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At least 127 records · Page 7

Saltstone First Quarter Calendar Year 2021 (1QCY21) Toxicity Characteristic Leaching Procedure (TCLP) Results

The aqueous waste from Tank 50 (salt solution) is sampled quarterly for transfers to the Saltstone Production Facility (SPF). Salt solution is treated at SPF and disposed of in the Saltstone Disposal Facility (SDF). Per request of customer, X-TTR-Z00023, Revision 0, two SDF waste form (saltstone) samples were prepared in the Savannah River National Laboratory (SRNL) from the Tank 50 Waste Acceptance Criteria (WAC) sample and Z-Area premix material for the first quarter of calendar year 2021(1QCY21). One sample contained a Full Premix which included 10:45:45 (by weight) of cement, slag and fly ash. The second sample contained 60:40 (by weight) of slag and fly ash only referred to as the “Cement-Free grout sample”. Results from this technical report support Task 2: ‘Grout Leaching Analyses’ of the Task Technical Request (TTR) prepared by Savannah River Remediation (SRR). After at least 28 days cured, a sample of each of the SDF waste forms was collected and shipped to a certified laboratory for analysis using the Toxicity Characteristic Leaching Procedure (TCLP). The 1QCY21 saltstone (Full Premix) and the Cement-Free grout samples met the South Carolina (SC) Code of Regulations for Hazardous Waste Management Regulations (HWMR) 61-79.261.24 and 61-79-268.48 requirements for a non-hazardous waste form with respect to Resource Conservation and Recovery Act (RCRA) metals and Underlying Hazardous Constituents (UHCs), and also met the SPF WAC that was in effect at the time of the tank sampling.

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

Saltstone Third Quarter Calendar Year 2021 (3QCY21) Toxicity Characteristic Leading Procedure (TCLP) Results

The aqueous waste from Tank 50 (salt solution) is sampled quarterly for transfers to the Saltstone Production Facility (SPF). Salt solution is treated at SPF and disposed of in the Saltstone Disposal Facility (SDF). Per request of customer, X-TTR-Z-00023, Revision 0, two SDF waste form (saltstone) samples were prepared in the Savannah River National Laboratory (SRNL) from the Tank 50 Waste Acceptance Criteria (WAC) sample and Z-Area premix material for the third quarter of calendar year 2021(3QCY21). One sample contained a Full Premix which included 10:45:45 (by weight) of cement, slag and fly ash. The second sample contained 60:40 (by weight) of slag and fly ash only referred to as the “Cement-Free grout sample”. Results from this technical report support Task 2: ‘Grout Leaching Analyses’ of the Task Technical Request (TTR) prepared by Savannah River Remediation (SRR). After at least 28 days cured, a sample of each of the SDF waste forms was collected and shipped to a certified laboratory for analysis using the Toxicity Characteristic Leaching Procedure (TCLP). The 3QCY21 saltstone (Full Premix) and the Cement-Free grout samples met the South Carolina (SC) Code of Regulations for Hazardous Waste Management Regulations (HWMR) 61-79.261.24 and 61-79-268.48 requirements for a non-hazardous waste form with respect to Resource Conservation and Recovery Act (RCRA) metals and Underlying Hazardous Constituents (UHCs), and also met the SPF WAC that was in effect at the time of the tank sampling.

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

A formaldehyde and nitrogen dioxide toxics monitor for environmental justice

DOE’s Integrated Field Laboratories (IFLs) require a vast array of measurements to measure urban air quality. Nitrogen dioxide (NO2) and formaldehyde (HCHO) are ubiquitous pollutants with numerous sources, most notably vehicle exhaust. High-spatial density measurements are critical to understanding how certain neighborhoods are more adversely impacted by pollutants. This report describes the results of a Phase I SBIR project to develop and demonstrate a rapid, affordable, low-power monitor to provide high spatial resolution mobile measurements of formaldehyde and nitrogen dioxide at street-level, where people live and walk. The spatial density will be achieved via rapid measurements on a mobile platform. This sensor will quantify spatial disparities in cities of the toxics, HCHO and NO2, as well as carbon monoxide and carbon dioxide for better source identification. These species are detected in the mid infrared by laser absorption spectroscopy, and fiberoptics are used. Tasks accomplished include identification and testing of the appropriate spectroscopic regions; coupling of laser light into a fiberoptic system; development of software to control miniature electronics to scan and control two lasers simultaneously; coupling of the mid infrared fiber into a multipass cell for enhanced pathlength and sensitivity; characterization of sources of instrument noise; and design work for a Phase II prototype.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Converting methoxy groups on lignin-derived aromatics from a toxic hurdle to a useful resource: a systems-driven approach

