C]Cimbi-36 binding in all cortical regions with no effects in cerebellum. These results confirm that [11C]Cimbi-36 binding is selective for 5-HT2A receptors in the cerebral cortex and that cerebellum is an appropriate reference tissue for quantification of 5-HT2A receptors in the human brain. Thus, we here describe [11C]Cimbi-36 as the first agonist PET radioligand to successfully image and quantify 5-HT2A receptors in the human brain. PMID:24780897

  20. 11C-radiolabeling study of methanol decomposition on copper oxide modified mesoporous SBA-15 silica

    NASA Astrophysics Data System (ADS)

    Tsoncheva, Tanya; Sarkadi-Priboczki, Eva

    2011-05-01

    11C-radiolabeling technique is applied to investigate methanol decomposition on copper oxide modified SBA-15. Nitrogen physisorption, XRD, FTIR, UV-vis and TPR techniques are used for catalyst characterization. Selective adsorption coverage of the catalytic active sites with 11C- and 12C-methanol molecules is carried out and the products of their conversion are followed. The mechanism of methyl formate, methylal and CO 2 formation from methanol is discussed.

  1. Quantification of [11C]yohimbine binding to α2 adrenoceptors in rat brain in vivo

    PubMed Central

    Phan, Jenny-Ann; Landau, Anne M; Wong, Dean F; Jakobsen, Steen; Nahimi, Adjmal; Doudet, Doris J; Gjedde, Albert

    2015-01-01

    We quantified the binding potentials (BPND) of [11C]yohimbine binding in rat brain to alpha-2 adrenoceptors to evaluate [11C]yohimbine as an in vivo marker of noradrenergic neurotransmission and to examine its sensitivity to the level of noradrenaline. Dual [11C]yohimbine dynamic positron emission tomography (PET) recordings were applied to five Sprague Dawley rats at baseline, followed by acute amphetamine administration (2 mg/kg) to induce elevation of the endogenous level of noradrenaline. The volume of distribution (VT) of [11C]yohimbine was obtained using Logan plot with arterial plasma input. Because alpha-2 adrenoceptors are distributed throughout the brain, the estimation of the BPND is complicated by the absence of an anatomic region of no displaceable binding. We used the Inhibition plot to acquire the reference volume, VND, from which we calculated the BPND. Acute pharmacological challenge with amphetamine induced a significant decline of [11C]yohimbine BPND of ~38% in all volumes of interest. The BPND was greatest in the thalamus and striatum, followed in descending order by, frontal cortex, pons, and cerebellum. The experimental data demonstrate that [11C]yohimbine binding is sensitive to a challenge known to increase the extracellular level of noradrenaline, which can benefit future PET investigations of pathologic conditions related to disrupted noradrenergic neurotransmission. PMID:25564241

  2. Reference region modeling approaches for amphetamine challenge studies with [11C]FLB 457 and PET.

    PubMed

    Sandiego, Christine M; Gallezot, Jean-Dominique; Lim, Keunpoong; Ropchan, Jim; Lin, Shu-fei; Gao, Hong; Morris, Evan D; Cosgrove, Kelly P

    2015-04-01

    Detecting fluctuations in synaptic dopamine levels in extrastriatal brain regions with [(11)C]FLB 457 and positron emission tomography (PET) is a valuable tool for studying dopaminergic dysfunction in psychiatric disorders. The evaluation of reference region modeling approaches would eliminate the need to obtain arterial input function data. Our goal was to explore the use of reference region models to estimate amphetamine-induced changes in [(11)C]FLB 457 dopamine D2/D3 binding. Six healthy tobacco smokers were imaged with [(11)C]FLB 457 at baseline and at 3 hours after amphetamine (0.4 to 0.5 mg/kg, per os) administration. Simplified reference tissue models, SRTM and SRTM2, were evaluated against the 2-tissue compartmental model (2TC) to estimate [(11)C]FLB 457 binding in extrastriatal regions of interest (ROIs), using the cerebellum as a reference region. No changes in distribution volume were observed in the cerebellum between scan conditions. SRTM and SRTM2 underestimated binding, compared with 2TC, in ROIs by 26% and 9%, respectively, with consistent bias between the baseline and postamphetamine scans. Postamphetamine, [(11)C]FLB 457 binding significantly decreased across several brain regions as measured with SRTM and SRTM2; no significant change was detected with 2TC. These data support the sensitivity of [(11)C]FLB 457 for measuring amphetamine-induced dopamine release in extrastriatal regions with SRTM and SRTM2. PMID:25564239

  3. On scale and magnitude of pressure build-up induced by large-scale geologic storage of CO2

    SciTech Connect

    Zhou, Q.; Birkholzer, J. T.

    2011-05-01

    The scale and magnitude of pressure perturbation and brine migration induced by geologic carbon sequestration is discussed assuming a full-scale deployment scenario in which enough CO{sub 2} is captured and stored to make relevant contributions to global climate change mitigation. In this scenario, the volumetric rates and cumulative volumes of CO{sub 2} injection would be comparable to or higher than those related to existing deep-subsurface injection and extraction activities, such as oil production. Large-scale pressure build-up in response to the injection may limit the dynamic storage capacity of suitable formations, because over-pressurization may fracture the caprock, may drive CO{sub 2}/brine leakage through localized pathways, and may cause induced seismicity. On the other hand, laterally extensive sedimentary basins may be less affected by such limitations because (i) local pressure effects are moderated by pressure propagation and brine displacement into regions far away from the CO{sub 2} storage domain; and (ii) diffuse and/or localized brine migration into overlying and underlying formations allows for pressure bleed-off in the vertical direction. A quick analytical estimate of the extent of pressure build-up induced by industrial-scale CO{sub 2} storage projects is presented. Also discussed are pressure perturbation and attenuation effects simulated for two representative sedimentary basins in the USA: the laterally extensive Illinois Basin and the partially compartmentalized southern San Joaquin Basin in California. These studies show that the limiting effect of pressure build-up on dynamic storage capacity is not as significant as suggested by Ehlig-Economides and Economides, who considered closed systems without any attenuation effects.

  4. Comparison of L-[1-11C]methionine and L-methyl-[11C]methionine for measuring in vivo protein synthesis rates with PET.

    PubMed

    Ishiwata, K; Vaalburg, W; Elsinga, P H; Paans, A M; Woldring, M G

    1988-08-01

    To evaluate the feasibility of using either L-[1-11C]-methionine or L-[methyl-11C]methionine for measuring protein synthesis rates by positron emission tomography (PET) in normal and neoplastic tissues, distribution and metabolic studies with 14C- and 11C-labeled methionines were carried out in rats bearing Walker 256 carcinosarcoma. The tissue distributions of the two 14C-labeled methionines were similar except for liver tissue. Similar distribution patterns were observed in vivo by PET using 11C-labeled methionines. The highest 14C incorporation rate into the protein-bound fraction was found in the liver followed by tumor, brain, and pancreas. The incorporation rates in liver and pancreas were different for the two methionines. By chloroform-methanol fractionation of these four tissues, in liver significantly different amounts of 14C were observed in macromolecules. Also in brain tissue slight differences were found. By HPLC analyses of the protein-free fractions of plasma, tumor, and brain tissue at 60 min after injection, for both methionines several 14C-labeled metabolites in different amounts, were detected. About half of the 14C-labeled material in the protein-free fraction was found to be methionine. In these three tissues the amount of nonprotein metabolites and [14C]bicarbonate amount ranged from 10% to 17% and 12% to 15% for L-[1-14C]methionine and L-[methyl-14C]methionine, respectively. From these results it can be concluded that the minor metabolic pathways have to be investigated in order to quantitatively model the protein synthesis by PET.

  5. Neutron detector simultaneously measures fluence and dose equivalent

    NASA Technical Reports Server (NTRS)

    Dvorak, R. F.; Dyer, N. C.

    1967-01-01

    Neutron detector acts as both an area monitoring instrument and a criticality dosimeter by simultaneously measuring dose equivalent and fluence. The fluence is determined by activation of six foils one inch below the surface of the moderator. Dose equivalent is determined from activation of three interlocked foils at the center of the moderator.

  6. Component build-up method for engineering analysis of missiles at low-to-high angles of attack

    NASA Technical Reports Server (NTRS)

    Hemsch, Michael J.

    1992-01-01

    Methods are presented for estimating the component build-up terms, with the exception of zero-lift drag, for missile airframes in steady flow and at arbitrary angles of attack and bank. The underlying and unifying bases of all these efforts are slender-body theory and its nonlinear extensions through the equivalent angle-of-attack concept. Emphasis is placed on the forces and moments which act on each of the fins, so that control cross-coupling effects as well as longitudinal and lateral-directional effects can be determined.

  7. Reactor vessel fluence evaluation and dosimetry

    SciTech Connect

    Lois, L. )

    1992-01-01

    The methodology currently in use for the estimation of the fast neutron fluence to the pressure vessel (inside surface and reactor cavity) is based on discrete ordinates two-dimensional codes such as DOT or its updated version DORT. This methodology assumes a P[sub 3] scattering, an S[sub 8] quadrature approximation, and cross sections based on the ENDF/B-IV file. Associated one-dimensional codes are often used for the cross-section collapsing portion of the calculation. The neutron spectrum at the pressure vessel location of interest is estimated assuming a [sup 235]U, [sup 239]Pu, or [sup 241]Pu source spectrum or an appropriate combination thereof. The two-dimensional codes and associated methodologies were benchmarked in the early eighties using the results of the PCA and PSF Oak Ridge National Laboratory reactor experiments. The benchmarking experiments were estimated to provide an uncertainty of [approx]10%. The results of the calculations applied to a reactor were estimated to have an uncertainty of [approx]20%. This level of uncertainty was assumed in the estimation of the margin term defined in 10CFR50.61

  8. 11C-Acetate PET Imaging in Patients with Multiple Sclerosis

    PubMed Central

    Shimosegawa, Eku; Okuno, Tatsusada; Koda, Toru; Sugimoto, Tomoyuki; Mochizuki, Hideki; Hatazawa, Jun; Nakatsuji, Yuji

    2014-01-01

    Background Activation of glial cells is a cardinal feature in multiple sclerosis (MS) pathology, and acetate has been reported to be selectively uptaken by astrocytes in the CNS. The aim of this study was to investigate the efficacy of PET with 11C-acetate for MS diagnosis. Materials and Methods Six patients with relapsing-remitting MS and 6 healthy volunteers (HV) were enrolled. The 11C-acetate brain uptake on PET was measured in patients with MS and HV. Volume-of-interest analysis of cerebral gray and white matter based on the segmentation technique for co-registered MRI and voxel-based statistical parametric analysis were performed. Correlation between 11C-acetate uptake and the lesion number in T1- and T2- weighted MR images were also assessed. Results The standardized uptake value (SUV) of 11C-acetate was increased in both white and gray matter in MS patients compared to HV. Voxel-based statistical analysis revealed a significantly increased SUV relative to that in the bilateral thalami (SUVt) in a broad area of white matter, particularly in the subcortical white matter of MS patients. The numbers of T2 lesions and T1 black holes were significantly correlated with SUV of 11C-acetate in white and gray matter. Conclusions The 11C-acetate uptake significantly increased in MS patients and correlated to the number of MRI lesions. These preliminary data suggest that 11C-acetate PET can be a useful clinical examination for MS patients. PMID:25369426

  9. (11)C[double bond, length as m-dash]O bonds made easily for positron emission tomography radiopharmaceuticals.

    PubMed

    Rotstein, Benjamin H; Liang, Steven H; Placzek, Michael S; Hooker, Jacob M; Gee, Antony D; Dollé, Frédéric; Wilson, Alan A; Vasdev, Neil

    2016-08-22

    The positron-emitting radionuclide carbon-11 ((11)C, t1/2 = 20.3 min) possesses the unique potential for radiolabeling of any biological, naturally occurring, or synthetic organic molecule for in vivo positron emission tomography (PET) imaging. Carbon-11 is most often incorporated into small molecules by methylation of alcohol, thiol, amine or carboxylic acid precursors using [(11)C]methyl iodide or [(11)C]methyl triflate (generated from [(11)C]carbon dioxide or [(11)C]methane). Consequently, small molecules that lack an easily substituted (11)C-methyl group are often considered to have non-obvious strategies for radiolabeling and require a more customized approach. [(11)C]Carbon dioxide itself, [(11)C]carbon monoxide, [(11)C]cyanide, and [(11)C]phosgene represent alternative reactants to enable (11)C-carbonylation. Methodologies developed for preparation of (11)C-carbonyl groups have had a tremendous impact on the development of novel PET tracers and provided key tools for clinical research. (11)C-Carbonyl radiopharmaceuticals based on labeled carboxylic acids, amides, carbamates and ureas now account for a substantial number of important imaging agents that have seen translation to higher species and clinical research of previously inaccessible targets, which is a testament to the creativity, utility and practicality of the underlying radiochemistry. PMID:27276357

  10. 11C-Colchicine distribution in tissues of colchicine -sensitive and -resistant neuroblastoma xenografts

    SciTech Connect

    Mehta, B.M.; Levchenko, A.; Broussard, E.

    1995-05-01

    Multidrug resistance (MDR), a major obstacle in chemotherapy of cancer is thought to be due to the overexpression of a membrane P-glycoprotein (Pgp). P-glycoprotein acts as an energy activated efflux pump, reducing the effective drug concentrations from the MDR tumors. Our earlier studies using neuroblastoma cell lines BE(2)-C (-sensitive), and BE(2)-C/CHCb (-resistant) to colchicine (CHC), showed that uptake of 3H-CHC as well as 14C-CHC in sensitive tumors was twice as much as in resistant tumors. In view of this finding we synthesized 11C-CHC to study the distribution in xenografted animals, since 11C-CHC can be used a a Positron Emission Tomography (PET) tracer in humans. Two groups of Balb/c nude mice (5 animals each) xenografted with BE(2)-C and BE(2)-C/CHCb cells (10 x 10{sup 6} cells per animal) were injected iv retroorbitally with 200 {mu}Ci/100 {mu}l of 11C-CHC per animal. One hour after injection animals were sacrificed by cervical dislocation and blood, tissues and tumors were excised to determine the amount of radioactivity. 11C-CHC biodistribution compared well with 3H-CHC and 14C-CHC distribution. Tumor uptake in sensitive was 1.21 {plus_minus} 0.84% ID/g compared to 0.76 {plus_minus} 0.43% ID/g in resistant tumors. Tumor to blood ratios is sensitive and resistant tumors were 1.62 {plus_minus} 0.41 and 0.69 {plus_minus}0.30 respectively. 11C-Isocolchicine, a byproduct of 11C-CHC synthesis, on the other hand had only 25% uptake as compared to 11C-CHC in both sensitive and resistant tumors. We interpret these results to mean that 11C-CHC behaves similarly to other forms of CHC as a marker of the MDR phenotype. In the future, we plan to use 11C-CHC for identification of MDR status of tumors in vivo using PET scanning.

  11. A pilot study comparing the pain sensations during PpIX build-up and clearance phases

    NASA Astrophysics Data System (ADS)

    Mikolajewska, P.; Juzeniene, A.; Iani, V.; Sollund, H.; Norsang, G.; Moan, J.

    2009-06-01

    It has been speculated that topical application of 5-aminolevulinic acid (ALA) or methyl 5-aminolevulinate (MAL) may be more painful during light exposure after longer application times of the compounds than after shorter times, even though the same levels of protoporphyrin IX (PpIX) is produced in both cases. The aim of our study was to investigate pain induction in the build-up and clearance phases of PpIX in the skin of healthy volunteers. 0.6 mmol/g of ALA (10% wt/wt) and MAL (11% wt/wt) creams were applied on the volunteers. The creams were maintained on the spots for 20- 24 hours and then wiped off. Subsequently, fresh creams were applied on the other arm of the volunteers for 4- 6 hours. Fluorescence emission spectra for all spots were measured every hour until the fluorescence levels were similar in both arms for ALA and MAL. Then the test areas were exposed to light until pain occurred. Time for pain to occur was recorded. The fluorescence of PpIX was measured before and after light exposure. PDT in the clearance phase seems to induce pain faster than in the build-up phase for ALA and MAL. Due to large interpersonal variations between volunteers further investigation is needed.

  12. Design and metrological evaluation of the new 5 MN hexapod-shaped multicomponent build-up system

    NASA Astrophysics Data System (ADS)

    Palumbo, Stefano; Germak, Alessandro; Mazzoleni, Fabrizio; Desogus, Sergio; Barbato, Giulio

    2016-06-01

    The new 5 MN hexapod-shaped multicomponent build-up system (HSM-BUS) represents significant progress in the field of reference transducers in the high force range. As with any build-up system, the presented hexapod-shaped multicomponent force transducer can lead, not only to measure forces 5 times higher than the capacity of a each single uniaxial force transducer (UFT), but gives also information about the other components of the force vector and of the moment vector. Furthermore, the calibration of such types of multicomponent force transducer regards only the calibration of the signal outputs coming from each UFT and the calibration of the geometry of the system. In this work, an a priori evaluation of the expected uncertainty is performed. As a first approximation, the effects of the calibration uncertainties of UFTs and of the geometrical tolerances given on the construction drawing were considered. Subsequently, with a finite element simulation of the mechanical behavior of the 5 MN HSM-BUS under load, a mathematical model of elastic deformations has been evaluated and applied for evaluating and correcting the systematic errors due to the deformation of the geometry under load.

  13. Effects of salinity build-up on the performance and bacterial community structure of a membrane bioreactor.

    PubMed

    Luo, Wenhai; Phan, Hop V; Hai, Faisal I; Price, William E; Guo, Wenshan; Ngo, Hao H; Yamamoto, Kazuo; Nghiem, Long D

    2016-01-01

    This study investigated the effects of salinity increase on bacterial community structure in a membrane bioreactor (MBR) for wastewater treatment. The influent salt loading was increased gradually to simulate salinity build-up in the bioreactor during the operation of a high retention-membrane bioreactor (HR-MBR). Bacterial community diversity and structure were analyzed using 454 pyrosequencing of 16S rRNA genes of MBR mixed liquor samples. Results show that salinity increase reduced biological performance but did not affect microbial diversity in the bioreactor. Unweighted UniFrac and taxonomic analyses were conducted to relate the reduced biological performance to the change of bacterial community structure. In response to the elevated salinity condition, the succession of halophobic bacteria by halotolerant/halophilic microbes occurred and thereby the biological performance of MBR was recovered. These results suggest that salinity build-up during HR-MBR operation could be managed by allowing for the proliferation of halotolerant/halophilic bacteria. PMID:26512852

  14. A method of limiting pressure build-up in motorcycle gasoline tanks due to tank deformation in an accident

    SciTech Connect

    Erza, M.A.; Erza, A.H.

    1982-01-01

    Most motorcycle accidents are angle collisions, constituting 57% of the multi vehicle accidents. In some of these collisions, the motorcycle gasoline tank is dented, decreasing the internal volume and increasing the internal pressure. If this happens when the gasoline tank is full, or nearly full, the pressure build-up can be quite severe, blowing off the gasoline tank cap and drenching the rider with gasoline. The gasoline ofte ignites, burning the rider severely. This pressure build-up can be reduced considerably by a simple device which traps air in the tank and consists of a short tube inserted in the tank filler hole projecting downwards a short distance. This paper shows how the corresponding pressure reduction can be calculated as a function of tank volume, indentation ratio and length of tube, to enable a designer to make the necessary trade-offs in the design. This device can be easily retrofitted to an existing motorcycle gasoline tank to increase its crash worthiness.

  15. Combination of dynamic (11)C-PIB PET and structural MRI improves diagnosis of Alzheimer's disease.

    PubMed

    Liu, Linwen; Fu, Liping; Zhang, Xi; Zhang, Jinming; Zhang, Xiaojun; Xu, Baixuan; Tian, Jiahe; Fan, Yong

    2015-08-30

    Structural magnetic resonance imaging (sMRI) is an established technique for measuring brain atrophy, and dynamic positron emission tomography with (11)C-Pittsburgh compound B ((11)C-PIB PET) has the potential to provide both perfusion and amyloid deposition information. It remains unclear, however, how to better combine perfusion, amyloid deposition and morphological information extracted from dynamic (11)C-PIB PET and sMRI with the goal of improving the diagnosis of Alzheimer's disease (AD) and mild cognitive impairment (MCI). We adopted a linear sparse support vector machine to build classifiers for distinguishing AD and MCI subjects from cognitively normal (CN) subjects based on different combinations of regional measures extracted from imaging data, including perfusion and amyloid deposition information extracted from early and late frames of (11)C-PIB separately, and gray matter volumetric information extracted from sMRI data. The experimental results demonstrated that the classifier built upon the combination of imaging measures extracted from early and late frames of (11)C-PIB as well as sMRI achieved the highest classification accuracy in both classification studies of AD (100%) and MCI (85%), indicating that multimodality information could aid in the diagnosis of AD and MCI. PMID:26095348

  16. Dosimetry of D- and L-enantiomers of /sup 11/C-labeled tryptophan and valine

    SciTech Connect

    Washburn, L.C.; Byrd, B.L.; Sun, T.T.; Crook, J.E.; Hubner, K.F.; Coffey, J.L.; Watson, E.E.

    1985-01-01

    We have previously reported the radiation dosimetry of /sup 11/C-labeled DL-tryptophan and DL-valine, as well as clinical pancreatic imaging studies with these agents. Because of significant uptake in both normal pancreas and in pancreatic tumors (thought to be due to the presence of the D-enantiomer), differential diagnosis of pancreatic carcinoma was not feasible. High-performance liquid chromatographic (HPLC) methods were developed for rapid resolution of /sup 11/C-labeled DL-tryptophan and DL-valine. Radiation dose estimates to the various organs in man were calculated for the D- and L-enantiomers of /sup 11/C-labeled tryptophan and valine, based on tissue distribution data in rats. The dose estimates were sufficiently low that 20-mCi doses of each of the enantiomeric amino acids were approved by the FDA for intravenous administration to humans. 21 refs., 3 tabs.

  17. Comparison of dosimetry between PET/CT and PET alone using (11)C-ITMM.

    PubMed

    Ito, Kimiteru; Sakata, Muneyuki; Oda, Keiichi; Wagatsuma, Kei; Toyohara, Jun; Ishibashi, Kenji; Ishii, Kenji; Ishiwata, Kiichi

    2016-03-01

    We used a new tracer, N-[4-[6-(isopropylamino) pyrimidin-4-yl]-1,3-thiazol-2-yl]-4-(11)C-methoxy-N-methylbenzamide ((11)C-ITMM), to compare radiation doses from positron emission tomography (PET)/computed tomography (CT) with previously published doses from PET alone. Twelve healthy volunteers [six males (mean age ± SD, 27.7 ± 6.7 years) and six females (31.8 ± 14.5 years)] in 12 examinations were recruited. Dose estimations from PET/CT were compared with those from PET alone. Regions of interest (ROIs) in PET/CT were delineated on the basis of low-dose CT (LD-CT) images acquired during PET/CT. Internal and external radiation doses were estimated using OLINDA/EXM 1.0 and CT-Expo software. The effective dose (ED) for (11)C-ITMM calculated from PET/CT was estimated to be 4.7 ± 0.5 μSv/MBq for the male subjects and 4.1 ± 0.7 μSv/MBq for the female subjects. The mean ED for (11)C-ITMM calculated from PET alone in a previous report was estimated to be 4.6 ± 0.3 μSv/MBq (males, n = 3). The ED values for (11)C-ITMM calculated from PET/CT in the male subjects were almost identical to those from PET alone. The absorbed doses (ADs) of the gallbladder, stomach, red bone marrow, and spleen calculated from PET/CT were significantly different from those calculated from PET alone. The EDs of (11)C-ITMM calculated from PET/CT were almost identical to those calculated from PET alone. The ADs in several organs calculated from PET/CT differed from those from PET alone. LD-CT images acquired during PET/CT may facilitate organ identification.

  18. (/sup 11/C)clorgyline and (/sup 11/C)-L-deprenyl and their use in measuring functional monoamine oxidase activity in the brain using positron emission tomography

    DOEpatents

    Fowler, J.S.; MacGregor, R.R.; Wolf, A.P.

    1986-04-17

    This invention involves a new strategy for imaging the activity of the enzyme monoamine oxidase in the living body by using /sup 11/C-labeled enzyme inhibitors which bind irreversibly to an enzyme as a result of catalysis. By using positron emission tomography to image the distribution of radioactivity produced by the body penetrating radiation emitted by carbon-11, a map of functionally active monoamine oxidase activity is obtained. Clorgyline and L-deprenyl are suicide enzyme inhibitors and irreversibly inhibit monoamine oxidase. When these inhibitors are labeled with carbon-11 they provide selective probes for monoamine oxidase localization and reactivity in vivo using positron emission tomography. 2 figs.

  19. Improved sensitivity of human brain MAO B measurement using deuterium substituted [{sup 11}C]L-deprenyl ([{sup 11}C]L-deprenyl-D2)

    SciTech Connect

    Fowler, J.S.; Volkow, N.D.; Wang, G.J.

    1995-05-01

    Post-mortem reports that human brain monoamine oxidase B (MAO B) increases in normal aging and neurodegenerative disorders due to the proliferation of MAO B-rich glial cells suggest that PET measures of MAO B may track gliosis. We have recently shown that the MAO B tracer [{sup 11}C]L-deprenyl has limited sensitivity in regions of high MAO B due to its rapid rate of trapping. This limits its utility for measuring MAO B in brain regions where MAO B is higher and/or where blood flow is low. We have recently demonstrated that [{sup 11}C]L-deprenyl-D2 has improved sensitivity in regions of high MAO B due to the deuterium isotope effect which reduces the rate of trapping. We report studies [{sup 11}C]L-deprenyl-D2 in normal human brain in 16 healthy men and women (age range 23-73) to assess tracer sensitivity, regional distribution, and reproducibility. Graphical analysis for irreversible systems was used to calculate Ki (influx constant) as an index of MAO B concentration in different brain regions. The uptake of carbon-11 in different brain regions was rapid, peaking at 5 minutes and plateauing from 30-60 minutes after an initial clearance. MAO B was highest in subcortical regions: thalamus{ge}basal ganglia>cingulate gyrus>frontal cortex=occipital cortex=cerebellum in agreement with post-mortem measurements. Ki values were highly correlated within an individual. Repeated measures at 1-4 week intervals were highly correlated (r=0.9; p=0.0001). In women (n=8: age range 23-73), Ki increased with increasing age for 8 brain regions (p < 0.04). Though men (N=8; age range 34-70) showed no correlation with age, a larger sample size is needed to adequately assess trends. In summary, the use of [{sup 11}C]L-deprenyl-D2 improves the measurement of MAO B in the human brain permitting its investigation as a positive tracer for glial cell proliferation in neurodegenerative disorders.

  20. Evaluation of [11C]metergoline as a PET radiotracer for 5HTR in nonhuman primates

    SciTech Connect

    Hooker, J.M.; Hooker, J.M.; Kim, S.W.; Reibel, A.T.; Alexoff, D.; Xu, Y.; Shea, C.

    2010-04-20

    Metergoline, a serotonin receptor antagonist, was labeled with carbon-11 in order to evaluate its pharmacokinetics and distribution in non-human primates using positron emission tomography. [{sup 11}C]Metergoline had moderate brain uptake and exhibited heterogeneous specific binding, which was blocked by pretreatment with metergoline and altanserin throughout the cortex. Non-specific binding and insensitivity to changes in synaptic serotonin limit its potential as a PET radiotracer. However, the characterization of [{sup 11}C]metergoline pharmacokinetics and binding in the brain and peripheral organs using PET improves our understanding of metergoline drug pharmacology.

  1. Synthesis and preclinical evaluation of the radiolabeled P-glycoprotein inhibitor [11C]MC113

    PubMed Central

    Mairinger, Severin; Wanek, Thomas; Kuntner, Claudia; Doenmez, Yaprak; Strommer, Sabine; Stanek, Johann; Capparelli, Elena; Chiba, Peter; Müller, Markus; Colabufo, Nicola A.; Langer, Oliver

    2013-01-01

    Objectives With the aim to develop a PET tracer to visualize P-glycoprotein (Pgp) expression levels in different organs, the Pgp inhibitor MC113 was labeled with 11C and evaluated using small-animal PET. Methods [11C]MC113 was synthesized by reaction of O-desmethyl MC113 with [11C]methyl triflate. Small-animal PET was performed with [11C]MC113 in FVB wild-type and Mdr1a/b(−/−) mice (n=3 per group) and in a mouse model of high (EMT6Ar1.0) and low (EMT6) Pgp expressing tumor grafts (n=5). In the tumor model, PET scans were performed before and after administration of the reference Pgp inhibitor tariquidar (15 mg/kg). Results Brain uptake of [11C]MC113, expressed as area under the time-activity curve from time 0 to 60 min (AUC0-60), was moderately but not significantly increased in Mdr1a/b(−/−) compared with wild-type mice (mean±SD AUC0-60, Mdr1a/b(−/−): 88±7 min, wild-type: 62±6 min, P=0.100, Mann Whitney test). In the tumor model, AUC0-60 values were not significantly different between EMT6Ar1.0 and EMT6 tumors. Neither in brain nor in tumors was activity concentration significantly changed in response to tariquidar administration. Half-maximum effect concentrations (IC50) for inhibition of Pgp-mediated rhodamine 123 efflux from CCRFvcr1000 cells were 375±60 nM for MC113 versus 8.5±2.5 nM for tariquidar. Conclusion [11C]MC113 showed higher brain uptake in mice than previously described Pgp PET tracers, suggesting that [11C]MC113 was only to a low extent effluxed by Pgp. However, [11C]MC113 was found unsuitable to visualize Pgp expression levels presumably due to insufficiently high Pgp binding affinity of MC113 in relation to Pgp densities in brain and tumors. PMID:22981987

  2. New developments of 11C post-accelerated beams for hadron therapy and imaging

    NASA Astrophysics Data System (ADS)

    Augusto, R. S.; Mendonca, T. M.; Wenander, F.; Penescu, L.; Orecchia, R.; Parodi, K.; Ferrari, A.; Stora, T.

    2016-06-01

    Hadron therapy was first proposed in 1946 and is by now widespread throughout the world, as witnessed with the design and construction of the CNAO, HIT, PROSCAN and MedAustron treatment centres, among others. The clinical interest in hadron therapy lies in the fact that it delivers precision treatment of tumours, exploiting the characteristic shape (the Bragg peak) of the energy deposition in the tissues for charged hadrons. In particular, carbon ion therapy is found to be biologically more effective, with respect to protons, on certain types of tumours. Following an approach tested at NIRS in Japan [1], carbon ion therapy treatments based on 12C could be combined or fully replaced with 11C PET radioactive ions post-accelerated to the same energy. This approach allows providing a beam for treatment and, at the same time, to collect information on the 3D distributions of the implanted ions by PET imaging. The production of 11C ion beams can be performed using two methods. A first one is based on the production using compact PET cyclotrons with 10-20 MeV protons via 14N(p,α)11C reactions following an approach developed at the Lawrence Berkeley National Laboratory [2]. A second route exploits spallation reactions 19F(p,X)11C and 23Na(p,X)11C on a molten fluoride salt target using the ISOL (isotope separation on-line) technique [3]. This approach can be seriously envisaged at CERN-ISOLDE following recent progresses made on 11C+ production [4] and proven post-acceleration of pure 10C3/6+ beams in the REX-ISOLDE linac [5]. Part of the required components is operational in radioactive ion beam facilities or commercial medical PET cyclotrons. The driver could be a 70 MeV, 1.2 mA proton commercial cyclotron, which would lead to 8.1 × 10711C6+ per spill. This intensity is appropriate using 11C ions alone for both imaging and treatment. Here we report on the ongoing feasibility studies of such approach, using the Monte Carlo particle transport code FLUKA [6,7] to simulate

  3. Effects of salinity build-up on biomass characteristics and trace organic chemical removal: implications on the development of high retention membrane bioreactors.

    PubMed

    Luo, Wenhai; Hai, Faisal I; Kang, Jinguo; Price, William E; Guo, Wenshan; Ngo, Hao H; Yamamoto, Kazuo; Nghiem, Long D

    2015-02-01

    This study investigated the impact of salinity build-up on the performance of membrane bioreactor (MBR), specifically in terms of the removal and fate of trace organic chemicals (TrOCs), nutrient removal, and biomass characteristics. Stepwise increase of the influent salinity, simulating salinity build-up in high retention MBRs, adversely affected the metabolic activity in the bioreactor, thereby reducing organic and nutrient removal. The removal of hydrophilic TrOCs by MBR decreased due to salinity build-up. By contrast, with the exception of 17α-ethynylestradiol, the removal of all hydrophobic TrOCs was not affected at high salinity. Moreover, salinity build-up had negligible impact on the residual accumulation of TrOCs in the sludge phase except for a few hydrophilic compounds. Additionally, the response of the biomass to salinity stress also dramatically enhanced the release of both soluble microbial products (SMP) and extracellular polymeric substances (EPS), leading to severe membrane fouling.

  4. Pressure Build-Up During the Fire Test in Type B(U) Packages Containing Water - 13280

    SciTech Connect

    Feldkamp, Martin; Nehrig, Marko; Bletzer, Claus; Wille, Frank

    2013-07-01

    The safety assessment of packages for the transport of radioactive materials with content containing liquids requires special consideration. The main focus is on water as supplementary liquid content in Type B(U) packages. A typical content of a Type B(U) package is ion exchange resin, waste of a nuclear power plant, which is not dried, normally only drained. Besides the saturated ion exchange resin, a small amount of free water can be included in these contents. Compared to the safety assessment of packages with dry content, attention must be paid to some more specific issues. An overview of these issues is provided. The physical and chemical compatibility of the content itself and the content compatibility with the packages materials must be demonstrated for the assessment. Regarding the mechanical resistance the package has to withstand the forces resulting from the freezing liquid. The most interesting point, however, is the pressure build-up inside the package due to vaporization. This could for example be caused by radiolysis of the liquid and must be taken into account for the storage period. If the package is stressed by the total inner pressure, this pressure leads to mechanical loads to the package body, the lid and the lid bolts. Thus, the pressure is the driving force on the gasket system regarding the activity release and a possible loss of tightness. The total pressure in any calculation is the sum of partial pressures of different gases which can be caused by different effects. The pressure build-up inside the package caused by the regulatory thermal test (30 min at 800 deg. C), as part of the cumulative test scenario under accident conditions of transport is discussed primarily. To determine the pressure, the temperature distribution in the content must be calculated for the whole period from beginning of the thermal test until cooling-down. In this case, while calculating the temperature distribution, conduction and radiation as well as evaporation

  5. Light parameters influence cell viability in antifungal photodynamic therapy in a fluence and rate fluence-dependent manner

    NASA Astrophysics Data System (ADS)

    Prates, Renato A.; da Silva, Eriques G.; Yamada, Aécio M.; Suzuki, Luis C.; Paula, Claudete R.; Ribeiro, Martha S.

    2009-05-01

    The aim of this study was to investigate the influence of light parameters on yeast cells. It has been proposed for many years that photodynamic therapy (PDT) can inactivate microbial cells. A number of photosensitizer and light sources were reported in different light parameters and in a range of dye concentrations. However, much more knowledge concerning the importance of fluence, fluence rate and exposure time are required for a better understanding of the photodynamic efficiency. Suspensions (106 CFU/mL) of Candida albicans, Candida krusei, and Cryptococcus neoformans var. grubii were used. Two fluence rates, 100 and 300 mW/cm2 were compared at 3, 6, and 9 min of irradiation, resulting fluences from 18 to 162 J/cm2. The light source was a laser emitting at λ = 660 nm with output power adjusted at 30 and 90 mW. As photosensitizer, one hundred-μM methylene blue was used. Temperature was monitored to verify possible heat effect and reactive oxygen species (ROS) formation was evaluated. The same fluence in different fluence rates showed dissimilar levels of inactivation on yeast cells as well as in ROS formation. In addition, the increase of the fluence rate showed an improvement on cell photoinactivation. PDT was efficient against yeast cells (6 log reduction), and no significant temperature increase was observed. Fluence per se should not be used as an isolate parameter to compare photoinactivation effects on yeast cells. The higher fluence rate was more effective than the lower one. Furthermore, an adequate duration of light exposure cannot be discarded.

  6. 18F-Choline, 11C-choline and 11C-acetate PET/CT: comparative analysis for imaging prostate cancer patients.

    PubMed

    Brogsitter, Claudia; Zöphel, Klaus; Kotzerke, Jörg

    2013-07-01

    Prostate cancer (PCA) is the second most common tumour in men worldwide. Whereas prostate specific antigen (PSA) is an established biochemical marker, the optimal imaging method for all clinical scenarios has not yet been found. With the rising number of PET centres there is an increasing availability and use of (18)F-/(11)C-choline or (11)C-acetate for staging of PCA. However, to date no final conclusion has been reached as to whether acetate or choline tracers should be preferred. In this review we provide an overview of the performance of choline and acetate PET for staging the primary and recurrent disease and lymph nodes in PCA, based on the literature of the last 10 years. Although predominantly choline has been used rather than acetate, both tracers performed in a similar manner in published studies. Choline as well as acetate have insufficient diagnostic accuracy for the staging of the primary tumour, due to a minimum detectable tumour size of 5 mm and inability to differentiate PCA from benign prostate hyperplasia, chronic prostatitis and high-grade intraepithelial neoplasia. Regarding lymph node staging, choline tracers have demonstrated a high specificity. Unfortunately, the sensitivity is only moderate. For staging recurrent disease, sensitivity depends on the level of serum PSA (PSA should be >2 ng/ml). This applies to both choline and acetate. However, despite these limitations, a significant number of patients with recurrent disease can benefit from PET imaging by a change in treatment planning.

  7. CMAD: A Self-consistent Parallel Code to Simulate the Electron Cloud Build-up and Instabilities

    SciTech Connect

    Pivi, M.T.F.; /SLAC

    2007-11-07

    We present the features of CMAD, a newly developed self-consistent code which simulates both the electron cloud build-up and related beam instabilities. By means of parallel (Message Passing Interface - MPI) computation, the code tracks the beam in an existing (MAD-type) lattice and continuously resolves the interaction between the beam and the cloud at each element location, with different cloud distributions at each magnet location. The goal of CMAD is to simulate single- and coupled-bunch instability, allowing tune shift, dynamic aperture and frequency map analysis and the determination of the secondary electron yield instability threshold. The code is in its phase of development and benchmarking with existing codes. Preliminary results on benchmarking are presented in this paper.

  8. Social dynamics within decomposer communities lead to nitrogen retention and organic matter build-up in soils.

    PubMed

    Kaiser, Christina; Franklin, Oskar; Richter, Andreas; Dieckmann, Ulf

    2015-01-01

    The chemical structure of organic matter has been shown to be only marginally important for its decomposability by microorganisms. The question of why organic matter does accumulate in the face of powerful microbial degraders is thus key for understanding terrestrial carbon and nitrogen cycling. Here we demonstrate, based on an individual-based microbial community model, that social dynamics among microbes producing extracellular enzymes ('decomposers') and microbes exploiting the catalytic activities of others ('cheaters') regulate organic matter turnover. We show that the presence of cheaters increases nitrogen retention and organic matter build-up by downregulating the ratio of extracellular enzymes to total microbial biomass, allowing nitrogen-rich microbial necromass to accumulate. Moreover, increasing catalytic efficiencies of enzymes are outbalanced by a strong negative feedback on enzyme producers, leading to less enzymes being produced at the community level. Our results thus reveal a possible control mechanism that may buffer soil CO2 emissions in a future climate.

  9. Assessment of indoor absorbed gamma dose rate from natural radionuclides in concrete by the method of build-up factors.

    PubMed

    Manić, Vesna; Nikezic, Dragoslav; Krstic, Dragana; Manić, Goran

    2014-12-01

    The specific absorbed gamma dose rates, originating from natural radionuclides in concrete, were calculated at different positions of a detection point inside the standard room, as well as inside an example room. The specific absorbed dose rates corresponding to a wall with arbitrary dimensions and thickness were also evaluated, and appropriate fitting functions were developed, enabling dose rate calculation for most realistic rooms. In order to make calculation simpler, the expressions fitting the exposure build-up factors for whole (238)U and (232)Th radionuclide series and (40)K were derived in this work, as well as the specific absorbed dose rates from a point source in concrete. Calculated values of the specific absorbed dose rates at the centre point of the standard room for (238)U, (232)Th and (40)K are in the ranges of previously obtained data.

  10. Expression of CD11c Is Associated with Unconventional Activated T Cell Subsets with High Migratory Potential.

    PubMed

    Qualai, Jamal; Li, Lin-Xi; Cantero, Jon; Tarrats, Antoni; Fernández, Marco Antonio; Sumoy, Lauro; Rodolosse, Annie; McSorley, Stephen J; Genescà, Meritxell

    2016-01-01

    CD11c is an α integrin classically employed to define myeloid dendritic cells. Although there is little information about CD11c expression on human T cells, mouse models have shown an association of CD11c expression with functionally relevant T cell subsets. In the context of genital tract infection, we have previously observed increased expression of CD11c in circulating T cells from mice and women. Microarray analyses of activated effector T cells expressing CD11c derived from naïve mice demonstrated enrichment for natural killer (NK) associated genes. Here we find that murine CD11c+ T cells analyzed by flow cytometry display markers associated with non-conventional T cell subsets, including γδ T cells and invariant natural killer T (iNKT) cells. However, in women, only γδ T cells and CD8+ T cells were enriched within the CD11c fraction of blood and cervical tissue. These CD11c+ cells were highly activated and had greater interferon (IFN)-γ secretory capacity than CD11c- T cells. Furthermore, circulating CD11c+ T cells were associated with the expression of multiple adhesion molecules in women, suggesting that these cells have high tissue homing potential. These data suggest that CD11c expression distinguishes a population of circulating T cells during bacterial infection with innate capacity and mucosal homing potential. PMID:27119555

  11. Expression of CD11c Is Associated with Unconventional Activated T Cell Subsets with High Migratory Potential

    PubMed Central

    Cantero, Jon; Tarrats, Antoni; Fernández, Marco Antonio; Sumoy, Lauro; Rodolosse, Annie; McSorley, Stephen J.

    2016-01-01

    CD11c is an α integrin classically employed to define myeloid dendritic cells. Although there is little information about CD11c expression on human T cells, mouse models have shown an association of CD11c expression with functionally relevant T cell subsets. In the context of genital tract infection, we have previously observed increased expression of CD11c in circulating T cells from mice and women. Microarray analyses of activated effector T cells expressing CD11c derived from naïve mice demonstrated enrichment for natural killer (NK) associated genes. Here we find that murine CD11c+ T cells analyzed by flow cytometry display markers associated with non-conventional T cell subsets, including γδ T cells and invariant natural killer T (iNKT) cells. However, in women, only γδ T cells and CD8+ T cells were enriched within the CD11c fraction of blood and cervical tissue. These CD11c+ cells were highly activated and had greater interferon (IFN)-γ secretory capacity than CD11c- T cells. Furthermore, circulating CD11c+ T cells were associated with the expression of multiple adhesion molecules in women, suggesting that these cells have high tissue homing potential. These data suggest that CD11c expression distinguishes a population of circulating T cells during bacterial infection with innate capacity and mucosal homing potential. PMID:27119555

  12. Temperature effect on the build-up of exponentially growing polyelectrolyte multilayers. An exponential-to-linear transition point.

    PubMed

    Vikulina, Anna S; Anissimov, Yuri G; Singh, Prateek; Prokopović, Vladimir Z; Uhlig, Katja; Jaeger, Magnus S; von Klitzing, Regine; Duschl, Claus; Volodkin, Dmitry

    2016-03-21

    In this study, the effect of temperature on the build-up of exponentially growing polyelectrolyte multilayer films was investigated. It aims at understanding the multilayer growth mechanism as crucially important for the fabrication of tailor-made multilayer films. Model poly(L-lysine)/hyaluronic acid (PLL/HA) multilayers were assembled in the temperature range of 25-85 °C by layer-by-layer deposition using a dipping method. The film growth switches from the exponential to the linear regime at the transition point as a result of limited polymer diffusion into the film. With the increase of the build-up temperature the film growth rate is enhanced in both regimes; the position of the transition point shifts to a higher number of deposition steps confirming the diffusion-mediated growth mechanism. Not only the faster polymer diffusion into the film but also more porous/permeable film structure are responsible for faster film growth at higher preparation temperature. The latter mechanism is assumed from analysis of the film growth rate upon switching of the preparation temperature during the film growth. Interestingly, the as-prepared films are equilibrated and remain intact (no swelling or shrinking) during temperature variation in the range of 25-45 °C. The average activation energy for complexation between PLL and HA in the multilayers calculated from the Arrhenius plot has been found to be about 0.3 kJ mol(-1) for monomers of PLL. Finally, the following processes known to be dependent on temperature are discussed with respect to the multilayer growth: (i) polymer diffusion, (ii) polymer conformational changes, and (iii) inter-polymer interactions. PMID:26911320

  13. System and Method for Determining Fluence of a Substance

    NASA Technical Reports Server (NTRS)

    Banks, Bruce A. (Inventor)

    2016-01-01

    A system and method for measuring a fluence of gas are disclosed. The system has a first light detector capable of outputting an electrical signal based on an amount of light received. A barrier is positionable adjacent the first light detector and is susceptible to a change in dimension from the fluence of the gas. The barrier permits a portion of light from being received by the first light detector. The change in the dimension of the barrier changes the electrical signal output from the first light detector. A second light detector is positionable to receive light representative of the first light detector without the barrier. The system and method have broad application to detect fluence of gas that may cause erosion chemical reaction causing erosive deterioration. One application is in low orbit Earth for detecting the fluence of atomic oxygen.

  14. Charge topology of the coherent dissociation of relativistic {sup 11}C and {sup 12}N nuclei

    SciTech Connect

    Artemenkov, D. A.; Bradnova, V.; Zaitsev, A. A.; Zarubin, P. I. Zarubina, I. G.; Kattabekov, R. R.; Kornegrutsa, N. K.; Mamatkulov, K. Z.; Rukoyatkin, P. A.; Rusakova, V. V.; Stanoeva, R.

    2015-09-15

    The charge topology of coherent-dissociation events is presented for {sup 11}C and {sup 12}N nuclei of energy 1.2 GeV per nucleon bombarding nuclear track emulsions. This topology is compared with respective data for {sup 7}Be, {sup 8,10}B, {sup 9,10}C, and {sup 14}N nuclei.

  15. 29 CFR 1977.5 - Persons protected by section 11(c).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... employees are afforded the full protection of section 11(c). For purposes of the Act, an employee is defined.... See, U.S. v. Silk, 331 U.S. 704 (1947); Rutherford Food Corporation v. McComb, 331 U.S. 722 (1947)....

  16. 29 CFR 1977.5 - Persons protected by section 11(c).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 9 2014-07-01 2014-07-01 false Persons protected by section 11(c). 1977.5 Section 1977.5 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) DISCRIMINATION AGAINST EMPLOYEES EXERCISING RIGHTS UNDER THE...

  17. 29 CFR 1977.3 - General requirements of section 11(c) of the Act.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 9 2014-07-01 2014-07-01 false General requirements of section 11(c) of the Act. 1977.3 Section 1977.3 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) DISCRIMINATION AGAINST EMPLOYEES EXERCISING RIGHTS UNDER...

  18. 29 CFR 1977.3 - General requirements of section 11(c) of the Act.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 9 2011-07-01 2011-07-01 false General requirements of section 11(c) of the Act. 1977.3 Section 1977.3 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) DISCRIMINATION AGAINST EMPLOYEES EXERCISING RIGHTS UNDER...

  19. 29 CFR 1977.5 - Persons protected by section 11(c).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 9 2012-07-01 2012-07-01 false Persons protected by section 11(c). 1977.5 Section 1977.5 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) DISCRIMINATION AGAINST EMPLOYEES EXERCISING RIGHTS UNDER THE...

  20. 29 CFR 1977.3 - General requirements of section 11(c) of the Act.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 false General requirements of section 11(c) of the Act. 1977.3 Section 1977.3 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) DISCRIMINATION AGAINST EMPLOYEES EXERCISING RIGHTS UNDER...

  1. 29 CFR 1977.3 - General requirements of section 11(c) of the Act.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 9 2013-07-01 2013-07-01 false General requirements of section 11(c) of the Act. 1977.3 Section 1977.3 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) DISCRIMINATION AGAINST EMPLOYEES EXERCISING RIGHTS UNDER...

  2. 29 CFR 1977.3 - General requirements of section 11(c) of the Act.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 9 2012-07-01 2012-07-01 false General requirements of section 11(c) of the Act. 1977.3 Section 1977.3 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) DISCRIMINATION AGAINST EMPLOYEES EXERCISING RIGHTS UNDER...

  3. 29 CFR 1977.5 - Persons protected by section 11(c).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 9 2011-07-01 2011-07-01 false Persons protected by section 11(c). 1977.5 Section 1977.5 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) DISCRIMINATION AGAINST EMPLOYEES EXERCISING RIGHTS UNDER THE...

  4. 29 CFR 1977.5 - Persons protected by section 11(c).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 false Persons protected by section 11(c). 1977.5 Section 1977.5 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) DISCRIMINATION AGAINST EMPLOYEES EXERCISING RIGHTS UNDER THE...

  5. Development of a (11)C-labeled tetrazine for rapid tetrazine-trans-cyclooctene ligation.

    PubMed

    Herth, Matthias M; Andersen, Valdemar L; Lehel, Szabolcs; Madsen, Jacob; Knudsen, Gitte M; Kristensen, Jesper L

    2013-05-01

    Tetrazine-trans-cyclooctene ligations are remarkably fast and selective reactions even at low micro-molar concentrations. In bioorthogonal radiochemistry, tools that enable conjugation of radioactive probes to pre-targeted vectors are of great interest. Herein, we describe the successful development of the first (11)C-labelled tetrazine and its reaction with trans-cyclooctenol.

  6. Building up College Towns

    ERIC Educational Resources Information Center

    Powers, Elia

    2007-01-01

    When it comes to college towns and neighborhoods near urban campuses, quaint will not cut it anymore. An increasing number of institutions are finding ways--directly or indirectly--to promote a mix of commercial and residential development just beyond their borders that they hope will lure students and faculty. This article discusses how…

  7. Imaging acetylcholinesterase density in peripheral organs in Parkinson's disease with 11C-donepezil PET.

    PubMed

    Gjerløff, Trine; Fedorova, Tatyana; Knudsen, Karoline; Munk, Ole L; Nahimi, Adjmal; Jacobsen, Steen; Danielsen, Erik H; Terkelsen, Astrid J; Hansen, John; Pavese, Nicola; Brooks, David J; Borghammer, Per

    2015-03-01

    Parkinson's disease is associated with early parasympathetic dysfunction leading to constipation and gastroparesis. It has been suggested that pathological α-synuclein aggregations originate in the gut and ascend to the brainstem via the vagus. Our understanding of the pathogenesis and time course of parasympathetic denervation in Parkinson's disease is limited and would benefit from a validated imaging technique to visualize the integrity of parasympathetic function. The positron emission tomography tracer 5-[(11)C]-methoxy-donepezil was recently validated for imaging acetylcholinesterase density in the brain and peripheral organs. Donepezil is a high-affinity ligand for acetylcholinesterase-the enzyme that catabolizes acetylcholine in cholinergic synapses. Acetylcholinesterase histology has been used for many years for visualizing cholinergic neurons. Using 5-[(11)C]-methoxy-donepezil positron emission tomography, we studied 12 patients with early-to-moderate Parkinson's disease (three female; age 64 ± 9 years) and 12 age-matched control subjects (three female; age 62 ± 8 years). We collected clinical information about motor severity, constipation, gastroparesis, and other parameters. Heart rate variability measurements and gastric emptying scintigraphies were performed in all subjects to obtain objective measures of parasympathetic function. We detected significantly decreased (11)C-donepezil binding in the small intestine (-35%; P = 0.003) and pancreas (-22%; P = 0.001) of the patients. No correlations were found between the (11)C-donepezil signal and disease duration, severity of constipation, gastric emptying time, and heart rate variability. In Parkinson's disease, the dorsal motor nucleus of the vagus undergoes severe degeneration and pathological α-synuclein aggregations are also seen in nerve fibres innervating the gastro-intestinal tract. In contrast, the enteric nervous system displays little or no loss of cholinergic neurons. Decreases in (11)C

  8. [PET using 11C-methionine in recognition of pseudoprogression in cerebral glioma after combined treatment].

    PubMed

    Skvortsova, T Yu; Brodskaya, Z L; Gurchin, A F

    2014-01-01

    The purpose of the study was to evaluate the value of PET using 11C-methionine (PET-Met) for distinction between true glioma progression and pseudoprogression (PsPr). 72 patients with treated cerebral glioma investigated by PET-Met were identified from prospective database. Entry criteria included new or progressive MR imaging enhancing lesions within first 6 months after irradiation and definite final diagnosis on the basis of the pathological study (n=17) or clinical-radiological follow-up on an average 16 months. PET examinations were assessed by visual inspection and calculating 11C-methionine uptake index (UI). Results. Pseudoprogression was defined as early radiological progression with subsequent regress or stabilization, without salvage therapy. 42 patients were considered to exhibit PsPr and 30 patients had true glioma progression. In PsPr group PET scans were either negative (n=6) or slightly increased tracer uptake (UI range 1.2-2.14) was seen in the site of contrast-enhanced lesion. The UI was 1.48±0.39 (mean±SD). In comparison with pretreatment PET 15 patients showed decrease 11C-methionine uptake on an average by 26%. In recurrence group PET-Met showed abnormal high focal 11C-methionine uptake in the lesion. The UI was 2.54±0.84 (range 1.54-5.4). An UI threshold value of greater than 1.9 optimized differentiation between glioma progression and PsPr with sensitivity of 83.5% and specificity of 97.0%. Conclusion. Metabolic characteristics of PsPr included negative tracer accumulation or slightly increased 11C-methionine uptake in the contrast-enhancing lesion with UI less than 1.9.

  9. Synthesis and PET studies of [11C-cyano]letrozole (Femara), an aromatase inhibitor drug

    SciTech Connect

    kil K. E.; Biegon A.; Kil, K.-E.; Biegon, A.; Ding, Y.-S.; Fischer, A.; Ferrieri, R.A.; Kim, S.-W.; Pareto, D.; Schueller, M.J.; Fowler, J.S.

    2008-11-10

    Aromatase, a member of the cytochrome P450 family, converts androgens such as androstenedione and testosterone to estrone and estradiol respectively. Letrozole (1-[bis-(4-cyanophenyl)methyl]-1H-1,2,4-triazole, Femara{reg_sign}) is a high affinity aromatase inhibitor (K{sub i}=11.5 nM) which has FDA approval for breast cancer treatment. Here we report the synthesis of carbon-11 labeled letrozole and its assessment as a radiotracer for brain aromatase in the baboon. Letrozole and its precursor (4-[(4-bromophenyl)-1H-1,2,4-triazol-1-ylmethyl]benzonitrile, 3) were prepared in two-step syntheses from 4-cyanobenzyl bromide and 4-bromobenzyl bromide, respectively. The [{sup 11}C]cyano group was introduced via the tetrakis(triphenylphosphine)palladium(0) catalyzed coupling of [{sup 11}C]cyanide with the bromo-precursor (3). PET studies in the baboon brain were carried out to assess regional distribution and kinetics, reproducibility of repeated measures and saturability. The free fraction of letrozole in the plasma, log D, and the [{sup 11}C-cyano]letrozole fraction in the arterial plasma were also measured. [{sup 11}C-cyano]Letrozole was synthesized in 60 min with a radiochemical yield of 79-80%, with a radiochemical purity greater than 98% and a specific activity of 4.16 {+-} 2.21 Ci/{micro}mol at the end of bombardment (n=4). PET studies in the baboon revealed initial rapid and high uptake and initial rapid clearance followed by slow clearance of carbon-11 from the brain with no difference between brain regions. The brain kinetics was not affected by co-injection of unlabeled letrozole (0.1 mg/kg). The free fraction of letrozole in plasma was 48.9% and log D was 1.84. [{sup 11}C-cyano]Letrozole is readily synthesized via a palladium catalyzed coupling reaction with [{sup 11}C]cyanide. Although it is unsuitable as a PET radiotracer for brain aromatase as revealed by the absence of regional specificity and saturability in brain regions, such as amygdala, which are known

  10. Radiosynthesis of 11C-Levetiracetam: A Potential Marker for PET Imaging of SV2A Expression

    PubMed Central

    2014-01-01

    The multistep preparation of 11C-levetiracetam (11C-LEV) was carried out by a one-pot radiosynthesis with 8.3 ± 1.6% (n = 8) radiochemical yield in 50 ± 5.0 min. Briefly, the propionaldehyde was converted to propan-1-imine in situ as labeling precursor by incubation with ammonia. Without further separation, the imine was reacted with 11C-HCN to form 11C-aminonitrile. This crude was then reacted with 4-chlorobutyryl chloride and followed by hydrolysis to yield 11C-LEV after purification by chiral high-performance liquid chromatography (HPLC). Both the radiochemical and enantiomeric purities of 11C-LEV were >98%. PMID:25313330

  11. Imaging Spectrum and Pitfalls of 11C-Methionine Positron Emission Tomography in a Series of Patients with Intracranial Lesions

    PubMed Central

    Matsuda, Hiroshi; Kubota, Kazoo

    2016-01-01

    11C-methionine (Met) positron emission tomography (PET) is one of the most commonly used PET tracers for evaluating brain tumors. However, few reports have described tips and pitfalls of 11C-Met PET for general practitioners. Physiological 11C-Met uptake, anatomical variations, vascular disorders, non-tumorous lesions such as inflammation or dysplasia, benign brain tumors and patient condition during 11C-Met PET examination can potentially affect the image interpretation and cause false positives and negatives. These pitfalls in the interpretation of 11C-Met PET images are important for not only nuclear medicine physicians but also general radiologists. Familiarity with the spectrum and pitfalls of 11C-Met images could help prevent unfavorable clinical results caused by misdiagnoses. PMID:27134530

  12. SU-E-T-59: Calculations of Collimator Scatter Factors (Sc) with and Without Custom-Made Build-Up Caps for CyberKnife

    SciTech Connect

    Wokoma, S; Yoon, J; Jung, J; Lee, S

    2014-06-01

    Purpose: To investigate the impact of custom-made build-up caps for a diode detector in robotic radiosurgery radiation fields with variable collimator (IRIS) for collimator scatter factor (Sc) calculation. Methods: An acrylic cap was custom-made to fit our SFD (IBA Dosimetry, Germany) diode detector. The cap has thickness of 5 cm, corresponding to a depth beyond electron contamination. IAEA phase space data was used for beam modeling and DOSRZnrc code was used to model the detector. The detector was positioned at 80 cm source-to-detector distance. Calculations were performed with the SFD, with and without the build-up cap, for clinical IRIS settings ranging from 7.5 to 60 mm. Results: The collimator scatter factors were calculated with and without 5 cm build-up cap. They were agreed within 3% difference except 15 mm cone. The Sc factor for 15 mm cone without buildup was 13.2% lower than that with buildup. Conclusion: Sc data is a critical component in advanced algorithms for treatment planning in order to calculate the dose accurately. After incorporating build-up cap, we discovered differences of up to 13.2 % in Sc factors in the SFD detector, when compared against in-air measurements without build-up caps.

  13. Spectroscopic Classification of Nova M31N 2015-11c

    NASA Astrophysics Data System (ADS)

    Williams, S. C.; Darnley, M. J.

    2015-12-01

    We obtained a spectrum of the M31 nova candidate M31N 2015-11c (PNV J00433852+4128026; ATel #8327) with the SPRAT spectrograph on the 2m Liverpool Telescope (Steele et al. 2004) on 2015 December 3.9 UT. The spectrum shows strong Balmer emission, with numerous Fe II lines also detected in emission (including the 42, 48, 49 and 74 multiplets), along with Na I (D) and [O I] (6300 and 6364 & Aring;).

  14. Comprehensive fluence model for absolute portal dose image prediction

    SciTech Connect

    Chytyk, K.; McCurdy, B. M. C.

    2009-04-15

    Amorphous silicon (a-Si) electronic portal imaging devices (EPIDs) continue to be investigated as treatment verification tools, with a particular focus on intensity modulated radiation therapy (IMRT). This verification could be accomplished through a comparison of measured portal images to predicted portal dose images. A general fluence determination tailored to portal dose image prediction would be a great asset in order to model the complex modulation of IMRT. A proposed physics-based parameter fluence model was commissioned by matching predicted EPID images to corresponding measured EPID images of multileaf collimator (MLC) defined fields. The two-source fluence model was composed of a focal Gaussian and an extrafocal Gaussian-like source. Specific aspects of the MLC and secondary collimators were also modeled (e.g., jaw and MLC transmission factors, MLC rounded leaf tips, tongue and groove effect, interleaf leakage, and leaf offsets). Several unique aspects of the model were developed based on the results of detailed Monte Carlo simulations of the linear accelerator including (1) use of a non-Gaussian extrafocal fluence source function, (2) separate energy spectra used for focal and extrafocal fluence, and (3) different off-axis energy spectra softening used for focal and extrafocal fluences. The predicted energy fluence was then convolved with Monte Carlo generated, EPID-specific dose kernels to convert incident fluence to dose delivered to the EPID. Measured EPID data were obtained with an a-Si EPID for various MLC-defined fields (from 1x1 to 20x20 cm{sup 2}) over a range of source-to-detector distances. These measured profiles were used to determine the fluence model parameters in a process analogous to the commissioning of a treatment planning system. The resulting model was tested on 20 clinical IMRT plans, including ten prostate and ten oropharyngeal cases. The model predicted the open-field profiles within 2%, 2 mm, while a mean of 96.6% of pixels over

  15. Preliminary Ionization Efficiencies of {sup 11}C and {sup 14}O with the LBNL ECR Ion Sources

    SciTech Connect

    Xie, Z.Q.; Cerny, J.; Guo, F.Q.; Joosten, R.; Larimer, R.M.; Lyneis, C.M.; McMahan, P.; Norman, E.B.; O'Neil, J.P.; Powell, J.; Rowe, M.W.; VanBrocklin, H.F.; Wutte, D.; Xu, X.J.; Haustein, P.

    1998-10-05

    High charge states, up to fully stripped {sup 11}C and {sup 14}O ion, beams have been produced with the electron cyclotron resonance ion sources (LBNL, ECR and AECR-U) at Lawrence Berkeley National Laboratory. The radioactive atoms of {sup 11}C and {sup 14}O were collected in batch mode with an LN{sub 2} trap and then bled into the ECR ion sources. Ionization efficiency as high as 11% for {sup 11}C{sup 4+} was achieved.

  16. Synthesis and biologic evaluation of 1-(/sup 11/C)-3,3-dimethylheptadecanoic acid

    SciTech Connect

    Jones, G.S. Jr.; Livni, E.; Strauss, H.W.; Hanson, R.N.; Elmaleh, D.R.

    1988-01-01

    1-(/sup 11/C)-3,3-dimethylheptadecanoic acid ((/sup 11/C)DMHDA) has been prepared for evaluation as a potential myocardial metabolism indicator based on an expected intrinsic stability toward beta-oxidative metabolic processes. Synthesis of this novel branched-chain fatty acid was accomplished by copper-catalyzed addition of tetradecylmagnesium bromide to diethylisopropylidenemalonate. Subsequent saponification and decarboxylation afforded 3,3-dimethylheptadecanoic acid (DMHDA) that was converted to the corresponding alkyl bromide by means of a modified Hunsdiecker reaction. Carboxylation of 2,2-dimethylhexadecylmagnesium bromide with /sup 11/CO/sub 2/ gave (/sup 11/C)DMHDA. Carbon-11 DMHDA showed moderate myocardial uptake in fasted rats, albeit lower than that reported for the 3-monomethyl analog. Considerable washout of radioactivity from the heart was also observed over the first 30 min postinjection. Imaging in dogs likewise showed disappointing heart uptake with much higher localization in the lung. These data suggest that gem-dimethyl substitution of the beta-position in long chain fatty acids is not only insufficient for enhanced myocardial uptake and retention, but also, may be deleterious when compared with beta-monomethylation.

