334 research outputs found
Evaluation of Column Separation Methods for Simplification of the Wet Chemistry Approach to Isolation of 211At: Evaluation of Column Separation Methods for Simplification of the Wet Chemistry Approach to Isolation of 211At
Difficulties with reproducibility of isolation yields when distilling 211At from irradiated bismuth targets led us to use a âwet chemistryâ approach for that process1. The wet chemistry approach has provided 211At isolation yields of ~ 78 % after decay and Bi attenuation corrections2. However, the use of diisopropyl ether (DIPE) in the separation process has made it difficult to reach our goal of automating the 211At isolation. Therefore, we have investigated the use of column materials to simplify the isolation of 211At and remove DIPE from the process. In this investigation we evaluated the use of a strong anion exchange resin (AG1Ă8), a strong cation exchange resin (AG MP-50) and a polyethylene glycol (PEG)-coated resin for separation of 211At from the bismuth target material.
Anion and cation resins AG1Ă8 and AG MP-50 were obtained from commercial sources. A PEG-coated resin was prepared by reaction of the Merrifield resin with mPEG-OH 2000 in the pres-ence of tBuOK at 80 °C for 3 days, followed by drying under vacuum. Prior to use of the PEG resin, it was soaked in H2O. Resins (400â800 mg) were loaded into polypropylene columns (Applied Separations, Inc.). Column elution studies were conducted with and without reductants (0.75M FeSO4/1M H2SO4 or Na2S2O5) to determine their effect on capture of 211At. After target dissolution in HNO3 (and in most cases subse-quent removal of HNO3 by distillation and redis-solution of solid in 8M HCl), 211At solution was loaded onto the column, then the column was washed with 2M HCl or H2O to separate the Bi, and finally was eluted with strong base to remove the 211At.
Initial studies were conducted with stable iodine to determine if reductants were effective in the presence of large amounts of bismuth ions. Studies with AG1Ă8 used 125I to determine if that radiohalogen could be captured and recovered from the column when eluting with boric acid buffers at pH 5.3, 8.0 or 10, or H2O at pH 7. Capture and recovery of 211At was evaluated under the same conditions. Further studies with AG1Ă8 involved eluting with 4M H2SO4. A limited study with AG MP-50 resin used 1M HCl as eluant. Studies with PEG-coated columns used 2M HCl, 4M HCl, 8M HCl, 16 M HNO3 and 8M HNO3 as initial (capture) eluants. Strong base (0.2, 1 or 12.5 M NaOH; 15M NH4OH) and 3 or 500 mM tetrabutylammonium bromide (TBAB) were evaluated for removal of 211At from the columns tested.
The efficiency for capture of 211At on the AG1Ă8 column was high (99%) when loading with strong acid, but decreased when using 0.1â0.2M boric acid (69â91 %) buffer. Low 211At capture efficiencies were obtained with AG MP-50 col-umns (15â29%). High 211At capture efficiencies (96â100%) were obtained with PEG-coated resins when loading with 8M HCl or 8M HNO3, irre-spective of whether reductant was in the acid solution.
Four column washings (2 mL of 2M HCl each) were required to remove all Bi prior to elution of 211At. No bismuth was detected in solution from the 4th washing in any of the elutions studied.
Low (< 6%) recovery of 211At from the AG1Ă8 columns was obtained using the conditions studied. Good (60â79%) recovery of 211At was obtained from PEG-coated resin using 15M NH4OH.
Isolation of the 211At from NH4OH solution was accomplished by distillation. In an initial study 211At distilled before obtaining a dry residue. However, later studies demonstrated that addi-tion of NaOH prior to distillation kept the 211At in the distilling flask.
