Designing a Low-Cost Mechatronic Device for Semi-Automatic Saffron Harvesting

This paper addresses the design of a novel mechatronic device for saffron harvesting. The main proposed challenge consists of proposing a new paradigm for semi-automatic harvesting of saffron flowers. The proposed novel solution is designed for being easily portable with user-friendly and cost-oriented features and with a fully electric battery-powered actuation. A preliminary concept design has been proposed as based on a specific novel cam mechanism in combination with an elastic spring for fulfilling the detachment of the flowers from their stems. Numerical calculations and simulations have been carried out to complete the full design of a proof-of-concept prototype. Preliminary experimental tests have been carried out to demonstrate the engineering feasibility and effectiveness of the proposed design solutions, whose concept has been submitted for patenting

Design and preliminary testing of a novel semi-automatic saffron harvesting device

This paper addresses the procedure for designing a novel mechatronic device for a semi-automatic saffron harvesting. The design process includes the kinematic analysis and synthesis of the proposed mechanism to fulfill a grasping and harvesting of saffron flower with a specific two-finger gripper design. Then, a cam mechanism and elastic spring elements are designed to provide a shaking movement that achieves the splitting of the flower from its steam and a consequent flower harvesting. This is followed by a suction system for collecting and storing the harvested flowers. A 3D printed prototype is reported and preliminarily tested for validating the engineering feasibility and effectiveness of the proposed design solution

Cooperation between Constitutive and Inducible Chemokines Enables T Cell Engraftment and Immune Attack in Solid Tumors

© 2019 Elsevier Inc. We investigated the role of chemokines in regulating T cell accumulation in solid tumors. CCL5 and CXCL9 overexpression was associated with CD8+ T cell infiltration in solid tumors. T cell infiltration required tumor cell-derived CCL5 and was amplified by IFN-γ-inducible, myeloid cell-secreted CXCL9. CCL5 and CXCL9 coexpression revealed immunoreactive tumors with prolonged survival and response to checkpoint blockade. Loss of CCL5 expression in human tumors was associated with epigenetic silencing through DNA methylation. Reduction of CCL5 expression caused tumor-infiltrating lymphocyte (TIL) desertification, whereas forced CCL5 expression prevented Cxcl9 expression and TILs loss, and attenuated tumor growth in mice through IFN-γ. The cooperation between tumor-derived CCL5 and IFN-γ-inducible CXCR3 ligands secreted by myeloid cells is key for orchestrating T cell infiltration in immunoreactive and immunoresponsive tumors. Dangaj et al. show that tumor cell-expressed CCL5 and macrophage- and DC-expressed CXCL9 are important for the infiltration of T cells into tumors, a process that also requires recognition of tumor antigens by T cells. CCL5 is often epigenetically silenced in tumor cells but can be reactivated by Decitabine

Neoantigen-specific CD8 T cells with high structural avidity preferentially reside in and eliminate tumors

Abstract The success of cancer immunotherapy depends in part on the strength of antigen recognition by T cells. Here, we characterize the T cell receptor (TCR) functional (antigen sensitivity) and structural (monomeric pMHC-TCR off-rates) avidities of 371 CD8 T cell clones specific for neoantigens, tumor-associated antigens (TAAs) or viral antigens isolated from tumors or blood of patients and healthy donors. T cells from tumors exhibit stronger functional and structural avidity than their blood counterparts. Relative to TAA, neoantigen-specific T cells are of higher structural avidity and, consistently, are preferentially detected in tumors. Effective tumor infiltration in mice models is associated with high structural avidity and CXCR3 expression. Based on TCR biophysicochemical properties, we derive and apply an in silico model predicting TCR structural avidity and validate the enrichment in high avidity T cells in patients’ tumors. These observations indicate a direct relationship between neoantigen recognition, T cell functionality and tumor infiltration. These results delineate a rational approach to identify potent T cells for personalized cancer immunotherapy

Myeloid antigen-presenting cell niches sustain antitumor T cells and license PD-1 blockade via CD28 costimulation

The mechanisms regulating exhaustion of tumor-infiltrating lymphocytes (TIL) and responsiveness to PD-1 blockade remain partly unknown. In human ovarian cancer, we show that tumor-specific CD8(+) TIL accumulate in tumor islets, where they engage antigen and upregulate PD-1, which restrains their functions. Intraepithelial PD-1(+)CD8 (+) TIL can be, however, polyfunctional. PD-1(+) TIL indeed exhibit a continuum of exhaustion states, with variable levels of CD28 costimulation, which is provided by antigen-presenting cells (APC) in intraepithelial tumor myeloid niches. CD28 costimulation is associated with improved effector fitness of exhausted CD8(+) TIL and is required for their activation upon PD-1 blockade, which also requires tumormyeloid APC. Exhausted TIL lacking proper CD28 costimulation in situ fail to respond to PD-1 blockade, and their response may be rescued by local CTLA-4 blockade and tumor APC stimulation via CD40L