  17. Varenicline-Induced Elevation of Dopamine in Smokers: A Preliminary [(11)C]-(+)-PHNO PET Study.

    PubMed

    Di Ciano, Patricia; Guranda, Mihail; Lagzdins, Dina; Tyndale, Rachel F; Gamaleddin, Islam; Selby, Peter; Boileau, Isabelle; Le Foll, Bernard

    2016-05-01

    Varenicline, a nicotinic partial agonist, is the most effective treatment for tobacco use disorder. However, its mechanism of action is still unclear and may involve stimulating dopaminergic transmission. Here we used PET imaging with [(11)C]-(+)-PHNO to explore for the first time the impact of varenicline on dopamine transmission in the D2-rich striatum and D3-rich extra-striatal regions and its relationship with craving, withdrawal and smoking. Eleven treatment-seeking smokers underwent two PET scans with [(11)C]-(+)-PHNO, each following 12-h overnight smoking abstinence both prior to receiving varenicline and following 10-11 days of varenicline treatment (ie, at steady-state drug levels). Subjective measures of craving and urges to smoke were also assessed on the days of the PET scans. Varenicline treatment significantly reduced [(11)C]-(+)-PHNO binding in the dorsal caudate (p=0.008) and reduced some craving measures. These findings provide the first evidence that varenicline is able to increase DA levels in the human brain, a factor that may contribute to its therapeutic efficacy. PMID:26442600

  18. Novel synthesis of [11C]GVG (Vigabatgrin) for pharmacokinetic studies of addiction treatment

    SciTech Connect

    Ding, Y.S.; Studenov, A.R.; Zhang, Z.; Gerasimov, M.; Schiffer, W.; Dewey, S.L.; Telang, F.

    2001-06-10

    We report here a novel synthetic route to prepare the precursor and to efficiently label GVG with C-11. 5-Bromo-3-(carbobenzyloxy)amino-1-pentene was synthesized in five steps from homoserine lactone. This was used in a two step radiosynthesis, displacement with [{sup 11}C]cyanide followed by acid hydrolysis to afford [{sup 11}C]GVG with high radiochemical yields (> 35%, not optimized) and high specific activity (2-5 Ci/{micro}mol). The [{sup 11}C]cyanide trapping was achieved at {minus}5 C with a mixture of Kryptofix and K{sub 2}CO{sub 3} without using conventional aqueous trapping procedure [7]. At this temperature, the excess NH{sub 3} from the target that may interfere with the synthesis would not be trapped [8]. This procedure would be advantageous to any moisture sensitive radiosynthetic steps, as it was the case for our displacement reaction. When conventional aqueous trapping procedure was used, any trace amount of water left, even after prolonged heating, resulted in either no reaction or extremely low yields for the displacement reaction. The entire synthetic procedure should be extendible to the labeling of the pharmacologically active S- form of GVG when using S-homoserine lactone.

  19. Kinetic analysis of [11C]vorozole binding in the human brain with positron emission tomography.

    PubMed

    Logan, Jean; Kim, Sung Won; Pareto, Deborah; Telang, Frank; Wang, Gene-Jack; Fowler, Joanna S; Biegon, Anat

    2014-01-01

    Using positron emission tomography, we investigated the kinetics of [11C]vorozole ([11C]VOR), a radiotracer for the enzyme aromatase that catalyzes the last step in estrogen biosynthesis. Six subjects were scanned under baseline conditions followed by retest 2 weeks later. The retest was followed by a blocking study with 2.5 mg of the aromatase inhibitor letrozole. The binding potential (BP(A)ND) was estimated from a Lassen plot using the total tissue distribution volume (VT) for baseline and blocked. for the thalamus was found to be 15 times higher than that for the cerebellum. From the letrozole studies, we found that [11C]VOR exhibits a slow binding compartment (small k4) that has a nonspecific and a blockable component. Because of the sensitivity of VT to variations in k4, a common value was used for the four highest binding regions. We also considered the tissue uptake to plasma ratio for 60 to 90 minutes as an outcome measure. Using the ratio method, the difference between the highest and lowest was 2.4 compared to 3.5 for the VT. The ratio method underestimates the high regions but is less variable and may be more suitable for patient studies. Because of its kinetics and distribution, this tracer is not a candidate for a bolus infusion or reference tissue methods.

  20. Production of L-(1-/sup 11/C)valine by HPLC resolution

    SciTech Connect

    Washburn, L.C.; Sun, T.T.; Byrd, B.L.; Callahan, A.P.

    1982-01-01

    Based on a recently developed analytical technique, preparative high-performance liquid chromatographic (HPLC) resolution of DL-(1-/sup 11/C)valine has been achieved. A conventional reverse-phase HPLC column and a chiral mobile phase (aqueous solution of L-proline, cupric acetate, and sodium acetate) were used. The copper can be removed from the L-valine fraction by precipitation as the sulfide, and final purification by cation-exchange chromatography yields L-(1-/sup 11/C)valine in a form that is acceptable for clinical positron tomographic studies. This purification method does not remove the L-proline introduced in the resolution process, but added L-proline did not affect the tissue distribution of L-(1-/sup 14/C)valine in rats. We have produced up to 60 mCi of L-(1-/sup 11/C)valine in an overall synthesis and resolution time of 50 min. This procedure should be adaptable to the rapid resolution of other C-/sup 11/-labeled amino acid racemates.

  1. Production of L-(1-/sup 11/C)valine by HPLC resolution

    SciTech Connect

    Washburn, L.C.; Sun, T.T.; Byrd, B.L.; Callahan, A.P.

    1982-01-01

    Based on a recently developed analytical technique, preparative high-performance liquid chromatographic (HPLC) resolution of DL-(1-/sup 11/C)valine has been achieved. A conventional reverse-phase HPLC column and a chiral mobile phase (aqueous solution of L-proline, cupric acetate, and sodium acetate) were used. The copper can be removed from the L-valine fraction by precipitation as the sulfide, and final purification by cation-exchange chromatography yields L-(1-/sup 11/C)valine in a form that is acceptable for clinical positron tomographic studies. This purification method does not remove the L-proline introduced in the resolution process, but added L-proline did not affect the tissue distribution of L-(1-/sup 14/C)valine in rats. We have produced up to 60 mCi of L-(1-/sup 11/C)valine in an overall synthesis and resolution time of 50 min. This procedure should be adapable to the rapid resolution of other C-11-labeled amino acid racemates.

  2. Effect of the thermoplastic masks on dose distribution in the build-up region for photon beams

    NASA Astrophysics Data System (ADS)

    Półtorak, Michał; Fujak, Edyta; Kukołowicz, Paweł

    2016-03-01

    The aim of the study was to investigate the influence of thermoplastic masks material (Klarity Medical&Equipment Co., Guangzhou, China) with different diameters of holes (ϕ 0.25 cm and ϕ 0.40 cm) on the dose distribution in the build-up region for photon beams. Measurements were made for external radiation beams produced by the linear accelerator (TrueBeam, Varian Medical Systems, Inc., Palo Alto, CA, USA) using the Markus parallel plane ionization chamber and the Unidos electrometer (both from PTW, Freiburg, Germany). Measurements were made in a solid water phantom for two photon energies 6 MV and 15 MV, at 90 cm source to skin distance, for four fields of 5 cm × 5 cm, 10 cm × 10 cm, 15 cm × 15 cm and 20 cm × 20 cm. Compared to the open field, the maximum dose with mask was closer to the surface of the phantom by about 1.4 mm and 1.2 mm for 6 MV and 15 MV X-Rays, respectively. The surface dose increase from 10% to 42% for 6 MV and from 5% to 28% for 15 MV X-Rays.

  3. Studies of E-Cloud Build up for the FNAL Main Injector and for theLHC

    SciTech Connect

    Furman, M.A.

    2006-06-14

    We present a summary of recent simulation studies of the electron-cloud (EC) build-up for the FNAL MI and for the LHC. In the first case we pay particular attention to the dependence on bunch intensity N{sub b} at injection energy assuming the nominal bunch spacing t{sub b} = 19 ns, and we focus on the dipole magnets and field-free regions. The saturated value of the average EC density shows a clear threshold in N{sub b} beyond which the beam will be approximately neutralized on average. For the case of the LHC we limit our discussion to arc dipoles at collision energy, and bunch spacings t{sub b} = 25 ns or t{sub b} = 75 ns. The main variables exercised in this study are N{sub b} and the peak value of the secondary emission yield (SEY) {delta}{sub max}. For t{sub b} = 25 ns we conclude that the EC power deposition is comfortably below the available cooling capacity of the cryogenic system if {delta}{sub max} is below {approx} 1.2 at nominal N{sub b}. For t{sub b} = 75 ns, the EC power deposition is insignificant. As a byproduct of this exercise, we reach a detailed understanding of the significant role played by the backscattered secondary electrons. This article summarizes the results, an slightly extends the discussions, presented in Refs. 1 and 2.

  4. Measurements and simulation of the radiation build-up process in a prebunched free-electron maser oscillator

    SciTech Connect

    Gilutin, L.; Pinhasi, Y.; Cohen, M.

    1995-12-31

    Numerical studies of the radiation buildup process in a prebunched free-electron maser oscillator (FEM), were carried out at Tel-Aviv University (TAU) and at the University of Maryland (UMD), and compared to the experimental measurements taken on the prebunched beam FEM experiments in TAU. We present measurements of the temporal evolution of radiation excited from noise until a steady-state operation is established. The evolution of the spectral characteristics of the radiation was investigated using the data collected by a fast digitizing scope, which recorded the IF signal obtained from heterodyning the laser radiation with a stable local oscillator. The mode competition process was observed. The experimental results were compared to analytical calculations of the spontaneous emission power and small-signal gain. Nonlinear {open_quote}amplifier{close_quote} simulation codes were employed for calculation of the extraction efficiency and saturation power. Multi-frequency simulations of the mode competition process were carried out using simulation (MALT ID) code, which is based on a space-time one-dimensional model of a free-electron laser oscillator. Conditions for establishment of single-(longitudinal) mode operation were identified and compared to the experimental measurements. Prebunching of the e-beam current permits external interference in the mode competition and coherence build-up process. We found experimentally and confirmed numerically that prebunching can determine the frequency of oscillation if the e-beam is injected with a sufficient bunching power, and shortens the oscillation buildup and coherence establishment time.

  5. Social dynamics within decomposer communities lead to nitrogen retention and organic matter build-up in soils

    PubMed Central

    Kaiser, Christina; Franklin, Oskar; Richter, Andreas; Dieckmann, Ulf

    2015-01-01

    The chemical structure of organic matter has been shown to be only marginally important for its decomposability by microorganisms. The question of why organic matter does accumulate in the face of powerful microbial degraders is thus key for understanding terrestrial carbon and nitrogen cycling. Here we demonstrate, based on an individual-based microbial community model, that social dynamics among microbes producing extracellular enzymes (‘decomposers') and microbes exploiting the catalytic activities of others (‘cheaters') regulate organic matter turnover. We show that the presence of cheaters increases nitrogen retention and organic matter build-up by downregulating the ratio of extracellular enzymes to total microbial biomass, allowing nitrogen-rich microbial necromass to accumulate. Moreover, increasing catalytic efficiencies of enzymes are outbalanced by a strong negative feedback on enzyme producers, leading to less enzymes being produced at the community level. Our results thus reveal a possible control mechanism that may buffer soil CO2 emissions in a future climate. PMID:26621582

  6. Spectral fluence of neutrons generated by radiotherapeutic linacs.

    PubMed

    Králík, Miloslav; Šolc, Jaroslav; Vondráček, Vladimir; Šmoldasová, Jana; Farkašová, Estera; Tichá, Ivana

    2015-02-01

    Spectral fluences of neutrons generated in the heads of the radiotherapeutic linacs Varian Clinac 2100 C/D and Siemens ARTISTE were measured by means of the Bonner spheres spectrometer whose active detector of thermal neutrons was replaced by an activation detector, i.e. a tablet made of pure manganese. Measurements with different collimator settings reveal an interesting dependence of neutron fluence on the area defined by the collimator jaws. The determined neutron spectral fluences were used to derive ambient dose equivalent rate along the treatment coach. To clarify at which components of the linac neutrons are mainly created, the measurements were complemented with MCNPX calculations based on a realistic model of the Varian Clinac.

  7. Proton dose calculation based on in-air fluence measurements.

    PubMed

    Schaffner, Barbara

    2008-03-21

    Proton dose calculation algorithms--as well as photon and electron algorithms--are usually based on configuration measurements taken in a water phantom. The exceptions to this are proton dose calculation algorithms for modulated scanning beams. There, it is usual to measure the spot profiles in air. We use the concept of in-air configuration measurements also for scattering and uniform scanning (wobbling) proton delivery techniques. The dose calculation includes a separate step for the calculation of the in-air fluence distribution per energy layer. The in-air fluence calculation is specific to the technique and-to a lesser extent-design of the treatment machine. The actual dose calculation uses the in-air fluence as input and is generic for all proton machine designs and techniques. PMID:18367787

  8. Fluence dependence of deuterium retention in oxidized SS-316

    NASA Astrophysics Data System (ADS)

    Oya, Yasuhisa; Suzuki, Sachiko; Matsuyama, Masao; Hayashi, Takumi; Yamanishi, Toshihiko; Asakura, Yamato; Okuno, Kenji

    2011-10-01

    The ion fluence dependence of deuterium retention in SS-316 during oxidation at a temperature of 673 K was studied to evaluate the dynamics of deuterium retention in the oxide layer of SS-316. The correlation between the chemical state of stainless steel and deuterium retention was evaluated using XPS and TDS. It was found that the major deuterium desorption temperatures were located at around 660 K and 935 K, which correspond to the desorption of deuterium trapped as hydroxide. The deuterium retention increased with increasing deuterium ion fluence, since the deuterium retention as hydroxide increased significantly. However, retention saturated at an ion fluence of ˜2.5 × 10 21 D + m -2. The XPS result showed that FeOOD was formed on the surface, although pure Fe also remained in the oxide layer. These facts indicate the nature of the oxide layer have a key role in deuterium trapping behavior.

  9. Fluence field optimization for noise and dose objectives in CT

    SciTech Connect

    Bartolac, Steven; Graham, Sean; Siewerdsen, Jeff; Jaffray, David

    2011-05-15

    Purpose: Selecting the appropriate imaging technique in computed tomography (CT) inherently involves balancing the tradeoff between image quality and imaging dose. Modulation of the x-ray fluence field, laterally across the beam, and independently for each projection, may potentially meet user-prescribed, regional image quality objectives, while reducing radiation to the patient. The proposed approach, called fluence field modulated CT (FFMCT), parallels the approach commonly used in intensity-modulated radiation therapy (IMRT), except ''image quality plans'' replace the ''dose plans'' of IMRT. This work studies the potential noise and dose benefits of FFMCT via objective driven optimization of fluence fields. Methods: Experiments were carried out in simulation. Image quality plans were defined by specifying signal-to-noise ratio (SNR) criteria for regions of interest (ROIs) in simulated cylindrical and oblong water phantoms, and an anthropomorphic phantom with bone, air, and water equivalent regions. X-ray fluence field patterns were generated using a simulated annealing optimization method that attempts to achieve the spatially-dependent prescribed SNR criteria in the phantoms while limiting dose (to the volume or subvolumes). The resulting SNR and dose distributions were analyzed and compared to results using a bowtie filtered fluence field. Results: Compared to using a fixed bowtie filtered fluence, FFMCT achieved superior agreement with the target image quality objectives, and resulted in integral dose reductions ranging from 39 to 52%. Prioritizing dose constraints for specific regions of interest resulted in a preferential reduction of dose to those regions with some tradeoff in SNR, particularly where the target low dose regions overlapped with regions where high SNR was prescribed. The method appeared fairly robust under increased complexity and heterogeneity of the object structure. Conclusions: These results support that FFMCT has the potential to meet

  10. Nickel Foil as Transmutation Detector for Neutron Fluence Measurements

    NASA Astrophysics Data System (ADS)

    Klupák, Vít; Viererbl, Ladislav; Lahodová, Zdena; Šoltés, Jaroslav; Tomandl, Ivo; Kudějová, Petra

    2016-02-01

    Activation detectors are very often used for determination of the neutron fluence in reactor dosimetry. However, there are few disadvantages concerning these detectors; it is the demand of the knowledge of the irradiation history and a loss of information due to a radioactive decay in time. Transmutation detectors TMD could be a solution in this case. The transmutation detectors are materials in which stable or long-lived nuclides are produced by nuclear reactions with neutrons. From a measurement of concentration of these nuclides, neutron fluence can be evaluated regardless of the cooling time.

  11. THE XMM CLUSTER SURVEY: THE BUILD-UP OF STELLAR MASS IN BRIGHTEST CLUSTER GALAXIES AT HIGH REDSHIFT

    SciTech Connect

    Stott, J. P.; Collins, C. A.; Hilton, M.; Capozzi, D.; Sahlen, M.; Lloyd-Davies, E.; Hosmer, M.; Liddle, A. R.; Mehrtens, N.; Romer, A. K.; Miller, C. J.; Stanford, S. A.; Viana, P. T. P.; Davidson, M.; Hoyle, B.; Kay, S. T.; Nichol, R. C.

    2010-07-20

    We present deep J- and K{sub s} -band photometry of 20 high redshift galaxy clusters between z = 0.8 and1.5, 19 of which are observed with the MOIRCS instrument on the Subaru telescope. By using near-infrared light as a proxy for stellar mass we find the surprising result that the average stellar mass of Brightest Cluster Galaxies (BCGs) has remained constant at {approx}9 x 10{sup 11} M {sub sun} since z {approx} 1.5. We investigate the effect on this result of differing star formation histories generated by three well-known and independent stellar population codes and find it to be robust for reasonable, physically motivated choices of age and metallicity. By performing Monte Carlo simulations we find that the result is unaffected by any correlation between BCG mass and cluster mass in either the observed or model clusters. The large stellar masses imply that the assemblage of these galaxies took place at the same time as the initial burst of star formation. This result leads us to conclude that dry merging has had little effect on the average stellar mass of BCGs over the last 9-10 Gyr in stark contrast to the predictions of semi-analytic models, based on the hierarchical merging of dark matter halos, which predict a more protracted mass build-up over a Hubble time. However, we discuss that there is potential for reconciliation between observation and theory if there is a significant growth of material in the intracluster light over the same period.

  12. Artifacts in time-resolved NUS: A case study of NOE build-up curves from 2D NOESY.

    PubMed

    Dass, Rupashree; Kasprzak, Paweł; Koźmiński, Wiktor; Kazimierczuk, Krzysztof

    2016-04-01

    Multidimensional NMR spectroscopy requires time-consuming sampling of indirect dimensions and so is usually used to study stable samples. However, dynamically changing compounds or their mixtures commonly occur in problems of natural science. Monitoring them requires the use multidimensional NMR in a time-resolved manner - in other words, a series of quick spectra must be acquired at different points in time. Among the many solutions that have been proposed to achieve this goal, time-resolved non-uniform sampling (TR-NUS) is one of the simplest. In a TR-NUS experiment, the signal is sampled using a shuffled random schedule and then divided into overlapping subsets. These subsets are then processed using one of the NUS reconstruction methods, for example compressed sensing (CS). The resulting stack of spectra forms a temporal "pseudo-dimension" that shows the changes caused by the process occurring in the sample. CS enables the use of small subsets of data, which minimizes the averaging of the effects studied. Yet, even within these limited timeframes, the sample undergoes certain changes. In this paper we discuss the effect of varying signal amplitude in a TR-NUS experiment. Our theoretical calculations show that the variations within the subsets lead to t1-noise, which is dependent on the rate of change of the signal amplitude. We verify these predictions experimentally. As a model case we choose a novel 2D TR-NOESY experiment in which mixing time is varied in parallel with shuffled NUS in the indirect dimension. The experiment, performed on a sample of strychnine, provides a near-continuous NOE build-up curve, whose shape closely reflects the t1-noise level. 2D TR-NOESY reduces the measurement time compared to the conventional approach and makes it possible to verify the theoretical predictions about signal variations during TR-NUS. PMID:26896866

  13. A STUDY OF THE BUILD-UP, INITIATION, AND ACCELERATION OF 2008 APRIL 26 CORONAL MASS EJECTION OBSERVED BY STEREO

    SciTech Connect

    Cheng, X.; Ding, M. D.; Zhang, J.

    2010-04-01

    In this paper, we analyze the full evolution, from a few days prior to the eruption to the initiation, final acceleration, and propagation, of the coronal mass ejection (CME) that occurred on 2008 April 26 using the unprecedented high cadence and multi-wavelength observations by the Solar Terrestrial Relations Observatory. There existed frequent filament activities and EUV jets prior to the CME eruption for a few days. These activities were probably caused by the magnetic reconnection in the lower atmosphere driven by photospheric convergence motions, which were evident in the sequence of magnetogram images from the Michelson Doppler Imager on board the Solar and Heliospheric Observatory. The slow low-layer magnetic reconnection may be responsible for the storage of magnetic free energy in the corona and the formation of a sigmoidal core field or a flux rope leading to the eventual eruption. The occurrence of EUV brightenings in the sigmoidal core field prior to the rise of the flux rope implies that the eruption was triggered by the inner tether-cutting reconnection, but not the external breakout reconnection. During the period of impulsive acceleration, the time profile of the CME acceleration in the inner corona is found to be consistent with the time profile of the reconnection electric field inferred from the footpoint separation and the Reuven Ramaty High Energy Solar Spectroscopic Imager 15-25 keV hard X-ray flux curve of the associated flare. The full evolution of this CME can be described in four distinct phases: the build-up phase, initiation phase, main acceleration phase, and propagation phase. The physical properties and the transition between these phases are discussed, in an attempt to provide a global picture of CME dynamic evolution.

  14. Artifacts in time-resolved NUS: A case study of NOE build-up curves from 2D NOESY

    NASA Astrophysics Data System (ADS)

    Dass, Rupashree; Kasprzak, Paweł; Koźmiński, Wiktor; Kazimierczuk, Krzysztof

    2016-04-01

    Multidimensional NMR spectroscopy requires time-consuming sampling of indirect dimensions and so is usually used to study stable samples. However, dynamically changing compounds or their mixtures commonly occur in problems of natural science. Monitoring them requires the use multidimensional NMR in a time-resolved manner - in other words, a series of quick spectra must be acquired at different points in time. Among the many solutions that have been proposed to achieve this goal, time-resolved non-uniform sampling (TR-NUS) is one of the simplest. In a TR-NUS experiment, the signal is sampled using a shuffled random schedule and then divided into overlapping subsets. These subsets are then processed using one of the NUS reconstruction methods, for example compressed sensing (CS). The resulting stack of spectra forms a temporal "pseudo-dimension" that shows the changes caused by the process occurring in the sample. CS enables the use of small subsets of data, which minimizes the averaging of the effects studied. Yet, even within these limited timeframes, the sample undergoes certain changes. In this paper we discuss the effect of varying signal amplitude in a TR-NUS experiment. Our theoretical calculations show that the variations within the subsets lead to t1 -noise, which is dependent on the rate of change of the signal amplitude. We verify these predictions experimentally. As a model case we choose a novel 2D TR-NOESY experiment in which mixing time is varied in parallel with shuffled NUS in the indirect dimension. The experiment, performed on a sample of strychnine, provides a near-continuous NOE build-up curve, whose shape closely reflects the t1 -noise level. 2D TR-NOESY reduces the measurement time compared to the conventional approach and makes it possible to verify the theoretical predictions about signal variations during TR-NUS.

  15. [(11) C]Carbon monoxide in labeling chemistry and positron emission tomography tracer development: scope and limitations.

    PubMed

    Rahman, Obaidur

    2015-03-01

    [(11) C]Carbon monoxide is an attractive precursor for labeling carbonyl position in a wide range of organic compounds. The use of [(11) C]carbon monoxide in transition metal-mediated coupling reactions has been explored by several groups during the last 15 years, and an impressive number of the synthesis of [carbonyl-(11) C]compounds have been published to date. The application of radical-mediated [(11) C]carbonylation has also been explored in some extent. However, the main limitations to apply this potential precursor in (11) C-labeling chemistry are low concentration, poor solubility in commonly used organic solvents, and low reactivity. A couple of technical solutions such as high-pressure reactor system, microfluidic system, and different approaches to confine [(11) C]CO to the reaction media at ambient pressure have been developed over the years. Although considerable advances in [(11) C]carbon monoxide chemistry have been reported in recent years, its application in positron emission tomography tracer development is still an area of work in progress. This review summarizes all contributions to the area of radiolabeling using [(11) C]carbon monoxide published between 1995 and 2014 and discusses the scope and limitations of this method in clinical positron emission tomography tracer development.

  16. Amino acids labelled with 11C as indicator of the effect of dietary treatment of hyperammonaemia.

    PubMed

    Hardell, L I; Stålnacke, C G; Lundqvist, H; Malmborg, P; Långström, B

    1984-01-01

    Short-lived radioactive carbon, 11C, (T 1/2 = 20 min) was incorporated into an essential amino acid [11C-methyl] -L-methionine, to form a true biological amino acid tracer with external detectability. This was tested in a study of the physiological tracer dynamics in a hyperammonaemic patient before and after a change in the dietary treatment. The protein intake was unchanged between the two investigations but the energy intake was increased from 53 to 63 kcal/kg BW/day. The tracer radioactivity was given per os. In the second investigation a relative decrease of radioactivity in the low molecular weight fraction of blood plasma was seen. Also the external measurements indicated a higher hepatic retention of radioactivity in the second investigation but no increased excretion of tracer. This may reflect an increased ability of the liver to utilize the incoming methionine from the vena porta. The hyperammonaemia remained over the second investigation but seven months later the ammonia content in the blood was almost normalized and the patient had also gained 3 kg in weight. The correlation between changes in tracer dynamics and changes in therapeutical effect of the diet is not further verified in this experiment but the investigation indicates the value of further studies in this topic using 11C-labelled amino acids also including the use of the newly introduced positron tomographic technique. It may be possible to develop this type of nuclide technique further to achieve a clinically useful method of optimizing therapeutic regiments in this type of metabolic disease. PMID:6393522

  17. Elevated serotonin transporter binding in depressed patients with Parkinson's disease: a preliminary PET study with [11C]DASB.

    PubMed

    Boileau, Isabelle; Warsh, Jerry J; Guttman, Mark; Saint-Cyr, Jean A; McCluskey, Tina; Rusjan, Pablo; Houle, Sylvain; Wilson, Alan A; Meyer, Jeffrey H; Kish, Stephen J

    2008-09-15

    This study investigated whether abnormalities in serotonin transporter binding occur in Parkinson's disease (PD) patients with concurrent depression. We estimated serotonin transporter levels in seven clinically depressed early-stage PD patients and in seven healthy matched-control subjects during a single positron emission tomography (PET) scan with the serotonin transporter radioligand, [(11)C]DASB. Depressed PD patients displayed a wide-spread increase (8-68%) in [(11)C]DASB specific binding outside of the striatum, which was significant in dorsolateral (37%) and prefrontal (68%) cortices. Elevated [(11)C]DASB binding was positively correlated with depressive symptoms but not with disease severity or duration. Compatible with recent PET/[(11)C]DASB findings in major depression, the present preliminary data suggest that increased [(11)C]DASB binding, possibly reflecting greater serotonin transporter density (up-regulation), might be a pathological feature of depression in Parkinson's disease-and possibly a characteristic of depressive illness in general.

  18. Nuclear reactions with 11C and 14O radioactive ion beams

    SciTech Connect

    Guo, Fanqing

    2004-12-09

    Radioactive ion beams (RIBs) have been shown to be a useful tool for studying proton-rich nuclides near and beyond the proton dripline and for evaluating nuclear models. To take full advantage of RIBs, Elastic Resonance Scattering in Inverse Kinematics with Thick Targets (ERSIKTT), has proven to be a reliable experimental tool for investigations of proton unbound nuclei. Following several years of effort, Berkeley Experiments with Accelerated Radioactive Species (BEARS), a RIBs capability, has been developed at the Lawrence Berkeley National Laboratory's 88-Inch Cyclotron. The current BEARS provides two RIBs: a 11C beam of up to 2x108 pps intensity on target and an 14O beam of up to 3x104 pps intensity. While the development of the 11C beam has been relatively easy, a number of challenges had to be overcome to obtain the 14O beam. The excellent 11C beam has been used to investigate several reactions. The first was the 197Au(11C,xn)208-xnAt reaction, which was used to measure excitation functions for the 4n to 8n exit channels. The measured cross sections were generally predicted quite well using the fusion-evaporation code HIVAP. Possible errors in the branching ratios of ?? decays from At isotopes as well as the presence of incomplete fusion reactions probably contribute to specific overpredictions. 15F has been investigated by the p(14O,p)14O reaction with the ERSIKTT technology. Several 14O+p runs have been performed. Excellent energy calibration was obtained using resonances from the p(14N,p)14N reaction in inverse kinematics, and comparing the results to those obtained earlier with normal kinematics. The differences between 14N+p and 14O+p in the stopping power function have been evaluated for better energy calibration. After careful calibration, the energy levels of 15F were fitted with an R-matrix calculation. Spins and parities were assigned to the two observed resonances. This new measurement of the 15F ground state supports the disappearance of the Z = 8

  19. Muon fluence measurements at the site boundary for 1985

    SciTech Connect

    Elwyn, A.J.

    1986-03-01

    Muon fluence (muons cm/sup -2/) was measured downstream of the experimental area beamlines, just beyond the Fermilab site boundary at Route 38. The purpose of these measurements was to obtain an estimate of the yearly off-site radiation exposure to the general population due to accelerator-produced muons during the 1985 800 GeV run.

  20. A simplified analytical method to estimate the bismuth build-up and the polonium activity in LiPb-bearing blankets of a fusion reactor

    SciTech Connect

    Zimin, S.

    1994-09-01

    Although neutron-induced activation in a fusion reactor is a nonlinear problem whose solution requires the use of both neutron transport and activation codes, a simplified analytical approach to bismuth and polonium build-up in lead is proposed to estimate the polonium inventory and the related biological hazards of LiPb-bearing blankets. All neutronic reactions of polonium build-up in lead and in its bismuth impurities are surveyed and discussed. The contribution of the different possible chains to the build-up of polonium is evaluated. A set of differential equations for the densities of {sup 209}Bi and {sup 210}Po isotopes in the lead is worked into simplified, easy-to-use expressions. These analytical formulas obtained for the densities can be used for the estimation of both the bismuth and the polonium densities after any reactor operation time and allow identification of the build-up mechanisms of those isotopes. A simplified formula for polonium inventory estimations at any blanket zone is proposed as well. The polonium inventory evaluation takes into account the initial conditions (primarily bismuth impurity in the lead) and the reactor operation conditions, such as the average availability of a fusion reactor and the blanket operation scenario. 44 refs., 11 figs., 5 tabs.

  1. Effects of salinity build-up on biomass characteristics and trace organic chemical removal: implications on the development of high retention membrane bioreactors.

    PubMed

    Luo, Wenhai; Hai, Faisal I; Kang, Jinguo; Price, William E; Guo, Wenshan; Ngo, Hao H; Yamamoto, Kazuo; Nghiem, Long D

    2015-02-01

    This study investigated the impact of salinity build-up on the performance of membrane bioreactor (MBR), specifically in terms of the removal and fate of trace organic chemicals (TrOCs), nutrient removal, and biomass characteristics. Stepwise increase of the influent salinity, simulating salinity build-up in high retention MBRs, adversely affected the metabolic activity in the bioreactor, thereby reducing organic and nutrient removal. The removal of hydrophilic TrOCs by MBR decreased due to salinity build-up. By contrast, with the exception of 17α-ethynylestradiol, the removal of all hydrophobic TrOCs was not affected at high salinity. Moreover, salinity build-up had negligible impact on the residual accumulation of TrOCs in the sludge phase except for a few hydrophilic compounds. Additionally, the response of the biomass to salinity stress also dramatically enhanced the release of both soluble microbial products (SMP) and extracellular polymeric substances (EPS), leading to severe membrane fouling. PMID:25496948

  2. Low-fluence carbon dioxide laser irradiation of lentigines

    SciTech Connect

    Dover, J.S.; Smoller, B.R.; Stern, R.S.; Rosen, S.; Arndt, K.A.

    1988-08-01

    Low-fluence carbon dioxide (CO2) laser irradiation of skin has previously been shown to induce damage limited primarily to the epidermis. To evaluate whether this technique was therapeutically effective for pigmented epidermal lesions, ten lentigines caused by methoxsalen and ultraviolet light therapy were treated in one patient using the CO2 laser at fluences ranging from 3.0 to 7.7 J/cm2 for 0.1-s exposures with 4.5-mm spot size. Based on substantial clearing in seven of ten lesions treated, 146 solar lentigines were treated in five patients at fluences of 3.0, 3.7, or 4.4 J/cm2. Biopsies were performed on a total of 30 lesions immediately and 24 hours, seven days, and six weeks after irradiation. Of 125 lesions followed up clinically for six weeks, 12 cleared completely, 81 lightened substantially, and 28 remained unchanged. Only two demonstrated atrophic change. Hyperpigmentation or hypopigmentation did not occur. All lesions that improved had been treated at 3.7 or 4.4 J/cm2. Immediate histologic injury consisted of vacuolar and spindly change and subsequent vesiculation limited to the basilar epidermis. Twenty-four hours later there was epidermal necrosis with regeneration, 0.1 mm of dermal basophilia and stromal condensation, and a mild inflammatory infiltrate. These alterations were dose-dependent, with near complete epidermal necrosis and superficial dermal involvement at the highest fluence, and only focal epidermal necrosis at the lowest. At seven days, epidermal regeneration was complete with traces of melanin remaining in keratinocytes. Melanophages first appeared at seven days and persisted at six weeks, by which time the inflammatory infiltrate had cleared. No lentiginous proliferation was evident and epidermal pigmentation had become normal. Low-fluence CO2 laser irradiation is an effective means of damaging the epidermis with only minimal dermal change.

  3. Synthesis of (11)C-Labeled Thiamine and Fursultiamine for in Vivo Molecular Imaging of Vitamin B1 and Its Prodrug Using Positron Emission Tomography.

    PubMed

    Doi, Hisashi; Mawatari, Aya; Kanazawa, Masakatsu; Nozaki, Satoshi; Nomura, Yukihiro; Kitayoshi, Takahito; Akimoto, Kouji; Suzuki, Masaaki; Ninomiya, Shinji; Watanabe, Yasuyoshi

    2015-06-19

    To enable in vivo analysis of the kinetics of vitamin B1 (thiamine) and its derivatives by positron emission tomography (PET), (11)C-labeled thiamine ([(11)C]-1) has been synthesized. This was carried out via a rapid, multistep synthesis consisting of Pd(0)-mediated C-[(11)C]methylation of a thiazole ring for 3 min and benzylation with 5-(bromomethyl)pyrimidine for 7 min. The [(11)C]-1 was also converted to (11)C-labeled fursultiamine ([(11)C]-2), a prodrug of vitamin B1, by disulfide formation with S-tetrahydrofurfurylthiosulfuric acid sodium salt. Characterization of [(11)C]-1 and [(11)C]-2 showed them to be suitable for use as PET probes for in vivo pharmacokinetic and medical studies. The total durations of the preparations of [(11)C]-1 and [(11)C]-2 were shorter than 60 and 70 min, respectively. The [(11)C]CH3I-based decay-corrected radiochemical yields of [(11)C]-1 and [(11)C]-2 were 9-16% and 4-10%, respectively. The radioactivities of the final injectable solutions of [(11)C]-1 and [(11)C]-2 were 400-700 and 100-250 MBq, respectively. The radiochemical purity of both [(11)C]-1 and [(11)C]-2 was 99%, and the chemical purities of [(11)C]-1 and [(11)C]-2 were 99% and 97-99%, respectively. In vivo PET imaging of normal rats was illustrated by the distribution of [(11)C]-1 and [(11)C]-2 following intravenous injection. PMID:25984933

  4. Effect of amphetamine on dopamine D2 receptor binding in nonhuman primate brain: a comparison of the agonist radioligand [11C]MNPA and antagonist [11C]raclopride.

    PubMed

    Seneca, Nicholas; Finnema, Sjoerd J; Farde, Lars; Gulyás, Balázs; Wikström, Håkan V; Halldin, Christer; Innis, Robert B

    2006-04-01

    PET measurements of stimulant-induced dopamine (DA) release are typically performed with antagonist radioligands that bind to both the high- and low-affinity state of the receptor. In contrast, an agonist radioligand binds preferentially to the high-affinity state and is expected to have greater sensitivity to DA, which is the endogenous agonist. [(11)C]MNPA, (R)-2-CH(3)O-N-n-propylnorapomorphine (MNPA), is a D(2) agonist radioligand with subnanomolar affinity to the D(2) receptor. The aim of the present study is to assess and compare the sensitivity of the agonist radioligand [(11)C]MNPA and antagonist radioligand [(11)C]raclopride to synaptic DA levels. Four cynomolgus monkeys were examined with [(11)C]MNPA and [(11)C]raclopride (16 PET measurements with each tracer) at baseline and after pretreatment with various doses of amphetamine. The effect of amphetamine was calculated by the change in binding potential (BP) analyzed with the multilinear reference tissue model (MRTM2). Amphetamine caused a reduction in [(11)C]MNPA BP of 4% at 0.1, 23% at 0.2, 25% at 0.5, and 46% at 1.0 mg/kg. [(11)C]Raclopride BP was reduced to a lesser extent by 2% at 0.1, 16% at 0.2, 15% at 0.5, and 23% at 1.0 mg/kg. The data were used to estimate the in vivo percentage of high-affinity state receptors to be approximately 60%. These results demonstrate that [(11)C]MNPA is more sensitive than [(11)C]raclopride to displacement by endogenous DA, and that it may provide additional information about the functional state of the D(2) receptor in illnesses such as schizophrenia and Parkinson's disease.

  5. Practical Radiosynthesis and Preclinical Neuroimaging of [11C]isradipine, A Calcium Channel Antagonist

    PubMed Central

    Rotstein, Benjamin H.; Liang, Steven H.; Belov, Vasily V.; Livni, Eli; Levine, Dylan B.; Bonab, Ali A.; Papisov, Mikhail I.; Perlis, Roy H.; Vasdev, Neil

    2016-01-01

    In the interest of developing in vivo positron emission tomography (PET) probes for neuroimaging of calcium channels, we have prepared a carbon-11 isotopologue of a dihydropyridine Ca2+-channel antagonist, isradipine. Desmethyl isradipine (4-(benzo[c][1,2,5]oxadiazol-4-yl)-5-(isopropoxycarbonyl)-2,6-dimethyl-1,4-dihydropyridine -3-carboxylic acid) was reacted with [11C]CH3I in the presence of tetrabutylammonium hydroxide in DMF in an HPLC injector loop to produce the radiotracer in a good yield (6 ± 3% uncorrected radiochemical yield) and high specific activity (143 ± 90 GBq·μmol−1 at end-of-synthesis). PET imaging of normal rats revealed rapid brain uptake at baseline (0.37 ± 0.08 %ID/cc (percent of injected dose per cubic centimeter) at peak, 15–60 s), which was followed by fast washout. After pretreatment with isradipine (2 mg·kg−1, i.p.), whole brain radioactivity uptake was diminished by 25–40%. This preliminary study confirms that [11C]isradipine can be synthesized routinely for research studies and is brain penetrating. Further work on Ca2+-channel radiotracer development is planned. PMID:26016546

  6. L-(1-/sup 11/C)leucine: routine synthesis by enzymatic resolution

    SciTech Connect

    Barrio, J.R.; Keen, R.E.; Ropchan, J.R.; MacDonald, N.S.; Baumgartner, F.J.; Padgett, H.C.; Phelps, M.E.

    1983-06-01

    L-(1-/sup 11/C)leucine, suitable for the determination of cerebal protein synthesis rates in man using positron emission tomography, has been synthesized using a modified Bucherer-Strecker reaction sequence. The isolation of the pure L-amino acid isomer from the enantiomeric mixture, initially obtained using either an open or closed reaction vessel, was achieved using a D-amino acid oxidase/catalase enzyme complex immobilized on a Sepharose support. The O/sub 2/ required by the D-amino acid oxidase as the hydrogen acceptor was supplied by catalase. The L-(1-/sup 11/C)leucine was obtained with a radiochemical purity of >99% and with a radiochemical yield of 25%. Using a remote, semiautomated synthesis system, typical production time was 30 to 40 min after preparation of H/sup 11/CN. The use of immobilized enzymes for rapid and effective resolution of amino acid enantiomers eliminates the possibility of protein contamination and assures the production of a sterile, pyrogen-free product.

  7. Measurement of the cosmogenic 11C background with the Borexino Counting Test Facility

    SciTech Connect

    Franco, D.

    2007-03-28

    Within next year, two organic liquid scintillator detectors, Borexino and KamLAND, will start the measurement of the mono-energetic 7Be solar neutrino flux in real time. Besides this objective, both of them have the potential to detect neutrinos from the pep fusion reaction and the CNO cycle in the Sun.For this purpose, two conditions are required: an extremely low radioactive contamination level and the efficient identification of the 11C background, produced in reactions induced by the residual cosmic muon flux on 12C. In the process, a free neutron is almost always produced. 11C can be tagged on an event by event basis by looking at the three-fold coincidence with the parent muon track and the subsequent neutron capture on protons. We tested successfully this coincidence method with the Borexino Counting Test Facility. The results are reported here.Moreover, we discuss on the effective potential of Borexino and KamLAND in detecting pep+CNO neutrinos compared to SNO+, a detector specifically designed for measuring the pep+CNO {nu} flux and that will take data from 2009.

  8. Cryogenic molecular separation system for radioactive {sup 11}C ion acceleration

    SciTech Connect

    Katagiri, K.; Noda, A.; Suzuki, K.; Nagatsu, K.; Nakao, M.; Hojo, S.; Wakui, T.; Noda, K.; Boytsov, A. Yu.; Donets, D. E.; Donets, E. D.; Donets, E. E.; Ramzdorf, A. Yu.

    2015-12-15

    A {sup 11}C molecular production/separation system (CMPS) has been developed as part of an isotope separation on line system for simultaneous positron emission tomography imaging and heavy-ion cancer therapy using radioactive {sup 11}C ion beams. In the ISOL system, {sup 11}CH{sub 4} molecules will be produced by proton irradiation and separated from residual air impurities and impurities produced during the irradiation. The CMPS includes two cryogenic traps to separate specific molecules selectively from impurities by using vapor pressure differences among the molecular species. To investigate the fundamental performance of the CMPS, we performed separation experiments with non-radioactive {sup 12}CH{sub 4} gases, which can simulate the chemical characteristics of {sup 11}CH{sub 4} gases. We investigated the separation of CH{sub 4} molecules from impurities, which will be present as residual gases and are expected to be difficult to separate because the vapor pressure of air molecules is close to that of CH{sub 4}. We determined the collection/separation efficiencies of the CMPS for various amounts of air impurities and found desirable operating conditions for the CMPS to be used as a molecular separation device in our ISOL system.

  9. [11C]Flumazenil brain uptake is influenced by the blood-brain barrier efflux transporter P-glycoprotein

    PubMed Central

    2012-01-01

    Background [11C]Flumazenil and positron emission tomography (PET) are used clinically to assess gamma-aminobutyric acid (GABA)-ergic function and to localize epileptic foci prior to resective surgery. Enhanced P-glycoprotein (P-gp) activity has been reported in epilepsy and this may confound interpretation of clinical scans if [11C]flumazenil is a P-gp substrate. The purpose of this study was to investigate whether [11C]flumazenil is a P-gp substrate. Methods [11C]Flumazenil PET scans were performed in wild type (WT) (n = 9) and Mdr1a/1b, (the genes that encode for P-gp) double knockout (dKO) (n = 10) mice, and in naive rats (n = 10). In parallel to PET scanning, [11C]flumazenil plasma concentrations were measured in rats. For 6 of the WT and 6 of the dKO mice a second, [11C]flumazenil scan was acquired after administration of the P-gp inhibitor tariquidar. Cerebral [11C]flumazenil concentrations in WT and Mdr1a/1b dKO mice were compared (genetic disruption model). Furthermore, pre and post P-gp-blocking cerebral [11C]flumazenil concentrations were compared in all animals (pharmacological inhibition model). Results Mdr1a/1b dKO mice had approximately 70% higher [11C]flumazenil uptake in the brain than WT mice. After administration of tariquidar, cerebral [11C]flumazenil uptake in WT mice increased by about 80% in WT mice, while it remained the same in Mdr1a/1b dKO mice. In rats, cerebral [11C]flumazenil uptake increased by about 60% after tariquidar administration. Tariquidar had only a small effect on plasma clearance of flumazenil. Conclusions The present study showed that [11C]flumazenil is a P-gp substrate in rodents. Consequently, altered cerebral [11C]flumazenil uptake, as observed in epilepsy, may not reflect solely GABAA receptor density changes but also changes in P-gp activity. PMID:22455873

  10. Kinetic Analysis of [11C]McN5652: A Serotonin Transporter Radioligand

    PubMed Central

    Szabo, Zsolt; Scheffel, Ursula; Mathews, William B.; Ravert, Hayden T.; Szabo, Katalina; Kraut, Michael; Palmon, Sally; Ricaurte, George A.; Dannals, Robert F.

    2007-01-01

    Summary The impulse response function of a radioligand is the most fundamental way to describe its pharmacokinetics and to assess its tissue uptake and retention pattern. This study investigates the impulse response function of [11C](+)McN5652, a radioligand used for positron emission tomography (PET) imaging of the serotonin transporter (SERT) in the brain. Dynamic PET studies were performed in eight healthy volunteers injected with [11C](+)McN5652 and subsequently with its pharmacologically inactive enantiomer [11C](−)McN5652. The impulse response function was calculated by deconvolution analysis of regional time-activity curves, and its peak value (fmax), its retention value at 75 minutes (fT), and its normalized retention (frel = fr/fmax) were obtained. Alternatively, compartmental models were applied to calculate the apparent total distribution volume (DVT) and its specific binding component (DVS). Both the noncompartmental (fT, frel) and the compartmental parameters (DV) were investigated with and without correction for nonspecific binding by simple subtraction of the corresponding value obtained with [11C](−)McN5652. The impulse response function obtained by deconvolution analysis demonstrated high tracer extraction followed by a slow decline in the form of a monoexponential function. Statistical analysis revealed that the best compartmental model in terms of analysis of variance F and condition number of the parameter variance-covariance matrix was the one that was based on a single tissue compartment with parameters k1and k2 and that also included the parameter of regional cerebral blood volume (BV). The parameter frel demonstrated low between-subject variance (coefficient of variation [CV] = 19%), a midbrain to cerebellum ratio of 1.85, and high correlation with the known density of SERT (r = 0.787 where r is the coefficient of linear correlation between the parameter and the known density of SERT). After correction for nonspecific binding, frel

  11. A comprehensive interpretation of the NEEM basal ice build-up using a multi-parametric approach

    NASA Astrophysics Data System (ADS)

    Goossens, Thomas; Sapart, Célia J.; Dahl-Jensen, Dorthe; Popp, Trevor; El Amri, Saïda; Tison, Jean-Louis

    2016-03-01

    stratified debris-rich layers and the ice containing dispersed debris layers respectively express an "open" or "closed" system melting/refreezing signature, somewhat blurred by mixing processes in the upper part of the sequence. Climatic reconstruction is therefore prohibited from these ice types. We propose a first interpretative framework for the build-up of the NEEM basal ice sequence, based on the origin of the various ice types.

  12. Precipitation dominates fire occurrence in Greece (1900-2010): its dual role in fuel build-up and dryness

    NASA Astrophysics Data System (ADS)

    Xystrakis, F.; Kallimanis, A. S.; Dimopoulos, P.; Halley, J. M.; Koutsias, N.

    2014-01-01

    Historical fire records and meteorological observations spanning over one century (1894-2010) were assembled in a database to collect long-term fire and weather data in Greece. Positive/negative events of fire occurrence on an annual basis were considered as the years where the annual values of the examined parameters were above (positive values) or below (negative values) the 95% confidence limits around the trend line of the corresponding parameter. To analyse the association of positive/negative events of fire occurrence with meteorological extremes, we proceeded with a cross-tabulation analysis based on a Monte Carlo randomization. Positive/negative values of total annual precipitation were randomly associated with the corresponding values of burned areas, and significant associations were observed for seasonal precipitation totals (spring and fire season). Fire season precipitation is the dominant factor coinciding with negative values of area burned, while years with high spring precipitation coincide with years with large areas burned. These results demonstrate the dual role of precipitation in controlling a fire's extent through fuel build-up and dryness. Additionally, there is a clear outperformance of precipitation-related variables compared with temperature-related weather revealing that, at least in Greece, total area burned at the national scale is controlled by precipitation totals rather than air temperature. This analysis improves our understanding of the underlying mechanisms of fire regimes and provides valuable information concerning the development of models relating fire activity to weather parameters, which are essential when facing a changing climate that may be associated with shifts in various aspects of the typical fire regimes of ecosystems. Our results may allow fire managers to more easily incorporate the effect of extreme weather conditions into long-term planning strategies. They contribute to the exploration of fire

  13. Rethinking the Concepts of Fluence (UV Dose) and Fluence Rate: The Importance of Photon-based Units - A Systemic Review.

    PubMed

    Bolton, James R; Mayor-Smith, Ian; Linden, Karl G

    2015-11-01

    After a critical review of the fundamental equations describing photobiological and photochemical processes occurring in a medium exposed to a quasi-collimated monochromatic UV light beam, the analysis in this review is extended to analogous processes driven by polychromatic UV light, such as that emitted by medium pressure mercury-vapor arc lamps. The analysis is based on the Second Law of Photochemistry, namely that all photochemical events must be independent, and the rate of such events must be proportional to the rate of photon absorption. A consistent application of the Second Law of Photochemistry leads to a concept change; hence it is proposed herein to use photon fluence and photon fluence rate, rather than fluence (UV dose) and fluence rate, respectively, in the analysis and interpretation of photobiological and photochemical processes. As a consequence, many equations that have been used in the past must be revised, and some experimental information (e.g. action spectra) needs to be re-analyzed. PMID:26277478

  14. New aspects on the preparation of [11C]acetate--a simple and fast approach via distillation.

    PubMed

    Mitterhauser, Markus; Wadsak, Wolfgang; Krcal, Andreas; Schmaljohann, Joern; Bartosch, Ewald; Eidherr, Harald; Viernstein, Helmut; Kletter, Kurt

    2004-12-01

    [11C]Acetate, initially developed for nuclear cardiology has gained increased interest also for oncological problems. A conjoint problem of all preparation methods is the high sensitivity of the Grignard-precursor to moisture, demanding long cleaning and drying procedures of apparatus and reaction vials. Our rationale was to simplify and accelerate the preparation of [11C]acetate by the development of an inert, sterile and disposable system. The present publication deals with the remote-controlled preparation of [11C]acetate via distillation into a buffer ready to use.

  15. Compensator models for fluence field modulated computed tomography

    SciTech Connect

    Bartolac, Steven; Jaffray, David

    2013-12-15

    Purpose: Fluence field modulated computed tomography (FFMCT) presents a novel approach for acquiring CT images, whereby a patient model guides dynamically changing fluence patterns in an attempt to achieve task-based, user-prescribed, regional variations in image quality, while also controlling dose to the patient. This work aims to compare the relative effectiveness of FFMCT applied to different thoracic imaging tasks (routine diagnostic CT, lung cancer screening, and cardiac CT) when the modulator is subject to limiting constraints, such as might be present in realistic implementations.Methods: An image quality plan was defined for a simulated anthropomorphic chest slice, including regions of high and low image quality, for each of the thoracic imaging tasks. Modulated fluence patterns were generated using a simulated annealing optimization script, which attempts to achieve the image quality plan under a global dosimetric constraint. Optimization was repeated under different types of modulation constraints (e.g., fixed or gantry angle dependent patterns, continuous or comprised of discrete apertures) with the most limiting case being a fixed conventional bowtie filter. For each thoracic imaging task, an image quality map (IQM{sub sd}) representing the regionally varying standard deviation is predicted for each modulation method and compared to the prescribed image quality plan as well as against results from uniform fluence fields. Relative integral dose measures were also compared.Results: Each IQM{sub sd} resulting from FFMCT showed improved agreement with planned objectives compared to those from uniform fluence fields for all cases. Dynamically changing modulation patterns yielded better uniformity, improved image quality, and lower dose compared to fixed filter patterns with optimized tube current. For the latter fixed filter cases, the optimal choice of tube current modulation was found to depend heavily on the task. Average integral dose reduction compared

  16. Production of radiohalogens and [11C]-methane at high specific activity

    NASA Astrophysics Data System (ADS)

    Nye, Jonathon Andrew

    2005-07-01

    The halogens, occupying Group VII of the periodic table, play an important role in the biochemical processes underlying health and disease. A variety of positron emitters covering a broad range of half-lives permit the imaging of the body's physiochemical behavior using PET. Neutron deficient isotopes of the halogen group can be produced by (p,n) reactions from enriched targets with low energy (<13MeV) biomedical cyclotrons. These cyclotrons are distributed relatively evenly throughout the United States at research institutions and commercial distribution sites (i.e., 100+ CTI RDS 11MeV proton cyclotrons). However, these sites concentrate on the core group of positron emitters: 15O, 13N, 11C, and primarily 18F-fluoride. The simplicity of the production process insures their role in the clinical/research environment, labeling H215 O, 13NH3, CH3-compounds and 18F-FDG. Halogens with half-lives longer than 18F have been avoided due to a combination of several factors, such as complexity of the target systems, expense of the enriched substrate, low reaction yields, and extensive post-processing to reclaim the target material. PET research over the last decade has forced a match between drug development and emerging small animal instrumentation, shifting focus to agents labeled with high specific activity 11CH3I and the long-lived radiohalogens, 76Br and 124I. A steady local supply of 18F-fluoride, 11C-methane, 76B-bromide, and 124I-iodide is essential to seize today's research opportunities or for limited distribution outside of our local area. To keep pace, new targetry developments are implemented to reliably produce these isotopes on a batch basis. The research presented details improvements on existing production methods for 18F-fluoride intended for nucleophilic substitution and high specific activity 11C-methane (→CH3I) for the N-methylation of a half-dozen neuroligands. A significant effort is placed on the novel use of low energy cyclotrons for the production

  17. Dopamine receptors in pituitary adenomas: PET visualization with 11C-N-methylspiperone

    SciTech Connect

    Muhr, C.; Bergstroem, M.L.; Lundberg, P.O.; Bergstroem, K.H.; Hartvig, P.; Lundqvist, H.; Antoni, G.; Langstroem B2

    1986-03-01

    Two patients with pituitary tumors were examined with positron emission tomography (PET) after intravenous administration of 11C-N-methylspiperone. In repeat studies the patients were given 1 mg of intravenous haloperidol prior to the administration of the radioligand to block the dopamine receptors. High uptakes of the radiolabeled ligand were seen in one of the tumors. With haloperidol pretreatment the uptake was lower, probably mainly showing the remaining unspecific binding. The most marked uptake and the largest effect of haloperidol pretreatment was seen in a patient with a hormonally active prolactinoma. Dopamine receptor binding in pituitary tumors can be demonstrated in vivo with PET, and quantification of this binding is possible using a compartmental model. This technique may be useful in improving our understanding of the variable response to medical treatment of prolactinomas with dopamine agonists as well as in the prediction of the effect of such treatment.

  18. A singly charged ion source for radioactive 11C ion acceleration

    NASA Astrophysics Data System (ADS)

    Katagiri, K.; Noda, A.; Nagatsu, K.; Nakao, M.; Hojo, S.; Muramatsu, M.; Suzuki, K.; Wakui, T.; Noda, K.

    2016-02-01

    A new singly charged ion source using electron impact ionization has been developed to realize an isotope separation on-line system for simultaneous positron emission tomography imaging and heavy-ion cancer therapy using radioactive 11C ion beams. Low-energy electron beams are used in the electron impact ion source to produce singly charged ions. Ionization efficiency was calculated in order to decide the geometric parameters of the ion source and to determine the required electron emission current for obtaining high ionization efficiency. Based on these considerations, the singly charged ion source was designed and fabricated. In testing, the fabricated ion source was found to have favorable performance as a singly charged ion source.

  19. Alzheimer's disease detection using 11C-PiB with improved partial volume effect correction

    NASA Astrophysics Data System (ADS)

    Raniga, Parnesh; Bourgeat, Pierrick; Fripp, Jurgen; Acosta, Oscar; Ourselin, Sebastien; Rowe, Christopher; Villemagne, Victor L.; Salvado, Olivier

    2009-02-01

    Despite the increasing use of 11C-PiB in research into Alzheimer's disease (AD), there are few standardized analysis procedures that have been reported or published. This is especially true with regards to partial volume effects (PVE) and partial volume correction. Due to the nature of PET physics and acquisition, PET images exhibit relatively low spatial resolution compared to other modalities, resulting in bias of quantitative results. Although previous studies have applied PVE correction techniques on 11C-PiB data, the results have not been quantitatively evaluated and compared against uncorrected data. The aim of this study is threefold. Firstly, a realistic synthetic phantom was created to quantify PVE. Secondly, MRI partial volume estimate segmentations were used to improve voxel-based PVE correction instead of using hard segmentations. Thirdly, quantification of PVE correction was evaluated on 34 subjects (AD=10, Normal Controls (NC)=24), including 12 PiB positive NC. Regional analysis was performed using the Anatomical Automatic Labeling (AAL) template, which was registered to each patient. Regions of interest were restricted to the gray matter (GM) defined by the MR segmentation. Average normalized intensity of the neocortex and selected regions were used to evaluate the discrimination power between AD and NC both with and without PVE correction. Receiver Operating Characteristic (ROC) curves were computed for the binary discrimination task. The phantom study revealed signal losses due to PVE between 10 to 40 % which were mostly recovered to within 5% after correction. Better classification was achieved after PVE correction, resulting in higher areas under ROC curves.

  20. Mannosylated polyion complexes for in vivo gene delivery into CD11c(+) dendritic cells.

    PubMed

    Raviv, Lior; Jaron-Mendelson, Michal; David, Ayelet

    2015-02-01

    Dendritic cells (DCs) possess unique abilities in initiating primary immune responses and thus represent prime targets for DNA-based vaccinations. Here, we describe the design and synthesis of mannosylated polyion complexes (PICs) composed of cationic polyethylenimine (PEI) and hydrophilic polyethylene glycol (PEG) segments, and bearing mono- and trivalent mannose as a ligand for targeting mannose receptor (MR/CD206)-positive DCs. Amino-terminated mannose (Man)-containing ligands in mono- and trivalent presentations (Man- and Man3-, respectively) were prepared and conjugated to PEG via an N-hydroxysuccinimide (NHS)-activated terminal. Thiolated PEI was conjugated to the mannosylated PEG via the maleimide (MAL)-activated terminal. The resulting positively charged diblock copolymers bearing mannoses (Man-PEG-b-PEI and Man3-PEG-b-PEI) were self-assembled with DNA to form PICs with lower surface charge than did their PEI building block and mean hydrodynamic diameters in the range of 100-450 nm, depending on the N/P ratio. Man3-PEG-b-PEI demonstrated a 3-4-fold greater transfection efficiency in MR-positive dendritic cell lines (THP-1, DC2.4), relative to Man-PEG-b-PEI, exhibited low cytotoxicity when compared with PEI, and showed low transfection efficiency in nondendritic HeLa cells. In preliminary in vivo experiments, Man-PEG-b-PEI/DNA and Man3-PEG-b-PEI/DNA demonstrated 2-3-fold higher gene delivery efficiency into CD11c(+) DCs collected from inguinal lymph nodes of C57/BL6 mice, when compared to PEI/DNA complexes, as shown by GFP expression measurements, 24 h post subcutaneous injection. The results indicate that the mannosylated PICs are a safe and effective gene delivery system, showing in vivo specificity toward CD11c(+) DCs.

  1. 11C level structure via the 10B(p, γ) reaction

    NASA Astrophysics Data System (ADS)

    Wiescher, M.; Boyd, R. N.; Blatt, S. L.; Rybarcyk, L. J.; Spizuoco, J. A.; Azuma, R. E.; Clifford, E. T. H.; King, J. D.; Görres, J.; Rolfs, C.; Vlieks, A.

    1983-10-01

    The reaction 10B(p, γ)11C has been investigated in the energy range Ep=0.07-2.20 MeV. The broad resonant structure previously observed in the ground state transition near Ep=1.2 MeV has been seen also in γ-ray transitions to excited states. The observed excitation functions as well as the γ-ray angular distributions can be explained by assuming several broad overlapping resonances. The low-energy data (Ep<0.6 MeV) reveal the existence of two s-wave resonances at Ep=0.010 and 0.56 MeV. Spectroscopic factors for several final states have been obtained from observation of direct capture processes to them; they are in fair agreement with results from stripping reaction studies. The present data also provide information on partial and total widths of the states at Ex=8-9 MeV. The energy range investigated corresponds to the temperature range of T=(0.01-5)×109 K. The thermonuclear reaction rates deduced from the present results are compared with previously reported values. NUCLEAR REACTIONS 10B(p, γ), Ep=0.07-2.20 MeV; measured γ yield for 11C states up to Ex=10.7 MeV. Deduced resonance parameters, branching ratios, and direct capture contributions for proton-unbound states; deduced spectroscopic factors, ΓγΓtot, and Γtot for several α-unbound states. Calculated thermonuclear reaction rate for T=(0.01-5)×109 K.

  2. Accurate on line measurements of low fluences of charged particles

    NASA Astrophysics Data System (ADS)

    Palla, L.; Czelusniak, C.; Taccetti, F.; Carraresi, L.; Castelli, L.; Fedi, M. E.; Giuntini, L.; Maurenzig, P. R.; Sottili, L.; Taccetti, N.

    2015-03-01

    Ion beams supplied by the 3MV Tandem accelerator of LABEC laboratory (INFN-Firenze), have been used to study the feasibility of irradiating materials with ion fluences reproducible to about 1%. Test measurements have been made with 7.5 MeV 7Li2+ beams of different intensities. The fluence control is based on counting ions contained in short bursts generated by chopping the continuous beam with an electrostatic deflector followed by a couple of adjustable slits. Ions are counted by means of a micro-channel plate (MCP) detecting the electrons emitted from a thin layer of Al inserted along the beam path in between the pulse defining slits and the target. Calibration of the MCP electron detector is obtained by comparison with the response of a Si detector.

  3. Swelling of several commercial alloys following high fluence neutron irradiation

    SciTech Connect

    Powell, R.W.; Peterson, D.T.; Zimmerschied, M.K.; Bates, J.F.

    1981-01-01

    Swelling values have been determined for a set of commercial alloys irradiated to a peak fluence of 17.8 x 10/sup 22/ n/cm/sup 2/ (E > 0.1 MeV) over the temperature range of 400 to 650/sup 0/C. The alloys studied fall into three classes: the ferritic alloys AISI 430F, AISI 416, EM-12, H-11 and 2 1/4 Cr-1 Mo; the superalloys Inconel 718 and Inconel X-750; and the refractory alloys TZM and Nb-1 Zr. After irradiation to a peak fluence approaching goal exposures envisioned for advanced fusion reactor first walls, all of the alloys display swelling resistance far superior to cold worked AISI 316. Of the three alloy classes examined the swelling resistance of the ferritics is the least sensitive to composition.

  4. Inertial confinement fusion method producing line source radiation fluence

    DOEpatents

    Rose, Ronald P.

    1984-01-01

    An inertial confinement fusion method in which target pellets are imploded in sequence by laser light beams or other energy beams at an implosion site which is variable between pellet implosions along a line. The effect of the variability in position of the implosion site along a line is to distribute the radiation fluence in surrounding reactor components as a line source of radiation would do, thereby permitting the utilization of cylindrical geometry in the design of the reactor and internal components.

