Time-domain Modeling of Light Matter Interactions in Active Plasmonic Metamaterials

Metamaterials are artificially engineered to obtain unprecedented electromagnetic control leading to new and exciting applications. In order to further the understanding of fundamental optical phenomena and explore the effects of dynamically changing media on light propagation, numerous modeling methods have been developed. Among them, due to the nature of transient, nonlinear, and impulsive behavior, the time domain modeling approach is viewed as the most viable method. In this work, we develop a time-domain model (method of finite-difference time-domain (FDTD)) of light matter interactions in active plasmonic metamaterials. In order to model the dispersion of plasmonic nanostructure in the time-domain, we introduce a generalized dispersive material model built on Padé approximants. The developed 3D FDTD solver is then applied to study several plasmonic nanostructures and metamaterials, such as metal-dielectric composite films, random nano-nets for transparent conducting electrodes, and a graphene photodetector enhanced by a fractal plasmonic metasurface. In addition to this we also developed a multi-physics time-domain model to investigate the properties of a silver nanohole array coated with Rhodamine-101 dye. With accurate modeling of the retrieved kinetic parameters, the simulated emission intensity shows clear lasing, which is in good agreement with our experimental measurements. By tracing the population inversion and polarization dynamics, the amplification and lasing regimes inside the nanohole cavity can be clearly distinguished. With the help of our systematic approach, we further the understanding of time-resolved physics in active plasmonic nanostructures with gain

Studies of plasmonic hot-spot translation by a metal-dielectric layered superlens

We have studied the ability of a lamellar near-field superlens to transfer an enhanced electromagnetic field to the far side of the lens. In this work, we have experimentally and numerically investigated superlensing in the visible range. By using the resonant hot-spot field enhancements from optical nanoantennas as sources, we investigated the translation of these sources to the far side of a layered silver-silica superlens operating in the canalization regime. Using near-field scanning optical microscopy (NSOM), we have observed evidence of superlens-enabled enhanced-field translation at a wavelength of about 680 nm. Specifically, we discuss our recent experimental and simulation results on the translation of hot spots using a silver-silica layered superlens design. We compare the experimental results with our numerical simulations and discuss the perspectives and limitations of our approach

LDC7559 inhibits microglial activation and GSDMD-dependent pyroptosis after subarachnoid hemorrhage

Mounting evidence indicates that inhibition of microglial activation and neuronal pyroptosis plays important roles in brain function recovery after subarachnoid hemorrhage (SAH). LDC7559 is a newly discovered gasdermin D (GSDMD) inhibitor. Previous studies have demonstrated that LDC7559 could inhibit microglial proliferation and pyroptosis. However, the beneficial effects of LDC7559 on SAH remain obscure. Based on this background, we investigated the potential role and the mechanism of LDC7559 on SAH-induced brain damage both in vivo and in vitro. The findings revealed that microglial activation and neuronal pyroptosis were evidently increased after SAH, which could be markedly suppressed by LDC7559 both in vivo and in vitro. Meanwhile, LDC7559 treatment reduced neuronal apoptosis and improved behavior function. Mechanistically, LDC7559 decreased the levels of GSDMD and cleaved GSDMD after SAH. In contrast, nod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome activation by nigericin increased GSDMD-mediated pyroptosis and abated the beneficial effects of LDC7559 on SAH-induced brain damage. However, LDC7559 treatment did not significantly affect the expression of NLRP3 after SAH. Taken together, LDC7559 might suppress neuronal pyroptosis and microglial activation after SAH by inhibiting GSDMD, thereby promoting brain functional recovery

Fabrication and realistic modeling of three-dimensional metal-dielectric composites

Historically, the methods used to describe the electromagnetic response of random, three-dimensional (3D), metal-dielectric composites (MDCs) have been limited to approximations such as effective-medium theories that employ easily-obtained, macroscopic parameters. Full-wave numerical simulations such as finite-difference time domain (FDTD) calculations are difficult for random MDCs due to the fact that the nanoscale geometry of a random composite is generally difficult to ascertain after fabrication. We have developed a fabrication method for creating semicontinuous metal films with arbitrary thicknesses and a modeling technique for such films using realistic geometries. We extended our two-dimensional simulation method to obtain realistic geometries of 3D MDC samples, and we obtained the detailed near-and far-field electromagnetic responses of such composites using FDTD calculations. Our simulation results agree quantitatively well with the experimentally measured far-field spectra of the real samples. (C) 2011 Society of Photo-Optical Instrumentation Engineers (SPIE). [DOI: 10.1117/1.3590208

Enhanced Graphene Photodetector with Fractal Metasurface.