These studies demonstrated that PEG-coated columns could be used to isolate 211At from HNO3-dissolved bismuth targets with good non-optimized (~60%) overall recovery yields. The studies are continuing with optimization of elu-tion conditions and automation of the process
A role of OCRL in clathrin-coated pit dynamics and uncoating revealed by studies of Lowe syndrome cells
Mutations in the inositol 5-phosphatase OCRL cause Lowe syndrome and Dent's disease. Although OCRL, a direct clathrin interactor, is recruited to late-stage clathrin-coated pits, clinical manifestations have been primarily attributed to intracellular sorting defects. Here we show that OCRL loss in Lowe syndrome patient fibroblasts impacts clathrin-mediated endocytosis and results in an endocytic defect. These cells exhibit an accumulation of clathrin-coated vesicles and an increase in U-shaped clathrin-coated pits, which may result from sequestration of coat components on uncoated vesicles. Endocytic vesicles that fail to lose their coat nucleate the majority of the numerous actin comets present in patient cells. SNX9, an adaptor that couples late-stage endocytic coated pits to actin polymerization and which we found to bind OCRL directly, remains associated with such vesicles. These results indicate that OCRL acts as an uncoating factor and that defects in clathrin-mediated endocytosis likely contribute to pathology in patients with OCRL mutations
Thick target preparation and isolation of 186Re from high current production via the 186W(d,2n)186Re reaction
Rhenium-186 has a half-life (t1/2 = 3.72 days) and emission of both gamma and beta particles that make it very attractive for use as a theranostic agent in targeted radionuclide therapy. 186Re can be readily prepared by the 185Re(n,Îł)186Re reac-tion1. However, that reaction results in low specific activity, severely limiting the use of reactor produced 186Re in radiopharmaceuticals. It has previously been shown that high specific activity 186Re can be produced by cyclotron irradiations of 186W with protons and deuterons2,3. In this investigation we evaluated the 186W(d,2n)186Re reaction using thick target irradiations at higher incident deuteron energies and beam currents than previously reported. We elected not to use copper or aluminum foils in the preparation of our 186W targets due to their activation in the deuteron beam, so part of the investigation was an evaluation of an alternate method for preparing thick targets that withstand ÎŒA beam currents. Irradiation of 186W. Initial thick targets (~600-1100 mg) were prepared using 96.86% enriched 186W by hydraulic pressing (6.9 MPa) of tungsten metal powder into an aluminum target support. Those thick targets were irradiated for 10 minu-tes at 10 ”A with nominal extracted deuteron energies of 15, 17, 20, 22, and 24 MeV.
Isolation of 186Re. Irradiated targets were dissolved with H2O2 and basified with (NH4)2CO3 prior to separation using column(s) of ~100â300 mg Analig Tc-02 resin. Columns were washed with (NH4)2CO3 and the rhenium was eluted with ~80ËC H2O. Gamma-ray spectroscopy was per-formed to assess production yields, extraction yields, and radionuclidic byproducts.
Recycling target material. When tested on a natural abundance W target, recovery of the oxidized WO4- target material from the resin was found to proceed rapidly with the addition of 4M HCl in the form of hydrated WO3. The excess water in the WO3 was then removed by calcination at 800 °C for 4 hours. This material was found to undergo reduction to metallic W at elevated temperatures (~1550 °C) in a tube furnace under an inert atmosphere (Ar). Quanti-fication of % reduction and composition analyses were accomplished with SEM, EDS, and XRD and were used to characterize and compare both the WO3 and reduced Wmetal products to a sample of commercially available material. Structural enhancement by surface annealing. In some experiments ~1 g WO3 pellets were prepared from Wmetal that had been chemically treated to simulate the target material recovery process described above. Following calcination, the WO3 was allowed to cool to ambient temperature, pulverized with a mortar and pestle and then uniaxially pressed at 13.8 MPa into 13 mm pellets. Conversion of the WO3 back to Wmetal in pellet form was accomplished in a tube furnace under flowing Ar at 1550 °C for 8 hours. Material characterization and product composition analyses were conducted with SEM, EDS, and XRD spectroscopy. Graphite-encased W targets. Irradiations were conducted at 20 ΌA with a nominal extracted deuteron energy of 17 MeV using thick targets (~750 mg) of natural abundance tungsten metal powder uniaxially pressed into an aluminum target support between layers of graphite pow-der (100 mg on top, 50 mg on the bottom). Targets were then dissolved as previously described and preliminary radiochemical isola-tion yields obtained by counting in a dose calibrator. Although irradiations of W targets were possible at 10 ΌA currents, difficulties were encountered in maintaining the structural integrity of the full-thickness pressed target pellets under higher beam currents. This led to further investigation of the target design for irradiations conducted at higher beam currents. Comprehensive target material characterization via analysis by SEM, EDS, XRD, and Raman Spectroscopy allowed for a complete redesign of the target maximizing the structural integrity of the pressed target pellet without impacting production or isolation. At the 10 A current, target mass loss following irradiation of an enriched 186W target was < 1 % and typical separation yields in excess of 70 % were observed. Saturated yields and percent of both 183Re (tœ = 70 days) and 184gRe (tœ = 35 days) relative to 186gRe (decay corrected to EOB) are reported in TABLE 1 below. The reason for the anomalously low yield at 24 MeV is unknown, but might be explained by poor beam alignment and/or rhenium volatility during irradiation. Under these irradiation conditions, recovery yields of the W target material from the recycling process were found to be in excess of 90% with no discernable differences noted when compared to commercially available Wmetal and WO3. Conceptually, increasing the structural integrity of pressed WO3 targets by high temperature heat treatment under an inert atmosphere is intriguing. However, the treated pellets lacked both density and structural stability resulting in disintegration upon manipulation , despite the initially encouraging energy dispersive X-ray spectroscopy (EDS) determination that 94.9% percent of the WO3 material in each pellet had been reduced to metallic W.
