Analyzing Flow Patterns in Unsaturated Fractured Rock of Yucca Mountain Using an Integrated Modeling Approach

Abstract This paper presents a series of modeling investigations to characterize percolation patterns in the unsaturated zone of Yucca Mountain, Nevada, a proposed underground repository site for storing high-level radioactive waste. The investigations are conducted using a modeling approach that integrates a wide variety of moisture, pneumatic, thermal, and isotopic geochemical field data into a comprehensive three-dimensional numerical model through model calibration. This integrated modeling approach, based on a dualcontinuum formulation, takes into account the coupled processes of fluid and heat flow and chemical isotopic transport in Yucca Mountain's highly heterogeneous, unsaturated fractured tuffs. In particular, the model results are examined against different types of field-measured data and used to evaluate different hydrogeological conceptual models and their effects on flow patterns in the unsaturated zone. The objective of this work to provide understanding of percolation patterns and flow behavior through the unsaturated zone, which is a crucial issue in assessing repository performance. Introduction Since the 1980s, the unsaturated zone (UZ) of the highly heterogeneous, fractured tuff at Yucca Mountain, Nevada, has been investigated by the U.S. Department of Energy as a possible repository site for storing high-level radioactive waste. Characterization of flow and transport processes in fractured rock of the Yucca Mountain UZ has received significant attention and generated tremendous interest in scientific communities over the last two decades. During this long and extensive study, many types of data have been collected from the Yucca Mountain UZ, and these data have helped to develop a conceptual understanding of various physical processes within the UZ system. The complexity of geological conditions and physical processes within the Yucca Mountain has posed a tremendous challenge for site-characterization effort, while quantitative evaluation of fluid flow, chemical transport, and heat transfer has proven to be essential. The need for quantitative investigations of flow and transport at the Yucca Mountain site has motivated a continual effort in developing and applying large, mountain-scale flow and transport models [e.g., Wu et al., 1999a and The site characterization studies of the unsaturated tuff at the Nevada Test Site and at Yucca Mountain began in the late 1970s and early 1980s. Those early hydrological, geological, and geophysical investigations of Yucca Mountain and the surrounding region were conducted to assess the feasibility of the site as a geological repository for storing high-level radioactive waste and to provide conceptual understanding of UZ flow processes In the early 1990s, more progress was made in UZ model development. Wittwer et al. [1992, 1995] developed a three-dimensional (3-D) site-scale model that incorporated several geological and hydrological complexities, such as geological layering, degree of welding, fault offsets, and different matrix and fracture properties. The 3-D model handled fracture-matrix flow using an effective continuum method (ECM) and was applied to evaluate various assumptions concerning faults and infiltration patterns. Using the ECM concept, Ahlers et al. [1995a, 1995b] continued development of the UZ site-scale model with increased numerical and spatial resolution. Their studies considered more processes, such as gas and heat flow analyses, and introduced an inverse modeling approach for estimating model-input properties. However, more comprehensive UZ models were not developed until a couple of years later, when the UZ models were developed for total system performance assessment-viability assessment (TSPA-VA) [e.g., Wu et al., 1999a and The next generation of UZ models included those primarily developed for the TSPA-site recommendation (SR) calculations [e.g., Wu et al., 2002a; Moridis et al., 2003; Robinson et al., 2003]. These TSPA-SR models were enhanced from the TSPA-VA model. More 4 importantly, the newer models took into account the coupled processes of flow and transport in highly heterogeneous, unsaturated fractured porous rock, and were applied to analyzing the effect of current and future climates on radionuclide transport through the UZ system. The site-scale UZ flow and transport models developed during the site characterization of Yucca Mountain have built upon the past research as well as the above-referenced work and many other studies [e.g., McLaren et al., 2000; Robinson et al., 1996 and 1997; This paper presents the results of our continuing effort to develop a realistic and representative UZ flow model to characterize the Yucca Mountain UZ system. More specifically, we focus on analyzing unsaturated flow patterns in the Yucca Mountain UZ under various climates and different hydrogeological conceptual models using an integrated modeling approach. This effort integrates different field-observed data, such as water potential, liquid saturation, perched water, gas pressure, chloride, and temperature logs into one single 3-D UZ flow and transport model. Using the dual-permeability modeling approach, the integrated modeling effort provides consistent model predictions for different, but inter-related hydrological, pneumatical, geochemical, and geothermal processes in the