Rock fractures transmit underground gas effectively once they have sufficient widths and interconnection. However, the fracture geometries needed for gas transport are strongly influenced by surrounding pressure conditions. In order to inspect and quantify the influence of surrounding pressure, we design and manufacture a set of gas flow apparatus that can be connected to the MTS815 material testing system, which provides loads and exhibits external pressures in the experiment. With the apparatus and MTS815, we test the fractured samples of sandstone and coal and obtain their relationship between permeability and external pressure. In particular, our permeability calculation based on collection of gas flux and pressure difference has involved the influence of non-Darcian flow. In addition, our study also includes a numerical simulation in the RFPA software platform to display the internal field changes of cracks. The results show that fracture permeability strongly depends on confining pressure, and a critical pressure probably occurs, about 1.5–2 MPa in our experiments, to split each of the permeability curves into two stages, a slow climb and an exponential rush. As a complement, the numerical simulation also demonstrates one more stage for the permeability curve, the post-rush steady fluctuation.

CO2-enhanced coalbed methane recovery, also known as CO2-ECBM, is a potential win-win approach for enhanced methane production while simultaneously sequestering injected anthropogenic CO2 to decrease CO2 emissions into the atmosphere. In this paper, CO2-ECBM is simulated using a coupled thermal–hydrological–mechanical (THM) numerical model that considers multiphase (gas and water) flow and solubility, multicomponent (CO2 and CH4) diffusion and adsorption, heat transfer and coal deformation. The coupled model is based on the TOUGH-FLAC simulator, which is applied here for the first time to model CO2-ECBM. The capacity of the simulator for modeling methane production is verified by a code-to-code comparison with the general-purpose finite-element solver COMSOL. Then, the TOUGH-FLAC simulator is applied in an isothermal simulation to study the variations in permeability evolution during a CO2-ECBM operation while considering four different stress-dependent permeability models that have been implemented into the simulator. Finally, the TOUGH-FLAC simulator is applied in non-isothermal simulations to model THM responses during a CO2-ECBM operation. The simulations show that the permeability evolution, mechanical stress, and deformation are all affected by changes in pressure, temperature and adsorption swelling, with adsorption swelling having the largest effect. The calculated stress changes do not induce any mechanical failure in the coal seam, except near the injection well in one case of a very unfavorable stress field.

An effective and safe operation for sequestration of CO2 in coal seams requires a clear understanding of injection-induced coupled hydromechanical processes such as the evolution of pore pressure, permeability, and induced caprock deformation. In this study, CO2 injection into coal seams was studied using a coupled flow-deformation model with a new stress-dependent porosity and permeability model that considers CO2-induced coal softening. Based on triaxial compression tests of coal samples extracted from the site of the first series of enhanced coalbed methane field tests in China, a softening phenomenon that a substantial (one-order-of-magnitude) decrease of Young's modulus and an increase of Poisson's ratio with adsorbed CO2 content was observed. Such softening was considered in the numerical simulation through an exponential relation between elastic properties (Young's modulus and Poisson's ratio) and CO2 pressure considering that CO2 content is proportional to the CO2 pressure. The results of the numerical simulation show that the softening of the coal strongly affects the CO2 sequestration performance, first by impeding injectivity and stored volume (cumulative injection) during the first week of injection, and thereafter by softening mediated rebound in permeability that tends to increase injectivity and storage over the longer term. A sensitivity study shows that stronger CO2-induced coal softening and higher CO2 injection pressure contribute synergistically to increase a significant increase of CO2 injectivity and adsorption, but also result in larger caprock deformations and uplift. Overall, the study demonstrates the importance of considering the CO2-induced softening when analyzing the performance and environmental impact of CO2-sequestration operations in unminable coal seams. © 2017 Society of Chemical Industry and John Wiley & Sons, Ltd.

As a complex two-phase flow in naturally fractured coal formations, the prediction and analysis of CBM production remain challenging. This study presents a discrete fracture approach to modeling coalbed methane (CBM) and water flow in fractured coal reservoirs, particularly the influence of fracture orientation, fracture density, gravity, and fracture skeleton on fluid transport. The discrete fracture model is first verified by two water-flooding cases with multi- A nd single-fracture configurations. The verified model is then used to simulate CBM production from a discrete fractured reservoir using four different fracture patterns. The results indicate that fluid behavior is significantly affected by orientation, density, and fracture connectivity. Finally, several cases are performed to investigate the influence of gravity and fracture skeleton. The simulation results show that gas migrates upwards to the top reservoir during fluid extraction owing to buoyancy and the connected fracture skeleton plays a dominant role in fluid transport and methane production efficiency. Overall, the developed discrete fracture model provides a powerful tool to study two-phase flow in fractured coal reservoirs.

