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Programmed death-ligand 1 (PD-L1) drives inhibition of antigen-specific T cell responses through engage- ment of its receptor programmed death-1 (PD-1) on activated T cells. Overexpression of these immune checkpoint proteins in the tumor microenvironment has motivated the design of targeted antibodies that disrupt this interaction. Despite clinical success of these antibodies, response rates remain low, necessi- tating novel approaches to enhance performance. Here, we report the development of antibody fusion pro- teins that block immune checkpoint pathways through a distinct mechanism targeting molecular trafficking. By engaging multiple receptor epitopes on PD-L1, our engineered multiparatopic antibodies induce rapid clustering, internalization, and degradation in an epitope- and topology-dependent manner. The comple- mentary mechanisms of ligand blockade and receptor downregulation led to more durable immune cell acti- vation and dramatically reduced PD-L1 availability in mouse tumors. Collectively, these multiparatopic anti- bodies offer mechanistic insight into immune checkpoint protein trafficking and how it may be manipulated to reprogram immune outcomes. 

Performance of photonic devices critically depends upon their efficiency on controlling the flow of light therein. In the recent past, the implementation of plasmonics, two-dimensional (2D) materials and metamaterials for enhanced light-matter interaction (through concepts such as sub-wavelength light confinement and dynamic wavefront shape manipulation) led to diverse applications belonging to spectroscopy, imaging and optical sensing etc. While 2D materials such as graphene, MoS2 etc., are still being explored in optical sensing in last few years, the application of plasmonics and metamaterials is limited owing to the involvement of noble metals having a constant electron density. The capability of competently controlling the electron density of noble metals is very limited. Further, due to absorption characteristics of metals, the plasmonic and metamaterial devices suffer from large optical loss. Hence, the photonic devices (sensors, in particular) require that an efficient dynamic control of light at nanoscale through field (electric or optical) variation using substitute low-loss materials. One such option may be plasmonic metasurfaces. Metasurfaces are arrays of optical antenna-like anisotropic structures (sub-wavelength size), which are designated to control the amplitude and phase of reflected, scattered and transmitted components of incident light radiation. The present review put forth recent development on metamaterial and metastructure-based various sensors. 

We report computer simulations of two-dimensional convex hard superellipse particle phases vs. particle shape parameters including aspect ratio, corner curvature, and sidewall curvature. Shapes investigated include disks, ellipses, squares, rectangles, and rhombuses, as well as shapes with non-uniform curvature including rounded squares, rounded rectangles, and rounded rhombuses. Using measures of orientational order, order parameters, and a novel stretched bond orientational order parameter, we systematically identify particle shape properties that determine liquid crystal and crystalline phases including their coarse boundaries and symmetry. We observe phases including isotropic, nematic, tetratic, plastic crystals, square crystals, and hexagonal crystals (including stretched variants). Our results catalog known benchmark shapes, but include new shapes that also interpolate between known shapes. Our results indicate design rules for particle shapes that determine two-dimensional liquid, liquid crystalline, and crystalline microstructures that can be realized via particle assembly.