Tumor Cell-Intrinsic BTLA Receptor Inhibits the Proliferation of Tumor Cells via ERK1/2.

B and T lymphocyte attenuator (BTLA) is an immune checkpoint molecule that mediates the escape of tumor cells from immunosurveillance. Consequently, BTLA and its ligand herpesvirus entry mediator (HVEM) are potentially immunotherapeutic targets. However, the potential effects of BTLA on tumor cells remain incompletely unknown. Here, we show that BTLA is expressed across a broad range of tumor cells. The depletion of BTLA or HVEM promotes cell proliferation and colony formation, which is reversed by the overexpression of BTLA in BTLA knockout cells. In contrast, overexpression of BTLA or HVEM inhibits tumor cell proliferation and colony formation. Furthermore, the proliferation of a subpopulation with high BTLA was also significantly slower than that of the low BTLA subpopulation. Mechanistically, the coordination of BTLA and HVEM inhibits its major downstream extracellular regulated protein kinase (ERK1/2) signaling pathway, thus preventing tumor cell growth. This study demonstrates that tumor cell-intrinsic BTLA/HVEM is a potential tumor suppressor and is likely to have a potential antagonist for immunotherapy, thus representing a potential biomarker for the optimal cancer immunotherapeutic treatment.

Impact of coupling topology upon noise robustness of small optical reservoirs.

In this work, we perform the numerical investigation of the performance of the small optical reservoir computing (RC) systems with four neurons using the commercial software for optical fiber communication system. The small optical RC system consists of the components of the optical fiber communication. The nonlinear function which is required in RC is provided by the erbium-doped optical fiber amplifiers (EDFA). We demonstrate that the EDFA should be operated in the saturated or non-linear regime to obtain a better performance of the small optical RC system. The performance of the small optical RC systems for different topological neuron structures is investigated. The results show that the interconnection between the neurons could offer a better performance than the systems without interconnection between the neurons. Moreover, the input signals with different noise levels are launched into the systems. The results show that the small optical RC system can classify the noisy input optical waveforms even when the signal-to-noise ratio is as low as - 2.55 dB.

Carrier Transport and Recombination Mechanism in Blue Phosphorescent Organic Light-Emitting Diode with Hosts Consisting of Cabazole- and Triazole-Moiety.

In this study, we demonstrated a blue phosphorescent organic light-emitting diode (BPOLED) based on a host with two carbazole and one trizole (2CbzTAZ) moiety, 9,9'-(2-(4,5-diphenyl-4H-1,2,4-triazol-3-yl)-1,3-phenylene)bis(9H-carbazole), that exhibits bipolar transport characteristics. Compared with the devices with a carbazole host (N,N'-dicarbazolyl-3,5-benzene, (mCP)), triazole host (3-(biphenyl-4-yl)-5-(4-tert-butylphenyl)-4-phenyl-4H-1,2,4-triazole, (TAZ)), or a physical mixture of mCP:TAZ, which exhibit hole, electron, and bipolar transport characteristics, respectively, the BPOLED with the bipolar 2CbzTAZ host exhibited the lowest driving voltage (6.55 V at 10 mA/cm2), the highest efficiencies (maximum current efficiency of 52.25 cd/A and external quantum efficiency of 23.89%), and the lowest efficiency roll-off, when doped with bis[2-(4,6-difluorophenyl)pyridinato-C2,N](picolinato)iridium(III) (FIrpic) as blue phosphor. From analyses of light leakage of the emission spectra of electroluminescence, transient electroluminescence, and partially doped OLEDs, it was found that the recombination zone was well confined inside the emitting layer and the recombination rate was most efficient in a 2CbzTAZ-based OLED. For the other cases using mCP, TAZ, and mCP:TAZ as hosts, electrons and holes transported with different routes that resulted in carrier accumulation on different organic molecules and lowered the recombination rate.

WW Domain-Containing Proteins YAP and TAZ in the Hippo Pathway as Key Regulators in Stemness Maintenance, Tissue Homeostasis, and Tumorigenesis.

