Search

We report modeling and experimental characterization results of the propagating photonic bound states in a silicon-on-insulator (SOI) metastructure. The photonic bound states in the metasurface can be excited by the interaction between the discrete resonant modes and the incident wave. The calculated dispersion diagram shows anticrossings with continuous spectral narrowing at surface normal- and oblique-incidence excitations. In the presentation, we will discuss the measured spatial and spectral responses of the reflected beam from the fabricated SOI metastructure.

A chip-scale silicon PIC-based tunable delay line using a 10-by-15 microring resonator array with integrated photodetectors and thermo-optic switching elements was implemented and experimentally characterized.

We present numerical modeling and experimental characterization of the photonic bound states in high-contrast Si-based subwavelength grating waveguide structures. The resonant modes in the grating waveguides show some of the unique features of the photonic bound states in the continuum: continuous narrowing of the resonance linewidth and cancellation of radiative waves. The calculated field distributions show strong internal field buildup around resonances. To verify our simulation results, a Si-based subwavelength grating waveguide was fabricated and experimentally characterized. The measured reflection spectra show two resonance peaks around λ0 = 1490 nm and λ0 = 1505 nm. According to the simulated results, these two peaks are located near a BIC condition. The captured infrared microscope images in the reflection measurement reveal the dynamical interaction between the incident light and the subwavelength grating waveguide. The demonstrated Si grating waveguides has potential to be used as highly efficient frequency-selective couplers between free-space optical waves to in-plane guided optical waves in existing Si integrated photonic circuits.

We report our in-house R&D efforts of designing and developing key integrated photonic devices and technologies for a chip-scale optical oscillator and/or clock. This would provide precision sources to RF-photonic systems. It could also be the basic building block for a photonic technology to provide positioning, navigation, and timing as well as 5G networks. Recently, optical frequency comb (OFC)-based timing systems have been demonstrated for ultra-precision time transfer. Our goal is to develop a semiconductor-based, integrated photonic chip to reduce the size, weight, and power consumption, and cost of these systems. Our approach is to use a self-referenced interferometric locking circuit to provide short-term stabilization to a micro-resonator-based OFC. For long-term stabilization, we use an epsilon-near-zero (ENZ) metamaterial to design an environment-insensitive cavity/resonator, thereby enabling a chip-scale optical long-holdover clock.

Understanding the near-field electromagnetic interactions that produce optical orbital angular momentum (OAM) is crucial for integrating twisted light into nanotechnology. Here, we examine the cathodoluminescence (CL) of plasmonic vortices carrying OAM generated in spiral nanostructures. The nanospiral geometry defines a photonic local density of states that is sampled by the electron probe in a scanning transmission electron microscope (STEM), thus accessing the optical response of the plasmonic vortex with high spatial and spectral resolution. We map the full spectral dispersion of the plasmonic vortex in spiral structures designed to yield increasing topological charge. Additionally, we fabricate nested nanospirals and demonstrate that OAM from one nanospiral can be coupled to the nested nanospiral, resulting in enhanced luminescence in concentric spirals of like handedness with respect to concentric spirals of opposite handedness. The results illustrate the potential for generating and coupling plasmonic vortices in chiral nanostructures for sensitive detection and manipulation of optical OAM., Tiny spirals make twisted light Nano-sized spiral structures developed by researchers in the US provide an excellent platform to generate and detect light beams carrying angular momentum. This so-called twisted light, with a helical wave shape, could be used to manipulate tiny objects in future devices such as quantum computers. Jordan Hachtel at Oak Ridge National Laboratory, Tennessee and co-workers fabricated ‘nanospirals’ on silver-coated silicon nitride membranes, and bombarded the samples with a high-energy electron beam from a scanning transmission electron microscope (STEM). The beam excites a coupled light-electron surface state called a plasmonic vortex, which emits twisted light. Crucially, the STEM technique can observe the luminescence coming from the vortex with nanoscale spatial resolution across the entire visible-light regime.

