A Fully-Human Antibody Specifically Targeting a Membrane-Bound Fragment of CADM1 Potentiates the T Cell-Mediated Death of Human Small-Cell Lung Cancer Cells

Small-cell lung cancer (SCLC) is the most aggressive form of lung cancer and the leading cause of global cancer-related mortality. Despite the earlier identification of membrane-proximal cleavage of cell adhesion molecule 1 (CADM1) in cancers, the role of the membrane-bound fragment of CAMD1 (MF-CADM1) is yet to be clearly identified. In this study, we first isolated MF-CADM1-specific fully human single-chain variable fragments (scFvs) from the human synthetic scFv antibody library using the phage display technology. Following the selected scFv conversion to human immunoglobulin G1 (IgG1) scFv-Fc antibodies (K103.1–4), multiple characterization studies, including antibody cross-species reactivity, purity, production yield, and binding affinity, were verified. Finally, via intensive in vitro efficacy and toxicity evaluation studies, we identified K103.3 as a lead antibody that potently promotes the death of human SCLC cell lines, including NCI-H69, NCI-H146, and NCI-H187, by activated Jurkat T cells without severe endothelial toxicity. Taken together, these findings suggest that antibody-based targeting of MF-CADM1 may be an effective strategy to potentiate T cell-mediated SCLC death, and MF-CADM1 may be a novel potential therapeutic target in SCLC for antibody therapy.     

Development of Deep-Learning-Based Single-Molecule Localization Image Analysis

Recent developments in super-resolution fluorescence microscopic techniques (SRM) have allowed for nanoscale imaging that greatly facilitates our understanding of nanostructures. However, the performance of single-molecule localization microscopy (SMLM) is significantly restricted by the image analysis method, as the final super-resolution image is reconstructed from identified localizations through computational analysis. With recent advancements in deep learning, many researchers have employed deep learning-based algorithms to analyze SMLM image data. This review discusses recent developments in deep-learning-based SMLM image analysis, including the limitations of existing fitting algorithms and how the quality of SMLM images can be improved through deep learning. Finally, we address possible future applications of deep learning methods for SMLM imaging.     

HDAC8-Selective Inhibition by PCI-34051 Enhances the Anticancer Effects of ACY-241 in Ovarian Cancer Cells

HDAC6 is overexpressed in ovarian cancer and is known to be correlated with tumorigenesis. Accordingly, ACY-241, a selective HDAC6 inhibitor, is currently under clinical trial and has been tested in combination with various drugs. HDAC8, another member of the HDAC family, has recently gained attention as a novel target for cancer therapy. Here, we evaluated the synergistic anticancer effects of PCI-34051 and ACY-241 in ovarian cancer. Among various ovarian cancer cells, PCI-34051 effectively suppresses cell proliferation in wild-type p53 ovarian cancer cells compared with mutant p53 ovarian cancer cells. In ovarian cancer cells harboring wild-type p53, PCI-34051 in combination with ACY-241 synergistically represses cell proliferation, enhances apoptosis, and suppresses cell migration. The expression of pro-apoptotic proteins is synergistically upregulated, whereas the expressions of anti-apoptotic proteins and metastasis-associated proteins are significantly downregulated in combination treatment. Furthermore, the level of acetyl-p53 at K381 is synergistically upregulated upon combination treatment. Overall, co-inhibition of HDAC6 and HDAC8 through selective inhibitors synergistically suppresses cancer cell proliferation and metastasis in p53 wild-type ovarian cancer cells. These results suggest a novel approach to treating ovarian cancer patients and the therapeutic potential in developing HDAC6/8 dual inhibitors.     

Novel Maskless Bumping for 3D Integration

A novel, maskless, low‐volume bumping material, called solder bump maker, which is composed of a resin and low‐melting‐point solder powder, has been developed. The resin features no distinct chemical reactions preventing the rheological coalescence of the solder, a deoxidation of the oxide layer on the solder powder for wetting on the pad at the solder melting point, and no major weight loss caused by out‐gassing. With these characteristics, the solder was successfully wetted onto a metal pad and formed a uniform solder bump array with pitches of 120 µm and 150 µm.     

Metalorganic Chemical Vapor Deposition of CdTe(133) Epilayers on Si(211) Substrates

Single-crystalline CdTe(133) films have been grown by metalorganic chemical vapor deposition on Si(211) substrates. We studied the effect of various growth parameters on the surface morphology and structural quality of CdTe films. Proper oxide removal from the Si substrate is considered to be the principal factor that influences both the morphology and epitaxial quality of the CdTe films. In order to obtain single-crystalline CdTe(133) films, a two-stage growth method was used, i.e., a low-temperature buffer layer step and a high- temperature growth step. Even when the low-temperature buffer layer shows polycrystalline structure, the overgrown layer shows single-crystalline structure. During the subsequent high-temperature growth, two-dimensional crystallites grow faster than other, randomly distributed crystallites in the buffer layer. This is because the capturing of adatoms by steps occurs more easily due to increased adatom mobility. From the viewpoint of crystallographic orientation, it is assumed that the surface structure of Si(211) consists of (111) terrace and (100) step planes with an interplanar angle of 54.8°. This surface structure may provide many preferable nucleation sites for adatoms compared with nominally flat Si(100) or (111) surfaces. The surface morphology of the resulting films shows macroscopic rectangular-shaped terrace—step structures that are considered to be a (111) terrace with two {112} step planes directed toward 〈110〉.     

