Mud loss is a common phenomenon in the drilling process with an important impact on the efficiency and safety of drilling. Mud loss in fractured formations is serious and previous methods have been ...based mostly on the single-fracture model, which had difficulty dealing with the loss of complex fracture networks in fractured reservoirs. A hydro-mechanically coupled model was constructed based on the poroelasticity. This model also coupled the fluid flow in fractures and matrix by fluid exchange term across fracture surface. The fully coupled model was solved using the extended finite element method (XFEM). The physical field characteristics were represented by enrichment functions, and grids were decoupled from fractures. Thus, the efficiency was improved greatly. A simple single-fracture model was used to verify this method, and a multi-fracture numerical model was then constructed to examine the influence of the fracture aperture, matrix permeability, fracture deformation, and mud viscosity on mud loss.
Any analysis of hydro-mechanically coupled production processes needs to consider flow in fractures and matrix coupled simultaneously. In this paper, fractures were described explicitly using a ...discrete fracture model. The fluid exchange term in the matrix and fracture governing equations was used to couple the flow in the fracture and matrix. Based on poroelasticity, the momentum and mass coupling of the standard equation were established for fractured porous media. An improved extended finite element method (I-XFEM) was used, and a solver was developed to solve the fully coupled model efficiently. In this model, fractures are decoupled from the grids, and the calculation efficiency was improved greatly. The improved enrichment functions were used to characterize the physical field and guarantee the calculation accuracy. The accuracy of the model was verified using a single-fracture model. A multi-fracture model was designed. The results showed that the cumulative production is positively related to the Elastic modulus and Poisson’s ratio, indicating that solid deformation on reservoir development has a significant influence and that the Elastic modulus and Poisson’s ratio have a significant effect on the reservoir stress sensitivity.
Interfacial exchange coupling and magnetization reversal characteristics in the perpendicular heterostructures consisting of an amorphous ferrimagnetic (FI) TbxCo(100-x) alloy layer exchange-coupled ...with a ferromagnetic (FM) Co/NiN multilayer have been investigated. As compared with pure TbxCo(100-x) alloy, the magnetization compensation composition of the heterostructures shift to a higher Tb content, implying Co/Ni also serves to compensate the Tb moment in TbCo layer. The net magnetization switching field Hc⊥ and interlayer interfacial coupling field Hex, are not only sensitive to the magnetization and thickness of the switched TbxCo(100-x) or Co/NiN layer, but also to the perpendicular magnetic anisotropy strength of the pinning layer. By tuning the layer structure we achieve simultaneously both large Hc⊥ = 1.31 T and Hex = 2.19 T. These results, in addition to the fundamental interest, are important to understanding of the interfacial coupling interaction in the FM/FI heterostructures, which could offer the guiding of potential applications in heat-assisted magnetic recording or all-optical switching recording technique.
•Novel soluble epoxide hydrolase (sEH) inhibitors have been discovered.•Isosteric replacements are improving bioavailability of the newly-synthesized soluble epoxide hydrolase inhibitors.•Docking ...experiments reveal that novel inhibitors bind in the catalytic pocket of the human sEH enzyme.•The inhibition of this enzyme has the potential to impact many different chronic inflammatory conditions.
We have previously identified and reported several potent piperidine-derived amide inhibitors of the human soluble epoxide hydrolase (sEH) enzyme. The inhibition of this enzyme leads to elevated levels of epoxyeicosatrienoic acids (EETs), which are known to possess anti-inflammatory, vasodilatory, and anti-fibrotic effects. Herein, we report the synthesis of 9 analogs of the lead sEH inhibitor and the follow-up structure-activity relationship and liver microsome stability studies. Our findings show that isosteric modifications that lead to significant alterations in the steric and electronic properties at a specific position in the molecule can reduce the efficacy by up to 75-fold. On the other hand, substituting hydrogen with deuterium produces a notable increase (∼30%) in the molecules’ half-lives in both rat and human microsomes, while maintaining sEH inhibition potency. These data highlight the utility of isosteric replacement for improving bioavailability, and the newly-synthesized inhibitor structures may thus, serve as a starting point for preclinical development. Our docking study reveals that in the catalytic pocket of sEH, these analogs are in proximity of the key amino acids involved in hydrolysis of EETs.
To assess the safety, tolerability, and pharmacology of LY3023703, a microsomal prostaglandin E synthase 1 (mPGES1) inhibitor, a multiple ascending dose study was conducted. Forty‐eight subjects ...received LY3023703, celecoxib (400 mg), or placebo once daily for 28 days. Compared with placebo, LY3023703 inhibited ex vivo lipopolysaccharide‐stimulated prostaglandin E2 (PGE2) synthesis 91% and 97% on days 1 and 28, respectively, after 30‐mg dosing, comparable to celecoxib's effect (82% inhibition compared to placebo). Unlike celecoxib, which also inhibited prostacyclin synthesis by 44%, LY3023703 demonstrated a maximal increase in prostacyclin synthesis of 115%. Transient elevations of serum aminotransferase were observed in one subject after 30‐mg LY3023703 dosing (10× upper limit of normal (ULN)), and one subject after 15‐mg dosing (about 1.5× ULN). Results from this study suggest that mPGES1 inhibits inducible PGE synthesis without suppressing prostacyclin generation and presents a novel target for inflammatory pain.
