A Framework for Modeling Subgrid Effects for Two-Phase Flows in Porous Media

In this paper, we study upscaling for two-phase flows in strongly heterogeneous porous media. Upscaling a hyperbolic convection equation is known to be very difficult due to the presence of nonlocal memory effects. Even for a linear hyperbolic equation with a shear velocity field, the upscaled equation involves a nonlocal history dependent diffusion term, which is not amenable to computation. By performing a systematic multiscale analysis, we derive coupled equations for the average and the fluctuations for the two-phase flow. The homogenized equations for the coupled system are obtained by projecting the fluctuations onto a suitable subspace. This projection corresponds exactly to averaging along streamlines of the flow. Convergence of the multiscale analysis is verified numerically. Moreover, we show how to apply this multiscale analysis to upscale two-phase flows in practical applications

TGF-β-responsive CAR-T cells promote anti-tumor immune function.

A chimeric antigen receptor (CAR) that responds to transforming growth factor beta (TGF-β) enables the engineering of T cells that convert this immunosuppressive cytokine into a potent T-cell stimulant. However, clinical translation of TGF-β CAR-T cells for cancer therapy requires the ability to productively combine TGF-β responsiveness with tumor-targeting specificity. Furthermore, the potential concern that contaminating, TGF-β?producing regulatory T (Treg) cells may preferentially expand during TGF-β CAR-T cell manufacturing and suppress effector T (Teff) cells demands careful evaluation. Here, we demonstrate that TGF-β CAR-T cells significantly improve the anti-tumor efficacy of neighboring cytotoxic T cells. Furthermore, the introduction of TGF-β CARs into mixed T-cell populations does not result in the preferential expansion of Treg cells, nor do TGF-β CAR-Treg cells cause CAR-mediated suppression of Teff cells. These results support the utility of incorporating TGF-β CARs in the development of adoptive T-cell therapy for cancer

Magnetization, crystal structure and anisotropic thermal expansion of single-crystal SrEr2O4

The magnetization, crystal structure, and thermal expansion of a nearly stoichiometric Sr$_{1.04(3)}$Er$_{2.09(6)}$O$_{4.00(1)}$ single crystal have been studied by PPMS measurements and in-house and high-resolution synchrotron X-ray powder diffraction. No evidence was detected for any structural phase transitions even up to 500 K. The average thermal expansions of lattice constants and unit-cell volume are consistent with the first-order Gr\"uneisen approximations taking into account only the phonon contributions for an insulator, displaying an anisotropic character along the crystallographic \emph{a}, \emph{b}, and \emph{c} axes. Our magnetization measurements indicate that obvious magnetic frustration appears below $\sim$15 K, and antiferromagnetic correlations may persist up to 300 K.Comment: 6 pages, 5 figure, 2 table

Mithramycin forms a stable dimeric complex by chelating with Fe(II): DNA-interacting characteristics, cellular permeation and cytotoxicity

Mith (mithramycin) forms a 2:1 stoichiometry drug–metal complex through the chelation with Fe(II) ion as studied using circular dichroism spectroscopy. The binding affinity between Mith and Fe(II) is much greater than other divalent metal ions, including Mg(II), Zn(II), Co(II), Ni(II) and Mn(II). The [(Mith)(2)–Fe(II)] complex binds to DNA and induces a conformational change of DNA. Kinetic analysis of surface plasmon resonance studies revealed that the [(Mith)(2)–Fe(II)] complex binds to DNA duplex with higher affinity compared with the [(Mith)(2)–Mg(II)] complex. A molecular model of the Mith-DNA–Metal(II) complex is presented. DNA-break assay showed that the [(Mith)(2)–Fe(II)] complex was capable of promoting the one-strand cleavage of plasmid DNA in the presence of hydrogen peroxide. Intracellular Fe(II) assays and fluorescence microscopy studies using K562 indicated that this dimer complex maintains its structural integrity and permeates into the inside of K562 cells, respectively. The [(Mith)(2)–Fe(II)] complex exhibited higher cytotoxicity than the drug alone in some cancer cell lines, probably related to its higher DNA-binding and cleavage activity. Evidences obtained in this study suggest that the biological effects caused by the [(Mith)(2)–Fe(II)] complex may be further explored in the future

A Case of Uveitis-Hyphema-Glaucoma Syndrome due to ExPRESS Miniature Implantation

