Isotope harvesting at heavy ion fragmentation facilities

Introduction The National Superconducting Cyclotron Laboratory (NSCL) is a national nuclear physics facility in which heavy ion beams are fragmented to produce exotic nuclei. In this process of fragmentation many nuclei are created, however, only one isotope is selected for experimentation. The remaining isotopes that are created go unused. The future upgrade of the NSCL to the Facility for Rare Isotope Beams (FRIB) will increase the incident energy of these heavy ion beams and amplify the current by three orders of magnitude. An aqueous beam dump will be created to collect the unused isotopes created in the process of fragmentation. Several of these isotopes are of interest for many applications including nuclear security, medical imaging, and therapy and are not currently available or are only available in very limited supply. Harvesting these isotopes from the aqueous beam dump could provide a consistent supply of these im-portant isotopes as an ancillary service to the existing experimental program. Material and Methods A liquid water target system was designed and tested to serve as a mock beam dump for exper-iments at the NSCL1. A 25 pnA 130 MeV/u 76Ge beam was fragmented using a 493 mg/cm2 thick beryllium production target. After fragmentation the beam was separated using the A1900 frag-ment separator2 set up for maximum 67Cu pro-duction using a 240 mg/cm2 aluminum wedge and a 2% momentum acceptance. The secondary beam was collected for four hours in the liquid water target system before being transferred to a collection vessel. Four additional four hour collections were made before finally shipping the five collections to Washington University and Hope College for chemical separation. Four of the five samples were separated using a two part separation scheme. First they were passed through and 3M Empore iminodiacetic acid functionalized chelation disk in a 1.25M ammonium acetate solution at pH 5. The flow through was collected and analyzed using an HPGe detector. Then 10mL of 6M HCl acid was passed through the chelation disk to remove the 2+ transition metals. The 10mL of 6M HCl acid was collected after passing through the disk and added to an anion-exchange column with 2.5 g AG1-X8 resin. The eluate was collected and then an additional 10mL of 6M HCl was passed through the column to remove the nickel. The 67Cu was then collected by passing 10mL of 0.5M HCl and the eluate was collected in 1mL fractions each analyzed by HPGe for 67Cu concentration and purity. The two highest 67Cu fractions were heated to dryness and reconstituted in 50 μL 0.1M ammonium acetate pH 5.5. 2 μL of 7.9 mg/mL NOTA-Bz-Trastuzumab was added to 45 μL of 67Cu and 3 μL 0.1M ammonium acetate pH 5.5. This solution was placed in a shaking incubator at 37 °C for twenty minutes and then analyzed by radio-instant thin layer chromatography in order to determine the per-cent of 67Cu bound to the antibody. Results and Conclusion 67Cu was collected into the liquid water target system with an average efficiency of 85 ± 5 %. The secondary beam was 73 % pure with the impurities, half-lives greater than 1 minute, listed in TABLE 1. Separation of 67Cu from the impurities resulted in an average recovery of 88 ± 3 % for a total recovery of 67Cu from the beam and separation of 75 ± 4 %. No detectable radioactive impurities were found in the final samples when analyzed using an HPGe detector. TABLE 2 shows the amount of 67Cu collected from the beam and the amount recovered decay corrected to end of bombardment. Labeling NOTA-Bz-Trastuzumab with 67Cu resulted in > 95 % radiochemical yield. Collection of the 73 % pure 67Cu beam in water and the resulting separation proved successful. These results demonstrate that radioisotopes can be collected from fragmented heavy ion beams and isolated in usable quantities and purity for many radiochemical applications. Further experimentation with an unpurified beam to better simulate conditions in the beam dump at the Facility for Rare Isotope Beams will be performed in the near future

NOX2, p22phox and p47phox are targeted to the nuclear pore complex in ischemic cardiomyocytes colocalizing with local reactive oxygen species.

BACKGROUND: NADPH oxidases play an essential role in reactive oxygen species (ROS)-based signaling in the heart. Previously, we have demonstrated that (peri)nuclear expression of the catalytic NADPH oxidase subunit NOX2 in stressed cardiomyocytes, e.g. under ischemia or high concentrations of homocysteine, is an important step in the induction of apoptosis in these cells. Here this ischemia-induced nuclear targeting and activation of NOX2 was specified in cardiomyocytes. METHODS: The effect of ischemia, mimicked by metabolic inhibition, on nuclear localization of NOX2 and the NADPH oxidase subunits p22(phox) and p47(phox), was analyzed in rat neonatal cardiomyoblasts (H9c2 cells) using Western blot, immuno-electron microscopy and digital-imaging microscopy. RESULTS: NOX2 expression significantly increased in nuclear fractions of ischemic H9c2 cells. In addition, in these cells NOX2 was found to colocalize in the nuclear envelope with nuclear pore complexes, p22(phox), p47(phox) and nitrotyrosine residues, a marker for the generation of ROS. Inhibition of NADPH oxidase activity, with apocynin and DPI, significantly reduced (peri)nuclear expression of nitrotyrosine. CONCLUSION: We for the first time show that NOX2, p22(phox) and p47(phox) are targeted to and produce ROS at the nuclear pore complex in ischemic cardiomyocytes

Involvement of PPAR-γ in the neuroprotective and anti-inflammatory effects of angiotensin type 1 receptor inhibition: effects of the receptor antagonist telmisartan and receptor deletion in a mouse MPTP model of Parkinson's disease

<p>Abstract</p> <p>Background</p> <p>Several recent studies have shown that angiotensin type 1 receptor (AT1) antagonists such as candesartan inhibit the microglial inflammatory response and dopaminergic cell loss in animal models of Parkinson's disease. However, the mechanisms involved in the neuroprotective and anti-inflammatory effects of AT1 blockers in the brain have not been clarified. A number of studies have reported that AT1 blockers activate peroxisome proliferator-activated receptor gamma (PPAR γ). PPAR-γ activation inhibits inflammation, and may be responsible for neuroprotective effects, independently of AT1 blocking actions.</p> <p>Methods</p> <p>We have investigated whether oral treatment with telmisartan (the most potent PPAR-γ activator among AT1 blockers) provides neuroprotection against dopaminergic cell death and neuroinflammation, and the possible role of PPAR-γ activation in any such neuroprotection. We used a mouse model of parkinsonism induced by the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and co-administration of the PPAR-γ antagonist GW9662 to study the role of PPAR-γ activation. In addition, we used AT1a-null mice lesioned with MPTP to study whether deletion of AT1 in the absence of any pharmacological effect of AT1 blockers provides neuroprotection, and investigated whether PPAR-γ activation may also be involved in any such effect of AT1 deletion by co-administration of the PPAR-γ antagonist GW9662.</p> <p>Results</p> <p>We observed that telmisartan protects mouse dopaminergic neurons and inhibits the microglial response induced by administration of MPTP. The protective effects of telmisartan on dopaminergic cell death and microglial activation were inhibited by co-administration of GW9662. Dopaminergic cell death and microglial activation were significantly lower in AT1a-null mice treated with MPTP than in mice not subjected to AT1a deletion. Interestingly, the protective effects of AT1 deletion were also inhibited by co-administration of GW9662.</p> <p>Conclusion</p> <p>The results suggest that telmisartan provides effective neuroprotection against dopaminergic cell death and that the neuroprotective effect is mediated by PPAR-γ activation. However, the results in AT1-deficient mice show that blockage of AT1, unrelated to the pharmacological properties of AT1 blockers, also protects against dopaminergic cell death and neuroinflammation. Furthermore, the results show that PPAR-γ activation is involved in the anti-inflammatory and neuroprotective effects of AT1 deletion.</p

Frações solúveis e insolúveis do hidrolisado proteico de resíduo de sardinha na alimentação do jundiá: consumo de ração e excreção de amônia

RESUMO O hidrolisado proteico de pescado é produzido por meio da hidrólise enzimática de resíduos da indústria de pescado, resultando em um ingrediente de excelente qualidade para ser utilizado na alimentação de peixes. O objetivo deste estudo foi determinar o efeito das frações do hidrolisado proteico de resíduo de sardinha sobre o consumo de ração e excreção de amônia de juvenis de jundiá. Foram testadas as frações solúveis e insolúveis do hidrolisado de músculo de sardinha, avaliadas individualmente e combinadas entre si. Juvenis de jundiás (9,76±0,55g) foram divididos em 12 aquários de 20L, na densidade de quatro peixes por aquário, resultando em uma biomassa média de 1,90±0,17g/L. O hidrolisado proteico foi produzido com carcaças limpas de sardinhas mediante o uso da enzima protease bacteriana Protamex(r) (Novozymes A/S) e dele derivaram as frações solúveis e insolúveis. As dietas foram isoproteicas (39% PB) e isoenergéticas (4450kcal EB/kg), e as frações do hidrolisado foram incluídas de forma a fornecerem 50% da proteína das rações. A fração solúvel apresentou grau de hidrólise mais elevado (20,1%) em relação à fração insolúvel (9,97%). As duas dietas contendo a fração solúvel do hidrolisado foram as mais consumidas. Com cinco horas de avaliação, a dieta contendo a fração solúvel do hidrolisado aumentou a excreção de amônia em relação à dieta contendo a fração insolúvel. Após 25 horas, a fração solúvel também aumentou a excreção de amônia, mas, desta vez, em relação à dieta contendo a combinação das duas frações. Conclui-se que a inclusão da fração solúvel do hidrolisado de músculo de sardinha estimula o consumo de ração, todavia, quando a inclusão é elevada, pode haver aumento da excreção de amônia de juvenis de jundiá