  5. Fluence estimation by deconvolution via l1-norm minimization

    NASA Astrophysics Data System (ADS)

    García Hernández, J. C.; Lazaro-Ponthus, D.; Gmar, M.; Barthe, J.

    2011-03-01

    Advances in radiotherapy irradiation techniques have led to very complex treatments requiring for a more stringent control. The dosimetric properties of electronic portal imaging devices (EPID) encouraged their use for treatment verification. Two main approaches have been proposed: the forward approach, where measured portal dose images are compared to predicted dose images and the backward approach, where EPID images are used to estimate the dose delivered to the patient. Both approaches need EPID images to be converted into a fluence distribution by deconvolution. However, deconvolution is an ill-posed problem which is very sensitive to small variations on input data. This study presents the application of a deconvolution method based on l1-norm minimization; this is a method known for being very stable while working with noisy data. The algorithm was first evaluated on synthetic images with different noise levels, the results were satisfactory. Deconvolution algorithm was then applied to experimental portal images; the required EPID response kernel and energy fluence images were computed by Monte-Carlo calculation, accelerator treatment head and EPID models had already been commissioned in a previous work. The obtained fluence images were in good agreement with simulated fluence images. This deconvolution algorithm may be generalized to an inverse problem with a general operator, where image formation is not longer modeled by a convolution but by a linear operation that might be seen as a position-dependent convolution. Moreover, this procedure would be detector independent and could be used for any detector type provided its response function is known.

  6. Temperature Dependence of the Flare Fluence Scaling Exponent

    NASA Astrophysics Data System (ADS)

    Kretzschmar, M.

    2015-12-01

    Solar flares result in an increase of the solar irradiance at all wavelengths. While the distribution of the flare fluence observed in coronal emission has been widely studied and found to scale as f(E)˜ E^{-α}, with α slightly below 2, the distribution of the flare fluence in chromospheric lines is poorly known. We used the solar irradiance measurements observed by the SDO/EVE instrument at a 10 s cadence to investigate the dependency of the scaling exponent on the formation region of the lines (or temperature). We analyzed all flares above the C1 level since the start of the EVE observations (May 2010) to determine the flare fluence distribution in 16 lines covering a wide range of temperatures, several of which were not studied before. Our results show a weak downward trend with temperature of the scaling exponent of the PDF that reaches from above 2 at lower temperature (a few 104 K) to {˜ }1.8 for hot coronal emission (several 106 K). However, because colder lines also have fainter contrast, we cannot exclude that this behavior is caused by including more noise for smaller flares for these lines. We discuss the method and its limitations and tentatively associate this possible trend with the different mechanisms responsible for the heating of the chromosphere and corona during flares.

  7. Correlating Fast Fluence to dpa in Atypical Locations

    NASA Astrophysics Data System (ADS)

    Drury, Thomas H.

    2016-02-01

    Damage to a nuclear reactor's materials by high-energy neutrons causes changes in the ductility and fracture toughness of the materials. The reactor vessel and its associated piping's ability to withstand stress without brittle fracture are paramount to safety. Theoretically, the material damage is directly related to the displacements per atom (dpa) via the residual defects from induced displacements. However in practice, the material damage is based on a correlation to the high-energy (E > 1.0 MeV) neutron fluence. While the correlated approach is applicable when the material in question has experienced the same neutron spectrum as test specimens which were the basis of the correlation, this approach is not generically acceptable. Using Monte Carlo and discrete ordinates transport codes, the energy dependent neutron flux is determined throughout the reactor structures and the reactor vessel. Results from the models provide the dpa response in addition to the high-energy neutron flux. Ratios of dpa to fast fluence are calculated throughout the models. The comparisons show a constant ratio in the areas of historical concern and thus the validity of the correlated approach to these areas. In regions above and below the fuel however, the flux spectrum has changed significantly. The correlated relationship of material damage to fluence is not valid in these regions without adjustment. An adjustment mechanism is proposed.

  8. Syntheses and pharmacological evaluation of two potent antagonists for dopamine D4 receptors: [11C]YM-50001 and N-[2-[4-(4-Chlorophenyl)-piperizin-1-yl]ethyl]-3-[11C]methoxybenzamide.

    PubMed

    Zhang, Ming-Rong; Haradahira, Terushi; Maeda, Jun; Okauchi, Takashi; Kawabe, Kouichi; Noguchi, Junko; Kida, Takayo; Suzuki, Kazutoshi; Suhara, Tetsuya

    2002-02-01

    Two benzamide derivatives as dopamine D4 receptor antagonists, YM-50001(4) and N- [2-[4-(4-chlorophenyl]piperizin-1-yl]ethyl]-3-methoxybenzamide (9), were labeled by positron-emitter (11C), and their pharmacological specificities to dopamine D4 receptors were examined by quantitative autoradiography and positron emission tomography (PET). Radiosyntheses were accomplished by O-methylation of corresponding phenol precursors (5 and 10) with [11C]CH3I followed by HPLC purifications. In vitro binding on rat brain slices showed different distribution patterns and pharmacological properties between the two radioligands. The [11C]4 showed the highest binding in the striatum, which was inhibited not only by 10 microM 4 but also by 10 microM raclopride, a selective dopamine D2 receptor antagonist. In contrast, [11C]9 showed the highest binding in the cerebral cortex, which was inhibited by several D4 receptor antagonists (9, RBI-254, L-745,870), but not by any other receptor ligands (D1/D5, D2/D3, 5-HT1A, 5-HT2A, sigma1 and alpha1) tested. In vivo brain distribution of [11C]9 in rat showed the highest uptake in the frontal cortex, a region that has a high density of D4 receptors. These results indicate that the pharmacological property of [11C]9 matches the rat brain D4 receptors, but that of [11C]4 rather appears to match the rat brain D2 receptors. The results for the benzamide [11C]9 prompted us to further evaluate its potential as a PET radioligand for D4 receptors by employing PET on monkey brain. Unfortunately, in contrast to rats, neither specific binding nor differences in regional uptake of radioactivity were observed in monkey brain after intravenous 11C]9 injection. Based on that specific activities of radioligands might be critical in mapping the neurotransmitter receptors if they are only faintly expressed in the brain, 11C]9 with an extremely high specific activity (1810 GBq/micromol) was used for PET study. However, the effort to determine the specific binding

  9. Brain serotonin synthesis in MDMA (ecstasy) polydrug users: an alpha-[(11) C]methyl-l-tryptophan study.

    PubMed

    Booij, Linda; Soucy, Jean-Paul; Young, Simon N; Regoli, Martine; Gravel, Paul; Diksic, Mirko; Leyton, Marco; Pihl, Robert O; Benkelfat, Chawki

    2014-12-01

    3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) use may have long-term neurotoxic effects. In this study, positron emission tomography with the tracer alpha-[(11) C]methyl-l-tryptophan ((11) C-AMT) was used to compare human brain serotonin (5-HT) synthesis capacity in 17 currently drug-free MDMA polydrug users with that in 18 healthy matched controls. Gender differences and associations between regional (11) C-AMT trapping and characteristics of MDMA use were also examined. MDMA polydrug users exhibited lower normalized (11) C-AMT trapping in pre-frontal, orbitofrontal, and parietal regions, relative to controls. These differences were more widespread in males than in females. Increased normalized (11) C-AMT trapping in MDMA users was also observed, mainly in the brainstem and in frontal and temporal areas. Normalized (11) C-AMT trapping in the brainstem and pre-frontal regions correlated positively and negatively, respectively, with greater lifetime accumulated MDMA use, longer durations of MDMA use, and shorter time elapsed since the last MDMA use. Although the possibility of pre-existing 5-HT alterations pre-disposing people to use MDMA cannot be ruled out, regionally decreased 5-HT synthesis capacity in the forebrain could be interpreted as neurotoxicity of MDMA on distal (frontal) brain regions. On the other hand, increased 5-HT synthesis capacity in the raphe and adjacent areas could be due to compensatory mechanisms.

  10. Quantification of the novel N-methyl-d-aspartate receptor ligand [11C]GMOM in man

    PubMed Central

    van der Doef, Thalia F; Klein, Pieter J; Oropeza-Seguias, Gisela M; Schuit, Robert C; Metaxas, Athanasios; Jobse, Ellen; Schwarte, Lothar A; Windhorst, Albert D; Lammertsma, Adriaan A; van Berckel, Bart NM; Boellaard, Ronald

    2015-01-01

    [11C]GMOM (carbon-11 labeled N-(2-chloro-5-thiomethylphenyl)-N′-(3-[11C]methoxy-phenyl)-N′-methylguanidine) is a PET ligand that binds to the N-methyl-d-aspartate receptor with high specificity and affinity. The purpose of this first in human study was to evaluate kinetics of [11C]GMOM in the healthy human brain and to identify the optimal pharmacokinetic model for quantifying these kinetics, both before and after a pharmacological dose of S-ketamine. Dynamic 90 min [11C]GMOM PET scans were obtained from 10 subjects. In six of the 10 subjects, a second PET scan was performed following an S-ketamine challenge. Metabolite corrected plasma input functions were obtained for all scans. Regional time activity curves were fitted to various single- and two-tissue compartment models. Best fits were obtained using a two-tissue irreversible model with blood volume parameter. The highest net influx rate (Ki) of [11C]GMOM was observed in regions with high N-methyl-d-aspartate receptor density, such as hippocampus and thalamus. A significant reduction in the Ki was observed for the entire brain after administration of ketamine, suggesting specific binding to the N-methyl-d-aspartate receptors. This initial study suggests that the [11C]GMOM could be used for quantification of N-methyl-d-aspartate receptors. PMID:26661185

  11. Quantification of the novel N-methyl-d-aspartate receptor ligand [11C]GMOM in man.

    PubMed

    van der Doef, Thalia F; Golla, Sandeep Sv; Klein, Pieter J; Oropeza-Seguias, Gisela M; Schuit, Robert C; Metaxas, Athanasios; Jobse, Ellen; Schwarte, Lothar A; Windhorst, Albert D; Lammertsma, Adriaan A; van Berckel, Bart Nm; Boellaard, Ronald

    2016-06-01

    [(11)C]GMOM (carbon-11 labeled N-(2-chloro-5-thiomethylphenyl)-N'-(3-[(11)C]methoxy-phenyl)-N'-methylguanidine) is a PET ligand that binds to the N-methyl-d-aspartate receptor with high specificity and affinity. The purpose of this first in human study was to evaluate kinetics of [(11)C]GMOM in the healthy human brain and to identify the optimal pharmacokinetic model for quantifying these kinetics, both before and after a pharmacological dose of S-ketamine. Dynamic 90 min [(11)C]GMOM PET scans were obtained from 10 subjects. In six of the 10 subjects, a second PET scan was performed following an S-ketamine challenge. Metabolite corrected plasma input functions were obtained for all scans. Regional time activity curves were fitted to various single- and two-tissue compartment models. Best fits were obtained using a two-tissue irreversible model with blood volume parameter. The highest net influx rate (Ki) of [(11)C]GMOM was observed in regions with high N-methyl-d-aspartate receptor density, such as hippocampus and thalamus. A significant reduction in the Ki was observed for the entire brain after administration of ketamine, suggesting specific binding to the N-methyl-d-aspartate receptors. This initial study suggests that the [(11)C]GMOM could be used for quantification of N-methyl-d-aspartate receptors. PMID:26661185

  12. Optimization and Biodistribution of [(11)C]-TKF, An Analog of Tau Protein Imaging Agent [(18)F]-THK523.

    PubMed

    Kong, Yanyan; Guan, Yihui; Hua, Fengchun; Zhang, Zhengwei; Lu, Xiuhong; Zhu, Tengfang; Zhao, Bizeng; Zhu, Jianhua; Li, Cong; Chen, Jian

    2016-01-01

    The quantification of neurofibrillary tangles (NFTs) using specific PET tracers can facilitate the diagnosis of Alzheimer's disease (AD) and allow monitoring of disease progression and treatment efficacy. [(18)F]-THK523 has shown high affinity and selectivity for tau pathology. However, its high retention in white matter, which makes simple visual inspection difficult, may limit its use in research or clinical settings. In this paper, we optimized the automated radiosynthesis of [(11)C]-TKF and evaluated its biodistribution and toxicity in C57 mice. [(11)C]-TKF can be made by reaction precursor with [(11)C]MeOTf or (11)CH₃I, but [(11)C]MeOTf will give us higher labeling yields and specific activity. [(11)C]-TKF presented better brain uptake in normal mouse than [(18)F]-THK523 (3.23% ± 1.25% ID·g(-1) vs. 2.62% ± 0.39% ID·g(-1) at 2 min post-injection). The acute toxicity studies of [(11)C]-TKF were unremarkable. PMID:27527142

  13. Tracer kinetic modeling of [(11)C]AFM, a new PET imaging agent for the serotonin transporter.

    PubMed

    Naganawa, Mika; Nabulsi, Nabeel; Planeta, Beata; Gallezot, Jean-Dominique; Lin, Shu-Fei; Najafzadeh, Soheila; Williams, Wendol; Ropchan, Jim; Labaree, David; Neumeister, Alexander; Huang, Yiyun; Carson, Richard E

    2013-12-01

    [(11)C]AFM, or [(11)C]2-[2-(dimethylaminomethyl)phenylthio]-5-fluoromethylphenylamine, is a new positron emission tomography (PET) radioligand with high affinity and selectivity for the serotonin transporter (SERT). The purpose of this study was to determine the most appropriate kinetic model to quantify [(11)C]AFM binding in the healthy human brain. Positron emission tomography data and arterial input functions were acquired from 10 subjects. Compartmental modeling and the multilinear analysis-1(MA1) method were tested using the arterial input functions. The one-tissue model showed a lack of fit in low-binding regions, and the two-tissue model failed to estimate parameters reliably. Regional time-activity curves were well described by MA1. The rank order of [(11)C]AFM binding potential (BPND) matched well with the known regional SERT densities. For routine use of [(11)C]AFM, several noninvasive methods for quantification of regional binding were evaluated, including simplified reference tissue models (SRTM and SRTM2), and multilinear reference tissue models (MRTM and MRTM2). The best methods for region of interest (ROI) analysis were MA1, MRTM2, and SRTM2, with fixed population kinetic values ( or b') for the reference methods. The MA1 and MRTM2 methods were best for parametric imaging. These results showed that [(11)C]AFM is a suitable PET radioligand to image and quantify SERT in humans. PMID:23921898

  14. Radiosynthesis and Evaluation of [11C]EMPA as a potential PET Tracer for Orexin 2 Receptors

    PubMed Central

    Wang, Changning; Moseley, Christian K.; Carlin, Stephen M.; Wilson, Colin M.; Neelamegam, Ramesh; Hooker, Jacob M.

    2013-01-01

    EMPA is a selective antagonist of orexin 2 (OX2) receptors. Previous literature with [3H]-EMPA suggest that it may be used as an imaging agent for OX2 receptors; however, brain penetration is known to be modest. To evaluate the potential of EMPA as a PET radiotracer in non-human primate (as a step to imaging in man), we radiolabeled EMPA with carbon-11. Radiosynthesis of [11C]N-ethyl-2-(N-(6-methoxypyridin-3-yl)-2-methylphenylsulfonamido)-N-(pyridin-3-ylmethyl)acetamide ([11C]EMPA), and evaluation as a potential PET tracer for OX2 receptors is described. Synthesis of an appropriate non-radioactive O-desmethyl precursor was achieved from EMPA with sodium iodide and chlorotrimethylsilane. Selective O-methylation using [11C]CH3I in the presence of cesium carbonate in DMSO at room temp afforded [11C]EMPA in 1.5–2.5% yield (non-decay corrected relative to trapped [11C]CH3I at EOS) with ≥95 % chemical and radiochemical purities. The total synthesis time was 34–36 min from EOB. Studies in rodent suggested that uptake in tissue was dominated by nonspecific binding. However, [11C]EMPA also showed poor uptake in both rats and baboon as measured with PET imaging. PMID:23601709

  15. Analysis of organ motion effects on the effective fluences for liver IMRT

    NASA Astrophysics Data System (ADS)

    Kuo, Hsiang-Chi; Chuang, Keh-Shih; Liu, Wen Shan; Wu, Andrew; Lalonde, Ron

    2007-07-01

    An effective fluence concept was employed to make forward dose calculations to investigate the effects of a distorted fluence map on dose plans. Fluence changes caused by organ motion were calculated using Chui's algorithm (2003 Med. Phys. 30 1736). In two test cases with various fluence maps, the effects of motion were simulated using a maximal displacement from 5 mm to 25 mm; 108 fluence maps that were calculated from 16 IMRT plans for eight liver cancer patients were analyzed and compared with and without gating. Fluoroscopic measurements were made of a moving diaphragm in this study. Fluence changes associated with superior-inferior organ motion, perpendicular to the moving MLC, were also examined. The effects of motion on the fluence maps were evaluated from both the fluence differences between static and motion and the χ function. The maximum displacements of the organs in all of these cases were analyzed and correlated with the change in fluence generated from the liver IMRT plans. The dosimetric effects on the target coverage were evaluated for each plan. The results indicate that, for the same fluence map, the mean fluence intensity error or the percentage of the fluence points that have an unacceptable error is linearly related to the extent of motion. For different fluence maps, the degree to which the fluence is distorted by motion is strongly related to the product of the motion extent and the fluence gradient in the direction of diaphragm motion. For eight liver patients and 16 IMRT plans in this work (with gated technique, motion extent from 0.5 cm to 1.0 cm; without gated technique, motion extent from 0.9 cm to 1.8 cm), the fluence modulations are mild, such that the respiratory motion of each patient did not strongly affect the CTV coverage. The mean dose error is 1.5% for free motion (0.9-1.8 cm) and is around 1% for gated motion (0.5-1 cm).

  16. Comparative evaluation of shear bond strength of three resin based dual-cure core build-up materials: An In-vitro study

    PubMed Central

    Jain, Gaurav; Narad, Aditi; Boruah, Lalit C.; Rajkumar, Balakrishnan

    2015-01-01

    Aim: The in-vitro study compared the shear bond strength (SBS) of three recently introduced dual-cure resin based core build-up materials namely ParaCore, FluoroCore, and MultiCore. Materials and Methods: One hundred twenty extracted permanent human mandibular molar teeth were taken and sectioned horizontally beneath the dentinoenamel junction to expose the coronal dentin. The specimens obtained were divided into three main groups based on the materials used and then further divided into four sub-groups based on time interval with ten samples each. The dentin surface was treated with the respective adhesives of the groups and then bulk filled with core build-up materials. The attained samples were than subjected to shear loading in Instron Universal Testing Machine. The data were tabulated and statistically analyzed using analysis of variance (ANOVA), Tukey's HSD, and Levene's test. Results: The mean SBS was highest in MultiCore at all time periods as compared to FluoroCore and ParaCore and was also higher at 48 h thermocycling in all three groups studied. Conclusion: MultiCore dual-cure resin based core build-up material showed the highest mean SBS as compared to FluoroCore and ParaCore. SBS was not negatively affected by thermocycling. PMID:26180422

  17. Together, slowly but surely: the role of social interaction and feedback on the build-up of benefit in collective decision-making.

    PubMed

    Bahrami, Bahador; Olsen, Karsten; Bang, Dan; Roepstorff, Andreas; Rees, Geraint; Frith, Chris

    2012-02-01

    That objective reference is necessary for formation of reliable beliefs about the external world is almost axiomatic. However, Condorcet (1785) suggested that purely subjective information--if shared and combined via social interaction--is enough for accurate understanding of the external world. We asked if social interaction and objective reference contribute differently to the formation and build-up of collective perceptual beliefs. In three experiments, dyads made individual and collective perceptual decisions in a two-interval, forced-choice, visual search task. In Experiment 1, participants negotiated their collective decisions with each other verbally and received feedback about accuracy at the end of each trial. In Experiment 2, feedback was not given. In Experiment 3, communication was not allowed but feedback was provided. Social interaction (Experiments 1 and 2 vs. 3) resulted in a significant collective benefit in perceptual decisions. When feedback was not available a collective benefit was not initially obtained but emerged through practice to the extent that in the second half of the experiments, collective benefits obtained with (Experiment 1) and without (Experiment 2) feedback were robust and statistically indistinguishable. Taken together, this work demonstrates that social interaction was necessary for build-up of reliable collaborative benefit, whereas objective reference only accelerated the process but--given enough opportunity for practice--was not necessary for building up successful cooperation.

  18. Comparison of autologous 111In-leukocytes, 18F-FDG, 11C-methionine, 11C-PK11195 and 68Ga-citrate for diagnostic nuclear imaging in a juvenile porcine haematogenous staphylococcus aureus osteomyelitis model

    PubMed Central

    Nielsen, Ole L; Afzelius, Pia; Bender, Dirk; Schønheyder, Henrik C; Leifsson, Páll S; Nielsen, Karin M; Larsen, Jytte O; Jensen, Svend B; Alstrup, Aage KO

    2015-01-01

    The aim of this study was to compare 111In-labeled leukocyte single-photon emission computed tomography (SPECT) and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) to PET with tracers that potentially could improve detection of osteomyelitis. We chose 11C-methionine, 11C-PK11195 and 68Ga-citrate and validated their diagnostic utility in a porcine haematogenous osteomyelitis model. Four juvenile 14-15 weeks old female pigs were scanned seven days after intra-arterial inoculation in the right femoral artery with a porcine strain of Staphylococcus aureus using a sequential scan protocol with 18F-FDG, 68Ga-citrate, 11C-methionine, 11C-PK11195, 99mTc-Nanocoll and 111In-labelled autologous leukocytes. This was followed by necropsy of the pigs and gross pathology, histopathology and microbial examination. The pigs developed a total of five osteomyelitis lesions, five lesions characterized as abscesses/cellulitis, arthritis in three joints and five enlarged lymph nodes. None of the tracers accumulated in joints with arthritis. By comparing the 10 infectious lesions, 18F-FDG accumulated in nine, 111In-leukocytes in eight, 11C-methionine in six, 68Ga-citrate in four and 11C-PK11195 accumulated in only one lesion. Overall, 18F-FDG PET was superior to 111In-leukocyte SPECT in marking infectious and proliferative, i.e. hyperplastic, lesions. However, leukocyte SPECT was performed as early scans, approximately 6 h after injection of the leukocytes, to match the requirements of the 18 h long scan protocol. 11C-methionine and possibly 68Ga-citrate may be useful for diagnosis of soft issue lesions. PMID:25973338

  19. 11C-Acetate PET/CT Imaging in Localized Prostate Cancer: A study with MRI and Histopathologic Correlation

    PubMed Central

    Mena, Esther; Turkbey, Baris; Mani, Haresh; Adler, Stephen; Valera, Vladimir A.; Bernardo, Marcelino; Shah, Vijay; Pohida, Thomas; McKinney, Yolanda; Kwarteng, Gideon; Daar, Dagane; Lindenberg, Maria L.; Eclarinal, Philip; Wade, Revia; Linehan, W. Marston; Merino, Maria J.; Pinto, Peter A.; Choyke, Peter L.; Kurdziel, Karen A.

    2012-01-01

    This work characterizes the uptake of 11C-Acetate in prostate cancer (PCa), benign prostate hyperplasia (BPH) and normal prostate tissue in comparison with multi-parametric MRI, whole mount histopathology and clinical markers, to evaluate its potential utility for delineating intra-prostatic tumors in a population of patients with localized PCa. METHODS 39 men with presumed localized PCa underwent dynamic/static abdomen-pelvic 11C-Acetate PET/CT for 30-minutes and 3T multi-parametric (MP) MRI prior to prostatectomy. PET/CT images were registered to MRI using pelvic bones for initial rotation-translation, followed by manual adjustments to account for prostate motion and deformation from the MRI endorectal coil. Whole-mount pathology specimens were sectioned using an MRI-based patient specific mold resulting in improved registration between the MRI, PET and pathology. 11C-Acetate PET standardized uptake values were compared with MP-MRI and pathology. RESULTS 11C-Acetate uptake was rapid but reversible, peaking at 3–5 minutes post-injection and reaching a relative plateau at ~10 minutes. The average SUVmax(10–12min) of tumors was significantly higher than that of normal prostate tissue (4.4±2.05, range 1.8–9.2 vs. 2.1±0.94, range 0.7–3.4; p<0.001); however it was not significantly different from benign prostatic hyperplasia (4.8±2.01; range 1.8–8.8). A sector-based comparison with histopathology, including all tumors > 0.5 cm, revealed a sensitivity and specificity of 61.6 % and 80.0 % for 11C-Acetate PET/CT, and 82.3% and 95.1% for MRI, respectively. Considering only tumors >0.9 cm the 11C-Acetate accuracy was comparable to that of MRI. In a small cohort (n=9), 11C-Acetate uptake was independent of fatty acid synthase expression based on immunohistochemistry. CONCLUSION 11C-Acetate PET/CT demonstrates higher uptake in tumor foci than normal prostate tissue; however 11C-Acetate uptake in tumors is similar to BPH nodules. While 11C-Acetate PET/CT is not

  20. An Improved Antagonist Radiotracer for the Kappa Opioid Receptor: Synthesis and Characterization of 11C-LY2459989

    PubMed Central

    Zheng, Ming-Qiang; Kim, Su Jin; Holden, Daniel; Lin, Shu-fei; Need, Anne; Rash, Karen; Barth, Vanessa; Mitch, Charles; Navarro, Antonio; Kapinos, Michael; Maloney, Kathleen; Ropchan, Jim; Carson, Richard E.; Huang, Yiyun

    2016-01-01

    The kappa opioid receptors (KOR) are implicated in a number of neuropsychiatric diseases and addictive disorders. Positron Emission Tomography (PET) with radioligands provides a means to image the KOR in vivo and investigate its function in health and disease. The purpose of this study was to develop the selective KOR antagonist 11C-LY2459989 as a PET radioligand and characterize its imaging performance in non-human primates. Methods LY2459989 was synthesized and assayed for in vitro binding to opioid receptors. Ex vivo studies in rodents were conducted to assess its potential as a tracer candidate. 11C-LY2459989 was synthesized by reaction of its iodophenyl precursor with 11C-cyanide followed by partial hydrolysis of the resulting 11C-cyanophenyl intermediate. Imaging experiments with 11C-LY2459989 were carried out in rhesus monkeys with arterial input function measurement. Imaging data were analyzed with kinetic models to derive in vivo binding parameters. Results LY2459989 is a full antagonist with high binding affinity and selectivity for KOR (Ki = 0.18, 7.68, and 91.3 nM, respectively, for κ, μ, and δ receptors). Ex vivo studies in rats indicated LY2459989 as an appropriate tracer candidate with high specific binding signals, and confirmed its KOR binding selectivity in vivo. 11C-LY2459989 was synthesized in high radiochemical purity and good specific activity. In rhesus monkeys, 11C-LY2459989 displayed a fast rate of peripheral metabolism. Similarly, 11C-LY2459989 displayed fast uptake kinetics in the brain and an uptake pattern consistent with the distribution of KOR in primates. Pretreatment with naloxone (1 mg/kg, i.v.) resulted in a uniform distribution of radioactivity in the brain. Further, specific binding of 11C-LY2459989 was dose-dependently reduced by the selective KOR antagonist LY2456302 and the unlabeled LY2459989. Regional binding potential (BPND) values derived from the multilinear analysis method (MA1), as a measure of in vivo specific

  1. [{sup 11}C]d-threo-Methylphenidate, a new radiotracer for the dopamine transporter. Characterization in baboon and human brain

    SciTech Connect

    Ding, Y.S.; Volkow, N.D.; Fowler, J.S.

    1995-05-01

    dl-threo Methylphenidate (MP, Ritalin) is a psychostimulant drug which binds to the dopamine transporter (DAT). We evaluated [{sup 11}C]d-threo-methylphenidate ([{sup 11}C]d-MP), the more active enantiomer, as a radiotracer for the DAT in baboons and human brain. Stereoselectivity, saturability and pharmacological specificity and reproducibility were examined. Stereoselectivity was examined in baboons by comparing [{sup 11C}]d-MP,[{sup 11}C]l-MP and [{sup 11}C]dl-MP. Unlabeled MP was used to assess the reversibility and saturability of the binding. GBR 12909,{beta}-(4-iodophenyl)tropane-2-carboxylic acid methyl ester ({beta}-CIT), tomoxetine and citalopram were used to assess the specificity of the binding. The ratios between the radioactivity in the striatum to that in cerebellum (ST/CB) were 3.3,2.2 and 1.1 for [{sup 11}C]d-MP,[{sup 11}C]dl-MP and [{sup 11}C]l-MP respectively. Most of the striatal binding of [{sup 11}C]d-threo-MP was displaced by injection of nonradioactive MP demonstrating reversibility. Pretreatment with MP (0.5 mg/kg), GBR12909 (1.5 mg/kg) or {beta}-CIT (0.3 mg/kg) reduced ST/CB by about 60% and the ratios of distribution volumes at the steady-state for the triatum to cerebellum (DV{sub st/}DV{sub cb}) by about 50%. Pretreatment with tomoxetine (3.0 mg/kg) or citalopram (2.0 mg/kg), inhibitors of the norepinephrine and serotonin transporter, had no effect. Studies of [{sup 11}C]d-MP in the human brain showed highest uptake in basal ganglia with a half clearance time of about 60 minutes. Repeated studies in 6 normal human subjects showed differences in DV{sub st/}DV{sub cb} between -7% and 8%. MP pretreatment decreased BG but no cortical or cerebellar binding and reduced Bmax/Kd by 91%.

  2. [11C]acetate PET Imaging is not Always Associated with Increased Lipogenesis in Hepatocellular Carcinoma in Mice

    PubMed Central

    Li, Lei; Che, Li; Wang, Chunmei; Blecha, Joseph E.; Li, Xiaolei; VanBrocklin, Henry F.; Calvisi, Diego F.; Puchowicz, Michelle; Chen, Xin; Seo, Youngho

    2015-01-01

    Purpose Altered metabolism, including increased glycolysis and de novo lipogenesis, is one of the hallmarks of cancer. Radiolabeled nutrients, including glucose and acetate, are extensively used for the detection of various tumors, including hepatocellular carcinomas (HCCs). High signal of [11C]acetate positron emission tomography (PET) in tumors is often considered to be associated with increased expression of Fatty Acid Synthase (FASN) and increased de novo lipogenesis in tumor tissues. Defining a subset of tumors with increased [11C]acetate PET signal and thus increased lipogenesis was suggested to help select a group of patients, who may benefit from lipogenesis-targeting therapies. Procedures To investigate whether [11C]acetate PET imaging is truly associated with increased de novo lipogenesis along with hepatocarcinogenesis, we performed [11C]acetate PET imaging in wildtype mice as well as two mouse HCC models, induced by myrAKT/RasV12 (AKT/Ras) and PIK3CA1047R/c-Met (PI3K/Met) oncogene combinations. In addition, we analyzed FASN expression and de novo lipogenesis rate in these mouse liver tissues. Results We found that while HCCs induced by AKT/Ras co-expression showed high levels of [11C]acetate PET signal compared to normal liver, HCCs induced by PI3K/Met overexpression did not. Intriguingly, elevated FASN expression and increased de novo lipogenesis rate were observed in both AKT/Ras and PI3K/Met HCCs. Conclusion Altogether, our study suggests that [11C]acetate PET imaging can be a useful tool for imaging of a subset of HCCs. However, at molecular level, the increased [11C]acetate PET imaging is not always associated with increased FASN expression or de novo lipogenesis. PMID:26567114

  3. Dopamine D3 Receptor Alterations in Cocaine-Dependent Humans Imaged with [11C](+)PHNO

    PubMed Central

    Matuskey, David; Gallezot, Jean-Dominique; Pittman, Brian; Williams, Wendol; Wanyiri, Jane; Gaiser, Edward; Lee, Dianne E.; Hannestad, Jonas; Lim, Keunpoong; Zheng, Minq-Qiang; Lin, Shu-fei; Labaree, David; Potenza, Marc N.; Carson, Richard E.; Malison, Robert T.; Ding, Yu-Shin

    2014-01-01

    Background Evidence from animal models and postmortem human studies points to the importance of the dopamine D3 receptor (D3R) in cocaine dependence (CD). The objective of this pilot study was to use the D3R-preferring radioligand [11C](+)PHNO to compare receptor availability in groups with and without CD. Methods Ten medically healthy, non-treatment seeking CD subjects (mean age 41±8) in early abstinence were compared to 10 healthy control (HC) subjects (mean age 41±6) with no history of cocaine or illicit substance abuse. Binding potential (BPND), a measure of available receptors, was determined with parametric images, computed using the simplified reference tissue model (SRTM2) with the cerebellum as the reference region. Results BPND in CD subjects was higher in D3R-rich areas including the substantia nigra ((SN) 29%; P=0.03), hypothalamus (28%; P=0.02) and amygdala (35%, P=0.03). No between-group differences were observed in the striatum or pallidum. BPND values in the SN (r = + 0.83; p =0.008) and pallidum (r = + 0.67; p = 0.03) correlated with years of cocaine use. Conclusions Between-group differences suggest an important role for dopaminergic transmission in the SN, hypothalamus and amygdala in CD. Such findings also highlight the potential relevance of D3R as a medication development target in CD. PMID:24717909

  4. Investigating expectation and reward in human opioid addiction with [(11) C]raclopride PET.

    PubMed

    Watson, Ben J; Taylor, Lindsay G; Reid, Alastair G; Wilson, Sue J; Stokes, Paul R; Brooks, David J; Myers, James F; Turkheimer, Federico E; Nutt, David J; Lingford-Hughes, Anne R

    2014-11-01

    The rewarding properties of some abused drugs are thought to reside in their ability to increase striatal dopamine levels. Similar increases have been shown in response to expectation of a positive drug effect. The actions of opioid drugs on striatal dopamine release are less well characterized. We examined whether heroin and the expectation of heroin reward increases striatal dopamine levels in human opioid addiction. Ten opioid-dependent participants maintained on either methadone or buprenorphine underwent [(11) C]raclopride positron emission tomography imaging. Opioid-dependent participants were scanned three times, receiving reward from 50-mg intravenous heroin (diamorphine; pharmaceutical heroin) during the first scan to generate expectation of the same reward at the second scan, during which they only received 0.1-mg intravenous heroin. There was no heroin injection during the third scan. Intravenous 50-mg heroin during the first scan induced pronounced effects leading to high levels of expectation at the second scan. There was no detectable increase in striatal dopamine levels to either heroin reward or expectation of reward. We believe this is the first human study to examine whether expectation of heroin reward increases striatal dopamine levels in opioid addiction. The absence of detectable increased dopamine levels to both the expectation and delivery of a heroin-related reward may have been due to the impact of substitute medication. It does however contrast with the changes seen in abstinent stimulant users, suggesting that striatal dopamine release alone may not play such a pivotal role in opioid-maintained individuals.

  5. Atomic oxygen flux and fluence calculation for Long Duration Exposure Facility (LDEF)

    NASA Technical Reports Server (NTRS)

    Bourassa, Roger J.; Gillis, James R.

    1991-01-01

    The LDEF mission was to study the effects of the space environment on various materials over an extended period of time. One of the important factors for materials degradation in low earth orbit is the atomic oxygen fluxes and fluences experienced by the materials. These fluxes and fluences are a function of orbital parameters, solar and geomagnetic activity, and material surface orientation. Calculations of atomic oxygen fluences and fluxes for the LDEF mission are summarized. Included are descriptions of LDEF orbital parameters, solar and geomagnetic data, computer code FLUXAV, which was used to perform calculations of fluxes and fluences, along with a discussion of the calculated fluxes and fluences.

  6. Imaging human brown adipose tissue under room temperature conditions with 11C-MRB, a selective norepinephrine transporter PET ligand

    PubMed Central

    Hwang, Janice J.; Yeckel, Catherine W.; Gallezot, Jean-Dominique; Aguiar, Renata Belfort-De; Ersahin, Devrim; Gao, Hong; Kapinos, Michael; Nabulsi, Nabeel; Huang, Yiyun; Cheng, David; Carson, Richard E.; Sherwin, Robert; Ding, Yu-Shin

    2015-01-01

    Introduction Brown adipose tissue (BAT) plays a critical role in adaptive thermogenesis and is tightly regulated by the sympathetic nervous system (SNS). However, current BAT imaging modalities require cold stimulation and are often unreliable to detect BAT in the basal state, at room temperature (RT). We have shown previously that BAT can be detected in rodents under both RT and cold conditions with 11C-MRB ((S,S)-11C-O-methylreboxetine), a highly selective ligand for the norepinephrine transporter (NET). Here, we evaluate this novel approach for BAT detection in adult humans under RT conditions. Methods Ten healthy, Caucasian subjects (5 M: age 24.6±2.6, BMI 21.6±2.7 kg/m2; 5 F: age 25.4±2.1, BMI 22.1±1.0 kg/m2) underwent 11C-MRB PET-CT imaging for cervical/supraclavicular BAT under RT and cold-stimulated conditions (RPCM Cool vest; enthalpy 15°C) compared to 18F-FDG PET-CT imaging. Uptake of 11C-MRB, was quantified as the distribution volume ratio (DVR) using the occipital cortex as a low NET density reference region. Total body fat and lean body mass were assessed via bioelectrical impedance analysis. Results As expected, 18F-FDG uptake in BAT was difficult to identify at RT but easily detected with cold stimulation (p=0.01). In contrast, BAT 11C-MRB uptake (also normalized for muscle) was equally evident under both RT and cold conditions (BAT DVR: RT 1.0±0.3 vs. cold 1.1±0.3, p=0.31; BAT/muscle DVR: RT 2.3±0.7 vs. cold 2.5±0.5, p=0.61). Importantly, BAT DVR and BAT/muscle DVR of 11C-MRB at RT correlated positively with core body temperature (r=0.76, p=0.05 and r=0.92, p=0.004, respectively), a relationship not observed with 18F-FDG (p=0.63). Furthermore, there were gender differences in 11C-MRB uptake in response to cold (p=0.03), which reflected significant differences in the change in 11C-MRB as a function of both body composition and body temperature. Conclusions Unlike 18F-FDG, the uptake of 11C-MRB in BAT offers a unique opportunity to

  7. Novel monoclonal antibody against alphaX subunit from horse CD11c/CD18 integrin.

    PubMed

    Espino-Solis, Gerardo Pavel; Quintero-Hernandez, Veronica; Olvera-Rodriguez, Alejandro; Calderon-Amador, Juana; Pedraza-Escalona, Martha; Licea-Navarro, Alexei; Flores-Romo, Leopoldo; Possani, Lourival Domingos

    2015-04-15

    The αX I-domain of the horse integrin CD11c was successfully expressed in Escherichia coli, purified, biochemically characterized and used as immunogen to generate murine monoclonal antibodies against horse CD11c, which are not yet commercially available. One monoclonal antibody mAb-1C4 against the αX I-domain, is an IgG2a able to interact with the recombinant I-domain, showing an EC50=2.4ng according to ELISA assays. By western blot with horse PBMCs lysates the mAb-1C4 recognized a protein of 150kDa which corresponds well with the CD11c molecule. Using immunohistochemistry in horse lymph node tissue sections, mAb-1C4 marked cells in situ, some with apparent dendritic morphology. Thus the mAb generated to a recombinant epitope from horse CD11c identified the molecule in intact cells within horse lymphoid tissue. By the labelling intensity, the histological location (paracortical and interfollicular areas) and the apparent morphology of the marked cells, we can say that these are putative horse dendritic cells (DCs). The development of a mAb to horse CD11c provides a new tool to better study the horse DC biology and opens other biotechnological avenues, such as DC targeting-based vaccines.

  8. Ammonia oxidation is not required for growth of Group 1.1c soil Thaumarchaeota

    PubMed Central

    Weber, Eva B.; Lehtovirta-Morley, Laura E.; Prosser, James I.; Gubry-Rangin, Cécile

    2015-01-01

    Thaumarchaeota are among the most abundant organisms on Earth and are ubiquitous. Within this phylum, all cultivated representatives of Group 1.1a and Group 1.1b Thaumarchaeota are ammonia oxidizers, and play a key role in the nitrogen cycle. While Group 1.1c is phylogenetically closely related to the ammonia-oxidizing Thaumarchaeota and is abundant in acidic forest soils, nothing is known about its physiology or ecosystem function. The goal of this study was to perform in situ physiological characterization of Group 1.1c Thaumarchaeota by determining conditions that favour their growth in soil. Several acidic grassland, birch and pine tree forest soils were sampled and those with the highest Group 1.1c 16S rRNA gene abundance were incubated in microcosms to determine optimal growth temperature, ammonia oxidation and growth on several organic compounds. Growth of Group 1.1c Thaumarchaeota, assessed by qPCR of Group 1.1c 16S rRNA genes, occurred in soil, optimally at 30°C, but was not associated with ammonia oxidation and the functional gene amoA could not be detected. Growth was also stimulated by addition of organic nitrogen compounds (glutamate and casamino acids) but not when supplemented with organic carbon alone. This is the first evidence for non-ammonia oxidation associated growth of Thaumarchaeota in soil. PMID:25764563

  9. BS69/ZMYND11 C-Terminal Domains Bind and Inhibit EBNA2

    PubMed Central

    Shen, Chih-Lung; Gonzalez-Hurtado, Elsie; Zhang, Zhi-Min; Xu, Muyu; Martinez, Ernest; Peng, Chih-Wen; Song, Jikui

    2016-01-01

    Epstein-Barr virus (EBV) nuclear antigen 2 (EBNA2) plays an important role in driving immortalization of EBV-infected B cells through regulating the expression of many viral and cellular genes. We report a structural study of the tumor suppressor BS69/ZMYND11 C-terminal region, comprised of tandem coiled-coil-MYND domains (BS69CC-MYND), in complex with an EBNA2 peptide containing a PXLXP motif. The coiled-coil domain of BS69 self-associates to bring two separate MYND domains in close proximity, thereby enhancing the BS69 MYND-EBNA2 interaction. ITC analysis of BS69CC-MYND with a C-terminal fragment of EBNA2 further suggests that the BS69CC-MYND homodimer synergistically binds to the two EBNA2 PXLXP motifs that are respectively located in the conserved regions CR7 and CR8. Furthermore, we showed that EBNA2 interacts with BS69 and down-regulates its expression at both mRNA and protein levels in EBV-infected B cells. Ectopic BS69CC-MYND is recruited to viral target promoters through interactions with EBNA2, inhibits EBNA2-mediated transcription activation, and impairs proliferation of lymphoblastoid cell lines (LCLs). Substitution of critical residues in the MYND domain impairs the BS69-EBNA2 interaction and abolishes the BS69 inhibition of the EBNA2-mediated transactivation and LCL proliferation. This study identifies the BS69 C-terminal domains as an inhibitor of EBNA2, which may have important implications in development of novel therapeutic strategies against EBV infection. PMID:26845565

  10. Kinetics of 11C-labeled opiates in the brain of rhesus monkeys

    SciTech Connect

    Hartvig, P.; Bergstroem, K.; Lindberg, B.; Lundberg, P.O.; Lundqvist, H.; Langstroem, B.; Svaerd, H.; Rane, A.

    1984-07-01

    The regional uptake in the brain of Rhesus monkeys of i.v. administered 11C-labeled morphine, codeine, heroin and pethidine was studied by means of positron emission tomography. The technique measures the sum of parent drug and radiolabeled metabolites. (For the sake of simplicity the drug derived radioactivity is denoted by the drug name.) Morphine had a limited uptake to discrete areas of the brain. The maximum normalized uptake, with respect to dose per kilogram body weight, was about 0.2, i.e., 20% of the calculated activity if the drug had been evenly distributed throughout the body of the monkey. Maximum radioactivity appeared 30 to 45 min after injection. Morphine left the brain slowly with an estimated half-life of more than 2 hr. An area with a normalized uptake of about 1.0 was detected centrally in the lowest horizontal transsection of the skull. The origin of this area was identified as the pituitary. Codeine, heroin and pethidine were taken up to the brain to a larger extent than morphine, with maximum normalized uptakes of 2.6, 4.6 and 6.3, respectively. Maximum radioactivities of these drugs were achieved earlier and the elimination rates were faster than for morphine. Differences in the uptake of these drugs to the brain, as well as differences in time to maximal normalized uptake and rate of disappearance are considered to reflect differences in the lipophilic character between the drugs. Pethidine had the most rapid and extensive uptake followed by heroin, codeine and morphine in order of decreasing lipophilicity.

  11. α-[11C]-Methyl-l-tryptophan–PET in 191 patients with tuberous sclerosis complex

    PubMed Central

    Luat, Aimee F.; Kumar, Ajay; Govindan, Rajkumar; Pawlik, Kathy; Asano, Eishi

    2013-01-01

    Objectives: This was an observational study done on a large cohort of patients with tuberous sclerosis complex (TSC) to determine whether i) the presence of α-[11C]-methyl-l-tryptophan (AMT) hotspots is related to the duration of seizure intractability, ii) the presence of AMT hotspots is related to specific TSC gene mutations, and iii) there is concordance between areas with an AMT hotspot and seizure lateralization/localization on scalp EEG. Methods: One hundred ninety-one patients (mean age: 6.7 years; median: 5 years; range: 3 months to 37 years) with TSC and intractable epilepsy were included. All patients underwent AMT-PET scan. AMT uptake in each tuber and normal-appearing cortex was measured and correlated with clinical, scalp EEG, and, if available, electrocorticographic data. Results: The longer the duration of seizure intractability, the greater the number of AMT hotspots (r = 0.2; p = 0.03). AMT hotspots were seen in both TSC1 and TSC2. There was excellent agreement in seizure focus lateralization between ictal scalp EEG and AMT-PET (Cohen κ 0.94) in 68 of 95 patients in whom both ictal video-EEG and AMT-PET showed lateralizing findings; in 28 of 68 patients (41%), AMT was more localizing. Furthermore, AMT-PET was localizing in 10 of 17 patients (58%) with nonlateralized ictal EEG. Conclusion: AMT-PET, when used together with video-EEG, provides additional lateralization/localization data, regardless of TSC mutation. The duration of seizure intractability may predict the multiplicity of areas with AMT hotspots. PMID:23851963

  12. Lack of endogenous opioid release during sustained visceral pain: a [11C]carfentanil PET study.

    PubMed

    Ly, Huynh Giao; Dupont, Patrick; Geeraerts, Brecht; Bormans, Guy; Van Laere, Koen; Tack, Jan; Van Oudenhove, Lukas

    2013-10-01

    Opioidergic neurotransmission in the central nervous system is involved in somatic pain, but its role in visceral pain remains unknown. We aimed to quantify endogenous opioid release in the brain during sustained painful gastric distension. Therefore, 2 dynamic [11C]carfentanil positron emission tomography scans were performed in 20 healthy subjects during 2 conditions: sustained (20 minutes) painful proximal gastric balloon distension at predetermined individual discomfort threshold (PAIN) and no distension (NO PAIN), in counterbalanced order. Pain levels were assessed during scanning using visual analogue scales and after scanning using the McGill Pain Questionnaire. Emotional state was rated after scanning using the Positive and Negative Affect Schedule. Distribution volume ratios in 21 volumes of interest in the pain matrix were used to quantify endogenous opioid release. During the PAIN compared to the NO PAIN condition, volunteers reported a significantly higher increase in negative affect (5.50±1.29 versus 0.10±1.08, P=.0147) as well as higher pain ratings (sensory: 74.05±9.23 versus 1.50±0.95, P<.0001; affective: 91.42±8.13 versus 4.33±6.56, P<.0001). No difference in endogenous opioid release was demonstrated in any of the volumes of interest. Thus, contrary to its somatic counterpart, no opioid release is detected in the brain during sustained visceral pain, despite similar pain intensities. Endogenous opioids may play a less important role in visceral compared to somatic pain.

  13. Development of a NiO target for the production of 11C at ISAC/TRIUMF

    NASA Astrophysics Data System (ADS)

    Bricault, Pierre G.; Ames, Friedhelm; Dombsky, Marik; Kunz, Peter; Lassen, Jens; Mjøs, Anders; Wong, John

    2016-01-01

    High intensity 11C beams are necessary for the investigation of the formation of 12C via the nuclear reaction 11C(p, γ)12N → 12C + e+ + ν. The production of intense carbon beams on-line is quite challenging due to the thermodynamic properties and chemical reactivity of carbon at high temperatures. A previous attempt, using a medical isotope cyclotron production method in batch mode, was not conclusive. The intensity obtained was at least one order of magnitude too low for a direct proton capture experiment using the DRAGON facility at ISAC/TRIUMF. Producing a 11C beams using the ISOL method requires a target capable of efficiently releasing the carbon isotopes. NiO has been selected as a target material because most of the nickel carbides are not stable at high temperature. The development of carbon beams using a composite NiO/Ni target on-line is described.

  14. Estimating the effect of endogenous dopamine on baseline [(11) C]-(+)-PHNO binding in the human brain.

    PubMed

    Caravaggio, Fernando; Kegeles, Lawrence S; Wilson, Alan A; Remington, Gary; Borlido, Carol; Mamo, David C; Graff-Guerrero, Ariel

    2016-11-01

    Endogenous dopamine (DA) levels at dopamine D2/3 receptors (D2/3 R) have been quantified in the living human brain using the agonist radiotracer [(11) C]-(+)-PHNO. As an agonist radiotracer, [(11) C]-(+)-PHNO is more sensitive to endogenous DA levels than antagonist radiotracers. We sought to determine the proportion of the variance in baseline [(11) C]-(+)-PHNO binding to D2/3 Rs which can be accounted for by variation in endogenous DA levels. This was done by computing the Pearson's coefficient for the correlation between baseline binding potential (BPND ) and the change in BPND after acute DA depletion, using previously published data. All correlations were inverse, and the proportion of the variance in baseline [(11) C]-(+)-PHNO BPND that can be accounted for by variation in endogenous DA levels across the striatal subregions ranged from 42-59%. These results indicate that lower baseline values of [(11) C]-(+)-PHNO BPND reflect greater stimulation by endogenous DA. To further validate this interpretation, we sought to examine whether these data could be used to estimate the dissociation constant (Kd) of DA at D2/3 R. In line with previous in vitro work, we estimated the in vivo Kd of DA to be around 20 nM. In summary, the agonist radiotracer [(11) C]-(+)-PHNO can detect the impact of endogenous DA levels at D2/3 R in the living human brain from a single baseline scan, and may be more sensitive to this impact than other commonly employed radiotracers. PMID:27341789

  15. Elevation of dopamine induced by cigarette smoking: novel insights from a [11C]-+-PHNO PET study in humans.

    PubMed

    Le Foll, Bernard; Guranda, Mihail; Wilson, Alan A; Houle, Sylvain; Rusjan, Pablo M; Wing, Victoria C; Zawertailo, Laurie; Busto, Usoa; Selby, Peter; Brody, Arthur L; George, Tony P; Boileau, Isabelle

    2014-01-01

    Positron emission tomography (PET) has convincingly provided in vivo evidence that psychoactive drugs increase dopamine (DA) levels in human brain, a feature thought critical to their reinforcing properties. Some controversy still exists concerning the role of DA in reinforcing smoking behavior and no study has explored whether smoking increases DA concentrations at the D3 receptor, speculated to have a role in nicotine's addictive potential. Here, we used PET and [(11)C]-(+)-PHNO ([(11)C]-(+)-4-propyl-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-ol) to test the hypothesis that smoking increases DA release (decreases [(11)C]-(+)-PHNO binding) in D2-rich striatum and D3-rich extra-striatal regions and is related to craving, withdrawal and smoking behavior. Ten participants underwent [(11)C]-(+)-PHNO scans after overnight abstinence and after smoking a cigarette. Motivation to smoke (smoking topography), mood, and craving were recorded. Smoking significantly decreased self-reported craving, withdrawal, and [(11)C]-(+)-PHNO binding in D2 and D3-rich areas (-12.0 and -15.3%, respectively). We found that motivation to smoke (puff rate) predicted magnitude of DA release in limbic striatum, and the latter was correlated with decreased craving and withdrawal symptoms. This is the first report suggesting that, in humans, DA release is increased in D3-rich areas in response to smoking. Results also support the preferential involvement of the limbic striatum in motivation to smoke, anticipation of pleasure from cigarettes and relief of withdrawal symptoms. We propose that due to the robust effect of smoking on [(11)C]-(+)-PHNO binding, this radiotracer represents an ideal translational tool to investigate novel therapeutic strategies targeting DA transmission.

  16. Kinetic brain analysis and whole-body imaging in monkey of [11C]MNPA: a dopamine agonist radioligand.

    PubMed

    Seneca, Nicholas; Skinbjerg, Mette; Zoghbi, Sami S; Liow, Jeih-San; Gladding, Robert L; Hong, Jinsoo; Kannan, Pavitra; Tuan, Edward; Sibley, David R; Halldin, Christer; Pike, Victor W; Innis, Robert B

    2008-09-01

    With a view to future extension of the use of the agonist radioligand [(11)C]MNPA ([O-methyl-(11)C]2-methoxy-N-propylnorapomorphine) from animals to humans, we performed two positron emission tomography (PET) studies in monkeys. First, we assessed the ability to quantify the brain uptake of [(11)C]MNPA with compartmental modeling. Second, we estimated the radiation exposure of [(11)C]MNPA to human subjects based on whole-body imaging in monkeys. Brain PET scans were acquired for 90 min and included concurrent measurements of the plasma concentration of unchanged radioligand. Time-activity data from striatum and cerebellum were quantified with two methods, a reference tissue model and distribution volume. Whole-body PET scans were acquired for 120 min using four bed positions from head to mid thigh. Regions of interest were drawn on compressed planar whole-body images to identify organs with the highest radiation exposures. After injection of [(11)C]MNPA, the highest concentration of radioactivity in brain was in striatum, with lowest levels in cerebellum. Distribution volume was well identified with a two-tissue compartmental model and was quite stable from 60 to 90 min. Whole-body PET scans showed the organ with the highest radiation burden (muSv/MBq) was the urinary bladder wall (26.0), followed by lungs (22.5), gallbladder wall (21.9), and heart wall (16.1). With a 2.4-h voiding interval, the effective dose was 6.4 muSv/MBq (23.5 mrem/mCi). In conclusion, brain uptake of [(11)C]MNPA reflected the density of D(2/3) receptors, quantified relative to serial arterial measurements, and caused moderate to low radiation exposure.

  17. Kinetic Analysis and Quantification of [11C]Martinostat for in vivo HDAC Imaging of the Brain

    PubMed Central

    Wey, Hsiao-Ying; Wang, Changning; Schroeder, Frederick A.; Logan, Jean; Price, Julie C.; Hooker, Jacob M.

    2015-01-01

    Epigenetic mechanisms mediated by histone deacetylases (HDACs) have been implicated in a wide-range of CNS disorders and may offer new therapeutic opportunities. In vivo evaluation of HDAC density and drug occupancy has become possible with [11C]Martinostat, which exhibits selectivity for a subset of class I/IIb HDAC enzymes. In this study, we characterize the kinetic properties of [11C]Martinostat in the nonhuman primate (NHP) brain in preparation for human neuroimaging studies. The goal of this work was to determine whether classic compartmental analysis techniques were appropriate and to further determine if arterial plasma is required for future NHP studies. Using an arterial plasma input function, several analysis approaches were evaluated for robust outcome measurements. [11C]Martinostat showed high baseline distribution volume (VT) ranging from 29.9–54.4 mL/cm3 in the brain and large changes in occupancy (up to 99%) with a blocking dose approaches full enzyme saturation. An averaged nondisplaceable tissue uptake (VND) of 8.6 ± 3.7 mL/cm3 suggests high specific binding of [11C]Martinostat. From a two-tissue compartment model, [11C]Martinostat exhibits a high K1 (averaged K1 of 0.65 mL/cm3/min) and a small k4 (average of 0.0085 min−1). Our study supports that [11C]Martinostat can be used to detect changes in HDAC density and occupancy in vivo and that simplified analysis not using arterial blood could be appropriate. PMID:25768025

  18. SPM analysis of parametric (R)-[11C]PK11195 binding images: plasma input versus reference tissue parametric methods.

    PubMed

    Schuitemaker, Alie; van Berckel, Bart N M; Kropholler, Marc A; Veltman, Dick J; Scheltens, Philip; Jonker, Cees; Lammertsma, Adriaan A; Boellaard, Ronald

    2007-05-01

    (R)-[11C]PK11195 has been used for quantifying cerebral microglial activation in vivo. In previous studies, both plasma input and reference tissue methods have been used, usually in combination with a region of interest (ROI) approach. Definition of ROIs, however, can be labourious and prone to interobserver variation. In addition, results are only obtained for predefined areas and (unexpected) signals in undefined areas may be missed. On the other hand, standard pharmacokinetic models are too sensitive to noise to calculate (R)-[11C]PK11195 binding on a voxel-by-voxel basis. Linearised versions of both plasma input and reference tissue models have been described, and these are more suitable for parametric imaging. The purpose of this study was to compare the performance of these plasma input and reference tissue parametric methods on the outcome of statistical parametric mapping (SPM) analysis of (R)-[11C]PK11195 binding. Dynamic (R)-[11C]PK11195 PET scans with arterial blood sampling were performed in 7 younger and 11 elderly healthy subjects. Parametric images of volume of distribution (Vd) and binding potential (BP) were generated using linearised versions of plasma input (Logan) and reference tissue (Reference Parametric Mapping) models. Images were compared at the group level using SPM with a two-sample t-test per voxel, both with and without proportional scaling. Parametric BP images without scaling provided the most sensitive framework for determining differences in (R)-[11C]PK11195 binding between younger and elderly subjects. Vd images could only demonstrate differences in (R)-[11C]PK11195 binding when analysed with proportional scaling due to intersubject variation in K1/k2 (blood-brain barrier transport and non-specific binding).

  19. Evaluation of myocardial metabolism, with /sup 13/N- and /sup 11/C-labeled amino acids and positron computed tomography

    SciTech Connect

    Henze, E.; Schelbert, H.R.; Barrio, J.R.; Egbert, J.E.; Hansen, H.W.; MacDonald, N.S.; Phelps, M.E.

    1982-08-01

    To evaluate the utility of labeled L-amino acids (AA) for imaging regional myocardial AA metabolism by positron computed tomography (PCT), the myocardial uptake and clearance of Ala,* Glu, Gln, Asp, Leu tagged with /sup 13/N, and of /sup 11/C-tagged Asp, and oxaloacetate (Oxal), were examined in 44 experiments at control, during ischemia, and after transaminase inhibition. The myocardial time-activity curves recorded after intracoronary tracer injection had two clearance phases (an early and a late) for all /sup 13/N AA, and three (early, intermediate, late) for the two /sup 11/C compounds, with significantly different clearance half-times of 18.7 +/- 8.0 (s.d.) sec for the early phase, 141.7 +/- 56.5 sec for the intermediate, and 61.2 +/- 43.5 min for the late phase. The residual fractions ranged from 0.07 to 0.23 in normal myocardium, and consistently increased with ischemia by 0.01-0.07 for /sup 13/N-labeled Ala, Glu, Asp, and Leu, but not for /sup 13/N Gln and /sup 11/C compounds. Transaminase inhibition shortened the half-times of the late phases of /sup 13/N-labeled Ala, Glu, Asp, and Leu; had no effect on t1/2 of /sup 13/N Gln and /sup 11/C Oxal; and resulted in a loss of /sup 11/C CO/sub 2/ production and of the intermediate phase for /sup 11/C Asp. On the PCT images, /sup 13/N activity from labeled Ala and Glu was not decreased in an ischemic segment despite a significant flow reduction, as demonstrated by /sup 13/N NH/sub 3/ imaging and labeled microspheres. From the results, a three-compartment tracer kinetic model is proposed for the noninvasive quantification of Krebscycle activity, protein synthesis, and metabolic derangements related to ischemia.

  20. Fluence and dose measurements for an accelerator neutron beam

    NASA Astrophysics Data System (ADS)

    Liu, Z.; Byun, S. H.; McNeill, F. E.; Mothersill, C. E.; Seymour, C. B.; Prestwich, W. V.

    2007-10-01

    The 3 MV Van de Graaff accelerator at McMaster University accelerator laboratory is extended to a neutron irradiation facility for low-dose bystander effects research. A long counter and an Anderson-Braun type neutron monitor have been used as monitors for the determination of the total fluence. Activation foils were used to determine the thermal neutron fluence rate (around 106 neutrons s-1). Meanwhile, the interactions of neutrons with the monitors have been simulated using a Monte Carlo N Particle (MCNP) code. Bystander effects, i.e. damage occurring in cells that were not traversed by radiation but were in the same radiation environment, have been well observed following both alpha and gamma irradiation of many cell lines. Since neutron radiation involves mixed field (including gamma and neutron radiations), we need to differentiate the doses for the bystander effects from the two radiations. A tissue equivalent proportional counter (TEPC) filled with propane based tissue equivalent gas simulating a 2 μm diameter tissue sphere has been investigated to estimate the neutron and gamma absorbed doses. A photon dose contamination of the neutron beam is less than 3%. The axial dose distribution follows the inverse square law and lateral and vertical dose distributions are relatively uniform over the irradiation area required by the biological study.

  1. Build-up and wash-off dynamics of atmospherically derived Cu, Pb, Zn and TSS in stormwater runoff as a function of meteorological characteristics.

    PubMed

    Murphy, Louise U; Cochrane, Thomas A; O'Sullivan, Aisling

    2015-03-01

    Atmospheric pollutants deposited on impermeable surfaces can be an important source of pollutants to stormwater runoff; however, modelling atmospheric pollutant loads in runoff has rarely been done, because of the challenges and uncertainties in monitoring their contribution. To overcome this, impermeable concrete boards (≈ 1m(2)) were deployed for 11 months in different locations within an urban area (industrial, residential and airside) throughout Christchurch, New Zealand, to capture spatially distributed atmospheric deposition loads in runoff over varying meteorological conditions. Runoff was analysed for total and dissolved Cu, Zn, Pb, and total suspended solids (TSS). Mixed-effect regression models were developed to simulate atmospheric pollutant loads in stormwater runoff. In addition, the models were used to explain the influence of different meteorological characteristics (e.g. antecedent dry days and rain depth) on pollutant build-up and wash-off dynamics. The models predicted approximately 53% to 69% of the variation in pollutant loads and were successful in predicting pollutant-load trends over time which can be useful for general stormwater planning processes. Results from the models illustrated the importance of antecedent dry days on pollutant build-up. Furthermore, results indicated that peak rainfall intensity and rain duration had a significant relationship with TSS and total Pb, whereas, rain depth had a significant relationship with total Cu and total Zn. This suggested that the pollutant speciation phase plays an important role in surface wash-off. Rain intensity and duration had a greater influence when the pollutants were predominantly in their particulate phase. Conversely, rain depth exerted a greater influence when a high fraction of the pollutants were predominantly in their dissolved phase. For all pollutants, the models were represented by a log-arctan relationship for pollutant build-up and a log-log relationship for pollutant wash

  2. DS02 fluence spectra for neutrons and gamma rays at Hiroshima and Nagasaki with fluence-to-kerma coefficients and transmission factors for sample measurements.