To determine the prognostic significance of kinesin superfamily gene (KIF) expression in patients with brain cancer, including low-grade glioma (LGG) and glioblastoma (GBM), we comprehensively analyzed KIFs in 515 LGG and 595 GBM patients. Among KIFs, KIF4A, 9, 18A, and 23 showed significant clinical implications in both LGG and GBM. The mRNA and protein expression levels of KIF4A, 9, 18A, and 23 were significantly increased in LGG and GBM compared with those in the normal control groups. The mRNA expression levels of KIF4A, 9, 18A, and 23 in LGG were significantly increased in the high-histologic-grade group compared with those with a low histologic grade. Genomic analysis showed that the percent of mRNA upregulation of KIF4A, 9, 18A, and 23 was higher than that of other gene alterations, including gene amplification, deep deletion, and missense mutation. In addition, LGG patients with KIF4A, 18A, and 23 gene alterations were significantly associated with a poor prognosis. In survival analysis, the group with high expression of KIF4A, 9, 18A, and 23 mRNA was significantly associated with a poor prognosis in both LGG and GBM patients. Gene Set Enrichment Analysis (GSEA) revealed that high mRNA expression of KIF4A, 18A, and 23 in LGG and GBM patients showed significant positive correlations with the cell cycle, E2F targets, G2M checkpoint, Myc target, and mitotic spindle. By contrast, high mRNA expression of KIF9 in both LGG and GBM patients was significantly negatively correlated with the cell cycle, G2M checkpoint, and mitotic spindle pathway. However, it was significantly positively correlated with EMT and angiogenesis. This study has extended our knowledge of KIF4A, 9, 18A, and 23 in LGG and GBM and shed light on their clinical relevance, which should help to improve the treatment and prognosis of LGG and GBM.

BACKGROUND AND AIM Elevated cytochrome p450 (CYP) 4A gene expression has been linked to the aggravation of various cancers and affects various regulated metabolites. In hepatocellular carcinoma (HCC), the clinicopathological value of CYP4A has not yet been explored, although CYP4A is expressed at high levels in the liver. The goal of this study was to evaluate the clinicopathological value of CYP4A11 expression in HCC. METHODS We performed immunohistochemical analysis of CYP4A11 and correlated the results with clinicopathological features of HCC (n = 155). Western blotting and reverse transcription-polymerase chain reaction against CYP4A11 and CYP4A22 were also performed for 15 and 20 pairs of fresh-frozen primary HCC and non-neoplastic liver tissue, respectively. Moreover, we analyzed the underlying mechanism by comparing the high and low CYP4A11 mRNA expression groups using gene set enrichment analysis. RESULTS CYP4A11 expression level was higher in non-neoplastic hepatocytes than those in HCC cells (P

The authors present an experimental demonstration of a fluidic-based plasmonic device for spectral analysis. The demonstrated device is based on the modification of surface plasmon resonance in periodically coupled metallic nanostructures using external refractive index perturbation for spectral analysis. The refractive index perturbation alters the resonance condition of the internal surface plasmon waves and introduces a spectral shift in the transmission band for spectral sampling. In this demonstration, precise control of the centre wavelength of the surface plasmon resonance was achieved by changing the local environment of the nanostructures via microfluidic channels. The fluidic-based approach has a great impact on existing resonance-based spectral analysis devices by offering an efficient way to acquire a very large number of spectral sampling.

A mouse was generated containing a floxed exon 3 of the gene for the kinesin family member KIF9. By in situ hybridization, expression of KIF9 mRNA was highest in the testis and was also strong in epithelia containing multi-ciliated cells such as the ependyma, bronchioles and oviduct. Deletion of the exon led to loss of KIF9 expression at the mRNA and protein level with no effect on viability. However, homozygous KIF9 knockout males were sterile. Although KIF9 knockout sperm were motile, they were unable to fertilize oocytes in an in vitro fertilization assay. Closer examination of sperm motility indicated a subtle difference in waveform. Our results suggest that KIF9 plays a role male fertility, possibly through regulation of flagellar waveforms in ciliated cells.

We are reporting micro-scale-thick ITO metafilm in the ENZ regime which permits the design of new ENZ photonic devices. Optical properties have been studied, as well as their potential application for the near-IR photonic devices.

