52 research outputs found
Numerical calculations of effective elastic properties of two cellular structures
Young's moduli of regular two-dimensional truss-like and eye-shape-like
structures are simulated by using the finite element method. The structures are
the idealizations of soft polymeric materials used in the electret
applications. In the simulations size of the representative smallest units are
varied, which changes the dimensions of the cell-walls in the structures. A
power-law expression with a quadratic as the exponential term is proposed for
the effective Young's moduli of the systems as a function of the solid volume
fraction. The data is divided into three regions with respect to the volume
fraction; low, intermediate and high concentrations. The parameters of the
proposed power-law expression in each region are later represented as a
function of the structural parameters, unit-cell dimensions. The presented
expression can be used to predict structure/property relationship in materials
with similar cellular structures. It is observed that the structures with
volume fractions of solid higher than 0.15 exhibit the importance of the
cell-wall thickness contribution in the elastic properties. The cell-wall
thickness is the most significant factor to predict the effective Young's
modulus of regular cellular structures at high volume fractions of solid. At
lower concentrations of solid, eye-like structure yields lower Young's modulus
than the truss-like structure with the similar anisotropy. Comparison of the
numerical results with those of experimental data of poly(propylene) show good
aggreement regarding the influence of cell-wall thickness on elastic properties
of thin cellular films.Comment: 7 figures and 2 table
EBAG9 controls CD8(+) T cell memory formation responding to tumor challenge in mice
Insight into processes that determine CD8(+) T cell memory formation has been obtained from infection models. These models are biased toward an inflammatory milieu and often employ high avidity CD8(+) T cells in adoptive transfer procedures. It is unclear whether these conditions mimic the differentiation processes of an endogenous repertoire that proceed upon non-inflammatory conditions prevailing in premalignant tumor lesions. We examined the role of cytolytic capacity on CD8(+) T cell fate decisions when primed by tumor cells or by minor histocompatibility antigen-mismatched leukocytes. CD8(+) memory commitment was analyzed in Ebag9-deficient mice that exhibit an enhanced tumor cell lysis. This property endowed Ebag9(-/-) mice with extended control of Tcl-1 oncogene-induced chronic lymphocytic leukemia progression. In Ebag9(-/-) mice, an expanded memory population was obtained for anti-HY and anti-SV40 T antigen-specific T cells, despite unchanged effector frequencies in the primary response. By comparing the single-cell transcriptomes of CD8(+) T cells responding to tumor cell vaccination, we found differential distribution of subpopulations between Ebag9(+/+) and Ebag9(-/-) T cells. In Ebag9(-/-) cells, these larger clusters contained genes encoding transcription factors regulating memory cell differentiation, along with anti-apoptotic gene functions. Our findings link EBAG9-controlled cytolytic activity and the commitment to the CD8(+) memory lineage
EBAG9-silencing exerts an immune checkpoint function without aggravating adverse effects
Chimeric antigen receptor (CAR) T cells have revolutionized treatment of B-cell malignancies. However, enhancing the efficacy of engineered T cells without compromising their safety is warranted. The estrogen receptor-binding fragment-associated antigen 9 (EBAG9) inhibits release of cytolytic enzymes from cytotoxic T lymphocytes. Here, we examined the potency of EBAG9-silencing for the improvement of adoptive T cell therapy. Micro-RNA-mediated EBAG9 downregulation in transplanted CTLs from immunized mice improved their cytolytic competence in a tumor model. In tolerant female recipient mice that received organ transplants, a minor histocompatibility antigen was turned into a rejection antigen by Ebag9 deletion, indicating an immune checkpoint function for EBAG9. Considerably less EBAG9-silenced human CAR T cells were needed for tumor growth control in a xenotransplantation model. Transcriptome profiling did not reveal additional risks regarding genotoxicity or aberrant differentiation. A single-step retrovirus transduction process links CAR or TCR expression with miRNA-mediated EBAG9 downregulation. Despite higher cytolytic efficacy, release of cytokines associated with cytokine release syndrome remains unaffected. Collectively, EBAG9-silencing enhances effector capacity of TCR- and CAR-engineered T cells, results in improved tumor eradication, facilitates efficient manufacturing, and decreases the therapeutic dose
CXCR5 CAR-T cells simultaneously target B cell non-Hodgkin's lymphoma and tumor-supportive follicular T helper cells
CAR-T cell therapy targeting CD19 demonstrated strong activity against advanced B cell leukemia, however shows less efficacy against lymphoma with nodal dissemination. To target both B cell Non-Hodgkin's lymphoma (B-NHLs) and follicular T helper (Tfh) cells in the tumor microenvironment (TME), we apply here a chimeric antigen receptor (CAR) that recognizes human CXCR5 with high avidity. CXCR5, physiologically expressed on mature B and Tfh cells, is also highly expressed on nodal B-NHLs. Anti-CXCR5 CAR-T cells eradicate B-NHL cells and lymphoma-supportive Tfh cells more potently than CD19 CAR-T cells in vitro, and they efficiently inhibit lymphoma growth in a murine xenograft model. Administration of anti-murine CXCR5 CAR-T cells in syngeneic mice specifically depletes endogenous and malignant B and Tfh cells without unexpected on-target/off-tumor effects. Collectively, anti-CXCR5 CAR-T cells provide a promising treatment strategy for nodal B-NHLs through the simultaneous elimination of lymphoma B cells and Tfh cells of the tumor-supporting TME
Determination of density, viscosity, and surface tension for the system isobutene-sulfuric acid-tert-butyl alcohol-water
Organspendermangel durch Transplantationsskandale? Analyse der realisierten Organspenden und des Potentials in Nordrhein-Westfalen 2010-2012
Zeta potential of motile spores of the green alga Ulva linza and the influence of electrostatic interactions on spore settlement and adhesion strength
Passive Transfer of Hepatitis C Antibodies by Kidney Transplantation from A Single Donor to Two Recipients
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