    PubMed

    Egbert, Stephen D; Kerr, George D; Cullings, Harry M

    2007-11-01

    Fluence spectra at several ground distances in Hiroshima and Nagasaki are provided along with associated fluence-to-kerma coefficients from the Dosimetry System 2002 (DS02). Also included are transmission factors for calculating expected responses of in situ sample measurements of neutron activation products such as (32)P,(36)Cl,(39)Ar,(41)Ca, (60)Co,(63)Ni,(152)Eu, and (154)Eu. The free-in-air (FIA) fluences calculated in 2002 are available for 240 angles, 69 energy groups, 101 ground distances, 5 heights, 4 radiation source components, 2 cities. The DS02 code uses these fluences partitioned to a prompt and delayed portion, collapsed to 58 energy groups and restricted to 97 ground distances. This is because the fluence spectra were required to be in the same format that was used in the older Dosimetry System 1986 (DS86) computer code, of which the DS02 computer code is a modification. The 2002 calculation fluences and the collapsed DS02 code fluences are presented and briefly discussed. A report on DS02, which is available on the website at the Radiation Effects Research Foundation, provides tables and figures of the A-bomb neutron and gamma-ray output used as the sources in the 2002 radiation transport calculations. While figures illustrating the fluence spectra at several ground ranges are presented in the DS02 Report, it does not include any tables of the calculated fluence spectra in the DS02 report. This paper provides, at several standard distances from the hypocenter, the numerical information which is required to translate the FIA neutron fluences given in DS02 to a neutron activation measurement or neutron and gamma-ray soft-tissue dose. PMID:17643260

  3. Radiation dosimetry of N-([11C]methyl)benperidol as determined by whole-body PET imaging of primates

    PubMed Central

    Antenor-Dorsey, Jo Ann V.; Laforest, Richard; Moerlein, Stephen M.; Videen, Tom O.

    2010-01-01

    Purpose N-([11C]methyl)benperidol ([11C]NMB) can be used for positron emission tomography (PET) measurements of D2-like dopamine receptor binding in vivo. We report the absorbed radiation dosimetry of i.v.-administered 11C-NMB, a critical step before applying this radioligand to imaging studies in humans. Materials and methods Whole-body PET imaging with a CTI/Siemens ECAT 953B scanner was done in a male and a female baboon. After i.v. injection of 444–1221 MBq of 11C-NMB, sequential images taken from the head to the pelvis were collected for 3 h. Volumes of interest (VOIs) were identified that entirely encompassed small organs (whole brain, striatum, eyes, and myocardium). Large organs (liver, lungs, kidneys, lower large intestine, and urinary bladder) were sampled by drawing representative regions within the organ volume. Time–activity curves for each VOI were extracted from the PET, and organ residence times were calculated by analytical integration of a multi-exponential fit of the time–activity curves. Human radiation doses were estimated using OLINDA/EXM 1.0 and the standard human model. Results Highest retention was observed in the blood and liver, each with total residence times of 1.5 min. The highest absorbed radiation doses were to the heart (10.5 mGy/kBq) and kidney (9.19 mGy/kBq), making these the critical organs for [11C]NMB. A heart absorption of 50 mGy would result from an injected dose of 4,762 MBq [11C]NMB. Conclusions Thus, this study suggests that up to 4,762 MBq of [11C]NMB can be safely administered to human subjects for PET studies. Total body dose and effective dose for [11C] NMB are 2.82 mGy/kBq and 3.7 mSv/kBq, respectively. PMID:18071701

  4. Distinct cerebral lesions in sporadic and 'D90A' SOD1 ALS: studies with [11C]flumazenil PET.

    PubMed

    Turner, M R; Hammers, A; Al-Chalabi, A; Shaw, C E; Andersen, P M; Brooks, D J; Leigh, P N

    2005-06-01

    Five to ten percent of amyotrophic lateral sclerosis (ALS) cases are associated with mutations of the superoxide dismutase-1 (SOD1) gene, and the 'D90A' mutation is associated with a unique phenotype and markedly slower disease progression (mean survival time 14 years). Relative sparing of inhibitory cortical neuronal circuits might be one mechanism contributing to the slower progression in patients homozygous for the D90A mutation (homD90A). The GABA(A) receptor PET ligand [11C]flumazenil has demonstrated motor and extra-motor cortical changes in sporadic ALS. In this study, we used [11C]flumazenil PET to explore differences in the pattern of cortical involvement between sporadic and genetically homogeneous ALS groups. Twenty-four sporadic ALS (sALS) and 10 homD90A patients underwent [11C]flumazenil PET of the brain. In addition, two subjects homozygous for the D90A mutation, but without symptoms or signs ('pre-symptomatic', psD90A), also underwent imaging. Results for each group were compared with those for 24 healthy controls of similar age. Decreases in the binding of [11C]flumazenil in the sALS group were found within premotor regions, motor cortex and posterior motor association areas. In the homD90A group of ALS patients, however, decreases were concentrated in the left fronto-temporal junction and anterior cingulate gyrus. In the two psD90A subjects, a small focus of reduced [11C]flumazenil binding at the left fronto-temporal junction was seen, similar to the pattern seen in the clinically affected patients. Within the sALS group, there was no statistically significant association between decreases in cortical [11C]flumazenil binding and revised ALS functional rating scale (ALSFRS-R score), whereas the upper motor neuron (UMN) score correlated with widespread and marked cortical decreases over the dominant hemisphere. In the homD90A group, there was a stronger statistical association between reduced cortical [11C]flumazenil binding and the ALSFRS-R, rather

  5. Synthesis and Evaluation of [11C]LY2795050 as a Novel Kappa Opioid Receptor Antagonist Radiotracer for PET Imaging

    PubMed Central

    Zheng, Ming-Qiang; Nabulsi, Nabeel; Kim, Su Jin; Tomasi, Giampaolo; Lin, Shu-fei; Mitch, Charles; Quimby, Steven; Barth, Vanessa; Rash, Karen; Masters, John; Navarro, Antonio; Seest, Eric; Morris, Evan E.; Carson, Richard E.; Huang, Yiyun

    2013-01-01

    Kappa opioid receptors (KOR) are believed to be involved in the pathophysiology of depression, anxiety disorders, drug abuse and alcoholism. To date, only one tracer, the kappa opioid receptor agonist [11C]GR103545, has been reported to be able to image KOR in primates. The goal of the present study was to synthesize the selective KOR antagonist [11C]LY2795050 and evaluate its potential as a PET tracer to image KOR in vivo. METHODS In vitro binding affinity of LY2795050 was measured in radioligand competition binding assays. Ex vivo experiments were conducted using microdosing of the unlabelled ligand in Sprague-Dawley rats, as well as wild-type and KOR knock-out mice, to assess the ligand’s potential as a tracer candidate. Imaging experiments with [11C]LY2795050 in monkeys were carried out on the Focus-220 PET scanner with arterial blood input function measurement. Binding parameters were determined with kinetic modeling analysis. RESULTS LY2795050 displays full antagonist activity and high binding affinity and selectivity for KOR. Microdosing studies in rodents and ex vivo analysis of tissue concentrations with LC/MS/MS identified LY2795050 as an appropriate tracer candidate able to provide specific binding signals in vivo. [11C]LY2795050 was prepared in an average yield of 12% and >99% radiochemical purity. In rhesus monkeys, [11C]LY2795050 displayed a moderate rate of peripheral metabolism, with ∼40% of parent compound remaining at 30 min postinjection. In the brain, [11C]LY2795050 displayed fast uptake kinetics (regional activity peak times < 20 min) and an uptake pattern consistent with the distribution of KOR in primates. Pretreatment with naloxone (1 mg/kg, iv) resulted in a uniform distribution of radioactivity. Further, specific binding of [11C]LY2795050 was reduced by the selective KOR antagonist LY2456302 in a dose-dependent manner. CONCLUSION [11C]LY2795050 displayed favorable pharmacokinetic properties and binding profiles in vivo, and therefore

  6. The automated radiosynthesis and purification of the opioid receptor antagonist, [6-O-methyl-11C]diprenorphine on the GE TRACERlab FXFE radiochemistry module.

    PubMed

    Fairclough, Michael; Prenant, Christian; Brown, Gavin; McMahon, Adam; Lowe, Jonathan; Jones, Anthony

    2014-05-15

    [6-O-Methyl-(11)C]diprenorphine ([(11)C]diprenorphine) is a positron emission tomography ligand used to probe the endogenous opioid system in vivo. Diprenorphine acts as an antagonist at all of the opioid receptor subtypes, that is, μ (mu), κ (kappa) and δ (delta). The radiosynthesis of [(11)C]diprenorphine using [(11)C]methyl iodide produced via the 'wet' method on a home-built automated radiosynthesis set-up has been described previously. Here, we describe a modified synthetic method to [(11)C]diprenorphine performed using [(11)C]methyl iodide produced via the gas phase method on a GE TRACERlab FXFE radiochemistry module. Also described is the use of [(11)C]methyl triflate as the carbon-11 methylating agent for the [(11)C]diprenorphine syntheses. [(11)C]Diprenorphine was produced to good manufacturing practice standards for use in a clinical setting. In comparison to previously reported [(11)C]diprenorphine radiosyntheisis, the method described herein gives a higher specific activity product which is advantageous for receptor occupancy studies. The radiochemical purity of [(11)C]diprenorphine is similar to what has been reported previously, although the radiochemical yield produced in the method described herein is reduced, an issue that is inherent in the gas phase radiosynthesis of [(11)C]methyl iodide. The yields of [(11)C]diprenorphine are nonetheless sufficient for clinical research applications. Other advantages of the method described herein are an improvement to both reproducibility and reliability of the production as well as simplification of the purification and formulation steps. We suggest that our automated radiochemistry route to [(11)C]diprenorphine should be the method of choice for routine [(11)C]diprenorphine productions for positron emission tomography studies, and the production process could easily be transferred to other radiochemistry modules such as the TRACERlab FX C pro.

  7. The fluence threshold of femtosecond laser blackening of metals: The effect of laser-induced ripples

    NASA Astrophysics Data System (ADS)

    Ou, Zhigui; Huang, Min; Zhao, Fuli

    2016-05-01

    With the primary controlling factor of the laser fluence, we have investigated femtosecond laser blackening of stainless steel, brass, and aluminum in visible light range. In general, low reflectance about 5% can be achieved in appropriate ranges of laser fluences for all the treated metal surfaces. Significantly, towards stainless steel and brass a fluence threshold of blackening emerges unusually: a dramatic reflectance decline occurs in a specific, narrow fluence range. In contrast, towards aluminum the reflectance declines steadily over a wide fluence range instead of the threshold-like behavior from steel and brass. The morphological characteristics and corresponding reflectance spectra of the treated surfaces indicates that the blackening threshold of stainless steel and brass corresponds to the fluence threshold of laser-induced subwavelength ripples. Such periodic ripples growing rapidly near ablation threshold absorb visible light efficiently through grating coupling and cavity trapping promoted by surface plasmon polaritons. Whereas, for aluminum, with fluence increasing the looming ripples are greatly suppressed by re-deposited nanoparticle aggregates that present intrinsic colors other than black, and until the formation of large scale "ravines" provided with strong light-trapping, sufficient blackening is achieved. In short, there are different fluence dependencies for femtosecond laser blackening of metals, and the specific blackening fluence threshold for certain metals in the visible range originates in the definite fluence threshold of femtosecond laser-induced ripples.

  8. Kinetics of (/sup 11/C)N,N-dimethylphenylethylamine in mice and humans: potential for measurement of brain MAO-B activity

    SciTech Connect

    Shinotoh, H.; Inoue, O.; Suzuki, K.; Yamasaki, T.; Iyo, M.; Hashimoto, K.; Tominaga, T.; Itoh, T.; Tateno, Y.; Ikehira, H.

    1987-06-01

    Carbon-11-labeled N,N-dimethylphenylethylamine ((/sup 11/C)DMPEA) was synthesized by the reaction of N-methylphenylethylamine with (/sup 11/C)methyl iodide. This newly synthesized radiotracer was developed for the purpose of in vivo measurement of monoamine oxidase-B activity in the brain using a metabolic trapping method. Initially, biodistribution was investigated in mice. The rapid and high uptake of /sup 11/C radioactivity in the brain was observed following intravenous injection of (/sup 11/C)DMPEA, the peak of which was reached at 1 min, followed by a decrease at 1-5 min and slowly thereafter. The kinetics of (/sup 11/C)DMPEA in the human brain were determined using positron emission tomography (PET) and showed that /sup 11/C radioactivity increased gradually over 60 min following initial rapid uptake of /sup 11/C radioactivity, with basal ganglia and thalamus showing high accumulation.

  9. Comparison of build-up region doses in oblique tangential 6 MV photon beams calculated by AAA and CCC algorithms in breast Rando phantom

    NASA Astrophysics Data System (ADS)

    Masunun, P.; Tangboonduangjit, P.; Dumrongkijudom, N.

    2016-03-01

    The purpose of this study is to compare the build-up region doses on breast Rando phantom surface with the bolus covered, the doses in breast Rando phantom and also the doses in a lung that is the heterogeneous region by two algorithms. The AAA in Eclipse TPS and the collapsed cone convolution algorithm in Pinnacle treatment planning system were used to plan in tangential field technique with 6 MV photon beam at 200 cGy total doses in Breast Rando phantom with bolus covered (5 mm and 10 mm). TLDs were calibrated with Cobalt-60 and used to measure the doses in irradiation process. The results in treatment planning show that the doses in build-up region and the doses in breast phantom were closely matched in both algorithms which are less than 2% differences. However, overestimate of doses in a lung (L2) were found in AAA with 13.78% and 6.06% differences at 5 mm and 10 mm bolus thickness, respectively when compared with CCC algorithm. The TLD measurements show the underestimate in buildup region and in breast phantom but the doses in a lung (L2) were overestimated when compared with the doses in the two plannings at both thicknesses of the bolus.

  10. Experimental Approach to Evaluate the 11C Perfusion and Diffusion in Small Animal Tissues for HadronPET Applications

    PubMed Central

    Martínez-Rovira, Immaculada; Boisgard, Raphaël; Pottier, Géraldine; Kuhnast, Bertrand; Jan, Sébastien

    2016-01-01

    The development of a reliable dose monitoring system in hadron therapy is essential in order to control the treatment plan delivery. Positron Emission Tomography (PET) is the only method used in clinics nowadays for quality assurance. However, the accuracy of this method is limited by the loss of signal due to the biological washout processes. Up to the moment, very few studies measured the washout processes and there is no database of washout data as a function of the tissue and radioisotope. One of the main difficulties is related to the complexity of such measurements, along with the limited time slots available in hadron therapy facilities. Thus, in this work, we proposed an alternative in vivo methodology for the measurement and modeling of the biological washout parameters without any radiative devices. It consists in the implementation of a point-like radioisotope source by direct injection on the tissues of interest and its measurement by means of high-resolution preclinical PET systems. In particular, the washout of 11C carbonate radioisotopes was assessed, considering that 11C is is the most abundant β+ emitter produced by carbon beams. 11C washout measurements were performed in several tissues of interest (brain, muscle and 9L tumor xenograf) in rodents (Wistar rat). Results show that the methodology presented is sensitive to the washout variations depending on the selected tissue. Finally, a first qualitative correlation between 11C tumor washout properties and tumor metabolism (via 18F-FDG tracer uptake) was found. PMID:27015269

  11. Production of pure quasi-monochromatic 11C beams for accurate radiation therapy and dose delivery verification

    NASA Astrophysics Data System (ADS)

    Lazzeroni, Marta; Brahme, Anders

    2015-09-01

    In the present study we develop a new technique for the production of clean quasi-monochromatic 11C positron emitter beams for accurate radiation therapy and PET-CT dose delivery imaging and treatment verification. The 11C ion beam is produced by projectile fragmentation using a primary 12C ion beam. The practical elimination of the energy spread of the secondary 11C fragments and other beam contaminating fragments is described. Monte Carlo calculation with the SHIELD-HIT10+ code and analytical methods for the transport of the ions in matter are used in the analysis. Production yields, as well as energy, velocity and magnetic rigidity distributions of the fragments generated in a cylindrical target are scored as a function of the depth within 1 cm thick slices for an optimal target consisting of a fixed 20 cm section of liquid hydrogen followed by a variable thickness section of polyethylene. The wide energy and magnetic rigidity spread of the 11C ion beam can be reduced to values around 1% by using a variable monochromatizing wedge-shaped degrader in the beam line. Finally, magnetic rigidity and particle species selection, as well as discrimination of the particle velocity through a combined Time of Flight and Radio Frequency-driven Velocity filter purify the beam from similar magnetic rigidity contaminating fragments (mainly 7Be and 3He fragments). A beam purity of about 99% is expected by the combined method.

  12. NK cells are necessary for recovery of corneal CD11c+ dendritic cells after epithelial abrasion injury

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mechanisms controlling CD11c(+) MHCII(+) DCs during corneal epithelial wound healing were investigated in a murine model of corneal abrasion. Selective depletion of NKp46(+) CD3- NK cells that normally migrate into the cornea after epithelial abrasion resulted in >85% reduction of the epithelial CD1...

  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. Automated synthesis of radiopharmaceuticals for positron emission tomography: an apparatus for labelling with [11C] methyl iodide (MIASA)

    PubMed Central

    Cork, D. G.; Yamato, H.; Yajima, K.; Hayashi, N.; Sugawara, T.; Kato, S.

    1994-01-01

    A fully automated apparatus for the routine synthesis and formulation of short-lived 11C (t1/2 = 20 min) labelled radiopharmaceuticals for positron emission tomography (PET) has been developed. [11C]Carbon dioxide is converted to [11C]methyl iodide, which can be used to label a wide variety of substrates by methylation at C, N, O, or S electron rich centres. The apparatus, MIASA (methyl iodide automated synthesis apparatus), was designed to operate as part of an automated labelling system in a shielded ‘hot’ laboratory. The apparatus was designed without the size constraints of typical instrumentation used in hot cells, although it is compact where necessary. Ample use of indicators and sensors, together with compact design of the reaction flasks for small dead space and efficient evaporation, led to good reliability and performance. The design of the hardware and software is described in this paper, together with a preparation of 3-N-[11C]methylspiperone as a sterile injectable solution in physiological saline. PMID:18924994

  15. The 11C Project:Measurement of Root Exudation at Elevated CO2 Levels in Low and High Nutrient Solutions

    NASA Astrophysics Data System (ADS)

    Leandre, Verida; Howell, Calvin

    2011-03-01

    Understanding the plant kingdom's mechanisms of resource management in variable environments is integral to predicting how plants will respond to an increase in atmospheric CO2 . The goal of this study is to determine the effects of changing nutrient conditions on the root exudation of barley plants at elevated CO2 levels. The 11 C group at the Triangle Universities Nuclear Laboratory (TUNL) tags various species of plants with short-lived positron-emitting radioisotopes in order to analyze metabolite transport in response to changes in the environment. 11 C is produced at TUNL using a tandem Van de Graaff particle accelerator, then transported from TUNL to the Duke Univ. Phytotron (100m) where plants are labeled with 11 C in a growth chamber. The chamber allows researchers to control the light intensity, air temperature, humidity and concentration of CO2 in the air. The plant absorbs 11 CO2 in a leaf that is placed inside a cuvette through which radioactive 11 CO2 gas flows. The sugars in the labeling leaf are tagged with 11 C and translocated throughout the plant similar to 12 C. Scintillation detectors are used to track the tagged sugars as they are translocated through the plant and exudated from the root into the nutrient solution or 11 CO2 gas is respired by the root. The labeling system, detector arrangement, electronics and data analysis will be described and preliminary results will be presented.

  16. Design of Infusion Schemes for Neuroreceptor Imaging: Application to [11C]Flumazenil-PET Steady-State Study

    PubMed Central

    Feng, Ling; Svarer, Claus; Madsen, Karine; Ziebell, Morten; Dyssegaard, Agnete; Ettrup, Anders; Hansen, Hanne Demant; Lehel, Szabolcs; Yndgaard, Stig; Paulson, Olaf Bjarne; Knudsen, Gitte Moos; Pinborg, Lars Hageman

    2016-01-01

    This study aims at developing a simulation system that predicts the optimal study design for attaining tracer steady-state conditions in brain and blood rapidly. Tracer kinetics was determined from bolus studies and used to construct the system. Subsequently, the system was used to design inputs for bolus infusion (BI) or programmed infusion (PI) experiments. Steady-state quantitative measurements can be made with one short scan and venous blood samples. The GABAA receptor ligand [11C]Flumazenil (FMZ) was chosen for this purpose, as it lacks a suitable reference region. Methods. Five bolus [11C]FMZ-PET scans were conducted, based on which population-based PI and BI schemes were designed and tested in five additional healthy subjects. The design of a PI was assisted by an offline feedback controller. Results. The system could reproduce the measurements in blood and brain. With PI, [11C]FMZ steady state was attained within 40 min, which was 8 min earlier than the optimal BI (B/I ratio = 55 min). Conclusions. The system can design both BI and PI schemes to attain steady state rapidly. For example, subjects can be [11C]FMZ-PET scanned after 40 min of tracer infusion for 40 min with venous sampling and a straight-forward quantification. This simulation toolbox is available for other PET-tracers. PMID:27123457

  17. Experimental Approach to Evaluate the 11C Perfusion and Diffusion in Small Animal Tissues for HadronPET Applications.

    PubMed

    Martínez-Rovira, Immaculada; Boisgard, Raphaël; Pottier, Géraldine; Kuhnast, Bertrand; Jan, Sébastien

    2016-01-01

    The development of a reliable dose monitoring system in hadron therapy is essential in order to control the treatment plan delivery. Positron Emission Tomography (PET) is the only method used in clinics nowadays for quality assurance. However, the accuracy of this method is limited by the loss of signal due to the biological washout processes. Up to the moment, very few studies measured the washout processes and there is no database of washout data as a function of the tissue and radioisotope. One of the main difficulties is related to the complexity of such measurements, along with the limited time slots available in hadron therapy facilities. Thus, in this work, we proposed an alternative in vivo methodology for the measurement and modeling of the biological washout parameters without any radiative devices. It consists in the implementation of a point-like radioisotope source by direct injection on the tissues of interest and its measurement by means of high-resolution preclinical PET systems. In particular, the washout of 11C carbonate radioisotopes was assessed, considering that 11C is is the most abundant β+ emitter produced by carbon beams. 11C washout measurements were performed in several tissues of interest (brain, muscle and 9L tumor xenograf) in rodents (Wistar rat). Results show that the methodology presented is sensitive to the washout variations depending on the selected tissue. Finally, a first qualitative correlation between 11C tumor washout properties and tumor metabolism (via 18F-FDG tracer uptake) was found. PMID:27015269

  18. Determination of Fatty Acid Metabolism with Dynamic 11C-Palmitate Positron Emission Tomography of Mouse Heart In Vivo

    PubMed Central

    Li, Yinlin; Huang, Tao; Zhang, Xinyue; Zhong, Min; Walker, Natalie N.; He, Jiang; Berr, Stuart S.; Keller, Susanna R.; Kundu, Bijoy K.

    2015-01-01

    The goal of this study was to establish a quantitative method for measuring FA metabolism with partial volume (PV) and spill-over (SP) corrections using dynamic 11C-palmitate PET images of mouse heart in vivo. Methods Twenty-minute dynamic 11C-palmitate PET scans of four 18–20 week old male C57BL/6 mice under isoflurane anesthesia were performed using a Focus 120 PET scanner. A model corrected blood input function (MCIF), by which the input function with SP and PV corrections and the metabolic rate constants (k1−k5) are simultaneously estimated from the dynamic 11C-palmitate PET images of mouse hearts in a 4-compartment tracer kinetic model, was used to determine rates of myocardial FA oxidation (MFAO), myocardial FA esterification (MFAE), myocardial FA utilization (MFAU) and myocardial FA uptake (MFAUp). Results The MFAO thus measured in C57BL/6 mice was 375.03±43.83 nmoles/min/g. This compares well with the MFAO measured in perfused working C57BL/6 mouse hearts ex vivo of about 350 nmoles/g/min and 400 nmoles/min/g. Conclusions FA metabolism was measured for the first time in mouse heart in vivo using dynamic 11C-palmitate PET in a 4-compartment tracer kinetic model. MFAO obtained with this model were validated by results previously obtained with mouse hearts ex vivo. PMID:26462138

  19. High fluence laser irradiation induces reactive oxygen species generation in human lung adenocarcinoma cells

    NASA Astrophysics Data System (ADS)

    Wang, Fang; Xing, Da; Chen, Tong-Sheng

    2006-09-01

    Low-power laser irradiation (LPLI) has been used for therapies such as curing spinal cord injury, healing wound et al. Yet, the mechanism of LPLI remains unclear. Our previous study showed that low fluences laser irradiation induces human lung adenocarcinoma cells (ASTC-a-1) proliferation, but high fluences induced apoptosis and caspase-3 activation. In order to study the mechanism of apoptosis induced by high fluences LPLI further, we have measured the dynamics of generation of reactive oxygen species (ROS) using H IIDCFDA fluorescence probes during this process. ASTC-a-1 cells apoptosis was induced by He-Ne laser irradiation at high fluence of 120J/cm2. A confocal laser scanning microscope was used to perform fluorescence imaging. The results demonstrated that high fluence LPLI induced the increase of mitochondria ROS. Our studies contribute to clarify the biological mechanism of high fluence LPLI-induced cell apoptosis.

  20. Constant-Fluence Area Scaling for Laser Propulsion

    SciTech Connect

    Sinko, John E.

    2008-04-28

    A series of experiments was conducted on polyoxymethylene (POM, trade name Delrin registered ) propellants in air at atmospheric pressure. A TEA CO{sub 2} laser with maximum output power up to 20 J was used to deliver 300 ns pulses of 10.6 {mu}m radiation to POM targets. Ablation at a constant fluence and a range of spot areas was achieved by varying combinations of the laser energy and spot size. Relevant empirical scaling laws governing laser propulsion parameters such as the momentum coupling coefficient (C{sub m}) and specific impulse (I{sub sp}) for spot areas within a range of about 0.05-0.25 cm{sup 2} are presented. Experimental measurements of imparted impulse, C{sub m}, I{sub sp}, and ablated mass per pulse were made using dynamic piezoelectric force sensors and a scientific balance. Finally, Schlieren ICCD imaging of shock waves and vapor plumes was performed and analyzed.

  1. Effects of high thermal neutron fluences on Type 6061 aluminum

    SciTech Connect

    Weeks, J.R.; Czajkowski, C.J. ); Farrell, K. )

    1992-01-01

    The control rod drive follower tubes of the High Flux Beam Reactor are contructed from precipitation-hardened 6061-T6 aluminum alloy and they operate in the high thermal neutron flux regions of the core. It is shown that large thermal neutron fluences up to {approximately}4 {times} 10{sup 23} n/cm{sup 2} at 333K cause large increases in tensile strength and relatively modest decreases in tensile elongation while significantly reducing the notch impact toughness at room temperature. These changes are attributed to the development of a fine distribution of precipitates of amorphous silicon of which about 8% is produced radiogenically. A proposed role of thermal-to-fast flux ratio is discussed.

  2. Effects of high thermal neutron fluences on Type 6061 aluminum

    SciTech Connect

    Weeks, J.R.; Czajkowski, C.J.; Farrell, K.

    1992-09-01

    The control rod drive follower tubes of the High Flux Beam Reactor are contructed from precipitation-hardened 6061-T6 aluminum alloy and they operate in the high thermal neutron flux regions of the core. It is shown that large thermal neutron fluences up to {approximately}4 {times} 10{sup 23} n/cm{sup 2} at 333K cause large increases in tensile strength and relatively modest decreases in tensile elongation while significantly reducing the notch impact toughness at room temperature. These changes are attributed to the development of a fine distribution of precipitates of amorphous silicon of which about 8% is produced radiogenically. A proposed role of thermal-to-fast flux ratio is discussed.

  3. The Meteoroid Fluence at Mars Due to Comet Siding Spring

    NASA Technical Reports Server (NTRS)

    Moorhead, Althea V.

    2014-01-01

    Long-period comet C/2013 A1 (Siding Spring) is headed for a close encounter with Mars on 2014 Oct 19. A collision between the comet and the planet has been ruled out, but the comets coma may envelop Mars and its man-made satellites. We present an analytic model of the dust component of cometary comae that describes the spatial distribution of cometary dust and meteoroids and their size distribution. If the coma reaches Mars, we estimate a total incident particle fluence on the planet and its satellites of 0.01 particles per square meter. We compare our model with numerical simulations, data from past comet missions, and recent Siding Spring observations.

  4. Downregulation of Brain Phosphodiesterase Type IV Measured with 11C-(R)-Rolipram Positron Emission Tomography in Major Depressive Disorder

    PubMed Central

    Fujita, Masahiro; Hines, Christina S.; Zoghbi, Sami S.; Mallinger, Alan G.; Dickstein, Leah P.; Liow, Jeih-San; Zhang, Yi; Pike, Victor W.; Drevets, Wayne C.; Innis, Robert B.; Zarate, Carlos A.

    2012-01-01

    Background Phosphodiesterase type IV (PDE4), an important component of the cyclic adenosine monophosphate (cAMP) cascade, selectively metabolizes cAMP in the brain to the inactive monophosphate. Basic studies suggest that PDE4 mediates the effects of several antidepressants. This study sought to quantify the binding of 11C-(R)-rolipram, a PDE4 inhibitor, as an indirect measure of this enzyme’s activity in the brain of individuals with major depressive disorder (MDD) compared with healthy control subjects. Methods 11C-(R)-Rolipram brain positron emission tomography scans were performed in 28 unmedicated MDD subjects and 25 age- and gender-matched healthy control subjects. Patients were moderately depressed and about one half were treatment-naive. 11C-(R)-Rolipram binding in the brain was measured using arterial 11C-(R)-rolipram levels to correct for the influence of cerebral blood flow. Results Major depressive disorder subjects showed a widespread, approximately 20% reduction in 11C-(R)-rolipram binding (p = .002), which was not caused by different volumes of gray matter. Decreased rolipram binding of similar magnitudes was observed in most brain areas. Rolipram binding did not correlate with the severity of depressive or anxiety symptoms. Conclusions This study is the first to demonstrate that brain levels of PDE4, a critical enzyme that regulates cAMP, are decreased in unmedicated individuals with MDD in vivo. These results are in line with human postmortem and rodent studies demonstrating downregulation of the cAMP cascade in MDD and support the hypothesis that agents such as PDE4 inhibitors, which increase activity within the cAMP cascade, may have antidepressant effects. PMID:22677471

  5. Amyloid-β 11C-PiB-PET imaging results from 2 randomized bapineuzumab phase 3 AD trials

    PubMed Central

    Schmidt, Mark E.; Margolin, Richard; Sperling, Reisa; Koeppe, Robert; Mason, Neale S.; Klunk, William E.; Mathis, Chester A.; Salloway, Stephen; Fox, Nick C.; Hill, Derek L.; Les, Andrea S.; Collins, Peter; Gregg, Keith M.; Di, Jianing; Lu, Yuan; Tudor, I. Cristina; Wyman, Bradley T.; Booth, Kevin; Broome, Stephanie; Yuen, Eric; Grundman, Michael; Brashear, H. Robert

    2015-01-01

    Objective: To evaluate the effects of bapineuzumab on brain β-amyloid (Aβ) burden using 11C-Pittsburgh compound B (11C-PiB)-PET. Methods: Two phase 3 clinical trials, 1 each in apolipoprotein APOE ε4 carriers and noncarriers, were conducted in patients with mild to moderate Alzheimer disease dementia. Bapineuzumab, an anti-Aβ monoclonal antibody, or placebo, was administered by IV infusion every 13 weeks for 78 weeks. PET substudies assessed change in brain fibrillar Aβ over 71 weeks using an 11C-PiB-PET standardized uptake value ratio (SUVr) global cortical average (GCA) comprising the average SUVr from 5 cortical regions of interest with cerebellar gray matter as the reference region. Results: A total of 115 carriers and 39 noncarriers were analyzed. The difference (δ) in mean baseline to 71 week change in 11C-PiB-PET GCA between bapineuzumab and placebo was significant in carriers (0.5 mg/kg vs placebo δ = −0.101; p = 0.004) and in pooled analyses of both carriers and noncarriers (0.5 mg/kg vs placebo δ = −0.068; p = 0.027; 1.0 mg/kg vs placebo δ = −0.133; p = 0.028) but not in the noncarrier trial separately. Analyses by individual region of interest and in mild disease yielded findings similar to the main trial results. Conclusions: The 11C-PiB-PET imaging results demonstrated reduction of fibrillar Aβ accumulation in patients with Alzheimer disease treated with bapineuzumab; however, as no clinical benefit was observed, the findings are consistent with the hypotheses that bapineuzumab may not have been initiated early enough in the disease course, the doses were insufficient, or the most critical Aβ species were inadequately targeted. PMID:26208959

  6. Molecular imaging of 1p/19q deletion in oligodendroglial tumours with 11C-methionine positron emission tomography

    PubMed Central

    Iwadate, Yasuo; Shinozaki, Natsuki; Matsutani, Tomoo; Uchino, Yoshio; Saeki, Naokatsu

    2016-01-01

    Objective Chromosome 1p/19q deletion is an established prognostic and predictive marker in the WHO grade III oligodendroglial tumours (OT). To estimate the genetic status preoperatively, the authors investigated the correlation between the uptake of 11C-methionine in positron emission tomography (PET) and the 1p/19q status in grades II and III OT. Methods We retrospectively reviewed 144 patients with gliomas who received 11C-methionine PET. 66 cases with grades II–III oligodendrogliomas or oligoastrocytomas underwent fluorescence in situ hybridisation to determine the 1p/19q status. The tissue uptake of 11C-methionine was expressed as the ratio of the maximum standardised uptake value (SUVmax) in tumour areas to the mean SUV (SUVmean) in the contralateral normal brain (tumour-to-normal tissue (T/N) ratio). Results The T/N ratio in 11C-methionine PET was significantly higher in grade III OT than in grade II tumours. The mean T/N ratio of the grade II tumours without 1p/19q deletion was significantly higher than that of the grade II tumours with 1p/19q deletion (mean 2.67 vs 1.94, respectively; p=0.0457). In grade III tumours, the mean T/N ratio of the tumours without 1p/19q deletion was also significantly higher than that of the tumours with 1p/19q deletion (mean 4.83 vs 3.49, respectively; p=0.0261). The rate of IDH1 mutation was lower and the rate of contrast enhancement on MRIs was higher in the 1p/19q non-deleted OT than those with 1p/19q deletion, which may contribute to the high T/N ratio. Conclusions Among suspected OT, 11C-methionine PET may help us preoperatively discriminate tumours with and without 1p/19q deletion. PMID:26848169

  7. PET studies of binding competition between endogenous dopamine and the D1 radiotracer [11C]NNC 756.

    PubMed

    Abi-Dargham, A; Simpson, N; Kegeles, L; Parsey, R; Hwang, D R; Anjilvel, S; Zea-Ponce, Y; Lombardo, I; Van Heertum, R; Mann, J J; Foged, C; Halldin, C; Laruelle, M

    1999-05-01

    NNC 756 ((+)-8-chloro-5-(2,3-dihydrobenzofuran-7-yl)-7-hydroxy-3-methyl-2,3,4,5- tetrahydro-1H-3-benzazepine) is a new high affinity dopamine (DA) D1 receptor antagonist. Labeled with C-11, it has been used as a PET radiotracer to visualize D1 receptors both in striatal and extrastriatal areas, such as the prefrontal cortex. The goal of this study was to evaluate several methods for derivation of D1 receptor binding potential (BP) with [11C]NNC 756 in baboons, and to use these methods to assess the vulnerability of [11C]NNC 756 binding to competition by endogenous DA. A three-compartment model provided a good fit to PET data acquired following a single bolus injection. BP values obtained with this analysis were in good agreement with values derived from in vitro studies. BP values measured following injection of the potent DA releaser amphetamine (1 mg/kg, n=2) were similar to values measured under control conditions. Kinetic parameters derived from single bolus experiments were used to design a bolus plus continuous infusion administration protocol aimed at achieving a state of sustained binding equilibrium. Injection of amphetamine during sustained equilibrium did not affect [11C]NNC 756 binding. Similar results were observed with another D1 radiotracer, [11C]SCH 23390. Doses of amphetamine used in this study are known to reduce by 20-40% the binding potential of several D2 receptors radiotracers. Therefore, the absence of displacement of [11C]NNC 756 by an endogenous DA surge may indicate important differences between D1 and D2 receptors in vivo, such as differences in proportion of high affinity states not occupied by DA at baseline. These findings may also imply that a simple binding competition model is inadequate to account for the effects of manipulation of endogenous DA levels on the in vivo binding of radiolabeled antagonists.

  8. In vivo visualization of central muscarinic receptors using [11C]quinuclidinyl benzilate and positron emission tomography in baboons.

    PubMed

    Varastet, M; Brouillet, E; Chavoix, C; Prenant, C; Crouzel, C; Stulzaft, O; Bottlaender, M; Cayla, J; Mazière, B; Mazière, M

    1992-03-24

    The muscarinic antagonist, quinuclidinyl benzilate (QNB), labeled with carbon 11 was used as a radioligand to visualize in vivo by positron emission tomography (PET) the central muscarinic acetylcholine receptors (mAChR) in baboons (Papio papio). The binding characteristics of [11C]QNB showed its specific binding to central mAChR. [11C]QNB brain uptake was high in cerebral cortex and striatum, areas that are rich in mAChR, whereas it decreased rapidly in cerebellum, evidencing non-specific binding in this structure that is almost devoid of mAChR. These results are consistent with the known cerebral distribution of mAChR in primates. [11C]QNB specific cerebral binding was enhanced by pretreatment with methyl-QNB, a peripherally acting muscarinic antagonist. Specifically labeled binding sites alone were blocked by prior administration of dexetimide, a muscarinic antagonist. Specific radioactivity was driven out from mAChR-rich regions by atropine and dexetimide, drugs with high affinity for mAChR. This competition was stereospecific since only dexetimide, the pharmacologically active isomer of benzetimide, was able to compete with the radioligand on its binding sites. A relationship between the occupancy of [11C]QNB-labeled receptors by atropine or dexetimide and the concomitant induction of a pharmacological effect was also detected by simultaneous PET scanning and electroencephalographic recording. Since mAChR form an important part of choline receptors in the central nervous system, [11C]QNB appears to be a suitable radiotracer to monitor cerebral physiological or pathological phenomena linked to the cholinergic system in living subjects. PMID:1521561

  9. Increase of bulk optical damage threshold fluences of KDP crystals by laser irradiation and heat treatment

    DOEpatents

    Swain, J.E.; Stokowski, S.E.; Milam, D.; Kennedy, G.C.; Rainer, F.

    1982-07-07

    The bulk optical damage threshold fluence of potassium dihydrogen phosphate (KDP) crystals is increased by irradiating the crystals with laser pulses of duration 1 to 20 nanoseconds of increasing fluence, below the optical damage threshold fluence for untreated crystals, or by baking the crystals for times of the order of 24 hours at temperatures of 110 to 165/sup 0/C, or by a combination of laser irradiation and baking.

  10. A Common Fluence Threshold for First Positive and Second Positive Phototropism in Arabidopsis thaliana1

    PubMed Central

    Janoudi, Abdul; Poff, Kenneth L.

    1990-01-01

    The relationship between the amount of light and the amount of response for any photobiological process can be based on the number of incident quanta per unit time (fluence rate-response) or on the number of incident quanta during a given period of irradiation (fluence-response). Fluence-response and fluence rate-response relationships have been measured for second positive phototropism by seedlings of Arabidopsis thaliana. The fluence-response relationships exhibit a single limiting threshold at about 0.01 micromole per square meter when measured at fluence rates from 2.4 × 10−5 to 6.5 × 10−3 micromoles per square meter per second. The threshold values in the fluence rateresponse curves decrease with increasing time of irradiation, but show a common fluence threshold at about 0.01 micromole per square meter. These thresholds are the same as the threshold of about 0.01 micromole per square meter measured for first positive phototropism. Based on these data, it is suggested that second positive curvature has a threshold in time of about 10 minutes. Moreover, if the times of irradiation exceed the time threshold, there is a single limiting fluence threshold at about 0.01 micromole per square meter. Thus, the limiting fluence threshold for second positive phototropism is the same as the fluence threshold for first positive phototropism. Based on these data, we suggest that this common fluence threshold for first positive and second positive phototropism is set by a single photoreceptor pigment system. PMID:11537470

  11. Heavy Ion Irradiation Fluence Dependence for Single-Event Upsets of NAND Flash Memory

    NASA Technical Reports Server (NTRS)

    Chen, Dakai; Wilcox, Edward; Ladbury, Raymond; Kim, Hak; Phan, Anthony; Seidleck, Christina; LaBel, Kenneth

    2016-01-01

    We investigated the single-event effect (SEE) susceptibility of the Micron 16 nm NAND flash, and found the single-event upset (SEU) cross section varied inversely with fluence. The SEU cross section decreased with increasing fluence. We attribute the effect to the variable upset sensitivities of the memory cells. The current test standards and procedures assume that SEU follow a Poisson process and do not take into account the variability in the error rate with fluence. Therefore, heavy ion irradiation of devices with variable upset sensitivity distribution using typical fluence levels may underestimate the cross section and on-orbit event rate.

  12. No-carrier-added carbon-11-labeled sn-1,2- and sn-1,3-diacylglycerols by (11C)propyl ketene method

    SciTech Connect

    Imahori, Y.; Fujii, R.; Ueda, S.; Ido, T.; Nishino, H.; Moriyama, Y.; Yamamoto, Y.L.; Nakahashi, H. )

    1991-08-01

    This article describes the preparation of sn-1,2-(11C)diacylglycerols and sn-1,3-(11C)diacylglycerols by a no-carrier-added reaction based on a labeling method using (1-11C)propyl ketene, which is one of the most potent acylating agents. (1-11C)Propyl ketene was produced by pyrolytic decomposition of (1-11C)butyric acid and was trapped in pyridine containing L-alpha-palmitoyl-lysophosphatidylcholine, producing L-alpha-palmitoyl-2-(1-11C)butyryl-sn-glycero-3-phosphorylcholine. The authors adopted an enzymatic reaction to remove the phosphorylcholine, in which L-alpha-palmitoyl-2-(1-11C)butyryl-sn-glycero-3-phosphorylcholine was incubated with phospholipase C, hydrolyzing to produce 1-palmitoyl-sn-2-(1-11C)butyrylglycerol. Total synthesis time was about 50 minutes and the specific activity was estimated at 93 GBq/mumol (2.5 Ci/mumol) at end of synthesis. Radiochemical yield was 3.8% based on the trapped 11CO2. sn-1,3-(11C)Diacylglycerol was also synthesized by (1-11C)propyl ketene reaction with 1-palmitoyl-sn-glycerol in a single procedure. The regional brain tissue radioactivities obtained in sn-1,2-(11C)diacylglycerol were higher than those of sn-1,3-(11C)diacylglycerol, and the regional values varied widely. In autoradiography of brain slices from conscious rats, sn-1,2-(11C)diacylglycerol incorporation sites were discretely localized, especially in the amygdala, cerebral cortex, and hippocampus, suggesting that intensive neuronal processing occurred in these areas on the basis of phosphatidylinositol turnover.

  13. Endotoxin-Induced Systemic Inflammation Activates Microglia: [11C]PBR28 Positron Emission Tomography in Nonhuman Primates

    PubMed Central

    Hannestad, Jonas; Gallezot, Jean-Dominique; Schafbauer, Thomas; Lim, Keunpoong; Kloczynski, Tracy; Morris, Evan D.; Carson, Richard E; Ding, Yu-Shin; Cosgrove, Kelly

    2013-01-01

    Microglia play an essential role in many brain diseases. Microglia are activated by local tissue damage or inflammation, but systemic inflammation can also activate microglia. An important clinical question is whether the effects of systemic inflammation on microglia mediates the deleterious effects of systemic inflammation in diseases such as Alzheimer's dementia, multiple sclerosis, and stroke. Positron Emission Tomography (PET) imaging with ligands that bind to Translocator Protein (TSPO) can be used to detect activated microglia. The aim of this study was to evaluate whether the effect of systemic inflammation on microglia could be measured with PET imaging in nonhuman primates, using the TSPO ligand [11C]PBR28. Methods Six female baboons (Papio anubis) were scanned before and at 1 h and/or 4h and/or 22h after intravenous administration of E. coli lipopolysaccharide (LPS; 0.1 mg/kg), which induces systemic inflammation. Regional time-activity data from regions of interest (ROIs) were fitted to the two-tissue compartmental model, using the metabolite-corrected arterial plasma curve as input function. Total volume of distribution (VT) of [11C]PBR28 was used as a measure of total ligand binding. The primary outcome was change in VT from baseline. Serum levels of tumor necrosis factor alpha (TNFα), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and interleukin-8 (IL-8) were used to assess correlations between systemic inflammation and microglial activation. In one baboon, immunohistochemistry was used to identify cells expressing TSPO. Results LPS administration increased [11C]PBR28 binding (F(3,6)=5.1, p=.043) with a 29±16 % increase at 1h (n = 4) and a 62±34% increase at 4h (n = 3) post-LPS. There was a positive correlation between serum IL-1β and IL-6 levels and the increase in [11C]PBR28 binding. TSPO immunoreactivity occurred almost exclusively in microglia and rarely in astrocytes. Conclusion In the nonhuman-primate brain, LPS-induced systemic

  14. Synthesis and PET studies of [11C-cyano]letrozole (Femara®), an aromatase inhibitor drug

    PubMed Central

    Kil, Kun-Eek; Biegon, Anat; Ding, Yu-Shin; Fischer, Andre; Ferrieri, Richard A.; Kim, Sung Won; Pareto, Deborah; Schueller, Michael J.; Fowler, Joanna S.

    2011-01-01

    Introduction Aromatase, a member of the cytochrome P450 family, converts androgens such as androstenedione and testosterone to estrone and estradiol respectively. Letrozole (1-[bis-(4-cyanophenyl)methyl]-1H-1,2,4-triazole, Femara®) is a high affinity aromatase inhibitor (Ki=11.5 nM) which has FDA approval for breast cancer treatment. Here we report the synthesis of carbon-11 labeled letrozole and its assessment as a radiotracer for brain aromatase in the baboon. Methods Letrozole and its precursor (4-[(4-bromophenyl)-1H-1,2,4-triazol-1-ylmethyl]benzonitrile, 3) were prepared in two-step syntheses from 4-cyanobenzyl bromide and 4-bromobenzyl bromide, respectively. The [11C]cyano group was introduced via the tetrakis(triphenylphosphine)palladium(0) catalyzed coupling of [11C]cyanide with the bromo-precursor (3). PET studies in the baboon brain were carried out to assess regional distribution and kinetics, reproducibility of repeated measures and saturability. The free fraction of letrozole in the plasma, log D, and the [11C-cyano]letrozole fraction in the arterial plasma were also measured. Results [11C-cyano]Letrozole was synthesized in 60 min with a radiochemical yield of 79–80%, with a radiochemical purity greater than 98% and a specific activity of 4.16±2.21 Ci/μmol at the end of bombardment (n=4). PET studies in the baboon revealed initial rapid and high uptake and initial rapid clearance followed by slow clearance of carbon-11 from the brain with no difference between brain regions. The brain kinetics was not affected by co-injection of unlabeled letrozole (0.1 mg/kg). The free fraction of letrozole in plasma was 48.9% and log D was 1.84. Conclusion [11C-cyano]Letrozole is readily synthesized via a palladium catalyzed coupling reaction with [11C]cyanide. Although it is unsuitable as a PET radiotracer for brain aromatase as revealed by the absence of regional specificity and saturability in brain regions, such as amygdala, which are known to contain

  15. Effects of salinity build-up on the performance of an anaerobic membrane bioreactor regarding basic water quality parameters and removal of trace organic contaminants.

    PubMed

    Song, Xiaoye; McDonald, James; Price, William E; Khan, Stuart J; Hai, Faisal I; Ngo, Hao H; Guo, Wenshan; Nghiem, Long D

    2016-09-01

    The effects of elevated inorganic salt concentration on anaerobic membrane bioreactor (AnMBR) treatment regarding basic biological performance and trace organic contaminant (TrOC) removal were investigated. A set of 33 TrOCs were selected to represent pharmaceuticals, steroids, and pesticides in municipal wastewater. Results show potential adverse effects of increase in the bioreactor salinity to 15g/L (as NaCl) on the performance of AnMBR with respect to chemical oxygen demand removal, biogas production, and the removal of most hydrophilic TrOCs. Furthermore, a decrease in biomass production was observed as salinity in the bioreactor increased. The removal of most hydrophobic TrOCs was high and was not significantly affected by salinity build-up in the bioreactor. The accumulation of a few persistent TrOCs in the sludge phase was observed, but such accumulation did not vary significantly as salinity in the bioreactor increased. PMID:27262094

  16. Essential role of the electroneutral Na+-HCO3- cotransporter NBCn1 in murine duodenal acid-base balance and colonic mucus layer build-up in vivo.

    PubMed

    Singh, Anurag Kumar; Xia, Weiliang; Riederer, Brigitte; Juric, Marina; Li, Junhua; Zheng, Wen; Cinar, Ayhan; Xiao, Fang; Bachmann, Oliver; Song, Penghong; Praetorius, Jeppe; Aalkjaer, Christian; Seidler, Ursula

    2013-04-15

    Duodenal epithelial cells need efficient defence strategies during gastric acidification of the lumen, while colonic mucosa counteracts damage by pathogens by building up a bacteria-free adherent mucus layer. Transport of HCO3(-) is considered crucial for duodenal defence against acid as well as for mucus release and expansion, but the transport pathways involved are incompletely understood. This study investigated the significance of the electroneutral Na(+)-HCO3(-) cotransporter NBCn1 for duodenal defence against acid and colonic mucus release. NBCn1 was localized to the basolateral membrane of duodenal villous enterocytes and of colonic crypt cells, with predominant expression in goblet cells. Duodenal villous enterocyte intracellular pH was studied before and during a luminal acid load by two-photon microscopy in exteriorized, vascularly perfused, indicator (SNARF-1 AM)-loaded duodenum of isoflurane-anaesthetized, systemic acid-base-controlled mice. Acid-induced HCO3(-) secretion was measured in vivo by single-pass perfusion and pH-stat titration. After a luminal acid load, NBCn1-deficient duodenocytes were unable to recover rapidly from intracellular acidification and could not respond adequately with protective HCO3(-) secretion. In the colon, build-up of the mucus layer was delayed, and a decreased thickness of the adherent mucus layer was observed, suggesting that basolateral HCO3(-) uptake is essential for optimal release of mucus. The electroneutral Na(+)-HCO3(-) cotransporter NBCn1 displays a differential cellular distribution in the murine intestine and is essential for HCO3(-)-dependent mucosal protective functions, such as recovery of intracellular pH and HCO3(-) secretion in the duodenum and secretion of mucus in the colon.

  17. Comparative evaluation of microleakage in Class II restorations using open vs. closed centripetal build-up techniques with different lining materials

    PubMed Central

    Sawani, Shefali; Arora, Vipin; Jaiswal, Shikha; Nikhil, Vineeta

    2014-01-01

    Background: Evaluation of microleakage is important for assessing the success of new restorative materials and methods. Aim and Objectives: Comparative evaluation of microleakage in Class II restorations using open vs. closed centripetal build-up techniques with different lining materials. Materials and Methods: Standardized mesi-occlusal (MO) and distoocclusal (DO) Class II tooth preparations were preparedon 53 molars and samples were randomly divided into six experimental groups and one control group for restorations. Group 1: Open-Sandwich technique (OST) with flowable composite at the gingival seat. Group 2: OST with resin-modified glass ionomer cement (RMGIC) at the gingival seat. Group 3: Closed-Sandwich technique (CST) with flowable composite at the pulpal floor and axial wall. Group 4: CST with RMGIC at the pulpal floor and axial wall. Group 5: OST with flowable composite at the pulpal floor, axial wall, and gingival seat. Group 6: OST with RMGIC at the pulpal floor, axial wall, and gingival seat. Group 7: Control — no lining material, centripetal technique only. After restorations and thermocycling, apices were sealed and samples were immersed in 0.5% basic fuchsin dye. Sectioning was followed by stereomicroscopic evaluation. Results: Results were analyzed using Post Hoc Bonferroni test (statistics is not a form of tabulation). Cervical scores of control were more than the exprimental groups (P < 0.05). Less microleakage was observed in CST than OST in all experimental groups (P < 0.05). However, insignificant differences were observed among occlusal scores of different groups (P > 0.05). Conclusion: Class II composite restorations with centripetal build-up alone or when placed with CST reduces the cervical microleakage when compared to OST. PMID:25125847

  18. Clinicopathologic and 11C-Pittsburgh compound B implications of Thal amyloid phase across the Alzheimer's disease spectrum.

    PubMed

    Murray, Melissa E; Lowe, Val J; Graff-Radford, Neill R; Liesinger, Amanda M; Cannon, Ashley; Przybelski, Scott A; Rawal, Bhupendra; Parisi, Joseph E; Petersen, Ronald C; Kantarci, Kejal; Ross, Owen A; Duara, Ranjan; Knopman, David S; Jack, Clifford R; Dickson, Dennis W

    2015-05-01

    Thal amyloid phase, which describes the pattern of progressive amyloid-β plaque deposition in Alzheimer's disease, was incorporated into the latest National Institute of Ageing - Alzheimer's Association neuropathologic assessment guidelines. Amyloid biomarkers (positron emission tomography and cerebrospinal fluid) were included in clinical diagnostic guidelines for Alzheimer's disease dementia published by the National Institute of Ageing - Alzheimer's Association and the International Work group. Our first goal was to evaluate the correspondence of Thal amyloid phase to Braak tangle stage and ante-mortem clinical characteristics in a large autopsy cohort. Second, we examined the relevance of Thal amyloid phase in a prospectively-followed autopsied cohort who underwent ante-mortem (11)C-Pittsburgh compound B imaging; using the large autopsy cohort to broaden our perspective of (11)C-Pittsburgh compound B results. The Mayo Clinic Jacksonville Brain Bank case series (n = 3618) was selected regardless of ante-mortem clinical diagnosis and neuropathologic co-morbidities, and all assigned Thal amyloid phase and Braak tangle stage using thioflavin-S fluorescent microscopy. (11)C-Pittsburgh compound B studies from Mayo Clinic Rochester were available for 35 participants scanned within 2 years of death. Cortical (11)C-Pittsburgh compound B values were calculated as a standard uptake value ratio normalized to cerebellum grey/white matter. In the high likelihood Alzheimer's disease brain bank cohort (n = 1375), cases with lower Thal amyloid phases were older at death, had a lower Braak tangle stage, and were less frequently APOE-ε4 positive. Regression modelling in these Alzheimer's disease cases, showed that Braak tangle stage, but not Thal amyloid phase predicted age at onset, disease duration, and final Mini-Mental State Examination score. In contrast, Thal amyloid phase, but not Braak tangle stage or cerebral amyloid angiopathy predicted (11)C-Pittsburgh compound B

  19. Optimization of [(11)C]raclopride positron emission tomographic rat studies: comparison of methods for image quantification.

    PubMed

    Torrent, Elia; Farré, Magí; Abasolo, Ibane; Millan, Olga; Llop, Jordi; Gispert, Juan Domingo; Ruiz, Alba; Pareto, Deborah

    2013-06-01

    The goal of this study was to compare different quantification approaches and reconstruction methods to estimate the binding potential in [11C]raclopride studies in rats. The final aim was to determine if the results obtained with short-acquisition scanning were comparable to the results obtained with long-acquistion (conventional) scanning. We analyzed two rat data sets: a baseline versus a pretreatment study (with cold raclopride) and a young versus an old animal group comparison. The study results support the contention that optimization of [11C]raclopride positron emission tomographic studies in rats by shortening the acquisition time is feasible. In addition, filtered backprojection is recommended as a reconstruction algorithm, although iterative methods may be more sensitive to detect within-group differences.

  20. Clinicopathologic and 11C-Pittsburgh compound B implications of Thal amyloid phase across the Alzheimer's disease spectrum.

    PubMed

    Murray, Melissa E; Lowe, Val J; Graff-Radford, Neill R; Liesinger, Amanda M; Cannon, Ashley; Przybelski, Scott A; Rawal, Bhupendra; Parisi, Joseph E; Petersen, Ronald C; Kantarci, Kejal; Ross, Owen A; Duara, Ranjan; Knopman, David S; Jack, Clifford R; Dickson, Dennis W

    2015-05-01

    Thal amyloid phase, which describes the pattern of progressive amyloid-β plaque deposition in Alzheimer's disease, was incorporated into the latest National Institute of Ageing - Alzheimer's Association neuropathologic assessment guidelines. Amyloid biomarkers (positron emission tomography and cerebrospinal fluid) were included in clinical diagnostic guidelines for Alzheimer's disease dementia published by the National Institute of Ageing - Alzheimer's Association and the International Work group. Our first goal was to evaluate the correspondence of Thal amyloid phase to Braak tangle stage and ante-mortem clinical characteristics in a large autopsy cohort. Second, we examined the relevance of Thal amyloid phase in a prospectively-followed autopsied cohort who underwent ante-mortem (11)C-Pittsburgh compound B imaging; using the large autopsy cohort to broaden our perspective of (11)C-Pittsburgh compound B results. The Mayo Clinic Jacksonville Brain Bank case series (n = 3618) was selected regardless of ante-mortem clinical diagnosis and neuropathologic co-morbidities, and all assigned Thal amyloid phase and Braak tangle stage using thioflavin-S fluorescent microscopy. (11)C-Pittsburgh compound B studies from Mayo Clinic Rochester were available for 35 participants scanned within 2 years of death. Cortical (11)C-Pittsburgh compound B values were calculated as a standard uptake value ratio normalized to cerebellum grey/white matter. In the high likelihood Alzheimer's disease brain bank cohort (n = 1375), cases with lower Thal amyloid phases were older at death, had a lower Braak tangle stage, and were less frequently APOE-ε4 positive. Regression modelling in these Alzheimer's disease cases, showed that Braak tangle stage, but not Thal amyloid phase predicted age at onset, disease duration, and final Mini-Mental State Examination score. In contrast, Thal amyloid phase, but not Braak tangle stage or cerebral amyloid angiopathy predicted (11)C-Pittsburgh compound B

  1. Unstable nuclei in coherent dissociation of relativistic nuclei 7,9Be, 10B and 10,11C

    NASA Astrophysics Data System (ADS)

    Artemenkov, D. A.; Bradnova, V.; Firu, E.; Kornegrutsa, N. K.; Haiduc, M.; Mamatkulov, K. Z.; Kattabekov, R. R.; Neagu, A.; Rukoyatkin, P. A.; Rusakova, V. V.; Sarkisyan, V. R.; Stanoeva, R.; Zaitsev, A. A.; Zarubin, P. I.; Zarubina, I. G.

    2016-06-01

    Contribution of the unstable nuclei 7Be, 8Be and ®B into coherent dissociation events (“white” stars) of relativistic nuclei 7,9Be, 10B and 10,11C is under study on the basis of a nuclear track emulsion exposed to beams of the JINR Nuclotron. Distributions over the opening angle of α-pairs indicate to a simultaneous presence of virtual 8Beg.s. and 8Be2+ states in the ground states of the 9Be and 10C nuclei. The core 9B is manifested in the 10C nucleus with a probability of (30 ± 4)%, Selection of the 10C “white” stars accompanied by 8Beg.s. (9B) leads to the appearance in the excitation energy distribution of 2α2p “quartets” of the distinct peak with a maximum at 4.1 ± 0.3 MeV. 8Beg.s. decays are presented in 21% 2He + 2H and 19% in the 3He of the all 11C “white” stars. 9Bg.s. decays are identified in “white” stars 11C → 2He + 2H constituting 14% of the 11C “white” stars. The 9B nucleus. is manifested in the “white” stars 10B → 2He + 2H with a probability of (9 ± 1)%. For the 10B case yield of 8Beg.s. nuclei with the respect to 9B is about a factor of 3 higher than 9B.

  2. Increased in vivo glial activation in patients with amyotrophic lateral sclerosis: Assessed with [11C]-PBR28

    PubMed Central

    Zürcher, Nicole R.; Loggia, Marco L.; Lawson, Robert; Chonde, Daniel B.; Izquierdo-Garcia, David; Yasek, Julia E.; Akeju, Oluwaseun; Catana, Ciprian; Rosen, Bruce R.; Cudkowicz, Merit E.; Hooker, Jacob M.; Atassi, Nazem

    2015-01-01

    Evidence from human post mortem, in vivo and animal model studies implicates the neuroimmune system and activated microglia in the pathology of amyotrophic lateral sclerosis. The study aim was to further evaluate in vivo neuroinflammation in individuals with amyotrophic lateral sclerosis using [11C]-PBR28 positron emission tomography. Ten patients with amyotrophic lateral sclerosis (seven males, three females, 38–68 years) and ten age- and [11C]-PBR28 binding affinity-matched healthy volunteers (six males, four females, 33–65 years) completed a positron emission tomography scan. Standardized uptake values were calculated from 60 to 90 min post-injection and normalized to whole brain mean. Voxel-wise analysis showed increased binding in the motor cortices and corticospinal tracts in patients with amyotrophic lateral sclerosis compared to healthy controls (pFWE < 0.05). Region of interest analysis revealed increased [11C]-PBR28 binding in the precentral gyrus in patients (normalized standardized uptake value = 1.15) compared to controls (1.03, p < 0.05). In patients those values were positively correlated with upper motor neuron burden scores (r = 0.69, p < 0.05), and negatively correlated with the amyotrophic lateral sclerosis functional rating scale (r = –0.66, p < 0.05). Increased in vivo glial activation in motor cortices, that correlates with phenotype, complements previous histopathological reports. Further studies will determine the role of [11C]-PBR28 as a marker of treatments that target neuroinflammation. PMID:25685708

  3. Expression of CD11c and EMR2 on neutrophils: potential diagnostic biomarkers for sepsis and systemic inflammation.

    PubMed

    Lewis, S M; Treacher, D F; Edgeworth, J; Mahalingam, G; Brown, C S; Mare, T A; Stacey, M; Beale, R; Brown, K A

    2015-11-01

    There is a need for cellular biomarkers to differentiate patients with sepsis from those with the non-infectious systemic inflammatory response syndrome (SIRS). In this double-blind study we determined whether the expression of known (CD11a/b/c, CD62L) and putative adhesion molecules [CD64, CD97 and epidermal growth factor (EGF)-like molecule containing mucin-like hormone receptor (EMR2)] on blood neutrophils could serve as useful biomarkers of infection and of non-infectious SIRS in critically ill patients. We studied 103 patients with SIRS, 83 of whom had sepsis, and 50 healthy normal subjects, using flow cytometry to characterize neutrophils phenotypically in whole blood samples. Patients with SIRS had an increased prevalence of neutrophils expressing CD11c, CD64 and EMR2 in comparison with healthy subjects (P < 0.001), but normal expression of CD11a, CD11b, CD62L and CD97. An increase in the percentage of neutrophils bearing CD11c was associated with sepsis, EMR2 with SIRS and CD64 with sepsis and SIRS. Neutrophils expressing CD11c had the highest sensitivity (81%) and specificity (80%) for the detection of sepsis, and there was an association between the percentage of neutrophils expressing EMR2 and the extent of organ failure (P < 0.05). Contrary to other reports, we did not observe an abnormal expression of CD11b or CD62L on neutrophils from patients with SIRS, and suggest that this discrepancy is due to differences in cell processing protocols. We propose that blood neutrophils expressing CD11c and EMR2 be considered as potential biomarkers for sepsis and SIRS, respectively.