The Hippo pathway is a conserved signaling pathway originally defined in Drosophila melanogaster two decades ago. Deregulation of the Hippo pathway leads to significant overgrowth in phenotypes and ultimately initiation of tumorigenesis in various tissues. The major WW domain proteins in the Hippo pathway are YAP and TAZ, which regulate embryonic development, organ growth, tissue regeneration, stem cell pluripotency, and tumorigenesis. Recent reports reveal the novel roles of YAP/TAZ in establishing the precise balance of stem cell niches, promoting the production of induced pluripotent stem cells (iPSCs), and provoking signals for regeneration and cancer initiation. Activation of YAP/TAZ, for example, results in the expansion of progenitor cells, which promotes regeneration after tissue damage. YAP is highly expressed in self-renewing pluripotent stem cells. Overexpression of YAP halts stem cell differentiation and yet maintains the inherent stem cell properties. A success in reprograming iPSCs by the transfection of cells with Oct3/4, Sox2, and Yap expression constructs has recently been shown. In this review, we update the current knowledge and the latest progress in the WW domain proteins of the Hippo pathway in relevance to stem cell biology, and provide a thorough understanding in the tissue homeostasis and identification of potential targets to block tumor development. We also provide the regulatory role of tumor suppressor WWOX in the upstream of TGF-ß, Hyal-2, and Wnt signaling that cross talks with the Hippo pathway.

Looking into meta-atoms of plasmonic nanowire metamaterial.

Nanowire-based plasmonic metamaterials exhibit many intriguing properties related to the hyperbolic dispersion, negative refraction, epsilon-near-zero behavior, strong Purcell effect, and nonlinearities. We have experimentally and numerically studied the electromagnetic modes of individual nanowires (meta-atoms) forming the metamaterial. High-resolution, scattering-type near-field optical microscopy has been used to visualize the intensity and phase of the modes. Numerical and analytical modeling of the mode structure is in agreement with the experimental observations and indicates the presence of the nonlocal response associated with cylindrical surface plasmons of nanowires.

Enhancing bright-field image of microorganisms by local plasmon of Ag nanoparticle array.

Inspecting biological cells with bright-field light microscopy often engenders a challenge, owing to their optical transparency. We show that imaging contrast can be greatly enhanced as yeast cells are placed on a silver nanoparticle array. Its near- and far-field traits, revealed by electrodynamic simulations, illustrate that the enhancement is attributed to the sensitivity of its plasmonic characteristics to the attached cells. This study demonstrates that the silver nanoparticle array can serve as the agent for concurrently enhancing Raman scattering and imaging contrast of microorganisms for identification and examination.

Revealing local, enhanced optical field characteristics of Au nanoparticle arrays with 10 nm gap using scattering-type scanning near-field optical microscopy.

Anomalous optical properties displayed by plasmonic structures are commonly attributed to the enhanced, local field within their corrugations. Though theoretical calculations of such field enhancements abound, experimental observations are relatively few, because only few optical microscopic techniques have enough spatial resolution. We used scattering-type scanning near-field optical microscopy to resolve local optical characteristics of a gold nanoparticle array with 10 nm gap between adjacent particles. Subnanometer-resolution measurement of the optical field intensity was achieved by use of etched silicon atomic force microscopy probe tip. The result shows that, with a p-polarized excitation scheme, the induced field is enhanced and the phase undergoes a large change in the gap region. The spatially-resolved signals are attributed to the electromagnetic interaction within an array of vertical dipoles. We show that scattering-type near-field optical microscopy is well-suited to the investigation of field enhancements in plasmon-enhanced sensing and spectroscopy array structures.

Transparent Raman-enhancing substrates for microbiological monitoring and in situ pollutant detection.

Opaque Raman-enhancing substrates made of Ag nanoparticles on incompletely oxidized aluminum templates have been rendered transparent by an ion-drift process to complete the oxidation. The result shows that the transparent substrates exhibit high/uniform surface-enhanced Raman scattering (SERS) capability and good optical transmissivity, allowing for concurrent SERS characterization and high contrast transmission-mode optical imaging of S. aureus bacteria. We also demonstrate that the transparent substrates can used in conjunction with optical fibers as SERS sensors for in situ detection of malachite green down to 10(-9) M.