EVALUATION OF NOVEL PREFORMED PARTICLE GELS FOR CONFORMANCE CONTROL AND ACID STIMULATION THROUGH CORE FLOODING TESTS

Acid stimulation and conformance control are two major methods to improve oil production. This study systematically evaluates two newly developed gels: Degradable Preformed Particle Gel (DPPG) and Re-crosslinkable Preformed Polymer Gel (RPPG). DPPG is designed to be a temporary plugging agent for acid stimulation and can self-degrade into a water-like fluid. RPPG is designed for reservoir sweep efficiency improvement and can re-crosslink to each other and form an immobile bulk gel after being placed in fractures or fracture-like conduits. For DPPG, this study evaluates the effect of monomer, crosslinker, and initiator concentration on the swelling and degradation performance. Results show that DPPG can swell up to 70 times its original size by absorbing water and can self-degrade in 10% HCl at 80 °C. Core flooding reveals that DPPG can serve as an excellent diverter for acid stimulation while it has very little damage to matrix after degradation. For RPPG, this study evaluates the fiber types and concentrations, swelling ratio, and fracture width effect on the injection pressure, water breakthrough pressure, and residual resistance factor (Frr). Results show that fiber can increase RPPG strength with an optimized fiber concentration. With increasing swelling ratio, the stable gel injection pressure decreases and water breakthrough pressure and Frr increases. Dehydration study reveals that the water content change significantly affects the RPPG properties. The dehydration behavior is related to the dehydration time which is related to the gel injection rate. Results show that at lower gel injection rate, the dehydration increases along the fracture, but decreases at higher gel injection rate --Abstract, p. i

Study on Apparent Permeability Model for Gas Transport in Shale Inorganic Nanopores

Inorganic nanopores occurring in the shale matrix have strong hydrophilicity and irreducible water (IW) film can be formed on the inner surface of the pores making gas flow mechanisms in the pores more complex. In this paper, the existence of irreducible water (IW) in inorganic pores is considered, and, based on the Knudsen number (K (Formula presented.)) correction in shale pores, a shale gas apparent permeability model of inorganic nano-pores is established. The effect of the K (Formula presented.) correction on the apparent permeability, the ratio of flow with pore radius and the effect of IW on the apparent permeability are assessed. The main conclusions are as follows: (1) at low pressure (less than 10 MPa) and for medium pore size (pore radius range of 10 nm–60 nm), the effect of the K (Formula presented.) correction should be considered; (2) considering the effect of the K (Formula presented.) correction, bulk phase transport replaces surface diffusion more slowly; considering the existence of IW, bulk phase transport replaces surface diffusion more slowly; (3) with increase in pressure, the IW effect on gas apparent permeability decreases. Under low pressure, the IW, where pore size is small, promotes fluid flow, while the IW in the large pores hinders fluid flow. In conditions of ultra-high pressure, the IW promotes gas flow

Comprehensive Evaluation of a High-Temperature Resistant Re-Crosslinkable Preformed Particle Gel for Water Management

Gel treatment has been widely applied to control conformance for improving oil recovery and control water production in mature oil fields. However, most of the hydrogel systems are limited when being applied in the harsh environments of high temperatures. A systematic evaluation was conducted in this study to evaluate a modified PPG product, the high temperature resistant re-crosslinkable preformed particle gel (HT-RPPG) which can re-crosslink to form a bulky material and keep thermostable in the large-opening features after placement. This material was developed to overcome the limitations of conventional PPGs in the reservoirs with large- opening features such as open fractures, void conduits, wormholes, and so on. The HT-RPPG can swell up to 18 times of its original size at room temperature (23˚C), and the swelling ratio is independent of brine concentration and types. We conducted a series of experiments to evaluate the effect of particle size, temperatures, swelling ratios, brine types on re-crosslinking time, as well as the gel strength, blocking performance and thermostability after re-crosslinking. Smaller particle sizes result in the HT-RPPGs swell and re-crosslink much faster. Higher temperatures increase the swelling and re-crosslinking rate, while the larger swelling ratios (more feeding brine) can slow down the re-crosslinking time. HT-RPPG re-crosslinking process can be delayed when the particles contact with Ca2+. Additionally, the re-crosslinking of HT-RPPG is a temperature-responsive reaction which can only start after reaching the target temperature of 100 °C or above. The HT-RPPG has kept its volume and strength stable at 100 to 130 °C for over 10 months so far. A blocking performance test was conducted by using the tubing model to simulate void-space conduit (VSC), and breakthrough pressure reached to 427 psi/ft

Viral small T oncoproteins transform cells by alleviating hippo-pathway-mediated inhibition of the YAP proto-oncogene