  4. Serotonin 2A Receptors in Obsessive-Compulsive Disorder: a Positron Emission Tomography Study with [11C]MDL 100907

    PubMed Central

    Simpson, H. Blair; Slifstein, Mark; Bender, James; Xu, Xiaoyan; Hackett, Elizabeth; Maher, Michael J.; Abi-Dargham, Anissa

    2014-01-01

    Background Serotonergic abnormalities are hypothesized to contribute to obsessive-compulsive disorder (OCD). This study used positron emission tomography (PET) with the radioligand [11C]MDL 100907 to examine whether the distribution of one of the serotonin receptors, the 5-HT2A receptor, is altered in OCD. Methods Nineteen OCD subjects, free of psychiatric medications and depression, and 19 matched healthy controls underwent PET scans following injection of [11C]MDL 100907. Total distribution volumes (VT) were derived by kinetic analysis using the arterial input function. Two measures of 5-HT2A availability were computed (BPND and BPP). Groups were compared using a region of interest (ROI) analysis and voxelwise analysis of spatially normalized parametric maps. ROIs included cortical regions (orbitofrontal, dorsolateral prefrontal, medial prefrontal, anterior cingulate, temporal, parietal, occipital, and insular cortex) and limbic regions (entorhinal cortex, parahippocampal gyrus, and medial temporal lobe). Results No significant group differences were observed in [11C]MDL 100907 BPND or BPP in the ROIs or in the voxelwise analysis of BPND maps. There was a significant correlation in the orbitofrontal cortex between [11C] MDL 100907 binding and age of onset, with earlier age of onset associated with higher binding. Conclusions In contrast to prior reports, people with OCD (free of psychiatric medications and depression) are not characterized as a group by major changes in 5-HT2A availability in cortical or limbic brain regions. Further research is warranted to examine potential differences in 5-HT2A availability between early and late onset OCD and to assess 5-HT2A function in relation to other neurotransmitter systems implicated in OCD. PMID:21855857

  5. Increased in vivo glial activation in patients with amyotrophic lateral sclerosis: assessed with [(11)C]-PBR28.

    PubMed

    Zürcher, Nicole R; Loggia, Marco L; Lawson, Robert; Chonde, Daniel B; Izquierdo-Garcia, David; Yasek, Julia E; Akeju, Oluwaseun; Catana, Ciprian; Rosen, Bruce R; Cudkowicz, Merit E; Hooker, Jacob M; Atassi, Nazem

    2015-01-01

    Evidence from human post mortem, in vivo and animal model studies implicates the neuroimmune system and activated microglia in the pathology of amyotrophic lateral sclerosis. The study aim was to further evaluate in vivo neuroinflammation in individuals with amyotrophic lateral sclerosis using [(11)C]-PBR28 positron emission tomography. Ten patients with amyotrophic lateral sclerosis (seven males, three females, 38-68 years) and ten age- and [(11)C]-PBR28 binding affinity-matched healthy volunteers (six males, four females, 33-65 years) completed a positron emission tomography scan. Standardized uptake values were calculated from 60 to 90 min post-injection and normalized to whole brain mean. Voxel-wise analysis showed increased binding in the motor cortices and corticospinal tracts in patients with amyotrophic lateral sclerosis compared to healthy controls (p FWE < 0.05). Region of interest analysis revealed increased [(11)C]-PBR28 binding in the precentral gyrus in patients (normalized standardized uptake value = 1.15) compared to controls (1.03, p < 0.05). In patients those values were positively correlated with upper motor neuron burden scores (r = 0.69, p < 0.05), and negatively correlated with the amyotrophic lateral sclerosis functional rating scale (r = -0.66, p < 0.05). Increased in vivo glial activation in motor cortices, that correlates with phenotype, complements previous histopathological reports. Further studies will determine the role of [(11)C]-PBR28 as a marker of treatments that target neuroinflammation.

  6. Involvement of SOCS3 in regulation of CD11c+ dendritic cell-derived osteoclastogenesis and severe alveolar bone loss.

    PubMed

    Zhang, Xiaoxia; Alnaeeli, Mawadda; Singh, Bhagirath; Teng, Yen-Tung A

    2009-05-01

    To investigate the role of suppressor of cytokine signaling (SOCS) molecules in periodontal immunity and RANKL-mediated dendritic cell (DC)-associated osteoclastogenesis, we analyzed SOCS expression profiles in CD4(+) T cells and the effect of SOCS3 expression in CD11c(+) DCs during periodontal inflammation-induced osteoclastogenesis and bone loss in nonobese diabetic (NOD) versus humanized NOD/SCID mice. Our results of ex vivo and in vitro analyses showed that (i) there is significantly higher SOCS3 expression associated with RANKL(+) T-cell-mediated bone loss in correlation with increased CD11c(+) DC-mediated osteoclastogenesis; (ii) the transfection of CD11c(+) DC using an adenoviral vector carrying a dominant negative SOCS3 gene significantly abrogates TRAP and bone-resorptive activity; and (iii) inflammation-induced TRAP expression, bone resorption, and SOCS3 activity are not associated with any detectable change in the expression levels of TRAF6 and mitogen-activated protein kinase signaling adaptors (i.e., Erk, Jnk, p38, and Akt) in RANKL(+) T cells. We conclude that SOCS3 plays a critical role in modulating cytokine signaling involved in RANKL-mediated DC-derived osteoclastogenesis during immune interactions with T cells and diabetes-associated severe inflammation-induced alveolar bone loss. Therefore, the development of SOCS3 inhibitors may have therapeutic potential as the target to halt inflammation-induced bone loss under pathological conditions in vivo. PMID:19255186

  7. In vivo imaging of brain aromatase in female baboons: [11C]vorozole kinetics and effect of the menstrual cycle.

    PubMed

    Pareto, Deborah; Biegon, Anat; Alexoff, David; Carter, Pauline; Shea, Coreen; Muench, Lisa; Xu, Youwen; Fowler, Joanna S; Kim, Sunny W; Logan, Jean

    2013-01-01

    The aim of this work was to quantify the brain distribution of the enzyme aromatase in the female baboon with positron emission tomography and the tracer [11C]vorozole using three different quantification methods for estimating the total distribution volume (V(T)): a graphical method, compartment modeling, and a tissue to plasma ratio. The graphical model and the compartment modeling gave similar estimates to the data and similar values (correlation R  =  .988; p  =  .0001). [11C]Vorozole shows a rapid uptake by the brain followed by a relatively constant accumulation, suggesting the possibility of using the tissue to plasma ratio as an estimate of V(T). The highest uptake of [11C]vorozole in the baboon brain was measured in the amygdala, followed by the preoptic area and hypothalamus, basal ganglia, and cortical areas. Pretreatment studies with vorozole or letrozole showed a generalized decrease in brain accumulation and V(T). The results suggested that the physiologic changes in gonadal hormone levels accompanying the menstrual cycle had a significant effect on brain aromatase V(T).

  8. Building up rhetorical structure trees

    SciTech Connect

    Marcu, D.

    1996-12-31

    I use the distinction between the nuclei and the satellites that pertain to discourse relations to introduce a compositionality criterion for discourse trees. I provide a first-order formalization of rhetorical structure trees and, on its basis, I derive an algorithm that constructs all the valid rhetorical trees that can be associated with a given discourse.

  9. Comparison of Fluence-Response Relationships of Phototropism in Light- and Dark-Grown Buckwheat 1

    PubMed Central

    Ellis, Richard J.

    1987-01-01

    Fluence-response relationships of phototropism in light- and dark-grown buckwheat (Fagopyrum esculentum Moench.) were compared using systematically varied fluence rates and irradiation times of unilateral monochromatic blue light. Etiolated seedlings respond to most fluence rates in a tri-phasic manner. Phase one differs from classic first positive in that reciprocity is not observed and the peak occurs at a wide variety of fluences, often orders of magnitude less than those characteristic of first positive. Light-grown plants display this pattern only when stimulated by low fluence rates. Phase three is an ascending arm directly related to irradiance time and is comparable to classic second positive. Phase two is a nearly indifferent zone separating phases one and three. At the lowest fluence rates, the maximal observed curvature is greater for dark-grown than for light-grown plants and the former curve more in response to short (2-second) exposures than do the latter. At the highest fluence rates, the maximal observed curvature is much greater for light-grown than for dark-grown seedlings, particularly at irradiation times of 2 to 3 minutes or more. Tropic curvatures correlate positively with increasing fluence rate up to some inflection range, above which the relationship becomes negative. This inflection range is approximately two orders of magnitude higher for light-grown plants. PMID:16665761

  10. Neutron fluence depth profiles in water phantom on epithermal beam of LVR-15 research reactor.

    PubMed

    Viererbl, L; Klupak, V; Lahodova, Z; Marek, M; Burian, J

    2010-01-01

    Horizontal channel with epithermal neutron beam at the LVR-15 research reactor is used mainly for boron neutron capture therapy. Neutron fluence depth profiles in a water phantom characterise beam properties. The neutron fluence (approximated by reaction rates) depth profiles were measured with six different types of activation detectors. The profiles were determined for thermal, epithermal and fast neutrons.

  11. Comparison of fluence-response relationships of phototropism in light- and dark-grown buckwheat.

    PubMed

    Ellis, R J

    1987-11-01

    Fluence-response relationships of phototropism in light- and dark-grown buckwheat (Fagopyrum esculentum Moench.) were compared using systematically varied fluence rates and irradiation times of unilateral monochromatic blue light. Etiolated seedlings respond to most fluence rates in a tri-phasic manner. Phase one differs from classic first positive in that reciprocity is not observed and the peak occurs at a wide variety of fluences, often orders of magnitude less than those characteristic of first positive. Light-grown plants display this pattern only when stimulated by low fluence rates. Phase three is an ascending arm directly related to irradiance time and is comparable to classic second positive. Phase two is a nearly indifferent zone separating phases one and three. At the lowest fluence rates, the maximal observed curvature is greater for dark-grown than for light-grown plants and the former curve more in response to short (2-second) exposures than do the latter. At the highest fluence rates, the maximal observed curvature is much greater for light-grown than for dark-grown seedlings, particularly at irradiation times of 2 to 3 minutes or more. Tropic curvatures correlate positively with increasing fluence rate up to some inflection range, above which the relationship becomes negative. This inflection range is approximately two orders of magnitude higher for light-grown plants.

  12. Synthesis and tissue biodistribution of [{omega}-{sup 11}C]palmitic acid. A novel PET imagining agent for cardiac fatty acid metabolism

    SciTech Connect

    Buckman, B.O.; VanBrocklin, H.F.; Katzenellenbogen, J.A.; Dence, C.S.; Bergmann, S.R.; Welch, M.J.

    1994-12-31

    In order to diagnose patients with medium-chain acyl-CoA dehydrogenase deficiency with a noninvasive diagnostic technique such as positron emission tomography, they have developed a synthesis of [{omega}-{sup 11}C]palmitic acid. The radiochemical synthesis was achieved by coupling an alkylfuran Grignard reagent (7) with [{sup 11}C]methyl iodide, followed by rapid oxidative cleavage of the furan ring to the carboxylate using ruthenium tetraoxide. Tissue biodistribution studies in rags comparing [{omega}-{sup 11}C]palmitic acid and [1-{sup 11}C]palmitic acid show that the %ID/g and %ID/organ in the heart tissue after administration of [{omega}-{sup 11}C]palmitic acid is approximately 50% greater than after administration of [1-{sup 11}C]palmitic acid, due to the diminished metabolism of the [{omega}-{sup 11}C]palmitic acid. These studies show as well, low uptake in nontarget tissues (blood, lung, kidney, and muscle). PET images of a dog heart obtained after administration of [{omega}-{sup 11}C]- and [1-{sup 11}C]palmitic acid show virtually identical uptake and distribution in the myocardium. The differing cardiac washout of labeled palmitates measured by dynamic PET studies may allow diagnosis of disorders in cardiac fatty acid metabolism.

  13. Low-fluence CO2 laser irradiation decreases enamel solubility

    NASA Astrophysics Data System (ADS)

    Esteves-Oliveira, M.; Apel, C.; Gutknecht, N.; Velloso, W. F.; Cotrim, M. E. B.; Eduardo, C. P.; Zezell, D. M.

    2008-04-01

    This study investigated whether subablative-pulsed CO2 laser (10.6 μm) irradiation, using fluences lower than 1 J/cm2, was capable of reducing enamel acid solubility. Fifty-one samples of bovine dental enamel were divided into three groups: control group, which was not irradiated (CG); group laser A (LA) irradiated with 0.3 J/cm2; and group laser B (LB) irradiated with 0.7 J/cm2. After irradiation, the samples were subjected to demineralization in an acetate buffer solution and were then analyzed by SEM. A finite-element model was used to calculate the temperature increase. The calcium and phosphorous content in the demineralization solution were measured with an ICP-OES. ANOVA and the t-test pairwise comparison ( p < 0.016) revealed that LB showed significantly lower mean Ca and P content values in the demineralization solution than other groups. A reduction in the enamel solubility can be obtained with pulsed CO2 laser irradiation (0.7 J/cm2, 135 mJ/pulse, 74 Hz, 100 μs) without any surface photomodification and a less than 2°C temperature increase at a 3-mm depth from the surface.

  14. Fluence thresholds for grazing incidence hard x-ray mirrors

    SciTech Connect

    Aquila, A.; Ozkan, C.; Sinn, H.; Tschentscher, T.; Mancuso, A. P.; Gaudin, J.; Sobierajski, R.; Klepka, M. T.; Dłużewski, P.; Morawiec, K.; Störmer, M.; Bajt, S.; Ohashi, H.; Koyama, T.; Tono, K.; Inubushi, Y. [RIKEN and others

    2015-06-15

    X-ray Free Electron Lasers (XFELs) have the potential to contribute to many fields of science and to enable many new avenues of research, in large part due to their orders of magnitude higher peak brilliance than existing and future synchrotrons. To best exploit this peak brilliance, these XFEL beams need to be focused to appropriate spot sizes. However, the survivability of X-ray optical components in these intense, femtosecond radiation conditions is not guaranteed. As mirror optics are routinely used at XFEL facilities, a physical understanding of the interaction between intense X-ray pulses and grazing incidence X-ray optics is desirable. We conducted single shot damage threshold fluence measurements on grazing incidence X-ray optics, with coatings of ruthenium and boron carbide, at the SPring-8 Angstrom compact free electron laser facility using 7 and 12 keV photon energies. The damage threshold dose limits were found to be orders of magnitude higher than would naively be expected. The incorporation of energy transport and dissipation via keV level energetic photoelectrons accounts for the observed damage threshold.

  15. Reference Materials for Reactor Neutron Fluence Rate and Temperature Measurements

    NASA Astrophysics Data System (ADS)

    Ingelbrecht, C.

    2003-06-01

    Certified reference materials are distributed by the European Commission through the BCR® programme (over 500 CRMs) including a series of activation and fission monitor materials originally proposed by the Euratom Working Group on Reactor Dosimetry. The current range (18 CRMs) includes materials to cover the complete energy spectrum, and suitable for different irradiation times. Fission monitors are 238UO2 or 237NpO2 in the form of microspheres. Activation monitors are high purity metals (Ni, Cu, Al, Fe, Nb, Rh, or Ti), certified for interfering trace impurities, or dilute aluminium-based alloys. Reference materials newly certified are IRMM-530R A1-0.1%Au, replacing the exhausted IRMM-530 material, used as comparator for k0- standardisation, and three new Al-Co alloys (0.01, 0.1 and 1.0%Co). Others in the process of certification are A1-0.1%Ag and A1-2%Sc for thermal and epithermal fluence rate measurements and two uranium-doped glass materials intended for dosimetry by the fission-track technique. Various alloy compositions have been prepared for use as melt-wire temperature monitors with melting points ranging from 198 to 327ºC.

  16. Fluence thresholds for grazing incidence hard x-ray mirrors

    NASA Astrophysics Data System (ADS)

    Aquila, A.; Sobierajski, R.; Ozkan, C.; Hájková, V.; Burian, T.; Chalupský, J.; Juha, L.; Störmer, M.; Bajt, S.; Klepka, M. T.; DłuŻewski, P.; Morawiec, K.; Ohashi, H.; Koyama, T.; Tono, K.; Inubushi, Y.; Yabashi, M.; Sinn, H.; Tschentscher, T.; Mancuso, A. P.; Gaudin, J.

    2015-06-01

    X-ray Free Electron Lasers (XFELs) have the potential to contribute to many fields of science and to enable many new avenues of research, in large part due to their orders of magnitude higher peak brilliance than existing and future synchrotrons. To best exploit this peak brilliance, these XFEL beams need to be focused to appropriate spot sizes. However, the survivability of X-ray optical components in these intense, femtosecond radiation conditions is not guaranteed. As mirror optics are routinely used at XFEL facilities, a physical understanding of the interaction between intense X-ray pulses and grazing incidence X-ray optics is desirable. We conducted single shot damage threshold fluence measurements on grazing incidence X-ray optics, with coatings of ruthenium and boron carbide, at the SPring-8 Angstrom compact free electron laser facility using 7 and 12 keV photon energies. The damage threshold dose limits were found to be orders of magnitude higher than would naively be expected. The incorporation of energy transport and dissipation via keV level energetic photoelectrons accounts for the observed damage threshold.

  17. The Fluence and Distance Distributions of Fast Radio Bursts

    NASA Astrophysics Data System (ADS)

    Vedantham, H. K.; Ravi, V.; Hallinan, G.; Shannon, R. M.

    2016-10-01

    Fast radio bursts (FRB) are millisecond-duration radio pulses with apparent extragalactic origins. All but two of the FRBs have been discovered using the Parkes dish, which employs multiple beams formed by an array of feed horns on its focal plane. In this paper, we show that (i) the preponderance of multiple-beam detections and (ii) the detection rates for varying dish diameters can be used to infer the index α of the cumulative fluence distribution function (the logN–logF function: α = 1.5 for a non-evolving population in a Euclidean universe). If all detected FRBs arise from a single progenitor population, multiple-beam FRB detection rates from the Parkes telescope yield the constraint 0.52 < α < 1.0 with 90% confidence. Searches at other facilities with different dish sizes refine the constraint to 0.5 < α < 0.9. Our results favor FRB searches with smaller dishes, because for α < 1 the gain in field of view for a smaller dish is more important than the reduction in sensitivity. Further, our results suggest that (i) FRBs are not standard candles, and (ii) the distribution of distances to the detected FRBs is weighted toward larger distances. If FRBs are extragalactic, these results are consistent with a cosmological population, which would make FRBs excellent probes of the baryonic content and geometry of the universe.

  18. Space Environment Effects: Model for Emission of Solar Protons (ESP): Cumulative and Worst Case Event Fluences

    NASA Technical Reports Server (NTRS)

    Xapsos, M. A.; Barth, J. L.; Stassinopoulos, E. G.; Burke, E. A.; Gee, G. B.

    1999-01-01

    The effects that solar proton events have on microelectronics and solar arrays are important considerations for spacecraft in geostationary and polar orbits and for interplanetary missions. Designers of spacecraft and mission planners are required to assess the performance of microelectronic systems under a variety of conditions. A number of useful approaches exist for predicting information about solar proton event fluences and, to a lesser extent, peak fluxes. This includes the cumulative fluence over the course of a mission, the fluence of a worst-case event during a mission, the frequency distribution of event fluences, and the frequency distribution of large peak fluxes. Naval Research Laboratory (NRL) and NASA Goddard Space Flight Center, under the sponsorship of NASA's Space Environments and Effects (SEE) Program, have developed a new model for predicting cumulative solar proton fluences and worst-case solar proton events as functions of mission duration and user confidence level. This model is called the Emission of Solar Protons (ESP) model.

  19. Space Environment Effects: Model for Emission of Solar Protons (ESP): Cumulative and Worst Case Event Fluences

    NASA Astrophysics Data System (ADS)

    Xapsos, M. A.; Barth, J. L.; Stassinopoulos, E. G.; Burke, E. A.; Gee, G. B.

    1999-12-01

    The effects that solar proton events have on microelectronics and solar arrays are important considerations for spacecraft in geostationary and polar orbits and for interplanetary missions. Designers of spacecraft and mission planners are required to assess the performance of microelectronic systems under a variety of conditions. A number of useful approaches exist for predicting information about solar proton event fluences and, to a lesser extent, peak fluxes. This includes the cumulative fluence over the course of a mission, the fluence of a worst-case event during a mission, the frequency distribution of event fluences, and the frequency distribution of large peak fluxes. Naval Research Laboratory (NRL) and NASA Goddard Space Flight Center, under the sponsorship of NASA's Space Environments and Effects (SEE) Program, have developed a new model for predicting cumulative solar proton fluences and worst-case solar proton events as functions of mission duration and user confidence level. This model is called the Emission of Solar Protons (ESP) model.

  20. La-138/139 isotopic data and neutron fluences for Oklo RZ10 reactor

    NASA Astrophysics Data System (ADS)

    Gould, C. R.; Sharapov, E. I.

    2012-08-01

    Background: Recent years have seen a renewed interest in the Oklo phenomenon, particularly in relation to the study of time variation of the fine structure constant α. The neutron fluence is one of the crucial parameters for Oklo reactors. Several approaches to its determination were elaborated in the past.Purpose: We consider whether it is possible to use the present isotopic 138La-139La data for RZ10 as an additional indicator of neutron fluences in the active cores of the reactors.Results: We calculate the dependence of the Oklo 138La abundance on neutron fluence and elemental lanthanum concentration.Conclusion: The neutron fluence in RZ10 can be deduced from lanthanum isotopic data, but requires reliable data on the primordial elemental abundance. Conversely, if the fluence is known, the isotope ratio provides information on the primordial lanthanum abundance that is not otherwise easily determined.

  1. Materials International Space Station Experiment-6 (MISSE-6) Atomic Oxygen Fluence Monitor Experiment

    NASA Technical Reports Server (NTRS)

    Banks, Bruce A.; Miller, Sharon K.; Waters, Deborah L.

    2010-01-01

    An atomic oxygen fluence monitor was flown as part of the Materials International Space Station Experiment-6 (MISSE-6). The monitor was designed to measure the accumulation of atomic oxygen fluence with time as it impinged upon the ram surface of the MISSE 6B Passive Experiment Container (PEC). This was an active experiment for which data was to be stored on a battery-powered data logger for post-flight retrieval and analysis. The atomic oxygen fluence measurement was accomplished by allowing atomic oxygen to erode two opposing wedges of pyrolytic graphite that partially covered a photodiode. As the wedges of pyrolytic graphite erode, the area of the photodiode that is illuminated by the Sun increases. The short circuit current, which is proportional to the area of illumination, was to be measured and recorded as a function of time. The short circuit current from a different photodiode, which was oriented in the same direction and had an unobstructed view of the Sun, was also to be recorded as a reference current. The ratio of the two separate recorded currents should bear a linear relationship with the accumulated atomic oxygen fluence and be independent of the intensity of solar illumination. Ground hyperthermal atomic oxygen exposure facilities were used to evaluate the linearity of the ratio of short circuit current to the atomic oxygen fluence. In flight, the current measurement circuitry failed to operate properly, thus the overall atomic oxygen mission fluence could only be estimated based on the physical erosion of the pyrolytic graphite wedges. The atomic oxygen fluence was calculated based on the knowledge of the space atomic oxygen erosion yield of pyrolytic graphite measured from samples on the MISSE 2. The atomic oxygen fluence monitor, the expected result and comparison of mission atomic oxygen fluence based on the erosion of the pyrolytic graphite and Kapton H atomic oxygen fluence witness samples are presented in this paper.

  2. Dependence of the phototropic response of Arabidopsis thaliana on fluence rate and wavelength

    PubMed Central

    Konjević, Radomir; Steinitz, Benjamin; Poff, Kenneth L.

    1989-01-01

    In the phototropic response of Arabidopsis thaliana seedlings, the shape of the fluence-response relation depends on fluence rate and wavelength. At low fluence rates, the response to 450-nm light is characterized by a single maximum at about 0.3 μmol·m-2. At higher fluence rates, the response shows two distinct maxima, I and II, at 0.3 and 3.5 μmol·m-2, respectively. The response to 500-nm light shows a single maximum at 2 μmol·m-2, and the response to 510-nm light shows a single maximum at 4.5 μmol·m-2, independent of fluence rate. The response to 490-nm light shows a maximal at 4.5 μmol·m-2 and a shoulder at about 0.6 μmol·m-2. Preirradiation with high-fluence 510-nm light from above, immediately followed by unilateral 450-nm light, eliminates maximum II but not maximum I. Preirradiation with high-fluence 450-nm light from above eliminates the response to subsequent unilateral irradiation with either 450-nm or 510-nm light. The recovery of the response following high-fluence 450-nm light is considerably slower than the recovery following high-fluence 510-nm light. Unilateral irradiation with low-fluence 510-nm light followed by 450-nm light results in curvature that is approximately the sum of those produced by either irradiation alone. Based on these results, it is proposed that phototropism in A. thaliana seedlings is mediated by at least two blue-light photoreceptor pigments. PMID:16594094

  3. CD11c gene expression in hairy cell leukemia is dependent upon activation of the proto-oncogenes ras and junD.

    PubMed

    Nicolaou, Fotini; Teodoridis, Jens M; Park, Heiyoung; Georgakis, Alexander; Farokhzad, Omid C; Böttinger, Erwin P; Da Silva, Nicolas; Rousselot, Philippe; Chomienne, Christine; Ferenczi, Katalin; Arnaout, M Amin; Shelley, C Simon

    2003-05-15

    Hairy cell leukemia (HCL) is a chronic lymphoproliferative disease, the cause of which is unknown. Diagnostic of HCL is abnormal expression of the gene that encodes the beta2 integrin CD11c. In order to determine the cause of CD11c gene expression in HCL the CD11c gene promoter was characterized. Transfection of the CD11c promoter linked to a luciferase reporter gene indicated that it is sufficient to direct expression in hairy cells. Mutation analysis demonstrated that of predominant importance to the activity of the CD11c promoter is its interaction with the activator protein-1 (AP-1) family of transcription factors. Comparison of nuclear extracts prepared from hairy cells with those prepared from other cell types indicated that hairy cells exhibit abnormal constitutive expression of an AP-1 complex containing JunD. Functional inhibition of AP-1 expressed by hairy cells reduced CD11c promoter activity by 80%. Inhibition of Ras, which represents an upstream activator of AP-1, also significantly inhibited the CD11c promoter. Furthermore, in the hairy cell line EH, inhibition of Ras signaling through mitogen-activated protein kinase/extracellular signal-regulated kinase kinases 1 and 2 (MEK1/2) reduced not only CD11c promoter activity but also reduced both CD11c surface expression and proliferation. Expression in nonhairy cells of a dominant-positive Ras mutant activated the CD11c promoter to levels equivalent to those in hairy cells. Together, these data indicate that the abnormal expression of the CD11c gene characteristic of HCL is dependent upon activation of the proto-oncogenes ras and junD.

  4. Kilometer-scale, late Miocene and early Pliocene surface uplift in East Greenland: tectonic forerunners for the build-up of the Greenland Ice Sheet

    NASA Astrophysics Data System (ADS)

    Japsen, Peter; Green, Paul F.; Bonow, Johan M.

    2015-04-01

    The tectonic origin of late Neogene uplift along NE Atlantic margins has been questioned. Evidence for these movements - such as the recent denudation of mountain ranges and abundant, late Cenozoic coarse sediment near them - has been explained as a result of climate change (Molnar and England, 1990). Identification of the causal relationship between uplift, tectonics and climate deterioration during the late Neogene thus critically depends on defining temporal relation between these events. We have previously argued that the elevated plateaux in East and West Greenland are the result of three tectonic phases of uplift and erosion (Bonow et al., 2014; Japsen et al., 2014). A late Eocene phase of uplift led to formation of a Palaeogene erosion surface near sea level. Uplift of this surface in the late Miocene led to formation of a lower, Neogene surface by incision below the uplifted Palaeogene surface. Finally, a Pliocene phase led to incision of valleys and fjords below the uplifted Neogene surface, resulting in mountain peaks reaching 3.7 km and 2.1 km a.s.l. in East and West Greenland, respectively. Data from West Greenland only provide broad constraints on the timing of the Pliocene phase, and we have not yet been able to define the timing of this phase firmly in the east. Here we present new apatite fission-track data from East Greenland that clearly constrain the timing of late Miocene and early Pliocene events of uplift and exhumation. It is thus clear that the final phase of Cenozoic tectonic uplift preceded the onset of large-scale glaciations in the late Pliocene to Pleistocene. Solgaard et al. (2013) showed that the the build-up of the Greenland Ice Sheet could not initiate in the case of the low-lying and almost flat topography in Greenland prior to the two phases of late Neogene uplift. Furthermore, these results showed that Early Pliocene uplift led to the final formation of the present-day, high coastal mountains in East Greenland that provided

  5. Ultra-fast fluence optimization for beam angle selection algorithms

    NASA Astrophysics Data System (ADS)

    Bangert, M.; Ziegenhein, P.; Oelfke, U.

    2014-03-01

    Beam angle selection (BAS) including fluence optimization (FO) is among the most extensive computational tasks in radiotherapy. Precomputed dose influence data (DID) of all considered beam orientations (up to 100 GB for complex cases) has to be handled in the main memory and repeated FOs are required for different beam ensembles. In this paper, the authors describe concepts accelerating FO for BAS algorithms using off-the-shelf multiprocessor workstations. The FO runtime is not dominated by the arithmetic load of the CPUs but by the transportation of DID from the RAM to the CPUs. On multiprocessor workstations, however, the speed of data transportation from the main memory to the CPUs is non-uniform across the RAM; every CPU has a dedicated memory location (node) with minimum access time. We apply a thread node binding strategy to ensure that CPUs only access DID from their preferred node. Ideal load balancing for arbitrary beam ensembles is guaranteed by distributing the DID of every candidate beam equally to all nodes. Furthermore we use a custom sorting scheme of the DID to minimize the overall data transportation. The framework is implemented on an AMD Opteron workstation. One FO iteration comprising dose, objective function, and gradient calculation takes between 0.010 s (9 beams, skull, 0.23 GB DID) and 0.070 s (9 beams, abdomen, 1.50 GB DID). Our overall FO time is < 1 s for small cases, larger cases take ~ 4 s. BAS runs including FOs for 1000 different beam ensembles take ~ 15-70 min, depending on the treatment site. This enables an efficient clinical evaluation of different BAS algorithms.

  6. Thermal and structural properties of low-fluence irradiated graphite

    NASA Astrophysics Data System (ADS)

    Lexa, Dusan; Dauke, Michael

    2009-02-01

    The release of Wigner energy from graphite irradiated by fast neutrons at a TRIGA Mark II research reactor has been studied by differential scanning calorimetry and simultaneous differential scanning calorimetry / synchrotron powder X-ray diffraction between 25 and 725 °C at a heating rate of 10 °C min -1. The graphite, having been subject to a fast-neutron fluence from 5.67 × 10 20 to 1.13 × 10 22 n m -2 at a fast-neutron flux ( E > 0.1 MeV) of 7.88 × 10 16 n m -2 s -1 and at temperatures not exceeding 100 °C, exhibits Wigner energies ranging from 1.2 to 21.8 J g -1 and a Wigner energy accumulation rate of 1.9 × 10 -21 J g -1 n -1 m 2. The differential-scanning-calorimeter curves exhibit, in addition to the well known peak at ˜200 °C, a pronounced fine structure consisting of additional peaks at ˜150, ˜230, and ˜280 °C. These peaks correspond to activation energies of 1.31, 1.47, 1.57, and 1.72 eV, respectively. Crystal structure of the samples is intact. The dependence of the c lattice parameter on temperature between 25 and 725 °C as determined by Rietveld refinement leads to the expected microscopic thermal expansion coefficient along the c axis of ˜26 × 10 -6 °C -1. At 200 °C, coinciding with the maximum in the differential-scanning-calorimeter curves, no measurable changes in the rate of thermal expansion have been detected - unlike its decrease previously seen in more highly irradiated graphite.

  7. The relative role of Amazonian and non-Amazonian fires in building up the aerosol optical depth in South America: A five year study (2005-2009)

    NASA Astrophysics Data System (ADS)

    Castro Videla, Fernando; Barnaba, Francesca; Angelini, Federico; Cremades, Pablo; Gobbi, Gian Paolo

    2013-03-01

    In South America (SA) biomass burning is the major source of atmospheric aerosols. Fires are mostly registered in the dry season (July-November) and are mainly concentrated in the Amazonia and Cerrado regions. Nonetheless, the growing systematic employment of fires for land clearing and pasture maintenance across the SA continent is introducing other, potentially significant, sources of BB aerosols. This study investigates the relative contributions of different SA biomass burning regions in building up the continental aerosol load. To this purpose, the SA continent is divided into four biomass burning source regions and their impact on the aerosol optical depth (AOD) is evaluated in eight different SA target domains. The dataset used includes multi-year (2005-2009) satellite observations of both aerosol and fires and model-based atmospheric trajectories. The methodology followed couples fire counts and atmospheric transport through the definition of a specific quantity, referred to as ‘fire weighted residence time’ (FWRT), which is used to assess the contribution of the four identified fire source regions to the continental aerosol load. Results show that local fires play an important role in building up the regional aerosols load all over SA. Nevertheless, in some regions, contribution of BB aerosols transported from outside their boundaries is comparable to the local one. The major ‘smoke exporter’ regions are found to be the eastern Brazil and the Amazonia-Cerrado regions. In the dry season, due to the typical continental circulation pattern, the first is estimated to contribute to half of the AOD in Northern Amazonia, Southern Amazonia and Cerrado regions, while over 30% of the AOD in Paraguay and North Argentina derives from the Amazonia-Cerrado fires. Due to the presence of the inter-tropical convergence zone, which decouples wind circulation of the two hemispheres, regions north of the Equator (Venezuela, Guyana, Suriname) are found to receive

  8. Evolutionary paths among different red galaxy types at 0.3 < z < 1.5 and the build-up of massive E-S0's

    NASA Astrophysics Data System (ADS)

    Gallego, Jesús; Prieto, Mercedes; Eliche-Moral, M. Carmen; Balcells, Marc; Cristóbal-Hornillos, David; Erwin, Peter; Abreu, David; Domínguez-Palmero, Lilian; Hempel, Angela; López-Sanjuan, Carlos; Guzmán, Rafael; Pérez-González, Pablo G.; Barro, Guillermo; Zamorano, Jaime

    2013-07-01

    Some recent observations seem to disagree with hierarchical theories of galaxy formation on the role of major mergers in a late build-up of massive early-type galaxies. We re-address this question by analysing the morphology, structural distortion level, and star formation enhancement of a sample of massive galaxies (M* > 5 × 1010M⊙) lying on the Red Sequence and its surroundings at 0.3 < z < 1.5. We have used an initial sample of ~1800 sources with Ks < 20.5 mag over an area ~155 arcmin2 on the Groth Strip, combining data from the Rainbow Extragalactic Database and the GOYA Survey. Red galaxy classes that can be directly associated to intermediate stages of major mergers and to their final products have been defined. For the first time we report observationally the existence of a dominant evolutionary path among massive red galaxies at 0.6 < z < 1.5, consisting in the conversion of irregular disks into irregular spheroids, and of these ones into regular spheroids. This result points to: 1) the massive red regular galaxies at low redshifts derive from the irregular ones populating the Red Sequence and its neighbourhood at earlier epochs up to z ~ 1.5; 2) the progenitors of the bulk of present-day massive red regular galaxies have been blue disks that have migrated to the Red Sequence majoritarily through major mergers at 0.6 < z < 1.2 (these mergers thus starting at z ~ 1.5); 3) the formation of E-S0's that end up with M* > 1011M⊙ at z = 0 through gas-rich major mergers has frozen since z ~ 0.6. Our results support that major mergers have played the dominant role in the definitive build-up of present-day E-S0's with M* > 1011M⊙ at 0.6 < z < 1.2, in good agreement with the hierarchical scenario proposed in the Eliche-Moral et al. (2010a) model (see also Eliche-Moral et al. 2010b). This study is published in Prieto et al. (2012). Supported by the Spanish Ministry of Science and Innovation (MICINN) under projects AYA2009-10368, AYA2006-12955, AYA2010-21887-C04

  9. Multidiagnostics analysis of ion dynamics in ultrafast laser ablation of metals over a large fluence range

    SciTech Connect

    Anoop, K. K.; Polek, M. P.; Bruzzese, R.; Amoruso, S.; Harilal, Sivanandan S.

    2015-02-28

    The ions dynamics in ultrafast laser ablation of metals is studied over a fluence range spanning from the ablation threshold up to ~75 J/cm2 by means of three established diagnostic techniques. Langmuir probe, Faraday cup and spectrally resolved ICCD imaging simultaneously monitor the laser-produced plasma ions produced during ultrafast laser ablation of a copper target. The fluence dependence of ion yield is analyzed observing the occurrence of three different regimes. Moreover, the specific ion yield shows a maximum at about 4-5 J/cm2, followed by a gradual reduction and a transition to a high-fluence regime above ~50 J/cm2. The fluence variation of the copper ions angular distribution is also analyzed, observing a gradual increase of forward peaking of Cu ions for fluences up to ~10 J/cm2. Then, a broader ion component is observed at larger angles for fluences larger than ~10 J/cm2. Finally, an experimental characterization of the ions angular distribution for several metallic targets (Mg, Al, Cr, Fe, Cu, and W) is carried out at a relatively high fluence of ~66 J/cm2. Interestingly, the ion emission from the volatile metals show a narrow forward peaked distribution and a high peak ion yield compared to the refractory metals. Moreover, the width of ion angular distributions presents a striking correlation with the peak ion yield.

  10. The Upper Limit on 3He Fluence in Solar Energetic Particle Events

    NASA Astrophysics Data System (ADS)

    Ho, G. C.; Roelof, E. C.; Mason, G. M.

    2005-03-01

    We investigated 201 3He-rich (3He/4He > 0.004 at 0.2-2.0 MeV nucleon-1) solar energetic particle (SEP) events from 1997 September through 2003 December using the Ultra Low Energy Isotope Spectrometer on the A dvanced Composition E xplorer. Both ``impulsive'' (flare-related) and ``gradual'' (CME-related) events are included. The 3He fluences varied only by a factor of 100 above our instrument sensitivity threshold, while the 4He fluences varied by factor of 10,000 above the same threshold. Moreover, there appears to be no significant correlation between the 3He and 4He fluences. We find it striking that with more than 6 years of continuous SEP data, we could not find any SEP event that has 3He fluence higher than 2.0×105 particles (cm2 sr MeV nucleon-1)-1, while the largest 4He fluence observed was 7.0×107 particles (cm2 sr MeV nucleon-1)-1. To the approximation that the event fluence is to first order proportional the number of particles released from the Sun, the observed upper limit for the 3He fluence seems to indicate that only a limited number of 0.2-2 MeV nucleon-1 3He can be released from the Sun in an SEP event.

  11. NK-CD11c+ Cell Crosstalk in Diabetes Enhances IL-6-Mediated Inflammation during Mycobacterium tuberculosis Infection

    PubMed Central

    Cheekatla, Satyanarayana Swamy; Tripathi, Deepak; Venkatasubramanian, Sambasivan; Nathella, Pavan Kumar; Paidipally, Padmaja; Ishibashi, Munenori; Welch, Elwyn; Tvinnereim, Amy R.; Ikebe, Mitsuo; Valluri, Vijaya Lakshmi; Babu, Subash; Kornfeld, Hardy; Vankayalapati, Ramakrishna

    2016-01-01

    In this study, we developed a mouse model of type 2 diabetes mellitus (T2DM) using streptozotocin and nicotinamide and identified factors that increase susceptibility of T2DM mice to infection by Mycobacterium tuberculosis (Mtb). All Mtb-infected T2DM mice and 40% of uninfected T2DM mice died within 10 months, whereas all control mice survived. In Mtb-infected mice, T2DM increased the bacterial burden and pro- and anti-inflammatory cytokine and chemokine production in the lungs relative to those in uninfected T2DM mice and infected control mice. Levels of IL-6 also increased. Anti-IL-6 monoclonal antibody treatment of Mtb-infected acute- and chronic-T2DM mice increased survival (to 100%) and reduced pro- and anti-inflammatory cytokine expression. CD11c+ cells were the major source of IL-6 in Mtb-infected T2DM mice. Pulmonary natural killer (NK) cells in Mtb-infected T2DM mice further increased IL-6 production by autologous CD11c+ cells through their activating receptors. Anti-NK1.1 antibody treatment of Mtb-infected acute-T2DM mice increased survival and reduced pro- and anti-inflammatory cytokine expression. Furthermore, IL-6 increased inflammatory cytokine production by T lymphocytes in pulmonary tuberculosis patients with T2DM. Overall, the results suggest that NK-CD11c+ cell interactions increase IL-6 production, which in turn drives the pathological immune response and mortality associated with Mtb infection in diabetic mice. PMID:27783671

  12. Translational characterization of [11C]GSK931145, a PET ligand for the glycine transporter type 1.

    PubMed

    Gunn, Roger N; Murthy, Venkatesha; Catafau, Ana M; Searle, Graham; Bullich, Santiago; Slifstein, Mark; Ouellet, Daniele; Zamuner, Stefano; Herance, Raul; Salinas, Cristian; Pardo-Lozano, Ricardo; Rabiner, Eugenii A; Farre, Magi; Laruelle, Marc

    2011-12-01

    The current interest in developing Glycine transporter Type 1 (GlyT-1) inhibitors, for diseases such as schizophrenia, has led to the demand for a GlyT-1 PET molecular imaging tool to aid drug development and dose selection. We report on [(11) C]GSK931145 as a novel GlyT-1 imaging probe in primate and man. Primate PET studies were performed to determine the level of specific binding following homologous competition with GSK931145 and the plasma-occupancy relationship of the GlyT-1 inhibitor GSK1018921. Human PET studies were performed to determine the test-retest reproducibility of [(11) C]GSK931145 and the plasma-occupancy relationship of GSK1018921. [(11) C]GSK931145 entered primate and human brain and yielded a heterogeneous pattern of uptake which was similar in both species with highest uptake in midbrain, thalamus, and cerebellum. Homologous competition in primates indicated no viable reference region and gave binding potential estimates between 1.5 and 3 for midbrain, thalamus and cerebellum, While the distribution and binding potential values were similar across species, both the plasma free fraction (f(P) : 0.8 vs. 8%) and delivery (K(1) : 0.025 vs. 0.126 ml cm(-3) min(-1) ) were significantly lower in humans. Test-retest reproducibility in humans calculated using a two tissue compartmental model was poor (VAR(V(T) ): 29-38%), but was improved using a pseudo reference tissue model (VAR(BP(ND) ): 16-23%). GSK1018921 EC(50) estimates were 22.5 and 45.7 ng/ml in primates and humans, respectively. PMID:21688322

  13. Compartmental analysis of washout effect in rat brain: in-beam OpenPET measurement using a 11C beam

    NASA Astrophysics Data System (ADS)

    Hirano, Yoshiyuki; Kinouchi, Shoko; Ikoma, Yoko; Yoshida, Eiji; Wakizaka, Hidekazu; Ito, Hiroshi; Yamaya, Taiga

    2013-12-01

    In-beam positron emission tomography (PET) is expected to enable visualization of a dose verification using positron emitters (β+ decay). For accurate dose verification, correction of the washout of the positron emitters should be made. In addition, the quantitative washout rate has a potential usefulness as a diagnostic index, but modeling for this has not been studied yet. In this paper, therefore, we applied compartment analyses to in-beam PET data acquired by our small OpenPET prototype, which has a physically opened field-of-view (FOV) between two detector rings. A rat brain was located at the FOV and was irradiated by a 11C beam. Time activity curves of the irradiated field were measured immediately after the irradiations, and the washout rate was obtained based on two models: the two-washout model (medium decay, k2m; slow decay, k2s) developed in a study of rabbit irradiation; and the two-compartment model used in nuclear medicine, where efflux from tissue to blood (k2), influx (k3) and efflux (k4) from the first to second compartments in tissue were evaluated. The observed k2m and k2s were 0.34 and 0.005 min-1, respectively, which was consistent with the rabbit study. Also k2m was close to the washout rate in cerebral blood flow (CBF) measurements by dynamic PET with 15O-water, while, k2, k3, and k4 were 0.16, 0.15 and 0.007 min-1. Our present work suggested the dynamics of 11C might be relevant to CBF or permeability of a molecule containing 11C atoms might be regulated by a transporter because the k2 was relatively low compared with a simple diffusion tracer.

  14. ATP11C is a major flippase in human erythrocytes and its defect causes congenital hemolytic anemia

    PubMed Central

    Arashiki, Nobuto; Takakuwa, Yuichi; Mohandas, Narla; Hale, John; Yoshida, Kenichi; Ogura, Hiromi; Utsugisawa, Taiju; Ohga, Shouichi; Miyano, Satoru; Ogawa, Seishi; Kojima, Seiji; Kanno, Hitoshi

    2016-01-01

    Phosphatidylserine is localized exclusively to the inner leaflet of the membrane lipid bilayer of most cells, including erythrocytes. This asymmetric distribution is critical for the survival of erythrocytes in circulation since externalized phosphatidylserine is a phagocytic signal for splenic macrophages. Flippases are P-IV ATPase family proteins that actively transport phosphatidylserine from the outer to inner leaflet. It has not yet been determined which of the 14 members of this family of proteins is the flippase in human erythrocytes. Herein, we report that ATP11C encodes a major flippase in human erythrocytes, and a genetic mutation identified in a male patient caused congenital hemolytic anemia inherited as an X-linked recessive trait. Phosphatidylserine internalization in erythrocytes with the mutant ATP11C was decreased 10-fold compared to that of the control, functionally establishing that ATP11C is a major flippase in human erythrocytes. Contrary to our expectations phosphatidylserine was retained in the inner leaflet of the majority of mature erythrocytes from both controls and the patient, suggesting that phosphatidylserine cannot be externalized as long as scramblase is inactive. Phosphatidylserine-exposing cells were found only in the densest senescent cells (0.1% of total) in which scramblase was activated by increased Ca2+ concentration: the percentage of these phosphatidylserine-exposing cells was increased in the patient’s senescent cells accounting for his mild anemia. Furthermore, the finding of similar extents of phosphatidylserine exposure by exogenous Ca2+-activated scrambling in both control erythrocytes and the patient’s erythrocytes implies that suppressed scramblase activity rather than flippase activity contributes to the maintenance of phosphatidylserine in the inner leaflet of human erythrocytes. PMID:26944472

  15. Dopamine response to psychosocial stress in chronic cannabis users: a PET study with [11C]-+-PHNO.

    PubMed

    Mizrahi, Romina; Suridjan, Ivonne; Kenk, Miran; George, Tony P; Wilson, Alan; Houle, Sylvain; Rusjan, Pablo

    2013-03-01

    A number of addictions have been linked with decreased striatal dopamine (DA) receptor availability and DA release. Stress has a key role in cannabis craving, as well as in modulation of dopaminergic signaling. The present study aimed to assess DA release in response to a laboratory stress task with [(11)C]-(+)-PHNO positron emission tomography in cannabis users (CU). Thirteen healthy CU and 12 healthy volunteers (HV) were scanned during a sensorimotor control task (SMCT) and under a stress condition using the validated Montreal imaging stress task (MIST). The simplified reference tissue model (SRTM) was used to obtain binding potential (BP(ND)) in striatal subdivisions: limbic striatum (LST), associative striatum (AST), and sensorimotor striatum (SMST). Stress-induced DA release (indexed as a percentage of reduction in [(11)C]-(+)-PHNO BP (ND)) between CU and HV was tested with analysis of variance. SMCT BP(ND) was significantly higher in CU compared with HV in the AST (F=10.38, p=0.003), LST (F=4.95, p=0.036), SMST (F=4.33, p=0.048), and whole striatum (F=9.02, p=0.006). Percentage of displacement (change in BP(ND) between SMCT and MIST PET scans) was not significantly different across groups in any brain region, except in the GP (-5.03±14.6 in CU, compared with 6.15±12.1 in HV; F=4.39, p=0.049). Duration of cannabis use was significantly associated with stress-induced [(11)C]-(+)-PHNO displacement by endogenous DA in the LST (r=0.566, p=0.044), with no effect in any other brain region. In conclusion, despite an increase in striatal BP(ND) observed during the control task, chronic cannabis use is not associated with alterations in stress-induced DA release. PMID:23212454

  16. Determination of [11C]PBR28 binding potential in vivo: a first human TSPO blocking study

    PubMed Central

    Owen, David R; Guo, Qi; Kalk, Nicola J; Colasanti, Alessandro; Kalogiannopoulou, Dimitra; Dimber, Rahul; Lewis, Yvonne L; Libri, Vincenzo; Barletta, Julien; Ramada-Magalhaes, Joaquim; Kamalakaran, Aruloly; Nutt, David J; Passchier, Jan; Matthews, Paul M; Gunn, Roger N; Rabiner, Eugenii A

    2014-01-01

    Positron emission tomography (PET) targeting the 18 kDa translocator protein (TSPO) is used to quantify neuroinflammation. Translocator protein is expressed throughout the brain, and therefore a classical reference region approach cannot be used to estimate binding potential (BPND). Here, we used blockade of the TSPO radioligand [11C]PBR28 with the TSPO ligand XBD173, to determine the non-displaceable volume of distribution (VND), and hence estimate the BPND. A total of 26 healthy volunteers, 16 high-affinity binders (HABs) and 10 mixed affinity binders (MABs) underwent a [11C]PBR28 PET scan with arterial sampling. Six of the HABs received oral XBD173 (10 to 90 mg), 2 hours before a repeat scan. In XBD173-dosed subjects, VND was estimated via the occupancy plot. Values of BPND for all subjects were calculated using this VND estimate. Total volume of distribution (VT) of MABs (2.94±0.31) was lower than VT of HABs (4.33±0.29) (P<0.005). There was dose-dependent occupancy of TSPO by XBD173 (ED50=0.34±0.13 mg/kg). The occupancy plot provided a VND estimate of 1.98 (1.69, 2.26). Based on these VND estimates, BPND for HABs is approximately twice that of MABs, consistent with predictions from in vitro data. Our estimates of [11C]PBR28 VND and hence BPND in the healthy human brain are consistent with in vitro predictions. XBD173 blockade provides a practical means of estimating VND for TSPO targeting radioligands. PMID:24643083

  17. Clinically different stages of Alzheimer's disease associated by amyloid deposition with [11C]-PIB PET imaging.

    PubMed

    Hatashita, Shizuo; Yamasaki, Hidetomo

    2010-01-01

    We investigated whether [11C]-PIB PET detects underlying amyloid deposition at clinically different stages of Alzheimer's disease (AD) and preclinical dementia. The Japanese cohort of 214 subjects underwent cognitive testing and 60-min dynamic [11C]-PIB PET. [11C]-PIB data were acquired from 35-60 min after injection. Regions of interest were defined on co-registered MRI. Distribution volume ratios (DVR) of PIB retention were determined using Logan graphical analysis. All 56 patients with AD showed a robust increase in PIB retention in cortical areas (typical PIB AD-pattern). A mean DVR value in 11 patients with moderate AD (CDR: 2.1 ± 0.4) showed significantly higher PIB retention (2.38 ± 0.42, p < 0.01) than amyloid-negative healthy control (HC) subjects. The DVR values in 23 patients with very mild AD (CDR: 0.5) and 22 patients with mild AD (CDR: 1.0) were 2.32 ± 0.45 and 2.34 ± 0.42, respectively, similar to moderate AD. In contrast, 28 (48%) of the 58 mild cognitive impairment (MCI) patients (MMSE: 27.3 ± 1.7) showed a typical AD-like pattern with a DVR value of 2.07 ± 0.34. Further, 17 (18%) of 91 HC subjects had a typical AD-like pattern with a DVR value of 2.06 ± 0.28. They did not significantly differ from very mild AD. The prevalence of AD among the 53 amyloid positive patients aged 75 years or older increased greatly to 74% whereas that of amyloid positive HC decreased by only 9% and amyloid positive MCI by 17%. Prodromal AD and AD dementia is identified, based on cognitive function and amyloid deposition by PIB PET imaging. Further, the cortical amyloid deposition could be detected at preclinical stage of AD.

  18. Labelling of the solvent DMSO as side reaction of methylations with n.c.a. [11C]CH3I.

    PubMed

    Klein, A T; Holschbach, M

    2001-09-01

    Competing labelling of solvent dimethyl sulfoxide (DMSO) can occur during the 11C-methylation of amine precursors. A kinetic analysis of the methylation reaction of DMSO with n.c.a. [11C]CH3I was performed at 120 degrees C resulting in rate constants. The rate constant for the formation of the intermediate, methylated DMSO ([11C]DMSO-M), is compared to the reaction of [11C]CH3I with two tertiary amines, namely Dexetimide and Desmethyloxotremorine-M. The specific activity of the labelled product is reduced due to partial 12C-methylation of the precursor amines by [11C]DMSO-M in cases of significant DMSO labelling as side reaction. PMID:11515652

  19. Range degradation and distal edge behavior of proton radiotherapy beams using 11C activation and Monte Carlo simulation

    NASA Astrophysics Data System (ADS)

    Elmekawy, Ahmed Farouk

    The distal edge of therapeutic proton radiation beams was investigated by different methods. Proton beams produced at the Hampton University Proton Therapy Institute (HUPTI) were used to irradiate a Polymethylmethacrylate (PMMA) phantom for three different ranges (13.5, 17.0 and 21.0 cm) to investigate the distal slope dependence of the Bragg peak. The activation of 11 C was studied by scanning the phantom less than 10 minutes post-irradiation with a Philips Big Bore Gemini(c) PET/CT. The DICOM images were imported into the Varian Eclipse(c) Treatment Planning System (TPS) for analysis and then analyzed by ImageJ(c) . The distal slope ranged from ?0.1671 +/- 0.0036 to -0.1986 +/- 0.0052 (pixel intensity/slice number) for ranges 13.5 to 21.0 cm respectively. A realistic description of the setup was modeled using the GATE 7.0 Monte Carlo simulation tool and compared to the experiment data. The results show the distal slope ranged from -0.1158+/-0.0133 to -0.0787+/-0.002 (Gy/mm). Additionally, low activity, 11C were simulated to study the 11C reconstructed half-life dependence versus the initial activity for six ranges chosen around the previous activation study. The results of the expected/nominal half-life vs. activity ranged from -5 x 10-4 +/- 2.8104 x 10-4 to 1.6 x 10-3 +/- 9.44 x 10-4 (%diff./Bq). The comparison between two experiments with proton beams on a PMMA phantom and multi-layer ion chamber, and two GATE simulations of a proton beam incident on a water phantom and 11C PET study show that: (i) the distal fall-off variation of the steepness of the slopes are found to be similar thus validating the sensitivity of the PET technique to the range degradation and (ii) the average of the super-ratios difference between all studies observed is primarily due to the difference in the dose deposited in the media.

  20. Development of 1-N-(11)C-Methyl-L- and -D-Tryptophan for pharmacokinetic imaging of the immune checkpoint inhibitor 1-Methyl-Tryptophan.

    PubMed

    Xie, Lin; Maeda, Jun; Kumata, Katsushi; Yui, Joji; Zhang, Yiding; Hatori, Akiko; Nengaki, Nobuki; Wakizaka, Hidekatsu; Fujinaga, Masayuki; Yamasaki, Tomoteru; Shimoda, Yoko; Higuchi, Makoto; Suhara, Tetsuya; Wang, Feng; Zhang, Ming-Rong

    2015-01-01

    1-Methyl-tryptophan (1MTrp) is known as a specific inhibitor targeting the immune-checkpoint protein indoleamine-2,3-dioxygenase, in two stereoisomers of levorotary (L) and dextrorotary (D). A long-standing debate exists in immunology and oncology: which stereoisomer has the potential of antitumor immunotherapy. Herein, we developed two novel radioprobes, 1-N-(11)C-methyl-L- and -D-tryptophan ((11)C-L-1MTrp and (11)C-D-1MTrp), without modifying the chemical structures of the two isomers, and investigated their utility for pharmacokinetic imaging of the whole body. (11)C-L-1MTrp and (11)C-D-1MTrp were synthesized rapidly with radiochemical yields of 47 ± 6.3% (decay-corrected, based on (11)C-CO2), a radiochemical purity of >98%, specific activity of 47-130 GBq/μmol, and high enantiomeric purity. PET/CT imaging in rats revealed that for (11)C-L-1MTrp, the highest distribution of radioactivity was observed in the pancreas, while for (11)C-D-1MTrp, it was observed in the kidney. Ex vivo biodistribution confirmed the PET/CT results, indicating the differences in pharmacokinetics between the two isomers. Both (11)C-L-1MTrp and (11)C-D-1MTrp are therefore useful PET probes for delineating the distribution and action of the checkpoint inhibitor 1MTrp in vivo. This study represents the first step toward using whole-body and real-time insight to disentangle the antitumor potential of the two stereoisomers of 1MTrp, and it can facilitate the development of 1MTrp immunotherapy. PMID:26552594

  1. Review of the Palisades pressure vessel accumulated fluence estimate and of the least squares methodology employed

    SciTech Connect

    Griffin, P.J.

    1998-05-01

    This report provides a review of the Palisades submittal to the Nuclear Regulatory Commission requesting endorsement of their accumulated neutron fluence estimates based on a least squares adjustment methodology. This review highlights some minor issues in the applied methodology and provides some recommendations for future work. The overall conclusion is that the Palisades fluence estimation methodology provides a reasonable approach to a {open_quotes}best estimate{close_quotes} of the accumulated pressure vessel neutron fluence and is consistent with the state-of-the-art analysis as detailed in community consensus ASTM standards.

  2. HSRL-2 Observations of Aerosol Variability During an Aerosol Build-up Event in Houston and Comparisons With WRF-Chem

    NASA Technical Reports Server (NTRS)

    Burton, Sharon P.; Saide, Pablo; Sawamura, Patricia; Hostetler, Chris; Ferrare, Rich; Scarino, Amy Jo; Berkoff, Tim; Harper, David; Cook, Tony; Rogers, Ray; Carmichael, Greg

    2015-01-01

    The NASA Langley airborne multi-wavelength High Spectral Resolution Lidar (HSRL-2) provides vertical distribution of aerosol optical properties as curtains of aerosol extinction, backscatter and depolarization along the flight track, plus intensive properties that are used to infer aerosol type and external mixing of types. Deployed aboard the NASA Langley King Air on the DISCOVER-AQ field mission in Houston in September 2013, HSRL-2 flew a pattern that included 18 ground sites, repeated four times a day, coordinated with a suite of airborne in situ measurements. The horizontally and vertically resolved curtains of HSRL-2 measurements give an unparalleled view of the spatial and temporal variability of aerosol, which provide broad context for interpreting other measurements and models. Detailed comparisons of aerosol extinction are made with the WRF-Chem chemical transport model along the HSRL-2 flight path. The period from Sept. 11-14 is notable for a large aerosol build-up and persistent smoke layers. We investigate the aerosol properties using the vertically resolved HSRL-2 measurements and aerosol typing analysis plus WRFChem model tracers and back trajectories, and modeling of humidification effects.

  3. High-resolution linkage and quantitative trait locus mapping aided by genome survey sequencing: building up an integrative genomic framework for a bivalve mollusc.

    PubMed

    Jiao, Wenqian; Fu, Xiaoteng; Dou, Jinzhuang; Li, Hengde; Su, Hailin; Mao, Junxia; Yu, Qian; Zhang, Lingling; Hu, Xiaoli; Huang, Xiaoting; Wang, Yangfan; Wang, Shi; Bao, Zhenmin

    2014-02-01

    Genetic linkage maps are indispensable tools in genetic and genomic studies. Recent development of genotyping-by-sequencing (GBS) methods holds great promise for constructing high-resolution linkage maps in organisms lacking extensive genomic resources. In the present study, linkage mapping was conducted for a bivalve mollusc (Chlamys farreri) using a newly developed GBS method-2b-restriction site-associated DNA (2b-RAD). Genome survey sequencing was performed to generate a preliminary reference genome that was utilized to facilitate linkage and quantitative trait locus (QTL) mapping in C. farreri. A high-resolution linkage map was constructed with a marker density (3806) that has, to our knowledge, never been achieved in any other molluscs. The linkage map covered nearly the whole genome (99.5%) with a resolution of 0.41 cM. QTL mapping and association analysis congruously revealed two growth-related QTLs and one potential sex-determination region. An important candidate QTL gene named PROP1, which functions in the regulation of growth hormone production in vertebrates, was identified from the growth-related QTL region detected on the linkage group LG3. We demonstrate that this linkage map can serve as an important platform for improving genome assembly and unifying multiple genomic resources. Our study, therefore, exemplifies how to build up an integrative genomic framework in a non-model organism.

  4. 'The letting go, the building up, [and] the gradual process of rebuilding': identity change and post-traumatic growth in myalgic encephalomyelitis/chronic fatigue syndrome.

    PubMed

    Arroll, Megan A; Howard, Alex

    2013-01-01

    The aim of this study was to explore the phenomenon of identity change and subsequent post-traumatic growth (PTG) in individuals with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Ten participants (average illness duration 7.4 years) were interviewed (average length, 79 minutes) via a semi-structured interview schedule and verbatim transcriptions were analysed with interpretative phenomenological analysis. The four superordinate themes revealed were 'comparisons of past to present self: "you have to be someone else, and you have to live with that''', 'the effect of social isolation on identity and subsequent insights into others' behaviours', 'contemplation of future and identity: ''where do I go from here?"', and 'PTG: "the letting go, the building up, [and] the gradual process of rebuilding"'. These themes outlined the experiences of those with ME/CFS as they underwent changes in identity due to the limitations the condition imposed on activities and roles, understanding others' behaviours after a period of isolation, the comparison of the past self with the present self and finally, the positive growth that was noted by two of the interviewees with regards to a new 'true' self. Despite the distressing and unpredictable nature of ME/CFS, it appears that individuals with this disorder can experience personal growth.

  5. Ecloud Build-Up Simulations for the FNAL MI for a Mixed Fill Pattern: Dependence on Peak SEY and Pulse Intensity During the Ramp

    SciTech Connect

    Furman, M. A.

    2010-12-11

    We present simulation results of the build-up of the electron-cloud density n{sub e} in three regions of the FNAL Main Injector (MI) for a beam fill pattern made up of 5 double booster batches followed by a 6th single batch. We vary the pulse intensity in the range N{sub t} = (2-5) x 10{sup 13}, and the beam kinetic energy in the range E{sub k} = 8-120 GeV. We assume a secondary electron emission model qualitatively corresponding to TiN, except that we let the peak value of the secondary electron yield (SEY) {delta}{sub max} vary as a free parameter in a fairly broad range. Our main conclusions are: (1) At fixed N{sub t} there is a clear threshold behavior of n{sub e} as a function of {delta}{sub max} in the range {approx} 1.1-1.3. (2) At fixed {delta}{sub max}, there is a threshold behavior of n{sub e} as a function of N{sub t} provided {delta}{sub max} is sufficiently high; the threshold value of N{sub t} is a function of the characteristics of the region being simulated. (3) The dependence on E{sub k} is weak except possibly at transition energy. Most of these results were informally presented to the relevant MI personnel in April 2010.

  6. Evolution of lateral structures during the functional stack build-up of P3HT:PCBM-based bulk heterojunction solar cells.