The stem rust resistance gene Sr2 has provided broad-spectrum protection against stem rust (Puccinia graminis Pers. f. sp. tritici) since its wide spread deployment in wheat from the 1940s. Because ...Sr2 confers partial resistance which is difficult to select under field conditions, a DNA marker is desirable that accurately predicts Sr2 in diverse wheat germplasm. Using DNA sequence derived from the vicinity of the Sr2 locus, we developed a cleaved amplified polymorphic sequence (CAPS) marker that is associated with the presence or absence of the gene in 115 of 122 (95%) diverse wheat lines. The marker genotype predicted the absence of the gene in 100% of lines which were considered to lack Sr2. Discrepancies were observed in lines that were predicted to carry Sr2 but failed to show the CAPS marker. Given the high level of accuracy observed, the marker provides breeders with a selection tool for one of the most important disease resistance genes of wheat.
Chronic hepatitis B virus (HBV) infection is epidemiologically associated with hepatocellular carcinoma (HCC), but its role in HCC remains poorly understood due to technological limitations. In this ...study, we systematically characterize HBV in HCC patients. HBV sequences were enriched from 48 HCC patients using an oligo-bead-based strategy, pooled together and sequenced using the FLX-Genome-Sequencer. In the tumors, preferential integration of HBV into promoters of genes (P < 0.001) and significant enrichment of integration into chromosome 10 (P < 0.01) were observed. Integration into chromosome 10 was significantly associated with poorly differentiated tumors (P < 0.05). Notably, in the tumors, recurrent integration into the promoter of the human telomerase reverse transcriptase (TERT) gene was found to correlate with increased TERT expression. The preferred region within the HBV genome involved in integration and viral structural alteration is at the 3'-end of hepatitis B virus X protein (HBx), where viral replication/transcription initiates. Upon integration, the 3'-end of the HBx is often deleted. HBx-human chimeric transcripts, the most common type of chimeric transcripts, can be expressed as chimeric proteins. Sequence variation resulting in non-conservative amino acid substitutions are commonly observed in HBV genome. This study highlights HBV as highly mutable in HCC patients with preferential regions within the host and virus genome for HBV integration/structural alterations.
Stem rust of small grain cereals, caused by Puccinia graminis, is a major disease of wheat, barley, and oat. In order to effectively utilize stem rust resistance in the improvement of small grain ...cereals, it is necessary to monitor the virulence composition and dynamics in the stem rust population. Races of P. graminis from barberry, wheat, barley, and oat were surveyed across the United States during 2003. Aecial infections on barberry were primarily due to P. graminis f. sp. secalis, as inoculations using aeciospores failed to produce infection on wheat and oat. Race QFCS of P. graminis f. sp. tritici was the most common race identified from wheat and barley. Race QFCS has virulence on stem rust resistance genes Sr5, 8a, 9a, 9d, 9g, 10, 17, and 21 that are used for race identification. Race TTTT was identified in 2003. This race possesses virulence to all 16 stem rust resistance genes present in the wheat stem rust differentials and should be targeted in breeding for stem rust resistance. Race QFCN appeared to be a new race in the U.S. stem rust population. Races QCCJ and MCCF were identified, but at low frequencies. Seven races of P. graminis f. sp. avenae were identified from oat, and races NA-27, NA-29, and NA-67 were the predominant races. Race NA-76 was identified for the first time in the United States.
We have studied the photochemical water splitting activity of individually dispersed, semiconductor nanosheets derived from the Dion−Jacobsen phase HCa2Nb3O10 by exfoliation with tetrabutylammonium ...hydroxide. The dimensions of the nanosheets are 0.001 × 1.2 × 1.2 μm3 based on TEM measurements and crystallographic data, and their band gap is determined as 3.53 eV based on the absorption band edge at 350 nm. When an aqueous suspension of the nanosheets is irradiated with light from a Hg lamp, hydrogen is produced at rates of up to 2.28 μmol/h with a quantum efficiency (QE) of 0.22%. No oxygen is evolved. Derivatization of the nanosheets with Pt nanoparticles increases the hydrogen production rate to 78.37 μmol (QE = 7.5%). Restacking of the nanosheets at low pH does not significantly affect the catalytic activity. Transient absorption measurements of the nanosheets reveal charge separation on a nanosecond time scale.
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