Isotope harvesting at heavy ion fragmentation facilities

Introduction The National Superconducting Cyclotron Laboratory (NSCL) is a national nuclear physics facility in which heavy ion beams are fragmented to produce exotic nuclei. In this process of fragmentation many nuclei are created, however, only one isotope is selected for experimentation. The remaining isotopes that are created go unused. The future upgrade of the NSCL to the Facility for Rare Isotope Beams (FRIB) will increase the incident energy of these heavy ion beams and amplify the current by three orders of magnitude. An aqueous beam dump will be created to collect the unused isotopes created in the process of fragmentation. Several of these isotopes are of interest for many applications including nuclear security, medical imaging, and therapy and are not currently available or are only available in very limited supply. Harvesting these isotopes from the aqueous beam dump could provide a consistent supply of these im-portant isotopes as an ancillary service to the existing experimental program. Material and Methods A liquid water target system was designed and tested to serve as a mock beam dump for exper-iments at the NSCL1. A 25 pnA 130 MeV/u 76Ge beam was fragmented using a 493 mg/cm2 thick beryllium production target. After fragmentation the beam was separated using the A1900 frag-ment separator2 set up for maximum 67Cu pro-duction using a 240 mg/cm2 aluminum wedge and a 2% momentum acceptance. The secondary beam was collected for four hours in the liquid water target system before being transferred to a collection vessel. Four additional four hour collections were made before finally shipping the five collections to Washington University and Hope College for chemical separation. Four of the five samples were separated using a two part separation scheme. First they were passed through and 3M Empore iminodiacetic acid functionalized chelation disk in a 1.25M ammonium acetate solution at pH 5. The flow through was collected and analyzed using an HPGe detector. Then 10mL of 6M HCl acid was passed through the chelation disk to remove the 2+ transition metals. The 10mL of 6M HCl acid was collected after passing through the disk and added to an anion-exchange column with 2.5 g AG1-X8 resin. The eluate was collected and then an additional 10mL of 6M HCl was passed through the column to remove the nickel. The 67Cu was then collected by passing 10mL of 0.5M HCl and the eluate was collected in 1mL fractions each analyzed by HPGe for 67Cu concentration and purity. The two highest 67Cu fractions were heated to dryness and reconstituted in 50 μL 0.1M ammonium acetate pH 5.5. 2 μL of 7.9 mg/mL NOTA-Bz-Trastuzumab was added to 45 μL of 67Cu and 3 μL 0.1M ammonium acetate pH 5.5. This solution was placed in a shaking incubator at 37 °C for twenty minutes and then analyzed by radio-instant thin layer chromatography in order to determine the per-cent of 67Cu bound to the antibody. Results and Conclusion 67Cu was collected into the liquid water target system with an average efficiency of 85 ± 5 %. The secondary beam was 73 % pure with the impurities, half-lives greater than 1 minute, listed in TABLE 1. Separation of 67Cu from the impurities resulted in an average recovery of 88 ± 3 % for a total recovery of 67Cu from the beam and separation of 75 ± 4 %. No detectable radioactive impurities were found in the final samples when analyzed using an HPGe detector. TABLE 2 shows the amount of 67Cu collected from the beam and the amount recovered decay corrected to end of bombardment. Labeling NOTA-Bz-Trastuzumab with 67Cu resulted in > 95 % radiochemical yield. Collection of the 73 % pure 67Cu beam in water and the resulting separation proved successful. These results demonstrate that radioisotopes can be collected from fragmented heavy ion beams and isolated in usable quantities and purity for many radiochemical applications. Further experimentation with an unpurified beam to better simulate conditions in the beam dump at the Facility for Rare Isotope Beams will be performed in the near future