Background The resistance to epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is one of the most important problems in lung cancer field. Mitogen-inducible gene 6 (Mig-6) is known to inhibit the kinase activity of epidermal growth factor receptor (EGFR) and studies of mouse models suggested tumor suppressive function of Mig-6 in lung cancer. On the contrary, the results of clinical studies showed that lung cancer patients with high expression of Mig-6 are associated with a poor prognosis. Recent study showed that unlike wild type (WT) EGFR, mutant EGFR phosphorylates Mig-6 and phosphorylated Mig-6 negatively regulates the degradation of EGFR mutants in lung adenocarcinoma. Here, we tried to untangle the controversies surrounding Mig-6 function in lung cancer and EGFR-TKI resistance. Methods We compared the expression and phosphorylation status of Mig6 in the EGFR-TKI resistant lung adenocarcinoma (PC9/GR cells) to EGFR-TKI sensitive lung adenocarcinoma (PC9 cells). We checked the function of Mig6 by knock down and overexpression in those cells and evaluated the efficacy of combination of Mig6 knock down and EGFR-TKI in PC9/GR. The correlation between Mig6 expression and the prognosis of lung adenocarcinoma were examined by The Cancer Genome Atlas (TCGA) data and clinical samples. Results Our results showed that the expression of Mig-6 was significantly increased PC9/GR cells compared to PC9 cells. And most of Mig-6 was phosphorylated in PC9 and PC9/GR cells. Moreover, overexpression of Mig-6 significantly increased the cell proliferation, invasion and epithelial mesenchymal transition (EMT) in PC9 cells. Combination of Mig-6 knock-down and EGFR-TKI treatment significantly overcame the EGFR-TKI resistance. In addition, our analyses of clinical samples confirmed that high Mig-6 expressions are correlated with a poor prognosis and EGFR-TKI resistance in lung adenocarcinoma. Conclusion Our work supports that Mig-6 is an oncoprotein in the context of EGFR-TKI resistant lung adenocarcinoma. We propose that targeting Mig-6 may be a promising strategy to overcome the EGFR-TKI resistance in lung cancer.

TEA Domain Transcription Factors (TEADs) are important in development and serve essential roles in tumorigenesis; however, the role of TEAD2 expression in hepatocellular carcinoma (HCC) has not been widely examined. The present study was conducted to investigate the expression status of TEAD2 in HCC and to evaluate whether the expression of TEAD2 is associated with the prognosis of patients with HCC. mRNA expression data was retrieved for Hippo pathway genes of 50 normal control and 377 HCC samples from The Cancer Genome Atlas data portal. Gene set enrichment, GeneNeighbors, ClassNeighbors and survival analyses were then performed based on the gene expression levels. The mRNA expression of TEAD2 and VGLL4 was significantly higher in HCC compared with the normal control samples, and the mRNA expression of TEAD2 was higher in advanced stages than in early stages. Specifically, survival analysis revealed that higher mRNA expression of TEAD2 was significantly associated with a less favorable overall survival rate (P=0.0067) and there was a trend towards significance between higher mRNA expression of VGLL4 and poor overall survival rate (P=0.051). According to the gene set enrichment analysis, patients with higher mRNA expression of TEAD2 and VGLL4 had strongly enhanced epithelial‑mesenchymal transition and angiogenesis, which are associated with tumor progression. In conclusion, increased mRNA expression of TEAD2 is associated with a poor prognosis in patients with HCC. TEAD2 may serve as a prognostic factor for HCC and a novel therapeutic target.

