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

Ethnicity predicts perceptions of smoking and smoking cessation among veterans

The objective of this study was to determine if race/ethnicity predicts motivation to quit smoking and preferences for cessation services among smokers serviced by a primarily psychiatric Veterans Affairs hospital. A self‐administered survey was given to a convenience sample of smokers ( n = 146) at the Battle Creek Veterans Affairs Medical Center. Univariate, bivariate and multivariate regression analyses were calculated to determine the association between race/ethnicity and motivation to quit smoking. Forty‐two per cent of the sample was non‐White. Non‐White patients smoked significantly less cigarettes per day as compared with White patients ( P = 0.002). In the multivariate analyses, compared with Whites, non‐Whites had 3.5 times greater odds of thinking that quitting smoking was extremely/very important to health ( P = 0.01), 4.0 times greater odds of thinking of quitting using tobacco products in the next 30 days ( P = 0.004) and 3.4 times greater odds of being interested in receiving smoking cessation services ( P = 0.007). Yet, non‐White patients were less likely to be interested in intensive nurse counselling and cessation medications. As the number of non‐Whites continues to increase in the military, novel strategies may be needed to capitalize on the high motivation to quit smoking and preference for non‐traditional interventions among non‐White smokers treated in Veterans Affairs hospitals.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90416/1/j.1365-2850.2011.01757.x.pd

Effectiveness of etoposide chemomobilization in lymphoma patients undergoing auto-SCT

The effectiveness of stem cell mobilization with G-CSF in lymphoma patients is suboptimal. We reviewed our institutional experience using chemomobilization with etoposide (VP-16; 375 mg/m2 on days +1 and +2) and G-CSF (5 μg/kg twice daily from day +3 through the final day of collection) in 159 patients with lymphoma. This approach resulted in successful mobilization (>2 × 106 CD34+ cells collected) in 94% of patients (83% within 4 apheresis sessions). Fifty-seven percent of patients yielded at least 5 × 106 cells in 2 days and were defined as good mobilizers. The regimen was safe with a low rate of rehospitalization. Average costs were $14 923 for good mobilizers and$27 044 for poor mobilizers (P<0.05). Using our data, we performed a ‘break-even’ analysis that demonstrated that adding two doses of Plerixafor to predicted poor mobilizers at the time of first CD34+ cell count would achieve cost neutrality if the frequency of good mobilizers were to increase by 21%, while the frequency of good mobilizers would need to increase by 25% if three doses of Plerixafor were used. We conclude that chemomobilization with etoposide and G-CSF in patients with lymphoma is effective, with future opportunities for cost-neutral improvement using novel agents

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

Engineered Vaginal Lactobacillus Strain for Mucosal Delivery of the Human Immunodeficiency Virus Inhibitor Cyanovirin-N

Women are at significant risk of human immunodeficiency virus (HIV) infection, with the cervicovaginal mucosa serving as a major portal for virus entry. Female-initiated preventatives, including topical microbicides, are urgently needed to help curtail the HIV/AIDS pandemic. Here we report on the development of a novel, live microbicide that employs a natural vaginal strain of Lactobacillus jensenii engineered to deliver the potent HIV inhibitor cyanovirin-N (CV-N). To facilitate efficient expression of CV-N by this bacterium, the L. jensenii 1153 genome was sequenced, allowing identification of native regulatory elements and sites for the chromosomal integration of heterologous genes. A CV-N expression cassette was optimized and shown to produce high levels of structurally intact CV-N when expressed in L. jensenii. Lactobacillus-derived CV-N was capable of inhibiting CCR5-tropic HIV(BaL) infectivity in vitro with a 50% inhibitory concentration of 0.3 nM. The CV-N expression cassette was stably integrated as a single copy into the bacterial chromosome and resolved from extraneous plasmid DNA without adversely affecting the bacterial phenotype. This bacterial strain was capable of colonizing the vagina and producing full-length CV-N when administered intravaginally to mice during estrus phase. The CV-N-producing Lactobacillus was genetically stable when propagated in vitro and in vivo. This work represents a major step towards the development of an inexpensive yet durable protein-based microbicide to block the heterosexual transmission of HIV in women