Lignin conversion to bioproducts is challenging for several reasons, including the toxicity generated from the abundant methoxy groups released as formaldehyde. Consequently, our project used the best understood methylotroph – for which there is growing knowledge of formaldehyde stress responses – to explore how genetic factors and single-cell phenotypic heterogeneity contribute to growth and production. Our major goals were to (1) understand the fundamentals of Methylobacterium growth on aromatics, (2) identify and understand the basis of physiological basis of single-cell heterogeneity, and (3) develop quantitative models that relate heterogeneity to physiological and evolutionary outcomes.

Source record↗

A Double-Pronged Sword: XJB-5-131 Is a Suppressor of Somatic Instability and Toxicity in Huntington’s Disease

Due to large increases in the elderly populations across the world, age-related diseases are expected to expand dramatically in the coming years. Among these, neurodegenerative diseases will be among the most devastating in terms of their emotional and economic impact on patients, their families, and associated subsidized health costs. There is no currently available cure or rescue for dying brain cells. Viable therapeutics for any of these disorders would be a breakthrough and provide relief for the large number of affected patients and their families. Neurodegeneration is accompanied by elevated oxidative damage and inflammation. While natural antioxidants have largely failed in clinical trials, preclinical phenotyping of the unnatural, mitochondrial targeted nitroxide, XJB-5-131, bodes well for further translational development in advanced animal models or in humans. Here we consider the usefulness of synthetic antioxidants for the treatment of Huntington’s disease. The mitochondrial targeting properties of XJB-5-131 have great promise. It is both an electron scavenger and an antioxidant, reducing both somatic expansion and toxicity simultaneously through the same redox mechanism. By quenching reactive oxygen species, XJB-5-131 breaks the cycle between the rise in oxidative damage during disease progression and the somatic growth of the CAG repeat which depends on oxidation.

59 BASIC BIOLOGICAL SCIENCES↗

Community response of soil microorganisms to combined contamination of polycyclic aromatic hydrocarbons and potentially toxic elements in a typical coking plant

Both polycyclic aromatic hydrocarbons (PAHs) and potentially toxic elements (PTEs) of coking industries impose negative effects on the stability of soil ecosystem. Soil microbes are regarded as an essential moderator of biochemical processes and soil remediation, while their responses to PAHs-PTEs combined contamination are largely unknown. In the present study, soil microbial diversity and community composition in the typical coking plant under the chronic co-exposure of PAHs and PTEs were investigated and microbial interaction networks were built to reveal microbial co-occurrence patterns. The results indicated that the concentrations of PAHs in the soil inside the coking plant were significantly higher than those outside the plant. The mean concentration of ∑16PAHs was 2894.4 ng·g −1 , which is 5.58 times higher than that outside the plant. The average Hg concentration inside the coking plant was 22 times higher than the background value of Hebei province. The soil fungal community inside the coking plant showed lower richness compared with that of outside community, and there are significant difference in the bacterial and fungal community composition between inside and outside of coking plant ( p < 0.01). Predicted contribution of different environmental factors to each dominant species based on random forest identified 20 and 25 biomarkers in bacteria and fungi, respectively, that were highly sensitive to coking plant soil in operation, such as Betaproteobacteria,Sordariomycetes and Dothideomycetes . Bacterial and fungal communities were shaped by the soil chemical properties (pH), PTEs (Hg), and PAHs together in the coking plant soils. Furthermore, the bacterial and fungal interaction patterns were investigated separately or jointly by intradomain and interdomain networks. Competition is the main strategy based on the co-exclusion pattern in fungal community, and the competitive relationship inside the coking plant is more complex than that outside the plant. In contrast, cooperation is the dominant strategy in bacterial networks based on the co-occurrence pattern. The present study provided insights into microbial response strategies and the interactions between bacteria and fungi under long-term combined contamination.

