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Methionine is an essential amino acid. Dietary methionine restriction is associated with decreased tumor growth in preclinical studies and extended lifespans in animal models. The mechanism by which methionine restriction inhibits tumor growth while sparing normal cells is not fully understood. In this study, we applied tensor decomposition-based feature extraction for gene selection from the gene expression profiles of two cell lines of RNA sequencing. We compared two human melanoma cell lines, A101D and MeWo. A101D is a typical cancer cell line that exhibits methionine dependence. MeWo is a methionine-independent cell line. We used the application on R, TDbasedUFE, to perform an enrichment analysis of the selected gene set. Consequently, concordance with existing research on the differences between methionine-dependent melanoma and methionine-independent melanoma was confirmed. Targeting methionine metabolism is considered a promising strategy for treating melanoma and other cancers.

This paper discusses the foundation of security theory for the Quantum stream cipher based on the Holevo-Yuen theory, which allows the use of "optical amplifiers". This type of cipher is a technology that provides information-theoretic security (ITS) to optical data transmission by randomizing ultrafast optical communication signals with quantum noise. In general, the quantitative security of ITS is evaluated in terms of the unicity distance in Shannon theory. However, the quantum version requires modeling beyond the Shannon model of a random cipher to utilize the characteristics of the physical layer. Therefore, as the first step, one has to develop a generalized unicity distance theory and apply it to the evaluation of security. Although a complete theoretical formulation has not yet been established, this paper explains a primitive structure of a generalization of the Shannon random cipher and shows that the realization of this is the generalized quantum stream cipher. In addition, we present several implementation methods of generalized quantum stream ciphers and their security.

Background/objectives: Amyotrophic Lateral Sclerosis is a progressive neurodegenerative disorder characterized by the loss of upper and lower motor neurons. Key factors contributing to neuronal death include mitochondrial energy damage, oxidative stress, and excitotoxicity. The frontal cortex is crucial for action initiation, planning, and voluntary movements whereas the spinal cord facilitates communication with the brain, walking, and reflexes. By investigating transcriptome data from the frontal cortex and spinal cord, we aim to elucidate common pathological mechanisms and pathways involved in ALS for understanding the disease progression and identifying potential therapeutic targets., Methods: In this study, we quantified gene and transcript expression patterns, predicted variants, and assessed their functional effects using computational tools. It also includes predicting variant-associated regulatory effects, constructing functional interaction networks, and performing a gene enrichment analysis., Results: We found novel genes for the upregulation of immune response, and the downregulation of metabolic-related and defective degradation processes in both the spinal cord and frontal cortex. Additionally, we observed the dysregulation of histone regulation and blood pressure-related genes specifically in the frontal cortex., Conclusions: These results highlight the distinct and shared molecular disruptions in ALS, emphasizing the critical roles of immune response and metabolic dysfunction in neuronal degeneration. Targeting these pathways may provide new therapeutic avenues to combat neurodegeneration and preserve neuronal health.

In this paper, we report a low-cost printing process of carbon nanotube (CNT)-based, all-organic microelectrode arrays (MEAs) suitable for in vitro neural stimulation and recording. Conventional MEAs have been mainly composed of expensive metals and manufactured through high-cost and complex lithographic processes, which have limited their accessibility for neuroscience experiments and their application in various studies. Here, we demonstrate a printing-based fabrication method for microelectrodes using organic CNT/paraffin ink, coupled with the deposition of an insulating layer featuring single-cell-sized sensing apertures. The simple microfabrication processes utilizing the economic and readily available ink offer potential for cost reduction and improved accessibility of MEAs. Biocompatibility of the fabricated microelectrode was suggested through a live/dead assay of cultured neural cells, and its large electric double layer capacitance was revealed by cyclic voltammetry that was crucial for preventing cytotoxic electrolysis during electric neural stimulation. Furthermore, the electrode exhibited sufficiently low electric impedance of 2.49 Ω·cm 2 for high signal-to-noise ratio neural recording, and successfully captured model electric waves in physiological saline solution. These results suggest the easily producible and low-cost printed all-organic microelectrodes are available for neural stimulation and recording, and we believe that they can expand the application of MEA in various neuroscience research.

Vibration-induced flow (VIF), in which a mean flow is induced around a microstructure by applying periodic vibrations, is increasingly used as an active flow-control technique at the microscale. In this study, we have developed a microdevice that actively controls the VIF patterns using elastic membrane protrusions (microballoons) actuated by pneumatic pressure. This device enables on-demand spatial and temporal fluid manipulation using a single device that cannot be achieved using a conventional fixed-structure arrangement. We successfully demonstrated that the device achieved displacements of up to 38 µm using the device within a pressure range of 0 to 30 kPa, indicating the suitability of the device for microfluidic applications. Using this active microballoon array, we demonstrated that the device can actively manipulate the flow field and induce swirling flows. Furthermore, we achieved selective actuation of the microballoon using this system. By applying air pressure from a multi-input channel system through a connection tube, the microballoons corresponding to each air channel can be selectively actuated. This enabled precise control of the flow field and periodic switching of the flow patterns using a single chip. In summary, the proposed microdevice provides active control of VIF patterns and has potential applications in advanced microfluidics, such as fluid mixing and particle manipulation.

To examine the effect of leaf chemical composition on selective herbivory by the Japanese giant flying squirrels ( Petaurista leucogenys ), we measured and compared the total phenolic, glucose, and water contents of leaves among their main food tree species, deciduous Quercus acutissima , and evergreen Q. sessilifolia and Phonitia serratifolia . Leaves of these three tree species were available in the warm season (April to October), but the flying squirrels mostly preferred the leaves of Q. acutissima, having higher glucose and water contents than those of the other two tree species. In the cold season (November to the next March), the two evergreen tree species were available, and the flying squirrels used both leaves without any apparent influence of the chemical compositions. On the other hand, the favorite parts of a single leaf differed among the three tree species. Flying squirrels dropped the individual leaves after partial consumption. Their feeding marks on the dropped leaves were distinguished into four types: apical, basal, central, and marginal parts of consumption. The basal parts of consumption were most frequent in Q. acutissima leaves in which more water was contained at the basal part, and the central part consumption followed, which may be related to a lower phenolic content and more glucose and water at the leaf center than its margin. In contrast, the apically consumed leaves dominated in Q. sessilifolia, with relatively homogeneous leaf chemical distribution except for more water at the center. In P. serratifolia , leaves consumed at the center were frequent, but those with marginal consumption were also observed, which may be related to its specific chemical distribution with less phenolics and more glucose at the leaf margin. Thus, the chemical distributions within the single leaf differ among tree species, and the flying squirrel's selectivity of the tree species and the part of each leaf depends partly on the relative compositions of preferable glucose and water and unpreferable phenolics.

