FMGN, RENUMN, POLY, TRIPOLY: Suite of Programs for calculating and analyzing flow and transport in fracture networks embedded in porous matrix blocks

This report describes a suite of programs developed at the Ernest Orlando Lawrence Berkeley National Laboratory (Berkeley Lab) for simulating flow and solute transport in fracture networks embedded in porous matrix blocks. The codes FMGN, RENUMN and TRIPOLY are extensions of the older codes FMG, RENUM and TRINET developed at the Berkeley Lab, and references are made to previous Berkeley Lab reports which describe those codes. The first section of this report describes the general background of TRIPOLY and the theory of treating the fluid and solute exchange between fractures and rock. The second section is a user`s manual for the programs FMGN, RENUMN, POLY and TRIPOLY. Note that the description of FMGN and RENUMN is very short in this section. FMGN and RENUMN are relatively unchanged from the old codes FMG and RENUM, and only the differences between the old and new versions are listed in this report. For work with FMGN and RENUMN we refer to the detailed description of theory and design in BILLAUX et al. and the user`s manual in BILLAUX et al. respectively. For the other codes POLY (newly developed) and TRIPOLY (features major changes compared to the old program version TRINET) a detailed user`s manual is enclosed in this report. It provides the user with sufficient information to run the programs. The third section of this report comprises some sample problems as a tutorial

Observations of joint persistence and connectivity across boreholes

Observations of joint persistence and connectivity are made by comparison of digital borehole wall images of fractures, fluid conductivity logs and hydraulic injections test results. The fractures were found to be generally impersistent across vertical boreholes about 8 m apart. Many hydraulic connections were found in the same volume of rock. Direct connections through single fractures seem to be rare and connectivity appears to be controlled by fracture networks, even over small volumes

A new Eulerian-Lagrangian finite element simulator for solute transport in discrete fracture-matrix systems

Fracture network simulators have extensively been used in the past for obtaining a better understanding of flow and transport processes in fractured rock. However, most of these models do not account for fluid or solute exchange between the fractures and the porous matrix, although diffusion into the matrix pores can have a major impact on the spreading of contaminants. In the present paper a new finite element code TRIPOLY is introduced which combines a powerful fracture network simulator with an efficient method to account for the diffusive interaction between the fractures and the adjacent matrix blocks. The fracture network simulator used in TRIPOLY features a mixed Lagrangian-Eulerian solution scheme for the transport in fractures, combined with an adaptive gridding technique to account for sharp concentration fronts. The fracture-matrix interaction is calculated with an efficient method which has been successfully used in the past for dual-porosity models. Discrete fractures and matrix blocks are treated as two different systems, and the interaction is modeled by introducing sink/source terms in both systems. It is assumed that diffusive transport in the matrix can be approximated as a one-dimensional process, perpendicular to the adjacent fracture surfaces. A direct solution scheme is employed to solve the coupled fracture and matrix equations. The newly developed combination of the fracture network simulator and the fracture-matrix interaction module allows for detailed studies of spreading processes in fractured porous rock. The authors present a sample application which demonstrate the codes ability of handling large-scale fracture-matrix systems comprising individual fractures and matrix blocks of arbitrary size and shape

A new Lagrangian-Eulerian finite element method for modeling contaminant transport in fractured porous formations

Fracture network simulators have been extensively used in the past for obtaining a better understanding of flow and transport processes in fractured rock. However, most of these models do not account for fluid or solute exchange between the fractures and the porous matrix, although diffusion into the matrix pores can have a major impact on the spreading of contaminants. In the present paper a new finite element code TRIPOLY is introduced which combines a powerful Lagrangian-Eulerian approach for solving flow and transport in networks of discrete fractures with an efficient method to account for the diffusive interaction between the fractures and the adjacent matrix blocks. The code is capable of handling large-scale fracture-matrix systems comprising individual fractures and matrix blocks of arbitrary size, shape, and dimension

Numerical investigation for the impact of CO2 geologic sequestration on regional groundwater flow