Shen, Qihui↗

3-O-Methyltolcapone and Its Lipophilic Analogues Are Potent Inhibitors of Transthyretin Amyloidogenesis with High Permeability and Low Toxicity

Transthyretin (TTR) is an amyloidogenic homotetramer involved in the transport of thyroxine in blood and cerebrospinal fluid. To date, more than 130 TTR point mutations are known to destabilise the TTR tetramer, leading to its extracellular pathological aggregation accumulating in several organs, such as heart, peripheral and autonomic nerves, and leptomeninges. Tolcapone is an FDA-approved drug for Parkinson’s disease that has been repurposed as a TTR stabiliser. We characterised 3-O-methyltolcapone and two newly synthesized lipophilic analogues, which are expected to be protected from the metabolic glucuronidation that is responsible for the lability of tolcapone in the organism. Immunoblotting assays indicated the high degree of TTR stabilisation, coupled with binding selectivity towards TTR in diluted plasma of 3-O-methyltolcapone and its lipophilic analogues. Furthermore, in vitro toxicity data showed their several-fold improved neuronal and hepatic safety compared to tolcapone. Calorimetric and structural data showed that both T4 binding sites of TTR are occupied by 3-O-methyltolcapone and its lipophilic analogs, consistent with an effective TTR tetramer stabilisation. Moreover, in vitro permeability studies showed that the three compounds can effectively cross the blood-brain barrier, which is a prerequisite for the inhibition of TTR amyloidogenesis in the cerebrospinal fluid. Our data demonstrate the relevance of 3-O-methyltolcapone and its lipophilic analogs as potent inhibitors of TTR amyloidogenesis.

59 BASIC BIOLOGICAL SCIENCES↗

Recruiting Perovskites to Degrade Toxic Trinitrotoluene

Everybody knows TNT, the most widely used explosive material and a universal measure of the destructiveness of explosions. A long history of use and extensive manufacture of toxic TNT leads to the accumulation of these materials in soil and groundwater, which is a significant concern for environmental safety and sustainability. Reliable and cost-efficient technologies for removing or detoxifying TNT from the environment are lacking. Despite the extreme urgency, this remains an outstanding challenge that often goes unnoticed. We report here that highly controlled energy release from explosive molecules can be accomplished rather easily by preparing TNT–perovskite mixtures with a tailored perovskite surface morphology at ambient conditions. These results offer new insight into understanding the sensitivity of high explosives to detonation initiation and enable many novel applications, such as new concepts in harvesting and converting chemical energy, the design of new, improved energetics with tunable characteristics, the development of powerful fuels and miniaturized detonators, and new ways for eliminating toxins from land and water.

36 MATERIALS SCIENCE↗

Cross-Feeding of a Toxic Metabolite in a Synthetic Lignocellulose-Degrading Microbial Community

The recalcitrance of complex organic polymers such as lignocellulose is one of the major obstacles to sustainable energy production from plant biomass, and the generation of toxic intermediates can negatively impact the efficiency of microbial lignocellulose degradation. Here, we describe the development of a model microbial consortium for studying lignocellulose degradation, with the specific goal of mitigating the production of the toxin formaldehyde during the breakdown of methoxylated aromatic compounds. Included are Pseudomonas putida, a lignin degrader; Cellulomonas fimi, a cellulose degrader; and sometimes Yarrowia lipolytica, an oleaginous yeast. Unique to our system is the inclusion of Methylorubrum extorquens, a methylotroph capable of using formaldehyde for growth. We developed a defined minimal “Model Lignocellulose” growth medium for reproducible coculture experiments. We demonstrated that the formaldehyde produced by P. putida growing on vanillic acid can exceed the minimum inhibitory concentration for C. fimi, and, furthermore, that the presence of M. extorquens lowers those concentrations. We also uncovered unexpected ecological dynamics, including resource competition, and interspecies differences in growth requirements and toxin sensitivities. Finally, we introduced the possibility for a mutualistic interaction between C. fimi and M. extorquens through metabolite exchange. This study lays the foundation to enable future work incorporating metabolomic analysis and modeling, genetic engineering, and laboratory evolution, on a model system that is appropriate both for fundamental eco-evolutionary studies and for the optimization of efficiency and yield in microbially-mediated biomass transformation.

