EVALUATION OF REMEDIATION TECHNOLOGIES FOR PLUTONIUM CONTAMINATED SOIL

Soils contaminated with radionuclides are an environmental concern at most Department of Energy (DOE) sites. Clean up efforts at many of these sites are ongoing using conventional remediation techniques. These remediation techniques are often expensive and may not achieve desired soil volume reduction. Several studies using alternative remediation techniques have been performed on plutonium-contaminated soils from the Nevada Test Site. Results to date exhibit less than encouraging results, but these processes were often not fully optimized, and other approaches are possible. Clemson University and teaming partner Waste Policy Institute, through a cooperative agreement with the National Environmental Technologies Laboratory, are assisting the Nevada Test Site (NTS) in re-evaluating technologies that have the potential of reducing the volume of plutonium contaminated soil. This efforts includes (1) a through literature review and summary of (a) NTS soil characterization and (b) volume reduction treatment technologies applied to plutonium-contaminated NTS soils, (2) an interactive workshop for vendors, representatives from DOE sites and end-users, and (3) bench scale demonstration of applicable vendor technologies at the Clemson Environmental Technologies Laboratory

CHARACTERIZATION OF PLUTONIUM CONTAMINATED SOILS FROM THE NEVADA TEST SITE IN SUPPORT OF EVALUATION OF REMEDIATION TECHNOLOGIES

ABSTRACT The removal of plutonium from Nevada Test Site (NTS) area soils has previously been attempted using various combinations of attrition scrubbing, size classification, gravitybased separation, flotation, air flotation, segmented gate, bioremediation, magnetic separation and vitrification. Results were less than encouraging, but the processes were not fully optimized. To support additional vendor treatability studies soil from the Clean Slate II site (located on the Tonopah Test Range, north of the NTS) were characterized and tested. These particular soils from the NTS are contaminated primarily with plutonium-239/240 and Am-241. Soils were characterized for Pu-239/240, Am-241 and gross alpha. In addition, wet sieving and the subsequent characterization were performed on soils before and after attrition scrubbing to determine the particle size distribution and the distribution of Pu-239/240 and gross alpha as a function of particle size. Sequential extraction was performed on untreated soil to provide information about how tightly bound the plutonium was to the soil. Magnetic separation was performed to determine if this could be useful as part of a treatment approach. The results indicate that about a 40% volume reduction of contaminated soil should be achievable by removing the >300 um size fraction of the soil. Attrition scrubbing does not effect particle size distribution, but does result in a slight shift of plutonium distribution to the fines. As such, attrition scrubbing may be able to slightly increase the ability to separate plutonium-contaminated particles from clean soil. This could add another 5-10% to the mass of the clean soil, bringing the total clean soil to 45-50%. Additional testing would be needed to determine the value of using attrition scrubbing as well as screening the soil through a sieve size slightly smaller than 300 um. Since only attrition scrubbing and wet sieving would be needed to attain this, it would be good to conduct this investigation. Magnetic separation did not work well. The sequential extraction studies indicated that a significant amount of plutonium was soluble in the "organic" and "resistant" extracts. As such chemical extraction based on these or similar extractants should also be considered as a possible treatment approach. WM '03 Conference, February 23-27, 2003 , Tucson, AZ 2 INTRODUCTION The removal of plutonium from Nevada Test Site (NTS) area soils has previously been attempted using various combinations of attrition, scrubbing, size classification, gravitybased separation, flotation, air flotation, segmented gate, bioremediation, magnetic separation, and vitrification (1). Results were less than encouraging, but the processes were not fully optimized. There is an opportunity for significant improvement through the utilization of more in depth studies

A competitive disinhibitory network for robust optic flow processing in Drosophila