Background The resistance of lung cancer to epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is one of the unconquered frontiers in chemotherapy. Mitogen-inducible gene 6 (Mig-6) is known to inhibit the kinase activity of epidermal growth factor receptor (EGFR). Similarly, numerous studies of mouse models suggested tumor suppressive function of Mig-6 in lung cancer. On the contrary, the results of clinical investigations revealed that lung cancer patients with elevated expression of Mig-6 are associated with a poor prognosis. More recent work showed that unlike wild type (WT) EGFR, mutant EGFR phosphorylates Mig-6 and phosphorylated Mig-6 negatively regulates the degradation of EGFR mutants in lung adenocarcinoma. Here, we tried to untangle the controversies surrounding Mig-6 function as a protagonist or an antagonist of EGFR-TKI resistant lung cancer. Methods We compared the expression and phosphorylation status of Mig-6 in the EGFR-TKI resistant lung adenocarcinoma (PC9/GR cells) to EGFR-TKI sensitive lung adenocarcinoma (PC9 cells). We investigated the function of Mig-6 by either depletion or overexpression of Mig-6 in those cells and evaluated the efficacy of combining of Mig-6 knock-down and EGFR-TKI treatment in PC9/GR. The correlation between Mig-6 expressions and the prognoses of lung adenocarcinoma was examined by The Cancer Genome Atlas (TCGA) data and clinical samples. Results Our results indicated that the expression of Mig-6 was significantly increased in PC9/GR cells compared to that of PC9 cells. The significant portion of Mig-6 existed as a phosphorylated form in PC9 and PC9/GR cells. Moreover, overexpression of Mig-6 significantly increased the cell proliferation, invasion and epithelial mesenchymal transition (EMT) in PC9 cells. Combination of Mig-6 knock-down and EGFR-TKI treatment significantly overcame the EGFR-TKI resistance of PC9/GR cells. In addition, our analyses of clinical samples confirmed that high Mig-6 expressions positively correlate with a poor prognosis and EGFR-TKI resistance in lung adenocarcinoma. Conclusion Our findings reinforce scientific notion of Mig-6 as an oncoprotein in the context of EGFR-TKI resistant lung adenocarcinoma. We propose that targeting Mig-6 may be a promising strategy to overcome the EGFR-TKI resistance in lung cancer.

Yes-associated protein 1 (YAP1) is a key transcriptional regulator in the Hippo signaling pathway that plays a critical role in the development and progression of several types of malignancies, including ovarian cancer. Herein, we investigated the expression of YAP1 and its clinical significance in a large population of patients with ovarian serous cystadenocarcinoma (OSC), which is the most common form of epithelial ovarian neoplasm, using the TCGA database. Surprisingly, cross-cancer mRNA expression and alterations in YAP1 were higher in OSC than in those of other types of cancers in the TCGA database. YAP1 mRNA expression was significantly higher in OSC compared with normal ovarian samples, and was higher in stages III and IV, than stages I and II. The level of YAP1 protein, which is mainly localized to the nucleus, was also higher in stage IV as compared with stages I, II and III. However, the protein level of pYAP1, which is inactive and is localized to the cytoplasm, was not significantly different between stages. The ratio of pYAP/YAP, which shows higher activity at a low ratio, was lower in stage III than in stages I and II. High YAP and low pYAP levels were significantly correlated with a poor prognosis in patients with OSC. The mRNA and protein expression of YAP1 were significantly increased in the proliferative subtype as compared to the differentiated, immunoreactive and mesenchymal subtypes. According to bioinformatics analysis, YAP1 is most highly correlated with the cell cycle. TGF-β signaling and WNT signaling were significantly increased in the high YAP1 group according to gene set enrichment analysis. Taken together, our results suggest that not only high YAP1 expression but also its subcellular distribution may be associated with poor overall survival in patients with OSC.

We discuss the development of a plasmonic spectrometer for in situ characterization of solar system surface and subsurface environments. The two goals of this effort are to (1) quantitatively demonstrate that a plasmonic spectrometer can be used to rapidly acquire high signal-to-noise spectra between 0.5–1.0 µm at a spectral resolution suitable for unambiguous detection of spectral slopes and features indicative of volatiles and characteristic surface mineralogies, and (2) demonstrate that this class of spectrometer can be used in conjunction with optical fibers to access subsurface materials and vertically map the geochemistry and mineralogy of subsurface layers, thereby demonstrating that a plasmonic spectrometer is feasible in a low-mass, low-power, compact configuration. Our prototype instrument, the Plasmonic Spectrometer for In situ CLassification Of Planetary Surfaces (PSICLOPS), consists of a broadband lamp/source, a fiber optic system to illuminate the sample surface and collect the reflected light, a mosaic filter element based on plasmon resonance, and a focal plane array detector. The critical filter element of the spectrometer is based on the internal plasmon resonance of metallic nanostructures. We developed a membrane-based plasmonic filter that can be directly implemented on an optical fiber. After developing a new fabrication process for nanostructures in thin Au membranes suspended in air, we found that we can control the central wavelength of the filter by changing the index of refraction of the surrounding medium. Therefore we explored several media (e.g. water, glycerol, and glucose) as a means of introducing a range of indices of refraction, and thus central wavelengths of the filter, using microfluidic channels. In addition to the development of the plasmon filter element, we constructed a testbed to explore the use of optical fibers for source illumination and signal transmission to the focal plane array. We discuss our preliminary design studies of the plasmonic nanostructure prototypes and their application to miniaturized instrumentation for in situ characterization of solar system surface and subsurface environments.

