Endothelin receptor A (ET
), a class A G-protein-coupled receptor (GPCR), is involved in the progression and metastasis of colorectal, breast, lung, ovarian, and prostate cancer. We overexpressed and ...purified human endothelin receptor type A in Escherichia coli and reconstituted it with lipid and membrane scaffold proteins to prepare an ET
nanodisc as a functional antigen with a structure similar to that of native GPCR. By screening a human naive immune single-chain variable fragment phage library constructed in-house, we successfully isolated a human anti-ET
antibody (AG8) exhibiting high specificity for ET
in the β-arrestin Tango assay and effective inhibitory activity against the ET-1-induced signaling cascade via ET
using either a CHO-K1 cell line stably expressing human ET
or HT-29 colorectal cancer cells, in which AG8 exhibited IC
values of 56 and 51 nM, respectively. In addition, AG8 treatment repressed the transcription of inhibin βA and reduced the ET
-induced phosphorylation of protein kinase B and extracellular regulated kinase. Furthermore, tumor growth was effectively inhibited by AG8 in a colorectal cancer mouse xenograft model. The human anti-ET
antibody isolated in this study could be used as a potential therapeutic for cancers, including colorectal cancer.
For the management of rotating machines, machine learning (ML) has been researched with the use of feature parameters that have physical and statistical meanings of vibration signals. Genetic ...algorithm (GA) and principal component analysis (PCA) are the algorithms used for the selection or extraction process of the features; equipment condition. This study proposes a new method to maximize the advantages of the extraction and selection algorithms, thereby improving the fault classification performance. The proposed method is estimated in a variety of equipment conditions by selecting and extracting the effective features for status classification. To evaluate the performance of the fault classification through feature selection and extraction of the ML, a comparative analysis with the proposed method and the original method is also performed. With Lab-scale gearbox, several types of fault tests are conducted, and seven different fault types of equipment conditions, including the normal status, are simulated. The results of the experiments show that, the performance of classification of GA for feature selection is 85%, while PCA for feature extraction is 53%. The performance result of the proposed method for fault classification is 95%, meaning that the performance of fault diagnosis is more efficient in terms of discriminative learning than the original method. Therefore, the proposed method with feature extraction and selection algorithm can improve the fault classification performance by 10% and more for fault diagnosis through ML.
Intercellular bridges are a conserved feature of spermatogenesis in mammalian germ cells and derive from arresting cell abscission at the final stage of cytokinesis. However, it remains to be fully ...understood how germ cell abscission is arrested in the presence of general cytokinesis components. The TEX14 (testis-expressed gene 14) protein is recruited to the midbody and plays a key role in the inactivation of germ cell abscission. To gain insights into the structural organization of TEX14 at the midbody, we have determined the crystal structures of the EABR endosomal sorting complex required for transport (ESCRT) and ALIX-binding region of CEP55 bound to the TEX14 peptide (or its chimeric peptides) and performed functional characterization of the CEP55–TEX14 interaction by multiexperiment analyses. We show that TEX14 interacts with CEP55-EABR via its AxGPPx₃Y (Ala793, Gly795, Pro796, Pro797, and Tyr801) and PP (Pro803 and Pro804) sequences, which together form the AxGPPx₃YxPP motif. TEX14 competitively binds to CEP55-EABR to prevent the recruitment of ALIX, which is a component of the ESCRT machinery with the AxGPPx₃Y motif. We also demonstrate that a high affinity and a low dissociation rate of TEX14 to CEP55, and an increase in the local concentration of TEX14, cooperatively prevent ALIX from recruiting ESCRT complexes to the midbody. The action mechanism of TEX14 suggests a scheme of how to inactivate the abscission of abnormal cells, including cancer cells.
The angle-variable tunable optical filter was strictly fabricated by two strategies of nanoimprint-coupled metal nanopatterning with improved cost-effectiveness and accessibility. The tunable optical ...properties and the performances of two strategies were experimentally examined and turned out to be well matched to numerical results. Tunable properties are obtained by three factors: size of fabricated Ag nanodisks, incident illumination angle, and fabrication strategies. The resonant extinction peak shifts were identified to show a large increase along with the increase in fabricated Ag disk size and increase in the incidence angle of illumination. When comparing a fabrication strategy, it was confirmed that the sample fabricated by the strip-off method has better stability on color changes with a consistent dependency on the incident angle. The presented strategies of fabrication are technically viable for obtaining well-defined plasmonic nanostructures so that it has the feasibility to apply for fascinating optical applications including display or tunable optical filters.
Abstract
Our density functional theory calculations show that tiny-gap semiconductor SiGe monolayer is a quantum valley Hall insulator with a spontaneous electric polarization and, under a small ...biaxial strain, undergoes a topological phase transition between the states with opposite valley Chern numbers. The topological phase transition entails abrupt inversion of the in-plane electric polarization corresponding to inversion of the sublattice pseudospin polarization, while the out-of-plane electric polarization shows a linear response to the biaxial strain as well as to the perpendicular electric field regardless of the phase transition. Thus, the quantum valley Hall state entails in-plane ferroelectricity corresponding to a sublattice pseudospin ferromagnetism.