Due to its physical and mechanical properties, Inconel 718 remains a difficult-to-cut material and there is an urgent need to develop a more sustainable and low-cost way to machine it. A novel approach for dry cutting Inconel 718 by actively and purposely utilizing the built-up layer (BUL), which can be called the self-protective tool (SPT) method, is proposed and investigated in detail in this paper. Various cutting experiments were carried out using the age-treated Inconel 718 and uncoated cemented carbide tools. The formation condition of the BUL, its formation mechanism, its stability, and its protective effect were examined by measuring the tools after cutting using a scanning electron microscope (SEM) and laser confocal microscopy (LCM). The influences of BUL on the cutting process were investigated using cutting force analysis and surface roughness analysis. The results confirmed that the stability of the BUL is very high, and the BUL can not only significantly protect the tool from wear but also reduce friction at the tool-chip interface and maintain surface roughness. It also revealed that the height of the BUL can play a very important role in its protective effect. Comparative experiments verified the effectiveness and generalizability of the proposed SPT method.

Huntington's disease (HD) is a progressive neurodegenerative disorder caused due to a CAG repeat expansion in the huntingtin ( HTT ) gene. The primary symptoms of HD include motor dysfunction such as chorea, dystonia, and involuntary movements. The primary motor cortex (BA4) is the key brain region responsible for executing motor/movement activities. Investigating patient and control samples from the BA4 region will provide a deeper understanding of the genes responsible for neuron degeneration and help to identify potential markers. Previous studies have focused on overall differential gene expression and associated biological functions. In this study, we illustrate the relationship between variants and differentially expressed genes/transcripts. We identified variants and their associated genes along with the quantification of genes and transcripts. We also predicted the effect of variants on various regulatory activities and found that many variants are regulating gene expression. Variants affecting miRNA and its targets are also highlighted in our study. Co-expression network studies revealed the role of novel genes. Function interaction network analysis unveiled the importance of genes involved in vesicle-mediated transport. From this unified approach, we propose that genes expressed in immune cells are crucial for reducing neuron death in HD.

Three-dimensional measurement is a high-throughput method that can record a large amount of information. Three-dimensional modelling of plants has the possibility to not only automate dimensional measurement, but to also enable visual assessment to be quantified, eliminating ambiguity in human judgment. In this study, we have developed new methods that could be used for the morphological analysis of plants from the information contained in 3D data. Specifically, we investigated characteristics that can be measured by scale (dimension) and/or visual assessment by humans. The latter is particularly novel in this paper. The characteristics that can be measured on a scale-related dimension were tested based on the bounding box, convex hull, column solid, and voxel. Furthermore, for characteristics that can be evaluated by visual assessment, we propose a new method using normal vectors and local curvature (LC) data. For these examinations, we used our highly accurate all-around 3D plant modelling system. The coefficient of determination between manual measurements and the scale-related methods were all above 0.9. Furthermore, the differences in LC calculated from the normal vector data allowed us to visualise and quantify the concavity and convexity of leaves. This technique revealed that there were differences in the time point at which leaf blistering began to develop among the varieties. The precise 3D model made it possible to perform quantitative measurements of lettuce size and morphological characteristics. In addition, the newly proposed LC-based analysis method made it possible to quantify the characteristics that rely on visual assessment. This research paper was able to demonstrate the following possibilities as outcomes: (1) the automation of conventional manual measurements, and (2) the elimination of variability caused by human subjectivity, thereby rendering evaluations by skilled experts unnecessary., Competing Interests: The authors declare no conflict of interest.

The photo-thermoelectric (PTE) effect in electronic materials effectively combines photo-absorption-induced local heating and associated thermoelectric conversion for uncooled and broadband photo-detection. In particular, this work comprehensively summarizes the operating mechanism of carbon nanotube (CNT)-film-based PTE sensors and ubiquitous non-destructive inspections realized by exploiting the material properties of CNT films. Formation of heterogeneous material junctions across the CNT-film-based PTE sensors, namely photo-detection interfaces, triggers the Seebeck effect with photo-absorption-induced local heating. Typical photo-detection interfaces include a channel-electrode boundary and a junction between P-type CNTs and N-type CNTs (PN junctions). While the original CNT film channel exhibits positive Seebeck coefficient values, the material selections of the counterpart freely govern the intensity and polarity of the PTE response signals. Based on these operating mechanisms, CNT film PTE sensors demonstrate a variety of physical and chemical non-destructive inspections. The device aggregates broad multi-spectral optical information regarding the targets and reconstructs their inner composite or layered structures. Arbitrary deformations of the device are attributed to the macroscopic flexibility of the CNT films to further monitor targets from omni-directional viewing angles without blind spots. Detection of blackbody radiation from targets using the device also visualizes their behaviors and associated changes.

