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  • Jimenez posted an update 9 months, 1 week ago

    Large-scale layers peeling after the laser irradiation of dual ion beam sputtering coatings is discovered and a model is established to explain it. The laser damage morphologies relate to the laser fluence, showing thermomechanical coupling failure at low energy and coating layers separation at high energy. High-pressure gradients appear in the interaction between laser and coatings, resulting in large-scale layer separation. A two-step laser damage model including defect-induced damage process and ionized air wave damage process is proposed to explain the two phenomena at different energy. At relatively high energies (higher than 20 J/cm2), ionization of the air can be initiated, leading to a peeling off effect. The peeling effect is related to the thermomechanical properties of the coating materials.The subiculum is the major output component of the hippocampal formation and one of the major brain structures most affected by Alzheimer’s disease. Our previous work revealed a hidden laminar architecture within the mouse subiculum. However, the rotation of the hippocampal longitudinal axis across species makes it unclear how the laminar organization is represented in human subiculum. Using in situ hybridization data from the Allen Human Brain Atlas, we demonstrate that the human subiculum also contains complementary laminar gene expression patterns similar to the mouse. In addition, we provide evidence that the molecular domain boundaries in human subiculum correspond to microstructural differences observed in high resolution MRI and fiber density imaging. Finally, we show both similarities and differences in the gene expression profile of subiculum pyramidal cells within homologous lamina. Overall, we present a new 3D model of the anatomical organization of human subiculum and its evolution from the mouse.Effective T cell-based immunotherapy of solid malignancies requires intratumoral activity of cytotoxic T cells and induction of protective immune memory. A major obstacle to intratumoral trafficking and activation of vaccine-primed or adoptively transferred tumor-specific T cells is the immunosuppressive tumor microenvironment (TME), which currently limits the efficacy of both anti-tumor vaccines and adoptive cell therapy (ACT). Combination treatments to overcome TME-mediated immunosuppression are therefore urgently needed. We combined intratumoral administration of the synthetic toll-like receptor 4 agonist glucopyranosyl lipid A (oil-in-water formulation, G100) with either active vaccination or adoptive transfer of tumor-specific CD8 T cells to mice bearing established melanomas or orthotopically inoculated glioblastomas. In combination with cancer vaccines or ACT, G100 significantly increased expression of innate immune genes, infiltration and expansion of activated effector T cells, antigen spreading, and durable immune responses. Complete tumor regression of both injected and non-injected tumors was observed only in mice receiving combination immunotherapy. TLR4-based intratumoral immune activation may be a viable approach to enhance the efficacy of therapeutic cancer vaccines and ACT in patients.The emergence of perpendicular magnetic anisotropy (PMA) in amorphous thin films, which eventually transforms the magnetic spins form an in-plane to the out-of-plane configuration, also known as a spin-reorientation transition (SRT), is a fundamental roadblock to attain the high flux concentration advantage of these functional materials for broadband applications. The present work is focused on unfolding the origin of PMA in amorphous thin films deposited by magnetron sputtering. The amorphous films were deposited under a broad range of sputtering pressure (1.6-6.2 mTorr), and its effect on the thin film growth mechanisms was correlated to the static global magnetic behaviours, magnetic domain structure, and dynamic magnetic performance. The films deposited under low-pressure revealed a dominant in-plane uniaxial anisotropy along with an emerging, however feeble, perpendicular component, which eventually evolved as a dominant PMA when deposited under high-pressure sputtering. This change in the nature of anisotropy redefined the orientation of spins from in-plane to out-of-plane. The SRT in amorphous films was attributed to the dramatic change in the growth mechanism of disorder atomic structure from a homogeneously dispersed to a porous columnar microstructure. We suggest the origin of PMA is associated with the columnar growth of the amorphous films, which can be eluded by a careful selection of a deposition pressure regime to avoid its detrimental effect on the soft magnetic performance. To the author’s best knowledge, no such report links the sputtering pressure as a governing mechanism of perpendicular magnetisation in technologically important amorphous thin films.While RSV is a major cause of respiratory morbidity in infants, vaccine development is hindered by the immaturity and Th2-bias of the infant immune system and the legacy of enhanced respiratory disease (ERD) after RSV infection following immunization with formalin inactivated (FI)-RSV vaccine in earlier clinical trials. Preclinical studies have demonstrated that an adenoviral vector-based RSV F vaccine candidate (Ad26.RSV.FA2) induces Th1-biased protective immune responses, without signs of ERD upon subsequent RSV challenge. We here developed an Ad26 vector encoding the RSV F protein stabilized in its prefusion conformation (Ad26.RSV.preF). In adult mice, Ad26.RSV.preF induced superior, Th1-biased IgG2a-dominated humoral responses as compared to Ad26.RSV.FA2, while maintaining the strong Th1-biased cellular responses. Similar to adult mice, Ad26.RSV.preF induced robust and durable humoral immunity in neonatal mice, again characterized by IgG2a-dominated RSV F-binding antibodies, and high and stable virus-neutralizing titers. In addition, vaccine-elicited cellular immune responses were durable and characterized by IFN-γ-producing CD4+ and CD8+ T cells, with a profound Th1 bias. In contrast, immunization of neonatal mice with FI-RSV resulted in IgG1 RSV F-binding antibodies associated with a Th2 phenotype, no detectable virus-neutralizing antibodies, and a Th2-biased cellular response. Oxythiamine chloride nmr These results are supportive for the clinical development of Ad26.RSV.preF for use in infants.

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