UZ. More importantly, such an integrated modeling exercise will improve the model's capability and credibility in describing and predicting current and future conditions and processes of the UZ system. At the same time, the combined model calibration will present a consistent check on modeled percolation fluxes and reveal better insight into the UZ flow patterns. The modeling study of this work consists of (1) UZ model description; (2) model development and calibration using liquid saturation, water potential, perched water, and pneumatic data; (3) assessing percolation patterns and flow behavior using thermal and geochemical data; and (4) simulated percolation pattern analysis. Conceptual Model of UZ Flow Over the past two decades, extensive scientific investigations have been conducted for the site characterization of Yucca Mountain, including data collection from surface mapping, sampling from many deep and shallow boreholes, constructing underground tunnels, and field testing [e.g., Rousseau, 1998]. of faults and perched water on the UZ system. As illustrated in In fact, the PTn's capability of attenuating episodic percolation fluxes has been observed in field tests of water release into the PTn matrix In addition, the possibility for capillary barriers exists at both upper and lower PTn contacts, as well as within the PTn layers PTn layers. However, the extent of lateral flow diversion within the PTn remains a topic of debate. For example, a recent study using a conceptual model with transitional changes in rock properties argues that lateral diversion may be small Perched Water Perched water has been encountered in a number of boreholes at Yucca Mountain, including UZ-14, SD-7, SD-9, SD-12, NRG-7a, G-2, and WT-24 ( Perched water may occur where percolation flux exceeds the capacity of the geological media to transmit vertical flux in the UZ [Rousseau et al., 1998]. Several conceptual models have been investigated for explaining the genesis of perched water at Yucca Mountain [e.g., Wu et al., 1999b and Faults In addition to possible capillary and permeability barriers, major faults in the UZ are also expected to play an important role in controlling percolation flux. Permeability within faults is much higher than that in the surrounding tuff Pneumatic permeability measurements taken along portions of faults revealed low airentry pressures, indicating that large fracture apertures are present in the fault zones. Highly brecciated fault zones may act as vertical capillary barriers to lateral flow. Once water is diverted into a fault zone, however, its high permeability could facilitate rapid vertical flow through the unsaturated system Heterogeneity A considerable amount of field data, obtained from tens of boreholes, two underground tunnels, and hundreds of outcrop samples at the site, constrains the distribution of rock properties within different units. In general, field data indicate that the Yucca Mountain formation is more heterogeneous vertically than horizontally, such that layer-wise representations are found to provide reasonable approximations of the complex geological system. This is because many model calibration results using this approximation are able to match different types of observation data obtained from different locations and depths [e.g., Bandurraga and Bodvarsson, 1999; 8 In summary, as shown in Ambient water flow in the UZ system is at a quasi-steady state condition, subject to spatially varying net infiltration on the ground surface. Hydrogeological units/layers are internally homogeneous, unless interrupted by faults or altered. There may exist capillary barriers in the PTn unit, causing lateral flow. Perched water results from permeability barrier effects. Major faults serve as fast vertical flow pathways for laterally diverted flow. Numerical Modeling Approach and Model Description Because of the complexity of the UZ geological system and the highly nonlinear nature of governing equations for UZ flow and transport, numerical modeling approaches were used in this study. Numerical simulations were carried out using the TOUGH2 and T2R3D codes [Pruess, 1991; Wu et al., 1996]. Most UZ flow simulations in this study were performed using an unsaturated flow module of the TOUGH2 code, which solves Richards' equation. Two active phases (liquid and gas) and heat flow was simulated using a two-phase fluid and heat flow module. Tracer and geochemical transport runs were carried out with the T2R3D code. Numerical Model Grids There are two 3-D numerical model grids used in this study, as shown in plan view in consists of 980 mesh columns of fracture and matrix continua, 86,440 gridblocks, and 350,000 connections in a dual-permeability grid. Vertically, the thermal grid has an average of 45 computational grid layers. Modeling Fracture-Matrix Interaction Modeling fracture and matrix flow and interaction under multiphase, multicomponent, isothermal or nonisothermal conditions has been a key issue for simulating fluid and heat flow in the Yucca Mountain UZ. Different modeling approaches have been tested for handling fracture-matrix interaction at Yucca Mountain The dual-permeability methodology considers global flow and transport occurring not only between fractures but also between matrix gridblocks. In this approach, the rockvolume domain is represented by two overlapping (yet interacting) fracture and matrix 10 continua, and local fracture-matrix