Huntington's disease (HD) is a neurodegenerative disorder with autosomal dominant inheritance caused by glutamine expansion in the Huntingtin gene (HTT). Striatal projection neurons (SPNs) in HD are more vulnerable to cell death. The executive striatal population is directly connected with the Brodmann Area (BA9), which is mainly involved in motor functions. Analyzing the disease samples from BA9 from the SRA database provides insights related to neuron degeneration, which helps to identify a promising therapeutic strategy. Most gene expression studies examine the changes in expression and associated biological functions. In this study, we elucidate the relationship between variants and their effect on gene/downstream transcript expression. We computed gene and transcript abundance and identified variants from RNA-seq data using various pipelines. We predicted the effect of genome-wide association studies (GWAS)/novel variants on regulatory functions. We found that many variants affect the histone acetylation pattern in HD, thereby perturbing the transcription factor networks. Interestingly, some variants affect miRNA binding as well as their downstream gene expression. Tissue-specific network analysis showed that mitochondrial, neuroinflammation, vasculature, and angiogenesis-related genes are disrupted in HD. From this integrative omics analysis, we propose that abnormal neuroinflammation acts as a two-edged sword that indirectly affects the vasculature and associated energy metabolism. Rehabilitation of blood-brain barrier functionality and energy metabolism may secure the neuron from cell death.

A simple tensor decomposition model was applied to the liver transcriptome analysis data to elucidate the cause of cadmium-induced gene overexpression. In addition, we estimated the mechanism by which prenatal Cd exposure disrupts insulin metabolism in offspring. Numerous studies have reported on the toxicity of Cd. A liver transcriptome analysis revealed that Cd toxicity induces intracellular oxidative stress and mitochondrial dysfunction via changes in gene expression, which in turn induces endoplasmic reticulum-associated degradation via abnormal protein folding. However, the specific mechanisms underlying these effects remain unknown. In this study, we found that Cd-induced endoplasmic reticulum stress may promote increased expression of tumor necrosis factor-α (TNF-α). Based on the high expression of genes involved in the production of sphingolipids, it was also found that the accumulation of ceramide may induce intracellular oxidative stress through the overproduction of reactive oxygen species. In addition, the high expression of a set of genes involved in the electron transfer system may contribute to oxidative stress. These findings allowed us to identify the mechanisms by which intracellular oxidative stress leads to the phosphorylation of insulin receptor substrate 1, which plays a significant role in the insulin signaling pathway.

A daily rest period (DRP) is a daily inter-work interval that contains sleep opportunity. This study investigates the joint association of DRP and sleep duration with worker health and productivity. A total of 13,306 Japanese daytime workers participated in this web-based cross-sectional survey. Participants reported on their DRPs and sleep duration; moreover, sleep difficulties, mental health, and presenteeism were assessed by the standardized questionnaires. The participants were divided into 10 groups based on their DRPs and sleep duration. Logistic regression analyses showed that the combination of quick return (QR: DRP of <11 h) and short sleep duration (<6 h) was found to be significantly associated with sleep difficulties (odds ratio [OR] = 4.45, 95% confidence interval [CI] = 2.83-7.01), poor mental health (OR = 3.04, 95% CI = 1.79-5.15), and presenteeism (OR = 2.35, 95% CI = 1.47-3.77) compared with the reference group (the combination of adequate DRP [15 h] and a normal sleep duration [≥6 h]). The combination of QR and normal sleep duration or adequate DRP and short sleep duration was significantly associated with high ORs for the outcomes. QR, short sleep duration, or both negatively affect worker health and productivity., Competing Interests: The authors declare no conflict of interest.

In the field of gene expression analysis, methods of integrating multiple gene expression profiles are still being developed and the existing methods have scope for improvement. The previously proposed tensor decomposition-based unsupervised feature extraction method was improved by introducing standard deviation optimization. The improved method was applied to perform an integrated analysis of three tissue-specific gene expression profiles (namely, adipose, muscle, and liver) for diabetes mellitus, and the results showed that it can detect diseases that are associated with diabetes (e.g., neurodegenerative diseases) but that cannot be predicted by individual tissue expression analyses using state-of-the-art methods. Although the selected genes differed from those identified by the individual tissue analyses, the selected genes are known to be expressed in all three tissues. Thus, compared with individual tissue analyses, an integrated analysis can provide more in-depth data and identify additional factors, namely, the association with other diseases.

We present a microgripper actuated by a soft microactuator for manipulating a single living cell. Soft actuators have attracted attention in recent years because their compliance which can adapt to soft targets. In this study, we propose a microgripper actuated by soft thermoresponsive hydrogels. The thermoresponsive gel swells in water when the temperature is low and shrinks when the temperature is high. Therefore, the microgripper can be driven by controlling the temperature of the thermoresponsive gel. The gels are actuated by irradiating with infrared (IR) laser to localize heating. The actuation characteristics of the gripper were theoretically analyzed and we designed a gripper that gripped a ≈10 µm size cell. Additionally, we succeeded in actuating the fabricated microgripper with laser irradiation and gripping a single living cell.

In this paper, we report a new discriminant index for evaluating the wearing condition of a blood pressure pulse wave measurement device with small variability. The prototype device consists of MEMS 3-axis force sensors, a 3-axis push-in adjustment mechanism, a fixed jig, and a signal processing board. The arterial tonometry method is used by this device to measure blood pressure pulse waves. However, to accurately measure the blood pressure pulse wave, the device must be appropriately worn. The evaluation of the wearing condition using the amplitude of the blood pressure pulse wave was complicated by the wearing process due to the large variability. Therefore, we propose the ratio of the blood pressure pulse wave component to the noise component as an index that can evaluate the wear condition of the device. The correlation coefficient between the discriminant index and the amplitude of the blood pressure pulse wave had a correlation coefficient of 0.879. Furthermore, the discriminant index reduced the coefficient of variation by 12.8%. Therefore, it was suggested that the discriminant index is an index that can evaluate the pressing amount, one of the wearing conditions of the blood pressure pulse wave measurement device with a small influence of variation.

It is unknown what determines genetic diversity and how genetic diversity is associated with various biological traits. In this work, we provide insight into these issues. By comparing genetic variation of 14,671 mammalian gene trees with thousands of individual human, chimpanzee, gorilla, mouse, and dog/wolf genomes, we found that intraspecific genetic diversity can be predicted by long-term molecular evolutionary rates rather than de novo mutation rates. This relationship was established during the early stage of mammalian evolution. Moreover, we developed a method to detect fluctuations of species-specific selection on genes based on the deviations of intraspecific genetic diversity predicted from long-term rates. We showed that the evolution of epithelial cells, rather than connective tissue, mainly contributed to morphological evolution of different species. For humans, evolution of the immune system and selective sweeps caused by infectious diseases are the most representative examples of adaptive evolution.