The use of powdered graphite as a target stabi-lizing agent provided successful irradiation of natural abundance W under conditions where non-stabilized targets failed (20 ”A at 17 MeV for 10 minutes). Target mass loss following irradiation of a natW target was < 1 % and a separation yield in excess of 97 % was obtained. In conclusion, the theranostic radionuclide 186Re was produced in thick targets via the 186W(d,2n) reaction. It was found that pressed W metal could be used for beam currents of 10 ΌA or less. For deuteron irradiations at higher beam currents, a method involving pressing W metal between two layers of graphite provides increased target stability. Both target configurations allow high recovery of radioactivity from the W target material, and a solid phase extraction method allows good recovery of 186Re. An effective approach to the recycling of enriched W has been developed using elevated temperature under an inert atmosphere. Further studies are underway with 186W targets sandwiched by graphite to assess 186Re production yields, levels of contaminant radiorhenium, power deposition, and enriched 186W material requirements under escalated irradiation conditions (20 ”A and 17 MeV for up to 2 hours)
Targetry investigations of 186Re production via proton induced reactions on natural Osmium disulfide and Tungsten disulfide targets
Introduction
Radioisotopes play an important role in nuclear medicine and represent powerful tools for imaging and therapy. With the extensive use of 99mTc-based imaging agents, therapeutic rhenium analogues are highly desirable. Rhenium-186 emits therapeutic â particles with an endpoint-energy of 1.07 MeV, allowing for a small, targeted tissue range of 3.6 mm. Additionally, its low abundance Îł-ray emission of 137.2 keV (9.42 %) allows for in vivo tracking of a radiolabeled compounds and dosimetry calculations. With a longer half-life of 3.718 days, synthesis and shipment of Re-186 based radiopharmaceuticals is not limited. Rhenium-186 can be produced either in a reactor or in an accelerator. Currently, Re-186 is produced in a reactor via the 185Re(n,Îł) reaction resulting in low specific activity which makes its therapeutic application limited.[1] Production in an accelerator, such as the PETtrace at the University of Missouri Research Reactor (MURR), can theoretically provide a specific activity of 34,600 Ci.mmolâ1 Re[2], which represents a 62 fold increase over reactor produced 186Re. The studies reported herein focused on the evaluation of accelerator-based reaction pathways to produce high specific activity (HSA) 186Re. Those pathways include proton and deuteron bombardment of tungsten and osmium targets by the following reactions: 186W(p,n)186Re, 186W(d,2n) 186Re, 189Os(p,α)186Re, and 192Os(p,α3n)186Re. Additional information on target design related to the determination and optimization of production rates, radionuclidic purity, and yield are presented.