Interconnection Technology Based on InSn Solder for Flexible Display Applications

A novel interconnection technology based on a 52InSn solder was developed for flexible display applications. The display industry is currently trying to develop a flexible display, and one of the crucial technologies for the implementation of a flexible display is to reduce the bonding process temperature to less than 150°C. InSn solder interconnection technology is proposed herein to reduce the electrical contact resistance and concurrently achieve a process temperature of less than 150°C. A solder bump maker (SBM) and fluxing underfill were developed for these purposes. SBM is a novel bumping material, and it is a mixture of a resin system and InSn solder powder. A maskless screen printing process was also developed using an SBM to reduce the cost of the bumping process. Fluxing underfill plays the role of a flux and an underfill concurrently to simplify the bonding process compared to a conventional flip‐chip bonding using a capillary underfill material. Using an SBM and fluxing underfill, a 20 μm pitch InSn solder SoP array on a glass substrate was successfully formed using a maskless screen printing process, and two glass substrates were bonded at 130°C.     

Tuning the spectrometric properties of white light by surface plasmon effect using Ag nanoparticles in a colour converting light-emitting diode

We report on the spectral tunability of white light by localized surface plasmon (LSP) effect in a colour converting hybrid device made of CdSe/ZnS quantum dots (QDs) integrated on InGaN/GaN blue light-emitting diodes (LEDs). Silver (Ag) nanoparticles (NPs) are mixed with QDs for generating LSP effect. When the plasmon absorption of Ag NPs is synchronized to the QW emission at 448 nm, the NPs selectively absorb the blue light and subsequently enhance the QD emission. Using this energy transfer scheme, the (x, y) chromaticity coordinates of the hybrid white LED was tuned from (0.32, 0.17) to (0.43, 0.26), and thereby generated warm white light emission with correlated colour temperature (CCT) around 1800 K. Moreover, a 47% enhancement in the external quantum efficiency (EQE) was realized.     

Endometrial Epithelial ARID1A Is Required for Uterine Immune Homeostasis during Early Pregnancy

A growing body of work suggests epigenetic dysregulation contributes to endometriosis pathophysiology and female infertility. The chromatin remodeling complex subunit AT-rich interaction domain 1A (ARID1A) must be properly expressed to maintain normal uterine function. Endometrial epithelial ARID1A is indispensable for pregnancy establishment in mice through regulation of endometrial gland function; however, ARID1A expression is decreased in infertile women with endometriosis. We hypothesized that ARID1A performs critical operations in the endometrial epithelium necessary for fertility besides maintaining gland function. To identify alterations in uterine gene expression resulting from loss of epithelial ARID1A, we performed RNA-sequencing analysis on pre-implantation uteri from Ltf^iCre/+Arid1a^f/f and control mice. Differential expression analysis identified 4181 differentially expressed genes enriched for immune-related ingenuity canonical pathways including agranulocyte adhesion and diapedesis and natural killer cell signaling. RT-qPCR confirmed an increase in pro-inflammatory cytokine and macrophage-related gene expression but a decrease in natural killer cell signaling. Immunostaining confirmed a uterus-specific increase in macrophage infiltration. Flow cytometry delineated an increase in inflammatory macrophages and a decrease in uterine dendritic cells in Ltf^iCre/+Arid1a^f/f uteri. These findings demonstrate a role for endometrial epithelial ARID1A in suppressing inflammation and maintaining uterine immune homeostasis, which are required for successful pregnancy and gynecological health.     

Miniaturized Flexible Electronic Systems with Wireless Power and Near‐Field Communication Capabilities

A class of thin, lightweight, flexible, near‐field communication (NFC) devices with ultraminiaturized format is introduced, and systematic investigations of the mechanics, radio frequency characteristics, and materials aspects associated with their optimized construction are presented. These systems allow advantages in mechanical strength, placement versatility, and minimized interfacial stresses compared to other NFC technologies and wearable electronics. Detailed experimental studies and theoretical modeling of the mechanical and electromagnetic properties of these systems establish understanding of the key design considerations. These concepts can apply to many other types of wireless communication systems including biosensors and electronic implants.     

Nanoshuttered OLEDs: Unveiled Invisible Auxiliary Electrode

In this study, organic light‐emitting diodes (OLEDs) with enhanced optical properties are fabricated by inserting a nanosized stripe auxiliary electrode layer (nSAEL) between the substrate and an indium tin oxide (ITO) layer. This design can avoid the shortcomings of conventional microsized layers while maintaining high optical uniformity due to the improved conductivity of the electrode. The primary advantage is that the nSAEL (submicrometer scale) is no longer visible to the naked eye. Moreover, the reflective shuttered (grating) structure of the nSAEL increases the forward‐directed light by the microcavity (MC) effect and minimizes the loss of light by the extracting the surface plasmon polariton (SPP) mode. In this study, the degree of the MC and SPP can be controlled with the parameters of the nSAEL by simply conjugating the conditions of laser interference lithography (LIL). Therefore, the current and power efficiencies of the device with an nSAEL with optimized parameters are 1.17 and 1.23 times higher than the reference device at 1000 cd/m², respectively, and at these parameters, the overall sheet resistance is reduced to less than half (48%). All of the processes are verified by comparing the computational simulation results and the experimental results obtained with the actual fabricated device.