Gambierol inhibits voltage-gated K + (K V ) channels in various excitable and non-excitable cells. The purpose of this work was to study the effects of gambierol on single rat fetal (F19-F20) adrenomedullary cultured chromaffin cells. These excitable cells have different types of K V channels and release catecholamines. Perforated whole-cell voltage-clamp recordings revealed that gambierol (100 nM) blocked only a fraction of the total outward K + current and slowed the kinetics of K + current activation. The use of selective channel blockers disclosed that gambierol did not affect calcium-activated K + (K Ca ) and ATP-sensitive K + (K ATP ) channels. The gambierol concentration necessary to inhibit 50% of the K + current-component sensitive to the polyether (IC 50 ) was 5.8 nM. Simultaneous whole-cell current-clamp and single-cell amperometry recordings revealed that gambierol did not modify the membrane potential following 11s depolarizing current-steps, in both quiescent and active cells displaying repetitive firing of action potentials, and it did not increase the number of exocytotic catecholamine release events, with respect to controls. The subsequent addition of apamin and iberiotoxin, which selectively block the K Ca channels, both depolarized the membrane and enhanced by 2.7 and 3.5-fold the exocytotic event frequency in quiescent and active cells, respectively. These results highlight the important modulatory role played by K Ca channels in the control of exocytosis from fetal (F19-F20) adrenomedullary chromaffin cells.

Glioblastoma multiforme (GBM) is the most common infiltrating lethal tumor of the brain. Tumor heterogeneity and the precise characterization of GBM remain challenging, and the disease-specific and effective biomarkers are not available at present. To understand GBM heterogeneity and the disease prognosis mechanism, we carried out a single-cell transcriptome data analysis of 3389 cells from four primary IDH-WT (isocitrate dehydrogenase wild type) glioblastoma patients and compared the characteristic features of the tumor and periphery cells. We observed that the marker gene expression profiles of different cell types and the copy number variations (CNVs) are heterogeneous in the GBM samples. Further, we have identified 94 differentially expressed genes (DEGs) between tumor and periphery cells. We constructed a tissue-specific co-expression network and protein-protein interaction network for the DEGs and identified several hub genes, including CX3CR1, GAPDH, FN1, PDGFRA, HTRA1, ANXA2 THBS1, GFAP, PTN, TNC , and VIM . The DEGs were significantly enriched with proliferation and migration pathways related to glioblastoma. Additionally, we were able to identify the differentiation state of microglia and changes in the transcriptome in the presence of glioblastoma that might support tumor growth. This study provides insights into GBM heterogeneity and suggests novel potential disease-specific biomarkers which could help to identify the therapeutic targets in GBM.

In recent years, remarkable progress has been achieved in the development of quantum computers. For further development, it is important to clarify properties of errors by quantum noise and environment noise. However, when the system scale of quantum processors is expanded, it has been pointed out that a new type of quantum error, such as nonlinear error, appears. It is not clear how to handle such new effects in information theory. First of all, one should make the characteristics of the error probability of qubits clear as communication channel error models in information theory. The purpose of this paper is to survey the progress for modeling the quantum noise effects that information theorists are likely to face in the future, to cope with such nontrivial errors mentioned above. This paper explains a channel error model to represent strange properties of error probability due to new quantum noise. By this model, specific examples on the features of error probability caused by, for example, quantum recurrence effects, collective relaxation, and external force, are given. As a result, it is possible to understand the meaning of strange features of error probability that do not exist in classical information theory without going through complex physical phenomena.

The development of the medical applications for substances or materials that contact cells is important. Hence, it is necessary to elucidate how substances that surround cells affect gene expression during incubation. In the current study, we compared the gene expression profiles of cell lines that were in contact with collagen-glycosaminoglycan mesh and control cells. Principal component analysis-based unsupervised feature extraction was applied to identify genes with altered expression during incubation in the treated cell lines but not in the controls. The identified genes were enriched in various biological terms. Our method also outperformed a conventional methodology, namely, gene selection based on linear regression with time course.

The positions of enhancers and promoters on genomic DNA remain poorly understood. Chromosomes cannot be observed during the cell division cycle because the genome forms a chromatin structure and spreads within the nucleus. However, high-throughput chromosome conformation capture (Hi-C) measures the physical interactions of genomes. In previous studies, DNA extrusion loops were directly derived from Hi-C heat maps. Multidimensional Scaling (MDS) is used in this assessment to more precisely locate enhancers and promoters. MDS is a multivariate analysis method that reproduces the original coordinates from the distance matrix between elements. We used Hi-C data of cultured osteosarcoma cells and applied MDS as the distance matrix of the genome. In addition, we selected columns 2 and 3 of the orthogonal matrix U as the desired structure. Overall, the DNA loops from the reconstructed genome structure contained bioprocesses involved in transcription, such as the pre-transcriptional initiation complex and RNA polymerase II initiation complex, and transcription factors involved in cancer, such as Foxm1 and CREB3. Therefore, our results are consistent with the biological findings. Our method is suitable for identifying enhancers and promoters in the genome.

Many types of 3D sensing devices are commercially available and were utilized in various technical fields. In most conventional systems with a 3D sensing device, the spatio-temporal resolution and the measurement range are constant during operation. Consequently, it is necessary to select an appropriate sensing system according to the measurement task. Moreover, such conventional systems have difficulties dealing with several measurement targets simultaneously due to the aforementioned constants. This issue can hardly be solved by integrating several individual sensing systems into one. Here, we propose a single 3D sensing system that adaptively adjusts the spatio-temporal resolution and the measurement range to switch between multiple measurement tasks. We named the proposed adaptive 3D sensing system "AdjustSense." In AdjustSense, as a means for the adaptive adjustment of the spatio-temporal resolution and measurement range, we aimed to achieve low-latency visual feedback for the adjustment by integrating not only a high-speed camera, which is a high-speed sensor, but also a direct drive motor, which is a high-speed actuator. This low-latency visual feedback can enable a large range of 3D sensing tasks simultaneously. We demonstrated the behavior of AdjustSense when the positions of the measured targets in the surroundings were changed. Furthermore, we quantitatively evaluated the spatio-temporal resolution and measurement range from the 3D points obtained. Through two experiments, we showed that AdjustSense could realize multiple measurement tasks: 360∘ 3D sensing, 3D sensing at a high spatial resolution around multiple targets, and local 3D sensing at a high spatio-temporal resolution around a single object.