Large-scale storage of carbon dioxide in saline aquifers may cause considerable pressure perturbation and brine migration in deep rock formations, which may have a significant influence on the regional groundwater system. With the help of parallel computing techniques, we conducted a comprehensive, large-scale numerical simulation of CO{sub 2} geologic storage that predicts not only CO{sub 2} migration, but also its impact on regional groundwater flow. As a case study, a hypothetical industrial-scale CO{sub 2} injection in Tokyo Bay, which is surrounded by the most heavily industrialized area in Japan, was considered, and the impact of CO{sub 2} injection on near-surface aquifers was investigated, assuming relatively high seal-layer permeability (higher than 10 microdarcy). A regional hydrogeological model with an area of about 60 km x 70 km around Tokyo Bay was discretized into about 10 million gridblocks. To solve the high-resolution model efficiently, we used a parallelized multiphase flow simulator TOUGH2-MP/ECO2N on a world-class high performance supercomputer in Japan, the Earth Simulator. In this simulation, CO{sub 2} was injected into a storage aquifer at about 1 km depth under Tokyo Bay from 10 wells, at a total rate of 10 million tons/year for 100 years. Through the model, we can examine regional groundwater pressure buildup and groundwater migration to the land surface. The results suggest that even if containment of CO{sub 2} plume is ensured, pressure buildup on the order of a few bars can occur in the shallow confined aquifers over extensive regions, including urban inlands

Kombinasi Format Factory, U-lead dan Microsoft Office Powerpoint dalam Upaya Meningkatkan Kualitas Media Pembelajaran

Peserta didik mempunyai gaya belajar yang berbeda-beda. Gaya belajar tersebut meliputi auditori, visual dan kinestetik (VAK). Seorang guru harus mampu memenuhi kebutuhan masing-masing gaya belajar peserta didik tersebut. Salah satu cara yang dapat dilakukan adalah dengan menggunakan media pembelajaran berbasis VAK. Media pembelajaran berbasis VAK dapat dipenuhi dengan menyisipkan file video di dalamnya. Selain itu, penggunaan file video sebagai media pembelajaran mendukung implementasi pembelajaran saintifik pada kurikulum 2013. Namun, belum semua guru memiliki kemampuan untuk mengemas file video tersebut dalam bentuk media pembelajaran. Tujuan penelitian ini adalah untuk meningkatkan kemampuan guru-guru di SMA Negeri 1 Teras dan SMA Negeri 1 Boyolali dalam membuat media pembelajaran berbasis VAK dengan kombinasi software Format Factory, U-Lead dan PowerPoint. Hasil penelitian menunjukkan bahwa terjadi peningkatan kemampuan para guru di SMA Negeri 1 Teras dan SMA Negeri 1 Boyolali dalam membuat media pembelajaran. Peningkatan kemampuan guru-guru tersebut berada di atas target yang direncanakan. Rerata peningkatan kemampuan guru-guru di SMA Negeri 1 Teras 7,87% di atas target, sedangkan di SMA Negeri 1 Boyolali 9,58% di atas target. Kata kunci: Media Pembelajaran, Format Factory, U-Lead, PowerPoint Students have different learning styles. Learning styles include visual learners, auditory learners, and kinesthetic learners. A teacher must be able to fulfill the needs of individual students\u27 learning styles. One way that can be applied is using Visual, Audio and Kinesthetic (VAK) learning media based. VAK-learning media based can be created by inserting video files on it. In addition, using video file as a learning media can support the implementation of scientific learning on the 2013 curriculum. However, not all teachers have the ability to use video files into a learning media. The purpose of this study is to improve the teachers\u27 ability at SMA Negeri 1 Teras and SMAN 1 Boyolali on making VAK-learning media based with a combination of Format Factory, U-Lead and PowerPoint software. The results showed that the teachers\u27 ability on making VAK-learning media based was increased. Increased the teachers\u27 ability was above planned target score. The mean score of the teachers\u27 ability at SMA Negeri 1 Teras 7.87% above the target, while at SMAN 1 Boyolali 9.58% above the target

Antibodies against endogenous retroviruses promote lung cancer immunotherapy

B cells are frequently found in the margins of solid tumours as organized follicles in ectopic lymphoid organs called tertiary lymphoid structures (TLS)$^{1,2}$. Although TLS have been found to correlate with improved patient survival and response to immune checkpoint blockade (ICB), the underlying mechanisms of this association remain elusive$^{1,2}$. Here we investigate lung-resident B cell responses in patients from the TRACERx 421 (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy) and other lung cancer cohorts, and in a recently established immunogenic mouse model for lung adenocarcinoma$^{3}$. We find that both human and mouse lung adenocarcinomas elicit local germinal centre responses and tumour-binding antibodies, and further identify endogenous retrovirus (ERV) envelope glycoproteins as a dominant anti-tumour antibody target. ERV-targeting B cell responses are amplified by ICB in both humans and mice, and by targeted inhibition of KRAS(G12C) in the mouse model. ERV-reactive antibodies exert anti-tumour activity that extends survival in the mouse model, and ERV expression predicts the outcome of ICB in human lung adenocarcinoma. Finally, we find that effective immunotherapy in the mouse model requires CXCL13-dependent TLS formation. Conversely, therapeutic CXCL13 treatment potentiates anti-tumour immunity and synergizes with ICB. Our findings provide a possible mechanistic basis for the association of TLS with immunotherapy response

Vasorelaxant activity of indole alkaloids from Tabernaemontana dichotoma.

