Design of a reflection-suppressed all-optical diode based on asymmetric L-shaped nonlinear photonic crystal cavity

A simple design method for suppressing the reflection of the all-optical diode based on the L-shaped photonic crystal (PC) cavity is proposed. Analyzing the linear resonant characteristics of the PC cavity and using the nonlinear coupled-mode theory, the strategy for obtaining reflection-suppressed structure is illustrated. Based on the design rule, a “reflection-suppressed all-optical diode” is presented, and numerical solutions indicate that the designed structure has a small reflection as well as an extremely large nonreciprocal transmission ratio

Tumor-Associated Macrophages: Therapeutic Targets for Skin Cancer

Tumor-associated macrophages (TAMs) and regulatory T cells (Tregs) are significant components of the microenvironment of solid tumors in the majority of cancers. TAMs sequentially develop from monocytes into functional macrophages. In each differentiation stage, TAMs obtain various immunosuppressive functions to maintain the tumor microenvironment (e.g., expression of immune checkpoint molecules, production of Treg-related chemokines and cytokines, production of arginase I). Although the main population of TAMs is immunosuppressive M2 macrophages, TAMs can be modulated into M1-type macrophages in each differential stage, leading to the suppression of tumor growth. Because the administration of certain drugs or stromal factors can stimulate TAMs to produce specific chemokines, leading to the recruitment of various tumor-infiltrating lymphocytes, TAMs can serve as targets for cancer immunotherapy. In this review, we discuss the differentiation, activation, and immunosuppressive function of TAMs, as well as their benefits in cancer immunotherapy

Evaluation of oral immunotherapy efficacy and safety by maintenance dose dependency: A multicenter randomized study

Background Generally, oral immunotherapy (OIT) aims for daily administration. Recently, the efficacy of treatment with OIT at a low dose has been reported. However, the optimal dose and the evaluation of dose-dependent OIT outcome have not been described. Methods A multicenter, parallel, open-labeled, prospective, non-placebo controlled, randomized study enrolled 101 Japanese patients for treatment with OIT. We hypothesized that target dose OIT would induce short-term unresponsiveness (StU) earlier than reduced dose OIT. StU was defined as no response to 6200 mg whole egg, 3400 mg milk, and 2600 mg wheat protein, as evaluated by oral food challenge after 2-week ingestion cessation. To compare the two doses of OIT efficacy, the maximum ingestion doses during the maintenance phase of OIT were divided into 100%-dose or 25%-dose groups against their target StU dose, respectively. A total of 51 patients were assigned to the 100%-dose group [hen's egg (HE) = 26, cow's milk (CM) = 13, wheat = 12] and 50 to the 25%-dose group (HE = 25, CM = 13, wheat = 12). Primary outcome was established by comparing StU at 1 year. Secondary outcome was StU at 2 years and established by comparing allergic symptoms and immunological changes. Results The year 1 StU rates (%) for the 100%- and 25%-dose groups were 26.9 vs. 20.0 (HE), 7.7 vs. 15.4 (CM), and 50.0 vs. 16.7 (wheat), respectively. The year 2 StU rates were 30.8 vs. 36.0 (HE), 7.7 vs. 23.1 (CM), and 58.3 vs. 58.3 (wheat), respectively. There were no statistically significant differences in StU between years 1 and 2. The total allergic symptom rate in the 25%-dose group was lower than that in the 100%-dose group for egg, milk, and wheat. Antigen-specific IgE levels for egg-white, milk, and wheat decreased at 12 months. Conclusions Reduced maintenance dose of egg OIT showed similar therapeutic efficacy to the target dose. However, we were not able to clearly demonstrate the efficacy, particularly for milk and wheat. Reducing the maintenance dose for eggs, milk, and wheat may effectively lower the symptoms associated with their consumption compared to the target OIT dose. Furthermore, aggressive reduction of the maintenance dose might be important for milk and wheat, compared to the 25%-dose OIT

Serum Level of Soluble CD163 May Be a Predictive Marker of the Effectiveness of Nivolumab in Patients With Advanced Cutaneous Melanoma

Antibodies against programmed cell death protein 1, such as nivolumab and pembrolizumab, are widely used for treating various cancers, including advanced melanoma. Nivolumab significantly prolongs survival in patients with metastatic melanoma, and sequential administration with lipilimumab may improve outcomes when switched at the appropriate time. Biomarkers are therefore needed to evaluate nivolumab efficacy soon after first administration. This study analyzed serum levels of soluble cluster of differentiation 163 (sCD163) in 59 cases of advanced cutaneous melanoma and 16 cases of advanced mucosal melanoma treated using nivolumab. Serum levels of sCD163 were significantly increased after 6 weeks in responders compared to non-responders after initial administration of nivolumab for cutaneous melanoma. In contrast, no significant difference between responders and non-responders was seen among patients with non-cutaneous melanoma. These results suggest that sCD163 may be useful as a biomarker for selecting patients with advanced cutaneous melanoma most likely to benefit from anti-melanoma immunotherapy

All-Optical Diode Suppressing Broadband Backward Transmission Using Single- and Four-Port Photonic Crystal Cavities

We present an all-optical diode suppressing broadband backward transmission using single-port and four-port photonic crystal (PC) cavities and its operation principle. We find that, by combining a four-port PC cavity and two power-dependent phase shifters that are composed by a 3-dB power divider and two single-port PC cavities, the backward transmission in the nonlinear-resonator-based all-optical diode becomes theoretically 0% for any input power and any input wavelength. To confirm the validity of our approach, the numerical analysis based on the nonlinear beam propagation method as well as the coupled mode theory is performed. The results prove that the forward transmission of -4 dB and large nonreciprocal transmission ratio of 35 dB are achievable

A rigorous definition of nonlinear parameter γ and effective area A_eff for photonic crystal optical waveguides

A rigorous definition of nonlinear parameter γ for high-index-contrast (HIC) periodic optical waveguides, such as photonic crystal (PC) optical waveguides, is proposed. The definition is fully vectorial, and approximations assumed in previous works are unnecessary. The γ values calculated by the proposed definition are compared with those obtained by previous definitions, the rigorous nonlinear mode solver, and measured values for weakly guiding optical fibers, HIC Si-nanowire waveguides, and PC waveguides. It is demonstrated that the γ values calculated by proposed definition agree well with those of the rigorous nonlinear mode solver and experiments for all three waveguides, showing the validity of the definition