The initial processes of the phase transition dynamics of liquid crystals (LCs) subject to UV pulse irradiation were clarified using a nanosecond time-resolved imaging technique called pattern-illumination time-resolved phase microscopy (PI-PM). Two types of LCs were studied: a photo-responsive LC and dye-doped LCs. We found two steps of molecular disordering processes in the phase transition, namely local disordering proceeding anisotropically, followed by the spreading of the isotropic phase. These two processes were separated for a photo-responsive LC while being simultaneously observed for the dye-doped LCs. It was found that the photomechanical dyes induced the phase transition process faster than the photothermal dyes.

Analysis of single-cell multiomics datasets is a novel topic and is considerably challenging because such datasets contain a large number of features with numerous missing values. In this study, we implemented a recently proposed tensor-decomposition (TD)-based unsupervised feature extraction (FE) technique to address this difficult problem. The technique can successfully integrate single-cell multiomics data composed of gene expression, DNA methylation, and accessibility. Although the last two have large dimensions, as many as ten million, containing only a few percentage of nonzero values, TD-based unsupervised FE can integrate three omics datasets without filling in missing values. Together with UMAP, which is used frequently when embedding single-cell measurements into two-dimensional space, TD-based unsupervised FE can produce two-dimensional embedding coincident with classification when integrating single-cell omics datasets. Genes selected based on TD-based unsupervised FE are also significantly related to reasonable biological roles.

(1) Background: Prolonged lockdowns with stay-at-home orders have been introduced in many countries since the outbreak of the COVID-19 pandemic. They have caused a drastic change in the everyday lives of people living in urbanized areas, and are considered to contribute to a modified perception of the public space. As research related to the impact of COVID-19 restrictions on mental health and well-being emerges, the associated longitudinal changes of brain hemodynamics in healthy adults remain largely unknown. (2) Methods: this study examined the hemodynamic activation patterns of the prefrontal and occipital cortices of 12 participants (5 male, M age = 47.80, SD age = 17.79, range 25 to 74, and 7 female, M age = 39.00, SD age = 18.18, range 21 to 65) passively viewing videos from three urban sites in Singapore (Urban Park, Neighborhood Landscape and City Center) at two different time points-T1, before the COVID-19 pandemic and T2, soon after the lockdown was over. (3) Results: We observed a significant and marginally significant decrease in average oxyhemoglobin (Oxy-Hb) over time for each of the visual conditions. For both green spaces (Urban Park and Neighborhood Landscape), the decrease was in the visual cortex, while for the City Center with no green elements, the marginal decrease was observed in the visual cortex and the frontal eye fields. (4) Conclusions: The results suggest that the COVID-19-related lockdown experienced by urban inhabitants may have contributed to decreased brain hemodynamics, which are further related to a heightened risk of mental health disorders, such as depression or a decline in cognitive functions. Moreover, the busy City Center scenes induced a hemodynamic pattern associated with stress and anxiety, while urban green spaces did not cause such an effect. Urban green scenes can be an important factor to offset the negative neuropsychological impact of busy urban environments post-pandemic.

Marine polycyclic ether natural products have gained significant interest from the chemical community due to their impressively huge molecular architecture and diverse biological functions. The structure assignment of this class of extraordinarily complex natural products has mainly relied on NMR spectroscopic analysis. However, NMR spectroscopic analysis has its own limitations, including configurational assignment of stereogenic centers within conformationally flexible systems. Chemical shift deviation analysis of synthetic model compounds is a reliable means to assign the relative configuration of "difficult" stereogenic centers. The complete configurational assignment must be ultimately established through total synthesis. The aim of this review is to summarize the indispensable role of organic synthesis in stereochemical assignment of marine polycyclic ethers.

The large p small n problem is a challenge without a de facto standard method available to it. In this study, we propose a tensor-decomposition (TD)-based unsupervised feature extraction (FE) formalism applied to multiomics datasets, in which the number of features is more than 100,000 whereas the number of samples is as small as about 100, hence constituting a typical large p small n problem. The proposed TD-based unsupervised FE outperformed other conventional supervised feature selection methods, random forest, categorical regression (also known as analysis of variance, or ANOVA), penalized linear discriminant analysis, and two unsupervised methods, multiple non-negative matrix factorization and principal component analysis (PCA) based unsupervised FE when applied to synthetic datasets and four methods other than PCA based unsupervised FE when applied to multiomics datasets. The genes selected by TD-based unsupervised FE were enriched in genes known to be related to tissues and transcription factors measured. TD-based unsupervised FE was demonstrated to be not only the superior feature selection method but also the method that can select biologically reliable genes. To our knowledge, this is the first study in which TD-based unsupervised FE has been successfully applied to the integration of this variety of multiomics measurements.

The bacterial flagellar motor is a reversible rotary molecular nanomachine, which couples ion flux across the cytoplasmic membrane to torque generation. It comprises a rotor and multiple stator complexes, and each stator complex functions as an ion channel and determines the ion specificity of the motor. Although coupling ions for the motor rotation were presumed to be only monovalent cations, such as H + and Na + , the stator complex MotA1/MotB1 of Paenibacillus sp. TCA20 (MotA1 TCA /MotB1 TCA ) was reported to use divalent cations as coupling ions, such as Ca 2+ and Mg 2+ . In this study, we initially aimed to measure the motor torque generated by MotA1 TCA /MotB1 TCA under the control of divalent cation motive force; however, we identified that the coupling ion of MotA1 TCA MotB1 TCA is very likely to be a monovalent ion. We engineered a series of functional chimeric stator proteins between MotB1 TCA and Escherichia coli MotB. E. coli Δ motAB cells expressing MotA1 TCA and the chimeric MotB presented significant motility in the absence of divalent cations. Moreover, we confirmed that MotA1 TCA /MotB1 TCA in Bacillus subtilis Δ motAB Δ motPS cells generates torque without divalent cations. Based on two independent experimental results, we conclude that the MotA1 TCA /MotB1 TCA complex directly converts the energy released from monovalent cation flux to motor rotation.