    PubMed

    Guo, Shuai; Ruderer, Matthias A; Rawolle, Monika; Körstgens, Volker; Birkenstock, Christopher; Perlich, Jan; Müller-Buschbaum, Peter

    2013-09-11

    Bulk heterojunction (BHJ) solar cells from 1,2-dichlorobenzene solution processed regioregular poly(3-hexylthiophene-2,5-diyl) (P3HT): phenyl-C61-butyric acid methyl ester (PCBM) are prepared and investigated at different steps of the multilayer stack build-up of the device. The inner structure is probed from the molecular to the mesoscale with grazing incidence small/wide-angle X-ray scattering (GISAXS/GIWAXS) and X-ray reflectivity (XRR). The surface morphology is detected with atomic force microscopy (AFM). Therefore, an in-depth knowledge of the three-dimensional morphology of the bulk heterojunction solar cell, starting from the cleaned ITO substrate up to the final post-treated solar cell, is generated. The active layer structure is influenced by the annealing as well as by the top contact deposition. Structures coarsen during the evaporation of the metal contacts. The P3HT crystal structure strongly depends on the device processing as well. These morphological changes together with the diffusion of aluminum atoms to the active layer are of importance for the device efficiency. PMID:23942383

  7. High-Resolution Linkage and Quantitative Trait Locus Mapping Aided by Genome Survey Sequencing: Building Up An Integrative Genomic Framework for a Bivalve Mollusc

    PubMed Central

    Jiao, Wenqian; Fu, Xiaoteng; Dou, Jinzhuang; Li, Hengde; Su, Hailin; Mao, Junxia; Yu, Qian; Zhang, Lingling; Hu, Xiaoli; Huang, Xiaoting; Wang, Yangfan; Wang, Shi; Bao, Zhenmin

    2014-01-01

    Genetic linkage maps are indispensable tools in genetic and genomic studies. Recent development of genotyping-by-sequencing (GBS) methods holds great promise for constructing high-resolution linkage maps in organisms lacking extensive genomic resources. In the present study, linkage mapping was conducted for a bivalve mollusc (Chlamys farreri) using a newly developed GBS method—2b-restriction site-associated DNA (2b-RAD). Genome survey sequencing was performed to generate a preliminary reference genome that was utilized to facilitate linkage and quantitative trait locus (QTL) mapping in C. farreri. A high-resolution linkage map was constructed with a marker density (3806) that has, to our knowledge, never been achieved in any other molluscs. The linkage map covered nearly the whole genome (99.5%) with a resolution of 0.41 cM. QTL mapping and association analysis congruously revealed two growth-related QTLs and one potential sex-determination region. An important candidate QTL gene named PROP1, which functions in the regulation of growth hormone production in vertebrates, was identified from the growth-related QTL region detected on the linkage group LG3. We demonstrate that this linkage map can serve as an important platform for improving genome assembly and unifying multiple genomic resources. Our study, therefore, exemplifies how to build up an integrative genomic framework in a non-model organism. PMID:24107803

  8. Orthorhombic 11C pyrrhotite from Michałkowa, Góry Sowie Block, The Sudetes, Poland - preliminary report

    NASA Astrophysics Data System (ADS)

    Rybicki, Maciej; Krzykawski, Tomasz

    2014-09-01

    This study provides the preliminary report about first occurrence of orthorhombic 11C pyrrhotite (Fe(1-x)S) from the Sudetes, Poland. Samples of pyrrhotite-containing two-pyroxene gabbro were found in a classic pegmatite locality in Michałkowa near Walim in the Góry Sowie Block. Based on microscopic methods, pyrrhotite is associated with pentlandite, chalcopyrite, chromite, ilmenite, gersdorffite, magnetite, biotite, magnesiohornblende, clinochlore, lizardite and talc. X-Ray diffraction (XRD) indicate that pyrrhotite has orthorhombic 11C structure and it is characterized by: a = 3.433(9) Å, b = 5.99(2) Å, c = 5.7432(5) Å, β = 90º and d102 = 2.06906 Å. Mössbauer studies confirmed the XRD data. Pyrrhotite has three sextets with hyperfine parameter values 30.8 T for sextet A, 27.9 T and 25.8 T for sextets B and C respectively, indicating orthorhombic structure, the composition near Fe10S11 and x = 0.0909

  9. Orthorhombic 11C Pyrrhotite from Michałkowa, Góry Sowie Block, The Sudetes, Poland - Preliminary Report

    NASA Astrophysics Data System (ADS)

    Rybicki, Maciej; Krzykawski, Tomasz

    2014-09-01

    This study provides the preliminary report about first occurrence of orthorhombic 11C pyrrhotite (Fe(i-x)S) from the Sudetes, Poland. Samples of pyrrhotite-containing two-pyroxene gabbro were found in a classic pegmatite locality in Michałkowa near Walim in the Góry Sowie Block. Based on microscopic methods, pyrrhotite is associated with pentlandite, chalcopyrite, chromite, ilmenite, gersdorffite, magnetite, biotite, magnesiohornblende, clinochlore, lizardite and talc. X-Ray diffraction (XRD) indicate that pyrrhotite has orthorhombic 11C structure and it is characterized by: a = 3.433(9) Å, b = 5.99(2) Å, c = 5.7432(5) Å, ß = 90° and d 102 = 2.06906 Å. Mössbauer studies confirmed the XRD data. Pyrrhotite has three sextets with hyperfine parameter values 30.8 T for sextet A, 27.9 T and 25.8 T for sextets B and C respectively, indicating orthorhombic structure, the composition near Fe10S11 and x = 0.0909.

  10. Application of Gray Markov SCGM(1,1)c Model to Prediction of Accidents Deaths in Coal Mining

    PubMed Central

    Lan, Jian-yi; Zhou, Ying

    2014-01-01

    The prediction of mine accident is the basis of aviation safety assessment and decision making. Gray prediction is suitable for such kinds of system objects with few data, short time, and little fluctuation, and Markov chain theory is just suitable for forecasting stochastic fluctuating dynamic process. Analyzing the coal mine accident human error cause, combining the advantages of both Gray prediction and Markov theory, an amended Gray Markov SCGM(1,1)c model is proposed. The gray SCGM(1,1)c model is applied to imitate the development tendency of the mine safety accident, and adopt the amended model to improve prediction accuracy, while Markov prediction is used to predict the fluctuation along the tendency. Finally, the new model is applied to forecast the mine safety accident deaths from 1990 to 2010 in China, and, 2011–2014 coal accidents deaths were predicted. The results show that the new model not only discovers the trend of the mine human error accident death toll but also overcomes the random fluctuation of data affecting precision. It possesses stronger engineering application. PMID:27419203

  11. Effects of Laser Wavelength and Fluence in Pulsed Laser Deposition of Ge Films

    SciTech Connect

    Yap, Seong Shan; Reenaas, Turid Worren; Siew, Wee Ong; Tou, Teck Yong; Ladam, Cecile

    2011-03-30

    Nanosecond lasers with ultra-violet, visible and infrared wavelengths: KrF (248 nm, 25 ns) and Nd:YAG (1064 nm, 532 nm, 355 nm, 5 ns) were used to ablate polycrystalline Ge target and deposit Ge films in vacuum (<10-6 Torr). Time-integrated optical emission spectra were obtained for laser fluence from 0.5-10 J/cm{sup 2}. Neutrals and ionized Ge species in the plasma plume were detected by optical emission spectroscopy. Ge neutrals dominated the plasma plume at low laser fluence while Ge{sup +} ions above some threshold fluence. The deposited amorphous thin-film samples consisted of particulates of size from nano to micron. The relation of the film properties and plume species at different laser fluence and wavelengths were discussed.

  12. Rate of F center formation in sapphire under low-energy low-fluence Ar+ irradiation

    NASA Astrophysics Data System (ADS)

    Epie, E. N.; Wijesundera, D. N.; Tilakaratne, B. P.; Chen, Q. Y.; Chu, W. K.

    2016-03-01

    Ionoluminescence, optical absorption spectroscopy and Rutherford backscattering spectrometry channelling (RBS-C) have been used to study the rate of F center formation with fluence in 170 keV Ar+ irradiated single crystals of α-Al2O3 (sapphire) at room temperature. Implantation fluences range between 1013 cm-2 and 5 ×1014 cm-2. F center density (NF) has been found to display an initial rapid linear increase with Ar+ fluence followed by saturation to a maximum value of 1.74 ×1015 cm-2. Experimental results show a 1-1 correlation between radiation damage in the oxygen sublattice and F center density. This suggest F center kinetics in sapphire under low-energy low-fluence Ar irradiation is a direct consequence of dynamic competition between oxygen defect creation and recombination. An attempt has also been made to extend this discussion to F center kinetics in sapphire under swift heavy ion irradiation.

  13. Rapid radiosynthesis of [11C] and [14C]azelaic, suberic, and sebacic acids for in vivo mechanistic studies of systemic acquired resistance in plants

    SciTech Connect

    Best M.; Fowler J.; Best, M.; Gifford, A.N.; Kim, S.W.; Babst, B.; Piel, M.; Roesch, F.; Fowler, J.S.

    2011-11-25

    A recent report that the aliphatic dicarboxylic acid, azelaic acid (1,9-nonanedioic acid) but not related acids, suberic acid (1,8-octanedioic acid) or sebacic (1,10-decanedioic acid) acid induces systemic acquired resistance to invading pathogens in plants stimulated the development of a rapid method for labeling these dicarboxylic acids with {sup 11}C and {sup 14}C for in vivo mechanistic studies in whole plants. {sup 11}C-labeling was performed by reaction of ammonium [{sup 11}C]cyanide with the corresponding bromonitrile precursor followed by hydrolysis with aqueous sodium hydroxide solution. Total synthesis time was 60 min. Median decay-corrected radiochemical yield for [{sup 11}C]azelaic acid was 40% relative to trapped [{sup 11}C]cyanide, and specific activity was 15 GBq/{micro}mol. Yields for [{sup 11}C]suberic and sebacic acids were similar. The {sup 14}C-labeled version of azelaic acid was prepared from potassium [{sup 14}C]cyanide in 45% overall radiochemical yield. Radiolabeling procedures were verified using {sup 13}C-labeling coupled with {sup 13}C-NMR and liquid chromatography-mass spectrometry analysis. The {sup 11}C and {sup 14}C-labeled azelaic acid and related dicarboxylic acids are expected to be of value in understanding the mode-of-action, transport, and fate of this putative signaling molecule in plants.

  14. N-11C-Methyl-Dopamine PET Imaging of Sympathetic Nerve Injury in a Swine Model of Acute Myocardial Ischemia: A Comparison with 13N-Ammonia PET

    PubMed Central

    Zhou, Weina; Wang, Xiangcheng; He, Yulin; Nie, Yongzhen; Zhang, Guojian; Wang, Cheng; Wang, Chunmei; Wang, Xuemei

    2016-01-01

    Objective. Using a swine model of acute myocardial ischemia, we sought to validate N-11C-methyl-dopamine (11C-MDA) as an agent capable of imaging cardiac sympathetic nerve injury. Methods. Acute myocardial ischemia was surgically generated in Chinese minipigs. ECG and serum enzyme levels were used to detect the presence of myocardial ischemia. Paired 11C-MDA PET and 13N-ammonia PET scans were performed at baseline, 1 day, and 1, 3, and 6 months after surgery to relate cardiac sympathetic nerve injury to blood perfusion. Results. Seven survived the surgical procedure. The ECG-ST segment was depressed, and levels of the serum enzymes increased. Cardiac uptake of tracer was quantified as the defect volume. Both before and immediately after surgery, the images obtained with 11C-MDA and 13N-ammonia were similar. At 1 to 6 months after surgery, however, 11C-MDA postsurgical left ventricular myocardial defect volume was significantly greater compared to 13N-ammonia. Conclusions. In the Chinese minipig model of acute myocardial ischemia, the extent of the myocardial defect as visualized by 11C-MDA is much greater than would be suggested by blood perfusion images, and the recovery from myocardial sympathetic nerve injury is much slower than the restoration of blood perfusion. 11C-MDA PET may provide additional biological information during recovery from ischemic heart disease. PMID:27034950

  15. Positron emission tomography ligand [11C]5-hydroxy-tryptophan can be used as a surrogate marker for the human endocrine pancreas.

    PubMed

    Eriksson, Olof; Espes, Daniel; Selvaraju, Ram K; Jansson, Emma; Antoni, Gunnar; Sörensen, Jens; Lubberink, Mark; Biglarnia, Ali-Reza; Eriksson, Jan W; Sundin, Anders; Ahlström, Håkan; Eriksson, Barbro; Johansson, Lars; Carlsson, Per-Ola; Korsgren, Olle

    2014-10-01

    In humans, a well-developed serotonin system is localized to the pancreatic islets while being absent in exocrine pancreas. Assessment of pancreatic serotonin biosynthesis could therefore be used to estimate the human endocrine pancreas. Proof of concept was tested in a prospective clinical trial by comparisons of type 1 diabetic (T1D) patients, with extensive reduction of β-cells, with healthy volunteers (HVs). C-peptide-negative (i.e., insulin-deficient) T1D subjects (n = 10) and HVs (n = 9) underwent dynamic positron emission tomography with the radiolabeled serotonin precursor [(11)C]5-hydroxy-tryptophan ([(11)C]5-HTP). A significant accumulation of [(11)C]5-HTP was obtained in the pancreas of the HVs, with large interindividual variation. A substantial and highly significant reduction (66%) in the pancreatic uptake of [(11)C]5-HTP in T1D subjects was observed, and this was most evident in the corpus and caudal regions of the pancreas where β-cells normally are the major constituent of the islets. [(11)C]5-HTP retention in the pancreas was reduced in T1D compared with nondiabetic subjects. Accumulation of [(11)C]5-HTP in the pancreas of both HVs and subjects with T1D was in agreement with previously reported morphological observations on the β-cell volume, implying that [(11)C]5-HTP retention is a useful noninvasive surrogate marker for the human endocrine pancreas. PMID:24848067

  16. A two-compartment description and kinetic procedure for measuring regional cerebral ( sup 11 C)nomifensine uptake using positron emission tomography

    SciTech Connect

    Salmon, E.; Brooks, D.J.; Leenders, K.L.; Turton, D.R.; Hume, S.P.; Cremer, J.E.; Jones, T.; Frackowiak, R.S. )

    1990-05-01

    S-(11C)Nomifensine (S-(11C)NMF) is a positron-emitting tracer suitable for positron emission tomography, which binds to both dopaminergic and noradrenergic reuptake sites in the striatum and the thalamus. Modelling of the cerebral distribution of this drug has been hampered by the rapid appearance of glucuronide metabolites in the plasma, which do not cross the blood--brain barrier. To date, (11C)NMF uptake has simply been expressed as regional versus nonspecific cerebellar activity ratios. We have calculated a free NMF input curve from red cell activity curves, using the fact that the free drug rapidly equilibrates between red cells and plasma, while glucuronides do not enter red cells. With this free (11C)NMF input function, all regional cerebral uptake curves could be fitted to a conventional two-compartment model, defining tracer distribution in terms of (11C)NMF regional volume of distribution. Assuming that the cerebellar volume of distribution of (11C)NMF represents the nonspecific volume of distribution of the tracer in striatum and thalamus, we have calculated an equilibrium partition coefficient for (11C)NMF between freely exchanging specific and nonspecific compartments in these regions, representing its binding potential to dopaminergic or noradrenergic uptake sites (or complexes). This partition coefficient was lower in the striatum when the racemate rather than the active S-enantiomer of (11C)NMF was administered. In the striatum of patients suffering from Parkinson's disease and multiple-system atrophy, the specific compartmentation of S-(11C)NMF was significantly decreased compared with that of age-matched volunteers.

  17. Using [(11)C]Ro15 4513 PET to characterise GABA-benzodiazepine receptors in opiate addiction: Similarities and differences with alcoholism.

    PubMed

    Lingford-Hughes, Anne; Myers, James; Watson, Ben; Reid, Alastair G; Kalk, Nicola; Feeney, Adrian; Hammers, Alexander; Riaño-Barros, Daniela A; McGinnity, Colm J; Taylor, Lindsay G; Rosso, Lula; Brooks, David J; Turkheimer, Federico; Nutt, David J

    2016-05-15

    The importance of the GABA-benzodiazepine receptor complex and its subtypes are increasingly recognised in addiction. Using the α1/α5 benzodiazepine receptor PET radioligand [(11)C]Ro15 4513, we previously showed reduced binding in the nucleus accumbens and hippocampus in abstinent alcohol dependence. We proposed that reduced [(11)C]Ro15 4513 binding in the nucleus accumbens was a marker of addiction whilst the reduction in hippocampus and positive relationship with memory was a consequence of chronic alcohol abuse. To examine this further we assessed [(11)C]Ro15 4513 binding in another addiction, opiate dependence, and used spectral analysis to estimate contributions of α1 and α5 subtypes to [(11)C]Ro15 4513 binding in opiate and previously acquired alcohol-dependent groups. Opiate substitute maintained opiate-dependent men (n=12) underwent an [(11)C]Ro15 4513 PET scan and compared with matched healthy controls (n=13). We found a significant reduction in [(11)C]Ro15 4513 binding in the nucleus accumbens in the opiate-dependent compared with the healthy control group. There was no relationship between [(11)C]Ro15 4513 binding in the hippocampus with memory. We found that reduced [(11)C]Ro15 4513 binding was associated with reduced α5 but not α1 subtypes in the opiate-dependent group. This was also seen in an alcohol-dependent group where an association between memory performance and [(11)C]Ro15 4513 binding was primarily driven by α5 and not α1 subtype. We suggest that reduced α5 levels in the nucleus accumbens are associated with addiction since we have now shown this in dependence to two pharmacologically different substances, alcohol and opiates.

  18. [11C]Doxepin binding to histamine H1 receptors in living human brain: reproducibility during attentive waking and circadian rhythm

    PubMed Central

    Shibuya, Katsuhiko; Funaki, Yoshihito; Hiraoka, Kotaro; Yoshikawa, Takeo; Naganuma, Fumito; Miyake, Masayasu; Watanuki, Shoichi; Sato, Hirotoshi; Tashiro, Manabu; Yanai, Kazuhiko

    2012-01-01

    Molecular imaging in neuroscience is a new research field that enables visualization of the impact of molecular events on brain structure and function in humans. While magnetic resonance-based imaging techniques can provide complex information at the level of system, positron emission tomography (PET) enables determination of the distribution and density of receptor and enzyme in the human brain. Previous studies using [11C]raclopride and [11C]FLB457 revealed that the release of neuronal dopamine was increased in human brain by psychostimulants or reward stimuli. Following on from these previous [11C]raclopride studies, we examined whether the levels of neuronal release of histamine might change [11C]doxepin binding to the H1 receptors under the influence of physiological stimuli. The purpose of the present study was to evaluate the test–retest reliability of quantitative measurement of [11C]doxepin binding between morning and afternoon and between resting and attentive waking conditions in healthy human subjects. There was a trend for a decrease in [11C]doxepin binding during attentive calculation tasks compared with that in resting conditions, but the difference (less than 10%) was not significant. Similarly, the binding potential of [11C]doxepin in the cerebral cortex was slightly higher in the morning than that in the afternoon, but it was also insignificant. These data suggest that higher histamine release during wakefulness could not decrease the [11C]doxepin binding in the brain. This study confirmed the reproducibility and reliability of [11C]doxepin in the previous imaging studies to measure the H1 receptor. PMID:22701403

  19. Using [11C]Ro15 4513 PET to characterise GABA-benzodiazepine receptors in opiate addiction: Similarities and differences with alcoholism

    PubMed Central

    Lingford-Hughes, Anne; Myers, James; Watson, Ben; Reid, Alastair G.; Kalk, Nicola; Feeney, Adrian; Hammers, Alexander; Riaño-Barros, Daniela A.; McGinnity, Colm J.; Taylor, Lindsay G.; Rosso, Lula; Brooks, David J.; Turkheimer, Federico; Nutt, David J.

    2016-01-01

    The importance of the GABA-benzodiazepine receptor complex and its subtypes are increasingly recognised in addiction. Using the α1/α5 benzodiazepine receptor PET radioligand [11C]Ro15 4513, we previously showed reduced binding in the nucleus accumbens and hippocampus in abstinent alcohol dependence. We proposed that reduced [11C]Ro15 4513 binding in the nucleus accumbens was a marker of addiction whilst the reduction in hippocampus and positive relationship with memory was a consequence of chronic alcohol abuse. To examine this further we assessed [11C]Ro15 4513 binding in another addiction, opiate dependence, and used spectral analysis to estimate contributions of α1 and α5 subtypes to [11C]Ro15 4513 binding in opiate and previously acquired alcohol-dependent groups. Opiate substitute maintained opiate-dependent men (n = 12) underwent an [11C]Ro15 4513 PET scan and compared with matched healthy controls (n = 13). We found a significant reduction in [11C]Ro15 4513 binding in the nucleus accumbens in the opiate-dependent compared with the healthy control group. There was no relationship between [11C]Ro15 4513 binding in the hippocampus with memory. We found that reduced [11C]Ro15 4513 binding was associated with reduced α5 but not α1 subtypes in the opiate-dependent group. This was also seen in an alcohol-dependent group where an association between memory performance and [11C]Ro15 4513 binding was primarily driven by α5 and not α1 subtype. We suggest that reduced α5 levels in the nucleus accumbens are associated with addiction since we have now shown this in dependence to two pharmacologically different substances, alcohol and opiates. PMID:26876472

  20. Sustained Recreational Use of Ecstasy Is Associated with Altered Pre and Postsynaptic Markers of Serotonin Transmission in Neocortical Areas: A PET Study with [11C]DASB and [11C]MDL 100907

    PubMed Central

    Urban, Nina BL; Girgis, Ragy R; Talbot, Peter S; Kegeles, Lawrence S; Xu, X; Frankle, W Gordon; Hart, Carl L; Slifstein, Mark; Abi-Dargham, Anissa; Laruelle, Marc

    2012-01-01

    3,4-Methylenedioxymethamphetamine (MDMA), the main psychoactive component of the recreational drug ecstasy, is a potent serotonin (5-HT) releaser. In animals, MDMA induces 5-HT depletion and toxicity in 5-HT neurons. The aim of this study was to investigate both presynaptic (5-HT transporter, SERT) and postsynaptic (5-HT2A receptor) markers of 5-HT transmission in recently abstinent chronic MDMA users compared with matched healthy controls. We hypothesized that MDMA use is associated with lower SERT density and concomitant upregulation of 5-HT2A receptors. Positron emission tomography studies using the SERT ligand [11C]DASB and the 5-HT2A receptor ligand [11C]MDL 100907 were evaluated in 13 current and recently detoxified MDMA users and 13 matched healthy controls. MDMA users reported a mean duration of ecstasy use of 8 years, regular exposure, and at least 2 weeks of abstinence before the scans. SERT and 5-HT2A receptor availability (binding potential, BPND) were analyzed with a two-tissue compartment model with arterial input function. Current recreational MDMA use was significantly associated with lower SERT BPND and higher 5-HT2A receptor BPND in cortical, but not subcortical regions. Decreased SERT BPND was regionally associated with upregulated 5-HT2A receptor BPND. In light of the animal literature, the most parsimonious interpretation is that repeated exposure to MDMA in humans, even in moderate amounts, leads to damage in 5-HT neuron terminals innervating the cortex. Alterations in mood, cognition, and impulse control associated with these changes might contribute to sustain MDMA use. The reversibility of these changes upon abstinence remains to be firmly established. PMID:22353758

  1. Light fluence correction for quantitative determination of tissue absorption coefficient using multi-spectral optoacoustic tomography

    NASA Astrophysics Data System (ADS)

    Brochu, Frederic M.; Joseph, James; Tomaszewski, Michal; Bohndiek, Sarah E.

    2015-07-01

    MultiSpectral Optoacoustic Tomography (MSOT) is a fast developing imaging modality, combining the high resolution and penetration depth of ultrasound with the excellent contrast from optical imaging of tissue. Absorption and scattering of the near infrared excitation light modulates the spectral profile of light as it propagates deep into biological tissue, meaning the images obtained provide only qualitative insight into the distribution of tissue chromophores. The goal of this work is to accurately recover the spectral profile of excitation light by modelling light fluence in the data reconstruction, to enable quantitative imaging. We worked with a commercial small animal MSOT scanner and developed our light fluence correction for its' cylindrical geometry. Optoacoustic image reconstruction pinpoints the sources of acoustic waves detected by the transducers and returns the initial pressure amplitude at these points. This pressure is the product of the dimensionless Grüneisen parameter, the absorption coefficient and the light fluence. Under the condition of constant Grüneisen parameter and well modelled light fluence, there is a linear relationship between the initial pressure amplitude measured in the optoacoustic image and the absorption coefficient. We were able to reproduce this linear relationship in different physical regions of an agarose gel phantom containing targets of known optical absorption coefficient, demonstrating that our light fluence model was working. We also demonstrate promising results of light fluence correction effects on in vivo data.

  2. Investigations of heat transfer, entropy generation and pressure build up for upward flow in a vertical channel equipped with a fin array

    NASA Astrophysics Data System (ADS)

    Nemitallah, Medhat A.; Zohir, Alaa E.

    2016-09-01

    The optimal thermal systems design criteria by maximizing the amount of heat transfer per pressure losses is a very important topic. In this work, flow and convection and radiation heat transfer characteristics are studied numerically for a flow in a vertical channel equipped with transverse fin array. The influences of fin height on heat transfer characteristics and fluid flow is investigated. Large number of fins is used (40 fins) in order to reach the fully developed conditions after few fins from the entrance. Based on the calculated data of temperature and velocity, the local entropy generation is calculated through the whole channel by solving the entropy generation equation. The results are validated against the available data in the literature and both results are in a good agreement. Optimizations for flow conditions and channel geometry are performed in order to obtain maximum heat transfer per pumping power losses. The results showed that the highest values of total heat transfer per pumping power losses are obtained at fin height to the gap width values of 0.1 and 0.3. The effect of heat transfer by radiation on entropy generation is examined and, the effect of the ratio, Gr/Re2, on the pressure field is also investigated. It was found that a positive pressure gradient appears downstream in the channel when the value of Gr/Re2 exceeds a certain limit. For Gr/Re2 values between 0 and 9, the pressure gradient is negative; however, when the value Gr/Re2 exceeds 9, the pressure starts to build up through the channel axis.

  3. Changing nutrient stoichiometry affects phytoplankton production, DOP build up and dinitrogen fixation - a mesocosm experiment in the eastern tropical North Atlantic

    NASA Astrophysics Data System (ADS)

    Meyer, J.; Löscher, C. R.; Neulinger, S. C.; Reichel, A. F.; Loginova, A.; Borchard, C.; Schmitz, R. A.; Hauss, H.; Kiko, R.; Riebesell, U.

    2015-07-01

    Ocean deoxygenation due to climate change may alter redox-sensitive nutrient cycles in the marine environment. The productive eastern tropical North Atlantic (ETNA) upwelling region may be particularly affected when the relatively moderate oxygen minimum zone (OMZ) deoxygenates further and microbially-driven nitrogen (N) loss processes are promoted. Consequently, water masses with a low N : P ratio could reach the euphotic layer, possibly influencing primary production in those waters. Previous mesocosm studies in the oligotrophic Atlantic Ocean identified N availability as controlling of primary production, while a possible co-limitation of nitrate and phosphate (P) could not be ruled out. To better understand the impact of changing N : P ratios on primary production and on N2 fixation in the ETNA surface ocean, we conducted land-based mesocosm experiments with natural plankton communities and applied a broad range of N : P ratios (2.67-48). Silicate was supplied at 15 μmol L-1 in all mesocosms. We monitored nutrient drawdown, bloom formation, biomass build up and diazotrophic feedback in response to variable nutrient stoichiometry. Our results confirmed N to be limiting to primary production. We found that excess P was channeled through particulate organic matter (POP) into the dissolved organic matter (DOP) pool. In mesocosms with low P availability, DOP was utilized while N2 fixation increased, suggesting a link between those two processes. Interestingly this observation was most pronounced in mesocosms where inorganic N was still available, indicating that bioavailable N does not necessarily has to have a negative impact on N2 fixation. We observed a shift from a mixed cyanobacterial/proteobacterial dominated active diazotrophic community towards diazotrophic diatom symbionts of the Richelia-Rhizosolenia symbiosis. We hypothesize that a potential change in nutrient stoichiometry in the ETNA might lead to a general shift within the diazotrophic community

  4. Trace organic solutes in closed-loop forward osmosis applications: influence of membrane fouling and modeling of solute build-up.

    PubMed

    D'Haese, Arnout; Le-Clech, Pierre; Van Nevel, Sam; Verbeken, Kim; Cornelissen, Emile R; Khan, Stuart J; Verliefde, Arne R D

    2013-09-15

    In this study, trace organics transport in closed-loop forward osmosis (FO) systems was assessed. The FO systems considered, consisted of an FO unit and a nanofiltration (NF) or reverse osmosis (RO) unit, with the draw solution circulating between both units. The rejection of trace organics by FO, NF and RO was tested. It was found that the rejection rates of FO were generally comparable with NF and lower than RO rejection rates. To assess the influence of fouling in FO on trace organics rejection, FO membranes were fouled with sodium alginate, bovine serum albumin or by biofilm growth, after which trace organics rejection was tested. A negative influence of fouling on FO rejection was found which was limited in most cases, while it was significant for some compounds such as paracetamol and naproxen, indicating specific compound-foulant interactions. The transport mechanism of trace organics in FO was tested, in order to differentiate between diffusive and convective transport. The concentration of trace organics in the final product water and the build-up of trace organics in the draw solution were modeled assuming the draw solution was reconcentrated by NF/RO and taking into account different transport mechanisms for the FO membrane and different rejection rates by NF/RO. Modeling results showed that if the FO rejection rate is lower than the RO rejection rate (as is the case for most compounds tested), the added value of the FO-RO cycle compared to RO only at steady-state was small for diffusively and negative for convectively transported trace organics. Modeling also showed that trace organics accumulate in the draw solution.

  5. Soil environmental conditions and microbial build-up mediate the effect of plant diversity on soil nitrifying and denitrifying enzyme activities in temperate grasslands.

    PubMed

    Le Roux, Xavier; Schmid, Bernhard; Poly, Franck; Barnard, Romain L; Niklaus, Pascal A; Guillaumaud, Nadine; Habekost, Maike; Oelmann, Yvonne; Philippot, Laurent; Salles, Joana Falcao; Schloter, Michael; Steinbeiss, Sibylle; Weigelt, Alexandra

    2013-01-01

    Random reductions in plant diversity can affect ecosystem functioning, but it is still unclear which components of plant diversity (species number - namely richness, presence of particular plant functional groups, or particular combinations of these) and associated biotic and abiotic drivers explain the observed relationships, particularly for soil processes. We assembled grassland communities including 1 to 16 plant species with a factorial separation of the effects of richness and functional group composition to analyze how plant diversity components influence soil nitrifying and denitrifying enzyme activities (NEA and DEA, respectively), the abundance of nitrifiers (bacterial and archaeal amoA gene number) and denitrifiers (nirK, nirS and nosZ gene number), and key soil environmental conditions. Plant diversity effects were largely due to differences in functional group composition between communities of identical richness (number of sown species), though richness also had an effect per se. NEA was positively related to the percentage of legumes in terms of sown species number, the additional effect of richness at any given legume percentage being negative. DEA was higher in plots with legumes, decreased with increasing percentage of grasses, and increased with richness. No correlation was observed between DEA and denitrifier abundance. NEA increased with the abundance of ammonia oxidizing bacteria. The effect of richness on NEA was entirely due to the build-up of nitrifying organisms, while legume effect was partly linked to modified ammonium availability and nitrifier abundance. Richness effect on DEA was entirely due to changes in soil moisture, while the effects of legumes and grasses were partly due to modified nitrate availability, which influenced the specific activity of denitrifiers. These results suggest that plant diversity-induced changes in microbial specific activity are important for facultative activities such as denitrification, whereas changes

  6. Building-Up of a DNA Barcode Library for True Bugs (Insecta: Hemiptera: Heteroptera) of Germany Reveals Taxonomic Uncertainties and Surprises

    PubMed Central

    Raupach, Michael J.; Hendrich, Lars; Küchler, Stefan M.; Deister, Fabian; Morinière, Jérome; Gossner, Martin M.

    2014-01-01

    During the last few years, DNA barcoding has become an efficient method for the identification of species. In the case of insects, most published DNA barcoding studies focus on species of the Ephemeroptera, Trichoptera, Hymenoptera and especially Lepidoptera. In this study we test the efficiency of DNA barcoding for true bugs (Hemiptera: Heteroptera), an ecological and economical highly important as well as morphologically diverse insect taxon. As part of our study we analyzed DNA barcodes for 1742 specimens of 457 species, comprising 39 families of the Heteroptera. We found low nucleotide distances with a minimum pairwise K2P distance <2.2% within 21 species pairs (39 species). For ten of these species pairs (18 species), minimum pairwise distances were zero. In contrast to this, deep intraspecific sequence divergences with maximum pairwise distances >2.2% were detected for 16 traditionally recognized and valid species. With a successful identification rate of 91.5% (418 species) our study emphasizes the use of DNA barcodes for the identification of true bugs and represents an important step in building-up a comprehensive barcode library for true bugs in Germany and Central Europe as well. Our study also highlights the urgent necessity of taxonomic revisions for various taxa of the Heteroptera, with a special focus on various species of the Miridae. In this context we found evidence for on-going hybridization events within various taxonomically challenging genera (e.g. Nabis Latreille, 1802 (Nabidae), Lygus Hahn, 1833 (Miridae), Phytocoris Fallén, 1814 (Miridae)) as well as the putative existence of cryptic species (e.g. Aneurus avenius (Duffour, 1833) (Aradidae) or Orius niger (Wolff, 1811) (Anthocoridae)). PMID:25203616

  7. Empirical assessment of the detection efficiency of CR-39 at high proton fluence and a compact, proton detector for high-fluence applications

    SciTech Connect

    Rosenberg, M. J. Séguin, F. H.; Waugh, C. J.; Rinderknecht, H. G.; Orozco, D.; Frenje, J. A.; Johnson, M. Gatu; Sio, H.; Zylstra, A. B.; Sinenian, N.; Li, C. K.; Petrasso, R. D.; Glebov, V. Yu.; Stoeckl, C.; Hohenberger, M.; Sangster, T. C.; LePape, S.; Mackinnon, A. J.; Bionta, R. M.; Landen, O. L.; and others

    2014-04-15

    CR-39 solid-state nuclear track detectors are widely used in physics and in many inertial confinement fusion (ICF) experiments, and under ideal conditions these detectors have 100% detection efficiency for ∼0.5–8 MeV protons. When the fluence of incident particles becomes too high, overlap of particle tracks leads to under-counting at typical processing conditions (5 h etch in 6N NaOH at 80 °C). Short etch times required to avoid overlap can cause under-counting as well, as tracks are not fully developed. Experiments have determined the minimum etch times for 100% detection of 1.7–4.3-MeV protons and established that for 2.4-MeV protons, relevant for detection of DD protons, the maximum fluence that can be detected using normal processing techniques is ≲3 × 10{sup 6} cm{sup −2}. A CR-39-based proton detector has been developed to mitigate issues related to high particle fluences on ICF facilities. Using a pinhole and scattering foil several mm in front of the CR-39, proton fluences at the CR-39 are reduced by more than a factor of ∼50, increasing the operating yield upper limit by a comparable amount.

  8. Empirical assessment of the detection efficiency of CR-39 at high proton fluence and a compact, proton detector for high-fluence applications

    SciTech Connect

    Rosenberg, M. J.; Séguin, F. H.; Waugh, C. J.; Rinderknecht, H. G.; Orozco, D.; Frenje, J. A.; Johnson, M. Gatu; Sio, H.; Zylstra, A. B.; Sinenian, N.; Li, C. K.; Petrasso, R. D.; Glebov, V. Yu.; Stoeckl, C.; Hohenberger, M.; Sangster, T. C.; LePape, S.; Mackinnon, A. J.; Bionta, R. M.; Landen, O. L.; Zacharias, R. A.; Kim, Y.; Herrmann, H. W.; Kilkenny, J. D.

    2014-04-14

    CR-39 solid-state nuclear track detectors are widely used in physics and in many inertial confinement fusion (ICF) experiments, and under ideal conditions these detectors have 100% detection efficiency for ~0.5–8 MeV protons. When the fluence of incident particles becomes too high, the overlap of particle tracks leads to under-counting at typical processing conditions (5h etch in 6N NaOH at 80°C). Short etch times required to avoid overlap can cause under-counting as well, as tracks are not fully developed. Experiments have determined the minimum etch times for 100% detection of 1.7–4.3-MeV protons and established that for 2.4-MeV protons, relevant for detection of DD protons, the maximum fluence that can be detected using normal processing techniques is ≲3 ×106 cm-2. A CR-39-based proton detector has been developed to mitigate issues related to high particle fluences on ICF facilities. Using a pinhole and scattering foil several mm in front of the CR-39, proton fluences at the CR-39 are reduced by more than a factor of ~50, increasing the operating yield upper limit by a comparable amount.

  9. Empirical assessment of the detection efficiency of CR-39 at high proton fluence and a compact, proton detector for high-fluence applications

    DOE PAGES

    Rosenberg, M. J.; Séguin, F. H.; Waugh, C. J.; Rinderknecht, H. G.; Orozco, D.; Frenje, J. A.; Johnson, M. Gatu; Sio, H.; Zylstra, A. B.; Sinenian, N.; et al

    2014-04-14

    CR-39 solid-state nuclear track detectors are widely used in physics and in many inertial confinement fusion (ICF) experiments, and under ideal conditions these detectors have 100% detection efficiency for ~0.5–8 MeV protons. When the fluence of incident particles becomes too high, the overlap of particle tracks leads to under-counting at typical processing conditions (5h etch in 6N NaOH at 80°C). Short etch times required to avoid overlap can cause under-counting as well, as tracks are not fully developed. Experiments have determined the minimum etch times for 100% detection of 1.7–4.3-MeV protons and established that for 2.4-MeV protons, relevant for detectionmore » of DD protons, the maximum fluence that can be detected using normal processing techniques is ≲3 ×106 cm-2. A CR-39-based proton detector has been developed to mitigate issues related to high particle fluences on ICF facilities. Using a pinhole and scattering foil several mm in front of the CR-39, proton fluences at the CR-39 are reduced by more than a factor of ~50, increasing the operating yield upper limit by a comparable amount.« less

  10. Empirical assessment of the detection efficiency of CR-39 at high proton fluence and a compact, proton detector for high-fluence applications.

    PubMed

    Rosenberg, M J; Séguin, F H; Waugh, C J; Rinderknecht, H G; Orozco, D; Frenje, J A; Johnson, M Gatu; Sio, H; Zylstra, A B; Sinenian, N; Li, C K; Petrasso, R D; Glebov, V Yu; Stoeckl, C; Hohenberger, M; Sangster, T C; LePape, S; Mackinnon, A J; Bionta, R M; Landen, O L; Zacharias, R A; Kim, Y; Herrmann, H W; Kilkenny, J D

    2014-04-01

    CR-39 solid-state nuclear track detectors are widely used in physics and in many inertial confinement fusion (ICF) experiments, and under ideal conditions these detectors have 100% detection efficiency for ∼0.5-8 MeV protons. When the fluence of incident particles becomes too high, overlap of particle tracks leads to under-counting at typical processing conditions (5 h etch in 6N NaOH at 80 °C). Short etch times required to avoid overlap can cause under-counting as well, as tracks are not fully developed. Experiments have determined the minimum etch times for 100% detection of 1.7-4.3-MeV protons and established that for 2.4-MeV protons, relevant for detection of DD protons, the maximum fluence that can be detected using normal processing techniques is ≲3 × 10(6) cm(-2). A CR-39-based proton detector has been developed to mitigate issues related to high particle fluences on ICF facilities. Using a pinhole and scattering foil several mm in front of the CR-39, proton fluences at the CR-39 are reduced by more than a factor of ∼50, increasing the operating yield upper limit by a comparable amount. PMID:24784597

  11. Brain Regional α-[11C]Methyl-L-Tryptophan Trapping in Medication-Free Patients With Obsessive-Compulsive Disorder

    PubMed Central

    Berney, Alexandre; Leyton, Marco; Gravel, Paul; Sibon, Igor; Sookman, Debbie; Neto, Pedro Rosa; Diksic, Mirko; Nakai, Akio; Pinard, Gilbert; Todorov, Christo; Okazawa, Hidehiko; Blier, Pierre; Nordahl, Thomas Edward; Benkelfat, Chawki

    2013-01-01

    Context The hypothesis of a serotonin (5-hydroxytryptamine [5-HT]) dysfunction in obsessive-compulsive disorder (OCD) stems largely from the clinical efficacy of 5-HT reuptake inhibitors. Serotonergic abnormalities in the unmedicated symptomatic state, however, remain to be fully characterized. Objective To investigate brain regional 5-HT synthesis, as indexed by positron emission tomography and the α-[11C]methyl-L-tryptophan trapping constant (K*), in treatment-free adults meeting criteria for OCD. Design Between-group comparison. Setting Department of Psychiatry and Montreal Neurological Institute, McGill University, and Department of Psychology, McGill University Health Centre, Quebec, Canada. Participants Twenty-one medication-free patients with OCD (15 men with a mean [SD] age of 33.2 [9.3] years and 6 women with a mean [SD] age of 35.8 [7.1] years) and 21 healthy controls matched for age and sex (15 men with a mean [SD] age of 32.9 [10.1] years and 6 women with a mean [SD] age of 36.5.5 [8.6] years). Main Outcome Measure The α-[11C]methyl-L-tryptophan brain trapping constant K*, which was analyzed with Statistical Parametric Mapping (SPM8) and with proportional normalization (extent threshold of 100 voxels with a peak threshold of P≤.005). Results Compared with healthy controls, the patients with OCD exhibited significantly greater α-[11C]methyl-L-tryptophan trapping in the right hippocampus and left temporal gyrus (Brodmann area 20). In the larger sub-sample of all men, these same differences were also evident, as well as higher K* values in the caudate nucleus. Individual differences in symptom severity correlated positively with K* values sampled from the caudate and temporal lobe of the patients with OCD, respectively. There were no regions where the patients exhibited abnormally low K* values. Volumetric analyses found no morphometric alterations that would account for the group differences. Conclusion The results support previous reports of greater

  12. Imaging Serotonergic Transmission with [11C]DASB-PET in Depressed and Non-Depressed Patients Infected with HIV

    PubMed Central

    Hammoud, Dima A.; Endres, Christopher J.; Hammond, Edward; Uzuner, Ovsev; Brown, Amanda; Nath, Avindra; Kaplin, Adam I.; Pomper, Martin G.

    2009-01-01

    Introduction Site-selective imaging can provide significant insight into the mechanism of HIV-associated neurological disease. The goal of this study was to evaluate the involvement of serotonergic transmission in HIV-associated depression using [11C]DASB, a serotonin transporter (5-HTT)-specific radiopharmaceutical for positron emission tomography (PET). Methods 9 depressed HIV+ subjects (HIV-D), 9 nondepressed HIV+ subjects (HIV-ND) and 7 healthy controls (HC) underwent an MRI scan and a [11C]DASB-PET scan. The outcome measure was 5-HTT binding potential normalized to nondisplaceable tissue radioligand (BPND). Results HIV-ND subjects had lower mean regional 5-HTT BPND estimates across regions, compared to HC, while HIV-D subjects demonstrated higher mean regional binding values than HIV-ND subjects in most regions. Prior to correction for the false discovery rate, HIV-ND had significantly lower BPND values compared to HC subjects in two regions (insula and anterior cingulate) and all HIV+ patients had significantly lower binding than HC in all regions except for the midbrain, thalamus and pons. After correction for the false discovery rate, only the insula showed significantly lower binding in HIV+ subjects compared to HC (P < 0.0045). Despite a significant difference in the duration of illness between the HIV-D and HIV-ND groups, there was no definite correlation between the duration of illness and BPND. Conclusion Lower [11C]DASB binding in HIV+ patients compared to HC may reflect serotonergic neuronal loss as a component of generalized HIV-associated neurodegeneration. Higher mean regional BPND values in HIV-D compared to HIV-ND subjects could reflect increased density of 5-HTT, leading to increased clearance of serotonin from the synapse, which could account, in part, for symptoms of depression. The lack of correlation between duration of illness and binding argues against these findings being the result of differential neurodegeneration only. Our findings

  13. [Detection of tumors in the central zone of the prostate with 11C-Choline PET/CT].

    PubMed

    Garcia, J R; Soler, M; Moragas, M; Ponce, A; Moreno, C; Riera, E

    2014-01-01

    Prostate tumors originate 68% in the peripheral region and 24% in the transitional region where tumors originating in the central zone are rare (8%). However, diagnosis of the tumors in the central zone is important since they exhibit greater aggressiveness conditioned by their location and different biological behavior. Magnetic resonance imaging shows problems in identifying lesions in the central prostate zone, since this region has a heterogeneous signal, mainly after the primary treatment. Ultrasound guided sextant biopsy shows a negative result in 28% of prostate tumors. Therefore, it is advisable to repeat or even to perform saturation biopsies. We present two patients, one of them with suspected biochemical prostate cancer and one with biochemical recurrence after radical treatment. In both, (11)C-Choline PET/CT allowed detection of the tumor focus in the central zone of the prostate, with negative complementary diagnostic test and biopsies. PMID:24119550

  14. [Radiosynthesis and preliminary evaluation of 5-([11C]methyloxy)-L-tryptophan as PET tumor imaging].

    PubMed

    He, Shan-zhen; Wang, Shu-xia; Hu, Kong-zhen; Yao, Bao-guo; Tang, Gang-hua

    2015-05-01

    The PET tracer 5-([11C]methyloxy)-L-tryptophan (5-(11)CMTP) was prepared by nucleophilic fluorination and alkylation reaction via a two-step procedure in order to develop specific tumor probe. The biodistribution and microPET imaging of 5-(11)CMTP were executed. The results unveiled that the overall radiochemical yield with no decay correction was (14.6 ±7.2) %, the radiochemical purity was more than 95% and high uptake and long retention time of 5-(11)CMTP in liver, kidney and blood were observed but low uptake in brain and muscle were found, furthermore, high uptake of 5-(11)CMTP in tumor tissue was observed. It seems that 5-(11)CMTP will be a potential amino acid tracer for tumors imaging with PET. PMID:26234137

  15. Fate of xylem-transported 11C- and 13C-labeled CO2 in leaves of poplar.

    PubMed

    Bloemen, Jasper; Bauweraerts, Ingvar; De Vos, Filip; Vanhove, Christian; Vandenberghe, Stefaan; Boeckx, Pascal; Steppe, Kathy

    2015-04-01

    In recent studies, assimilation of xylem-transported CO2 has gained considerable attention as a means of recycling respired CO2 in trees. However, we still lack a clear and detailed picture on the magnitude of xylem-transported CO2 assimilation, in particular within leaf tissues. To this end, detached poplar leaves (Populus × canadensis Moench 'Robusta') were allowed to take up a dissolved (13)CO2 label serving as a proxy of xylem-transported CO2 entering the leaf from the branch. The uptake rate of the (13)C was manipulated by altering the vapor pressure deficit (VPD) (0.84, 1.29 and 1.83 kPa). Highest tissue enrichments were observed under the highest VPD. Among tissues, highest enrichment was observed in the petiole and the veins, regardless of the VPD treatment. Analysis of non-labeled leaves showed that some (13)C diffused from the labeled leaves and was fixed in the mesophyll of the non-labeled leaves. However, (13)C leaf tissue enrichment analysis with elemental analysis coupled to isotope ratio mass spectrometry was limited in spatial resolution at the leaf tissue level. Therefore, (11)C-based CO2 labeling combined with positron autoradiography was used and showed a more detailed spatial distribution within a single tissue, in particular in secondary veins. Therefore, in addition to (13)C, (11) C-based autoradiography can be used to study the fate of xylem-transported CO2 at leaf level, allowing the acquisition of data at a yet unprecedented resolution.

  16. Synthesis and Preclinical Evaluation of Sulfonamido-based [11C-Carbonyl]-Carbamates and Ureas for Imaging Monoacylglycerol Lipase

    PubMed Central

    Wang, Lu; Mori, Wakana; Cheng, Ran; Yui, Joji; Hatori, Akiko; Ma, Longle; Zhang, Yiding; Rotstein, Benjamin H.; Fujinaga, Masayuki; Shimoda, Yoko; Yamasaki, Tomoteru; Xie, Lin; Nagai, Yuji; Minamimoto, Takafumi; Higuchi, Makoto; Vasdev, Neil; Zhang, Ming-Rong; Liang, Steven H.

    2016-01-01

    Monoacylglycerol lipase (MAGL) is a 33 kDa member of the serine hydrolase superfamily that preferentially degrades 2-arachidonoylglycerol (2-AG) to arachidonic acid in the endocannabinoid system. Inhibition of MAGL is not only of interest for probing the cannabinoid pathway but also as a therapeutic and diagnostic target for neuroinflammation. Limited attempts have been made to image MAGL in vivo and a suitable PET ligand for this target has yet to be identified and is urgently sought to guide small molecule drug development in this pathway. Herein we synthesized and evaluated the physiochemical properties of an array of eleven sulfonamido-based carbamates and ureas with a series of terminal aryl moieties, linkers and leaving groups. The most potent compounds were a novel MAGL inhibitor, N-((1-(1H-1,2,4-triazole-1-carbonyl)piperidin-4-yl) methyl)-4-chlorobenzenesulfonamide (TZPU; IC50 = 35.9 nM), and the known inhibitor 1,1,1,3,3,3-hexafluoropropan-2-yl 4-(((4-chlorophenyl)sulfonamido) methyl)piperidine-1-carboxylate (SAR127303; IC50 = 39.3 nM), which were also shown to be selective for MAGL over fatty acid amide hydrolase (FAAH), and cannabinoid receptors (CB1 & CB2). Both of these compounds were radiolabeled with carbon-11 via [11C]COCl2, followed by comprehensive ex vivo biodistribution and in vivo PET imaging studies in normal rats to determine their brain permeability, specificity, clearance and metabolism. Whereas TZPU did not show adequate specificity to warrant further evaluation, [11C]SAR127303 was advanced for preliminary PET neuroimaging studies in nonhuman primate. The tracer showed good brain permeability (ca. 1 SUV) and heterogeneous regional brain distribution which is consistent with the distribution of MAGL. PMID:27279908

  17. A General Tank Test of NACA Model 11-C Flying-boat Hull, Including the Effect of Changing the Plan Form of the Step

    NASA Technical Reports Server (NTRS)

    Dawson, John R

    1935-01-01

    The results of a general tank test model 11-C, a conventional pointed afterbody type of flying-boat hull, are given in tables and curves. These results are compared with the results of tests on model 11-A, from which model 11-C was derived, and it is found that the resistance of model 11-C is somewhat greater. The effect of changing the plan form of the step on model 11-C is shown from the results of tests made with three swallow-tail and three pointed steps formed by altering the original step of the model. These results show only minor differences from the results obtained with the original model.

  18. Evaluation of Oatp and Mrp2 activities in hepatobiliary excretion using newly developed positron emission tomography tracer [11C]dehydropravastatin in rats.

    PubMed

    Shingaki, Tomotaka; Takashima, Tadayuki; Ijuin, Ryosuke; Zhang, Xuan; Onoue, Tomohiro; Katayama, Yumiko; Okauchi, Takashi; Hayashinaka, Emi; Cui, Yilong; Wada, Yasuhiro; Suzuki, Masaaki; Maeda, Kazuya; Kusuhara, Hiroyuki; Sugiyama, Yuichi; Watanabe, Yasuyoshi

    2013-10-01

    We developed a pravastatin derivative, sodium (3R,5R)-3,5-dihydroxy-7-((1S,2S,6S,8S)-6-hydroxy-2-methyl-8-((1-[(11)C]-(E)-2-methyl-but-2-enoyl)oxy)-1,2,6,7,8,8a-hexahydronaphthalen-1-yl)heptanoate ([(11)C]DPV), as a positron emission tomography (PET) probe for noninvasive measurement of hepatobiliary transport, and conducted pharmacokinetic analysis in rats as a feasibility study for future clinical study. Transport activities of DPV in freshly isolated rat hepatocytes and rodent multidrug resistance-associated protein 2 (rMrp2; human, MRP2)-expressing membrane vesicles were similar to those of pravastatin. Rifampicin diminished the uptake of DPV and pravastatin by the hepatocytes, with similar inhibition potency. [(11)C]DPV underwent biotransformation to produce at least two metabolites in rat, but metabolism of [(11)C]DPV occurred negligibly in human hepatocytes during a 90-minute incubation. After intravenous injection, [(11)C]DPV was mainly distributed to the liver and kidneys, where the tissue uptake clearances (CLuptake,liver and CLuptake,kidney) were blood-flow-limited (73.6 ± 4.8 and 24.6 ± 0.6 ml/min per kilogram, respectively). Systemic elimination of [(11)C]DPV was delayed in rifampicin-treated rat and an Mrp2-deficient mutant rat, Eisai hyperbilirubinemic mutant rat (EHBR). Rifampicin treatment decreased both CLuptake,liver and CLuptake,kidney of [(11)C]DPV by 30% (P < 0.05), whereas these parameters were unchanged in EHBR. Meanwhile, the canalicular efflux clearance (CLint,bile) of [(11)C]DPV, which was 12.2 ± 1.5 ml/min per kilogram in the control rat, decreased by 60% and 89% in rifampicin-treated rat and EHBR (P < 0.05), respectively. These results indicate that [(11)C]DPV is taken up into the liver by organic anion-transporting polypeptides (rodent, Oatps; human, OATP) and excreted into bile by Mrp2 in rat, and that rifampicin may inhibit Mrp2 as well as Oatps, and consequently increase systemic exposure of [(11)C]DPV. PET using [(11)C]DPV is

  19. CD11c/CD18 Dominates Adhesion of Human Monocytes, Macrophages and Dendritic Cells over CD11b/CD18

    PubMed Central

    Ungai-Salánki, Rita; Orgován, Norbert; Szabó, Bálint; Horváth, Róbert; Erdei, Anna; Bajtay, Zsuzsa

    2016-01-01

    Complement receptors CR3 (CD11b/CD18) and CR4 (CD11c/CD18) belong to the family of beta2 integrins and are expressed mainly by myeloid cell types in humans. Previously, we proved that CR3 rather than CR4 plays a key role in phagocytosis. Here we analysed how CD11b and CD11c participate in cell adhesion to fibrinogen, a common ligand of CR3 and CR4, employing human monocytes, monocyte-derived macrophages (MDMs) and monocyte-derived dendritic cells (MDDCs) highly expressing CD11b as well as CD11c. We determined the exact numbers of CD11b and CD11c on these cell types by a bead-based technique, and found that the ratio of CD11b/CD11c is 1.2 for MDDCs, 1.7 for MDMs and 7.1 for monocytes, suggesting that the function of CD11c is preponderant in MDDCs and less pronounced in monocytes. Applying state-of-the-art biophysical techniques, we proved that cellular adherence to fibrinogen is dominated by CD11c. Furthermore, we found that blocking CD11b significantly enhances the attachment of MDDCs and MDMs to fibrinogen, demonstrating a competition between CD11b and CD11c for this ligand. On the basis of the cell surface receptor numbers and the measured adhesion strength we set up a model, which explains the different behavior of the three cell types. PMID:27658051

  20. Direct measurement of the breakout reaction {sup 11}C({alpha},p){sup 14}N in explosive hydrogen-burning process

    SciTech Connect

    Hayakawa, S.; Kubono, S.; Kahl, D.; Yamaguchi, H.; Binh, Dam N.; Hashimoto, T.; Wakabayashi, Y.; He, J. J.; Iwasa, N.; Kato, S.; Komatsubara, T.; Kwon, Y. K.; Teranishi, T.; Wanajo, S.

    2012-11-12

    We determined the {sup 11}C({alpha},p){sup 14}N reaction rate relevant to the nucleosynthesis in explosive hydrogen-burning stars. The measurement was performed by means of the thick target method in inverse kinematics with {sup 11}C RI beams. We derived the excitation functions for the ground-state transition and excited-state transitions using time-of-flight information for the first time. The present reaction rate is compared to the previous one.

  1. Direct measurement of the {sup 11}C({alpha},p){sup 14}N reaction at CRIB: A path from pp-chain to CNO

    SciTech Connect

    Hayakawa, S.; Kubono, S.; Kahl, D.; Yamaguchi, H.; Binh, D. N.; Hashimoto, T.; Wakabayashi, Y.; He, J. J.; Iwasa, N.; Kato, S.; Komatsubara, T.; Kwon, Y. K.; Teranishi, T.; Wanajo, S.

    2012-11-20

    We determined the total reaction rate of the {sup 11}C({alpha},p){sup 14}N reaction relevant to the nucleosynthesis in explosive hydrogen-burning stars. The measurement was performed by means of the thick target method in inverse kinematics with {sup 11}C RI beams. We performed the identification of the ground-state transition and excited-state transitions using time-of-flight information for the first time.

  2. Multidiagnostic analysis of ion dynamics in ultrafast laser ablation of metals over a large fluence range

    SciTech Connect

    Anoop, K. K. Bruzzese, R.; Amoruso, S.; Polek, M. P.; Harilal, S. S.

    2015-02-28

    The dynamics of ions in ultrafast laser ablation of metals is studied over fluences ranging from the ablation threshold up to ≈75 J/cm{sup 2} by means of three well-established diagnostic techniques. Langmuir probe, Faraday cup, and spectrally resolved intensified charge coupled device imaging simultaneously monitored the ions produced during ultrafast laser ablation of a pure copper target with 800 nm, ≈50 fs, Ti: Sapphire laser pulses. The fluence dependence of ion yield is analyzed, resulting in the observance of three different regimes. The specific ion yield shows a maximum at about 4–5 J/cm{sup 2}, followed by a gradual reduction and a transition to a high-fluence regime above ≈50 J/cm{sup 2}. The fluence dependence of the copper ions angular distribution is also analyzed, observing a gradual increase in forward-peaking of Cu ions for fluences up to ≈10 J/cm{sup 2}. A broader ion component is observed at larger angles for fluences larger than ≈10 J/cm{sup 2}. Finally, an experimental characterization of the ionic angular distribution for several metallic targets (Mg, Al, Cr, Fe, Cu, and W) is carried out at a relatively high fluence of ≈66 J/cm{sup 2}. Interestingly, the ion emission from the volatile metals shows a narrow, forward-peaked distribution, and a high peak ion yield compared to the refractory metals. Moreover, the width of ionic angular distributions presents a striking correlation with the peak ion yield.

  3. An assessment of fracture resistance of three composite resin core build-up materials on three prefabricated non-metallic posts, cemented in endodontically treated teeth: an in vitro study

    PubMed Central

    Pal, Bhupinder; Pujari, Prashant

    2015-01-01

    Endodontically treated teeth with excessive loss of tooth structure would require to be restored with post and core to enhance the strength and durability of the tooth and to achieve retention for the restoration. The non-metallic posts have a superior aesthetic quality. Various core build-up materials can be used to build-up cores on the posts placed in endodontically treated teeth. These materials would show variation in their bonding with the non-metallic posts thus affecting the strength and resistance to fracture of the remaining tooth structure. Aims. The aim of the study was to assess the fracture resistance of three composite resin core build-up materials on three prefabricated non-metallic posts, cemented in extracted endodontically treated teeth. Material and Methods. Forty-five freshly extracted maxillary central incisors of approximately of the same size and shape were selected for the study. They were divided randomly into 3 groups of 15 each, depending on the types of non-metallic posts used. Each group was further divided into 3 groups (A, B and C) of 5 samples each depending on three core build-up material used. Student’s unpaired ‘t’ test was also used to analyse and compare each group with the other groups individually, and decide whether their comparisons were statistically significant. Results. Luxacore showed the highest fracture resistance among the three core build-up materials with all the three posts systems. Ti-core had intermediate values of fracture resistance and Lumiglass had the least values of fracture resistance. PMID:25755926

  4. Increase of 20-HETE synthase after brain ischemia in rats revealed by PET study with 11C-labeled 20-HETE synthase-specific inhibitor

    PubMed Central

    Kawasaki, Toshiyuki; Marumo, Toshiyuki; Shirakami, Keiko; Mori, Tomoko; Doi, Hisashi; Suzuki, Masaaki; Watanabe, Yasuyoshi; Chaki, Shigeyuki; Nakazato, Atsuro; Ago, Yukio; Hashimoto, Hitoshi; Matsuda, Toshio; Baba, Akemichi; Onoe, Hirotaka

    2012-01-01

    20-Hydroxyeicosatetraenoic acid (20-HETE), an arachidonic acid metabolite known to be produced after cerebral ischemia, has been implicated in ischemic and reperfusion injury by mediating vasoconstriction. To develop a positron emission tomography (PET) probe for 20-HETE synthase imaging, which might be useful for monitoring vasoconstrictive processes in patients with brain ischemia, we synthesized a 11C-labeled specific 20-HETE synthase inhibitor, N′(4-dimethylaminohexyloxy)phenyl imidazole ([11C]TROA). Autoradiographic study showed that [11C]TROA has high-specific binding in the kidney and liver consistent with the previously reported distribution of 20-HETE synthase. Using transient middle cerebral artery occlusion in rats, PET study showed significant increases in the binding of [11C]TROA in the ipsilateral hemisphere of rat brains after 7 and 10 days, which was blocked by co-injection of excess amounts of TROA (10 mg/kg). The increased [11C]TROA binding on the ipsilateral side returned to basal levels within 14 days. In addition, quantitative real-time PCR revealed that increased expression of 20-HETE synthase was only shown on the ipsilateral side on day 7. These results indicate that [11C]TROA might be a useful PET probe for imaging of 20-HETE synthase in patients with cerebral ischemia. PMID:22669478

  5. Kinetic modeling of 11C-LY2795050, a novel antagonist radiotracer for PET imaging of the kappa opioid receptor in humans

    PubMed Central

    Naganawa, Mika; Zheng, Ming-Qiang; Nabulsi, Nabeel; Tomasi, Giampaolo; Henry, Shannan; Lin, Shu-Fei; Ropchan, Jim; Labaree, David; Tauscher, Johannes; Neumeister, Alexander; Carson, Richard E; Huang, Yiyun

    2014-01-01

    11C-LY2795050 is a novel kappa opioid receptor (KOR) antagonist tracer for positron emission tomography (PET) imaging. The purpose of this first-in-human study was to determine the optimal kinetic model for analysis of 11C-LY2795050 imaging data. Sixteen subjects underwent baseline scans and blocking scans after oral naltrexone. Compartmental modeling and multilinear analysis-1 (MA1) were applied using the arterial input functions. Two-tissue compartment model and MA1 were found to be the best models to provide reliable measures of binding parameters. The rank order of 11C-LY2795050 distribution volume (VT) matched the known regional KOR densities in the human brain. Blocking scans with naltrexone indicated no ideal reference region for 11C-LY2795050. Three methods for calculation of the nondisplaceable distribution volume (VND) were assessed: (1) individual VND estimated from naltrexone occupancy plots, (2) mean VND across subjects, and (3) a fixed fraction of cerebellum VT. Approach (3) produced the lowest intersubject variability in the calculation of binding potentials (BPND, BPF, and BPP). Therefore, binding potentials of 11C-LY2795050 can be determined if the specific binding fraction in the cerebellum is presumed to be unchanged by diseases and experimental conditions. In conclusion, results from the present study show the suitability of 11C-LY2795050 to image and quantify KOR in humans. PMID:25182664

  6. Effect of composite surface treatment and aging on the bond strength between a core build-up composite and a luting agent

    PubMed Central

    COTES, Caroline; CARDOSO, Mayra; de MELO, Renata Marques; VALANDRO, Luiz Felipe; BOTTINO, Marco Antonio

    2015-01-01

    Objective The purpose of this study was to assess the influence of conditioning methods and thermocycling on the bond strength between composite core and resin cement. Material and Methods Eighty blocks (8×8×4 mm) were prepared with core build-up composite. The cementation surface was roughened with 120-grit carbide paper and the blocks were thermocycled (5,000 cycles, between 5°C and 55°C, with a 30 s dwell time in each bath). A layer of temporary luting agent was applied. After 24 h, the layer was removed, and the blocks were divided into five groups, according to surface treatment: (NT) No treatment (control); (SP) Grinding with 120-grit carbide paper; (AC) Etching with 37% phosphoric acid; (SC) Sandblasting with 30 mm SiO2 particles, silane application; (AO) Sandblasting with 50 mm Al2O3 particles, silane application. Two composite blocks were cemented to each other (n=8) and sectioned into sticks. Half of the specimens from each block were immediately tested for microtensile bond strength (µTBS), while the other half was subjected to storage for 6 months, thermocycling (12,000 cycles, between 5°C and 55°C, with a dwell time of 30 s in each bath) and µTBS test in a mechanical testing machine. Bond strength data were analyzed by repeated measures two-way ANOVA and Tukey test (α=0.05). Results The µTBS was significantly affected by surface treatment (p=0.007) and thermocycling (p=0.000). Before aging, the SP group presented higher bond strength when compared to NT and AC groups, whereas all the other groups were statistically similar. After aging, all the groups were statistically similar. SP submitted to thermocycling showed lower bond strength than SP without thermocycling. Conclusion Core composites should be roughened with a diamond bur before the luting process. Thermocycling tends to reduce the bond strength between composite and resin cement. PMID:25760269

  7. Femtosecond laser ablation of dentin and enamel: relationship between laser fluence and ablation efficiency

    NASA Astrophysics Data System (ADS)

    Chen, Hu; Liu, Jing; Li, Hong; Ge, Wenqi; Sun, Yuchun; Wang, Yong; Lü, Peijun

    2015-02-01

    The objective was to study the relationship between laser fluence and ablation efficiency of a femtosecond laser with a Gaussian-shaped pulse used to ablate dentin and enamel for prosthodontic tooth preparation. A diode-pumped thin-disk femtosecond laser with wavelength of 1025 nm and pulse width of 400 fs was used for the ablation of dentin and enamel. The laser spot was guided in a line on the dentin and enamel surfaces to form a groove-shaped ablation zone under a series of laser pulse energies. The width and volume of the ablated line were measured under a three-dimensional confocal microscope to calculate the ablation efficiency. Ablation efficiency for dentin reached a maximum value of 0.020 mm3/J when the laser fluence was set at 6.51 J/cm2. For enamel, the maximum ablation efficiency was 0.009 mm3/J at a fluence of 7.59 J/cm2. Ablation efficiency of the femtosecond laser on dentin and enamel is closely related to the laser fluence and may reach a maximum when the laser fluence is set to an appropriate value.