Isotope harvesting at heavy ion fragmentation facilities

Introduction The National Superconducting Cyclotron Laboratory (NSCL) is a national nuclear physics facility in which heavy ion beams are fragmented to produce exotic nuclei. In this process of fragmentation many nuclei are created, however, only one isotope is selected for experimentation. The remaining isotopes that are created go unused. The future upgrade of the NSCL to the Facility for Rare Isotope Beams (FRIB) will increase the incident energy of these heavy ion beams and amplify the current by three orders of magnitude. An aqueous beam dump will be created to collect the unused isotopes created in the process of fragmentation. Several of these isotopes are of interest for many applications including nuclear security, medical imaging, and therapy and are not currently available or are only available in very limited supply. Harvesting these isotopes from the aqueous beam dump could provide a consistent supply of these im-portant isotopes as an ancillary service to the existing experimental program. Material and Methods A liquid water target system was designed and tested to serve as a mock beam dump for exper-iments at the NSCL1. A 25 pnA 130 MeV/u 76Ge beam was fragmented using a 493 mg/cm2 thick beryllium production target. After fragmentation the beam was separated using the A1900 frag-ment separator2 set up for maximum 67Cu pro-duction using a 240 mg/cm2 aluminum wedge and a 2% momentum acceptance. The secondary beam was collected for four hours in the liquid water target system before being transferred to a collection vessel. Four additional four hour collections were made before finally shipping the five collections to Washington University and Hope College for chemical separation. Four of the five samples were separated using a two part separation scheme. First they were passed through and 3M Empore iminodiacetic acid functionalized chelation disk in a 1.25M ammonium acetate solution at pH 5. The flow through was collected and analyzed using an HPGe detector. Then 10mL of 6M HCl acid was passed through the chelation disk to remove the 2+ transition metals. The 10mL of 6M HCl acid was collected after passing through the disk and added to an anion-exchange column with 2.5 g AG1-X8 resin. The eluate was collected and then an additional 10mL of 6M HCl was passed through the column to remove the nickel. The 67Cu was then collected by passing 10mL of 0.5M HCl and the eluate was collected in 1mL fractions each analyzed by HPGe for 67Cu concentration and purity. The two highest 67Cu fractions were heated to dryness and reconstituted in 50 μL 0.1M ammonium acetate pH 5.5. 2 μL of 7.9 mg/mL NOTA-Bz-Trastuzumab was added to 45 μL of 67Cu and 3 μL 0.1M ammonium acetate pH 5.5. This solution was placed in a shaking incubator at 37 °C for twenty minutes and then analyzed by radio-instant thin layer chromatography in order to determine the per-cent of 67Cu bound to the antibody. Results and Conclusion 67Cu was collected into the liquid water target system with an average efficiency of 85 ± 5 %. The secondary beam was 73 % pure with the impurities, half-lives greater than 1 minute, listed in TABLE 1. Separation of 67Cu from the impurities resulted in an average recovery of 88 ± 3 % for a total recovery of 67Cu from the beam and separation of 75 ± 4 %. No detectable radioactive impurities were found in the final samples when analyzed using an HPGe detector. TABLE 2 shows the amount of 67Cu collected from the beam and the amount recovered decay corrected to end of bombardment. Labeling NOTA-Bz-Trastuzumab with 67Cu resulted in > 95 % radiochemical yield. Collection of the 73 % pure 67Cu beam in water and the resulting separation proved successful. These results demonstrate that radioisotopes can be collected from fragmented heavy ion beams and isolated in usable quantities and purity for many radiochemical applications. Further experimentation with an unpurified beam to better simulate conditions in the beam dump at the Facility for Rare Isotope Beams will be performed in the near future

Sequence variations in the FII, FV, F13A1, FGB and PAI-1 genes are associated with differences in myocardial perfusion

Aims: Coronary artery disease (CAD) is a significant cause of morbidity and mortality in modern societies. The association between genetic markers and CAD is still poorly understood. In this study, we evaluated the effect of five genetic variants: Factor V Leiden (FV:c.1691G > A) (rs6025), Factor II prothrombin (FII:c.20210G > A; rs1799963), plasminogen activator inhibitor 1 (PAI-1) -675(4G/5G; SERPINE1:g.4329_4330insG; rs34857375), beta-fibrinogen -455G > A (FGB:c.4577G > A; rs1800790) and Factor XIII (F13A1:c.103G > T; rs5985) on myocardial perfusion. Materials & methods: We examined 523 patients using exercise rest myocardial perfusion single photon emission computed tomography, where the summed stress score (SSS), summed rest score and summed difference score (SDS) indexes, were calculated. In order to examine the independent prognostic ability of genotype on SSS and SDS, multiple linear regression models were used. Results: It was found that Factor V Leiden, Factor XIII, beta-fibrinogen and PAI-1 genotypes were independent prognostic predictors of SSS and SDS with Factor XIII exhibiting the strongest association. Moreover, Factor II prothrombin proved an independent prognostic predictor of SSS. Conclusion: Our study provides the first evidence of an association between these polymorphisms and myocardial perfusion, suggesting that the process of coronary artery disease and also patients' prognosis, may be modified by the FV:c.16916 > A, F/Pc.20210G > A, PAI-1 -675 (4G15G), beta-fibrinogen FGB:c.4577G > A and F13A1:c.103G > T genotypes