This study presents the development and application of a fully coupled two-phase (methane and water) flow, transport, and poromechanics numerical model for the analysis of geomechanical impacts on coalbed methane (CBM) production. The model considers changes in two-phase fluid flow properties, i.e., coal porosity, permeability, water retention, and relative permeability curves through changes in cleat fractures induced by effective stress variations and desorption-induced shrinkage. The coupled simulator is first verified for poromechanics coupling, and simulation parameters of a CBM reservoir model are calibrated by history matching against one year of CBM production field data from Shanxi Province, China. Then, the verified simulator and the calibrated CBM reservoir model are used for predicting the impact of geomechanics on the production rate for twenty years of continuous CBM production. The simulation results show that desorption-induced shrinkage is the dominant process in increasing permeability in the near wellbore region. Away from the wellbore, desorption-induced shrinkage is weaker, and permeability is reduced by pressure depletion and increased effective stress. A sensitivity analysis shows that for coal with a higher sorption strain, a larger initial Young's modulus and a smaller Poisson's ratio promote the enhancement of permeability as well as an increased production rate. Moreover, the conceptual model of the cleat system, whether dominated by vertical cleats with permeability correlated to horizontal stress or with permeability correlated to mean stress, can have a significant impact on the predicted production rate. Overall, the study clearly demonstrates and confirms the critical importance of considering geomechanics for an accurate prediction of CBM production.

Live-attenuated Listeria monocytogenes has shown encouraging potential as an immunotherapy platform in preclinical and clinical settings. However, additional safety measures will enable application across malignant and infectious diseases. Here, we describe a new vaccine platform, termed Lm-RIID (L. monocytogenes recombinase-induced intracellular death), that induces the deletion of genes required for bacterial viability yet maintains potent T cell responses to encoded antigens. Lm-RIID grows normally in broth but commits suicide inside host cells by inducing Cre recombinase and deleting essential genes flanked by loxP sites, resulting in a self-limiting infection even in immunocompromised mice. Lm-RIID vaccination of mice induces potent CD8⁺ T cells and protects against virulent challenges, similar to live L. monocytogenes vaccines. When combined with α-PD-1, Lm-RIID is as effective as live-attenuated L. monocytogenes in a therapeutic tumor model. This impressive efficacy, together with the increased clearance rate, makes Lm-RIID ideal for prophylactic immunization against diseases that require T cells for protection.

Stimulator of interferon genes (STING) is a cytosolic receptor that senses both exogenous and endogenous cytosolic cyclic dinucleotides (CDNs), activating TBK1/IRF3 (interferon regulatory factor 3), NF-κB (nuclear factor κB), and STAT6 (signal transducer and activator of transcription 6) signaling pathways to induce robust type I interferon and proinflammatory cytokine responses. CDN ligands were formulated with granulocyte-macrophage colony-stimulating factor (GM-CSF)-producing cellular cancer vaccines--termed STINGVAX--that demonstrated potent in vivo antitumor efficacy in multiple therapeutic models of established cancer. We found that rationally designed synthetic CDN derivative molecules, including one with an Rp,Rp dithio diastereomer and noncanonical c[A(2',5')pA(3',5')p] phosphate bridge structure, enhanced antitumor efficacy of STINGVAX in multiple aggressive therapeutic models of established cancer in mice. Antitumor activity was STING-dependent and correlated with increased activation of dendritic cells and tumor antigen-specific CD8(+) T cells. Tumors from STINGVAX-treated mice demonstrated marked PD-L1 (programmed death ligand 1) up-regulation, which was associated with tumor-infiltrating CD8(+)IFNγ(+) T cells. When combined with PD-1 (programmed death 1) blockade, STINGVAX induced regression of palpable, poorly immunogenic tumors that did not respond to PD-1 blockade alone.

Nanoparticle-mediated mRNA delivery has emerged as a promising therapeutic modality, but its growth is still limited by the discovery and optimization of effective and well-tolerated delivery strategies. Lipid nanoparticles containing charged or ionizable lipids are an emerging standard for in vivo mRNA delivery, so creating facile, tunable strategies to synthesize these key lipid-like molecules is essential to advance the field. Here, we generate a library of N-substituted glycine oligomers, peptoids, and undertake a multistage down-selection process to identify lead candidate peptoids as the ionizable component in our Nutshell nanoparticle platform. First, we identify a promising peptoid structural motif by clustering a library of >200 molecules based on predicted physical properties and evaluate members of each cluster for reporter gene expression in vivo. Then, the lead peptoid motif is optimized using design of experiments methodology to explore variations on the charged and lipophilic portions of the peptoid, facilitating the discovery of trends between structural elements and nanoparticle properties. We further demonstrate that peptoid-based Nutshells leads to expression of therapeutically relevant levels of an anti-respiratory syncytial virus antibody in mice with minimal tolerability concerns or induced immune responses compared to benchmark ionizable lipid, DLin-MC3-DMA. Through this work, we present peptoid-based nanoparticles as a tunable delivery platform that can be optimized toward a range of therapeutic programs.