Funding Information: We thank R. Parekh and Janelia CAT for introducing us to FAFB and training us in EM tracing. K. Coates and F. Li for reviewing some of our manually traced neurons in FAFB. S. Huston for tracing of CNMNs, VCNMN and some cLPTCrn cells together with S. Imtiaz and B. Gorko, and for helping identify neck motor neurons. A. Li and R. Wilson for their help in reconstructing DNa02. S. Namiki and G. Card for their help in identifying DNs. J. Goldammer for identifying potential split-Gal4 candidates for H2rn cells and helping identify S-Neurons. H. Otsuna, G. Jefferis and P. Schlegel for introducing us to their tools for computational neuroanatomy and for helping with EM data analysis. A. Zhao for his input on LPT naming, response predictions and feedback on the manuscript. N. Eckstein and J. Funke for sharing neurotransmitter predictions for LPT partners before publication. We thank the Princeton FlyWire team and members of the Murthy and Seung laboratories, as well as members of the Allen Institute for Brain Science, for development and maintenance of FlyWire (supported by BRAIN Initiative grants MH117815 and NS126935 to Murthy and Seung). We also acknowledge members of the Princeton FlyWire team and the FlyWire consortium for neuron proofreading and annotation (Supplementary Table lists all contributors). We thank the Murphy and Seung laboratories and the Jefferis laboratory for their contribution with 31.83% and 46.27% of the total editions in FlyWire neurons, respectively. In addition, we acknowledge the contribution of the Seeds and Hampel laboratory, the Wilson laboratory, the Bidaye laboratory, the Borst laboratory, the Kim laboratory and the Selcho laboratory for additional contributions. We thank members of the Cambridge Connectomics Group (G. Jefferis and M. Costa) including L. Serratosa, A. Javier, S. Fang, K. Eichler and P. Schlegel for contributing to the proofreading of FlyWire Neurons. Proofreading in Cambridge was supported by the Wellcome Trust (Collaborative Award 203261/Z/16/Z) and National Institutes of Health (NIH) (BRAIN Initiative 1RF1MH120679-01). Development and administration of the FAFB tracing environment and analysis tools were funded in part by NIH BRAIN Initiative grant 1RF1MH120679-01 to D. Bock and G. Jefferis, with software development effort and administrative support provided by T. Kazimiers (Kazmos) and E. Perlman (Yikes). We also thank G. Maimon and C. Lyu for sharing sytGCaMP7f flies before publication. G. Rubin and H. Dionne (Rubin laboratory) for transgene constructs and reinjections. M. Silies for sharing the UAS-GCaMP6f, UAS-FLP recombinant line. E. S\u00F6nmez for help with testing Split-Gal4 combinations and help with validating FlpStop recombinants. The CR Fly Platform for assisting fly stock generation, maintenance and GABA staining. L. Venkatasubramanian for her help with the initial bIPS>TrpA1 behavior experiments. T. Fujiwara for help with finding and testing potential Split-Gal4 combinations for H2rn and uLPTCrns and help with building the two-photon calcium imaging setup. W. Stagnaro for sharing unpublished work about multisensory processing in LPTCrns and bIPS cells. Past and present Chiappe Laboratory members for useful discussions and feedback on experiments and the manuscript. This work was supported by the Champalimaud Foundation and the research infrastructure Congento, LISBOA-01-0145-FEDER-022170. M.E.C. is supported by European Research Council Starting Grant ERC-2017-STG-759782 537 and European Research Council Consolidator Grant ERC-2022-CoC-101088936. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Publisher Copyright: © The Author(s) 2025.Many animals navigate using optic flow, detecting rotational image velocity differences between their eyes to adjust direction. Forward locomotion produces strong symmetric translational optic flow that can mask these differences, yet the brain efficiently extracts these binocular asymmetries for course control. In Drosophila melanogaster, monocular horizontal system neurons facilitate detection of binocular asymmetries and contribute to steering. To understand these functions, we reconstructed horizontal system cells’ central network using electron microscopy datasets, revealing convergent visual inputs, a recurrent inhibitory middle layer and a divergent output layer projecting to the ventral nerve cord and deeper brain regions. Two-photon imaging, GABA receptor manipulations and modeling, showed that lateral disinhibition reduces the output’s translational sensitivity while enhancing its rotational selectivity. Unilateral manipulations confirmed the role of interneurons and descending outputs in steering. These findings establish competitive disinhibition as a key circuit mechanism for detecting rotational motion during translation, supporting navigation in dynamic environments.publishersversioninpres