Graphene has been demonstrated to be a promising photodetection material because of its ultrabroadband optical absorption, compatibility with CMOS technology, and dynamic tunability in optical and electrical properties. However, being a single atomic layer thick, graphene has intrinsically small optical absorption, which hinders its incorporation with modern photodetecting systems. In this work, we propose a gold snowflake-like fractal metasurface design to realize broadband and polarization-insensitive plasmonic enhancement in graphene photodetector. We experimentally obtain an enhanced photovoltage from the fractal metasurface that is an order of magnitude greater than that generated at a plain gold-graphene edge and such an enhancement in the photovoltage sustains over the entire visible spectrum. We also observed a relatively constant photoresponse with respect to polarization angles of incident light, as a result of the combination of two orthogonally oriented concentric hexagonal fractal geometries in one metasurface

Efficacy and toxicities of gemcitabine and cisplatin combined with endostar in advanced thymoma and thymic carcinoma

Background Thymoma and thymic carcinoma are rare thymic epithelial tumors. We investigated the efficacy of first‐line gemcitabine and cisplatin (GP) chemotherapy versus gemcitabine and cisplatin chemotherapy combined with the anti‐angiogenic drug endostar (GP + E) in advanced thymoma and thymic carcinoma. Methods The records of 45 patients with invasive metastatic thymomas or thymic carcinomas treated with GP as first‐line therapy between August 2008 and July 2017 at the Department of Respiratory Medicine, Peking University Cancer Hospital and Institute were retrospectively reviewed. Results Eighteen patients (75%) in the GP + E group achieved a partial response and six (25%) had stable disease. In GP only group, nine (42.8%) patients achieved a partial response, 11 (52.4%) had stable disease, and one (4.8%) had progressive disease. The GP + E group had a significantly higher overall response rate (75% vs. 42.9%; P = 0.028), and median progression‐free survival (PFS) and overall survival (OS) of 19 and 76 months, respectively. In the GP only group, median PFS and OS were 16 and 29 months, respectively. PFS and OS were not significantly different between the groups. Conclusions GP has moderate efficacy and could represent a suitable first‐line therapy for thymic carcinoma and thymoma. Chemotherapy combined with endostar could improve the overall response rate, but did not prolong PFS or OS

Timing of Brain Radiation Therapy Impacts Outcomes in Patients with Non-small Cell Lung Cancer Who Develop Brain Metastases

Background and objective Radiotherapy combined with chemotherapy or molecular targeted therapy remains the standard of treatment for brain metastases from non-small cell lung cancer (NSCLC). The aim of this study is to determine if the deferral of brain radiotherapy impacts patient outcomes. Methods Between May 2003 and December 2015, a total of 198 patients with brain metastases from NSCLC who received both brain radiotherapy and systemic therapy (chemotherapy or targeted therapy) were identified. The rate of grade 3-4 adverse reactions related to chemotherapy and radiotherapy had no significant difference between two groups. 127 patients received concurrent brain radiotherapy and systemic therapy, and 71 patients received deferred brain radiotherapy after at least two cycles of chemotherapy or targeted therapy. Disease specific-graded prognostic assessment was similar in early radiotherapy group and deferred radiotherapy group. Results Median overall survival (OS) was longer in early radiotherapy group compared to deferred radiotherapy group (17.9 months vs 12.6 months; P=0.038). Progression free survival (PFS) was also improved in patients receiving early radiotherapy compared to those receiving deferred radiotherapy (4.0 months vs 3.0 months; P<0.01). Receiving tyrosine kinase inhibitor (TKI) therapy after the diagnosis of brain metastases as any line therapy improved the OS (20.0 months vs 10.7 months; P<0.01), whereas receiving TKI as first line therapy did not (17.9 months vs 15.2 months; P=0.289). Conclusion Our study suggests that the use of deferred brain radiotherapy may resulted in inferior OS in patients with NSCLC who develop brain metastases. A prospective multi-central randomized study is imminently needed