flow and transport is approximated as a quasi-steady state. When applied in this work, however, the traditional dual-permeability concept is first modified by using an active fracture model Model Input Parameters Since the Richards' and two-active-phases flow equations are used in modeling unsaturated flow of water and air through fracture and matrix, relative permeability and capillary pressure curves are needed for the two media. In addition, other intrinsic fracture and matrix properties are also needed, such as porosity, permeability, density, and fracture geometric parameters, as well as rock thermal properties. In our modeling study, the van Genuchten models of relative permeability and capillary pressure functions The model input parameters of fractured and matrix rock were determined by two steps: (1) using field and laboratory measurements Model Boundary Conditions The ground surface of the mountain (or the tuff-alluvium contact in the area of significant alluvial cover) is taken as the top model boundary, while the water table is treated as the bottom model boundary. For flow simulations, net infiltration is applied to fractures along the top boundary using a source term. The bottom boundary at the water table is treated as a Dirichlet-type boundary. All the lateral boundaries, as shown in Net infiltration of water, resulting from precipitation that penetrates the top-soil layer of the mountain, is the most important factor affecting the overall hydrological, geochemical and thermal-hydrological behavior of the UZ. Net infiltration is the ultimate source of groundwater recharge and deep-zone percolation through the UZ, and provides a vehicle for transporting radionuclides from the repository to the water table. To cover the various possible scenarios and uncertainties of current and future climates at Yucca Mountain, we have incorporated a total of nine net infiltration maps, provided by US Geological Survey (USGS) scientists [Hevesi and Flint, 2000; As shown in Model Calibration The complexities of the heterogeneous geological formation at the Yucca Mountain UZ, A total of 18 flow simulation scenarios are studied in this work, as listed in In these calibrations, the gas flow model uses the UZ thermal model grid Comparison of model simulation results and field-measured pneumatic data for boreholes UZ-7a is shown in Flow Patterns and Analyses The primary objective of modeling UZ flow at Yucca Mountain is to estimate percolation flux through the UZ system. This is because percolation is the most critical factor that affects overall repository performance under current and future climates. However, in situ Past studies [e.g., Wu et al., 2002a] have shown that it is very difficult even to quantify the range of percolation fluxed by using hydrological data alone. Percolation patterns inside the UZ strongly depend on infiltration rates and their spatial distribution, among other factors. Therefore, over the past two decades, significant research effort has been devoted to estimating the infiltration rates [e.g., Flint et al., 1996; Hevesi and Flint, 2000; 17 Simulated Percolation Fluxes Percolation Patterns at Repository: Percolation fluxes at the repository horizon, as predicted using 18 3-D UZ flow simulation results of Flow Pattern Analyses Simulated In this study, heat flow simulations use the 3-D thermal model grid Temperature distributions at the bottom boundary of the thermal model are taken from deep-borehole-measured temperature profiles All Cl transport simulations were run using the T2R3D code for 100,000 years to approximate the current, steady-state condition under the infiltration scenarios considered. Chloride is treated as a conservative component transported through the UZ, subject to advection, diffusion, and first-order delay. The mechanical dispersion effect through the fracture-matrix system was ignored. A constant molecular diffusion coefficient of 2.032 × 10 -9 m 2 /s is used for matrix diffusion for Cl and the half-life for radioactive decay is 301,000 years. Concluding Remarks This paper presents a large-scale modeling study to characterize percolation patterns in the unsaturated zone of Yucca Mountain, Nevada, a proposed underground repository site for storing high-level radioactive waste. The modeling studies are conducted using an integrated modeling approach, which incorporates a wide variety of field data into a This study summarizes our current research effort to characterize UZ flow patterns at Yucca Mountain. Even with the significant progress made in quantitative evaluation of UZ flow and transport processes at the site using numerical models over the last two decades, there still exist a number of limitations and shortcomings with these models and their results. In general, accuracy and reliability of UZ site-scale models and simulation results are critically dependent on the accuracy of estimated model-related properties and other types of input parameters as well as hydrogeological conceptual models. The main limitations and uncertainties with the current UZ site-scale models are (1) the lack of indepth knowledge of the mountain system (including the geological and conceptual models and the availability of field and laboratory data), and (2) the approximations of a large volume-averaged modeling approach. As a result, continual research effort is still 26 needed toward a better understanding of the Yucca Mountain UZ system