Cytochrome P450 family 4 (CYP4) enzymes are known as microsomal omega (ω)-hydroxylases that metabolize fatty acids, eicosanoids, vitamin D and carcinogens. Thus, CYP4 enzymes may influence tumor development and progression. The aim of the present study was to evaluate the CYP4 expression profile in hepatocellular carcinoma (HCC) and its clinical relevance. The present study obtained CYP4 mRNA expression data for 377 HCC cases from The Cancer Genome Atlas cohort and performed Kaplan‑Meier survival, Gene Ontology functional enrichment, and gene set enrichment analysis (GSEA). In addition, the level of CYP4F2 protein expression was evaluated in matched pairs of HCC and non‑tumor tissue samples and the results were correlated with the clinicopathological characteristics of HCC (n=113). HCC survival analyses indicated better overall survival in patients with high CYP4F2, CYP4F12 and CYP4V2 mRNA expression levels; the results for histological grade and Tumor‑Node‑Metastasis stage supported these results. GSEA revealed high levels of CYP4F2, CYP4F12 and CYP4V2 mRNA expression to be negatively correlated with the expression of cell cycle‑associated genes. CYP4F2 protein expression was higher in non‑neoplastic liver tissue than in HCC tissue and positively correlated with favorable pathological tumor stage (I vs. II‑IV; P=0.022) and was a good independent prognostic factor for overall survival (P=0.004). These results demonstrate that the expression levels of the genes CYP4F2, CYP4F12 and CYPV2 are favorable prognostic factors in HCC and suggest the potential predictive diagnostic and prognostic roles of CYP4F2, CYP4F12 and CYPV2 gene expression in HCC.

Oxidative stress occurs due to the excessive generation of cellular reactive oxygen species and antioxidant system dysfunction. The thioredoxin (TXN) system and TXN-domain-containing protein (TXNDC) family form networks maintaining the cellular reducing environment. Recently, the importance of these genes in the tumor environment has been emphasized. To investigate the clinical significance of TXNs and TXNDC family members in HCC. Genomic data from 367 hepatocellular carcinoma (HCC) patients who underwent hepatic resections were analyzed to determine genetic alterations in mRNA and protein levels between patients and healthy controls. In addition, functional enrichment and survival analyses were performed. HCC patients were shown to have enhanced expression of TXN, TXNRD1, and TXNDC7/9/14 mRNA and protein compared with controls. In accordance with the survival analyses, strong associations were found that patients with TXN, TXNRD1, and TXNDC1/7/9 alterations were proven to have poor prognosis in overall survival. Moreover, gene set enrichment analysis and network analyses revealed that positive correlations were found in mRNA expression of TXN, TXNRD1, and TXNDC7/9 genes with upregulation of the tumor-promoting genes, specifically mTORC1, E2F targets, and Myc targets. On the other hand, elevated expressions of TXNIP and TXNDC11 genes were correlated with suppression of the above tumor-promoting genes. TXN system and TXNDC family gene panel obtained from the resected tissue of the HCC patients could be used to predict survival prognosis of HCC, and these genes could be considered as potential therapeutic targets for improving HCC survival.

Aim We evaluated the relationships between the use of smart devices, such as smartphones and tablet computers, and the development levels and language scores in young children. Methods A cross-sectional analysis with 117 children aged three to five years was conducted. The participants were recruited from kindergartens in South Korea between November 2015 and April 2016. Parental questionnaires to assess smart device usage status by children, developmental screening test and receptive-expressive language scale were administered; metrics included smart device usage frequency and usage time, appropriate smart device usage level, developmental levels and language scores. Results Smart device usage frequency was significantly positively correlated with fine motor skill development [Spearman's correlation coefficient (rs ) = 0.426] in three-year-old children. Appropriate smart device usage level was also positively correlated with social development (rs = 0.466). However, smart device usage time was significantly negatively correlated with expressive language months (rs = -0.481). There were no such correlations in children aged four to five years. For the subcategories of appropriate usage level, the suitability of social relationship was significantly positively correlated with social development in three-year-old children (rs = 0.474). Conclusion In three-year-old children, smart device usage was positively correlated with fine motor development and negatively correlated with language development.