Primary human cells can be transformed into tumor cells by a defined set of genetic alterations including telomerase, oncogenic RasV12, and the tumor suppressors p53 and pRb. SV40 small T (ST) is required for anchorage-independent growth in vitro and in vivo. Here, we identify the Hippo tumor suppressor pathway as a critical target of ST in cellular transformation. We report that ST uncouples YAP from the inhibitory activity of the Hippo pathway through PAK1-mediated inactivation of NF2. Membrane-tethered activated PAK is sufficient to bypass the requirement for ST in anchorage-independent growth. PAK acts via YAP to mediate the transforming effects of ST. Activation of endogenous YAP is required for ST-mediated transformation and is sufficient to bypass ST in anchorage-independent growth and xenograft tumor formation. Our findings uncover the Hippo tumor suppressor pathway as a final gatekeeper to transformation and tumorigenesis of primary cells

Molecular and clinical characteristics of ATP1A3-related diseases

ObjectiveWith detailed studies of ATP1A3-related diseases, the phenotypic spectrum of ATP1A3 has greatly expanded. This study aimed to potentially identify the mechanisms by which ATP1A3 caused neurological dysfunction by analyzing the clinical features and phenotypes of ATP1A3-related diseases, and exploring the distribution patterns of mutations in the subregions of the ATP1A3 protein, thus providing new and effective therapeutic approaches.MethodsDatabases of PubMed, Online Mendelian Inheritance in Man, and Human Gene Mutation Database, Wanfang Data, and Embase were searched for case reports of ATP1A3-related diseases. Following case screening, we collected clinical information and genetic testing results of patients, and analyzed the disease characteristics on the clinical phenotype spectrum associated with mutations, genetic characteristics of mutations, and effects of drug therapy.ResultsWe collected 902 clinical cases related to ATP1A3 gene. From the results of previous studies, we further clarified the clinical characteristics of ATP1A3-related diseases, such as alternating hemiplegia of childhood (AHC), rapid-onset dystonia-parkinsonism; cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss syndrome, and relapsing encephalopathy with cerebellar ataxia, frequency of mutations in different phenotypes and their distribution in gene and protein structures, and differences in mutations in different clinical phenotypes. Regarding the efficacy of drug treatment, 80 of the 124 patients with AHC were treated with flunarizine, with an effectiveness rate of ~64.5%.ConclusionsNervous system dysfunction due to mutations of ATP1A3 gene was characterized by a group of genotypic–phenotypic interrelated disease pedigrees with multiple clinical manifestations. The presented results might help guide the diagnosis and treatment of ATP1A3-related diseases and provided new ideas for further exploring the mechanisms of nervous system diseases due to ATP1A3 mutations

Response of Merkel cell polyomavirus-positive Merkel cell carcinoma xenografts to a survivin inhibitor

Merkel cell carcinoma (MCC) is a neuroendocrine skin cancer associated with high mortality. Merkel cell polyomavirus (MCV), discovered in 2008, is associated with ∼80% of MCC. The MCV large tumor (LT) oncoprotein upregulates the cellular oncoprotein survivin through its conserved retinoblastoma protein-binding motif. We confirm here that YM155, a survivin suppressor, is cytotoxic to MCV-positive MCC cells in vitro at nanomolar levels. Mouse survival was significantly improved for NOD-Scid-Gamma mice treated with YM155 in a dose and duration dependent manner for 3 of 4 MCV-positive MCC xenografts. One MCV-positive MCC xenograft (MS-1) failed to significantly respond to YM155, which corresponds with in vitro dose-response activity. Combination treatment of YM155 with other chemotherapeutics resulted in additive but not synergistic cell killing of MCC cell lines in vitro. These results suggest that survivin targeting is a promising therapeutic approach for most but not all MCV-positive MCCs. © 2013 Dresang et al

The cellular chloride channels CLIC1 and CLIC4 contribute to virus-mediated cell motility

Ion channels regulate many aspects of cell physiology, including cell proliferation, motility, and migration, and aberrant expression and activity of ion channels is associated with various stages of tumor development, with K⁺ and Cl⁻ channels now being considered the most active during tumorigenesis. Accordingly, emerging in vitro and preclinical studies have revealed that pharmacological manipulation of ion channel activity offers protection against several cancers. Merkel cell polyomavirus (MCPyV) is a major cause of Merkel cell carcinoma (MCC), primarily because of the expression of two early regulatory proteins termed small and large tumor antigens (ST and LT, respectively). Several molecular mechanisms have been attributed to MCPyV-mediated cancer formation but, thus far, no studies have investigated any potential link to cellular ion channels. Here we demonstrate that Cl⁻ channel modulation can reduce MCPyV ST-induced cell motility and invasiveness. Proteomic analysis revealed that MCPyV ST up-regulates two Cl⁻ channels, CLIC1 and CLIC4, which when silenced, inhibit MCPyV ST-induced motility and invasiveness, implicating their function as critical to MCPyV-induced metastatic processes. Consistent with these data, we confirmed that CLIC1 and CLIC4 are up-regulated in primary MCPyV-positive MCC patient samples. We therefore, for the first time, implicate cellular ion channels as a key host cell factor contributing to virus-mediated cellular transformation. Given the intense interest in ion channel modulating drugs for human disease. This highlights CLIC1 and CLIC4 activity as potential targets for MCPyV-induced MCC

Cigarette smoke induces endoplasmic reticulum stress and the unfolded protein response in normal and malignant human lung cells

