Oncogenes induce cell proliferation leading to replicative stress, DNA damage and genomic instability. A wide variety of cellular stresses activate c-Jun N-terminal kinase (JNK) proteins, but few studies have directly addressed the roles of JNK isoforms in tumor development. Herein, we show that jnk2 knockout mice expressing the Polyoma Middle T Antigen transgene developed mammary tumors earlier and experienced higher tumor multiplicity compared to jnk2 wildtype mice. Lack of jnk2 expression was associated with higher tumor aneuploidy and reduced DNA damage response, as marked by fewer pH2AX and 53BP1 nuclear foci. Comparative genomic hybridization further confirmed increased genomic instability in PyV MT/jnk2−/− tumors. In vitro, PyV MT/jnk2−/− cells underwent replicative stress and cell death as evidenced by lower BrdU incorporation, and sustained chromatin licensing and DNA replication factor 1 (CDT1) and p21Waf1 protein expression, and phosphorylation of Chk1 after serum stimulation, but this response was not associated with phosphorylation of p53 Ser15. Adenoviral overexpression of CDT1 led to similar differences between jnk2 wildtype and knockout cells. In normal mammary cells undergoing UV induced single stranded DNA breaks, JNK2 localized to RPA (Replication Protein A) coated strands indicating that JNK2 responds early to single stranded DNA damage and is critical for subsequent recruitment of DNA repair proteins. Together, these data support that JNK2 prevents replicative stress by coordinating cell cycle progression and DNA damage repair mechanisms.
Summary The goal of this work was to pursue strategies to improve oil recovery in highly fractured carbonate reservoirs by altering the wettability from oil-wet to preferentially water-wet at high temperature (100°C or above), high salinity, and especially in high hardness environments. Cationic surfactants and anionic surfactants were investigated for their compatibility with hard brine at a high temperature. Sequestration agents were added to improve aqueous solubility. The performance of surfactant formulations was evaluated by measuring contact angles on calcite plates and spontaneous imbibition in originally oil-wet dolomite cores. Cationic surfactants altered the wettability of oil-aged calcite plates toward a more water-wet state in the presence of hard brines; oil recovery by spontaneous imbibition from dolomite cores was 50 to 65% of original oil in place (OOIP). Anionic surfactant formulations changed the carbonate wettability to strongly water-wet only when the brine salinity and divalent-ion concentration were reduced. The wettability could be altered in hard brines if a sequestration agent [e.g., ethylene diamine tetraacetic acid (EDTA)] is added to anionic surfactant formulations; up to 45% of OOIP was recovered by spontaneous imbibition. EDTA provides alkalinity, saponification, chelation of divalent ions, and dissolution of dolomite, which may contribute to the increase of imbibition rate and ultimate oil recovery in fractured carbonates.
The performance of surfactant-enhanced oil recovery (EOR) in fractured carbonates relies on spontaneous imbibition or low IFT-aided gravity drainage. This work investigated the synergism between wettability effects and IFT reduction mediated by a variety of surfactants through experiments and numerical simulation studies. Experiments have shown that oil can be recovered from oil-wet Silurian dolomite fracture blocks either by capillarity driven imbibition, gravity-driven imbibition or low tension-aided gravity drainage. The mixture of wettability alteration (WA) surfacant with IFT reduction surfactant exhibits the synergistic effect on the imbibition oil recovery from oil-wet carbonate rocks. It was found that divalent ion scavengers help the wettability altertion capability of some sulfonate surfactants in hard brine, which leads to the high oil recovery up to 70% OOIP (IFTϩWA), compared with oil recovery of 30-50% OOIP by sulfonate surfactant only (only IFT reduction). We proposed a mechanism that the presence of a sufficient amount of divalent ion scavengers in the anionic surfactant formulation reduces the free divalent cations in hard brine, which then promotes the release of surfactant monomers from the micelles and enhances wettability alteration by surfactant adsorption. The UTCHEM simulation results confirmed the existence of synergism between IFT reduction and WA in spontaneous imbibition processes. According to the capillary desaturation curve (CDC), that residual oil saturation after gravity drainage is approximately 10% to 20% higher than gravity-driven spontaneous imbibition when two processes have the similar trapping numbers, confirming that the wettability alteration contributes to the ultimate oil recovery.
The objective of this study is to develop strategies to improve oil recovery in highly fractured carbonate reservoirs at high temperatures (100°C and above). Such reservoirs usually contain high salinity and high hardness formation brines. The use of nonionic surfactants or anionic surfactants (Carboxylates and Sulfonates) to alter oil-wet reservoirs towards more water-wet was investigated under harsh reservoir conditions. A nonionic surfactant Ethomeen® T/25 has shown aqueous stability at high salinity and temperature with high effectiveness in wettability alteration and imbibition oil recovery. Anionic surfactant formulations were developed to recover oil mainly by gravity drainage since they did not show wettability alteration effect in hard brine. Both experimental and simulation studies have shown that sulfonate/carboxylate surfactants achieve high performance in wettability alteration and spontaneous imbibition only when they mix with chelating agents in formulations. Chelating agents, especially EDTA.4Na and sodium polyacrylate (NaPA) have been tested for their compatibility and effectiveness in the surfactant formulations. By sequestering divalent ions in hard brine, chelating agents free anionic surfactants to react at the solid-fluid interface to alter wettability of carbonates from oil-wet towards more water-wet. The chelating agents trigger mineral dissolution, but that does not lead to wettability alteration or contribute to the imbibition oil recovery directly.
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