Frequency-stabilized optical frequency combs have created many high-precision applications. Accurate timing, ultralow phase noise, and narrow linewidth are prerequisites for achieving the ultimate ...performance of comb-based systems. Ultrastable cavity-based comb-noise stabilization methods have enabled sub-10
-level frequency instability. However, these methods are complex and alignment sensitive, and their use has been mostly confined to advanced metrology laboratories. Here, we have established a simple, compact, alignment-free, and potentially low-cost all-fiber photonics-based stabilization method for generating multiple ultrastable combs. The achieved performance includes 1-femtosecond timing jitter, few times 10
-level frequency instability, and <5-hertz linewidth, rivalling those of cavity-stabilized combs. This method features flexibility in configuration: As a representative example, two combs were stabilized with 180-hertz repetition rate difference and ~1-hertz relative linewidth and could be used as an ultrastable, octave-spanning dual-comb spectroscopy source. The demonstrated method constitutes a mechanically robust and reconfigurable tool for generating multiple ultrastable combs suitable for field applications.
There is still a lack of sufficient research on the mechanism behind neurogenic bladder (NB) treatment. The aim of this study was to explore the effect of overexpressed stromal cell-derived factor-1 ...(SDF-1) secreted by engineered immortalized mesenchymal stem cells (imMSCs) on the NB. In this study, primary bone marrow mesenchymal stem cells (BM-MSCs) were transfected into immortalized upregulated SDF-1-engineered BM-MSCs (imMSCs/eSDF-1
+
) or immortalized normal SDF-1-engineered BM-MSCs (imMSCs/eSDF-1−). NB rats induced by bilateral pelvic nerve (PN) transection were treated with imMSCs/eSDF-1
+
, imMSCs/eSDF-1
−
, or sham. After a 4-week treatment, the bladder function was assessed by cystometry and voiding pattern analysis. The PN and bladder tissues were evaluated via immunostaining and western blotting analysis. We found that imMSCs/eSDF-1
+
expressed higher levels of SDF-1 in vitro and in vivo. The treatment of imMSCs/eSDF-1
+
improved NB and evidently stimulated the recovery of bladder wall in NB rats. The recovery of injured nerve was more effective in the NB+imMSCs/eSDF-1
+
group than in other groups. High SDF-1 expression improved the levels of vascular endothelial growth factor and basic fibroblast growth factor. Apoptosis was decreased after imMSCs injection, and was detected rarely in the NB+imMSCs/eSDF-1
+
group. Injection of imMSCs boosted the expression of neuronal nitric oxide synthase, p-AKT, and p-ERK in the NB+imMSCs/eSDF-1
+
group than in other groups. Our findings demonstrated that overexpression of SDF-1 induced additional MSC homing to the injured tissue, which improved the NB by accelerating the restoration of injured nerve in a rat model.
Previously we have demonstrated transglutaminase 2 (TGase 2) inhibition abrogated renal cell carcinoma (RCC) using GK921 (3-(phenylethynyl)-2-(2-(pyridin-2-yl)ethoxy)pyrido3,2-bpyrazine), although ...the mechanism of TGase 2 inhibition remains unsolved. Recently, we found that the increase of TGase 2 expression is required for p53 depletion in RCC by transporting the TGase 2 (1–139 a.a)–p53 complex to the autophagosome, through TGase 2 (472–687 a.a) binding p62. In this study, mass analysis revealed that GK921 bound to the N terminus of TGase 2 (81–116 a.a), which stabilized p53 by blocking TGase 2 binding. This suggests that RCC survival can be stopped by p53-induced cell death through blocking the p53–TGase 2 complex formation using GK921. Although GK921 does not bind to the active site of TGase 2, GK921 binding to the N terminus of TGase 2 also inactivated TGase 2 activity through acceleration of non-covalent self-polymerization of TGase 2 via conformational change. This suggests that TGase 2 has an allosteric binding site (81–116 a.a) which changes the conformation of TGase 2 enough to accelerate inactivation through self-polymer formation.
This paper investigates the correlation between the random lasing properties of organic waveguides made by poly-(9-9dioctylfluorene) (PFO) thin films and the morphology of wrinkled corrugated ...substrates. The capability to individually control the wrinkle wavelength, shape, and height allows us to separately investigate their role on the sample emission properties. We demonstrate that the main parameter determining the presence of coherent random lasing is the substrate roughness and that, contrary to what could be qualitatively expected, as the roughness increases, coherent random lasing is progressively reduced. Coherent random lasing is observed only for a substrate roughness below 33 nm, while higher roughness leads to amplified spontaneous emission (up to 70 nm) or to the absence of light amplification in the film (above 70 nm). We demonstrate that this result is due to a progressive reduction of the light amplification efficiency in the PFO film, evidencing that coherent random lasing can be obtained only with a right interplay between light amplification and scattering. Besides clarifying the basic aspects of random lasing in organic waveguides, our work opens the way to the realization of organic random lasers with predictable emission properties, thanks to the high control level of the scattering properties of the wrinkled corrugated surfaces.
We have investigated the valley Chern number and gapless edge states in wide-gap semiconductor SiC and BN monolayers by using the density functional theory calculations. We found that while SiC ...monolayer has a non-quantized valley Chern number due to a partial mixing of the Berry curvature peaks pertaining to the opposite valleys, there exist topologically protected gapless edge states within the bulk gap, leading to a quantum valley Hall effect. Doping of the opposite charge carriers causes a backscattering-free valley current flowing on the opposite edge, which can be used for experimental confirmation and application at room temperature. BN monolayer, on the other hand, was found to have gapped edge states due to the too large staggered AB-sublattice potentials.
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