  8. Mechanical Behaviour of Cyanate Ester/epoxy Blends after Reactor Irradiation to High Neutron Fluences

    NASA Astrophysics Data System (ADS)

    Prokopec, R.; Humer, K.; Fillunger, H.; Maix, R. K.; Weber, H. W.

    2008-03-01

    The mechanical strength of conventional epoxy resins drops dramatically after irradiation to a fast neutron fluence of 1×1022 m-2 (E>0.1 MeV). Recent results demonstrated that cyanate ester/epoxy blends were not affected at this fluence level. The aim of this study is to investigate the performance potential of these blends at higher fluence levels without significant degradation of their mechanical properties. Short-beam shear as well as static tensile tests were carried out at 77 K prior to and after irradiation to fast neutron fluences of up to 4×1022 m-2 (E>0.1 MeV) in the TRIGA reactor at ambient temperature (340 K). In addition, load controlled tension-tension fatigue measurements were performed, in order to simulate the pulsed operation conditions of a tokamak. Initial results show that only a small reduction of the mechanical strength under static and dynamic load is observed at a fast neutron fluence of 2×1022 m-2 (E>0.1 MeV). After exposure to 4×1022 m-2 (E>0.1 MeV) the interlaminar shear strength of materials with a cyanate ester content of 40% or more is only reduced by 20% to 30%.

  9. Coupling of Monte Carlo adjoint leakages with three-dimensional discrete ordinates forward fluences

    SciTech Connect

    Slater, C.O.; Lillie, R.A.; Johnson, J.O.; Simpson, D.B.

    1998-04-01

    A computer code, DRC3, has been developed for coupling Monte Carlo adjoint leakages with three-dimensional discrete ordinates forward fluences in order to solve a special category of geometrically-complex deep penetration shielding problems. The code extends the capabilities of earlier methods that coupled Monte Carlo adjoint leakages with two-dimensional discrete ordinates forward fluences. The problems involve the calculation of fluences and responses in a perturbation to an otherwise simple two- or three-dimensional radiation field. In general, the perturbation complicates the geometry such that it cannot be modeled exactly using any of the discrete ordinates geometry options and thus a direct discrete ordinates solution is not possible. Also, the calculation of radiation transport from the source to the perturbation involves deep penetration. One approach to solving such problems is to perform the calculations in three steps: (1) a forward discrete ordinates calculation, (2) a localized adjoint Monte Carlo calculation, and (3) a coupling of forward fluences from the first calculation with adjoint leakages from the second calculation to obtain the response of interest (fluence, dose, etc.). A description of this approach is presented along with results from test problems used to verify the method. The test problems that were selected could also be solved directly by the discrete ordinates method. The good agreement between the DRC3 results and the direct-solution results verify the correctness of DRC3.

  10. MECHANICAL BEHAVIOUR OF CYANATE ESTER/EPOXY BLENDS AFTER REACTOR IRRADIATION TO HIGH NEUTRON FLUENCES

    SciTech Connect

    Prokopec, R.; Humer, K.; Fillunger, H.; Maix, R. K.; Weber, H. W.

    2008-03-03

    The mechanical strength of conventional epoxy resins drops dramatically after irradiation to a fast neutron fluence of 1x10{sup 22} m{sup -2} (E>0.1 MeV). Recent results demonstrated that cyanate ester/epoxy blends were not affected at this fluence level. The aim of this study is to investigate the performance potential of these blends at higher fluence levels without significant degradation of their mechanical properties. Short-beam shear as well as static tensile tests were carried out at 77 K prior to and after irradiation to fast neutron fluences of up to 4x10{sup 22} m{sup -2} (E>0.1 MeV) in the TRIGA reactor at ambient temperature (340 K). In addition, load controlled tension-tension fatigue measurements were performed, in order to simulate the pulsed operation conditions of a tokamak. Initial results show that only a small reduction of the mechanical strength under static and dynamic load is observed at a fast neutron fluence of 2x10{sup 22} m{sup -2} (E>0.1 MeV). After exposure to 4x10{sup 22} m{sup -2} (E>0.1 MeV) the interlaminar shear strength of materials with a cyanate ester content of 40% or more is only reduced by 20% to 30%.

  11. Intensity modulation under geometrical uncertainty: a deconvolution approach to robust fluence.

    PubMed

    Fan, Yankhua; Nath, Ravinder

    2010-07-21

    A deconvolution algorithm has been developed to obtain robust fluence for external beam radiation treatment under geometrical uncertainties. Usually, the geometrical uncertainty is incorporated in the dose optimization process for inverse treatment planning to determine the additional intensity modulation of the beam to counter the geometrical uncertainty. Most of these approaches rely on dose convolution which is subject to the error caused by patient surface curvature and internal inhomogeneity. In this work, based on an 1D deconvolution algorithm developed by Ulmer and Kaissl, a fluence-deconvolution approach was developed to obtain robust fluence through the deconvolution of the nominal static one given by any treatment planning system. It incorporates the geometrical uncertainty outside the dose optimization procedure and therefore avoids the error of dose convolution. Robust fluences were calculated for a 4 x 4 cm flat field, a prostate IMRT and a head and neck IMRT plan in a commercial treatment planning system. The corresponding doses were simulated for 30 fractions with the random Gaussian distribution of the iso-centers showing good agreement with the nominal static doses. The feasibility of this deconvolution approach for clinical IMRT planning has been demonstrated. Because it is separated from the optimization procedure, this method is more flexible and easier to integrate into different existing treatment planning systems to obtain robust fluence.

  12. Effect of laser fluence on yeast cell viability in laser-assisted cell transfer

    NASA Astrophysics Data System (ADS)

    Lin, Yafu; Huang, Yong; Wang, Gaoyan; Tzeng, Tzeng-Rong J.; Chrisey, Douglas B.

    2009-08-01

    Matrix-assisted pulsed-laser evaporation direct-write (MAPLE DW) has been emerging as a promising biological construct fabrication technique. The post-transfer cell viability in MAPLE DW depends on various operation conditions such as the applied laser fluence; unfortunately, the effect of laser fluence on the post-transfer cell viability has not been well elucidated. This work aims to study the effect of laser fluence on the post-transfer cell viability and the cell recovery ability in MAPLE DW of yeast cells (Saccharomyces cerevisiae). It has been observed that (1) yeast cell viability decreases as the laser fluence increases from 85 to around 1500mJ/cm2 and (2) some of the MAPLE DW process-induced cell damage is reversible. The post-transfer yeast cell recovery is a function of laser fluence; however, this dependence relationship is not monotonic. Future work is needed to better understand the physical and chemical mechanisms of the above observations.

  13. Temperature, illumination and fluence dependence of current and voltage in electron irradiated solar cells

    NASA Technical Reports Server (NTRS)

    Obenschain, A. F.; Faith, T. J.

    1973-01-01

    Emperical equations have been derived from measurements of solar cell photovoltaic characteristics relating light generated current, IL, and open circuit voltage, VO, to cell temperature, T, intensity of illumination, W, and 1 Mev electron fluence, phi both 2 ohm-cm and 10 ohm-cm cells were tested. The temperature dependency of IL is similar for both resistivities at 140mw/sq cm; at high temperature the coefficient varies with fluence as phi 0.18, while at low temperatures the coefficient is relatively independent of fluence. Fluence dependent degration causes a decrease in IL at a rate proportional to phi 0.153 for both resistivities. At all intensities other than 560 mw/sq cm, a linear dependence of IL on illumination was found. The temperature coefficient of voltage was, to a good approximation, independent of both temperature and illumination for both resistivities. Illumination dependence of VOC was logarithmic, while the decrease with fluence of VOC varied as phi 0.25 for both resistivities.

  14. Advanced [18F]FDG and [11C]flumazenil PET analysis for individual outcome prediction after temporal lobe epilepsy surgery for hippocampal sclerosis

    PubMed Central

    Yankam Njiwa, J.; Gray, K.R.; Costes, N.; Mauguiere, F.; Ryvlin, P.; Hammers, A.

    2014-01-01

    Purpose We have previously shown that an imaging marker, increased periventricular [11C]flumazenil ([11C]FMZ) binding, is associated with failure to become seizure free (SF) after surgery for temporal lobe epilepsy (TLE) with hippocampal sclerosis (HS). Here, we investigated whether increased preoperative periventricular white matter (WM) signal can be detected on clinical [18F]FDG-PET images. We then explored the potential of periventricular FDG WM increases, as well as whole-brain [11C]FMZ and [18F]FDG images analysed with random forest classifiers, for predicting surgery outcome. Methods Sixteen patients with MRI-defined HS had preoperative [18F]FDG and [11C]FMZ-PET. Fifty controls had [18F]FDG-PET (30), [11C]FMZ-PET (41), or both (21). Periventricular WM signal was analysed using Statistical Parametric Mapping (SPM8), and whole-brain image classification was performed using random forests implemented in R (http://www.r-project.org). Surgery outcome was predicted at the group and individual levels. Results At the group level, non-seizure free (NSF) versus SF patients had periventricular increases with both tracers. Against controls, NSF patients showed more prominent periventricular [11C]FMZ and [18F]FDG signal increases than SF patients. All differences were more marked for [11C]FMZ. For individuals, periventricular WM signal increases were seen at optimized thresholds in 5/8 NSF patients for both tracers. For SF patients, 1/8 showed periventricular signal increases for [11C]FMZ, and 4/8 for [18F]FDG. Hence, [18F]FDG had relatively poor sensitivity and specificity. Random forest classification accurately identified 7/8 SF and 7/8 NSF patients using [11C]FMZ images, but only 4/8 SF and 6/8 NSF patients with [18F]FDG. Conclusion This study extends the association between periventricular WM increases and NSF outcome to clinical [18F]FDG-PET, but only at the group level. Whole-brain random forest classification increases [11C]FMZ-PET's performance for predicting

  15. Brain and whole-body imaging in nonhuman primates with [11C]MeS-IMPY, a candidate radioligand for beta-amyloid plaques.

    PubMed

    Seneca, Nicholas; Cai, Lisheng; Liow, Jeih-San; Zoghbi, Sami S; Gladding, Robert L; Hong, Jinsoo; Pike, Victor W; Innis, Robert B

    2007-08-01

    [(11)C]MeS-IMPY ([S-methyl-(11)C]N,N-dimethyl-4-(6-(methylthio)imidazo[1,2-a]pyridine-2-yl)aniline) is a potential radioligand for imaging beta-amyloid plaques with positron emission tomography (PET). The aims of this study were to evaluate [(11)C]MeS-IMPY uptake in nonhuman primate brain and to estimate radiation exposure from serial whole-body images. Eight PET studies were performed in rhesus monkeys to measure the brain uptake and washout of [(11)C]MeS-IMPY. Time-activity data were analyzed with one-tissue and two-tissue compartmental models using radiometabolite-corrected plasma input function. In addition, two whole-body PET scans were acquired for 120 min to determine the biodistribution of [(11)C]MeS-IMPY. Tomographic PET images were compressed into a single planar image to identify organs with the highest radiation exposures. Estimates of the absorbed dose of radiation were calculated using OLINDA 1.0. Injection of [(11)C]MeS-IMPY caused little change in pulse rate, blood pressure, respiratory rate and temperature. [(11)C]MeS-IMPY showed high standardized brain uptake values of approximately 500% and 600% between 2 and 3 min in cortical regions and the cerebellum, respectively. The brain uptake of [(11)C]MeS-IMPY was widespread and quite uniform across all cortical regions. Activity rapidly washed out of the brain, with 20% of peak activity remaining at 40 min. Thus, all brain regions showed minimal retention of radioactivity, consistent with these healthy young animals having negligible amyloid plaques. Regional brain activity fitted well into a one-tissue compartment model. The average volume of distribution in all brain regions was 7.66+/-2.14 ml/cm(3) (n=4). The organs with the highest radiation exposure (muSv/MBq) were the gallbladder wall (33.4), urinary bladder (17) and lungs (12.9), with a resulting effective dose of 4.9 microSv/MBq (18 mrem/mCi). The high brain uptake, rapid washout and quantifiable volume of distribution in nonhuman primate brain

  16. Multicompartmental analysis of (/sup 11/C)-carfentanil binding to opiate receptors in humans measured by positron emission tomography

    SciTech Connect

    Frost, J.J.; Douglass, K.H.; Mayberg, H.S.; Dannals, R.F.; Links, J.M.; Wilson, A.A.; Ravert, H.T.; Crozier, W.C.; Wagner, H.N. Jr.

    1989-06-01

    (11C)-Carfentanil is a high affinity opiate agonist that can be used to localize mu opiate receptors in humans by positron emission tomography (PET). A four-compartment model was used to obtain quantitative estimates of rate constants for receptor association and dissociation. PET studies were performed in five normal subjects in the absence and presence of 1 mg/kg naloxone. Arterial plasma concentration of (11C)-carfentanil and its labeled metabolites were determined during each PET study. The value of k3/k4 = Bmax/kD was determined for each subject in the presence and absence of naloxone. There was a significant reduction in the value of k3/k4 from 3.4 +/- 0.92 to 0.26 +/- 0.13 in the thalamus (p less than 0.01) and from 1.8 +/- 0.33 to 0.16 +/- 0.065 in the frontal cortex (p less than 0.001). Mean values of frontal cortex/occipital cortex and thalamus/occipital cortex ratios were determined for the interval 35-70 min after injection when receptor binding is high relative to nonspecific binding. The relationship between the measured region/occipital cortex values and the corresponding values of k3/k4 in the presence and absence of naloxone was: regions/occipital cortex = 0.95 + 0.74 (k3/k4) with r = 0.98 (n = 20). Simulation studies also demonstrated a linear relationship between the thalamus/occipital cortex or frontal cortex/occipital cortex ratio and k3/k4 for less than twofold increases or decreases in k3/k4. Simulation studies in which thalamic blood flow was varied demonstrated no significant effect on the region/occipital cortex ratio at 35-70 min for a twofold increase or fourfold decrease in blood flow. Therefore, the region/occipital cortex ratio can be used to quantitate changes in k3/k4 when tracer kinetic modeling is not feasible.

  17. Building up analgesia in humans via the endogenous μ-opioid system by combining placebo and active tDCS: a preliminary report.

    PubMed

    DosSantos, Marcos F; Martikainen, Ilkka K; Nascimento, Thiago D; Love, Tiffany M; DeBoer, Misty D; Schambra, Heidi M; Bikson, Marom; Zubieta, Jon-Kar; DaSilva, Alexandre F

    2014-01-01

    Transcranial Direct Current Stimulation (tDCS) is a method of non-invasive brain stimulation that has been frequently used in experimental and clinical pain studies. However, the molecular mechanisms underlying tDCS-mediated pain control, and most important its placebo component, are not completely established. In this pilot study, we investigated in vivo the involvement of the endogenous μ-opioid system in the global tDCS-analgesia experience. Nine healthy volunteers went through positron emission tomography (PET) scans with [11C]carfentanil, a selective μ-opioid receptor (MOR) radiotracer, to measure the central MOR activity during tDCS in vivo (non-displaceable binding potential, BPND)--one of the main analgesic mechanisms in the brain. Placebo and real anodal primary motor cortex (M1/2mA) tDCS were delivered sequentially for 20 minutes each during the PET scan. The initial placebo tDCS phase induced a decrease in MOR BPND in the periaqueductal gray matter (PAG), precuneus, and thalamus, indicating activation of endogenous μ-opioid neurotransmission, even before the active tDCS. The subsequent real tDCS also induced MOR activation in the PAG and precuneus, which were positively correlated to the changes observed with placebo tDCS. Nonetheless, real tDCS had an additional MOR activation in the left prefrontal cortex. Although significant changes in the MOR BPND occurred with both placebo and real tDCS, significant analgesic effects, measured by improvements in the heat and cold pain thresholds, were only observed after real tDCS, not the placebo tDCS. This study gives preliminary evidence that the analgesic effects reported with M1-tDCS, can be in part related to the recruitment of the same endogenous MOR mechanisms induced by placebo, and that such effects can be purposely optimized by real tDCS. PMID:25029273

  18. Ablation of CD11c(hi) dendritic cells exacerbates Japanese encephalitis by regulating blood-brain barrier permeability and altering tight junction/adhesion molecules.

    PubMed

    Kim, Jin Hyoung; Hossain, Ferdaus Mohd Altaf; Patil, Ajit Mahadev; Choi, Jin Young; Kim, Seong Bum; Uyangaa, Erdenebelig; Park, Sang-Youel; Lee, John-Hwa; Kim, Bumseok; Kim, Koanhoi; Eo, Seong Kug

    2016-10-01

    Japanese encephalitis (JE), characterized by extensive neuroinflammation following infection with neurotropic JE virus (JEV), is becoming a leading cause of viral encephalitis due to rapid changes in climate and demography. The blood-brain barrier (BBB) plays an important role in restricting neuroinvasion of peripheral leukocytes and virus, thereby regulating the progression of viral encephalitis. In this study, we explored the role of CD11c(hi) dendritic cells (DCs) in regulating BBB integrity and JE progression using a conditional depletion model of CD11c(hi) DCs. Transient ablation of CD11c(hi) DCs resulted in markedly increased susceptibility to JE progression along with highly increased neuro-invasion of JEV. In addition, exacerbated JE progression in CD11c(hi) DC-ablated hosts was closely associated with increased expression of proinflammatory cytokines (IFN-β, IL-6, and TNF-α) and CC chemokines (CCL2, CCL3, CXCL2) in the brain. Moreover, our results revealed that the exacerbation of JE progression in CD11c(hi) DC-ablated hosts was correlated with enhanced BBB permeability and reduced expression of tight junction and adhesion molecules (claudin-5, ZO-1, occluding, JAMs). Ultimately, our data conclude that the ablation of CD11c(hi) DCs provided a subsidiary impact on BBB integrity and the expression of tight junction/adhesion molecules, thereby leading to exacerbated JE progression. These findings provide insight into the secondary role of CD11c(hi) DCs in JE progression through regulation of BBB integrity and the expression of tight junction/adhesion molecules. PMID:27638116

  19. Ablation of CD11c(hi) dendritic cells exacerbates Japanese encephalitis by regulating blood-brain barrier permeability and altering tight junction/adhesion molecules.

    PubMed

    Kim, Jin Hyoung; Hossain, Ferdaus Mohd Altaf; Patil, Ajit Mahadev; Choi, Jin Young; Kim, Seong Bum; Uyangaa, Erdenebelig; Park, Sang-Youel; Lee, John-Hwa; Kim, Bumseok; Kim, Koanhoi; Eo, Seong Kug

    2016-10-01

    Japanese encephalitis (JE), characterized by extensive neuroinflammation following infection with neurotropic JE virus (JEV), is becoming a leading cause of viral encephalitis due to rapid changes in climate and demography. The blood-brain barrier (BBB) plays an important role in restricting neuroinvasion of peripheral leukocytes and virus, thereby regulating the progression of viral encephalitis. In this study, we explored the role of CD11c(hi) dendritic cells (DCs) in regulating BBB integrity and JE progression using a conditional depletion model of CD11c(hi) DCs. Transient ablation of CD11c(hi) DCs resulted in markedly increased susceptibility to JE progression along with highly increased neuro-invasion of JEV. In addition, exacerbated JE progression in CD11c(hi) DC-ablated hosts was closely associated with increased expression of proinflammatory cytokines (IFN-β, IL-6, and TNF-α) and CC chemokines (CCL2, CCL3, CXCL2) in the brain. Moreover, our results revealed that the exacerbation of JE progression in CD11c(hi) DC-ablated hosts was correlated with enhanced BBB permeability and reduced expression of tight junction and adhesion molecules (claudin-5, ZO-1, occluding, JAMs). Ultimately, our data conclude that the ablation of CD11c(hi) DCs provided a subsidiary impact on BBB integrity and the expression of tight junction/adhesion molecules, thereby leading to exacerbated JE progression. These findings provide insight into the secondary role of CD11c(hi) DCs in JE progression through regulation of BBB integrity and the expression of tight junction/adhesion molecules.

  20. MBP-Positive and CD11c-Positive Cells Are Associated with Different Phenotypes of Korean Patients with Non-Asthmatic Chronic Rhinosinusitis

    PubMed Central

    Chang, Dong-Yeop; Eun, Kyung Mi; Shin, Hyun-Woo; Mo, Ji-Hun; Shin, Eui-Cheol; Jin, Hong Ryul; Shin, Sue; Roh, Eun Youn; Han, Doo Hee; Kim, Dae Woo

    2014-01-01

    Background Asthmatic nasal polyps primarily exhibit eosinophilic infiltration. However, the identities of the immune cells that infiltrate non-asthmatic nasal polyps remain unclear. Thus, we thought to investigate the distribution of innate immune cells and its clinical relevance in non-asthmatic chronic rhinosinusitis (CRS) in Korea. Methods Tissues from uncinate process (UP) were obtained from controls (n = 18) and CRS without nasal polyps (CRSsNP, n = 45). Nasal polyps (NP) and UP were obtained from CRS with nasal polyps (CRSwNP, n = 56). The innate immune cells was evaluated by immunohistochemistry such as, eosinophil major basic protein (MBP), tryptase, CD68, CD163, CD11c, 2D7, human neutrophil elastase (HNE) and its distribution was analyzed according to clinical parameters. Results In comparisons between UP from each group, CRSwNP had a higher number of MPB+, CD68+, and CD11c+ cells relative to CRSsNP. Comparisons between UP and NP from CRSwNP indicated that NP have a higher infiltrate of MBP+, CD163+, CD11c+, 2D7+ and HNE+ cells, whereas fewer CD68+ cells were found in NP. In addition, MBP+ and CD11c+ cells were increased from UP of CRSsNP, to UP of CRSwNP, and to NP of CRSwNP. Moreover, in UP from CRSwNP, the number of MBP+ and CD11c+ cells positively correlated with CT scores. In the analysis of CRSwNP phenotype, allergic eosinophilic polyps had a higher number of MBP+, tryptase+, CD11c+, 2D7+ cells than others, whereas allergic non-eosinophilic polyps showed mainly infiltration of HNE+ and 2D7+ cells. Conclusions The infiltration of MBP+ and CD11c+ innate immune cells show a significant association with phenotype and disease extent of CRS and allergic status also may influences cellular phenotype in non-asthmatic CRSwNP in Korea. PMID:25361058

  1. Evaluation of a novel PDE10A PET radioligand, [(11) C]T-773, in nonhuman primates: brain and whole body PET and brain autoradiography.

    PubMed

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

    2015-07-01

    Phosphodiesterase 10A (PDE10A) is considered to be a key target for the treatment of several neuropsychiatric diseases. The characteristics of [(11) C]T-773, a novel positron emission tomography (PET) radioligand with high binding affinity and selectivity for PDE10A, were evaluated in autoradiography and in nonhuman primate (NHP) PET. Brain PET measurements were performed under baseline conditions and after administration of a selective PDE10A inhibitor, MP-10. Total distribution volume (VT ) and binding potential (BPND ) were calculated using various kinetic models. Whole body PET measurements were performed to calculate the effective dose of [(11) C]T-773. Autoradiography studies in postmortem human and monkey brain sections showed high accumulation of [(11) C]T-773 in the striatum and substantia nigra which was blocked by MP-10. Brain PET showed high accumulation of [(11) C]T-773 in the striatum, and the data could be fitted using a two tissue compartment model. BPND was approximately 1.8 in the putamen when the cerebellum was used as the reference region. Approximately 70% of PDE10A binding was occupied by 1.8 mg/kg of MP-10. Whole body PET showed high accumulation of [(11) C]T-773 in the liver, kidney, heart, and brain in the initial phase. The radioligand was partly excreted via bile and the gastrointestinal tract, and partly excreted through the urinary tract. The calculated effective dose was 0.007 mSv/MBq. In conclusion, [(11) C]T-773 was demonstrated to be a promising PET radioligand for PDE10A with favorable brain kinetics. Dosimetry results support multiple PET measurements per person in human studies. Further research is required with [(11) C]T-773 in order to test the radioligand's potential clinical applications.

  2. Evaluation of [11C]MRB for assessment of occupancy of norepinephrine transporters: Studies with atomoxetine in non-human primates

    PubMed Central

    Gallezot, Jean-Dominique; Weinzimmer, David; Nabulsi, Nabeel; Lin, Shu-Fei; Fowles, Krista; Sandiego, Christine; McCarthy, Timothy J.; Maguire, R. Paul; Carson, Richard E.; Ding, Yu-Shin

    2013-01-01

    [11C]MRB is one of the most promising radioligands used to measure brain norepinephrine transporters (NET) with positron emission tomography (PET). The objective of this study was to evaluate the suitability of [11C]MRB for drug occupancy studies of NET using atomoxetine (ATX), a NET uptake inhibitor used in the treatment of depression and attention-deficit hyperactivity disorder (ADHD). A second goal of the study was identification of a suitable reference region. Ten PET studies were performed in three anesthetized rhesus monkeys following an infusion of ATX or placebo. [11C]MRB arterial input functions and ATX plasma levels were also measured. A dose-dependent reduction of [11C]MRB volume of distribution was observed after correction for [11C]MRB plasma free fraction. ATX IC50 was estimated to be 31±10 ng/mL plasma. This corresponds to an effective dose (ED50) of 0.13 mg/kg, which is much lower than the therapeutic dose of ATX in ADHD (1.0–1.5 mg/kg). [11C]MRB binding potential BPND in the thalamus was estimated to be 1.8±0.3. Defining a reference region for a NET radiotracer is challenging due to the widespread and relatively uniform distribution of NET in the brain. Three regions were evaluated for use as reference region: caudate, putamen and occipital cortex. Caudate was found to be the most suitable for preclinical drug occupancy studies in rhesus monkeys. The IC50 estimate obtained using MRTM2 BPND without arterial blood sampling was 21±3 ng/mL (using caudate as the reference region). This study demonstrated that [11C]MRB is suitable for drug occupancy studies of NET. PMID:20869448

  3. No effect of dopamine depletion on the binding of the high-affinity D 2/3 radiotracer [11C]FLB 457 in the human cortex.

    PubMed

    Frankle, W Gordon; Mason, N Scott; Rabiner, Eugenii A; Ridler, Khanum; May, Maureen A; Asmonga, Deanna; Chen, Chi-Min; Kendro, Steve; Cooper, Thomas B; Mathis, Chester A; Narendran, Rajesh

    2010-12-01

    The use of PET and SPECT endogenous competition-binding techniques has contributed to the understanding of the role of dopamine (DA) in several neuropsychiatric disorders. An important limitation of these imaging studies is the fact that measurements of changes in synaptic DA have been restricted to the striatum. The ligands previously used, such as [(11)C]raclopride and [(123)I]IBZM, do not provide sufficient signal-to-noise ratio to quantify D(2) receptors in extrastriatal areas, such as cortex, where the concentration of D(2) receptors is much lower than that in the striatum. Recently, we published a comparison study of the ability of two high-affinity DA D(2) radioligands [(11)C]FLB 457 and [(11)C]fallypride to measure amphetamine-induced changes in DA transmission in the human cortex. Our findings support the use of [(11)C]FLB 457 to measure changes in cortical synaptic DA induced by amphetamine. The goal of this study is to examine the effects of DA depletion with α-methyl-para-tyrosine (α-MPT) on [(11)C]FLB 457 binding in the cortex. Six healthy volunteers underwent two PET scans, first under control conditions and subsequently after DA depletion. The simplified reference tissue model as well as kinetic modeling with an arterial input function was used to derive the binding potential (BP(ND)) in seven cortical regions. We found no effect of DA depletion with α-MPT on [(11)C]FLB 457 binding in any of the regions examined. In contrast to the measurement of DA release, the combination of low D(2) receptor density and low basal DA levels in the cortex greatly reduce the power to detect alterations in [(11)C]FLB 457 binding secondary to DA depletion.

  4. Tissue effects of Ho:YAG laser with varying fluences and pulse widths

    NASA Astrophysics Data System (ADS)

    Vari, Sandor G.; van der Veen, Maurits J.; Pergadia, Vani R.; Shi, Wei-Qiang; Duffy, J. T.; Weiss, Andrew B.; Fishbein, Michael C.; Grundfest, Warren S.

    1994-02-01

    We investigated the effect of varying fluence and pulse width on the ablation rate and consequent thermal damage of the Ho:YAG (2.130 micrometers ) laser. The rate of ablation on fresh bovine knee joint tissues, fibrous cartilage, hyaline cartilage, and bone in saline was determined after varying the fluence (160 - 640 J/cm2) and pulse width (150, 250, 450 microsecond(s) ec, FWHM) at a repetition rate of 2 Hz. A 400/440 micrometers fiber was used. The ablation rate increased linearly with the fluence. In fibrocartilage, different pulse durations generated significant changes in the ablation rates, but showed minor effects on hyaline cartilage and bone. The heat of ablation for all three tissue types decreased after lengthening the pulse.

  5. Comparison of fluence rate distributions made be side-firing fibers in an optical phantom

    NASA Astrophysics Data System (ADS)

    Royston, David; Richards, Philip Q.

    1999-07-01

    Side-firing fibers are used to provide coagulative therapy to the urologic tract. These fibers use different optical technologies to deflect the beam transverse to the fibers' optical axis. This produces emitted beams which differ in both beam direction and divergence angles. The relative optical performance of 13 fibers was studied in an optical phantom suspension. The fluence rate distribution created by each side-firing fiber was determined. The fluence rate distribution accounts for both the direct and spurious beams emitted from side-firing fibers as well as the light scattering produced by the target tissue. Based upon limited clinical dosimetry studies, the relative fluence rate distribution appears to indicate general exposure conditions for the evaluated fibers.

  6. Improved ion implant fluence uniformity in hydrogen enhanced glow discharge plasma immersion ion implantation into silicon

    SciTech Connect

    Luo, J.; Li, L. H. E-mail: paul.chu@cityu.edu.hk; Liu, H. T.; Xu, Y.; Zuo, X. J.; Zhu, P. Z.; Ma, Y. F.; Yu, K. M.; Fu, Ricky K. Y.; Chu, Paul K. E-mail: paul.chu@cityu.edu.hk

    2014-06-15

    Enhanced glow discharge plasma immersion ion implantation does not require an external plasma source but ion focusing affects the lateral ion fluence uniformity, thereby hampering its use in high-fluence hydrogen ion implantation for thin film transfer and fabrication of silicon-on-insulator. Insertion of a metal ring between the sample stage and glass chamber improves the ion uniformity and reduces the ion fluence non-uniformity as the cathode voltage is raised. Two-dimensional multiple-grid particle-in-cell simulation confirms that the variation of electric field inside the chamber leads to mitigation of the ion focusing phenomenon and the results are corroborated experimentally by hydrogen forward scattering.

  7. A new proton fluence model for E greater than 10 MeV

    NASA Technical Reports Server (NTRS)

    Feynman, Joan; Armstrong, T. P.; Dao-Gibner, L.; Silverman, S.

    1988-01-01

    Researchers describe a new engineering model for the fluence of protons with energies greater than 10 MeV. The data set used is a combination of observations made primarily from the Earth's surface between 1956 and 1963 and observations made from spacecraft in the vicinity of Earth between 1963 and 1985. With this data set we find that the distinction between ordinary proton events and anomalously large proton events made in earlier work disappears. The greater than 10 MeV fluences at 1 AU calculated with the new model are about twice those expected on the basis of models now in use. In contrast to earlier models, results do not depend critically on the fluence from any one event.

  8. Fluence Evaluations For Applications of In Situ Gamma-Ray Spectrometry in Non-Flat Terrain

    SciTech Connect

    Miller, Kevin M.

    1999-02-28

    Evaluations of gamma-ray fluence are made for source geometries that depart from the flat ground geometry that is used in standard applications of in situ spectrometry. Geometries considered include uniform source distributions for soil mounds on top of flat terrain, cylindrical wells, and rectangular trenches. The results indicate that scaling the standard fluence values for flat terrain by the ratio of solid angle subtended by the soil to 2π leads to fluence estimates that are accurate to within a few percent. Practical applications of in situ spectrometry in non-flat terrain also appears to be simplified by the fact that the angular correction factor for a typical coaxial detector in these geometries may typically be about the same as that computed for flat ground.

  9. The effect of local fluence on the micropatterning of poly(ethylene terephthalate) foils through proton beam writing

    NASA Astrophysics Data System (ADS)

    de Souza, C. T.; Stori, E. M.; Boufleur, L. A.; Papaléo, R. M.; Dias, J. F.

    2016-07-01

    In this work, we investigate the influence of ion fluence on the development of microstructures produced by 2.2 MeV H+ impinging on 12-μm-thick poly(ethylene terephthalate) (PET, Mylar®) foils. Several lines of 1 × 100 pixels corresponding to approximately 2.5 × 101.5 µm2 were patterned on PET foils using different ion fluences (from 1012 to 1017 H+/cm2) and etching times (from 1 to 60 min). We observe the presence of three different behaviors according to the ion fluence. Long etching times are necessary to open the structure in the low fluence regime, while moderate fluences require shorter etching times. In the high fluence regime, a more complex scenario emerges where short etching times lead to structures either fully or partially developed.

  10. D2 dopamine receptors in neuroleptic-naive schizophrenic patients. A positron emission tomography study with (11C)raclopride

    SciTech Connect

    Farde, L.; Wiesel, F.A.; Stone-Elander, S.; Halldin, C.; Nordstroem, A.L.H.; Hall, H.; Sedvall, G. )

    1990-03-01

    Several groups have reported increased densities of D2 dopamine receptors in the basal ganglia of schizophrenic brains postmortem. The significance of this finding has been questioned, since an upregulation of receptor number may be a neuronal response to neuroleptic drug treatment. We have used positron emission tomography and ({sup 11}C)raclopride to examine central D2 dopamine receptor binding in 20 healthy subjects and 18 newly admitted, young, neuroleptic-naive patients with schizophrenia. An in vivo saturation procedure was applied for quantitative determination of D2 dopamine receptor density (Bmax) and affinity (Kd). When the two groups were compared, no significant difference in Bmax or Kd values was found in the putamen or the caudate nucleus. The hypothesis of generally elevated central D2 dopamine receptor densities in schizophrenia was thus not supported by the present findings. In the patients but not in the healthy controls, significantly higher densities were found in the left than in the right putamen but not in the caudate nucleus.

  11. First direct measurement of the 11C (α ,p )14N stellar reaction by an extended thick-target method

    NASA Astrophysics Data System (ADS)

    Hayakawa, S.; Kubono, S.; Kahl, D.; Yamaguchi, H.; Binh, D. N.; Hashimoto, T.; Wakabayashi, Y.; He, J. J.; Iwasa, N.; Kato, S.; Komatsubara, T.; Kwon, Y. K.; Teranishi, T.

    2016-06-01

    The 11C(α,p ) 14N reaction is an important α -induced reaction competing with β -limited hydrogen-burning processes in high-temperature explosive stars. We directly measured its reaction cross sections both for the ground-state transition (α ,p0) and the excited-state transitions (α ,p1) and (α ,p2) at relevant stellar energies 1.3-4.5 MeV by an extended thick-target method featuring time of flight for the first time. We revised the reaction rate by numerical integration including the (α ,p1) and (α ,p2) contributions and also low-lying resonances of (α ,p0) using both the present and the previous experimental data which were totally neglected in the previous compilation works. The present total reaction rate lies between the previous (α ,p0) rate and the total rate of the Hauser-Feshbach statistical model calculation, which is consistent with the relevant explosive hydrogen-burning scenarios such as the ν p process.

  12. Limitations of SRTM, Logan graphical method, and equilibrium analysis for measuring transient dopamine release with [(11)C]raclopride PET.

    PubMed

    Sullivan, Jenna M; Kim, Su Jin; Cosgrove, Kelly P; Morris, Evan D

    2013-01-01

    Conventional PET methods to estimate [(11)C]raclopride binding potential (BP ND) assume that endogenous dopamine concentration does not change during the scan time. However, this assumption is purposely violated in studies using pharmacological or behavioral stimuli to invoke acute dopamine release. When the assumption of steady-state dopamine is violated, conventional analysis methods may produce biased or even unusable estimates of BP ND. To illustrate this problem, we examined the effect of scan duration on ΔBP ND estimated by three common analysis methods (simplified reference tissue model, Logan graphical reference method, and equilibrium analysis) applied to simulated and experimental single-scan activation studies. The activation - dopamine release - in both the simulated and experimental studies was brief. Simulations showed ΔBP ND to be highly dependent on the window of data used to determine BP ND in the activation state. A similar pattern was seen in the data from human smoking studies. No such pattern of ΔBP ND dependence on the window of data used was apparent in simulations where dopamine was held constant. The dependence of ΔBP ND on the duration of data analyzed illustrates the inability of conventional methods to reliably quantify short-lived increases in endogenous dopamine. PMID:23638336

  13. N-(/sup 11/C)-methyl-p-substituted phentermine analogs as potential brain blood flow agents for positron tomography

    SciTech Connect

    Kizuka, H.; Elmaleh, D.R.; Boudreaux, G.J.; Anderton, K.D.; Strauss, H.W.; Ackerman, R.H.; Brownell, G.L.

    1984-01-01

    The addition of a methyl group to the ..cap alpha..-position of amphetamine increases both the lipophilicity of the agent and its resistance to metabolism by monoamine oxidase. In addition, since tritium substituted phenteramine analog studies suggested that the p-halo phentermines had a greater concentration in the brain and prolonged retention time, the authors evaluated the biological behavior of positron labeled ..cap alpha..-methylamphetamine (phenteramine) in rats, dogs and monkeys. The N-(/sup 11/C) methyl analogs of p-chloro (I) and p-fluoro (II) phentermines were prepared by methylation of their primary amines using /sup 11/Ch/sub 3/I. Biodistribution studies in rats shows brain uptake is in the range of 1% dose/gr at 5 and 15 min for both agents. The activity in blood and eyes is low. Sequential images of the dogs' brain over 1 hour revealed a clearance of <15%. Images of the monkey brain were also obtained using a MGH positron camera PCR-I.

  14. 11C-Methionine-PET: a novel and sensitive tool for monitoring of early response to treatment in multiple myeloma.

    PubMed

    Lückerath, Katharina; Lapa, Constantin; Albert, Christa; Herrmann, Ken; Jörg, Gerhard; Samnick, Samuel; Einsele, Herrmann; Knop, Stefan; Buck, Andreas K

    2015-04-10

    Multiple myeloma (MM) remains an essentially incurable hematologic malignancy. However, new treatment modalities and novel drugs have been introduced and thus additional tools for therapy monitoring are increasingly needed. Therefore, we evaluated the radiotracers 11C-Methionine (paraprotein-biosynthesis) and 18F-FDG (glucose-utilization) for monitoring response to anti-myeloma-therapy and outcome prediction. Influence of proteasome-inhibition on radiotracer-uptake of different MM cell-lines and patient-derived CD138+ plasma cells was analyzed and related to tumor-biology. Mice xenotransplanted with MM.1S tumors underwent MET- and FDG-μPET. Tumor-to-background ratios before and after 24 h, 8 and 15 days treatment with bortezomib were correlated to survival. Treatment reduced both MET and FDG uptake; changes in tracer-retention correlated with a switch from high to low CD138-expression. In xenotransplanted mice, MET-uptake significantly decreased by 30-79% as early as 24 h after bortezomib injection. No significant differences were detected thus early with FDG. This finding was confirmed in patient-derived MM cells. Importantly, early reduction of MET- but not FDG-uptake correlated with improved survival and reduced tumor burden in mice. Our results suggest that MET is superior to FDG in very early assessment of response to anti-myeloma-therapy. Early changes in MET-uptake have predictive potential regarding response and survival. MET-PET holds promise to individualize therapies in MM in future.

  15. Hα3: an Hα imaging survey of HI selected galaxies from ALFALFA. III. Nurture builds up the Hubble sequence in the Great Wall

    NASA Astrophysics Data System (ADS)

    Gavazzi, G.; Savorgnan, G.; Fossati, M.; Dotti, M.; Fumagalli, M.; Boselli, A.; Gutiérrez, L.; Hernández Toledo, H.; Giovanelli, R.; Haynes, M. P.

    2013-05-01

    ). Conclusions: In the dwarf regime we find evidence for an evolution of HI-rich LTGs into ETGs through HI-poor LTGs and PSB galaxies driven by the environment. We identify ram-pressure as the mechanism most likely responsible for this transformation. We conclude that infall of galaxies has proceeded for the last 7.5 Gyr, building up the Coma cluster at a rate of approximately 100 galaxies with log (M∗/M⊙) > 9.0 per Gyr. Based on observations taken at the observatory of San Pedro Martir (Baja California, Mexico), belonging to the Mexican Observatorio Astronómico Nacional.Appendices are available in electronic form at http://www.aanda.org

  16. Analytical solution of the radiative transfer equation for infinite-space fluence

    SciTech Connect

    Liemert, Andre; Kienle, Alwin

    2011-01-15

    This Brief Report presents the derivation of analytical expressions for the fluence of the steady state radiative transfer equation in an infinitely extended and anisotropically scattering medium in arbitrary dimensions for different source types. The fluence, which is composed of an infinite sum of diffusion-like Green's functions, was compared to the Monte Carlo method. Within the stochastic nature of the Monte Carlo simulations, an exact agreement was found in the steady state and time domains. It is shown that the use of low-order approximations is sufficient for many relevant cases.

  17. The fragmentation of 510 MeV/nucleon iron-56 in polyethylene. I. Fragment fluence spectra

    NASA Technical Reports Server (NTRS)

    Zeitlin, C.; Miller, J.; Heilbronn, L.; Frankel, K.; Gong, W.; Schimmerling, W.

    1996-01-01

    The fragmentation of 510 MeV/nucleon iron ions in several thicknesses of polyethylene has been measured. Non-interacting primary beam particles and fragments have been identified and their LETs calculated by measuring ionization energy loss in a stack of silicon detectors. Fluences, normalized to the incident beam intensity and corrected for detector effects, are presented for each fragment charge and target. Histograms of fluence as a function of LET are also presented. Some implications of these data for measurements of the biological effects of heavy ions are discussed.

  18. A new monitor for routine thermal and epithermal neutron fluence rate monitoring in k0 INAA.

    PubMed

    Koster-Ammerlaan, M J J; Bacchi, M A; Bode, P; De Nadai Fernandes, E A

    2008-12-01

    The Zr-Au set for monitoring the thermal and epithermal neutron fluence rate and the epithermal spectrum parameter alpha is not always practicable for routine application of INAA in well-thermalized facilities. An alternative set consisting of Cr, Au and Mo provides values for the thermal neutron fluence rate, f and alpha that are not significantly different from those found via the Zr-Au method and the Cd-covered Zr-method. The IRMM standard SMELS-II was analyzed using the (Au-Cr-Mo) monitor and a good agreement was obtained.

  19. A comparison study of 11C-methionine and 18F-fluorodeoxyglucose positron emission tomography-computed tomography scans in evaluation of patients with recurrent brain tumors

    PubMed Central

    Sharma, Rajnish; D’Souza, Maria; Jaimini, Abhinav; Hazari, Puja Panwar; Saw, Sanjeev; Pandey, Santosh; Singh, Dinesh; Solanki, Yachna; Kumar, Nitin; Mishra, Anil K.; Mondal, Anupam

    2016-01-01

    Introduction: 11C-methonine ([11C]-MET) positron emission tomography-computed tomography (PET-CT) is a well-established technique for evaluation of tumor for diagnosis and treatment planning in neurooncology. [11C]-MET reflects amino acid transport and has been shown to be more sensitive than magnetic resonance imaging (MRI) in stereotactic biopsy planning. This study compared fluorodeoxyglucose (FDG) PET-CT and MET PET-CT in the detection of various brain tumors. Materials and Methods: Sixty-four subjects of brain tumor treated by surgery, chemotherapy, and/or radiotherapy were subjected to [18F]-FDG, [11C]-MET, and MRI scan. The lesion was analyzed semiquantitatively using tumor to normal contralateral ratio. The diagnosis was confirmed by surgery, stereotactic biopsy, clinical follow-up, MRI, or CT scans. Results: Tumor recurrence was found in 5 out of 22 patients on [F-18] FDG scan while [11C]-MET was able to detect recurrence in 18 out of 22 patients in low-grade gliomas. Two of these patients were false positive for the presence of recurrence of tumor and later found to be harboring necrosis. Among oligodendroglioma, medulloblastoma and high-grade glioma out of 42 patients 39 were found to be concordant MET and FDG scans. On semiquantitative analysis, mean T/NT ratio was found to be 2.96 ± 0.94 for lesions positive for recurrence of tumors and 1.18 ± 0.74 for lesions negative for recurrence of tumor on [11C]-MET scan. While the ratio for FDG scan on semiquantitative analysis was found to be 2.05 ± 1.04 for lesions positive for recurrence of tumors and 0.52 ± 0.15 for lesions negative for recurrence of tumors. Conclusion: The study highlight that [11C]-MET is superior to [18F]-FDG PET scans to detect recurrence in low-grade glioma. A cut-off value of target to nontarget value of 1.47 is a useful parameter to distinguish benign from malignant lesion on an [11C]-MET Scan. Both [18F]-FDG and [11C]-MET scans were found to be useful in high-grade astrocytoma

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

    SciTech Connect

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

    2011-10-25

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

  1. Quantification of [(11)C]PIB PET for imaging myelin in the human brain: a test-retest reproducibility study in high-resolution research tomography.

    PubMed

    Veronese, Mattia; Bodini, Benedetta; García-Lorenzo, Daniel; Battaglini, Marco; Bongarzone, Salvatore; Comtat, Claude; Bottlaender, Michel; Stankoff, Bruno; Turkheimer, Federico E

    2015-11-01

    An accurate in vivo measure of myelin content is essential to deepen our insight into the mechanisms underlying demyelinating and dysmyelinating neurological disorders, and to evaluate the effects of emerging remyelinating treatments. Recently [(11)C]PIB, a positron emission tomography (PET) tracer originally conceived as a beta-amyloid marker, has been shown to be sensitive to myelin changes in preclinical models and humans. In this work, we propose a reference-region methodology for the voxelwise quantification of brain white-matter (WM) binding for [(11)C]PIB. This methodology consists of a supervised procedure for the automatic extraction of a reference region and the application of the Logan graphical method to generate distribution volume ratio (DVR) maps. This approach was assessed on a test-retest group of 10 healthy volunteers using a high-resolution PET tomograph. The [(11)C]PIB PET tracer binding was shown to be up to 23% higher in WM compared with gray matter, depending on the image reconstruction. The DVR estimates were characterized by high reliability (outliers <1%) and reproducibility (intraclass correlation coefficient (ICC) >0.95). [(11)C]PIB parametric maps were also found to be significantly correlated (R(2)>0.50) to mRNA expressions of the most represented proteins in the myelin sheath. On the contrary, no correlation was found between [(11)C]PIB imaging and nonmyelin-associated proteins.

  2. Estimating endogenous dopamine levels at D2 and D3 receptors in humans using the agonist radiotracer [(11)C]-(+)-PHNO.

    PubMed

    Caravaggio, Fernando; Nakajima, Shinichiro; Borlido, Carol; Remington, Gary; Gerretsen, Philip; Wilson, Alan; Houle, Sylvain; Menon, Mahesh; Mamo, David; Graff-Guerrero, Ariel

    2014-11-01

    Using positron emission tomography (PET) and an acute dopamine depletion challenge it is possible to estimate endogenous dopamine levels occupying dopamine D2/3 receptors (D2/3R) in humans in vivo. Our group has developed [(11)C]-(+)-PHNO, the first agonist radiotracer with preferential in vivo affinity for D3R. Thus, the use of [(11)C]-(+)-PHNO offers the novel possibility of (i) estimating in vivo endogenous dopamine levels at D2/3R using an agonist radiotracer, and (ii) estimating endogenous dopamine levels at D3R in extrastriatal regions such as the substantia nigra, hypothalamus, and ventral pallidum. Ten healthy participants underwent a [(11)C]-(+)-PHNO PET scan under baseline conditions and another under acute endogenous dopamine depletion achieved via oral administration of alpha-methyl-para-tyrosine (64 mg/kg). [(11)C]-(+)-PHNO binding was sensitive to acute dopamine depletion, allowing in vivo estimates of endogenous dopamine in D2R-rich regions (caudate and putamen), mixed D2/3R-rich regions (ventral striatum and globus pallidus), and extrastriatal D3R-rich regions (hypothalamus and ventral pallidum). Dopamine depletion decreased self-reported vigor, which was correlated with the reduction in dopamine levels in the globus pallidus. [(11)C]-(+)-PHNO is a suitable radiotracer for use in estimating endogenous dopamine levels at D2R and D3R in neuropsychiatric populations.

  3. Estimating Endogenous Dopamine Levels at D2 and D3 Receptors in Humans using the Agonist Radiotracer [11C]-(+)-PHNO

    PubMed Central

    Caravaggio, Fernando; Nakajima, Shinichiro; Borlido, Carol; Remington, Gary; Gerretsen, Philip; Wilson, Alan; Houle, Sylvain; Menon, Mahesh; Mamo, David; Graff-Guerrero, Ariel

    2014-01-01

    Using positron emission tomography (PET) and an acute dopamine depletion challenge it is possible to estimate endogenous dopamine levels occupying dopamine D2/3 receptors (D2/3R) in humans in vivo. Our group has developed [11C]-(+)-PHNO, the first agonist radiotracer with preferential in vivo affinity for D3R. Thus, the use of [11C]-(+)-PHNO offers the novel possibility of (i) estimating in vivo endogenous dopamine levels at D2/3R using an agonist radiotracer, and (ii) estimating endogenous dopamine levels at D3R in extrastriatal regions such as the substantia nigra, hypothalamus, and ventral pallidum. Ten healthy participants underwent a [11C]-(+)-PHNO PET scan under baseline conditions and another under acute endogenous dopamine depletion achieved via oral administration of alpha-methyl-para-tyrosine (64 mg/kg). [11C]-(+)-PHNO binding was sensitive to acute dopamine depletion, allowing in vivo estimates of endogenous dopamine in D2R-rich regions (caudate and putamen), mixed D2/3R-rich regions (ventral striatum and globus pallidus), and extrastriatal D3R-rich regions (hypothalamus and ventral pallidum). Dopamine depletion decreased self-reported vigor, which was correlated with the reduction in dopamine levels in the globus pallidus. [11C]-(+)-PHNO is a suitable radiotracer for use in estimating endogenous dopamine levels at D2R and D3R in neuropsychiatric populations. PMID:24874713

  4. Inhibition of acetylcholinesterase in CSF versus brain assessed by 11C-PMP PET in AD patients treated with galantamine.

    PubMed

    Darreh-Shori, T; Kadir, A; Almkvist, O; Grut, M; Wall, A; Blomquist, G; Eriksson, B; Långström, B; Nordberg, A

    2008-02-01

    The relationship between acetylcholinesterase (AChE) activity in the CSF and brain of patients with Alzheimer's disease (AD) was investigated in 18 mild AD patients following galantamine treatment. The first 3 months of the study had a randomized double-blind placebo-controlled design, during which 12 patients received galantamine (16-24 mg/day) and six patients placebo. This was followed by 9 months galantamine treatment in all patients. Activities and protein levels of both the "read-through" AChE (AChE-R) and the synaptic (AChE-S) variants in CSF were assessed in parallel together with the regional brain AChE activity by (11)C-PMP and PET. The AChE-S inhibition was 30-36% in CSF, which correlated well with the in vivo AChE inhibition in the brain. No significant AChE inhibition was observed in the placebo group. The increased level of the AChE-R protein was 16% higher than that of AChE-S. Both the AChE inhibition and the increased level of AChE-R protein positively correlated with the patient's performance in cognitive tests associated with visuospatial ability and attention. In conclusion, AChE levels in CSF closely mirror in vivo brain AChE levels prior to and after treatment with the cholinesterase inhibitors. A positive cognitive response seems to dependent on the AChE inhibition level, which is balanced by an increased protein level of the AChE-R variant in the patients.

  5. {sup 11}C-methionine PET improves the target volume delineation of meningiomas treated with stereotactic fractionated radiotherapy

    SciTech Connect

    Grosu, Anca-Ligia . E-mail: anca-ligia.grosu@lrz.tum.de; Weber, Wolfgang A.; Astner, Sabrina T.; Adam, Markus; Krause, Bernd J.; Schwaiger, Markus; Molls, Michael; Nieder, Carsten

    2006-10-01

    Purpose: To evaluate the role of {sup 11}C-methionine positron emission tomography (MET-PET) in target volume delineation for meningiomas and to determine the interobserver variability. Methods and Materials: Two independent observers performed treatment planning in 10 patients according to a prospective written protocol. In the first step, they used coregistered computed tomography (CT) and magnetic resonance imaging (MRI). In the second step, MET-PET was added to CT/MRI (image fusion based on mutual information). Results: The correlation between gross tumor volume (GTVs) delineated by the two observers based on CT/MRI was r = 0.855 (Spearman's correlation coefficient, p = 0.002) and r = 0.988 (p = 0.000) when MET-PET/CT/MRI were used. The number of patients with agreement in more then 80% of the outlined volume increased with the availability of MET-PET from 1 in 10 to 5 in 10. The median volume of intersection between the regions delineated by two observers increased significantly from 69% (from the composite volume) to 79%, by the addition of MET-PET (p = 0.005). The information of MET-PET was useful to delineate GTV in the area of cavernous sinus, orbit, and base of the skull. Conclusions: The hypothesis-generating findings of potential normal tissue sparing and reduced interobserver variability provide arguments for invasive studies of the correlation between MET-PET images and histologic tumor extension and for prospective trials of target volume delineation with CT/MRI/MET-PET image fusion.

  6. Postpartum and Depression Status are Associated With Lower [11C]raclopride BPND in Reproductive-Age Women

    PubMed Central

    Moses-Kolko, Eydie L; Price, Julie C; Wisner, Katherine L; Hanusa, Barbara H; Meltzer, Carolyn C; Berga, Sarah L; Grace, Anthony A; di Scalea, Teresa Lanza; Kaye, Walter H; Becker, Carl; Drevets, Wayne C

    2012-01-01

    The early postpartum period is associated with increased risk for affective and psychotic disorders. Because maternal dopaminergic reward system function is altered with perinatal status, dopaminergic system dysregulation may be an important mechanism of postpartum psychiatric disorders. Subjects included were non-postpartum healthy (n=13), postpartum healthy (n=13), non-postpartum unipolar depressed (n=10), non-postpartum bipolar depressed (n=7), postpartum unipolar (n=13), and postpartum bipolar depressed (n=7) women. Subjects underwent 60 min of [11C]raclopride–positron emission tomography imaging to determine the nondisplaceable striatal D2/3 receptor binding potential (BPND). Postpartum status and unipolar depression were associated with lower striatal D2/3 receptor BPND in the whole striatum (p=0.05 and p=0.02, respectively) that reached a maximum of 7–8% in anteroventral striatum for postpartum status (p=0.02). Unipolar depression showed a nonsignificant trend toward being associated with 5% lower BPND in dorsal striatum (p=0.06). D2/3 receptor BPND did not differ significantly between unipolar depressed and healthy postpartum women or between bipolar and healthy subjects; however, D2/3 receptor BPND was higher in dorsal striatal regions in bipolar relative to unipolar depressives (p=0.02). In conclusion, lower striatal D2/3 receptor BPND in postpartum and unipolar depressed women, primarily in ventral striatum, and higher dorsal striatal D2/3 receptor BPND in bipolar relative to unipolar depressives reveal a potential role for the dopamine (DA) system in the physiology of these states. Further studies delineating the mechanisms underlying these differences in D2/3 receptor BPND, including study of DA system responsivity to rewarding stimuli, and increasing power to assess unipolar vs bipolar-related differences, are needed to better understand the affective role of the DA system in postpartum and depressed women. PMID:22257897

  7. Nonuniform Cardiac Denervation Observed by 11C-meta-Hydroxyephedrine PET in 6-OHDA-Treated Monkeys

    PubMed Central

    Joers, Valerie; Seneczko, Kailie; Goecks, Nichole C.; Kamp, Timothy J.; Hacker, Timothy A.; Brunner, Kevin G.; Engle, Jonathan W.; Barnhart, Todd E.; Nickles, R. Jerome; Holden, James E.; Emborg, Marina E.

    2012-01-01

    Parkinson's disease presents nonmotor complications such as autonomic dysfunction that do not respond to traditional anti-parkinsonian therapies. The lack of established preclinical monkey models of Parkinson's disease with cardiac dysfunction hampers development and testing of new treatments to alleviate or prevent this feature. This study aimed to assess the feasibility of developing a model of cardiac dysautonomia in nonhuman primates and preclinical evaluations tools. Five rhesus monkeys received intravenous injections of 6-hydroxydopamine (total dose: 50 mg/kg). The animals were evaluated before and after with a battery of tests, including positron emission tomography with the norepinephrine analog 11C-meta-hydroxyephedrine. Imaging 1 week after neurotoxin treatment revealed nearly complete loss of specific radioligand uptake. Partial progressive recovery of cardiac uptake found between 1 and 10 weeks remained stable between 10 and 14 weeks. In all five animals, examination of the pattern of uptake (using Logan plot analysis to create distribution volume maps) revealed a persistent region-specific significant loss in the inferior wall of the left ventricle at 10 (P<0.001) and 14 weeks (P<0.01) relative to the anterior wall. Blood levels of dopamine, norepinephrine (P<0.05), epinephrine, and 3,4-dihydroxyphenylacetic acid (P<0.01) were notably decreased after 6-hydroxydopamine at all time points. These results demonstrate that systemic injection of 6-hydroxydopamine in nonhuman primates creates a nonuniform but reproducible pattern of cardiac denervation as well as a persistent loss of circulating catecholamines, supporting the use of this method to further develop a monkey model of cardiac dysautonomia. PMID:22539969

  8. Nanostructured copper, chromium, and tin oxide multicomponent materials as catalysts for methanol decomposition: 11C-radiolabeling study.

    PubMed

    Tsoncheva, Tanya; Sarkadi-Priboczki, Eva; Dimitrov, Momtchil; Genova, Izabela

    2013-01-01

    Copper and chromium modified tin oxide nanocomposites were obtained via incipient wetness impregnation of high surface area nanosized SnO(2) with the corresponding metal acetylacetonates and their further decomposition in air. Powder X-ray diffraction (XRD), Nitrogen physisorption, UV-Vis, and Temperature-programmed reduction (TPR) with hydrogen were applied for the samples characterization. The catalytic activity of the obtained materials was tested in methanol conversion. A new approach based on the selective coverage of the surface with (11)C-methanol was used for the characterization of the catalytic sites. It was demonstrated that the products distribution could be controlled by the surface coverage with methanol and the role of different active sites was discussed. The modification of SnO(2) with copper oxide increased the activity in methanol decomposition to CO(2)via dioxymethylene intermediates, but the catalyst suffered considerable loss of activity due to the reduction transformations by the reaction medium and formation of an inactive intermetallic alloy. The modification with chromium changed the acid-basic properties of SnO(2) by the formation of Cr(2)O(3) nanoparticles as well as anchored to the support chromate species. The former particles facilitated the formation of dimethyl ether (DME), while the latter species converted methanol predominantly to hydrocarbons. The fraction of chromate species increased in Cu-Cr-Sn oxide multicomponent nanocomposites and promoted the formation of hydrocarbons over DME at low temperatures, while at higher temperatures, the activity of the copper species leading to CO(2) formation was more pronounced. PMID:23031492

  9. Examining Endogenous Dopamine in Treated Schizophrenia using [11C]-(+)-PHNO Positron Emission Tomography: A Pilot study

    PubMed Central

    Caravaggio, Fernando; Borlido, Carol; Wilson, Alan; Graff-Guerrero, Ariel

    2015-01-01

    Background Using positron emission tomography (PET) it is possible to estimate endogenous dopamine (DA) occupying D2/3 receptors (D2/3R) in the living human brain. Persons with schizophrenia (SZ) (previously medicated and naïve) have increased endogenous DA occupying D2/3R in the caudate. It is unknown whether currently medicated patients demonstrate increased DA levels at D2/3R. Moreover, DA levels have not been estimated in SZ using agonist radiotracers, which may offer a more sensitive quantification over antagonists. Methods Using the agonist radiotracer [11C]-(+)-PHNO, DA levels were estimated at D2/3R (ΔBPND) in three patients with SZ (Male, Mage=30±16). Patients were currently being treated long-term with Olanzapine (147±88 nmol/L). Results were compared to ten healthy controls (HC’s). Results Medicated persons with SZ had greater ΔBPND in the left caudate (U=2, Z=−2.20, p=.03) and right putamen (U=2, Z=−2.20, p=.03). No differences were observed in the ventral striatum or globus pallidus. Conclusions It is possible to estimate endogenous DA at D2/3R in SZ patients currently taking antipsychotics. Despite medication, patients continue to have increased endogenous DA at D2/3R. This lends more biological support to the clinical observation that relapses in symptoms can occur in the face of complete antipsychotic discontinuation. Future studies with larger samples are warranted. PMID:25814099

  10. Radiosynthesis of [11C]SNAP-7941—the first PET-tracer for the melanin concentrating hormone receptor 1 (MCHR1)

    PubMed Central

    Philippe, C.; Schirmer, E.; Mitterhauser, M.; Shanab, K.; Lanzenberger, R.; Karanikas, G.; Spreitzer, H.; Viernstein, H.; Wadsak, W.

    2012-01-01

    The melanin concentrating hormone (MCH) system is a new target to treat human disorders. Our aim was the preparation of the first PET-tracer for the MCHR1. [11C]SNAP-7941 is a carbon-11 labeled analog of the published MCHR1 antagonist SNAP-7941. The optimum reaction conditions were 2 min reaction time, ≤25 °C reaction temperature, and 2 mg/mL precursor (SNAP-acid) in acetonitrile, using [11C]CH3OTf as methylation agent. [11C]SNAP-7941 was prepared in a reliable and feasible manner with high radiochemical yields (2.9±1.6 GBq; 11.5±6.4% EOB, n=15). PMID:22858577

  11. CD11c(hi) Dendritic Cells Regulate Ly-6C(hi) Monocyte Differentiation to Preserve Immune-privileged CNS in Lethal Neuroinflammation.