Material and Methods
Osmium and tungsten metals are very hard and thus very brittle. Attempts at pressing the pure metal into aluminum backings resulted in chalky targets, which easily crumbled during handling. Osmium disulfide (OsS2) and tungsten disulfide (WS2) were identified to provide a softer, less brittle chemical form for targets. OsS2 and WS2 targets were prepared using a unilateral press with a 13 mm diameter die to form pressed powder discs. A simple target holder design (FIG. 1) was implemented to provide a stabilizing platform for the pressed discs. The target material was sealed in place with epoxy using a thin aluminum foil pressed over the target face. Initial irradiations of OsS2 were performed using the 16 MeV GE PETtrace cyclotron at MURR. Irradiations were performed for 30â60 minutes with proton beam currents of 10â20 ”A. Following irradiation, the OsS2 targets were dissolved in NaOCl and the pH adjusted using NaOH. The resultant aqueous solution was mixed with methyl ethyl ketone (MEK), with the lipophilic perrhenate being extracted into the MEK layer and the osmium and iridium remaining in the aqueous layer. The MEK extracts were then passed through an acidic alumina column to remove any remaining osmium and iridium. Determination of rhenium and iridium activities was done by gamma spectroscopy on an HPGe detector. Preliminary irradiations on WS2 targets were performed at MURR with the beam degraded to 14 MeV with a proton beam current of 10 ”A for 60 minutes. After irradiation, WS2 was dissolved using 30% H2O2 with gentle heating and counted on an HPGe detector to determine the radio-nuclides produced.
Results and Conclusion
Thin natOsS2 targets were produced, irradiated at 16 MeV for 10 ”Ah, and analyzed for radiorhenium. Under these irradiation conditions, rhenium isotopes were produced in nanocurie quantities while iridium isotopes were produced in microcurie quantities. Future studies with higher proton energies are planned to increase the production of rhenium and decrease the production of iridium. After optimizing irradiation conditions, enriched 189Os will be used for irradiations to reduce the production of unwanted radionuclides. A liquid-liquid extraction method separated the bulk of the rhenium from the iridium. The majority of the rhenium produced was recovered in the first organic aliquot with little iridium observed while the majority of the iridium and osmium was retained in the first aqueous aliquot. Target production with WS2 was successful. A thin target of natWS2 was produced and irradiated at 14 MeV for 10 ”Ah. Under these irradiation conditions, several rhenium isotopes were produced in microcurie quantities. Target parameters to maximize 186Re production remain to be determined before enriched 186W targets are used for irradiations to reduce the production of unwanted radionuclides. In conclusion, the potential production routes for accelerator-produced high specific activity 186Re are being evaluated. Cyclotron-based irradiations of natOsS2 targets established the feasibility of producing rhenium via the natOs(p,αxn)Re reaction. Current results indicate higher proton energies are necessary to reduce the production of unwanted iridium isotopes while increasing the production of rhenium isotopes. Preliminary irradiations were performed using the 50.5 MeV Scanditronix MC50 clinical cyclotron at the University of Washington to determine irradiation parameters for future higher energy irradiations (20â30 MeV). A rapid liquid-liquid extraction method isolated rhenium from the bulk of the iridium and osmium following irradiation. Preliminary studies indicate WS2 may also provide a suitable target material to produce 186Re via the (p,n) reaction pathway
Privacy, Ethics, and Institutional Research
Despite widespread agreement that privacy in the context of education is important, it can be difficult to pin down precisely why and to what extent it is important, and it is challenging to determine how privacy is related to other important values. But that task is crucial. Absent a clear sense of what privacy is, it will be difficult to understand the scope of privacy protections in codes of ethics. Moreover, privacy will inevitably conflict with other values, and understanding the values that underwrite privacy protections is crucial for addressing conflicts between privacy and institutional efficiency, advising efficacy, vendor benefits, and student autonomy.