The aim of this study was to search for bioactive natural products from medicinal plants targeting vasorelaxant activity and we found the methanol extract from bark of Tabernaemontana dichotoma showed vasorelaxant activity on rat aorta. We isolated eight indole alkaloids including 10-methoxyalstonerine (1), a new macroline type indole alkaloid, from bark of T. dichotoma. These were respectively identified as 10-methoxyaffinisine (2), lochnerine (3), cathafoline (4), (−)-alstonerine (5), 19,20-dehydro-10-methoxytalcarpine (6), alstonisine (7), and alstonal (8) based on spectroscopic analysis. Among them, sarpagine type (2 and 3), akuammiline type (4), and macroline oxindole type (7 and 8) showed potent vasorelaxant activity. Mechanism of action on vasorelaxant activity of 10-methoxyaffinisine (2), cathafoline (4), and alstonisine (7) was clarified. Effects of 10-methoxyaffinisine (2), cathafoline (4), and alstonisine (7) were partially mediated the NO release from endothelial cells. Furthermore, 10-methoxyaffinisine (2) and alstonisine (7) attribute to the inhibitory effect of VDC and ROC, and cathafoline (4) have inhibitory effect on Ca2+ influx via ROC. In addition, 10-methoxyaffinisine (2) as a major compound from bark of T. dichotoma showed hypotensive effect on normotensive rats in vivo

The evolution of lung cancer and impact of subclonal selection in TRACERx

Lung cancer is the leading cause of cancer-associated mortality worldwide1. Here we analysed 1,644 tumour regions sampled at surgery or during follow-up from the first 421 patients with non-small cell lung cancer prospectively enrolled into the TRACERx study. This project aims to decipher lung cancer evolution and address the primary study endpoint: determining the relationship between intratumour heterogeneity and clinical outcome. In lung adenocarcinoma, mutations in 22 out of 40 common cancer genes were under significant subclonal selection, including classical tumour initiators such as TP53 and KRAS. We defined evolutionary dependencies between drivers, mutational processes and whole genome doubling (WGD) events. Despite patients having a history of smoking, 8% of lung adenocarcinomas lacked evidence of tobacco-induced mutagenesis. These tumours also had similar detection rates for EGFR mutations and for RET, ROS1, ALK and MET oncogenic isoforms compared with tumours in never-smokers, which suggests that they have a similar aetiology and pathogenesis. Large subclonal expansions were associated with positive subclonal selection. Patients with tumours harbouring recent subclonal expansions, on the terminus of a phylogenetic branch, had significantly shorter disease-free survival. Subclonal WGD was detected in 19% of tumours, and 10% of tumours harboured multiple subclonal WGDs in parallel. Subclonal, but not truncal, WGD was associated with shorter disease-free survival. Copy number heterogeneity was associated with extrathoracic relapse within 1 year after surgery. These data demonstrate the importance of clonal expansion, WGD and copy number instability in determining the timing and patterns of relapse in non-small cell lung cancer and provide a comprehensive clinical cancer evolutionary data resource

What does 'acceptance' mean? Public reflections on the idea that addiction is a brain disease

Public responses to the dissemination of neuroscientific explanations of addiction and other mental disorders are an interesting sociocultural phenomenon. We investigated how 55 members of the Australian public deliberated on the idea that 'addiction is a brain disease'. Our findings point to the diverse ways in which the public understands and utilises this proposition. Interviewees readily accepted that drugs affect brain functioning but were ambivalent about whether to label addiction as a 'disease'. Contrary to the prediction of neuroscientific advocates and social science critics, acceptance of a neurobiological conception of addiction did not necessarily affect beliefs about addicted persons' responsibility for their addiction. We discuss the theoretical and applied implications of these findings. Theoretically, we examine the complexity surrounding how people adopt new knowledge and its role in reshaping ethical beliefs. We also discuss the implications of these findings for the ethics of communication of neuroscientific information to reduce stigma and enhance social support for the treatment of addicted individuals