The bacterial flagellum is a motility organelle consisting of a long helical filament as a propeller and a rotary motor that drives rapid filament rotation to produce thrust. Salmonella enterica serovar Typhimurium has two genes of flagellin, fljB and fliC , for flagellar filament formation and autonomously switches their expression at a frequency of 10 -3 -10 -4 per cell per generation. We report here differences in their structures and motility functions under high-viscosity conditions. A Salmonella strain expressing FljB showed a higher motility than one expressing FliC under high viscosity. To examine the reasons for this motility difference, we carried out structural analyses of the FljB filament by electron cryomicroscopy and found that the structure was nearly identical to that of the FliC filament except for the position and orientation of the outermost domain D3 of flagellin. The density of domain D3 was much lower in FljB than FliC, suggesting that domain D3 of FljB is more flexible and mobile than that of FliC. These differences suggest that domain D3 plays an important role not only in changing antigenicity of the filament but also in optimizing motility function of the filament as a propeller under different conditions.

Hydrothermal hydrolysis in hot pressurized liquid water (HPLW) is attractive for biomass conversion into valuable products because it achieves high reaction rates without catalysts and additives. The hydrothermal hydrolysis of high crystalline cellulose requires higher reaction temperature than polysaccharides having low crystallinity. It can be expected to increase the reaction rate or decrease temperature by decreasing the crystallinity. In the present study ashless filter paper as a fibrous pure cellulose sample was pretreated with ionic liquids (ILs) such as imidazolium chloride ILs containing alkyl side chains ranging from two to six carbons, and with an aqueous solution of bis(ethylenediamine ammonium) copper (BEDC). Herein, the pretreatment with ILs was to regenerate filter paper: dissolving in ILs at 373 K for 120 min or in an aqueous BEDC solution at room temperature, precipitating by adding water, washing the solid, and then drying. Subsequently, the pretreated filter paper samples were hydrolyzed at 533 K and 5.0 MPa in HPLW in a small semi-batch reactor, and the effects of the pretreatment with ILs or BEDC on reaction rates and product yields were examined. While the crystallinity indexes with all ILs and BEDC after the pretreatments decreased to 44 to 47 from the original sample of 87, the reaction rates and product yields were significantly affected by the IL species. At 533 K and 5.0 MPa, the dissolution rate with [AMIM][Cl] was nine times as fast as that for untreated sample.

In this paper, we demonstrate that 20 μm microbeads can be preferentially assembled into substrate trenches of similar width by employing a polymer (depletant) that induces the depletion volume effect (depletion attraction). In previous works, we proved that this strategy is useful to assemble mesoscale parts in a site-specific manner. Here, we show that it is also applicable to assemble functional parts, such as fluorescent particles, into trenches engraved on the surface of two- and three-dimensional template components. A convenient advantage of this strategy is that it is independent of material properties for assembling mesoscale functional components into desired patterns.

We investigated the adsorption characteristics of geosmin and 2-methylisoborneol (MIB) on graphene oxide (GO) in the absence and presence of natural organic matter (NOM). The graphene oxide had fast adsorption kinetics for both compounds because of its open-layered structure, with adsorption equilibrium being achieved within 15 min of contact. Although NOM did not affect the adsorption of geosmin on GO, it delayed that of MIB, probably because of competition for adsorption sites. The adsorption isotherms show that GO had a greater capacity for geosmin adsorption than for MIB because geosmin was more hydrophobic. Moreover, NOM interfered with the adsorption of MIB onto the GO, but increased the amount of adsorbed geosmin, which likely occurred because NOM increased the dispersibility of GO, which then increased the number of GO adsorption sites. The difference in the effects of NOM on GO adsorption of geosmin and MIB may be explained by their hydrophobicity. Although the adsorption of geosmin and MIB by GO was fast, its capacity to adsorb both compounds was substantially lower than that of activated carbon because of its higher hydrophilicity.

Here we report a quantum dot light emitting diode (QLED), in which a layer of colloidal silicon quantum dots (SiQDs) works as the optically active component, exhibiting a strong electroluminescence (EL) spectrum peaking at 620 nm. We could not see any fluctuation of the EL spectral peak, even in air, when the operation voltage varied in the range from 4 to 5 V because of the possible advantage of the inverted device structure. The pale-orange EL spectrum was as narrow as 95 nm. Interestingly, the EL spectrum was narrower than the corresponding photoluminescence (PL) spectrum. The EL emission was strong enough to be seen by the naked eye. The currently obtained brightness (∼4200 cd/m 2 ), the 0.033% external quantum efficiency (EQE), and a turn-on voltage as low as 2.8 V show a sufficiently high performance when compared to other orange-light-emitting Si-QLEDs in the literature. We also observed a parasitic emission from the neighboring compositional layer (i.e., the zinc oxide layer), and its intensity increased with the driving voltage of the device.

The steady streaming (SS) phenomenon is gaining increased attention in the microfluidics community, because it can generate net mass flow from zero-mean vibration. We developed numerical simulation and experimental measurement tools to analyze this vibration-induced flow, which has been challenging due to its unsteady nature. The validity of these analysis methods is confirmed by comparing the three-dimensional (3D) flow field and the resulting particle trajectories induced around a cylindrical micro-pillar under circular vibration. In the numerical modeling, we directly solved the flow in the Lagrangian frame so that the substrate with a micro-pillar becomes stationary, and the results were converted to a stationary Eulerian frame to compare with the experimental results. The present approach enables us to avoid the introduction of a moving boundary or infinitesimal perturbation approximation. The flow field obtained by the micron-resolution particle image velocimetry (micro-PIV) measurement supported the three-dimensionality observed in the numerical results, which could be important for controlling the mass transport and manipulating particulate objects in microfluidic systems., Competing Interests: The authors declare no conflict of interest.