Yes-associated protein 1 (YAP1) is a transcriptional regulator of the Hippo pathway, which regulates the development and progression of a number of types of cancer, including that of the colon. In the present study, the expression levels of Hippo pathway genes and their clinical significance were investigated in 458 patients with colon adenocarcinoma (COAD), the most frequently diagnosed neoplastic disease globally, using data obtained from The Cancer Genome Atlas database. Notably, mRNA expression of YAP1 was higher in COAD than in other types of gastrointestinal tract cancer. Expression of YAP1 mRNA was higher in COAD than in normal colon samples and was significantly higher in Tumor-Node-Metastasis (TNM) stages III-IV than in stages I-II. YAP1 protein levels, a protein primarily localized in the nucleus, was greater in TNM stages III-IV than in stages I-II. The level of pYAP1, which is inactive and localized in the cytoplasm, was significantly higher in TNM stages III-IV than in stages I-II. However, the YAP1/pYAP1 ratio, which is representative of activity, was higher in TNM stages III-IV than in stages I-II. High mRNA expression of YAP1, TAZ and TEAD4 was associated with a poor prognosis in patients with COAD. Bioinformatics analysis revealed that YAP1 was associated with DNA duplication, cell proliferation and development. Wnt signaling and transforming growth factor-β signaling were significantly higher in the high-YAP1 group, according to data from Gene Set Enrichment Analysis. Taken together, the results indicate that the subcellular distribution of YAP1 and high mRNA expression of YAP1, TAZ and TEAD4 may be associated with poorer overall survival rates in patients with COAD.

Accelerated eutrophication of surface water sources has resulted in an increased presence of cyanobacterial blooms in fresh water. The release of hepatotoxins like microcystins from such blooms can have a catastrophic impact on local human and wildlife ecosystems. Therefore, a rapid, low-cost, reliable, and highly sensitive method for low-concentration detection of microcystins is needed to minimize risks to public health. In this paper, we report the first experimental demonstration of microcystin-leucine-arginine (MC-LR) detection in water at low part-per-trillion levels using a portable optical sensor. The demonstrated biosensor utilizes a highly sensitive electromagnetic surface wave in periodically coupled artificial nanostructures to directly probe the interaction between immobilized antibodies and MC-LR. The surface customization reported here uses a layer-by-layer polyelectrolyte adsorption process to provide highly stable and site-directed immobilization of target antibodies. Steady-state analysis of the sensor's response confirms that the plasmonic sensor can detect the presence of MC-LR antigens at part-per-trillion levels. The demonstrated sensor is an important first step toward realizing a lab-on-a-chip sensing system for in situ, autonomous, real-time, distributed environmental monitoring of MC levels in drinking water.

The NADPH oxidase (NOX) family is overexpressed in many cancers and is associated with cancer cell proliferation and metastasis; however, little is known about the role of the NOX family in colorectal cancer (CRC). To identify the expression of the NOX family in CRC and to investigate the relationship between the expression of NOXs with the prognosis of the patients. In the TCGA data portal, mRNA expression data were obtained from 41 normal samples and 458 CRC samples to analyze mRNA expression and gene alteration. We compared the survival differences according to the degree of expression of NOX family in CRC patients and performed Gene Set Enrichment Analysis (GSEA). The mRNA expression of NOX1, 3, 4, and DUOX1, 2 was significantly increased in the colorectal adenocarcinoma. Especially, the higher T and N stage, the more NOX4 expression was significantly increased. Survival analyses showed that NOX4 and NOX5 were associated with poor prognosis; however, NOX1 and DUOX2 were significantly associated with better prognosis. In the results of GSEA of CRC patients, the NOX4 gene was significantly associated with Angiogenesis, EMT and notch signaling. The NOX family is overexpressed in CRC and is associated with the prognosis of the patient. Therefore, NOX family can predict CRC patient survival and the role of the NOX family as a molecular target in the treatment of CRC.