Colloid facilitated transport in fractured rocks : parameter estimation and comparison with experimental data.

Colloid-facilitated migration of plutonium in fractured rock has been implicated in both field and laboratory studies . Other reactive radionuclides may also experience enhanced mobility due to groundwater colloids. Model prediction of this process is necessary for assessment of contaminant boundaries in systems for which radionuclides are already in the groundwater and for performance assessment of potential repositories for radioactive waste. Therefore, a reactive transport model is developed and parameterized using results from controlled laboratory fracture column experiments. Silica, montmorillonite and clinoptilolite colloids are used in the experiments along with plutonium and Tritium . . The goal of the numerical model is to identify and parameterize the physical and chemical processes that affect the colloid-facilitated transport of plutonium in the fractures. The parameters used in this model are similar in form to those that might be used in a field-scale transport model

Variations of X Chromosome Inactivation Occur in Early Passages of Female Human Embryonic Stem Cells

X chromosome inactivation (XCI) is a dosage compensation mechanism essential for embryonic development and cell physiology. Human embryonic stem cells (hESCs) derived from inner cell mass (ICM) of blastocyst stage embryos have been used as a model system to understand XCI initiation and maintenance. Previous studies of undifferentiated female hESCs at intermediate passages have shown three possible states of XCI; 1) cells in a pre-XCI state, 2) cells that already exhibit XCI, or 3) cells that never undergo XCI even upon differentiation. In this study, XCI status was assayed in ten female hESC lines between passage 5 and 15 to determine whether XCI variations occur in early passages of hESCs. Our results show that three different states of XCI already exist in the early passages of hESC. In addition, we observe one cell line with skewed XCI and preferential expression of X-linked genes from the paternal allele, while another cell line exhibits random XCI. Skewed XCI in undifferentiated hESCs may be due to clonal selection in culture instead of non-random XCI in ICM cells. We also found that XIST promoter methylation is correlated with silencing of XIST transcripts in early passages of hESCs, even in the pre-XCI state. In conclusion, XCI variations already take place in early passages of hESCs, which may be a consequence of in vitro culture selection during the derivation process. Nevertheless, we cannot rule out the possibility that XCI variations in hESCs may reflect heterogeneous XCI states in ICM cells that stochastically give rise to hESCs