Parkinson's disease (PD) is a chronic, progressive neurodegenerative disease characterized by both motor and nonmotor features. The diagnose of PD is based on a review of patients' signs and symptoms, and neurological and physical examinations. So far, no tests have been devised that can conclusively diagnose PD. In this study, we explore both microRNA and gene biomarkers for PD. Microarray gene expression profiles for PD patients and healthy control are analyzed using a principal component analysis (PCA)-based unsupervised feature extraction (FE). 244 genes are selected to be potential gene biomarkers for PD. In addition, we implement these genes into Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and find that the 15 microRNAs (miRNAs), hsa-miR-92a-3p, 16-5p, 615-3p, 877-3p, 100-5p, 320a, 877-5p, 23a-3p, 484, 23b-3p, 15a-5p, 324-3p, 19b-3p, 7b-5p and 505-3p, significantly target these 244 genes. These miRNAs are shown to be significantly related to PD. This reveals that both selected genes and miRNAs are potential biomarkers for PD.

MicroRNA (miRNA) transfection is known to degrade target mRNAs and to decrease mRNA expression. In contrast to the notion that most of the gene expression alterations caused by miRNA transfection involve downregulation, they often involve both up- and downregulation; this phenomenon is thought to be, at least partially, mediated by sequence-nonspecific off-target effects. In this study, I used tensor decomposition-based unsupervised feature extraction to identify genes whose expression is likely to be altered by miRNA transfection. These gene sets turned out to largely overlap with one another regardless of the type of miRNA or cell lines used in the experiments. These gene sets also overlap with the gene set associated with altered expression induced by a Dicer knockout. This result suggests that the off-target effect is at least as important as the canonical function of miRNAs that suppress translation. The off-target effect is also suggested to consist of competition for the protein machinery between transfected miRNAs and miRNAs in the cell. Because the identified genes are enriched in various biological terms, these genes are likely to play critical roles in diverse biological processes., Competing Interests: The author declares no conflict of interest.

We developed an asymmetric fluorescent sensor 1 for Cu 2+ , based on 4,4-difluoro-4-bora-3a,4a-diaza- s -indacene (BODIPY), by introducing 4-carboxyphenyl and bis(pyridin-2-ylmethyl)amine groups at the 5- and 3-positions, respectively, of the BODIPY core. We then investigated the photophysical and cation-sensing properties of the sensor. BODIPY 1 showed large absorption and fluorescence spectral shifts on binding to Cu 2+ . The fluorescence peak at 580 nm red-shifted to 620 nm. The binding stoichiometry of BODIPY 1 and Cu 2+ was 1:3. The ratio of the fluorescence intensity at 620 nm to that at 580 nm ( F 620 / F 580 ) increased with increasing concentration of Cu 2+ (3⁻10 equiv); this enabled ratiometric determination of Cu 2+ . Although BODIPY 1 showed good selectivity for Cu 2+ , there was an interfering effect of Fe 3+ . BODIPY 1 could be used for the naked-eye detection of Cu 2+ in a water-containing sample.

Amyotrophic lateral sclerosis (ALS) is among the severe neuro degenerative diseases that lack widely available effective treatments. As the disease progresses, patients lose the control of voluntary muscles. Although the neuronal degeneration is the cause of this disease, the failure mechanism is still unknown. In order to seek genetic mechanisms that initiate and progress ALS, the association of microRNA (miRNA) expression with this disease was considered. Serum miRNAs from healthy controls, sporadic ALS (sALS), familial ALS (fALS) and ALS mutation carriers were investigated. Principal component analysis (PCA)-based unsupervised feature extraction (FE) was applied to these serum miRNA profiles. As a result, we predict miRNAs that can discriminate patients from healthy controls with high accuracy. Thus, these miRNAs can be potential prognosis miRNA biomarkers for ALS.

Neopeltolide, an antiproliferative marine macrolide, is known to specifically inhibit complex III of the mitochondrial electron transport chain (mETC). However, details of the biological mode-of-action(s) remain largely unknown. This work demonstrates potent cytotoxic activity of synthetic neopeltolide analogue, 8,9-dehydroneopeltolide (8,9-DNP), against starved human pancreatic adenocarcinoma PANC-1 cells and human non-small cell lung adenocarcinoma A549 cells. 8,9-DNP induced rapid dissipation of the mitochondrial membrane potential and depletion of intracellular ATP level in nutrient-deprived medium. Meanwhile, in spite of mTOR inhibition under starvation conditions, impairment of cytoprotective autophagy was observed as the lipidation of LC3-I to form LC3-II and the degradation of p62 were suppressed. Consequently, cells were severely deprived of energy sources and underwent necrotic cell death. The autophagic flux inhibited by 8,9-DNP could be restored by glucose, and this eventually rescued cells from necrotic death. Thus, 8,9-DNP is a potent anti-austerity agent that impairs mitochondrial ATP synthesis and cytoprotective autophagy in starved tumor cells., Competing Interests: The authors declare no conflict of interest.