We report on the experimental demonstration of active Archimedean nanospirals that exhibit unique far-field patterns from the interaction of locally excited surface plasmon waves with an active medium. The captured far-field images show complicated internal mode structures such as plasmonic vortex-like modes.

In this presentation, we report on the experimental demonstration of a new class of metasurfaces, plasmonic metamembranes. Compared to conventional plasmonic metasurfaces, the demonstrated metamembrane has a mechanically flexible structure offering new designs and operation of plasmonic metasurfaces.

Developments of EGFR-TKI and immunotherapy targeting the PD1/PD-L1 pathway are considered most important medical breakthroughs in lung cancer treatment. Nowadays, 3rd generation EGFR TKI is widely used for T790M positive 1st and 2nd EGFR-TKI resistant lung cancer patients. Immunotherapy is powerful option for lung cancer patients without drug targets and chemotherapy resistant patients. It also has changed the concept of conventional anti-cancer therapy in the point of regulating tumor microenvironment. There are many studies linking these two important pathways. Recent studies demonstrated that PD-L1 expression is significantly correlated to the mutation status of EGFR, and activation of EGFR signaling can also induce the expression of PD-L1. However, the real linker between PD-L1 and EGFR signaling remains to be revealed. Our previous study revealed that the Hippo pathway effector YAP confers EGFR-TKI resistance in lung adenocarcinoma, and inhibition of YAP restores sensitivity to EGFR-TKIs. Thus, we examined whether PD-L1 is relevant, in terms of conferring EGFR-TKI resistance and whether YAP directly regulates the expression of PD-L1 in this context. First, we compared the expression levels of PD-L1 and YAP between EGFR-TKI-resistant PC9 cells and the parental PC9 adenocarcinoma cells. The expression levels of both YAP and PD-L1 were markedly higher in the EGFR-TKI-resistant cells compared to the parental cells, suggesting differential expression pattern between two cell types. YAP knockdown significantly decreased the expression of PD-L1 in the EGFR-TKI-resistant cells, while YAP overexpression increased the expression of PD-L1 in the parental PC9 cells. Then, our results revealed that YAP regulates the transcription of PD-L1, and the YAP/TEAD complex binds to the PD-L1 promoter. Surprisingly, knockdown of PD-L1 was sufficient to decrease cell proliferation and wound healing in the EGFR-TKI-resistant PC9 cells. These data suggest a PD1-independent oncogenic function of PD-L1. The Hippo effector YAP plays a crucial role in linking the PD-L1 and EGFR-TKI resistance by directly regulating the expression of PD-L1 in lung cancer. Targeting PD-L1 directly or via YAP could provide an effective therapeutic strategy for EGFR-TKI-resistant lung adenocarcinoma.

In this paper, we report an experimental demonstration of malaria pathogen detection in a whole blood lysate using plasmonic nanostructures. The plasmon sensor utilizes extraordinary optical transmission through a nanostructure to directly probe antibody-antigen interactions. The measured refractive index sensitivity of the nanostructured sensor is 378 nm per refractive index unit in the visible range. The surface chemistry reported here provides highly site directed and stable antibody immobilization. To validate the observed response of the optical sensor, positive and negative control tests were performed. Results confirm that a refractive index change induced by the interaction between immobilized antibodies and malaria parasites is successfully detected by the fabricated sensor. The demonstrated plasmonic sensor is a compact, highly sensitive, cost effective, selective diagnostic tool for many portable biosensing applications, such as point-of-care diagnostics.