Effects of Local Radiation Combined with Chemotherapy in the treatment of Patients with Extensive-stage Small Cell Lung Cancer

Background and objective Chemotherapy is a highly efficient primary treatment for extensive-stage small cell lung cancer (ES-SCLC). However, patients receiving such treatment are prone to develop drug resistance. Local treatment is palliative and thus can alleviate the local symptoms and improve quality of life, but limited evidence is available for prolonging survival. Hence, this study evaluated the role of local treatment in chemotherapy of patients with ES-SCLC. Methods A total of 302 ES-SCLC cases were enrolled in this retrospective study. Prognostic factors were analyzed by Kaplan-Meier and Cox multivariate proportional hazards model. Results Median progression-free survival (PFS) and median survival time (MST) of the patients were 4.4 and 10.4 months, respectively. 1-, 2-, and 3-year survival rates were 37.8%, 10.2% and 4.4%, correspondingly. The MST of the primary tumor radiotherapy plus chemotherapy group was 14.3 months, whereas that of the chemotherapy group was 8.2 months (P<0.01). The MSTs of multiple-site, single-site, and non-metastasis local treatments were 18.7, 12.3 and 8.9 months, respectively (P<0.01). The MSTs of initiative, passive, and non-metastasis local treatments were 16.0, 10.9 and 9.4 months, correspondingly (P<0.01). The MSTs of patients with prophylactic cranial irradiation (PCI) and those without PCI were 19.8 and 9.9 months, respectively (P<0.01). Primary tumor radiotherapy, metastasis local treatment, and PCI were independent prognostic factors for ES-SCLC. Conclusion Primary tumor radiotherapy, metastasis local treatment, and PCI can significantly improve survival in patients with ES-SCLC

Construction of an endoplasmic reticulum stress-related signature in lung adenocarcinoma by comprehensive bioinformatics analysis

Abstract Background Lung Adenocarcinoma (LUAD) is a major component of lung cancer. Endoplasmic reticulum stress (ERS) has emerged as a new target for some tumor treatments. Methods The expression and clinical data of LUAD samples were downloaded from The Cancer Genome Atlas (TCGA) and The Gene Expression Omnibus (GEO) database, followed by acquiring ERS-related genes (ERSGs) from the GeneCards database. Differentially expressed endoplasmic reticulum stress-related genes (DE-ERSGs) were screened and used to construct a risk model by Cox regression analysis. Kaplan–Meier (K-M) curves and receiver operating characteristic (ROC) curves were plotted to determine the risk validity of the model. Moreover, enrichment analysis of differentially expressed genes (DEGs) between the high- and low- risk groups was conducted to investigate the functions related to the risk model. Furthermore, the differences in ERS status, vascular-related genes, tumor mutation burden (TMB), immunotherapy response, chemotherapy drug sensitivity and other indicators between the high- and low- risk groups were studied. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate the mRNA expression levels of prognostic model genes. Results A total of 81 DE-ERSGs were identified in the TCGA-LUAD dataset, and a risk model, including HSPD1, PCSK9, GRIA1, MAOB, COL1A1, and CAV1, was constructed by Cox regression analysis. K-M and ROC analyses showed that the high-risk group had a low survival, and the Area Under Curve (AUC) of ROC curves of 1-, 3- and 5-years overall survival was all greater than 0.6. In addition, functional enrichment analysis suggested that the risk model was related to collagen and extracellular matrix. Furthermore, differential analysis showed vascular-related genes FLT1, TMB, neoantigen, PD-L1 protein (CD274), Tumor Immune Dysfunction and Exclusion (TIDE), and T cell exclusion score were significantly different between the high- and low-risk groups. Finally, qRT-PCR results showed that the mRNA expression levels of 6 prognostic genes were consistent with the analysis. Conclusion A novel ERS-related risk model, including HSPD1, PCSK9, GRIA1, MAOB, COL1A1, and CAV1, was developed and validated, which provided a theoretical basis and reference value for ERS-related fields in the study and treatment of LUAD