My task in this paper is to seek a better understanding of the concept of privacy in institutional research, canvas a number of important moral values underlying privacy generally (including several that are explicit in the AIR Statement), and examine how those moral values should bear upon institutional research by considering several recent cases
Signaling in Secret: Pay-for-Performance and the Incentive and Sorting Effects of Pay Secrecy
Key Findings: Pay secrecy adversely impacts individual task performance because it weakens the perception that an increase in performance will be accompanied by increase in pay; Pay secrecy is associated with a decrease in employee performance and retention in pay-for-performance systems, which measure performance using relative (i.e., peer-ranked) criteria rather than an absolute scale (see Figure 2 on page 5); High performing employees tend to be most sensitive to negative pay-for- performance perceptions; There are many signals embedded within HR policies and practices, which can influence employeesâ perception of workplace uncertainty/inequity and impact their performance and turnover intentions; and When pay transparency is impractical, organizations may benefit from introducing partial pay openness to mitigate these effects on employee performance and retention
Whatever happened to curriculum theory? Critical realism and curriculum change
In the face of what has been characterised as a âcrisisâ in curriculum â an apparent decline of some aspects of curriculum studies combined with the emergence of new types of national curriculum which downgrade knowledge â some writers have been arguing for the use of realist theory to address these issues. This paper offers a contribution to this debate, drawing upon critical realism, and especially upon the social theory of Margaret Archer. The paper first outlines the supposed crisis in curriculum, before providing an overview of some of the key tenets of critical realism. The paper concludes by speculating on how critical realism may offer new ways of thinking to inform policy and practice in a key curricular problematic. This is the issue of curriculum change
Assessing managerial power theory: A meta-analytic approach to understanding the determinants of CEO compensation
Although studies about the determinants of CEO compensation are ubiquitous, the balance of
evidence for one of the more controversial theoretical approaches, managerial power theory,
remains inconclusive. The authors provide a meta-analysis of 219 U.S.-based studies, focusing
on the relationships between indicators of managerial power and levels of CEO compensation
and CEO pay-performance sensitivities. The results indicate that managerial power theory is
well equipped for predicting core compensation variables such as total cash and total
compensation but less so for predicting the sensitivity of pay to performance. In most situations
where CEOs are expected to have power over the pay setting process, they receive significantly
higher levels of total cash and total compensation. In contrast, where boards are expected to
have more power, CEOs receive lower total cash and total compensation. In addition, powerful
directors also appear to be able to establish tighter links between CEO compensation and firm
performance and can accomplish this even in the face of powerful CEOs. The authors discuss
the implications for theory and research regarding the determinants of executive compensation
Presidential Commission on the Supreme Court of the United States Final Report
On April 9, 2021, President Joseph R. Biden, Jr. issued Executive Order 14023 establishing this Commission, to consist of âindividuals having experience with and knowledge of the Federal judiciary and the Supreme Court of the United States.â The Order charged the Commission with producing a report for the President that addresses three sets of questions. First, the Report should include â[a]n account of the contemporary commentary and debate about the role and operation of the Supreme Court in our constitutional system and about the functioning of the constitutional process by which the President nominates and, by and with the advice and consent of the Senate, appoints Justices to the Supreme Court.â Second, the Report should consider the âhistorical background of other periods in the Nationâs history when the Supreme Courtâs role and the nominations and advice-and-consent process were subject to critical assessment and prompted proposals for reform.â Third, the Report should provide an analysis of the principal arguments for and against particular proposals to reform the Supreme Court, âincluding an appraisal of [their] merits and legality,â and should be informed by âa broad spectrum of ideas.â
The Report begins by explaining the genesis of todayâs Court reform debate, including by identifying developments that gave rise to President Bidenâs decision to issue the April 2021 Executive Order, particularly the debates surrounding the most recent nominations. This Introduction emphasizes that the Courtâs composition and jurisprudence long have been subjects of public controversy and debate in the nationâs civic life: The Court serves as a crucial guardian of the rule of law and also plays a central role in major social and political conflicts. Its decisions have profound effects on the life of the nation. Though conflict surrounding the processes by which the President nominates and the Senate confirms Justices is not new, it has become more intensely partisan in recent years.
The Introduction also articulates three common and interrelated ideas frequently invoked in reform debates and throughout the Chapters of the Report: the importance of protecting or enhancing the Courtâs legitimacy; the role of judicial independence in our system of government; and the value of democracy and its relationship to the Supreme Courtâs decisionmaking. These important ideas can mean different things to different people. The Introduction discusses the range of meanings ascribed to these terms, with the aim of clarifying how they are deployed in arguments for and against reform
Schools, teachers, and curriculum change: A balancing act?
Educational change is a fact of life for teachers across the world, as schools are subjected to constant and ubiquitous pressures to innovate. And, yet, many school practices remain remarkably persistent in the face of such innovation. This paradox of innovation without change is perplexing for policymakers and practitioners alike. This paper investigates the gap between policy and practice, between innovation and the changes in social practices that occur in response to such innovation. It draws upon empirical data from two case studies in Scotland — schools responding to new curriculum policy—exploring contrasting approaches to the management of innovation. One is a laissez faire approach, and the other a more directive managerial strategy. Through an analytical separation of culture, structure, and agency, derived from the social theory of Margaret Archer, the paper sheds light on the social processes that accompanied innovation in these two settings demonstrating how teacher culture and differing management styles impact upon externally initiated policy
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