To determine the prognostic significance of kinesin superfamily gene (KIF) expression in patients with brain cancer, including low-grade glioma (LGG) and glioblastoma multiforme (GBM), we comprehensively analyzed KIFs in 515 LGG and 595 GBM patients. Among KIFs, KIF4A, 9, 18A, and 23 showed significant clinical implications in both LGG and GBM. The mRNA and protein expression levels of KIF4A, 9, 18A, and 23 were significantly increased in LGG and GBM compared with those in the normal control groups. The mRNA expression levels of KIF4A, 9, 18A, and 23 in LGG were significantly increased in the high-histologic-grade group compared with those with a low histologic grade. Genomic analysis showed that the percent of mRNA upregulation of KIF4, 9, 18A, and 23 was higher than that of other gene alterations, including gene amplification, deep deletion, and missense mutation. In addition, LGG patients with KIF4A, 18A, and 23 gene alterations were significantly associated with a poor prognosis. In survival analysis, the group with high expression of KIF4A, 9, 18A, and 23 mRNA was significantly associated with a poor prognosis in both LGG and GBM patients. Gene Set Enrichment Analysis (GSEA) revealed that high mRNA expression of KIF4A, 18A, and 23 in LGG and GBM patients showed significant positive correlations with the cell cycle, E2F targets, G2M checkpoint, Myc target, and mitotic spindle. By contrast, high mRNA expression of KIF9 in both LGG and GBM patients was significantly negatively correlated with the cell cycle, G2M checkpoint, and mitotic spindle pathway. However, it was significantly positively correlated with EMT and angiogenesis. This study has extended our knowledge of KIF4A, 9, 18A, and 23 in LGG and GBM and shed light on their clinical relevance, which should help to improve the treatment and prognosis of LGG and GBM. Citation Format: SangYeon Cho, DongWoon Kim. Integrative analysis of KIF4A, 9, 18A, and 23 and their clinical significance in low-grade glioma and glioblastoma multiforme [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5245.

In this paper, we report the experimental demonstration of wavefront sensing using curved subwavelength apertures. The demonstrated subwavelength structure has an ability to convert the shape of an incident wavefront into a two-dimensional array of focused surface plasmon (SP) waves. The detection principle is based on the phase-dependent spatial displacement of the focal point in circular apertures. The unit-cell structure of the demonstrated device consists of a circular disk surrounded by subwavelength concentric rings to excite highly enhanced SP waves at a designed wavelength. The excited surface waves, carrying the wavefront information of the incident beam, constructively interfere with each other and can be focused inside the disk. For demonstration, a 3-by-3 concentric-ring aperture array was fabricated and experimentally characterized. The focused SP waves within each of the fabricated 3-by-3 apertures under an optical excitation beam with a concave wavefront move toward the center of the array. When the shape of the incident wavefront was changed to convex, the focused spots in the array move away from the center. By measuring the spatial displacement of the focused spot, the shape of the incident wavefront can be directly measured. The demonstrated approach does not require complicated 3-D integration or optical alignment and offers a very high spatial resolution in wavefront detection, and thus, it has great potential for revolutionizing existing wavefront sensors.

Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex-derived reactive oxygen species (ROS) promote chronic liver inflammation and remodeling that can drive hepatocellular carcinoma development. The role of NOX expression in hepatocellular carcinoma (HCC) has been partially investigated; however, the clinical relevance of collective or individual NOX family member expression for HCC survival remains unclear. Here, we obtained NOX mRNA expression data for 377 HCC samples and 21 normal liver controls from the TCGA data portal and performed Kaplan-Meier survival, gene ontology functional enrichment, and gene set enrichment analyses. Although most NOX genes exhibited little change, some were significantly induced in HCC compared to that in normal controls. In addition, HCC survival analyses indicated better overall survival in patients with high NOX4 and DUOX1 expression, whereas patients with high NOX1/2/5 expression showed poor prognoses. Gene-neighbour and gene set enrichment analyses revealed that NOX1/2/5 were strongly correlated with genes associated with cancer cell survival and metastasis, whereas increased NOX4 and DUOX1 expression was associated with genes that inhibit tumour progression. On the basis of these data, NOX family gene expression analysis could be a predictor of survival and identify putative therapeutic targets in HCC.

Even though the primo vascular system (PVS) has been observed in large caliber lymph vessels by several independent teams, the presence of the PVS in the thoracic duct has been reported by only one team, probably because reproducing the experiment is technically difficult. This brief report presents a new, relatively straightforward method, which is a simple modification of the previous method of dye injection into the lumbar node, to observe the PVS in a thoracic duct of a rat by injecting Alcian blue into the renal node. When this new method was applied to a rat, the branching of the primo vessel in the thoracic duct was clearly displayed. Thus, this new method is expected to extend the network of the PVS from abdominal lymph ducts to thoracic ones.