Simple analytical methods are needed for determining the cadmium (Cd) content of brown rice samples. In the present study, we developed a new analytical procedure consisting of the digestion of rice using HCl, Cd purification using anion exchange resin, and then determining the Cd content using fluorescence spectroscopy. Digestion with 0.1 M HCl for 10 min at room temperature was sufficient to extract Cd from the ground rice samples. The Cd in the extract was successfully purified in preference to other metals using Dowex 1X8 chloride form resin. Low concentrations of Cd in the eluate could be determined using fluorescence spectroscopy with a fluoroionophore. Overall, the actual limit of quantification value for the Cd content in rice was about 0.1 mg-Cd/kg-rice, which was sufficiently low compared with the regulatory value (0.4 mg-Cd/kg-rice) given by the Codex Alimentarius Commission. We analyzed authentic brown rice samples using our new analytical procedure and the results agreed well with those determined using inductively coupled plasma optical emission spectrometry (ICP-OES). Since the fluoroionophore recognized Zn 2+ and Hg 2+ as well as Cd 2+ , a sample containing high concentration of Zn 2+ or Hg 2+ might cause a false positive result.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. An ALS drug, Riluzole, has been shown to induce two different anticancer effects on hepatocellular carcinoma (HCC). In light of this finding, we explore the relationship between ALS and cancer, especially for HCC, from the molecular biological viewpoint. We establish biomarkers that can discriminate between ALS patients and healthy controls. A principal component analysis (PCA) based unsupervised feature extraction (FE) is used to find gene biomarkers of ALS based on microarray gene expression data. Based on this method, 101 probes were selected as biomarkers for ALS with 95% high accuracy to discriminate between ALS patients and controls. Most of the genes corresponding to these probes are shown to be related to various cancers. These findings might provide a new insight for developing new therapeutic options or drugs for both ALS and cancer., Competing Interests: The authors declare that they have no conflicts of interest.

Gastroesophageal reflux disease (GERD) is a common upper gastrointestinal disease. However, the role of exosomal microRNAs (miRNAs) and esophageal miRNAs in GERD has not been studied. A rat model of acid reflux esophagitis was used to establish a novel diagnosis marker for GERD and examine dynamics of miRNA expression in GERD. Rats were sacrificed 3 (acute phase), 7 (sub-acute phase) and 21 days (chronic phase) after induction of esophagitis. Exosomes were extracted from serum, and the expression patterns of serum miRNAs were analyzed. Four upregulated miRNAs (miR-29a-3p, 128-3p, 223-3p and 3473) were identified by microarray analysis. The expression levels of exosomal miR-29a-3p were significantly higher in the chronic phase of reflux esophagitis compared with controls, and increased expression of miR-29a-3p was specific to chronic reflux esophagitis. Esophageal miR-223-3p expression was higher compared with controls, and gradually decreased from acute to chronic phase in esophagitis. In conclusion, exosomal miR-29a-3p and esophageal miR-223-3p might play roles in GERD., Competing Interests: The authors declare no conflict of interest.

MicroRNA(miRNA)-mRNA interactions are important for understanding many biological processes, including development, differentiation and disease progression, but their identification is highly context-dependent. When computationally derived from sequence information alone, the identification should be verified by integrated analyses of mRNA and miRNA expression. The drawback of this strategy is the vast number of identified interactions, which prevents an experimental or detailed investigation of each pair. In this paper, we overcome this difficulty by the recently proposed principal component analysis (PCA)-based unsupervised feature extraction (FE), which reduces the number of identified miRNA-mRNA interactions that properly discriminate between patients and healthy controls without losing biological feasibility. The approach is applied to six cancers: hepatocellular carcinoma, non-small cell lung cancer, esophageal squamous cell carcinoma, prostate cancer, colorectal/colon cancer and breast cancer. In PCA-based unsupervised FE, the significance does not depend on the number of samples (as in the standard case) but on the number of features, which approximates the number of miRNAs/mRNAs. To our knowledge, we have newly identified miRNA-mRNA interactions in multiple cancers based on a single common (universal) criterion. Moreover, the number of identified interactions was sufficiently small to be sequentially curated by literature searches.

This paper reports on a micro saddle coil for local high-resolution magnetic resonance imaging (MRI) fabricated by embedding a flexible coil pattern into a polydimethyilsiloxane (PDMS) tube. We can change the sensitivity of the micro coil by deforming the shape of the coil from a saddle-shaped mode to a planar-shaped mode. The inductance, the resistance, and the Q-factor of the coil in the saddle-shaped mode were 2.45 μH, 3.31 Ω, and 39.9, respectively. Those of the planar-shaped mode were 3.07 μH, 3.92 Ω, and 42.9, respectively. In MRI acquired in saddle-shaped mode, a large visible area existed around the coil. Although the sensitive area was considerably reduced in the planar-shaped mode, clear MRI images were obtained. The signal-to-noise ratios (SNR) of the saddle-shaped and planar-shaped modes were 194.9 and 505.9, respectively, at voxel size of 2.0 × 2.0 × 2.0 mm³ and 11.7 and 37.4, respectively, at voxel size of 0.5 × 0.5 × 1.0 mm³. The sensitivity of the saddle-shaped and the planar-shaped modes were about 3 times and 10 times higher, respectively, than those of the medical head coil at both voxel sizes. Thus, the micro saddle coil enabled large-area imaging and highly sensitive imaging by switching the shape of the coil.

The interaction of simple and ternary Cu(II) complexes of 1,10-phenanthrolines with DNA has been studied extensively because of their various interesting and important functions such as DNA cleavage activity, cytotoxicity towards cancer cells, and DNA based asymmetric catalysis. Such functions are closely related to the DNA binding modes of the complexes such as intercalation, groove binding, and electrostatic surface binding. A variety of spectroscopic methods have been used to study the DNA binding mode of the Cu(II) complexes. Of all these methods, DNA-fiber electron paramagnetic resonance (EPR) spectroscopy affords unique information on the DNA binding structures of the complexes. In this review we summarize the results of our DNA-fiber EPR studies on the DNA binding structure of the complexes and discuss them together with the data accumulated by using other measurements.

MicroRNA (miRNA) is a critical regulator of cell growth, differentiation, and development. To identify important miRNAs in a biological process, many bioinformatical tools have been developed. We have developed MiRaGE (MiRNA Ranking by Gene Expression) method to infer the regulation of gene expression by miRNAs from changes of gene expression profiles. The method does not require precedent array normalization. We applied the method to elucidate possibly important miRNAs during embryonic stem (ES) cell differentiation to neuronal cells and we infer that certain miRNAs, including miR-200 family, miR-429, miR-302 family, and miR-17-92 cluster members may be important to the maintenance of undifferentiated status in ES cells.