Insect-Specific microRNA Involved in the Development of the Silkworm Bombyx mori

MicroRNAs (miRNAs) are endogenous non-coding genes that participate in post-transcription regulation by either degrading mRNA or blocking its translation. It is considered to be very important in regulating insect development and metamorphosis. We conducted a large-scale screening for miRNA genes in the silkworm Bombyx mori using sequence-by-synthesis (SBS) deep sequencing of mixed RNAs from egg, larval, pupal, and adult stages. Of 2,227,930 SBS tags, 1,144,485 ranged from 17 to 25 nt, corresponding to 256,604 unique tags. Among these non-redundant tags, 95,184 were matched to the silkworm genome. We identified 3,750 miRNA candidate genes using a computational pipeline combining RNAfold and TripletSVM algorithms. We confirmed 354 miRNA genes using miRNA microarrays and then performed expression profile analysis on these miRNAs for all developmental stages. While 106 miRNAs were expressed in all stages, 248 miRNAs were egg- and pupa-specific, suggesting that insect miRNAs play a significant role in embryogenesis and metamorphosis. We selected eight miRNAs for quantitative RT-PCR analysis; six of these were consistent with our microarray results. In addition, we searched for orthologous miRNA genes in mammals, a nematode, and other insects and found that most silkworm miRNAs are conserved in insects, whereas only a small number of silkworm miRNAs has orthologs in mammals and the nematode. These results suggest that there are many miRNAs unique to insects

Genetic Basis of Virulence Attenuation Revealed by Comparative Genomic Analysis of Mycobacterium tuberculosis Strain H37Ra versus H37Rv

Tuberculosis, caused by Mycobacterium tuberculosis, remains a leading infectious disease despite the availability of chemotherapy and BCG vaccine. The commonly used avirulent M. tuberculosis strain H37Ra was derived from virulent strain H37 in 1935 but the basis of virulence attenuation has remained obscure despite numerous studies. We determined the complete genomic sequence of H37Ra ATCC25177 and compared that with its virulent counterpart H37Rv and a clinical isolate CDC1551. The H37Ra genome is highly similar to that of H37Rv with respect to gene content and order but is 8,445 bp larger as a result of 53 insertions and 21 deletions in H37Ra relative to H37Rv. Variations in repetitive sequences such as IS6110 and PE/PPE/PE-PGRS family genes are responsible for most of the gross genetic changes. A total of 198 single nucleotide variations (SNVs) that are different between H37Ra and H37Rv were identified, yet 119 of them are identical between H37Ra and CDC1551 and 3 are due to H37Rv strain variation, leaving only 76 H37Ra-specific SNVs that affect only 32 genes. The biological impact of missense mutations in protein coding sequences was analyzed in silico while nucleotide variations in potential promoter regions of several important genes were verified by quantitative RT-PCR. Mutations affecting transcription factors and/or global metabolic regulations related to in vitro survival under aging stress, and mutations affecting cell envelope, primary metabolism, in vivo growth as well as variations in the PE/PPE/PE-PGRS family genes, may underlie the basis of virulence attenuation. These findings have implications not only for improved understanding of pathogenesis of M. tuberculosis but also for development of new vaccines and new therapeutic agents

Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants

Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Peer reviewe

Germline variation at 8q24 and prostate cancer risk in men of European ancestry

Chromosome 8q24 is a susceptibility locus for multiple cancers, including prostate cancer. Here we combine genetic data across the 8q24 susceptibility region from 71,535 prostate cancer cases and 52,935 controls of European ancestry to define the overall contribution of germline variation at 8q24 to prostate cancer risk. We identify 12 independent risk signals for prostate cancer (p < 4.28 × 10−15), including three risk variants that have yet to be reported. From a polygenic risk score (PRS) model, derived to assess the cumulative effect of risk variants at 8q24, men in the top 1% of the PRS have a 4-fold (95%CI = 3.62–4.40) greater risk compared to the population average. These 12 variants account for ~25% of what can be currently explained of the familial risk of prostate cancer by known genetic risk factors. These findings highlight the overwhelming contribution of germline variation at 8q24 on prostate cancer risk which has implications for population risk stratification

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population.

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (Pinteraction = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications