Voltage-based magnetization switching and reading in magnetoelectric spin-orbit nanodevices.

As CMOS technologies face challenges in dimensional and voltage scaling, the demand for novel logic devices has never been greater, with spin-based devices offering scaling potential, at the cost of significantly high switching energies. Alternatively, magnetoelectric materials are predicted to enable low-power magnetization control, a solution with limited device-level results. Here, we demonstrate voltage-based magnetization switching and reading in nanodevices at room temperature, enabled by exchange coupling between multiferroic BiFeO3 and ferromagnetic CoFe, for writing, and spin-to-charge current conversion between CoFe and Pt, for reading. We show that, upon the electrical switching of the BiFeO3, the magnetization of the CoFe can be reversed, giving rise to different voltage outputs. Through additional microscopy techniques, magnetization reversal is linked with the polarization state and antiferromagnetic cycloid propagation direction in the BiFeO3. This study constitutes the building block for magnetoelectric spin-orbit logic, opening a new avenue for low-power beyond-CMOS technologies.

Evaluation of Durability Performance for Chloride Ingress Considering Long-Term Aged GGBFS and FA Concrete and Analysis of the Relationship between Concrete Mixture Characteristic and Passed Charge Using Machine Learning Algorithm.

In this study, accelerated chloride diffusion tests are performed on ordinary Portland cement (OPC), ground granulated blast furnace slag (GGBFS), and fly ash (FA) concretes aged 4-6 years. Passed charge is evaluated according to ASTM-C-1202 for 12 mixtures, considering water-binder (W/B) ratios (0.37, 0.42, and 0.47), GGBFS replacement rates (0%, 30%, 50%), and FA replacement rates (0% and 30%). The effects of aged days on passed charge reduction behavior are quantified through repetitive regression analysis. Among existing machine learning (ML) models, linear, lasso, and ridge models are used to analyze the correlation of aged days and mix properties with passed charge. Passed charge analysis considering long-term age shows a significant variability decrease of passed charge by W/B ratio with increasing age and added admixtures (GGBFS and FA). Furthermore, the higher the water-binder ratio in GGBFS and FA concretes, the greater the decrease in passed charge due to aged days. The ML model-based regression analysis shows high correlation when compressive strength and independent variables are considered together. Future work includes a correlational analysis between mixture properties and chloride ingress durability performance using deep learning models based on the time series properties of evaluation data.

Controlling the Interlayer Dzyaloshinskii-Moriya Interaction by Electrical Currents.

The recently discovered interlayer Dzyaloshinskii-Moriya interaction (IL-DMI) in multilayers with perpendicular magnetic anisotropy favors canting of spins in the in-plane direction. It could thus stabilize intriguing spin textures such as Hopfions. A key requirement for nucleation is to control the IL-DMI. Therefore, we investigate the influence of an electric current on a synthetic antiferromagnet with growth-induced IL-DMI. The IL-DMI is quantified by using out-of-plane hysteresis loops of the anomalous Hall effect while applying a static in-plane magnetic field at varied azimuthal angles. We observe a shift in the azimuthal dependence with an increasing current, which we conclude to originate from the additional in-plane symmetry breaking introduced by the current flow. Fitting the angular dependence, we demonstrate the presence of an additive current-induced term that linearly increases the IL-DMI in the direction of current flow. This opens the possibility of easily manipulating 3D spin textures by currents.

Multimodal Wearable Ionoskins Enabling Independent Recognition of External Stimuli Without Crosstalk.

Wearable ionoskins are one of the representative examples of the many useful applications offered by deformable stimuli-responsive sensory platforms. Herein, ionotronic thermo-mechano-multimodal response sensors are proposed, which can independently detect changes in temperature and mechanical stimuli without crosstalk. For this purpose, mechanically robust, thermo-responsive ion gels composed of poly(styrene-ran-n-butyl methacrylate) (PS-r-PnBMA, copolymer gelator) and 1-butyl-3-methylimidazolium bis(trifluoromethyl sulfonyl)imide ([BMI][TFSI], ionic liquid) are prepared. The optical transmittance change arising from the lower critical solution temperature (LCST) phenomenon between PnBMA and [BMI][TFSI] is exploited to track the external temperature, creating a new concept of the temperature coefficient of transmittance (TCT). The TCT of this system (-11.5% °C-1 ) is observed to be more sensitive to temperature fluctuations than the conventional metric of temperature coefficient of resistance. The tailoring molecular characteristics of gelators selectively improved the mechanical robustness of the gel, providing an additional application opportunity for strain sensors. This functional sensory platform, which is attached to a robot finger, can successfully detect thermal and mechanical environmental changes through variations in the optical (transmittance) and electrical (resistance) properties of the ion gel, respectively, indicating the high practicality of on-skin multimodal wearable sensors.

Human embryonic stem cell-specific role of YAP in maintenance of self-renewal and survival.

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.

All-Electrical Spin-to-Charge Conversion in Sputtered BixSe1-x.

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 BixSe1-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.

Hypermethylation of PDX1, EN2, and MSX1 predicts the prognosis of colorectal cancer.

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.

ZNF204P is a stemness-associated oncogenic long non-coding RNA in hepatocellular carcinoma.

Hepatocellular carcinoma is a major health burden, and though various treatments through much research are available, difficulties in early diagnosis and drug resistance to chemotherapy-based treatments render several ineffective. Cancer stem cell model has been used to explain formation of heterogeneous cell population within tumor mass, which is one of the underlying causes of high recurrence rate and acquired chemoresistance, highlighting the importance of CSC identification and understanding the molecular mechanisms of CSC drivers. Extracellular CSCmarkers such as CD133, CD90 and EpCAM have been used successfully in CSC isolation, but studies have indicated that increasingly complex combinations are required for accurate identification. Pseudogene-derived long non-coding RNAs are useful candidates as intracellular CSC markers - factors that regulate pluripotency and self-renewal - given their cancer-specific expression and versatile regulation across several levels. Here, we present the use of microarray data to identify stemness-associated factors in liver cancer, and selection of sole pseudogenederived lncRNA ZNF204P for experimental validation. ZNF204P knockdown impairs cell proliferation and migration/invasion. As the cytosolic ZNF204P shares miRNA binding sites with OCT4 and SOX2, well-known drivers of pluripotency and self-renewal, we propose that ZNF204P promotes tumorigenesis through the miRNA-145-5p/OCT4, SOX2 axis. [BMB Reports 2022; 55(6): 281-286].

SdhA blocks disruption of the Legionella-containing vacuole by hijacking the OCRL phosphatase.

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.

Microfluidic device with brain extracellular matrix promotes structural and functional maturation of human brain organoids.

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.

Forward-Looking Ultrasound Wearable Scanner System for Estimation of Urinary Bladder Volume.

Accurate measurement of bladder volume is an important tool for evaluating bladder function. In this study, we propose a wearable bladder scanner system that can continuously measure bladder volume in daily life for urinary patients who need urodynamic studies. The system consisted of a 2-D array, which included integrated forward-looking piezoelectric transducers with thin substrates. This study aims to estimate the volume of the bladder using a small number of piezoelectric transducers. A least-squares method was implemented to optimize an ellipsoid in a quadratic surface equation for bladder volume estimation. Ex-vivo experiments of a pig bladder were conducted to validate the proposed system. This work presents the potential of the approach for wearable bladder monitoring, which has similar measurement accuracy compared to the commercial bladder imaging system. The wearable bladder scanner can be improved further as electronic voiding diaries by adding a few more features to the current function.

A simple method to improve the quality and yield of human pluripotent stem cell-derived cerebral organoids.

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.

Mortality Rate of Patients With COVID-19 Based on Underlying Health Conditions.

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.

Skyrmion Phase in MnSi Thin Films Grown on Sapphire by a Conventional Sputtering.

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

NEUROD1 Intrinsically Initiates Differentiation of Induced Pluripotent Stem Cells into Neural Progenitor Cells.

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 (ATACseq). 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.

Chromatin Interaction Changes during the iPSC-NPC Model to Facilitate the Study of Biologically Significant Genes Involved in Differentiation.

Given the difficulties of obtaining diseased cells, differentiation of neurons from patient-specific human induced pluripotent stem cells (iPSCs) with neural progenitor cells (NPCs) as intermediate precursors is of great interest. While cellular and transcriptomic changes during the differentiation process have been tracked, little attention has been given to examining spatial re-organization, which has been revealed to control gene regulation in various cells. To address the regulatory mechanism by 3D chromatin structure during neuronal differentiation, we examined the changes that take place during differentiation process using two cell types that are highly valued in the study of neurodegenerative disease - iPSCs and NPCs. In our study, we used Hi-C, a derivative of chromosome conformation capture that enables unbiased, genome-wide analysis of interaction frequencies in chromatin. We showed that while topologically associated domains remained mostly the same during differentiation, the presence of differential interacting regions in both cell types suggested that spatial organization affects gene regulation of both pluripotency maintenance and neuroectodermal differentiation. Moreover, closer analysis of promoter-promoter pairs suggested that cell fate specification is under the control of cis-regulatory elements. Our results are thus a resourceful addition in benchmarking differentiation protocols and also provide a greater appreciation of NPCs, the common precursors from which required neurons for applications in neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, schizophrenia and spinal cord injuries are utilized.

DNA Methylation of Intragenic CpG Islands are Required for Differentiation from iPSC to NPC.

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.

Direct nanofluidic channels via hardening and wrinkling of thin polymer films.

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.

Ultra-Low Power Electrochromic Heat Shutters Through Tailoring Diffusion-Controlled Behaviors.

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.

Frequency modulation of laser ultrasound transducer using carbon nanotube-coated polyethylene microsphere.

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.