    PubMed

    Kim, Jin Hyoung; Choi, Jin Young; Kim, Seong Bum; Uyangaa, Erdenebelig; Patil, Ajit Mahadev; Han, Young Woo; Park, Sang-Youel; Lee, John Hwa; Kim, Koanhoi; Eo, Seong Kug

    2015-12-02

    Although the roles of dendritic cells (DCs) in adaptive defense have been defined well, the contribution of DCs to T cell-independent innate defense and subsequent neuroimmunopathology in immune-privileged CNS upon infection with neurotropic viruses has not been completely defined. Notably, DC roles in regulating innate CD11b(+)Ly-6C(hi) monocyte functions during neuroinflammation have not yet been addressed. Using selective ablation of CD11c(hi)PDCA-1(int/lo) DCs without alteration in CD11c(int)PDCA-1(hi) plasmacytoid DC number, we found that CD11c(hi) DCs are essential to control neuroinflammation caused by infection with neurotropic Japanese encephalitis virus, through early and increased infiltration of CD11b(+)Ly-6C(hi) monocytes and higher expression of CC chemokines. More interestingly, selective CD11c(hi) DC ablation provided altered differentiation and function of infiltrated CD11b(+)Ly-6C(hi) monocytes in the CNS through Flt3-L and GM-CSF, which was closely associated with severely enhanced neuroinflammation. Furthermore, CD11b(+)Ly-6C(hi) monocytes generated in CD11c(hi) DC-ablated environment had a deleterious rather than protective role during neuroinflammation, and were more quickly recruited into inflamed CNS, depending on CCR2, thereby exacerbating neuroinflammation via enhanced supply of virus from the periphery. Therefore, our data demonstrate that CD11c(hi) DCs provide a critical and unexpected role to preserve the immune-privileged CNS in lethal neuroinflammation via regulating the differentiation, function, and trafficking of CD11b(+)Ly-6C(hi) monocytes.

  12. Visualization of angiogenesis during cancer development in the polyoma middle T breast cancer model: molecular imaging with (R)-[11C]PAQ

    PubMed Central

    2014-01-01

    Background Vascular endothelial growth factor receptor 2 (VEGFR2) is a crucial mediator of tumour angiogenesis. High expression levels of the receptor have been correlated to poor prognosis in cancer patients. Reliable imaging biomarkers for stratifying patients for anti-angiogenic therapy could therefore be valuable for increasing treatment success rates. The aim of this study was to investigate the pharmacokinetics and angiogenesis imaging abilities of the VEGFR2-targeting positron emission tomography (PET) tracer (R)-[11C]PAQ. Methods (R)-[11C]PAQ was evaluated in the mouse mammary tumour virus-polyoma middle T (MMTV-PyMT) model of metastatic breast cancer. Mice at different stages of disease progression were imaged with (R)-[11C]PAQ PET, and results were compared to those obtained with [18 F]FDG PET and magnetic resonance imaging. (R)-[11C]PAQ uptake levels were also compared to ex vivo immunofluorescence analysis of tumour- and angiogenesis-specific biomarkers. Additional pharmacokinetic studies were performed in rat and mouse. Results A heterogeneous uptake of (R)-[11C]PAQ was observed in the tumorous mammary glands. Ex vivo analysis confirmed the co-localization of areas with high radioactivity uptake and areas with elevated levels of VEGFR2. In some animals, a high focal uptake was observed in the lungs. The lung uptake correlated to metastatic and angiogenic activity, but not to uptake of [18 F]FDG PET. The pharmacokinetic studies revealed a limited metabolism and excretion during the 1-h scan and a distribution of radioactivity mainly to the liver, kidneys and lungs. In rat, a high uptake was additionally observed in adrenal and parathyroid glands. Conclusion The results indicate that (R)-[11C]PAQ is a promising imaging biomarker for visualization of angiogenesis, based on VEGFR2 expression, in primary tumours and during metastasis development. PMID:24670127

  13. Imaging brain inflammation with [(11)C]PK11195 by PET and induction of the peripheral-type benzodiazepine receptor after transient focal ischemia in rats.

    PubMed

    Rojas, Santiago; Martín, Abraham; Arranz, Maria J; Pareto, Deborah; Purroy, Jesús; Verdaguer, Esther; Llop, Jordi; Gómez, Vanessa; Gispert, Joan D; Millán, Olga; Chamorro, Angel; Planas, Anna M

    2007-12-01

    [(11)C]PK11195 is used in positron emission tomography (PET) studies for imaging brain inflammation in vivo as it binds to the peripheral-type benzodiazepine receptor (PBR) expressed by reactive glia and macrophages. However, features of the cellular reaction required to induce a positive [(11)C]PK11195 signal are not well characterized. We performed [(11)C]PK11195 PET and autoradiography in rats after transient focal cerebral ischemia. We determined [(3)H]PK11195 binding and PBR expression in brain tissue and examined the lesion with several markers. [(11)C]PK11195 standard uptake value increased at day 4 and grew further at day 7 within the ischemic core. Accordingly, ex vivo [(3)H]PK11195 binding increased at day 4, and increases further at day 7. The PET signal also augmented in peripheral regions, but to a lesser extent than in the core. Binding in the region surrounding infarction was supported by [(11)C]PK11195 autoradiography at day 7 showing that the radioactive signal extended beyond the infarcted core. Enhanced binding was preceded by increases in PBR mRNA expression in the ipsilateral hemisphere, and a 18-kDa band corresponding to PBR protein was detected. Peripheral-type benzodiazepine receptor immunohistochemistry showed subsets of ameboid microglia/macrophages within the infarcted core showing a distinctive strong PBR expression from day 4. These cells were often located surrounding microhemorrhages. Reactive astrocytes forming a rim surrounding infarction at day 7 also showed some PBR immunostaining. These results show cellular heterogeneity in the level of PBR expression, supporting that PBR is not a simple marker of inflammation, and that the extent of [(11)C]PK11195 binding depends on intrinsic features of the inflammatory cells.

  14. Low-intensity red and infrared laser effects at high fluences on Escherichia coli cultures.

    PubMed

    Barboza, L L; Campos, V M A; Magalhães, L A G; Paoli, F; Fonseca, A S

    2015-10-01

    Semiconductor laser devices are readily available and practical radiation sources providing wavelength tenability and high monochromaticity. Low-intensity red and near-infrared lasers are considered safe for use in clinical applications. However, adverse effects can occur via free radical generation, and the biological effects of these lasers from unusually high fluences or high doses have not yet been evaluated. Here, we evaluated the survival, filamentation induction and morphology of Escherichia coli cells deficient in repair of oxidative DNA lesions when exposed to low-intensity red and infrared lasers at unusually high fluences. Cultures of wild-type (AB1157), endonuclease III-deficient (JW1625-1), and endonuclease IV-deficient (JW2146-1) E. coli, in exponential and stationary growth phases, were exposed to red and infrared lasers (0, 250, 500, and 1000 J/cm2) to evaluate their survival rates, filamentation phenotype induction and cell morphologies. The results showed that low-intensity red and infrared lasers at high fluences are lethal, induce a filamentation phenotype, and alter the morphology of the E. coli cells. Low-intensity red and infrared lasers have potential to induce adverse effects on cells, whether used at unusually high fluences, or at high doses. Hence, there is a need to reinforce the importance of accurate dosimetry in therapeutic protocols. PMID:26445339

  15. Fluence dependent electrical conductivity in aluminium thin films grown by infrared pulsed laser deposition

    NASA Astrophysics Data System (ADS)

    Rebollar, Esther; Martínez-Tong, Daniel E.; Sanz, Mikel; Oujja, Mohamed; Marco, José F.; Ezquerra, Tiberio A.; Castillejo, Marta

    2016-11-01

    We studied the effect of laser fluence on the morphology, composition, structure and electric conductivity of deposits generated by pulsed laser ablation of a metallic aluminium target in vacuum using a Q-switched Nd:YAG laser (1064 nm, 15 ns). Upon irradiation for one hour at a repetition rate of 10 Hz, a smooth layer of several tens of nanometres, as revealed by atomic force microscopy (AFM) was deposited on glass. Surface chemical composition was determined by X-ray photoelectron spectroscopy, and to study the conductivity of deposits both I-V curves and conductive-AFM measurements were performed. Irradiation at fluences around 2.7 J/cm2 resulted in deposition of amorphous aluminium oxide films. Differently, at higher fluences above 7 J/cm2, the films are constituted by metallic aluminium. Optical emission spectroscopy revealed that highly ionized species are more abundant in the ablation plumes generated at higher fluences. The results demonstrate the possibility to control by PLD the metal or dielectric character of the films.

  16. Low-intensity red and infrared laser effects at high fluences on Escherichia coli cultures

    PubMed Central

    Barboza, L.L.; Campos, V.M.A.; Magalhães, L.A.G.; Paoli, F.; Fonseca, A.S.

    2015-01-01

    Semiconductor laser devices are readily available and practical radiation sources providing wavelength tenability and high monochromaticity. Low-intensity red and near-infrared lasers are considered safe for use in clinical applications. However, adverse effects can occur via free radical generation, and the biological effects of these lasers from unusually high fluences or high doses have not yet been evaluated. Here, we evaluated the survival, filamentation induction and morphology of Escherichia coli cells deficient in repair of oxidative DNA lesions when exposed to low-intensity red and infrared lasers at unusually high fluences. Cultures of wild-type (AB1157), endonuclease III-deficient (JW1625-1), and endonuclease IV-deficient (JW2146-1) E. coli, in exponential and stationary growth phases, were exposed to red and infrared lasers (0, 250, 500, and 1000 J/cm2) to evaluate their survival rates, filamentation phenotype induction and cell morphologies. The results showed that low-intensity red and infrared lasers at high fluences are lethal, induce a filamentation phenotype, and alter the morphology of the E. coli cells. Low-intensity red and infrared lasers have potential to induce adverse effects on cells, whether used at unusually high fluences, or at high doses. Hence, there is a need to reinforce the importance of accurate dosimetry in therapeutic protocols. PMID:26445339

  17. Low-intensity red and infrared laser effects at high fluences on Escherichia coli cultures.

    PubMed

    Barboza, L L; Campos, V M A; Magalhães, L A G; Paoli, F; Fonseca, A S

    2015-10-01

    Semiconductor laser devices are readily available and practical radiation sources providing wavelength tenability and high monochromaticity. Low-intensity red and near-infrared lasers are considered safe for use in clinical applications. However, adverse effects can occur via free radical generation, and the biological effects of these lasers from unusually high fluences or high doses have not yet been evaluated. Here, we evaluated the survival, filamentation induction and morphology of Escherichia coli cells deficient in repair of oxidative DNA lesions when exposed to low-intensity red and infrared lasers at unusually high fluences. Cultures of wild-type (AB1157), endonuclease III-deficient (JW1625-1), and endonuclease IV-deficient (JW2146-1) E. coli, in exponential and stationary growth phases, were exposed to red and infrared lasers (0, 250, 500, and 1000 J/cm2) to evaluate their survival rates, filamentation phenotype induction and cell morphologies. The results showed that low-intensity red and infrared lasers at high fluences are lethal, induce a filamentation phenotype, and alter the morphology of the E. coli cells. Low-intensity red and infrared lasers have potential to induce adverse effects on cells, whether used at unusually high fluences, or at high doses. Hence, there is a need to reinforce the importance of accurate dosimetry in therapeutic protocols.

  18. Calculated values of atomic oxygen fluences and solar exposure on selected surfaces of LDEF

    NASA Technical Reports Server (NTRS)

    Gillis, J. R.; Pippin, H. G.; Bourassa, R. J.; Gruenbaum, P. E.

    1995-01-01

    Atomic oxygen (AO) fluences and solar exposure have been modeled for selected hardware from the Long Duration Exposure Facility (LDEF). The atomic oxygen exposure was modeled using the microenvironment modeling code SHADOWV2. The solar exposure was modeled using the microenvironment modeling code SOLSHAD version 1.0.

  19. Corrosion behaviors of Mo coating on stainless steel 316 substrates implanted by different nitrogen ion fluences

    NASA Astrophysics Data System (ADS)

    Mojtahedzadeh Larijani, Madjid; Bafandeh, Nastaran

    2014-03-01

    The molybdenum nitride coating was produced by nitrogen ion implantation of the molybdenum layer deposited on the stainless steel 316 (SS) substrates. At first, molybdenum layers were deposited on the substrates by ion beam sputtering method, then nitrogen ions with an energy of 30 keV and a fluence between 1×1017 and 12×1017 N+ cm-2 were implanted in Mo/SS system. Crystal structure and topography of the surface are investigated by grazing incidence X-ray diffraction (GIXRD) and atomic force microscopy (AFM) image respectively. XRD patterns showed the formation of molybdenum nitride phases in all implanted samples. Corrosion tests showed that the corrosion resistance of the samples strongly depends on the nitrogen applied fluences. A considerable improvement of corrosion performance by increasing ions fluences was observed. The lowest corrosion current density with amount of 0.1 μA/cm2 was obtained at 12×1017 ions/cm2 fluence in our case.

  20. New method for estimation of fluence complexity in IMRT fields and correlation with gamma analysis

    NASA Astrophysics Data System (ADS)

    Hanušová, T.; Vondráček, V.; Badraoui-Čuprová, K.; Horáková, I.; Koniarová, I.

    2015-01-01

    A new method for estimation of fluence complexity in Intensity Modulated Radiation Therapy (IMRT) fields is proposed. Unlike other previously published works, it is based on portal images calculated by the Portal Dose Calculation algorithm in Eclipse (version 8.6, Varian Medical Systems) in the plane of the EPID aS500 detector (Varian Medical Systems). Fluence complexity is given by the number and the amplitudes of dose gradients in these matrices. Our method is validated using a set of clinical plans where fluence has been smoothed manually so that each plan has a different level of complexity. Fluence complexity calculated with our tool is in accordance with the different levels of smoothing as well as results of gamma analysis, when calculated and measured dose matrices are compared. Thus, it is possible to estimate plan complexity before carrying out the measurement. If appropriate thresholds are determined which would distinguish between acceptably and overly modulated plans, this might save time in the re-planning and re-measuring process.

  1. Ultra low fluence rate photodynamic therapy: simulation of light emitted by the Cerenkov effect

    NASA Astrophysics Data System (ADS)

    Gonzales, Jonathan; Wang, Fred; Zamora, Genesis; Trinidad, Anthony; Marcu, Laura; Cherry, Simon; Hirschberg, Henry

    2014-03-01

    PDT has been shown to be most effective at low fluence rates. Many radionuclides used for both diagnostic and therapeutic purposes produce measurable amounts of visible radiation when they decay via the Cerenkov effect which occurs when a charged particle travels faster in a dielectric medium than the speed of light in that medium. Cerenkov radiation from radiopharmaceuticals could serve as a source of extended duration, low level "internal" light, to mediate PDT, with the ultimate goals of overcoming some its current limitations. Using laser light, we are exploring the effects of fluence rates that could be generated by Cerenkov radiation on PDT efficacy. ALA or TPPS2a mediated PDT of rat gliomas monolayers or multicell spheroids ( F98, C6) was performed with 410 nm laser light exposure over an extended period of 24-96hrs. Photosensitizers were delivered either as a bolus or continuously with light exposure. At fluence rate of 20μW/cm2 effective PDT was obtained as measured by decrease in cell viability or inhibition of spheroid growth. PDT is effective at ultra low fluence rates if given over long time periods. No lower threshold has been ascertained. Since the half-life of 90Y, a radionuclide with a high Cherenkov yield is 64 hrs it is a good candidate to supply sufficient light activation for PDT. The combination of radionuclide and photodynamic therapies could improve the effectiveness of cancer treatment by exploiting synergies between these two modalities.

  2. Sea surface temperature and salinity patterns in the northern North Atlantic and the Arctic during interglacial MIS 11c: Implications for oceanic circulation reconstruction

    NASA Astrophysics Data System (ADS)

    Kandiano, E.; van der Meer, M.; Schouten, S.; Fahl, K.; Polyak, L. V.; Cronin, T. M.; Bauch, H. A.; Sinninghe Damste, J. S.

    2013-12-01

    Sea surface temperature (SST) patterns in the northern North Atlantic, the Nordic seas, and the western Arctic Ocean (AO) were reconstructed across the MIS 11c interglacial, a potential future climate analogue, using planktic foraminiferal abundances, alkenone-based Uk'37 and glycerol dialkyl glycerol tetraether (GDGT)-based TEX86 analyses. Foraminiferal SST reconstructions were supported by foraminiferal counts of small-sized fractions and rare foraminiferal species, stable oxygen isotope measurements on benthic and planktic foraminifers, and ice rafted debris records. Additionally, the hydrogen isotopic (δD) compositions of long chain alkenones were determined to assess variations in paleo sea surface salinity in the North Atlantic. In the North Atlantic our newly produced TEX86 -based SSTs range between 14 and 19 °C in agreement with summer foraminiferal SST (13 and 18 °C) and alkenone SSTs (13 and 16 °C). However, the former showed higher fluctuations than SSTs based on foraminiferal abundances. In concordance with δ18O records TEX86 SSTs demonstrate notable variability in the middle of MIS 11c, between 400 and 410 ka, which is consistent with the intra-MIS 11c cold event in the Arctic indicated by planktic foraminifers. This pattern implies that the interglacial MIC 11c climate was probably not as stable as it widely believed. The preliminary alkenone δD data show that during MIS 11c salinity values in the North Atlantic were similar to Holocene values. Foraminiferal SST records imply that during MIS 11c at least parts of the AO experienced unusually warm and probably ice free conditions, whereas the Nordic seas remained rather cold, especially during the early phase of this period, as it is inferred from foraminiferal and alkenone SSTs. At the same time all our SST records show that the North Atlantic was 1-2°C warmer than present during MIS 11c. This pattern suggests that during MIS 11c the North Atlantic Current was deflected to the west, which

  3. Distribution of Intravenously Administered Acetylcholinesterase Inhibitor and Acetylcholinesterase Activity in the Adrenal Gland: 11C-Donepezil PET Study in the Normal Rat

    PubMed Central

    Watabe, Tadashi; Naka, Sadahiro; Ikeda, Hayato; Horitsugi, Genki; Kanai, Yasukazu; Isohashi, Kayako; Ishibashi, Mana; Kato, Hiroki; Shimosegawa, Eku; Watabe, Hiroshi; Hatazawa, Jun

    2014-01-01

    Purpose Acetylcholinesterase (AChE) inhibitors have been used for patients with Alzheimer's disease. However, its pharmacokinetics in non-target organs other than the brain has not been clarified yet. The purpose of this study was to evaluate the relationship between the whole-body distribution of intravenously administered 11C-Donepezil (DNP) and the AChE activity in the normal rat, with special focus on the adrenal glands. Methods The distribution of 11C-DNP was investigated by PET/CT in 6 normal male Wistar rats (8 weeks old, body weight  = 220±8.9 g). A 30-min dynamic scan was started simultaneously with an intravenous bolus injection of 11C-DNP (45.0±10.7 MBq). The whole-body distribution of the 11C-DNP PET was evaluated based on the Vt (total distribution volume) by Logan-plot analysis. A fluorometric assay was performed to quantify the AChE activity in homogenized tissue solutions of the major organs. Results The PET analysis using Vt showed that the adrenal glands had the 2nd highest level of 11C-DNP in the body (following the liver) (13.33±1.08 and 19.43±1.29 ml/cm3, respectively), indicating that the distribution of 11C-DNP was the highest in the adrenal glands, except for that in the excretory organs. The AChE activity was the third highest in the adrenal glands (following the small intestine and the stomach) (24.9±1.6, 83.1±3.0, and 38.5±8.1 mU/mg, respectively), indicating high activity of AChE in the adrenal glands. Conclusions We demonstrated the whole-body distribution of 11C-DNP by PET and the AChE activity in the major organs by fluorometric assay in the normal rat. High accumulation of 11C-DNP was observed in the adrenal glands, which suggested the risk of enhanced cholinergic synaptic transmission by the use of AChE inhibitors. PMID:25225806

  4. 11C-choline vs. 18F-FDG PET/CT in assessing bone involvement in patients with multiple myeloma

    PubMed Central

    Nanni, Cristina; Zamagni, Elena; Cavo, Michele; Rubello, Domenico; Tacchetti, Paola; Pettinato, Cinzia; Farsad, Mohsen; Castellucci, Paolo; Ambrosini, Valentina; Montini, Gian Carlo; Al-Nahhas, Adil; Franchi, Roberto; Fanti, Stefano

    2007-01-01

    Background Multiple Myeloma (MM) is a B cell neoplasm causing lytic or osteopenic bone abnormalities. Whole body skeletal survey (WBSS), Magnetic resonance (MR) and 18F-FDG PET/CT are imaging techniques routinely used for the evaluation of bone involvement in MM patients. Aim As MM bone lesions may present low 18F-FDG uptake; the aim of this study was to assess the possible added value and limitations of 11C-Choline to that of 18F-FDG PET/CT in patients affected with MM. Methods Ten patients affected with MM underwent a standard 11C-Choline PET/CT and an 18F-FDG PET/CT within one week. The results of the two scans were compared in terms of number, sites and SUVmax of lesions. Results Four patients (40%) had a negative concordant 11C-Choline and 18F-FDG PET/CT scans. Two patients (20%) had a positive 11C-Choline and 18F-FDG PET/CT scans that identified the same number and sites of bone lesions. The remaining four patients (40%) had a positive 11C-Choline and 18F-FDG PET/CT scan, but the two exams identified different number of lesions. Choline showed a mean SUVmax of 5 while FDG showed a mean SUVmax of 3.8 (P = 0.042). Overall, 11C-Choline PET/CT scans detected 37 bone lesions and 18F-FDG PET/CT scans detected 22 bone lesions but the difference was not significant (P = 0.8). Conclusion According to these preliminary data, 11C-Choline PET/CT appears to be more sensitive than 18F-FDG PET/CT for the detection of bony myelomatous lesions. If these data are confirmed in larger series of patients, 11C-Choline may be considered a more appropriate functional imaging in association with MRI for MM bone staging. PMID:17584499

  5. Ringhals unit 3 and 4 - Fluence determination in a historic and future perspective

    SciTech Connect

    Green, E.L.

    2011-07-01

    Document available in abstract form only, full text of document follows: The Ringhals site is situated on the Swedish southwest coastline. At the site, there are four operating nuclear power plants. Historically, the Swedish policy has been that the nuclear power plants were to be closed in 2010. The present position is to operate the units until their technical and economic lifetime has run out. The units shall be maintained and invested in to ensure a lifetime of at least 50 years, but the actions taken shall not limit the time to this date. When the initial surveillance capsules were evaluated, it was noted that the material properties of the weld material of unit 3 and 4 showed some deviations from the expected behaviour. Currently there is an extensive project running for re-evaluating the embrittlement situation from a long-term operating perspective. One part of the project is aimed at more accurately determining the fluence levels of the reactor pressure vessels (RPVs). The basis for the early evaluations of the dosimeters in the surveillance capsules and the corresponding fluence evaluation had an operating lifetime of 25 years as a target value. Therefore, the accuracy and refinement of the measurement and calculation were taken to be good enough to suit this life span. Looking back at the results from the dosimetry measurements there are a few discrepancies. Some of the dosimeters were disintegrated and some measurements had comparatively large uncertainties. When starting this project there were some re-evaluations done with the old fluence prediction model. For every new run and refinement there appeared new difficulties, and the decision was to start the evaluation from scratch. Then there are two questions remaining regarding the fluence: What is the current fluence level? What will the resulting fluence be after 60 years of operation, when we have up-rated output power of both reactors? This paper aims to describe the view of the fluence evaluation

  6. Irradiation Programs and Test Plans to Assess High-Fluence Irradiation Assisted Stress Corrosion Cracking Susceptibility.

    SciTech Connect

    Teysseyre, Sebastien

    2015-03-01

    . Irradiation assisted stress corrosion cracking (IASCC) is a known issue in current reactors. In a 60 year lifetime, reactor core internals may experience fluence levels up to 15 dpa for boiling water reactors (BWR) and 100+ dpa for pressurized water reactors (PWR). To support a safe operation of our fleet of reactors and maintain their economic viability it is important to be able to predict any evolution of material behaviors as reactors age and therefore fluence accumulated by reactor core component increases. For PWR reactors, the difficulty to predict high fluence behavior comes from the fact that there is not a consensus of the mechanism of IASCC and that little data is available. It is however possible to use the current state of knowledge on the evolution of irradiated microstructure and on the processes that influences IASCC to emit hypotheses. This report identifies several potential changes in microstructure and proposes to identify their potential impact of IASCC. The susceptibility of a component to high fluence IASCC is considered to not only depends on the intrinsic IASCC susceptibility of the component due to radiation effects on the material but to also be related to the evolution of the loading history of the material and interaction with the environment as total fluence increases. Single variation type experiments are proposed to be performed with materials that are representative of PWR condition and with materials irradiated in other conditions. To address the lack of IASCC propagation and initiation data generated with material irradiated in PWR condition, it is proposed to investigate the effect of spectrum and flux rate on the evolution of microstructure. A long term irradiation, aimed to generate a well-controlled irradiation history on a set on selected materials is also proposed for consideration. For BWR, the study of available data permitted to identify an area of concern for long term performance of component. The efficiency of

  7. Neutron fluence-to-dose conversion coefficients for embryo and fetus.

    PubMed

    Chen, Jing; Meyerhof, Dorothy; Vlahovich, Slavica

    2004-01-01

    A problem of concern in radiation protection is the exposure of pregnant women to ionising radiation, because of the high radiosensitivity of the embryo and fetus. External neutron exposure is of concern when pregnant women travel by aeroplane. Dose assessments for neutrons frequently rely on fluence-to-dose conversion coefficients. While neutron fluence-to-dose conversion coefficients for adults are recommended in International Commission on Radiological Protection publications and International Commission on Radiological Units and Measurements reports, conversion coefficients for embryos and fetuses are not given in the publications. This study undertakes Monte Carlo calculations to determine the mean absorbed doses to the embryo and fetus when the mother is exposed to neutron fields. A new set of mathematical models for the embryo and fetus has been developed at Health Canada and is used together with mathematical phantoms of a pregnant female developed at Oak Ridge National Laboratory. Monoenergetic neutrons from 1 eV to 10 MeV are considered in this study. The irradiation geometries include antero-posterior (AP), postero-anterior (PA), lateral (LAT), rotational (ROT) and isotropic (ISO) geometries. At each of these standard irradiation geometries, absorbed doses to the fetal brain and body are calculated; for the embryo at 8 weeks and the fetus at 3, 6 or 9 months. Neutron fluence-to-absorbed dose conversion coefficients are derived for the four age groups. Neutron fluence-to-equivalent dose conversion coefficients are given for the AP irradiations which yield the highest radiation dose to the fetal body in the neutron energy range considered here. The results indicate that for neutrons <10 MeV more protection should be given to pregnant women in the first trimester due to the higher absorbed dose per unit neutron fluence to the fetus. PMID:15353732

  8. Monte Carlo fluence simulation for prospective evaluation of interstitial photodynamic therapy treatment plans

    NASA Astrophysics Data System (ADS)

    Cassidy, Jeffrey; Betz, Vaughn; Lilge, Lothar

    2015-03-01

    Photodynamic therapy (PDT) delivers a localized cytotoxic dose that is a function of tissue oxygen availability, photosensitive drug concentration, and light fluence. Providing safe and effective PDT requires an understanding of all three elements and the physiological response to the radicals generated. Interstitial PDT (IPDT) for solid tumours poses particular challenges due to complex organ geometries and the associated limitations for diffusion theory based fluence rate prediction, in addition to restricted access for light delivery and dose monitoring. As a first step towards enabling a complete prospective IPDT treatment-planning platform, we demonstrate use of our previously developed FullMonte tetrahedral Monte Carlo simulation engine for modeling of the interstitial fluence field due to intravesicular insertion of brief light sources. The goal is to enable a complete treatment planning and monitoring work flow analogous to that used in ionizing radiation therapy, including plan evaluation through dose-volume histograms and algorithmic treatment plan optimization. FullMonte is to our knowledge the fastest open-source tetrahedral MC light propagation software. Using custom hardware acceleration, we achieve 4x faster computing with 67x better power efficiency for limited-size meshes compared to the software. Ongoing work will improve the performance advantage to 16x with unlimited mesh size, enabling algorithmic plan optimization in reasonable time. Using FullMonte, we demonstrate significant new plan-evaluation capabilities including fluence field visualization, generation of organ dose-volume histograms, and rendering of isofluence surfaces for a representative bladder cancer mesh from a real patient. We also discuss the advantages of MC simulations for dose-volume histogram generation and the need for online personalized fluence-rate monitoring.

  9. Signal and noise of diamond pixel detectors at high radiation fluences

    NASA Astrophysics Data System (ADS)

    Tsung, J.-W.; Havranek, M.; Hügging, F.; Kagan, H.; Krüger, H.; Wermes, N.

    2012-09-01

    CVD diamond is an attractive material option for LHC vertex detectors mainly because of its strong radiation-hardness causal to its large band gap and strong lattice. In particular, pixel detectors operating close to the interaction point profit from tiny leakage currents and small pixel capacitances of diamond resulting in low noise figures when compared to silicon. On the other hand, the charge signal from traversing high energy particles is smaller in diamond than in silicon by a factor of about 2.2. Therefore, a quantitative determination of the signal-to-noise ratio (S/N) of diamond in comparison with silicon at fluences in excess of 1015 neq cm-2, which are expected for the LHC upgrade, is important. Based on measurements of irradiated diamond sensors and the FE-I4 pixel readout chip design and performance, we determine the signal and the noise of diamond pixel detectors irradiated with high particle fluences. To characterize the effect of the radiation damage on the materials and the signal decrease, the change of the mean free path λe/h of the charge carriers is determined as a function of irradiation fluence. We make use of the FE-I4 pixel chip developed for ATLAS upgrades to realistically estimate the expected noise figures: the expected leakage current at a given fluence is taken from calibrated calculations and the pixel capacitance is measured using a purposely developed chip (PixCap). We compare the resulting S/N figures with those for planar silicon pixel detectors using published charge loss measurements and the same extrapolation methods as for diamond. It is shown that the expected S/N of a diamond pixel detector with pixel pitches typical for LHC, exceeds that of planar silicon pixels at fluences beyond 1015 particles cm-2, the exact value only depending on the maximum operation voltage assumed for irradiated silicon pixel detectors.

  10. SU-E-J-69: Iterative Deconvolution of the Initial Photon Fluence for EPID Dosimetry: A Monte Carlo Based Study

    SciTech Connect

    Czarnecki, D; Voigts-Rhetz, P von; Shishechian, D Uchimura; Zink, K

    2015-06-15

    Purpose: Developing a fast and accurate calculation model to reconstruct the applied photon fluence from an external photon radiation therapy treatment based on an image recorded by an electronic portal image device (EPID). Methods: To reconstruct the initial photon fluence the 2D EPID image was corrected for scatter from the patient/phantom and EPID to generate the transmitted primary photon fluence. This was done by an iterative deconvolution using precalculated point spread functions (PSF). The transmitted primary photon fluence was then backprojected through the patient/phantom geometry considering linear attenuation to receive the initial photon fluence applied for the treatment.The calculation model was verified using Monte Carlo simulations performed with the EGSnrc code system. EPID images were produced by calculating the dose deposition in the EPID from a 6 MV photon beam irradiating a water phantom with air and bone inhomogeneities and the ICRP anthropomorphic voxel phantom. Results: The initial photon fluence was reconstructed using a single PSF and position dependent PSFs which depend on the radiological thickness of the irradiated object. Appling position dependent point spread functions the mean uncertainty of the reconstructed initial photon fluence could be reduced from 1.13 % to 0.13 %. Conclusion: This study presents a calculation model for fluence reconstruction from EPID images. The{sup Result} show a clear advantage when position dependent PSF are used for the iterative reconstruction. The basic work of a reconstruction method was established and further evaluations must be made in an experimental study.

  11. Comparison of [11C]cocaine binding at tracer and pharmacological doses of baboon brain: A PET study

    SciTech Connect

    Volkow, N.D.; Fowler, J.S.; Logan, J.

    1994-05-01

    In vitro studies have shown that cocaine (C) binds to both high and low affinity sites on the dopamine transporter (DAT). We have previously characterized the binding of tracer doses of [{sup 11}C]cocaine (C*)to a high affinity site on the DAT. To assess if in vivo C also binds to low affinity sites we used PET to compare binding of tracer doses (17.8{plus_minus}12.2 {mu}g C) of C* to pharmacological doses (8 mg of C coadministered with C*). Sixteen paired studies were done to assess test/retest variability, specific versus non specific binding and to characterize binding profile. Dynamic scans were started immediately after injection of C* (5-8 mCi) for 50 min on the CTI-931 (6 x 6 x 6.5 mm FWHM). Time activity curves for tissue concentration and for unchanged tracer in plasma were used to calculate the transport constant between plasma and tissue (K1) and to obtain the distribution volume (DV). The ratio of the DV in striatum (ST) to that in cerebellum (CB) (which corresponds to Bmax/Kd-1) was used as model parameter. Peak brain uptake of C* was significantly higher for tracer than for pharmacological doses (0.041 versus 0.033 % dose/cc), as were the values for K1 (1.07{plus_minus}0.21 versus 0.68{plus_minus}0.26 (t=3.0 p<0.01)). Repeated measures were reproducible for tracer ({plus_minus}2%) and pharmacological doses of C* ({plus_minus}4%). Tracer dose C* showed highest binding and slowest clearance in ST which was reduced by C (0.5-2.0 mg/kg iv, -25 to -30%) and by drugs that inhibit DAT (2mg/kg nomifensine - 21%, 0.5 mg/kg methylphenidate -12%) and was increased by serotonin transporter inhibitors (5HT-Ti) (2 mg/kg citalopram +11%, 0.5 mg/kg fluoxetine +6%) and not changed by NE transporter inhibitors (0.5 mg/kg desipramine or 2 mg/kg tomoxetine). The increase with (5HT-Ti) may reflect neurotransmitter interactions or changes in bioavailability. At pharmacological doses C* showed homogeneous distribution and was not changed by C nor by any of the above drugs.

  12. Space Environment Effects: Model for Emission of Solar Protons (ESP)--Cumulative and Worst-Case Event Fluences

    NASA Astrophysics Data System (ADS)

    Xapsos, M. A.; Barth, J. L.; Stassinopoulos, E. G.; Burke, Edward A.; Gee, G. B.

    1999-12-01

    The effects that solar proton events have on microelectronics and solar arrays are important considerations for spacecraft in geostationary and polar orbits and for interplanetary missions. Designers of spacecraft and mission planners are required to assess the performance of microelectronic systems under a variety of conditions. A number of useful approaches exist for predicting information about solar proton event fluences and, to a lesser extent, peak fluxes. This includes the cumulative fluence over the course of a mission, the fluence of a worst-case event during a mission, the frequency distribution of event fluences, and the frequency distribution of large peak fluxes. Naval Research Laboratory (NRL) and NASA Goddard Space Flight Center, under the sponsorship of NASA's Space Environments and Effects (SEE) Program, have developed a new model for predicting cumulative solar proton fluences and worst-case solar proton events as functions of mission duration and user confidence level. This model is called the Emission of Solar Protons (ESP) model.

  13. Space Environment Effects: Model for Emission of Solar Protons (ESP)--Cumulative and Worst-Case Event Fluences

    NASA Technical Reports Server (NTRS)

    Xapsos, M. A.; Barth, J. L.; Stassinopoulos, E. G.; Burke, Edward A.; Gee, G. B.

    1999-01-01

    The effects that solar proton events have on microelectronics and solar arrays are important considerations for spacecraft in geostationary and polar orbits and for interplanetary missions. Designers of spacecraft and mission planners are required to assess the performance of microelectronic systems under a variety of conditions. A number of useful approaches exist for predicting information about solar proton event fluences and, to a lesser extent, peak fluxes. This includes the cumulative fluence over the course of a mission, the fluence of a worst-case event during a mission, the frequency distribution of event fluences, and the frequency distribution of large peak fluxes. Naval Research Laboratory (NRL) and NASA Goddard Space Flight Center, under the sponsorship of NASA's Space Environments and Effects (SEE) Program, have developed a new model for predicting cumulative solar proton fluences and worst-case solar proton events as functions of mission duration and user confidence level. This model is called the Emission of Solar Protons (ESP) model.

  14. Massive accumulation of 11C-Pittsburg compound B in the occipital lobes of a patient with early-onset dementia accompanied by muscle weakness and hypertonicity.

    PubMed

    Ito, Kimiteru; Sano, Terunori; Kamiya, Kouhei; Nakata, Yasuhiro; Shigemoto, Yoko; Sato, Noriko; Oya, Yasushi; Matsuda, Hiroshi

    2013-12-01

    A 44-year-old woman underwent 11C-Pittsburg compound B (11C-PiB), 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT), 99mTc-ethyl-cysteinate-dimer single photon emission computed tomography, and magnetic resonance imaging after presenting with progressive dementia, muscle weakness, and hypertonicity. Some of her family members had died of muscle weakness with early-onset dementia of unknown etiology. Neurological and psychological examinations revealed moderate dementia in general fields and muscle weakness in her upper limbs. 11C-PiB PET/CT revealed abnormal accumulations of amyloid in the bilateral occipital lobes, while physiological uptakes of 11C-PiB in areas that normally show high uptake, such as white matter, appeared relatively decreased. Meanwhile, cerebrospinal fluid (CSF) amyloid-β was decreased, and CSF total and phosphorylated tau proteins were increased. This case may be representative of a new category of amyloid deposition disease characterized by early-onset dementia, muscle weakness, and hypertonicity, or at least, a new uptake pattern of PiB in variant AD.

  15. Pd0-mediated rapid cross-coupling reactions, the rapid C-[11C]methylations, revolutionarily advancing the syntheses of short-lived PET molecular probes.

    PubMed

    Suzuki, Masaaki; Doi, Hisashi; Koyama, Hiroko; Zhang, Zhouen; Hosoya, Takamitsu; Onoe, Hirotaka; Watanabe, Yasuyoshi

    2014-06-01

    Positron emission tomography is a noninvasive method for monitoring drug (or diagnostic) behavior and its localization on the target molecules in the living systems, including the human body, using a short-lived positron-emitting radionuclide. New methodologies for introducing representative short-lived radionuclides, (11)C and (18)F, into the carbon frameworks of biologically active organic compounds have been established by developing rapid C-[(11)C]methylations and C-[(18)F]fluoromethylations using rapid Pd(0)-mediated cross-coupling reactions between [(11)C]methyl iodide (sp(3)-hybridized carbon) and an excess amount of organotributylstannane or organoboronic acid ester having sp(2) (phenyl, heteroaromatic, or alkenyl), sp(alkynyl), or sp(3) (benzyl and cinnamyl)-hybridized carbons; and [(18)F]fluoromethyl halide (iodide or bromide) and an organoboronic acid ester, respectively. These rapid reactions provide a firm foundation for an efficient and general synthesis of short-lived (11)C- or (18)F-labeled PET molecular probes to promote in vivo molecular imaging studies.

  16. Mapping of serotonin transporters by positron emission tomography with [11C]DASB in conscious common marmosets: comparison with rhesus monkeys.

    PubMed

    Yokoyama, Chihiro; Yamanaka, Hajime; Onoe, Kayo; Kawasaki, Akihiro; Nagata, Hiroko; Shirakami, Keiko; Doi, Hisashi; Onoe, Hirotaka

    2010-08-01

    The common marmoset (Callithrix jacchus) is unique among the primates in its small body size, reproductive efficacy, and characteristic social behavior, making it useful as an animal model in neuroscientific research. To assess the brain serotonergic systems, we investigated the binding of [(11)C]-3-amino-4-(2-dimetylaminomethyl-phenylsulfanyl)-benzonitrile ([(11)C]DASB) to brain serotonin transporter (SERT) in conscious common marmosets using positron emission tomography (PET), and compared with findings for rhesus monkeys. Both species showed globally similar distribution patterns of [(11)C]DASB uptake in the brain, with highest activity in the midline of the brain and lowest in the cerebellum, and higher activity in some subcortical regions than in surrounding cortex, while the common marmoset brain showed almost equal or rather higher binding potential (BP) values (BP(ND)) in cortical regions and hippocampus, and lower BP(ND) than the rhesus monkey brain in some subcortical regions. Test-retest reproducibility of BP(ND) at an interval of several months was high, indicating reliable and stable measurements of serotonin transporters in both species. These results suggest that SERT imaging by PET with [(11)C]DASB under conscious state is valuable for investigating the physiological serotonergic functions in common marmosets (182).

  17. Compartmental analysis of (11C)flumazenil kinetics for the estimation of ligand transport rate and receptor distribution using positron emission tomography

    SciTech Connect

    Koeppe, R.A.; Holthoff, V.A.; Frey, K.A.; Kilbourn, M.R.; Kuhl, D.E. )

    1991-09-01

    The in vivo kinetic behavior of (11C)flumazenil ((11C)FMZ), a non-subtype-specific central benzodiazepine antagonist, is characterized using compartmental analysis with the aim of producing an optimized data acquisition protocol and tracer kinetic model configuration for the assessment of (11C)FMZ binding to benzodiazepine receptors (BZRs) in human brain. The approach presented is simple, requiring only a single radioligand injection. Dynamic positron emission tomography data were acquired on 18 normal volunteers using a 60- to 90-min sequence of scans and were analyzed with model configurations that included a three-compartment, four-parameter model, a three-compartment, three-parameter model, with a fixed value for free plus nonspecific binding; and a two-compartment, two-parameter model. Statistical analysis indicated that a four-parameter model did not yield significantly better fits than a three-parameter model. Goodness of fit was improved for three- versus two-parameter configurations in regions with low receptor density, but not in regions with moderate to high receptor density. Thus, a two-compartment, two-parameter configuration was found to adequately describe the kinetic behavior of (11C)FMZ in human brain, with stable estimates of the model parameters obtainable from as little as 20-30 min of data. Pixel-by-pixel analysis yields functional images of transport rate (K1) and ligand distribution volume (DV), and thus provides independent estimates of ligand delivery and BZR binding.

  18. Comparative double-tracer whole-body autoradiography: uptake of 11C-, 18F- and 3H-labeled compounds in rat tumors.

    PubMed

    d'Argy, R; Paul, R; Frankenberg, L; Stålnacke, C G; Lundqvist, H; Kangas, L; Halldin, C; Någren, K; Roeda, D; Haaparanta, M

    1988-01-01

    The uptake of various labeled compounds by tumors was studied by double-tracer whole-body autoradiography (DTWBA) in rats. Each animal carried two types of tumors: mammary carcinomas and the Walker 256 carcinosarcomas. The markers used were [18F]- and [3H]fluorodeoxyglucose (glucose utilization), [3H]thymidine (cell proliferation), [11C]methionine (amino acid metabolism) and [11C]- and [3H]toremifene (estrogen-receptor-avid agents). In each experiment, the distribution of a substance labeled with short-lived radionuclide (11C or 18F) was compared with that of another substance labeled with a long-lived nuclide (3H). Quantification was done by combining computerized image analysis of the autoradiograms with liquid scintillation counting of punched tissue pieces obtained from the cryosections. The relationships between the uptakes of the various radiopharmaceuticals were recorded in tumors and normal tissues. The dynamics of [18F]fluorodeoxyglucose and [11C]methionine were determined in tumors and some selected tissues by positron emission tomography (PET). The uptake rate between fluorodeoxyglucose and thymidine in the mammary tumor was five times higher than the ratio in the Walker tumor. The corresponding figure for FDG/methionine was four times. Thymidine, compared with methionine, was twice as efficient. Thus, the mammary tumors were best imaged with FDG or thymidine. The non-steroid antiestrogen toremifene was taken up in very low amounts by these tumors. By DTWBA, experimental tumors may serve as their own control. PMID:2978293

  19. Cutting Edge: IL-4, IL-21, and IFN-γ Interact To Govern T-bet and CD11c Expression in TLR-Activated B Cells.

    PubMed

    Naradikian, Martin S; Myles, Arpita; Beiting, Daniel P; Roberts, Kenneth J; Dawson, Lucas; Herati, Ramin Sedaghat; Bengsch, Bertram; Linderman, Susanne L; Stelekati, Erietta; Spolski, Rosanne; Wherry, E John; Hunter, Christopher; Hensley, Scott E; Leonard, Warren J; Cancro, Michael P

    2016-08-15

    T-bet and CD11c expression in B cells is linked with IgG2c isotype switching, virus-specific immune responses, and humoral autoimmunity. However, the activation requisites and regulatory cues governing T-bet and CD11c expression in B cells remain poorly defined. In this article, we reveal a relationship among TLR engagement, IL-4, IL-21, and IFN-γ that regulates T-bet expression in B cells. We find that IL-21 or IFN-γ directly promote T-bet expression in the context of TLR engagement. Further, IL-4 antagonizes T-bet induction. Finally, IL-21, but not IFN-γ, promotes CD11c expression independent of T-bet. Using influenza virus and Heligmosomoides polygyrus infections, we show that these interactions function in vivo to determine whether T-bet(+) and CD11c(+) B cells are formed. These findings suggest that T-bet(+) B cells seen in health and disease share the common initiating features of TLR-driven activation within this circumscribed cytokine milieu.

  20. 76 FR 16851 - Notice of Intent To Rule on Passenger Facility Charge (PFC) Application 11-11-C-00-BUR, To Impose...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-25

    ...-11-C-00-BUR, To Impose and Use PFC Revenue at Bob Hope Airport, Burbank, CA AGENCY: Federal Aviation... invites public comment on the application to impose and use PFC revenue at Bob Hope Airport, under the... rule and invites public comment on the application to impose and use PFC revenue at Bob Hope...

  1. Salmonella inhibits monocyte differentiation into CD11c hi MHC-II hi cells in a MyD88-dependent fashion.

    PubMed

    Rydström, Anna; Wick, Mary Jo

    2010-05-01

    Monocytes and DCs originate from a shared precursor in the bone marrow, and steady-state DCs in lymphoid organs develop directly from the precursor rather than via a monocyte intermediate. However, monocytes can differentiate into DCs in tissues such as the lung and gut mucosa and into macrophages in most tissues. As Ly6C hi monocytes accumulate in lymphoid organs during oral Salmonella infection, we investigated their ability to develop into potential DCs, identified as CD11c hi MHC-II hi cells, in infected hosts. Ly6C hi monocytes, isolated from the blood of Salmonella-infected mice, developed into CD11c hi MHC-II hi cells after culture with GM-CSF or Flt3L. In contrast, the same monocytes cultured in the presence of GM-CSF and heat-killed Salmonella did not differentiate into CD11c hi MHC-II hi cells. The bacteria-induced differentiation block was dependent on TLRs, as monocytes from MyD88-/- mice converted into CD11c hi MHC-II hi cells even in the presence of bacteria. We hypothesized that Salmonella-activated wild-type monocytes secreted mediators that inhibited differentiation of MyD88-/--derived monocytes. However, IL-6, IL-10, TNF-alpha, or IL-12p70 did not account for the inhibition. Finally, monocyte-derived CD11c hi MHC-II hi cells pulsed with OVA peptide or protein did not induce proliferation of antigen-specific CD4+ T cells but rather, suppressed the ability of DCs to activate CD4+ T cells. Overall, the data show that Ly6C hi monocytes from Salmonella-infected mice develop into CD11c hi MHC-II hi cells with poor antigen-presentation capacity when cultured ex vivo, and that monocyte exposure to Salmonella inhibits their differentiation into CD11c hi MHC-II hi cells in a MyD88-dependent fashion.

  2. Synthesis and in vivo evaluation of [11C]tariquidar, a positron emission tomography radiotracer based on a third-generation P-glycoprotein inhibitor

    PubMed Central

    Bauer, Florian; Kuntner, Claudia; Bankstahl, Jens P.; Wanek, Thomas; Bankstahl, Marion; Stanek, Johann; Mairinger, Severin; Dörner, Bernd; Löscher, Wolfgang; Müller, Markus; Erker, Thomas; Langer, Oliver

    2013-01-01

    The aim of this study was to develop a positron emission tomography (PET) tracer based on the dual P-glycoprotein (P-gp) breast cancer resistance protein (BCRP) inhibitor tariquidar (1) to study the interaction of 1 with P-gp and BCRP in the blood-brain barrier (BBB) in vivo. O-desmethyl-1 was synthesized and reacted with [11C]methyl triflate to afford [11C]-1. Small-animal PET imaging of [11C]-1 was performed in naïve rats, before and after administration of unlabeled 1 (15 mg/kg, n=3) or the dual P-gp/BCRP inhibitor elacridar (5 mg/kg, n=2), as well as in wild-type, Mdr1a/b(−/−), Bcrp1(−/−) and Mdr1a/b(−/−)Bcrp1(−/−) mice (n=3). In vitro autoradiography was performed with [11C]-1 using brain sections of all 4 mouse types, with and without co-incubation with unlabeled 1 or elacridar (1 μM). In PET experiments in rats, administration of unlabeled 1 or elacridar increased brain activity uptake by a factor of 3-4, whereas blood activity levels remained unchanged. In Mdr1a/b(−/−), Bcrp1(−/−) and Mdr1a/b(−/−)Bcrp1(−/−) mice, brain-to-blood ratios of activity at 25 min after tracer injection were 3.4, 1.8 and 14.5 times higher, respectively, as compared to wild-type animals. Autoradiography showed approximately 50% less [11C]-1 binding in transporter knockout mice compared to wild-type mice and significant displacement by unlabeled elacridar in wild-type and Mdr1a/b(−/−) mouse brains. Our data suggest that [11C]-1 interacts specifically with P-gp and BCRP in the BBB. However, further investigations are needed to assess if [11C]-1 behaves in vivo as a transported or a non-transported inhibitor. PMID:20621487

  3. Pre-clinical characterization of [11C]R05013853 as a novel radiotracer for imaging of the glycine transporter type 1 by positron emission tomography.

    PubMed

    Borroni, Edilio; Zhou, Yun; Ostrowitzki, Susanne; Alberati, Daniela; Kumar, Anil; Hainzl, Dominik; Hartung, Thomas; Hilton, John; Dannals, Robert F; Wong, Dean F

    2013-07-15

    A specific positron emission tomography (PET) radiotracer for the glycine transporter type 1 (GlyT1) would constitute an imaging biomarker to investigate the distribution of GlyT1 in normal individuals and those with neuropsychiatric disorders. In addition it could demonstrate the ability of a novel drug to reach its target in the brain and enable receptor occupancy studies, thus facilitating drug development. In this article we describe the evaluation in non-human primates of two candidate PET radiotracers ([(11)C]RO5013852 and [(11)C]RO5013853) previously characterized in the rat. Both radiotracers showed acceptable uptake in the baboon brain and heterogeneous distribution consistent with that reported for GlyT1. In vivo blockade studies with two specific glycine reuptake inhibitors (GRIs), RO5013853 and bitopertin (RG1678, reduced uptake of both tracers to homogenous levels across brain regions and demonstrated specificity of the signal. [(11)C]RO5013853 showed a larger specific signal and slightly higher brain uptake and was therefore selected for further characterization. Quantitative compartmental analysis of PET data showed that the 2-tissue compartment model with 5 parameters was the most appropriate to describe the kinetics of [(11)C]RO5013853. Two additional methods were used: a) the Logan graphical analysis using plasma input and, b) a linear parametric imaging approach with the 2-tissue compartmental model. These produced VT estimates of comparable magnitude, namely, pons, thalamus and cerebellum>caudate, putamen and cortical regions. High resolution autoradiography with tritiated RO5013853 was used to confirm the binding pattern observed by PET. In vivo metabolism studies in the baboon demonstrated the formation of a single, radiolabeled metabolite more polar than the parent compound. Finally, [(11)C]RO5013853 was used to quantify the degree of cerebral GlyT1 occupancy observed in the baboon following oral administration of bitopertin, a selective GRI

  4. A case of mistaken identity: CD11c-eYFP(+) cells in the normal mouse brain parenchyma and neural retina display the phenotype of microglia, not dendritic cells.

    PubMed

    Dando, Samantha J; Naranjo Golborne, Cecilia; Chinnery, Holly R; Ruitenberg, Marc J; McMenamin, Paul G

    2016-08-01

    Under steady-state conditions the central nervous system (CNS) is traditionally thought to be devoid of antigen presenting cells; however, putative dendritic cells (DCs) expressing enhanced yellow fluorescent protein (eYFP) are present in the retina and brain parenchyma of CD11c-eYFP mice. We previously showed that these mice carry the Crb1(rd8) mutation, which causes retinal dystrophic lesions; therefore we hypothesized that the presence of CD11c-eYFP(+) cells within the CNS may be due to pathology associated with the Crb1(rd8) mutation. We generated CD11c-eYFP Crb1(wt/wt) mice and compared the distribution and immunophenotype of CD11c-eYFP(+) cells in CD11c-eYFP mice with and without the Crb1(rd8) mutation. The number and distribution of CD11c-eYFP(+) cells in the CNS was similar between CD11c-eYFP Crb1(wt/wt) and CD11c-eYFP Crb1(rd8/rd8) mice. CD11c-eYFP(+) cells were distributed throughout the inner retina, and clustered in brain regions that receive input from the external environment or lack a blood-brain barrier. CD11c-eYFP(+) cells within the retina and cerebral cortex of CD11c-eYFP Crb1(wt/wt) mice expressed CD11b, F4/80, CD115 and Iba-1, but not DC or antigen presentation markers, whereas CD11c-eYFP(+) cells within the choroid plexus and pia mater expressed CD11c, I-A/I-E, CD80, CD86, CD103, DEC205, CD8α and CD135. The immunophenotype of CD11c-eYFP(+) cells and microglia within the CNS was similar between CD11c-eYFP Crb1(wt/wt) and CD11c-eYFP Crb1(rd8/rd8) mice; however, CD11c and I-A/I-E expression was significantly increased in CD11c-eYFP Crb1(rd8/rd8) mice. This study demonstrates that the overwhelming majority of CNS CD11c-eYFP(+) cells do not display the phenotype of DCs or their precursors and are most likely a subpopulation of microglia. GLIA 2016. GLIA 2016;64:1331-1349.

  5. Combining [11C]-AnxA5 PET Imaging with Serum Biomarkers for Improved Detection in Live Mice of Modest Cell Death in Human Solid Tumor Xenografts

    PubMed Central

    Cheng, Qing; Lu, Li; Grafström, Jonas; Olofsson, Maria Hägg; Thorell, Jan-Olov; Samén, Erik; Johansson, Katarina; Ahlzén, Hanna-Stina; Stone-Elander, Sharon; Linder, Stig; Arnér, Elias S. J.

    2012-01-01

    Background In vivo imaging using Annexin A5-based radioligands is a powerful technique for visualizing massive cell death, but has been less successful in monitoring the modest cell death typically seen in solid tumors after chemotherapy. Here we combined dynamic positron emission tomography (PET) imaging using Annexin A5 with a serum-based apoptosis marker, for improved sensitivity and specificity in assessment of chemotherapy-induced cell death in a solid tumor model. Methodology/Principal Findings Modest cell death was induced by doxorubicin in a mouse xenograft model with human FaDu head and neck cancer cells. PET imaging was based on 11C-labeled Sel-tagged Annexin A5 ([11C]-AnxA5-ST) and a size-matched control. 2-deoxy-2-[18F]fluoro-D-glucose ([18F]-FDG) was utilized as a tracer of tissue metabolism. Serum biomarkers for cell death were ccK18 and K18 (M30 Apoptosense® and M65). Apoptosis in tissue sections was verified ex vivo for validation. Both PET imaging using [11C]-AnxA5-ST and serum ccK18/K18 levels revealed treatment-induced cell death, with ccK18 displaying the highest detection sensitivity. [18F]-FDG uptake was not affected by this treatment in this tumor model. [11C]-AnxA5-ST gave robust imaging readouts at one hour and its short half-life made it possible to perform paired scans in the same animal in one imaging session. Conclusions/Significance The combined use of dynamic PET with [11C]-AnxA5-ST, showing specific increases in tumor binding potential upon therapy, with ccK18/K18 serum measurements, as highly sensitive markers for cell death, enabled effective assessment of modest therapy-induced cell death in this mouse xenograft model of solid human tumors. PMID:22870292

  6. Heightened D3 Dopamine Receptor Levels in Cocaine Dependence and Contributions to the Addiction Behavioral Phenotype: A Positron Emission Tomography Study with [11C]-(+)-PHNO

    PubMed Central

    Payer, Doris E; Behzadi, Arian; Kish, Stephen J; Houle, Sylvain; Wilson, Alan A; Rusjan, Pablo M; Tong, Junchao; Selby, Peter; George, Tony P; McCluskey, Tina; Boileau, Isabelle

    2014-01-01

    The dopamine system is a primary treatment target for cocaine dependence (CD), but research on dopaminergic abnormalities (eg, D2 receptor system deficiencies) has so far failed to translate into effective treatment strategies. The D3 receptor system has recently attracted considerable clinical interest, and D3 antagonism is now under investigation as a novel avenue for addiction treatment. The objective here was to evaluate the status and behavioral relevance of the D3 receptor system in CD, using the positron emission tomography (PET) radiotracer [11C]-(+)-PHNO. Fifteen CD subjects (many actively using, but all abstinent 7–240 days on scan day) and fifteen matched healthy control (HC) subjects completed two PET scans: one with [11C]-(+)-PHNO to assess D3 receptor binding (BPND; calculated regionally using the simplified reference tissue model), and for comparison, a second scan with [11C]raclopride to assess D2/3 binding. CD subjects also completed a behavioral battery to characterize the addiction behavioral phenotype. CD subjects showed higher [11C]-(+)-PHNO BPND than HC in the substantia nigra, which correlated with behavioral impulsiveness and risky decision making. In contrast, [11C]raclopride BPND was lower across the striatum in CD, consistent with previous literature in ⩾2 week abstinence. The data suggest that in contrast to a D2 deficiency, CD individuals may have heightened D3 receptor levels, which could contribute to addiction-relevant traits. D3 upregulation is emerging as a biomarker in preclinical models of addiction, and human PET studies of this receptor system can help guide novel pharmacological strategies for treatment. PMID:23921256

  7. Quantification of human opiate receptor concentration and affinity using high and low specific activity ( sup 11 C)diprenorphine and positron emission tomography

    SciTech Connect

    Sadzot, B.; Price, J.C.; Mayberg, H.S.; Douglass, K.H.; Dannals, R.F.; Lever, J.R.; Ravert, H.T.; Wilson, A.A.; Wagner, H.N. Jr.; Feldman, M.A. )

    1991-03-01

    (11C)Diprenorphine, a weak partial opiate agonist, and positron emission tomography were used to obtain noninvasive regional estimates of opiate receptor concentration (Bmax) and affinity (Kd) in human brain. Different compartmental models and fitting strategies were compared statistically to establish the most reliable method of parameter estimation. Paired studies were performed in six normal subjects using high (769-5,920 Ci/mmol) and low (27-80 Ci/mmol) specific activity (SA) (11C)diprenorphine. Two subjects were studied a third time using high SA (11C)diprenorphine after a pretreatment with 1-1.5 mg/kg of the opiate antagonist naloxone. After the plasma radioactivity was corrected for metabolites, the brain data were analyzed using a three-compartment model and nonlinear least-squares curve fitting. Linear differential equations were used to describe the high SA (low receptor occupancy) kinetics. The k3/k4 ratio varied from 1.0 +/- 0.2 (occipital cortex) to 8.6 +/- 1.6 (thalamus). Nonlinear differential equations were used to describe the low SA (high receptor occupancy) kinetics and the curve fits provided the konf2 product. The measured free fraction of (11C)diprenorphine in plasma (f1) was 0.30 +/- 0.03, the average K1/k2 ratio from the two naloxone studies was 1.1 +/- 0.2, and the calculated free fraction of (11C)diprenorphine in the brain (f2) was 0.3. Using the paired SA studies, the estimated kinetic parameters, and f2, separate estimates of Bmax and Kd were obtained. Bmax varied from 2.3 +/- 0.5 (occipital cortex) to 20.6 +/- 7.3 (cingulate cortex) nM. The average Kd (eight brain regions) was 0.85 +/- 0.17 nM.

  8. Pharmacokinetic modeling of P-glycoprotein function at the rat and human blood–brain barriers studied with (R)-[11C]verapamil positron emission tomography

    PubMed Central

    2012-01-01

    Background This study investigated the influence of P-glycoprotein (P-gp) inhibitor tariquidar on the pharmacokinetics of P-gp substrate radiotracer (R)-[11C]verapamil in plasma and brain of rats and humans by means of positron emission tomography (PET). Methods Data obtained from a preclinical and clinical study, in which paired (R)-[11C]verapamil PET scans were performed before, during, and after tariquidar administration, were analyzed using nonlinear mixed effects (NLME) modeling. Administration of tariquidar was included as a covariate on the influx and efflux parameters (Qin and Qout) in order to investigate if tariquidar increased influx or decreased outflux of radiotracer across the blood–brain barrier (BBB). Additionally, the influence of pilocarpine-induced status epilepticus (SE) was tested on all model parameters, and the brain-to-plasma partition coefficient (VT-NLME) was calculated. Results Our model indicated that tariquidar enhances brain uptake of (R)-[11C]verapamil by decreasing Qout. The reduction in Qout in rats during and immediately after tariquidar administration (sevenfold) was more pronounced than in the second PET scan acquired 2 h after tariquidar administration (fivefold). The effect of tariquidar on Qout in humans was apparent during and immediately after tariquidar administration (twofold reduction in Qout) but was negligible in the second PET scan. SE was found to influence the pharmacological volume of distribution of the central brain compartment Vbr1. Tariquidar treatment lead to an increase in VT-NLME, and pilocarpine-induced SE lead to increased (R)-[11C]verapamil distribution to the peripheral brain compartment. Conclusions Using NLME modeling, we were able to provide mechanistic insight into the effects of tariquidar and SE on (R)-[11C]verapamil transport across the BBB in control and 48 h post SE rats as well as in humans. PMID:23072492

  9. Tariquidar-induced P-glycoprotein inhibition at the rat blood-brain barrier studied with (R)-11C-verapamil and PET

    PubMed Central

    Bankstahl, Jens P.; Kuntner, Claudia; Abrahim, Aiman; Karch, Rudolf; Stanek, Johann; Wanek, Thomas; Wadsak, Wolfgang; Kletter, Kurt; Müller, Markus; Löscher, Wolfgang; Langer, Oliver

    2013-01-01

    The multidrug efflux transporter P-glycoprotein (P-gp) is expressed in high concentrations at the blood-brain barrier (BBB) and believed to be implicated in resistance to central nervous system drugs. We used small-animal positron emission tomography (PET) and (R)-11C-verapamil together with tariquidar, a new-generation P-gp modulator, to study the functional activity of P-gp at the BBB of rats. To enable a comparison with human PET data we performed kinetic modeling to estimate the rate constants of radiotracer transport across the rat BBB. Methods A group of 7 Wistar Unilever rats underwent paired (R)-11C-verapamil PET scans at an interval of 3 h, one baseline scan and one scan after i.v. injection of tariquidar (15 mg/kg, n=5) or vehicle (n=2). Results Following tariquidar administration, the distribution volume DV of (R)-11C-verapamil was 12-fold higher as compared to baseline (3.68±0.81 versus 0.30±0.08; p=0.0007, paired t-test), whereas the DVs were essentially the same when only vehicle was administered. The increase in DV could mainly be attributed to an increased influx rate constant K1 of (R)-11C-verapamil into the brain, which was about 8-fold higher after tariquidar. A dose-response assessment with tariquidar provided an estimated half-maximum effect dose (ED50) of 8.4±9.5 mg/kg. Conclusion Our data demonstrate that (R)-11C-verapamil PET combined with tariquidar administration is a promising approach to measure P-gp function at the BBB. PMID:18632828

  10. Occupancy of dopamine D2/3 receptors in rat brain by endogenous dopamine measured with the agonist positron emission tomography radioligand [11C]MNPA.

    PubMed

    Seneca, Nicholas; Zoghbi, Sami S; Skinbjerg, Mette; Liow, Jeih-San; Hong, Jinsoo; Sibley, David R; Pike, Victor W; Halldin, Christer; Innis, Robert B

    2008-10-01

    Estimates of dopamine D(2/3) receptor occupancy by endogenous dopamine using positron emission tomography (PET) in animals have varied almost threefold. This variability may have been caused by incomplete depletion of dopamine or by the use of antagonist radioligands, which appear less sensitive than agonist radioligands to changes in endogenous dopamine. PET scans were performed in rats with the agonist PET radioligand [(11)C]MNPA ([O-methyl-(11)C]2-methoxy-N-propylnorapomorphine). [(11)C]MNPA was injected as a bolus plus constant infusion to achieve steady-state concentration in the body and equilibrium receptor binding in the brain. Radioligand binding was compared at baseline and after treatment with reserpine plus alpha-