Purpose: To report a case of a 69-year-old patient who developed uveitis-glaucoma-hyphema syndrome after an uneventful EX-PRESS (Optonol, Ltd. Neve Ilan, Israel) mini shunt surgery for advanced primary open angle glaucoma and to discuss management options and clinical implications. Uveitis-glaucoma-hyphema syndrome is a rare but serious complication usually described after cataract surgery. It is often described in anterior chamber intraocular lenses, sulcus lenses, as well as malpositioned or subluxed lenses resulting in chafing of the lens-iris interface. Clinical manifestations include increased intraocular pressure, anterior chamber inflammation, and recurrent hyphema. Patient and Methods: We report a case of a 69-year-old African American man who developed uveitis-glaucoma-hyphema syndrome 8 years after uneventful implantation of an EX-PRESS miniature shunt. Slit-lamp examination demonstrated persistent inflammation without evidence of iris atrophy nor IOL dislocation; however, gonioscopy demonstrated localized iris atrophy under the shunt with surrounding iris billowing and a layered hyphema. Results: A localized laser iridoplasty around the shunt was performed leading to resolution of uveitis and hyphema. No other complications occurred during follow-up. Conclusions: Given the increasing prevalence of glaucoma procedures involving implants, uveitis-glaucoma-hyphema syndrome may become more prevalent as new sources of intraocular devices may cause potential complications. Laser iridoplasty provides a minimally invasive approach to treating a localized source of chafing and reduce further surgical intervention.https://scholarlycommons.henryford.com/merf2020caserpt/1136/thumbnail.jp

Incommensurate antiferromagnetic order in the manifoldly-frustrated SrTb2_2O4_4 with transition temperature up to 4.28 K

The N$\acute{\rm e}$el temperature of the new frustrated family of Sr\emph{RE}$_2$O$_4$ (\emph{RE} = rare earth) compounds is yet limited to $\sim$ 0.9 K, which more or less hampers a complete understanding of the relevant magnetic frustrations and spin interactions. Here we report on a new frustrated member to the family, SrTb$_2$O$_4$ with a record $T_{\rm N}$ = 4.28(2) K, and an experimental study of the magnetic interacting and frustrating mechanisms by polarized and unpolarized neutron scattering. The compound SrTb$_2$O$_4$ displays an incommensurate antiferromagnetic (AFM) order with a transverse wave vector \textbf{Q}$^{\rm 0.5 K}_{\rm AFM}$ = (0.5924(1), 0.0059(1), 0) albeit with partially-ordered moments, 1.92(6) $\mu_{\rm B}$ at 0.5 K, stemming from only one of the two inequivalent Tb sites mainly by virtue of their different octahedral distortions. The localized moments are confined to the \emph{bc} plane, 11.9(66)$^\circ$ away from the \emph{b} axis probably by single-ion anisotropy. We reveal that this AFM order is dominated mainly by dipole-dipole interactions and disclose that the octahedral distortion, nearest-neighbour (NN) ferromagnetic (FM) arrangement, different next NN FM and AFM configurations, and in-plane anisotropic spin correlations are vital to the magnetic structure and associated multiple frustrations. The discovery of the thus far highest AFM transition temperature renders SrTb$_2$O$_4$ a new friendly frustrated platform in the family for exploring the nature of magnetic interactions and frustrations.Comment: 19 pages, 8 Figures, 1 Tabl

Surface grafting of electrospun fibers using ATRP and RAFT for the control of biointerfacial interactions

BACKGROUND The ability to present signalling molecules within a low fouling 3D environment that mimics the extracellular matrix is an important goal for a range of biomedical applications, both in vitro and in vivo. Cell responses can be triggered by non-specific protein interactions occurring on the surface of a biomaterial, which is an undesirable process when studying specific receptor-ligand interactions. It is therefore useful to present specific ligands of interest to cell surface receptors in a 3D environment that minimizes non-specific interactions with biomolecules, such as proteins. METHOD In this study, surface-initiated atom transfer radical polymerization (SI-ATRP) of poly(ethylene glycol)-based monomers was carried out from the surface of electrospun fibers composed of a styrene/vinylbenzyl chloride copolymer. Surface initiated radical addition-fragmentation chain transfer (SI-RAFT) polymerisation was also carried out to generate bottle brush copolymer coatings consisting of poly(acrylic acid) and poly(acrylamide). These were grown from surface trithiocarbonate groups generated from the chloromethyl styrene moieties existing in the original synthesised polymer. XPS was used to characterise the surface composition of the fibers after grafting and after coupling with fluorine functional XPS labels. RESULTS Bottle brush type coatings were able to be produced by ATRP which consisted of poly(ethylene glycol) methacrylate and a terminal alkyne-functionalised monomer. The ATRP coatings showed reduced non-specific protein adsorption, as a result of effective PEG incorporation and pendant alkynes groups existing as part of the brushes allowed for further conjugation of via azide-alkyne Huisgen 1,3-dipolar cycloaddition. In the case of RAFT, carboxylic acid moieties were effectively coupled to an amine label via amide bond formation. In each case XPS analysis demonstrated that covalent immobilisation had effectively taken place. CONCLUSION Overall, the studies presented an effective platform for the preparation of 3D scaffolds which contain effective conjugation sites for attachment of specific bioactive signals of interest, as well as actively reducing non-specific protein interactions.This research was supported by the Cooperative Research Centre for Polymers (CRCP)