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Despite numerous observations regarding the relationship between DNA methylation changes and cancer progression, only a few genes have been verified as diagnostic biomarkers of colorectal cancer (CRC). To more practically detect methylation changes, we performed targeted bisulfite sequencing. Through co-analysis of RNA-seq, we identified cohort-specific DNA methylation markers: CpG islands of the intragenic regions of PDX1, EN2, and MSX1. We validated that these genes have oncogenic features in CRC and that their expression levels are increased in correlation with the hypermethylation of intragenic regions. The reliable depth of the targeted bisulfite sequencing data enabled us to design highly optimized quantitative methylation-specific PCR primer sets that can successfully detect subtle changes in the methylation levels of candidate regions. Furthermore, these methylation levels can divide CRC patients into two groups denoting good and poor prognoses. In this study, we present a streamlined workflow for screening clinically significant differentially methylated regions. Our discovery of methylation markers in the PDX1, EN2, and MSX1 genes suggests their promising performance as prognostic markers and their clinical application in CRC patients.

Efficient cardiac differentiation of human pluripotent stem cells (hPSCs) is essential for their use in the field of basic research as well as in cell-based therapy. Regulation of the Wnt/β-catenin pathway is a key step in the process of cardiac differentiation of hPSCs. In this study, we reported cyclosporin A (CsA), a strong immunosuppressor, as an inducer of cardiac differentiation in human embryonic stem cells (hESCs). Our results showed that CsA promoted cardiac differentiation in the mesodermal differentiation stage of hESCs and that this effect was mediated by the inhibition of Wnt/β-catenin signaling. Therefore, our results provide novel information about CsA as a Wnt/β-catenin inhibitor as well as a strategy for the cardiac differentiation of hESCs.

One of the major obstacles to realizing spintronic devices such as MESO logic devices is the small signal magnitude used for magnetization readout, making it important to find materials with high spin-to-charge conversion efficiency. Although intermixing at the junction of two materials is a widely occurring phenomenon, its influence on material characterization and the estimation of spin-to-charge conversion efficiencies is easily neglected or underestimated. Here, we demonstrate all electrical spin-to-charge conversion in Bi$_x$Se$_{1-x}$ nanodevices and show how the conversion efficiency can be overestimated by tens of times depending on the adjacent metal used as a contact. We attribute this to the intermixing-induced compositional change and the properties of a polycrystal that lead to drastic changes in resistivity and spin Hall angle. Strategies to improve the spin-to-charge conversion signal in similar structures for functional devices are discussed., Main text (18 pages, 3 figures, 2 tables) and supporting information (18 pages)

Human embryonic stem cells (hESCs) have unique characteristics, such as self-renewal and pluripotency, which are distinct from those of other cell types. These characteristics of hESCs are tightly regulated by complex signaling mechanisms. In this study, we demonstrate that yes-associated protein (YAP) functions in an hESC-specific manner to maintain self-renewal and survival in hESCs. hESCs were highly sensitive to YAP downregulation to promote cell survival. Interestingly, hESCs displayed dynamic changes in YAP expression in response to YAP downregulation. YAP was critical for the maintenance of self-renewal. Additionally, the function of YAP in maintenance of self-renewal and cell survival was hESC-specific. Doxycycline upregulated YAP in hESCs and attenuated the decreased cell survival induced by YAP downregulation. However, decreased expression of self-renewal markers triggered by YAP downregulation and neural/cardiac differentiation were affected by doxycycline treatment. Collectively, the results reveal the mechanism underlying the role of YAP and the novel function of doxycycline in hESCs.

One of the major obstacles to realizing spintronic devices such as MESO logic devices is the small signal magnitude used for magnetization readout, making it important to find materials with high spin-to-charge conversion efficiency. Although intermixing at the junction of two materials is a widely occurring phenomenon, its influence on material characterization and the estimation of spin-to-charge conversion efficiencies are easily neglected or underestimated. Here, we demonstrate all-electrical spin-to-charge conversion in Bi

Ion gels consisting of room-temperature ionic liquids and polymer gelators are considered attractive solid-state electrolyte platforms for functional electrochemical applications due to their tunab...

Background: Alternative transcription initiation (ATI) has been frequently observed in cancer suggesting that it contributes to the malignant transformation of the cells. However, ATI remains largely unexplored mainly due to the lack of tools for detecting ATI. We propose a computational method for integrating bulk ATAC-seq and bulk RNA-seq to identify ATI and understand their differential usage between tissues. We hypothesize that differential ATAC-seq intensity can be used as a guide for looking for differential promoter usage, which might enable the identification of novel ATI events in a transcript-agnostic way. Methods: We recently published methods for RNA-seq base-level analysis for identifying structural variations in transcripts. Building on this, we developed a supervised sparse non-negative matrix factorization approach that integrates base-level RNA-seq and ATAC-seq, which aims to identify ATIs as well as characterize the latent structure of the underlying isoforms. This method equips many unique features that can be useful for the identification of novel ATIs. Because the method scans an entire collection of DNA accessible regions provided by ATAC-seq, it enables a comprehensive screening of novel ATI candidates that are not limited to the known promoters. Additionally, the uncompressed view of base-level RNA-seq allows us to infer the structure of individual isoforms independently of known gene annotation. The predicted isoforms can be further used to deconvolute base-level RNA-seq of individual cases into the isoforms and thus infer expression levels of each isoform. Results: We applied this method to a sub-cohort (N=350) of TCGA pan-cancer samples in which both ATAC-seq and RNA-seq are available. Empiric comparison to existing methods confirmed known true positive ATIs including important cancer genes such as CDKN2A and ALK. In particular, the method successfully identified the ATIs including some challenging cases such as ATIs located at internal introns or at constitutive exons in other transcripts. The deconvolution analysis applied to the extended cohort to all available ~10,000 TCGA pan-caner samples across 32 tissue types revealed that ATIs were predominantly differentiated across tissue types. By applying the method to a set of transcription regulator genes, we identified ~1% of the genes had ATIs including the novel cancer-specific genes with known ATIs that had not been previously reported as relevant to cancer. Additionally, we provide examples in which the isoform’s function relative to cancer appears mechanistically interesting. Conclusion: We propose a multi-omics integration method that is independent of known gene annotation, enabling a robust identification of ATIs. Our results strongly demonstrate our ability to pick up known as well as novel ATIs that are otherwise difficult to identify by existing methods. Citation Format: Hyo Young Choi, Won-Young Choi, David N. Hayes. Novel framework for systematically detecting alternative transcript initiation by integrating ATAC-seq and RNA-seq [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2076.

This study aims to promote and revitalise quality control by efficiently separating impurities from recycled fine aggregates and soil. To meet this end, equipment that can apply the impact of a rotor hammer and multi-stage wind pressure was developed. Furthermore, the applicability of this equipment to recycled soil and fine aggregate was examined by testing their physical properties. The results confirmed that it is possible to apply the equipment to recycled soil and fine aggregates while satisfying all regulations. Additionally, concrete properties such as slump, air content, compressive strength, and drying shrinkage, by mixing ratio, of the recycled fine aggregates were tested, and it was proved that up to 60% of the recycled fine aggregates could be used at a compression strength of 27 MPa.

In this study, rationally designed random copolymers containing highly flexible, low glass transition temperature (Tg) segments are suggested as effective polymeric gelators for high-performance ion gel electrolytes. To this end, a series of poly(styrene-ran-butyl acrylate) copolymers (PS-r-PBAs) is prepared by a one-pot reversible additional-fragmentation chain transfer polymerization. Physically crosslinked ion gel electrolytes are produced by self-assembly when blended with ionic liquids of 1-butyl-3-methylimidazolium bis(trifluoromethyl sulfonyl)imide ([BMI][TFSI]). The properties of gels based on PS-r-PBAs and PS-ran-poly(methyl methacrylate)s (PS-r-PMMAs) are compared at similar molecular conditions. As a result, the effectiveness of the high chain flexibility of butyl acrylate is shown by higher ionic conductivity. The gels with PS-r-PBAs are further optimized in terms of the molecular characteristics of copolymers (e.g., the content of Sty and total molecular weight) and gel composition. The versatility of PS-r-PBA-containing gels as practical electrolyte platforms is demonstrated by preparing all-in-one type electrochromic devices, for which electrochromic ion gels are prepared by incorporating chromophores into the gels. To extend the functionality of the electrochromic devices, dot-shaped electrochromic gel arrays are fabricated for actively controllable smart windows that can reduce the window strike of birds.

In this letter, we report the characteristics of zero-bias capacitive micromachined ultrasonic transducers (CMUTs) in various aspects, considering the transmission and reception sensitivity and evaluation of the long-term stability with ac transmission in immersion. The main idea of the zero-bias CMUT implementation is that the charge is injected by the dielectric charging effects in an insulation layer in the pull-in state. The CMUT was fabricated by a local oxidation of silicon (LOCOS) process, and the insulation layer consists of Si3 N4 –SiO2 and SiO2, which have been commonly used in previous studies. A study on the charging effects is reported to quantitatively observe the voltage shift by charge transfer with time dependence at different temperatures and collapsing time dependence. Therefore, we successfully implemented a zero-bias CMUT with a transmission efficiency of 4.62 kPa/V at a center frequency of 7.53 MHz in Si3 N4–SiO2 and a transmission efficiency of 6.78 kPa/V at a center frequency of 7.86 MHz in SiO2 immersion.

An ultrasound transducer was fabricated by dropping a multi-walled carbon nanotube solution containing a mixture of carbon nanotubes and ethoxyethanol directly on the surface of polyethylene microspheres. The frequency modulation depended on the diameter of the polyethylene microspheres. To investigate this relationship, three types of polyethylene microspheres with different diameters were used in simulations and experiments. These specimens were attached to polydimethylsiloxane and glass plates. A comparison revealed that the 50 μm diameter polyethylene spheres coated with carbon nanotubes had the highest ultrasound frequency. This work showed that smaller polyethylene microspheres generate higher ultrasound frequencies.

Intravacuolar bacterial pathogens establish intracellular niches by constructing membrane-encompassed compartments. The vacuoles surrounding the bacteria are remarkably stable, facilitating microbial replication and preventing exposure to host cytoplasmically-localized innate immune sensing mechanisms. To maintain integrity of the membrane compartment, the pathogen is armed with defensive weapons that prevent loss of vacuole integrity and potential exposure to host innate signaling. In some cases, the microbial components that maintain vacuolar integrity have been identified, but the basis for why the compartment degrades in their absence is unclear. In this review, we point out that lessons from the microbial-programmed degradation of the vacuole by the cytoplasmically-localized Shigella flexneri provide critical insights into how degradation of pathogen vacuoles occurs. We propose that in the absence of bacterial-encoded guard proteins, aberrant trafficking of host membrane-associated components results in a dysfunctional pathogen compartment. As a consequence, the vacuole is poisoned and replication is terminated.

In this work, we investigate the correlation between the molecular configuration of copolymer gelators and the resulting gel performance. Two copolymers exhibiting phase homogeneity without noticeable phase separation, poly(ethyl methacrylate)-ran-polystyrene (PEMA-r-PS) and disordered PEMA-b-PS, are prepared as gelators. To ensure an accurate comparison, factors closely related to gel properties (e.g., total molecular weight of gelators, styrene fraction of both copolymers, and gel composition) were fixed. Both gelators produce ion gels with similar conductivities when blended with an ionic liquid of 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([EMI][TFSI]). However, there is a significant difference in their mechanical robustness. For example, the elastic modulus (∼2.20 × 105 Pa) of PEMA-r-PS-based gels was ∼113% higher than that (∼1.03 × 105 Pa) of the gel containing PEMA-b-PS. This result is explained by the difference in gel network structure. Namely, PEMA-r-PS gels contain a high density of smaller [EMI][TFSI]-insoluble styrene domains, which are advantageous for obtaining mechanically robust ion gels without sacrificing ionic conductivity. Moreover, the versatility of PEMA-r-PS gels as an electrochemical platform is demonstrated via application in electrochromic devices and stretchable ionic motion sensors. Overall, this work suggests that tuning the molecular configuration of copolymer gelators is another effective way to obtain high-performance ion gel electrolytes for various electrochemical applications.

Topological spin textures such as magnetic skyrmions have attracted considerable interest due to their potential application in spintronic devices. However, there still remain several challenges to overcome before their practical application, for instance, achieving high scalability and thermal stability. Recent experiments have proposed a new class of skyrmion materials in the Heusler family, Mn1.4Pt0.9Pd0.1Sn and Mn2Rh0.95Ir0.05Sn, which possess noncollinear magnetic structures. Motivated by these experimental results, we suggest another Heusler compound hosted by Mn3Ga to overcome the above limitations. We fabricate Mn3-xPdxGa thin films, focusing on the magnetic compensation point. In Mn2.3Pd0.7Ga, we find a spin-reorientation transition around TSR = 320 K. Below the TSR, we observe the topological Hall effect and a positive magnetic entropy change, which are the hallmarks of a chiral noncollinear spin texture. By integrating all the data, we determine the magnetic phase diagram, displaying a wide chiral noncollinear spin phase even at room temperature. We believe that this compensated ferrimagnet shows promise for opening a new avenue toward chiral spin-based, high-density, and low-power devices.

SUMMARY Legionella pneumophila grows intracellularly within a replication vacuole via action of Icm/Dot-secreted proteins. One such protein, SdhA, maintains the integrity of the vacuolar membrane, thereby preventing cytoplasmic degradation of bacteria. We show here that SdhA binds and blocks the action of OCRL (OculoCerebroRenal syndrome of Lowe), an inositol 5-phosphatase pivotal for controlling endosomal dynamics. OCRL depletion results in enhanced vacuole integrity and intracellular growth of a sdhA mutant, consistent with OCRL participating in vacuole disruption. Overexpressed SdhA alters OCRL function, enlarging endosomes, driving endosomal accumulation of phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2), and interfering with endosomal trafficking. SdhA interrupts Rab guanosine triphosphatase (GTPase)-OCRL interactions by binding to the OCRL ASPM-SPD2-Hydin (ASH) domain, without directly altering OCRL 5-phosphatase activity. The Legionella vacuole encompassing the sdhA mutant accumulates OCRL and endosomal antigen EEA1 (Early Endosome Antigen 1), consistent with SdhA blocking accumulation of OCRL-containing endosomal vesicles. Therefore, SdhA hijacking of OCRL is associated with blocking trafficking events that disrupt the pathogen vacuole., Graphical Abstract, In brief The Legionella SdhA protein supports intracellular growth in both mammalian macrophages and amoebae by preventing disintegration of the membrane-encompassed replication compartment. Choi et al. show that SdhA binds OculoCerebroRenal syndrome of Lowe (OCRL) protein, preventing early endosomal compartments of the host cell from docking and destabilizing the replication compartment.

The interaction between the perfluorosulfonic acid (PFSA) ionomer and platinum group metal (PGM) catalyst in polymer electrolyte fuel cell (PEFC) inks is a critical issue for designing high-performance PEFC electrodes. During the ink fabrication, the complex interparticle interaction of the ink components determines the agglomerate morphology and size distribution. Among the ink components, the ionomer, which has amphiphilic in nature due to its hydrophobic backbone and the hydrophilic ionic group, mostly effective parameter for interparticle interaction. Therefore, understanding the interaction and molecular structure of ionomer is required for a high-performance catalyst layer. The backbone length of the ionomer which controls the spacing between ionic pendant groups is the main parameter of the ionomer character. In this study, the three different ionic spacing ionomers, made in the Solvay industry: Aquivion D72-25BS, Aquivion D83-24BS, and D98-25BS, were used for investigating the adsorption behavior of the catalyst ink and PEFC catalyst layer morphology. During the fabrication of PEFC ink and catalyst layer, all samples have same sulfonic acid molality to avoid the ionic clustering effect in the side chain. Ex-situ measurements were carried out to quantify the interparticle interaction and agglomerate size distribution in the PEFC ink. The dynamic lights scattering (DLS) carry out to determine the aggregation size distribution. The rheological behavior was conducted to understand the interparticle interactions and the agglomeration behavior of the inks by steady-shear and dynamic-oscillatory-shear measurements. It is noted that increasing the ionomer backbone length, which favors interaction via hydrophobic interaction on a carbon support, suppresses the agglomeration of ink components and decreases ink viscosity. The in situ electrochemical tests were carried out to figure out the relationship between ink formulation and catalyst layer morphology. It was found that the long ionomer backbone length helps to suppress the O2 transport resistance and ORR kinetic loss by uniform distribution from ionomer backbone-carbon supports interaction.

To address the global climate change issues, polymer electrolyte fuel cells (PEFCs) are receiving attention as electrochemical energy conversion devices employing green hydrogen. Notably, the PEFC fuel cell is because the electrochemical reaction occurs on the Catalyst Layer (CL), the CL is the core of the Membrane Electrode Assembly (MEA). The conventional CL is usually prepared from catalyst ink comprising the various catalyst, ionomer, and solvents and deposited via blade coating to the decal substrate. Therefore, it is necessary to confirm the optimal decal transfer conditions based on analyzing the characteristics of the catalyst ink and the decal substrate. In the study, the characterize the internal microstructure of the catalyst ink was confirmed through rheology, and the coating velocity was tunable based on catalyst property. In addition, the characteristics of the various decal substrate were confirmed through Atomic Force Microscopy (AFM) and Contact Angle, and differences including variations in loading amount were confirmed despite the same slurry. The structure of CL on the decal sheet was confirmed through a scanning electron microscope (SEM) surface image and cross-section image, and the distribution of Pt and ionomer was confirmed through Energy Dispersive X-Ray Spectrometer (EDS) mapping. The definition of electrochemical performance between catalyst ink characterizes and decal substrates property was investigated through polarization curves and electrochemical impedance spectroscopy (EIS). Also, cyclic voltammetry (CV) techniques are used to characterize electrochemical surface areas (ECSA) areas of the CL. As a result, the property between the catalyst ink and the decal substrate, based on the difference that occurs in the rheology characterized in the catalyst ink, leads to a variation in the CL structure. Therefore, it is very important to determine the decal process conditions by understanding the characteristics of various catalyst ink on rheology and decal sheet.

Brain organoids derived from human pluripotent stem cells provide a highly valuable in vitro model to recapitulate human brain development and neurological diseases. However, the current systems for brain organoid culture require further improvement for the reliable production of high-quality organoids. Here, we demonstrate two engineering elements to improve human brain organoid culture, (1) a human brain extracellular matrix to provide brain-specific cues and (2) a microfluidic device with periodic flow to improve the survival and reduce the variability of organoids. A three-dimensional culture modified with brain extracellular matrix significantly enhanced neurogenesis in developing brain organoids from human induced pluripotent stem cells. Cortical layer development, volumetric augmentation, and electrophysiological function of human brain organoids were further improved in a reproducible manner by dynamic culture in microfluidic chamber devices. Our engineering concept of reconstituting brain-mimetic microenvironments facilitates the development of a reliable culture platform for brain organoids, enabling effective modeling and drug development for human brain diseases., Brain organoids derived from human pluripotent stem cells can model human brain development and disease, though current culture systems fail to ensure reliable production of high-quality organoids. Here the authors combine human brain extracellular matrix and culture in a microfluidic device to promote structural and functional maturation of human brain organoids.

We present an implementation of a compact sensor system based on an ultrasonic pulse-echo method to detect urban sinkholes in advance. Road depression is caused by damages of artificial structures buried underground such as drain pipes. Previous works on sinkhole detection have been performed variously based on electromagnetic, seismic and resistivity. However, there are technical difficulties such as obtaining a high-resolution image in shallow depth, and implementing a compact surveying device. The goal of this work is to fabricate a miniaturized sinkhole detection system based on low cost ultrasonic transducers with a resonant frequency of 40 kHz, and detect near-ground range. Motivated by biomedical ultrasonic imaging methods, we detected air layers below the asphalt using the pulse-echo method. To improve multi-channel image quality, a linear array system was implemented and images were acquired by classical synthetic aperture imaging for laboratory case study. Feasibility tests of the multi-channel sinkhole detector based on an ultrasonic transducer were successful. We present and analyze images obtained by demonstrating an asphalt model which is working under laboratory conditions and simulations Finite Element Analysis (FEA).

The development of cerebral organoid technology has allowed the human neural tissue to be collected for studying human brain development and neurological diseases. Human pluripotent stem cell-derived cerebral organoids (hCOs) are a theoretically infinite source of fresh human brain tissue for various research purposes. However, hCOs have limitations, including core necrotic cell death. To solve this problem, we tested a simple method, which has been previously overlooked. In this study, we mechanically cut 70-day-old hCOs with a scalpel blade into 2 to 4 pieces, each depending on their original size. After culturing cut hCOs for additional 7 days, their size was less variable and smaller than uncut hCOs and there were no histological differences between uncut and cut hCOs. Note that hypoxia-inducible factor (HIF)−1α was expressed in the central area of uncut hCOs but not in cut hCOs. Uncut hCOs, therefore, showed broad core areas stained with terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL), whereas cut hCOs did not. In conclusion, this simple mechanical cutting method allowed us to acquire a larger number of hCOs without a necrotic core., Human pluripotent stem cell; Cerebral organoids; Necrosis; Mechanical cutting.

Objective:The aim of this study was to evaluate the mortality rates of 566,602 patients with coronavirus disease (COVID-19) based on sex, age, and the presence or absence of underlying diseases and determine whether the underlying disease provides prognostic information specifically related to death.Methods:The mortality rate was evaluated using conditional probability to identify the significant factors, and adjusted odds ratios (ORs) using a multivariable logistic regression analysis were estimated.Results:The mortality rate of patients with underlying health conditions was 12%, which was 4 times higher than that of patients without underlying health conditions. Furthermore, the mortality rates of women and men with underlying health conditions were 5.5 and 3.4 times higher than the mortality rates of patients without underlying health conditions, respectively. In a multivariable logistic regression analysis including sex, age, and underlying health conditions, male sex (OR: 1.83), age ≥ 41 y (ORs > 2.70), and underlying health conditions (OR: 2.20) were confirmed as risk factors for death.Conclusions:More attention should be paid to older patients with underlying diseases and male patients with underlying diseases as the probability of death in this population was significantly higher.

As the width of the line decreases, there are advantages such as improved performance, reduced unit price, and reduced power consumption, but high accuracy is required. Heat deformation by exposure light is one of several factors that reduces accuracy. These variations cause overlay and focus problems and can sometimes lead to serious overlay and CD variation. Because the linewidth is reduced to x nm, the overlay error of several nm and the critical dimension (CD) value are also greatly affected. Currently, it can be solved to some extent by stage adjustment and fine-tuning, but the problem still remains. In this paper, we checked the mechanism of wafer deformation due to energy absorption during exposure, changing the conditions of pattern linewidth and line and space (L/S).

The lifetime of the EUV pellicle might be reduced, if contaminant particles accumulate on the pellicle during the EUV lithography process. Through the simulation, the temperature change, deformation, and stress of the pellicle with the type, shape, size, number and location of contaminated particles were examined. And the lifetime expectancy of pellicles for EUV lithography of various structures was compared through a relative comparison of failure points due to thermal deformation. The difference in thermal properties such as heat capacity, thermal conductivity, emissivity, and thermal expansion coefficient of the pellicle and the contaminated particle generated thermal stress in the area where the pellicle and the contaminated particle abutted, and the thermal stress increased as the exposure was repeated. In addition, if exposure continued even after the convergence of temperature, deformation, and thermal stress, physical fatigue due to exposure and cooling could accumulate and shorten the lifetime of the pellicle.

Topologically protected chiral skyrmion is an intriguing spin texture, which has attracted much attention because of fundamental research and future spintronic applications. MnSi with the non-centrosymmetric structure is well-known material hosting skyrmion phase. To date, preparation of MnSi crystals has been investigated by using special instruments with ultrahigh vacuum chamber. Here, we introduce a facile way to grow MnSi films on sapphire substrate using a relatively low vacuum environment of conventional magnetron sputtering. Although as-grown MnSi films have polycrystalline nature, the stable skyrmion phase in a broad range of temperatures and magnetic fields is observed by magnetotransport properties including phenomenological scaling analysis of Hall resistivities contribution. Our findings provide not only a general way to prepare the materials possessing skyrmion phase, but also insight into further research to stimulate more degrees of freedom in our inquisitiveness.

Cell type specification is a delicate biological event in which every step is under tight regulation. From a molecular point of view, cell fate commitment begins with chromatin alteration, which kickstarts lineage-determining factors to initiate a series of genes required for cell specification. Several important neuronal differentiation factors have been identified from ectopic over-expression studies. However, there is scarce information on which DNA regions are modified during induced pluripotent stem cell (iPSC) to neuronal progenitor cell (NPC) differentiation, the cis regulatory factors that attach to these accessible regions, or the genes that are initially expressed. In this study, we identified the DNA accessible regions of iPSCs and NPCs via the Assay for Transposase-Accessible Chromatin sequencing (ATAC-seq). We identified which chromatin regions were modified after neuronal differentiation and found that the enhancer regions had more active histone modification changes than the promoters. Through motif enrichment analysis, we found that NEUROD1 controls iPSC differentiation to NPC by binding to the accessible regions of enhancers in cooperation with other factors such as the Hox proteins. Finally, by using Hi-C data, we categorized the genes that directly interacted with the enhancers under the control of NEUROD1 during iPSC to NPC differentiation.

The effects of gene body DNA methylation on gene regulation still remains highly controversial. In this study, we generated whole genome bisulfite sequencing (WGBS) data with high sequencing depth in induced pluripotent stem cell (iPSC) and neuronal progentior cell (NPC), and investigated the relationship between DNA methylation changes in CpG islands (CGIs) and corresponding gene expression during NPC differentiation. Interestingly, differentially methylated CGIs were more abundant in intragenic regions compared to promoters and these methylated intragenic CGIs (iCGIs) were associated with neuronal development-related genes. When we compared gene expression level of methylated and unmethylated CGIs in intragenic regions, DNA methylation of iCGI was positively correlated with gene expression in contrast with promoter CGIs (pCGIs). To gain insight into regulatory mechanism mediated by iCGI DNA methylation, we executed motif searching in hypermethylated iCGIs and found NEUROD1 as a hypermethylated iCGI binding transcription factor. This study highlights give rise to possibility of activating role of hypermethylation in iCGIs and involvement of neuronal development related TFs. Graphical Abstract The relationship between iCGI DNA methylation and expression of associated genes in neuronal developmental process. During iPSC to NPCdifferentiation, iCGI containing neural developmental genes show iCGI's DNA hypermethylation which is accompanied by gene activation and NEUROD1which is one of the core neuronal TFs interacts with hypermethylated iCGI regions.

In this study, we propose a rational route to create wrinkling patterns with individually controllable location and direction in thin polymer films. Optical and atomic force microscopy analysis confirmed the formation of straight wrinkles with a typical width of 1.51 to 1.55 μm and a height of 60 to 65 nm. Confocal fluorescence microscopy revealed that each wrinkle produces a continuous hollow channel that interconnects neighboring holes in the polymer film, demonstrating potential applications as nanoscale fluidic channel and reactor. Moreover, we propose a mechanism that considers the elastic deformation energy and interface energies as crucial parameters that govern the mechanical instabilities, which provides scaling relationships between the height, width, and thickness of the wrinkles. This offers additional opportunities for control over the size and aspect ratio of the wrinkles and channels.

In this study, we propose low power consumption, all-in-one type electrochromic devices (ECDs) for effective heat shutters. Considering diffusion-controlled device operation, polymeric viologens (poly-viologens) are synthesized to lower the diffusivity of EC chromophores and to minimize self-bleaching. In comparison with devices based on mono-viologens corresponding to the monomer of poly-viologens, poly-viologen-containing ECDs exhibit advantages of lower coloration voltage (ca, -0.55 V) and higher coloration/bleaching cyclic stability (>1500 cycles). In particular, poly-viologen ECDs show remarkably reduced self-bleaching as designed, resulting in extremely low power consumption (∼8.3 μW/cm2) to maintain the colored state. Moreover, we successfully demonstrate solar heat shutters that suppress the increment of indoor temperature by taking the advantage of low-power operation and near-IR absorption of the colored poly-viologen-based ECDs. Overall, these results imply that the control of the diffusivity of EC chromophores is an effective methodology for achieving single-layered, low-power electrochemical heat shutters that can save indoor cooling energy when applied as smart windows for buildings or vehicles.