<p>Abstract</p> <p>Background</p> <p>Although lung cancer is among the few malignancies for which we know the primary etiological agent (i.e., cigarette smoke), a precise understanding of the temporal sequence of events that drive tumor progression remains elusive. In addition to finding that cigarette smoke (CS) impacts the functioning of key pathways with significant roles in redox homeostasis, xenobiotic detoxification, cell cycle control, and endoplasmic reticulum (ER) functioning, our data highlighted a defensive role for the unfolded protein response (UPR) program. The UPR promotes cell survival by reducing the accumulation of aberrantly folded proteins through translation arrest, production of chaperone proteins, and increased degradation. Importance of the UPR in maintaining tissue health is evidenced by the fact that a chronic increase in defective protein structures plays a pathogenic role in diabetes, cardiovascular disease, Alzheimer's and Parkinson's syndromes, and cancer.</p> <p>Methods</p> <p>Gene and protein expression changes in CS exposed human cell cultures were monitored by high-density microarrays and Western blot analysis. Tissue arrays containing samples from 110 lung cancers were probed with antibodies to proteins of interest using immunohistochemistry.</p> <p>Results</p> <p>We show that: 1) CS induces ER stress and activates components of the UPR; 2) reactive species in CS that promote oxidative stress are primarily responsible for UPR activation; 3) CS exposure results in increased expression of several genes with significant roles in attenuating oxidative stress; and 4) several major UPR regulators are increased either in expression (i.e., BiP and eIF2α) or phosphorylation (i.e., phospho-eIF2α) in a majority of human lung cancers.</p> <p>Conclusion</p> <p>These data indicate that chronic ER stress and recruitment of one or more UPR effector arms upon exposure to CS may play a pivotal role in the etiology or progression of lung cancers, and that phospho-eIF2α and BiP may have diagnostic and/or therapeutic potential. Furthermore, we speculate that upregulation of UPR regulators (in particular BiP) may provide a pro-survival advantage by increasing resistance to cytotoxic stresses such as hypoxia and chemotherapeutic drugs, and that UPR induction is a potential mechanism that could be attenuated or reversed resulting in a more efficacious treatment strategy for lung cancer.</p

Experimental Study of Degradable Preformed Particle Gel (DPPG) as Temporary Plugging Agent for Carbonate Reservoir Matrix Acidizing to Improve Oil Recovery

Preformed particle gel (PPG) is an effective technique for conformance improvement in petroleum reservoirs. It can selectively penetrate high-permeability channels to form effective plugging and divert the chasing injection fluid to low-permeability unswept oil zones. However, conventional PPG would be dehydrated under acidic conditions and could not be easily degraded, which will cause a certain amount of damage to the target formation. Therefore, this study proposed to introduce acid-resistant functional groups and a self-degradable cross-linking structure into the conventional PPG\u27s compositions to develop a degradable PPG (DPPG). The influence mechanism of the chemical composition, swelling performance, and temporary plugging performance of DPPG was studied. Results show that the DPPG can swell up to 70 times its original size by absorbing water, and swollen DPPG can finally self-degrade to a water-like fluid in acid solution. After injecting of DPPG swelled by 20 times its original volume, the injection pressure could reach 1250 psi. Even during the chase acid treatment period, the average pressure was around 130 psi, which shows excellent plugging performance. Subsequent injection of acid would react with carbonate rocks around the plugging zones, increasing the swept volume. In addition, after acid treatments, the DPPG could be self-degraded into a dilute solution like water, so it has very little damage to the reservoir matrix. Therefore, the DPPG has good temporary plugging and acidizing steering performance in acidizing operations. The research in this article can provide the experimental basis and reference for expanding the further application of DPPG in petroleum reservoir stimulation

In Situ Surface Decorated Polymer Microsphere Technology for Enhanced Oil Recovery in High-Temperature Petroleum Reservoirs

Polymer microspheres have been applied for petroleum reservoir enhanced oil recovery (EOR) in the past decade because they can overcome some drawbacks inherent in in situ polymer gel systems. A novel in situ surface decorated polymer microsphere technology was developed for chemical EOR in high-temperature reservoirs. The swelling performance of the conventional polymer microspheres at room temperature was systematically analyzed and verified by an environmental scanning electron microscope. Their swelling and degradation mechanisms at a high temperature (150 °C) were also examined. To improve the long-term thermal stability of the polymer microsphere, different concentrations of polyethylenimine (PEI) were used as an in situ surface decorating agent. The decorated microspheres remained stable at 150 °C for more than three months, and thermogravimetric analysis indicated that the in situ surface decorated polymer microspheres could remain stable at temperatures up to 310 °C. PEI-decorated 3D network structures on the surface of the microspheres prevented water molecules from entering inner structures, thereby inhibiting the polymer microspheres from swelling in aqueous solution under high temperatures. A sandpack flooding experiment showed how the in situ surface decorated polymer microspheres could effectively plug the porous media for water control and oil recovery improvement even after aging at 150 °C for two months. In situ surface polymer microspheres decorated with PEI can help petroleum engineers better apply this gel technology