Design parameters of free-form color splitters for subwavelength pixelated image sensors

Summary: Metasurface-based color splitters are emerging as next-generation optical components for image sensors, replacing classical color filters and microlens arrays. In this work, we report how the design parameters such as the device dimensions and refractive indices of the dielectrics affect the optical efficiency of the color splitters. Also, we report how the design grid resolution parameters affect the optical efficiency and discover that the fabrication of a color splitter is possible even in legacy fabrication facilities with low structure resolutions

Sample-efficient inverse design of freeform nanophotonic devices with physics-informed reinforcement learning

Finding an optimal device structure in the vast combinatorial design space of freeform nanophotonic design has been an enormous challenge. In this study, we propose physics-informed reinforcement learning (PIRL) that combines the adjoint-based method with reinforcement learning to improve the sample efficiency by an order of magnitude compared to conventional reinforcement learning and overcome the issue of local minima. To illustrate these advantages of PIRL over other conventional optimization algorithms, we design a family of one-dimensional metasurface beam deflectors using PIRL, exceeding most reported records. We also explore the transfer learning capability of PIRL that further improves sample efficiency and demonstrate how the minimum feature size of the design can be enforced in PIRL through reward engineering. With its high sample efficiency, robustness, and ability to seamlessly incorporate practical device design constraints, our method offers a promising approach to highly combinatorial freeform device optimization in various physical domains

CXCR4 is a key regulator of neutrophil release from the bone marrow under basal and stress granulopoiesis conditions

The number of neutrophils in the blood is tightly regulated to ensure adequate protection against microbial pathogens while minimizing damage to host tissue. Neutrophil homeostasis in the blood is achieved through a balance of neutrophil production, release from the bone marrow, and clearance from the circulation. Accumulating evidence suggests that signaling by CXCL12, through its major receptor CXCR4, plays a key role in maintaining neutrophil homeostasis. Herein, we generated mice with a myeloid lineage–restricted deletion of CXCR4 to define the mechanisms by which CXCR4 signals regulate this process. We show that CXCR4 negatively regulates neutrophil release from the bone marrow in a cell-autonomous fashion. However, CXCR4 is dispensable for neutrophil clearance from the circulation. Neutrophil mobilization responses to granulocyte colony-stimulating factor (G-CSF), CXCL2, or Listeria monocytogenes infection are absent or impaired, suggesting that disruption of CXCR4 signaling may be a common step mediating neutrophil release. Collectively, these data suggest that CXCR4 signaling maintains neutrophil homeostasis in the blood under both basal and stress granulopoiesis conditions primarily by regulating neutrophil release from the bone marrow

CXCR4 dimerization and beta-arrestin-mediated signaling account for the enhanced chemotaxis to CXCL12 in WHIM syndrome.

WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome is an immune deficiency linked in many cases to heterozygous mutations causing truncations in the cytoplasmic tail of CXC chemokine receptor 4 (CXCR4). Leukocytes expressing truncated CXCR4 display enhanced responses to the receptor ligand CXCL12, including chemotaxis, which likely impair their trafficking and contribute to the immunohematologic clinical manifestations of the syndrome. CXCR4 desensitization and endocytosis are dependent on beta-arrestin (betaarr) recruitment to the cytoplasmic tail, so that the truncated CXCR4 are refractory to these processes and so have enhanced G protein-dependent signaling. Here, we show that the augmented responsiveness of WHIM leukocytes is also accounted for by enhanced betaarr2-dependent signaling downstream of the truncated CXCR4 receptor. Indeed, the WHIM-associated receptor CXCR4(1013) maintains association with betaarr2 and triggers augmented and prolonged betaarr2-dependent signaling, as revealed by ERK1/2 phosphorylation kinetics. Evidence is also provided that CXCR4(1013)-mediated chemotaxis critically requires betaarr2, and disrupting the SHSK motif in the third intracellular loop of CXCR4(1013) abrogates betaarr2-mediated signaling, but not coupling to G proteins, and normalizes chemotaxis. We also demonstrate that CXCR4(1013) spontaneously forms heterodimers with wild-type CXCR4. Accordingly, we propose a model where enhanced functional interactions between betaarr2 and receptor dimers account for the altered responsiveness of WHIM leukocytes to CXCL12