Phase II Randomized, Double-Masked, Vehicle-Controlled Trial of Recombinant Human Nerve Growth Factor for Neurotrophic Keratitis

Purpose: To evaluate the safety and efficacy of topical recombinant human nerve growth factor (rhNGF) for treating moderate-to-severe neurotrophic keratitis (NK), a rare degenerative corneal disease resulting from impaired corneal innervation. Design: Phase II multicenter, randomized, double-masked, vehicle-controlled trial. Participants: Patients with stage 2 (moderate) or stage 3 (severe) NK in 1 eye. Methods: The REPARO phase II study assessed safety and efficacy in 156 patients randomized 1:1:1 to rhNGF 10 \u3bcg/ml, 20 \u3bcg/ml, or vehicle. Treatment was administered 6 drops per day for 8 weeks. Patients then entered a 48- or 56-week follow-up period. Safety was assessed in all patients who received study treatment, whereas efficacy was by intention to treat. Main Outcome Measures: Corneal healing (defined as <0.5-mm maximum diameter of fluorescein staining in the lesion area) was assessed by masked central readers at week 4 (primary efficacy end point) and week 8 (key secondary end point) of controlled treatment. Corneal healing was reassessed post hoc by masked central readers using a more conservative measure (0-mm staining in the lesion area and no other persistent staining). Results: At week 4 (primary end point), 19.6% of vehicle-treated patients achieved corneal healing (<0.5-mm lesion staining) versus 54.9% receiving rhNGF 10 \u3bcg/ml (+35.3%; 97.06% confidence interval [CI], 15.88\u201354.71; P < 0.001) and 58.0% receiving rhNGF 20 \u3bcg/ml (+38.4%; 97.06% CI, 18.96\u201357.83; P < 0.001). At week 8 (key secondary end point), 43.1% of vehicle-treated patients achieved less than 0.5-mm lesion staining versus 74.5% receiving rhNGF 10 \u3bcg/ml (+31.4%; 97.06% CI, 11.25\u201351.49; P = 0.001) and 74.0% receiving rhNGF 20 \u3bcg/ml (+30.9%; 97.06% CI, 10.60\u201351.13; P = 0.002). Post hoc analysis of corneal healing by the more conservative measure (0-mm lesion staining and no other persistent staining) maintained statistically significant differences between rhNGF and vehicle at weeks 4 and 8. More than 96% of patients who healed after controlled rhNGF treatment remained recurrence free during follow-up. Treatment with rhNGF was well tolerated; adverse effects were mostly local, mild, and transient. Conclusions: Topical rhNGF is safe and more effective than vehicle in promoting healing of moderate-to-severe NK

Nicotinic acetylcholine receptor subunit variants are associated with blood pressure; findings in the Old Order Amish and replication in the Framingham Heart Study

