Final report: Phase stability and segregation in Alloy 22 base metal and weldments

At the outset of this project, the design of the waste disposal containers relied heavily on encasement in a multi-layered container, featuring a corrosion barrier of Alloy 22, a Ni-Cr- Mo-W based alloy with excellent corrosion resistance over a wide range of conditions. The fundamental concern from the perspective of the Yucca Mountain Project, however, was the inherent uncertainty in the (very) long-term stability of the base metal and welds. Should the properties of the selected materials change over the long service life of the waste packages, it was conceivable that the desired performance characteristics (such as corrosion resistance) would become compromised, leading to premature failure of the system. To address this, we studied aspects of the phase stability and solute segregation characteristics of Alloy 22 base metal, and the manner in which these affected corrosion resistance. This work was conducted as an independent validation, to add to confidence in the extrapolated behavior of the container materials over time periods that are not feasibly tested in a laboratory

Phase Stability and Segregation in Alloy 22 Base Metal and Weldments

The current design of the waste disposal containers relies heavily on encasement in a multi-layered container, featuring a corrosion barrier of Alloy 22, a Ni-Cr-Mo-W based alloy with excellent corrosion resistance over a wide range of conditions. The fundamental concern from the perspective of the Yucca Mountain Project, however, is the inherent uncertainty in the (very) long-term stability of the base metal and welds. Should the properties of the selected materials change over the long service life of the waste packages, it is conceivable that the desired performance characteristics (such as corrosion reistance) will become compromised, leading to premature failure of the system. To address this, we will study the phase stability and solute segregation characteristics of Alloy 22 base metal and welds. A better understanding of the underlying microstructural evolution tendencies, and their connections with corrosion behavior will (in turn) produce a higher confidence in the extrapolated behavior of the container materials over time periods that are not feasibly tested in a laboratory. Additionally, the knowledge gained here may potentially lead to cost savings through development of safe and realistic design constraints and model assumptions throughout the entire disposal system

Phase stability and segregation in Alloy 22 base metal and weldments

Subtask 1: Microstructural Characterization of Phase Stability and Variability in Alloy 22. Develop an improved understanding of Alloy 22 and the extent to which compositional and microstructural variations are present in otherwise “nominal” as-procured material. Subtask 2: Electrochemical Methods to Detect Susceptibility of Alloy 22 to Localized Corrosion. Study the influence that compositional and microstructural variations have on the corrosion performance of Alloy 22

A Diffusion Network Event History Estimator

Research on the diffusion of political decisions across jurisdictions typically accounts for units’ influence over each other with (1) observable measures or (2) by inferring latent network ties from past decisions. The former approach assumes that interdependence is static and perfectly captured by the data. The latter mitigates these issues but requires analytical tools that are separate from the main empirical methods for studying diffusion. As a solution, we introduce network event history analysis (NEHA), which incorporates latent network inference into conventional discrete-time event history models. We demonstrate NEHA’s unique methodological and substantive benefits in applications to policy adoption in the American states. Researchers can analyze the ties and structure of inferred networks to refine model specifications, evaluate diffusion mechanisms, or test new or existing hypotheses. By capturing targeted relationships unexplained by standard covariates, NEHA can improve models, facilitate richer theoretical development, and permit novel analyses of the diffusion process

Crossover Scaling in Dendritic Evolution at Low Undercooling

We examine scaling in two-dimensional simulations of dendritic growth at low undercooling, as well as in three-dimensional pivalic acid dendrites grown on NASA's USMP-4 Isothermal Dendritic Growth Experiment. We report new results on self-similar evolution in both the experiments and simulations. We find that the time dependent scaling of our low undercooling simulations displays a cross-over scaling from a regime different than that characterizing Laplacian growth to steady-state growth

Technical Aspects of Flow Cytometry-based Measurable Residual Disease Quantification in Acute Myeloid Leukemia: Experience of the European LeukemiaNet MRD Working Party

Measurable residual disease (MRD) quantified by multiparameter flow cytometry (MFC) is a strong and independent prognostic factor in acute myeloid leukemia (AML). However, several technical factors may affect the final read-out of the assay. Experts from the MRD Working Party of the European LeukemiaNet evaluated which aspects are crucial for accurate MFC-MRD measurement. Here, we report on the agreement, obtained via a combination of a cross-sectional questionnaire, live discussions, and a Delphi poll. The recommendations consist of several key issues from bone marrow sampling to final laboratory reporting to ensure quality and reproducibility of results. Furthermore, the experiences were tested by comparing two 8-color MRD panels in multiple laboratories. The results presented here underscore the feasibility and the utility of a harmonized theoretical and practical MFC-MRD assessment and are a next step toward further harmonization

Treatment as prevention effect of direct-acting antivirals on primary hepatitis C virus incidence: Findings from a multinational cohort between 2010 and 2019.

BACKGROUND Broad direct-acting antiviral (DAA) access may reduce hepatitis C virus (HCV) incidence through a "treatment as prevention" (TasP) effect. We assessed changes in primary HCV incidence following DAA access among people living with HIV (PLHIV). METHODS We used pooled individual-level data from six cohorts from the International Collaboration on Hepatitis C Elimination in HIV Cohorts (InCHEHC). Follow-up started from the first recorded negative HCV antibody test date and ended at last negative antibody test or estimated infection date. Follow-up was restricted to 2010-2019. We used segmented Poisson regression to model trends across pre-, limited- (i.e., restrictions on access) and broad-DAA access periods. FINDINGS Overall, 45,942 participants had at least one HCV antibody negative result and follow-up between 2010 and 2019. We observed 2042 incident HCV infections over 248,189 person-years (PY). Pooled incidence decreased from 0.91 per 100 PY in 2015 to 0.41 per 100 PY in 2019. Compared to the average pre-DAA period incidence (0.90 per 100 PY), average incidence was similar during the limited-DAA access period (Incidence rate ratio [IRR] = 0.98; 95%CI = 0.87, 1.11), and 52% lower during the broad-DAA access period (IRR = 0.48; 95%CI = 0.42, 0.52). The average annual decline in HCV incidence was 2% in the pre-DAA period; an additional 9% annual decline in incidence was observed during the limited-DAA access period (IRR = 0.91; 95%CI = 0.82, 1.00) and a further 20% decline in the broad-DAA access period (IRR = 0.80, 95%CI = 0.73, 0.89). INTERPRETATION Our findings suggest that broad DAA access has a TasP effect on primary HCV incidence among PLHIV. Based on the initial years of DAA availability, the countries in the InCHEHC collaboration are on track to meet the World Health Organization's 80% HCV incidence reduction target for PLHIV by 2030. FUNDING This study was funded by the Australian Government National Health and Medical Research Council (Grant number GNT1132902)

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin