Formation Permeability Research Articles

A Grand Challenge: Update on Improved Recovery From Tight/Shale Reservoirs

_ This is the third of a series of six articles on SPE’s Grand Challenges in Energy, formulated as the output of a 2023 workshop held by the SPE Research and Development Technical Section in Austin, Texas. Described in a JPT article last year, each of the challenges will be discussed separately in this series: geothermal energy; net-zero operations; improving recovery from tight/shale resources; carbon capture, storage, and utilization; digital transformation; and education and advocacy. _ The exploration and extraction of hydrocarbons from tight or shale formations have revolutionized the global energy landscape, unlocking vast oil and gas reserves previously considered inaccessible. According to estimates, substantial oil production has been reported for various tight plays in the US in 2024 (Fig. 1). However, the production process in tight or shale formations is not without its own set of challenges ranging from technological hurdles to environmental concerns. Therefore, understanding the current outlook is essential for stakeholders to navigate the complex terrain. To address the significant issues outlined by SPE in July 2023 (Halsey et al. 2023), this article intends to explore the complexities of hydrocarbon extraction from tight and shale reservoirs. Description of Tight/Shale Formations First, we present a succinct description of tight or shale formations. Tight or shale oil and gas are hydrocarbons found in oil-bearing mudstone, and shale gas is produced from gas shale or associated with tight oil (Boak and Kleinberg 2020). Tight unconventional formations are characterized by the presence of fine-grained sedimentary rocks that are high in organic matter, such as shale, where hydrocarbons are firmly embedded within the rock matrix. Challenges in Tight or Shale Oil Production The Existence of Complex Geometry. Tight and shale formations are known for their complex geological structures, which can make it difficult to predict the distribution and behavior of hydrocarbons within the reservoir. Additionally, shale formations can exhibit significant variability in their thickness, composition, and the occurrence of natural fractures. Hence, it is crucial to understand and navigate the intricate geology of unconventional shale formations to achieve successful shale oil production (Jiang et al. 2016). Ultralow Reservoir Permeability. The low permeability of tight formations restricts the flow of hydrocarbons, necessitating techniques such as hydraulic fracturing to create artificial pathways for extraction. However, the effective stimulation of fractures requires the use of cutting-edge drilling and extraction methods, such as multistage hydraulic fracturing (fracking) and horizontal drilling, which in turn require precise engineering and a thorough understanding of reservoir characteristics (Pokalai et al. 2015).

Optimizing cluster spacing in multistage hydraulically fractured shale gas wells: balancing fracture interference and stress shadow impact

Horizontal drilling and multistage hydraulic fracturing have seen widespread application in shale formations during the past decade, leading to significant economic productivity gains through the creation of extensive fracture surfaces. The determination of the ideal cluster spacing in shale gas wells is contingent upon the unique geological and formation characteristics. Generally, reducing the spacing between clusters has the potential to augment gas recovery, albeit at the expense of higher drilling and completion costs, as well as the influence of stress shadows on fracture propagation. This study introduces an integrated methodology designed to explore the impact of cluster interference on well performance. Commencing with a fracture propagation model accommodating stress shadow effects for an equivalent slurry volume injection, analytical rate transient analysis (RTA) was amalgamated with reservoir numerical simulation to compute the effective fracture surface area (Aca.) for hydrocarbon production. The correlation between the effective fracture surface area determined by RTA and the actual stimulated fracture area (Aca.) derived from numerical simulations was established in relation to cluster spacing. The findings of this research reveal that wells featuring a greater number of stages and tighter cluster spacing tend to exhibit elevated cluster interference, resulting in a lower effective-to-actual fracture surface area ratio and heightened stress shadow effects impeding fracture propagation. A cluster spacing of 33 feet with six clusters per stage emerges as the optimal choice at formation permeability of 0.00005 md that decreased to 18 ft at formation permeability of 0.00001 md. ACe either stabilizes or decreases above the optimal value, suggesting that more clusters would not have a major impact on increasing the effective stimulated area. Allowing 20% interference, regardless of the permeability of the formation, maximized cumulative production while preventing thief zones and excessive cluster interference. The insights gained from this study will serve as a valuable resource for completion and reservoir engineers, enabling them to fine-tune cluster spacing to maximize well revenue in the dynamic landscape of shale gas extraction.

Bacterial discrimination by Fourier transform infrared spectroscopy, MALDI-mass spectrometry and whole-genome sequencing.

Aim: Proof-of-concept study, highlighting the clinical diagnostic ability of FT-IR compared with MALDI-TOF MS, combined with WGS. Materials & methods: 104 pathogenic isolates of Neisseriameningitidis, Streptococcus pneumoniae, Streptococcus pyogenes and Staphylococcus aureus were analyzed. Results: Overall prediction accuracy was 99.6% in FT-IR and 95.8% in MALDI-TOF-MS. Analysis of N. meningitidis serogroups was superior in FT-IR compared with MALDI-TOF-MS. Phylogenetic relationship of S. pyogenes was similar by FT-IR and WGS, but not S. aureus or S. pneumoniae. Clinical severity was associated with the zinc ABC transporter and DNA repair genes in S. pneumoniae and cell wall proteins (biofilm formation, antibiotic and complement permeability) in S. aureus via WGS. Conclusion: FT-IR warrants further clinical evaluation as a promising diagnostic tool.

Hydrogeochemical and isotopic characterization of the main karst aquifers of the middle Valseriana (Northern Italy): Nossana and Ponte del Costone springs

Karst springs are one of the most exploited drinking water resources in the world. Isotopic and chemical analyses on these waters reveal essential insights into their hydrodynamics. Valseriana (Northern Italy) is a valley within the Italian Pre-Alps, characterized by high water availability. The main reasons are a bedrock consisting of very permeable carbonate formations and a mean annual precipitation above 1800 mm/y. In this context, the Valseriana spring catchments have become strategically important for the water exploitation and the domestic supply of Bergamo and the neighboring municipalities. This study general aim is to expand the knowledge on the two main karst systems (Nossana and Ponte del Costone), which together include twenty-three major and minor springs, by defining a state-of-the-art that will be useful in future decades to preserve this crucial resource. Specific objectives include i) verifying the applicability of the 3H/3He dating method in karst environments, ii) defining groups of springs according to their chemical and isotopic characteristics for possible safeguard actions, and iii) establishing a conceptual model of the internal dynamics of the two spring systems. A chemical and isotopic sampling campaign was specifically conducted between May 2018 and July 2019. A total of 34 water points were sampled, including natural springs, rivers, wells, karst caves, and nearby mines. Water sampling for 3H/3He isotopic analyses was proved possible through careful selection of the sampling points and the insertion of the pump tubing in the spring fractures. A first classification of springs into uniform hydrochemical groups was obtained by applying the hierarchical cluster analysis technique on major ions contents. These outputs were combined with information from the 3H/3He dating analyses and resulted in three different classes of springs. The three classes showed a clustering for elevations: at high, medium, and valley bottom elevations, respectively. Finally, the elaborations simplified the two karst systems by a hierarchical flow system model, dynamically controlled by different karst network development and infiltration water.

Preparation and performance evaluation of intelligent plugging agent for thermo‐sensitive water‐based drilling fluid

AbstractIn the process of unconventional oil and gas exploitation, the invasion of a large amount of drilling fluid into the formation is one of the most critical reasons leading to wellbore instability. A temperature‐sensitive polymer (AOS) was synthesized from acrylamide, oligo (ethylene glycol) methyl ether methacrylate (OEGMA), and sodium p‐styrene sulfonate by emulsion polymerization. The material is a solid‐free fluid with good fluidity at room temperature, after injection into the formation, the fluid is gradually transformed into hard gel above the lower critical solution temperature (LCST) (90°C), thus blocking micro‐fractures and improving wellbore stability. Infrared and NMR characterization confirmed the successful preparation of the target product. The transmittance of AOS with ambient temperature was measured by UV–vis spectrophotometer, and the LCST behavior of AOS was verified by rheological and viscoelastic measurements. The interaction mechanism between AOS and sodium bentonite was evaluated according to the American Petroleum Institute standard. The results show that after aging at 180°C, the filtration loss is reduced by 93%, and the medium permeability (100, 200 mD) formation is effectively plugged, with a plugging efficiency is as high as 74.7%.

Critical pressure (Pc) and critical temperature (Tc) of Midra shale

The critical pressure (Pc) and critical temperature (Tc) of shale gas depend on the characteristic pore size because of the importance of fluid–rock interactions in the matrix. This size dependency is neglected in highly permeable formations, where gas composition is only implemented because the fluid–fluid interactions are dominant. This study determines the critical properties by accounting for the characteristic pore size in the shale matrix and gas composition. The analyzed components are carbon dioxide, ethane, methane, n-butane, nitrogen, pentane, and propane. It shows that the bulk properties overestimate the actual critical properties. The overestimation varies between 15 and 26% in a uniform 5 nm conduit with a circular cross section, and it increases nonlinearly when decreasing the conduit size. Overestimation versus size is presented to provide a convenient tool for correcting the existing data. This study also determines the critical properties of Midra shale by accounting for the pore-throat size and pore-body size distributions. The former distribution is based on the mercury injection capillary pressure measurements of eight samples, whereas the latter is based on the nitrogen adsorption measurements of six samples. This study indicates that common bulk properties overestimate the critical properties of the studied shale between 5 and 22%. The results have applications in characterizing multiphase transport in shale gas reservoirs.

Pathways and Environmental Impacts of Methane Migration: Case Studies in the Marcellus Shale, USA

Gas migration incidents, particularly stream contamination cases, have been rarely investigated and gone through the peer review process, with the exception of three sites in northeast Pennsylvania (Dimock and two Sugar Runs in Lycoming and Bradford counties, respectively) where air emission surveys, dissolved methane measurements, and structural (hydro)geologic interpretations have been used to demonstrate potential environmental impacts due to shale gas operations. In addition to reviewing previously published work from these three sites, we report and analyze unpublished new data trying to determine if a direct relationship between methane migration, stream contamination, and air emissions exists at those sites. Our analysis indicates that subsurface methane migration, stream methane contamination, and air emissions might not be all present or detectable at a faulty/leaky shale gas well. Which of these signs of contamination, if any, exist is largely controlled by the local (hydro)geologic conditions. In each case, the most likely migration pathway was from gas charged zones up well annular spaces to confined permeable formations, then laterally to a direct discharge or by vertically controlled joints to streams, water wells, and the atmosphere. The confining units act as barriers to the buoyant movement of stray gases, allowing subsurface travel of gas for 1–4 km from a leaky gas well. The knowledge we learn from these three sites can guide the future investigations of methane contamination cases in other regions.

Modeling gas flow in low-permeability formations: An efficient combination of mixed finite elements and high order time integration schemes

Numerical simulation of gas flow in low permeability formations is a challenging task due to the high nonlinearity induced by (i) the compressibility of the gas, (ii) the Klinkenberg slippage effect and (iii) the Langmuir adsorption of the gas on the pore surface. Because of these nonlinearities, modeling gas flow in low permeability formations requires a great deal of computational effort. In this work, we develop an efficient numerical model using advanced spatial and temporal discretization methods for a simultaneous solution of the coupled equations of gas flow, cubic Peng-Robinson equation of state, slippage effect and Langmuir adsorption. The spatial discretization is performed with the lumped hybrid formulation of the mixed finite element method which is well adapted for fluid flow in heterogeneous porous media. The time integration is performed with high-order methods via the method of lines (MOL) which allows large time steps and efficient solution of the nonlinear system of equations. Numerical experiments, performed for gas extraction in a heterogeneous domain, point out the high efficiency of the new model since it can be until 10 times more efficient than the classical first-order time discretization method. Results of global sensitivity analysis show that the intrinsic gas-phase permeability and the Klinkenberg factor are the most influential parameters controlling the pumping rate in the case of gas extraction in a homogeneous domain.

Evaluation of underground gas storage capacity in the depleted gas reservoir with water evaporation and salt precipitation

Water evaporation and salt precipitation will occur in gas reservoirs and underground gas storage (UGS) with high-salinity formation water during production and operation. This phenomenon seriously affects the efficient and safe operation and gas storage capacity. This work focuses on quantitatively evaluating the UGS capacity based on depleted gas reservoirs considering water evaporation and salt precipitation. The core flooding experiments are conducted to analyze the influence of water evaporation and salt precipitation on rock properties under different water salinity during multi-cycle injection-production. A numerical model considering water evaporation is established to determine the salt precipitation radius around the gas well. According to the experimental and simulation results, a new analytical model is developed to calculate the underground natural gas storage capacity based on material balance principles. The field case study is presented to show the practical potential of the established model. Both formation porosity and permeability in near-well region may be finally improved by water evaporation and salt precipitation under irreducible water condition. In the presence of movable-water, formation porosity and permeability of the near-well region may be firstly improved and finally reduced due to continuous salt precipitation in porous media. Salt-precipitation radius achieves 28.5 m after ten cycles. The UGS capacity is 101.11 × 108 m3 without considering salt precipitation, 1.11% higher than original geological reserves. The UGS capacity considering both irreducible-water evaporation and salt precipitation is 101.03 × 108 m3. However, when the moveable-water evaporation volume increases to 15Virr, the final UGS capacity is further decreased to 98.55 × 108 m3. The UGS capacity has decreased by 0.82%, 1.64%, and 2.45% compared with irreducible water. The continuous evaporation of movable water and salt deposition will reduce the gas storage capacity and cause damage to the UGS. This work provides an effective method to investigate the quantitative impact of water evaporation and salt precipitation on UGS capacity.

Prediction of the Effects of Pulsating Hydraulic Fracturing on the Porous Structure and Permeability of Coal Based on NMR and AE Spectra.

Pulsating hydraulic fracturing has been an environmentally friendly method to improve the permeability of rock formations to stimulate gas production and reduce hazard risks. It has the advantage of fracturing the reservoir with lower cracking pressure and less water volume, as the mechanical strength of rock materials has been reduced by the hydraulic pulse pressure. Many researchers have found significant changes in hard rocks after cyclic loading. However, the existing work still cannot clearly explain the mechanism of the rock damage by pulsating hydraulic fracturing within a short-time experiment. To solve the issue, an investigation of the effects of pulsating hydraulic fracturing on CBM production has been carried out in lab and field applications. Results indicate that the long-term hydraulic pulse pressure can cause a linear decline in cracking pressure directly measured in the lab. It plays an essential role in the permeability enhancement by generating more flow channels for CBM production. The low-field NMR quantitatively evaluates the increase in porosity, which reveals significant incremental ratios of over 20% in the porosity of macropores, mesopores, and micropores of coal caused by fatigue damage. It is first proven that hydraulic pulse pressure has a significant influence on the porosity components of macropores, mesopores, and micropores. To validate the effectiveness of the technique on the field scale, a field application of pulsating hydraulic fracturing has been carried out in a coal mine. It shows that gas production has been largely enhanced with a long and stable production stage and higher gas flux after the applied pulsating load. The gas concentration and gas flux of the fractured boreholes are about 2 times that of the nonfractured boreholes. This work provides an investigation of the effects of pulsating hydraulic fracturing on CBM production, which gives a better understanding of the mechanism for the engineers in the field.

Building responses to soil removal, dewatering, and artificial recharge during deep excavation in water-rich sandy strata

In water-rich sandy strata, deep excavations necessitate dewatering within the excavation site, leading to significant groundwater drawdowns and surface subsidence behind walls, which can result in severe damage to adjacent buildings. Nonetheless, the individual impacts of soil removal and dewatering in such permeable sandy formations on building responses remain ambiguous,with scant reported protective experience in literature. This study introduces a validated three-dimensional fluid-solid coupling finite-element model to simulate the construction of an 18-19.8 m deep subway station in Nantong, China. Artificial recharge was applied to mitigate adverse effects on nearby buildings caused by drainage. The investigation explores the separate effects of soil removal, dewatering, and water recharging on the settlements of buildings with three different foundations (natural, raft, and piled footings). Additionally, the influence of post-recharging groundwater levels on building responses was scrutinized. The present findings indicate that discharging confined aquifers significantly contributes to building settlements, while artificial recharge can substantially reverse the deformations in buildings, especially those with natural and raft foundations. As excavation depth and the bearing capacity of the building foundation increase, the relative impact of soil removal on building settlements grows, whereas the influence of dewatering diminishes. Compared to enhancing foundation-bearing capacity, artificial recharge emerges as a more cost-effective strategy to safeguard pre-existing buildings near deep excavations in water-rich sandy strata, provided the post-recharging groundwater levels achieve a certain threshold.

Investigating ZMP Accumulation in C2C12 Myotubes with AICAR and Prodrug-39

5’Adenosine monophosphate (AMP) is a signaling molecule and a known regulator of enzymes in glycolysis, glycogen breakdown, and may play a role in regulating protein synthesis. It is also a known activator of AMP-dependent protein kinase (AMPK), a key energy sensor within the cell. Activation of AMPK has been linked to the regulation of mitochondrial biogenesis, upregulation of BCAA catabolism, and increased skeletal muscle glucose uptake and fatty acid oxidation. AMPK can be activated pharmacologically with 5-Aminoimidazole-4-carboxamide ribonucleoside (AICAR), an adenosine analogue. AICAR enters the cell through adenosine transporters and undergoes phosphorylation by Adenosine Kinase forming AICAR monophosphate (ZMP). Unfortunately, the poor bioavailability of AICAR limits its use pharmacologically. Prodrug-39 (P39) is comprised of ZMP with a 4-nitrophenol group to allow membrane permeability and subsequent ZMP formation without the need of membrane transporters. We investigated the ZMP accumulation in C2C12 myotubes following exposure to different concentrations of P39 or AICAR. Based on preliminary data, we hypothesized that AICAR treatments would be more effective at producing ZMP over short periods of time and when treatment concentrations were high, but that P39 treatments would result in greater and more consistent ZMP accumulation over longer periods of time when treatment concentrations were low. We first measured the absorbance of 4-nitrophenol (4NP) within the cell media to determine phosphodiesterase cleavage of P39. Nitrophenol absorbance was 3.9 times higher at 1000 μM compared to 100 μM treatment of P39 after 15 minute incubation, and 13.3 times higher at 11 hours. The nitrophenol absorbance per hour increased linearly between 250 μM to 1000 μM of P39. Adenine nucleotide content and ZMP accumulation in treated cells was determined following organic protein extraction and UV-Vis ultra-performance liquid chromatography (UPLC). After 13 hours of treatment with 500 μM AICAR or P39, ZMP accumulation was 14 fold higher following AICAR treatment compared to P39 (59.7±5.0 vs 4.2±0.1 μmol/g protein). Interestingly, ZMP accumulation was not different between 100 μM treatments (5.6±1.3 vs. 5.7±1.5 μmol/g protein). This suggests that phosphodiesterase cleavage of P39 is likely the limiting factor for ZMP accumulation. Interestingly, while ZMP accumulation following 13 hour incubation with 100 μM AICAR or P39 was not different, ATP content was approximately 50% higher in P39 treated cells (33.7±5.8 vs. 51.0±5.8 μmol/g protein). While the measurement of ZMP accumulation at very low treatment concentrations (10 μM) is very diffcult, P39 exposure for 1 to 1.5 hours resulted in a 3 to 8 fold increase in ZMP content compared to AICAR. This data illustrates the potential for P39 as a drug capable of accumulating greater ZMP than AICAR at very low treatment concentrations, however the capacity of phosphodiesterase activity may limit the application of this drug. This work was funded by a grant from Skylark Biosciences. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Liposomal Nanocarriers of Preassembled Glycocalyx Restore Venular Permeability in Sepsis: Assessed Quantitatively with a Novel Microchamber System

Background: The endothelial glycocalyx (EG), covering the luminal side of endothelial cells, regulates vascular permeability and senses wall shear stress. In sepsis, EG undergoes degradation leading to increased permeability and edema formation. We hypothesized that restoring EG integrity using liposomal nanocarriers of preassembled glycocalyx (LNPG) will restore normal venular permeability in a lipopolysaccharide (LPS)-induced sepsis model of mice. Methods: To test this hypothesis, we designed a unique perfusion microchamber in which the vascular permeability of isolated and cannulated mice mesenteric venules could be assessed by measuring the concentration of Evans blue dye (EBD) by fluorescent spectroscopy in microliter-samples of extravascular solution (ES). Results: Histamine-induced time- and dose-dependent increases in EBD in the ES could be measured, confirming the sensitivity of the microchamber system. Notably, the histamine-induced increase in permeability was significantly attenuated by histamine receptor (H1) antagonist, triprolidine hydrochloride. Subsequently, mice were treated with LPS, or LPS + LNPG. Compared to control mice, venules from LPS-treated mice showed a significant increased permeability, which was significantly reduced by LNPG administration. Moreover, in the presence of wall shear stress, intraluminal administration of LNPG significantly reduced the permeability in isolated venules from LPS-treated mice. Conclusion: Our newly developed microchamber system can quantitatively measure the permeability of isolated venules. LPS-induced sepsis increases permeability of venules that is attenuated by in vivo LNPG administration, which is also reestablished endothelial vasomotor responses to shear stress. Thus, LNPG presents a promising therapeutic potential for restoring EG function and thereby mitigating the increased permeability in sepsis. Support: National Institute of Health [grant number: HL144528, Dong Sun] and the Uehara Memorial Foundation [grant number: 202241049, Shinya Ishiko) and Hungarian Academy of Sciences Post-Covid 2021-34 (AK) and MIT of Hungary, National Research, Development, and Innovation Fund, OTKA K 132596 (AK). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Research on the helium seepage mechanism in the strata surrounding bedded salt cavern helium storage and its tightness evaluation

To improve the safety and scale of helium storage, large-scale or strategic helium storage in underground salt caverns can be implemented. Salt caverns leached from bedded salt formations have been considered as potential underground storage sites for helium in China. However, the salt formations are typical lacustrine sedimentary rocks with an interbedded structure, thus the sealing feasibility of such salt caverns must be evaluated before they can be used. To this end, the helium seepage equation in deep strata and permeability evolution function are derived with the help of experimental results and theoretical analysis. Based on these, a helium seepage model considering slippage effect and threshold pressure gradient is proposed to evaluate the sealing properties of salt caverns for helium storage. The analysis results indicate that it is feasible to use bedded salt mine formations for helium storage when the formations permeability parameters and reservoir design parameters meet the long-term tightness evaluation criteria, including permeability, porosity, salt pillar width, salt roof thickness and operating pressure and duration. More importantly, specific recommendations are provided for the operation parameters, design parameters and formation permeability thresholds of salt caverns for ensuring helium storage safety while maintaining stable cavern operations. The threshold permeability of the target salt formations should be approximately 1 × 10−18 m2 to ensure tightness. The minimum and maximum operating pressure are recommended to be 10 MPa and 18 MPa respectively for 50 years of this helium storage. The salt pillar width should be 300 m, and the salt roof thickness should be 40 m.

Application of ultra-fine particles of potato as eco-friendly green additives for drilling a borehole: A filtration, rheological and morphological evaluation

Drilling fluid is crucial for oil and gas well drilling operations, serving key functions such as facilitating the removal of drill cuttings, maintaining borehole stability and controlling formation pressures. When the drilling fluid is lost into formations, it can alter the formation's integrity, contaminate groundwater and cause permeability damage. In addition, environmental concerns arise from the waste produced during drilling activities, particularly when discarded drilling fluids contain hazardous substances like heavy metals. This study explores the potential of integrating ultrafine potato powder (PP) into water-based drilling fluids (WBDFs) as environmentally friendly additives. Several analytical techniques including X-ray fluorescence (XRF), Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), scanning electronic microscope (SEM) and differential scanning calorimetry (DSC) were used to comprehensively characterize the prepared PPs. The study included API and HPHT filtration test, permeability plugging test and rheological evaluations of drilling fluids, assessing parameters such as filter loss, filter cake, apparent viscosity, plastic viscosity, yield point and gel strength under varied conditions of different particle sizes of PP, concentrations of PP, and temperature and pressure measurements. The obtaining results emphasize PP's potential to enhance the wellbore stability and reduce the fluid loss, the filtration of water or oil into the permeable formation, achieving 43% reduction in the filtration rate and 70% reduction in the filter cake thickness. Adding 0.5 wt% ultrafine PP improved the maximum gel strength to 32.2 lb/100 ft2, while the same concentration and particle size raised the plastic viscosity from 3 to 6.8 cP, which subsequently dropped to 6 cP in high temperature conditions. PP performed better compared with the reference fluid in improving the thinning behavior of the drilling fluids. Moreover, permeability plugging tests confirm that adding PP effectively lowered the filtration rate, with higher concentrations achieving greater reductions over time. These findings suggest that PP holds promise as an effective additive for drilling fluids, contributing to enhanced drilling efficiency, improved wellbore stability and a reduced likelihood of instability and lost circulation. The characterization and rheological analysis of PP biodegradable drilling fluids provide valuable insights for optimizing fluid formulations, tailoring them to specific operational conditions, and achieving a balance between fluidity, wellbore stability, and cuttings transport. This research highlights the potential of PP as a sustainable and efficient solution in the realm of drilling fluid additives.

Understanding Plugging Agent Emplacement Depth with Polymer Shear Thinning: Insights from Experiments and Numerical Modeling

Polymer-plugging agents are widely employed in profile control and water-plugging measures, serving as a crucial component for efficient reservoir development. However, quantitatively monitoring the emplacement depth of polymer-plugging agents in low-permeability and high-permeability layers remains a challenging bottleneck. Presently, insufficient attention on shear thinning, a critical rheological property for water shut-off and profile control, has limited our understanding of polymer distribution laws. In this study, polymer shear-thinning experiments are firstly conducted to explore polymer variations with flow rate. The novelty of the research is that varying polymer viscosity is implemented instead of the fixed-fluid viscosity that is conventionally used. The fitted correlation is then integrated into the 2D and 3D heterogeneous numerical models for simulations, and a multivariate nonlinear regression analysis is performed based on the simulation results. The results show that lower polymer emplacement depth ratios corresponded to higher viscosity loss rates under the same flow rate. An increase in the initial permeability ratio corresponds to a decrease in the emplacement ratio, along with a reduction in the fraction of the plugging agent penetrating the low permeability formations. The model was applied to the Kunan Oilfield and demonstrated a polymer reduction of approximately 3000 tons compared to traditional methods. Despite the slightly complex nature of the multivariate nonlinear mathematical model, it presents clear advantages in controlling plugging agent distribution and estimating dosage, laying good theoretical ground for the effective and efficient recovery of subsurface resources.

Laboratory Investigation on Permeability Change and Economic Analysis Using Some Selected Nanoparticles for Enhanced Oil Recovery

Enhanced oil recovery using nanoparticles is an emerging technique that can potentially alter permeability and wettability of porous media for improved oil mobilization. This study experimentally investigates the permeability alteration caused by three commonly used nanoparticle types – copper (ii) oxide, zinc oxide and silicon oxide. Core flooding experiments were conducted on reservoir rock samples before and after treatment with nanoparticle dispersions. Results show decrease in permeability by 35% for copper (ii) oxide, 30% for zinc oxide and 10% silicon oxide respectively. Pore-scale analysis indicates that permeability change occurs through mechanisms like pore throat blocking/wettability alteration. Nanoparticle concentration is also found to influence the permeability variation, with optimal dosage. Among the systems tested, Silicon oxide is the most effective formulation for enhancing oil recovery applications based on its ability to recover oil with minimal alteration to formation permeability. From the result, Silicon oxide had a cumulative recovery of 17ml, 18.0ml and 18.5ml thereby generating a percentage recovery of 73.91%, 78.26% and 80.43% while Zinc oxide had a cumulative recovery of 15.5ml, 18.0ml and 16.5ml thereby generating a percentage recovery of 77.50%, 78.26% and 71.74ml%, lastly Copper (ii) oxide had a cumulative recovery of 16.5ml, 17.0 and 16.0 generating a percentage recovery of 75%, 73.91% and 72.72% respectively with a concentration of 0.1%, 0.3%, and 0.5%. This study demonstrates the potential of Silicon oxide nanoparticles for enhanced oil recovery through permeability manipulation in porous media, however, the economic analysis shows that it’s quite expensive due to its cost of production and won’t be ideal for use. Hence Zinc oxide which also has a high volume of oil recovery, and less production cost can be used.

Abstract P05: Novel PROTAC-based EZH2 Degraders Effectively Target Lymphoid Malignancies by Depleting Enzyme-Independent Functions of EZH2

Abstract Overexpression or mutation of the epigenetic silencer EZH2 correlates with invasive cancer growth, resistance, and poor survival outcomes. Previously, we have established a methylation-independent role for EZH2 in the transcriptional activation of oncogenes in NKTL. As EZH2 enzymatic inhibitors have proven ineffective against NKTL, we embarked on the development of novel EZH2 Proteolysis Targeting Chimera (PROTAC) compounds. EZH2 PROTACs consist of an EZH2- and E3-ligase binding domain which promotes targeted ubiquitination of the EZH2 protein thereby marking it for proteasomal degradation. Our initial efforts focused on the iterative synthesis of EZH2 PROTAC candidates optimizing factors such as permeability, solubility and stable ternary complex formation. Through extensive screening, we identified C2911 and C1311, which successfully trigger the dose-dependent degradation of EZH2 and PRC2 components concomitant with a significant loss of survival and induction of apoptosis in both NKTL and DLBCL. These effects were rescued by pre-treatment with proteasome inhibitor Bortezomib or when E3 ligase activity was disrupted through siRNA knockdown. In NKTL, we show that EZH2 PROTAC treatment decreased JAK3 and phospho-STAT5 protein expression and identified the suppression of the JAK-STAT-MYC axis as a potential mechanism of action. EZH2 PROTAC treatment effectively reactivates transcription of canonical EZH2 target genes such as MYT1 and ANPEP and downregulates expression of oncogenes c-Myc and E2F1. Pharmacokinetic studies in vivo demonstrate that these PROTACs exhibit good plasma stability, half-life (>4h) and low clearance thereby establishing potential for future clinical development. The efficacy of EZH2 PROTACs in xenograft mice are currently being evaluated. Collectively, our data supports the discovery of novel EZH2 PROTACs and the critical role it plays in successfully targeting the oncogenic role of EZH2 in NKTL or other non-canonical EZH2-driven cancers through protein depletion where enzymatic-only inhibition was ineffective. We are further investigating the mechanisms stabilizing EZH2 protein levels to enhance PROTAC-mediated cytotoxicity. Citation Format: Nurulhuda Mustafa, Zubaida Talal Alnaseri, Darrel Tan Egk Jian, David Quach Thanh Truong, Wan Hsin Lim, Wee Joo Chng. Novel PROTAC-based EZH2 Degraders Effectively Target Lymphoid Malignancies by Depleting Enzyme-Independent Functions of EZH2 [abstract]. In: Proceedings of Frontiers in Cancer Science; 2023 Nov 6-8; Singapore. Philadelphia (PA): AACR; Cancer Res 2024;84(8_Suppl):Abstract nr P05.

Oxidized guanosines induce mitochondrial dysfunction and loss of viability in β-cells

The production of reactive oxygen species and oxidative stress promote β-cell dysfunction and impair insulin secretion, thereby contributing to the pathogenesis of type 2 diabetes mellitus (T2DM). The nucleobase guanine is highly sensitive to oxidation, which results in the formation of 8-oxoguanosine (8oxoG) and 8-oxodeoxyguanosine (8oxodG). The urinary excretion of 8oxoG is associated with the risk of mortality in people with T2DM, including from diabetic complications such as cardiovascular disease. However, the cellular mechanisms responsible for this association are poorly defined. Therefore, in this study, we examined the effect of 8oxoG, 8oxodG and other oxidized guanosine derivatives, on the INS-1E β-cell line. Exposure of INS-1E cells to 8oxoG and 8oxodG decreased metabolic activity and promoted cell death by apoptosis. The change in cell viability was similar to that induced by treatment of INS-1E cells with the inflammatory cytokines interleukin 1β (Il-1β) and tumour necrosis factor α (TNFα). Changes in mitochondrial membrane permeability and superoxide radical formation were also observed with 8oxoG, but there was no significant change in the oxidation state of mitochondrial cytochromes or hydrogen peroxide levels in the INS-1E cells. Interestingly, exposure to 8oxoG and 8-oxodG also increased the mRNA expression of stress response genes, including NADPH dehydrogenase quinone 1 (NQO1), and thioredoxin-interacting protein (TXNIP). Together, these results support a potential role of oxidized guanosine derivatives in the induction of β-cell dysfunction, which could be relevant to the pathogenesis of T2DM.

Dietary vitamin A modifies the gut microbiota and intestinal tissue transcriptome, impacting intestinal permeability and the release of inflammatory factors, thereby influencing Aβ pathology.

Alzheimer's disease (AD) is an age-related neurodegenerative disorder with no effective interventions for curing or modifying its progression. However, emerging research suggests that vitamin A in the diet may play a role in both the prevention and treatment of AD, although the exact mechanisms are not fully understood. This study aims to investigate the dietary vitamin A modifies the gut microbiota and intestinal tissue transcriptome, impacting intestinal permeability and the release of inflammatory factors, thereby influencing Aβ pathology shedding light on its potential as a dietary intervention for AD prevention and treatment. The APP/PS1-AD mouse model was employed and divided into three dietary groups: vitamin A-deficient (VAD), normal vitamin A (VAN), and vitamin A-supplemented (VAS) for a 12-week study. Neurobehavioral functions were assessed using the Morris Water Maze Test (MWM). Enzyme-linked immunosorbent assay (ELISA) was used to quantify levels of Diamine Oxidase (DAO), D-lactate, IL-6, IL-1β, and TNF-a cytokines. Serum vitamin A levels were analyzed via LC-MS/MS analysis. Immunohistochemical analysis and morphometry were performed to evaluate the deposition of Aβ in brain tissue. The gut microbiota of APP/PS1 mice was analyzed using 16S rRNA sequencing analysis. Additionally, transcriptomic analysis was conducted on intestinal tissue from APP/PS1 mice. No significant changes in food intake and body weight were observed among the groups. However, the VAD and VAS groups showed reduced food intake compared to the VAN group at various time points. In terms of cognitive function, the VAN group performed better in the Morris Water Maze Test, indicating superior learning and memory abilities. The VAD and VAS groups exhibited impaired performance, with the VAS group performing relatively better than the VAD group. Serum vitamin A concentrations differed significantly among the groups, with the VAS group having the highest concentration. Aβ levels were significantly higher in the VAD group compared to both the VAN and VAS groups. Microbial analysis revealed that the VAS and VAN groups had higher microbial diversity than the VAD group, with specific taxa characterizing each group. The VAN group was characterized by taxa such as Actinohacteriota and Desulfovibrionaceae, while the VAD group was characterized by Parabacteroides and Tannerellaceae. The VAS group showed similarities with both VAN and VAD groups, with taxa like Desulfobacterota and Desulfovibrionaceae being present. The VAD vs. VAS, VAD vs. VAN, and VAS vs. VAN comparisons identified 571, 313, and 243 differentially expressed genes, respectively, which associated with cellular and metabolic processes, and pathway analysis revealed enrichment in pathways related to chemical carcinogenesis, drug metabolism, glutathione metabolism, and immune-related processes. The VAD group exhibited higher levels of D-lactate, diamine oxidase, and inflammatory cytokines (TNF-a, IL-1β, IL-6) compared to the VAN and VAS groups. Dietary vitamin A supplementation modulates the gut microbiota, intestinal permeability, inflammatory factors, and Aβ protein formation, offering insights into the pathogenesis of AD and potential therapeutic avenues for further exploration. This research highlights the intricate interplay between diet, gut microbiota, and neurodegenerative processes, emphasizing the importance of dietary interventions in managing AD-related pathologies.