<p>Abstract</p> <p>Background</p> <p>Systemic blood pressure, influenced by both genetic and environmental factors, is regulated via sympathetic nerve activity. We assessed the role of genetic variation in three subunits of the neuromuscular nicotinic acetylcholine receptor positioned on chromosome 2q, a region showing replicated evidence of linkage to blood pressure.</p> <p>Methods</p> <p>We sequenced <it>CHRNA1</it>, <it>CHRND </it>and <it>CHRNG </it>in 24 Amish subjects from the Amish Family Diabetes Study (AFDS) and identified 20 variants. We then performed association analysis of non-redundant variants (n = 12) in the complete AFDS cohort of 1,189 individuals, and followed by genotyping blood pressure-associated variants (n = 5) in a replication sample of 1,759 individuals from the Framingham Heart Study (FHS).</p> <p>Results</p> <p>The minor allele of a synonymous coding SNP, rs2099489 in <it>CHRNG</it>, was associated with higher systolic blood pressure in both the Amish (p = 0.0009) and FHS populations (p = 0.009) (minor allele frequency = 0.20 in both populations).</p> <p>Conclusion</p> <p><it>CHRNG </it>is currently thought to be expressed only during fetal development. These findings support the Barker hypothesis, that fetal genotype and intra-uterine environment influence susceptibility to chronic diseases later in life. Additional studies of this variant in other populations, as well as the effect of this variant on acetylcholine receptor expression and function, are needed to further elucidate its potential role in the regulation of blood pressure. This study suggests for the first time in humans, a possible role for genetic variation in the neuromuscular nicotinic acetylcholine receptor, particularly the gamma subunit, in systolic blood pressure regulation.</p

Healthy ageing and depletion of intracellular glutathione influences T cell membrane thioredoxin-1 levels and cytokine secretion

Background: During ageing an altered redox balance has been observed in both intracellular and extracellular compartments, primarily due to glutathione depletion and metabolic stress. Maintaining redox homeostasis is important for controlling proliferation and apoptosis in response to specific stimuli for a variety of cells. For T cells, the ability to generate specific response to antigen is dependent on the oxidation state of cell surface and cytoplasmic protein-thiols. Intracellular thiols are maintained in their reduced state by a network of redox regulating peptides, proteins and enzymes such as glutathione, thioredoxins and thioredoxin reductase. Here we have investigated whether any relationship exists between age and secreted or cell surface thioredoxin-1, intracellular glutathione concentration and T cell surface thioredoxin 1 (Trx-1) and how this is related to interleukin (IL)-2 production.Results: Healthy older adults have reduced lymphocyte surface expression and lower circulating plasma Trx-1 concentrations. Using buthionine sulfoximine to deplete intracellular glutathione in Jurkat T cells we show that cell surface Trx-1 is lowered, secretion of Trx-1 is decreased and the response to the lectin phytohaemagglutinin measured as IL-2 production is also affected. These effects are recapitulated by another glutathione depleting agent, diethylmaleate.Conclusion: Together these data suggest that a relationship exists between the intracellular redox compartment and Trx-1 proteins. Loss of lymphocyte surface Trx-1 may be a useful biomarker of healthy ageing. © 2013 Carilho Torrao et al.; licensee Chemistry Central Ltd

Lipid (per) oxidation in mitochondria:an emerging target in the ageing process?

Lipids are essential for physiological processes such as maintaining membrane integrity, providing a source of energy and acting as signalling molecules to control processes including cell proliferation, metabolism, inflammation and apoptosis. Disruption of lipid homeostasis can promote pathological changes that contribute towards biological ageing and age-related diseases. Several age-related diseases have been associated with altered lipid metabolism and an elevation in highly damaging lipid peroxidation products; the latter has been ascribed, at least in part, to mitochondrial dysfunction and elevated ROS formation. In addition, senescent cells, which are known to contribute significantly to age-related pathologies, are also associated with impaired mitochondrial function and changes in lipid metabolism. Therapeutic targeting of dysfunctional mitochondrial and pathological lipid metabolism is an emerging strategy for alleviating their negative impact during ageing and the progression to age-related diseases. Such therapies could include the use of drugs that prevent mitochondrial uncoupling, inhibit inflammatory lipid synthesis, modulate lipid transport or storage, reduce mitochondrial oxidative stress and eliminate senescent cells from tissues. In this review, we provide an overview of lipid structure and function, with emphasis on mitochondrial lipids and their potential for therapeutic targeting during ageing and age-related disease