Dynamic Relative Permeability and Simulation of WAG Injection Processes

In this work, we investigate the impact of mobility changes due to flow reversals from co-current to counter-current flow on the displacement performance of water alternating gas (WAG) injection processes. In WAG processes, the injected gas will migrate toward the top of the formation while the injected water will migrate toward the bottom of the formation. The segregation of gas, oil and water phases will result in counter-current flow occurring in the vertical direction in some portions of the reservoir during the displacement process. Previous experimental and theoretical studies of counter-current flow have shown that the relative mobility of each of the phases in a porous medium is considerably less when counter-current flow prevails as compared to co-current flow settings. A reduction of the relative permeability in the vertical direction results in a dynamic anisotropy in phase mobilities. This effect has, to the best of our knowledge, not previously been considered in the modeling and simulation of WAG processes. A new flow model that accounts for flow reversals in the vertical direction has been implemented and tested in a three-phase compositional reservoir simulator. In order to investigate the impact of flow reversals, results from the new flow model are compared to cases where counter-current flow effects on the phase mobilities are ignored. A range of displacement settings, covering relevant slug sizes, have been investigated to gauge the impact of mobility reductions due to flow reversals. Significant differences, in terms of saturation distribution, producing GOR and oil recovery, are observed between the conventional flow model (ignoring mobility reductions due to counter-current flow) and the proposed new model that accounts for reductions in phase mobility during counter-current flow. Accordingly, we recommend that an explicit representation of flow transitions between co-current and counter-current flow (and the related impact on phase mobilities) should be considered to ensure accurate and optimal design of WAG injection processes.     

Free Convection Boundary Layer Flow from a Heated Upward Facing Horizontal Flat Plate Embedded in a Porous Medium Filled by a Nanofluid with Convective Boundary Condition

The steady laminar incompressible free convective flow of a nanofluid over a permeable upward facing horizontal plate located in porous medium taking into account the thermal convective boundary condition is studied numerically. The nanofluid model used involves the effect of Brownian motion and the thermophoresis. Using similarity transformations the continuity, the momentum, the energy, and the nanoparticle volume fraction equations are transformed into a set of coupled similarity equations, before being solved numerically, by an implicit finite difference numerical method. Our analysis reveals that for a true similarity solution, the convective heat transfer coefficient related with the hot fluid and the mass transfer velocity must be proportional to x ^−2/3, where x is the horizontal distance along the plate from the origin. Effects of the various parameters on the dimensionless longitudinal velocity, the temperature, the nanoparticle volume fraction, as well as on the rate of heat transfer and the rate of nanoparticle volume fraction have been presented graphically and discussed. It is found that Lewis number, the Brownian motion, and the convective heat transfer parameters increase the heat transfer rate whilst the thermophoresis decreases the heat transfer rate. It is also found that Lewis number and the convective heat transfer parameter enhance the nanoparticle volume fraction rate whilst the thermophoresis parameter decreases nanoparticle volume fraction rate. A very good agreement is found between numerical results of the present article for special case and published results. This close agreement supports the validity of our analysis and the accuracy of the numerical computations.     

Directed evolution of cyclic peptides for inhibition of autophagy

In recent decades it has become increasingly clear that induction of autophagy plays an important role in the development of treatment resistance and dormancy in many cancer types. Unfortunately, chloroquine (CQ) and hydroxychloroquine (HCQ), two autophagy inhibitors in clinical trials, suffer from poor pharmacokinetics and high toxicity at therapeutic dosages. This has prompted intense interest in the development of targeted autophagy inhibitors to re-sensitize disease to treatment with minimal impact on normal tissue. We utilized Scanning Unnatural Protease Resistant (SUPR) mRNA display to develop macrocyclic peptides targeting the autophagy protein LC3. The resulting peptides bound LC3A and LC3B—two essential components of the autophagosome maturation machinery—with mid-nanomolar affinities and disrupted protein–protein interactions (PPIs) between LC3 and its binding partners in vitro. The most promising LC3-binding SUPR peptide accessed the cytosol at low micromolar concentrations as measured by chloroalkane penetration assay (CAPA) and inhibited starvation-mediated GFP-LC3 puncta formation in a concentration-dependent manner. LC3-binding SUPR peptides re-sensitized platinum-resistant ovarian cancer cells to cisplatin treatment and triggered accumulation of the adapter protein p62 suggesting decreased autophagic flux through successful disruption of LC3 PPIs in cell culture. In mouse models of metastatic ovarian cancer, treatment with LC3-binding SUPR peptides and carboplatin resulted in almost complete inhibition of tumor growth after four weeks of treatment. These results indicate that SUPR peptide mRNA display can be used to develop cell-penetrating macrocyclic peptides that target and disrupt the autophagic machinery in vitro and in vivo.

SUPR peptide mRNA display was used to evolve a cell-permeable, macrocyclic peptide for autophagy inhibition.     