Methylorubrum extorquens↗

Co-Exposure of Nanopolystyrene and Other Environmental Contaminants—Their Toxic Effects on the Survival and Reproduction of Enchytraeus crypticus

Plastics in all shapes and sizes have become widespread across ecosystems due to intense anthropogenic use. As such, they can interact with other contaminants that accumulate in the terrestrial environment, such as pharmaceuticals, metals or nanomaterials (NMs). These interactions can potentiate combined toxic effects in the exposed soil organisms, with hazardous long-term consequences to the full ecosystem. In the present study, a terrestrial model species, Enchytraeus crypticus (oligochaeta), was exposed through contaminated soil with nanopolystyrene (representative of nanoplastics (NPls)), alone and in combination with diphenhydramine (DPH, representative of pharmaceuticals), silver nitrate (AgNO3, representative of metals) and vanadium nanoparticles (VNPs, representative of NMs). AgNO3 and VNPs decreased E. crypticus reproduction at 50 mg/kg, regardless of the presence of NPls. Moreover, at the same concentration, both single and combined VNP exposures decreased the E. crypticus survival. On the other hand, DPH and NPls individually caused no effect on organisms’ survival and reproduction. However, the combination of DPH (10 and 50 mg/kg) with 300 mg NPls/kg induced a decrease in reproduction, showing a relevant interaction between the two contaminants (synergism). Our findings indicate that the NPls can play a role as vectors for other contaminants and can potentiate the effects of pharmaceuticals, such as DPH, even at low and sub-lethal concentrations, highlighting the negative impact of mixtures of contaminants (including NPls) on soil systems.

Mendes, Luís A. (ORCID:0000000245738290)↗

Peptides having reduced toxicity that stimulate cholesterol efflux

The present invention provides a family of non-naturally occurring polypeptides having cholesterol efflux activity that parallels that of full-length apolipoproteins (e.g., Apo AI and Apo E), and having high selectivity for ABCA1 that parallels that of full-length apolipoproteins. Further, the peptides of the invention have little or no toxicity when administered at therapeutic and higher doses. The invention also provides compositions comprising such polypeptides, methods of identifying, screening and synthesizing such polypeptides, and methods of treating, preventing or diagnosing diseases and disorders associated with dyslipidemia, hypercholesterolemia, or inflammation; or diseases involving abnormal glucose metabolism, e.g., diabetes, metabolic syndrome; or Alzheimer's Disease or frontotemporal dementia.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Peptides having reduced toxicity that stimulate cholesterol efflux

The present invention provides a family of non-naturally occurring polypeptides having cholesterol efflux activity that parallels that of full-length apolipoproteins (e.g., Apo AI and Apo E), and having high selectivity for ABCA1 that parallels that of full-length apolipoproteins. Further, the peptides of the invention have little or no toxicity when administered at therapeutic and higher doses. The invention also provides compositions comprising such polypeptides, methods of identifying, screening and synthesizing such polypeptides, and methods of treating, preventing or diagnosing diseases and disorders associated with dyslipidemia, hypercholesterolemia, or inflammation; or diseases involving abnormal glucose metabolism, e.g., diabetes, metabolic syndrome; or Alzheimers Disease or frontotemporal dementia.

Bielicki, John K.↗

Peptides having reduced toxicity that stimulate cholesterol efflux

The present invention provides a family of non-naturally occurring polypeptides having cholesterol efflux activity that parallels that of full-length apolipoproteins (e.g., Apo AI and Apo E), and having high selectivity for ABCA1 that parallels that of full-length apolipoproteins. Further, the peptides of the invention have little or no toxicity when administered at therapeutic and higher doses. The invention also provides compositions comprising such polypeptides, methods of identifying, screening and synthesizing such polypeptides, and methods of treating, preventing or diagnosing diseases and disorders associated with dyslipidemia, hypercholesterolemia, or inflammation; or diseases involving abnormal glucose metabolism, e.g., diabetes, metabolic syndrome; or Alzheimer's Disease or frontotemporal dementia.

59 BASIC BIOLOGICAL SCIENCES↗

Long-Term Toxicity and Health-Related Quality of Life After Adjuvant Chemoradiation Therapy or Radiation Therapy Alone for High-Risk Endometrial Cancer in the Randomized PORTEC-3 Trial

The survival results of the PORTEC-3 trial showed a significant improvement in both overall and failure-free survival with chemoradiation therapy versus pelvic radiation therapy alone. The present analysis was performed to compare long-term adverse events (AE) and health-related quality of life (HRQOL).

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Impact of High-Dose-Rate and Low-Dose-Rate Brachytherapy Boost on Toxicity, Functional and Cancer Outcomes in Patients Receiving External Beam Radiation Therapy for Prostate Cancer: A National Population-Based Study

External beam radiation therapy (EBRT) with brachytherapy boost reduces cancer recurrence in patients with prostate cancer compared with EBRT monotherapy. However, randomized controlled trials or large-scale observational studies have not compared brachytherapy boost types directly.

62 RADIOLOGY AND NUCLEAR MEDICINE↗