Equation of state of finite-size hadrons: thermodynamical consistency

A method is presented to derive hadronic gas equation of state incorporating the effect of finite size of baryons in a thermodynamically consistent way. The model contains a more realistic picture of incorporating the effect of excluded volume unlike earlier methods. The results obtained by our calculation and those by the thermodynamically inconsistent methods used in many earlier works are compared.     

Experimental and computational studies of the thermal decomposition of halon 1211

Thermal pyrolysis of halon 1211 (CBrClF₂), diluted in nitrogen, in a tubular alumina reactor, has been studied over the temperature range of 773–1073 K at residence times from 0.3 to 2 s. At temperatures below 973 K, the major products were CCl₂F₂, CBr₂F₂, C₂Cl₂F₄, C₂BrClF₄, C₂F₄, and C₂Br₂F₄. Further increasing temperature resulted in the formation of CBrF₃, CClF₃, and many other species whose formation necessitated the rupture of C? F bonds. Coke formation was also observed on the surface of the reactor at high temperatures. A kinetic reaction scheme involving 16 species and 25 reaction steps was developed and applied to model the thermal pyrolysis of halon 1211 over the temperature range of 773–973 K. Sensitivity analysis suggests that the reaction CBrClF₂ + CClF₂→CCl₂F₂ + CBrF₂ constitutes the major pathway for the decomposition of halon 1211 under the conditions investigated. © 2005 Wiley Periodicals, Inc. Int J Chem Kinet 37: 134–146, 2005     

In situ forming PLGA implant for 90 days controlled release of leuprolide acetate for treatment of prostate cancer

In prostate cancer, hormone therapy via leuprolide acetate drug (LUP) is used to lower the level of testosterone down to castration level to effectively control the development of prostate cancer. The objective of this study was to evaluate the effective parameters in degradation and controlled release of an injectable in situ formed polymeric implant, loaded with leuprolide acetate, in order to achieve an optimum formulation for sustained drug release for 90 days with minimum burst release. The main problem associating with such implants is their high burst release. Designing an injectable implant with sustained and minimum burst release has thus become an attractive challenge in drug delivery field. Effects of type of poly(lactic‐co‐glycolic acid) 75:25 copolymers (RG752, RG756) and addition of nano‐hydroxyapatite (HA) particles on degradation rates of the implants and release profiles were examined in vitro and in vivo in a rabbit animal model. Results showed that implants containing polymers with higher molecular weights had significantly lower weight loss and molecular weight reduction. Adding nanoparticles of hydroxyapatite into poly(lactic‐co‐glycolic acid) implants caused further reduction in degradation rates, leading to a more sustained drug release in vivo, with reduced burst release. Different conventional kinetic models were applied to drug release and degradation data. The degradation data fit well to the first‐order degradation model. Higuchi model was the best kinetic release model fitted to the experimental in vitro release data. This study led to an optimum formulation (RG756:RG752 3:1 + 5% HA) with sustained leuprolide release and testosterone suppression over a 90‐day period with significant decrease of burst release phase (50%, p < 0.001) compared with the conventional Eligard formulation. The histopathology test showed that the formulated implant had no effects of toxicity or tissue necrosis in organs of the animal model. Copyright © 2017 John Wiley & Sons, Ltd.     

Synthetic Approaches towards the Sulfonamide Substituted‐1,5‐Diarylimidazole‐2‐thiones as Selective Cyclooxygense‐2 inhibitors

A new series of sulfonamide substituted 1,5‐diarylimidazole, possessing C‐2 alkylthio moiety, were synthesized for their cyclooxygense‐2 (COX‐2) inhibitory activity starting from condensation of N,N‐dibenzylaminosulfonylphenacylamine hydrochloride ( 2 ) and corresponding isothiocyanate in the presence of Et₃N, followed by alkylation in the basic medium. In concomitant with these intermediates, 2‐arylamino‐5‐arylthiazole derivatives 5 were also produced. The ratio of these two products was variable with different isothiocyanates. Final debenzylation was achieved using concentrated sulfuric acid to give the title sulfonamides 8 .     

Performance evaluation of CAESAR–QSAR output using PAHs as a case study

The set of 16 polycyclic aromatic hydrocarbon compounds was examined with the Internet available quantitative structure–activity relationship (QSAR) CAESAR models. For mutagenicity, carcinogenicity, developmental toxicity, and skin sensitization, the report includes the predicted classifications, the analysis of applicability domains, and the similarity sets, which consist of the similar compounds from the training sets. These results were further analyzed with chemometrical methods, that is, hierarchical clustering, principal component analysis, and self‐organizing maps, which were used for clustering and to define the cluster indicators. Such analysis assists the users in planning the application of QSAR models for hazard communication in regulatory compliance and in research of new active compounds. Copyright © 2013 John Wiley & Sons, Ltd.