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In this paper, we have analyzed quantum confinement effects in nanosheet MOSFETs by using a quantum drift‐diffusion (QDD) model. The QDD model is a device simulator which allows to simulate quantum confinement effects in the inversion layer for advanced MOSFETs. The quantum confinement effects in nanosheets have been analyzed by comparing the simulation results by QDD and drift‐diffusion (DD) model. The drain current ratio of DD to QDD is 250.1% at VG = 0.5 V and 180.1% at VG = 0 V. While the maximum electron density of DD exists at the interface between the insulator and the silicon sheet, that of QDD goes to near the center of the silicon sheet. The electron areal density ratio of DD to QDD is 118.3% in the direction of the 10 nm width of the silicon sheet and 176.9% in the direction of the 4 nm width. [ABSTRACT FROM AUTHOR]

This study proposes a rudder-roll stabilization (RRS) autopilot by using novel response models developed by Yasukawa and Yoshimura (YY models) since they include the roll-coupling effect. The statistical optimal control theory which used Akaike information criterion (AIC) was used. To verify the proposed RRS autopilot, numerical simulations based were also performed on the onboard monitoring data of a fishery research vessel; the results confirmed its effectiveness for course keeping and roll reduction. • New response models including the roll-coupling effect are used in an RRS autopilot. • The proposed system is validated based on onboard monitoring data. • The system effectiveness is discussed in terms of course deviation and roll angle. [ABSTRACT FROM AUTHOR]

Being overweight exacerbates various metabolic diseases, necessitating the identification of target molecules for obesity control. In the current study, we investigated common physiological features related to metabolism in mice with low weight gain: (1) G protein‐coupled receptor, family C, group 5, member B‐knockout; (2) gastric inhibitory polypeptide receptor‐knockout; and (3) Iroquois‐related homeobox 3‐knockout. Moreover, we explored genes involved in metabolism by analyzing differentially expressed genes (DEGs) between low‐weight gain mice and the respective wild‐type control mice. The common characteristics of the low‐weight gain mice were low inguinal white adipose tissue (iWAT) and liver weight despite similar food intake along with lower blood leptin levels and high energy expenditure. The DEGs of iWAT, epididymal (gonadal) WAT, brown adipose tissue, muscle, liver, hypothalamus, and hippocampus common to these low‐weight gain mice were designated as candidate genes associated with metabolism. One such gene tetraspanin 7 (Tspan7) from the iWAT was validated using knockout and overexpressing mouse models. Mice with low Tspan7 expression gained more weight, while those with high Tspan7 expression gained less weight, confirming the involvement of the Tspan7 gene in weight regulation. Collectively, these findings suggest that the candidate gene list generated in this study contains potential target molecules for obesity regulation. Further validation and additional data from low‐weight gain mice will aid in understanding the molecular mechanisms associated with obesity. [ABSTRACT FROM AUTHOR]

Molecular mechanisms for the establishment of transcriptional memory are poorly understood. 5,6-dichloro-1-D-ribofuranosyl-benzimidazole (DRB) is a P-TEFb kinase inhibitor that artificially induces the poised RNA polymerase II (RNAPII), thereby manifesting intermediate steps for the establishment of transcriptional activation. Here, using genetics and DRB, we show that mammalian Absent, small, or homeotic discs 1-like (Ash1l), a member of the trithorax group proteins, methylates Lys36 of histone H3 to promote the establishment of Hox gene expression by counteracting Polycomb silencing. Importantly, we found that Ash1l-dependent Lys36 di-, tri-methylation of histone H3 in a coding region and exclusion of Polycomb group proteins occur independently of transcriptional elongation in embryonic stem (ES) cells, although both were previously thought to be consequences of transcription. Genome-wide analyses of histone H3 Lys36 methylation under DRB treatment have suggested that binding of the retinoic acid receptor (RAR) to a certain genomic region promotes trimethylation in the RAR-associated gene independent of its ongoing transcription. Moreover, DRB treatment unveils a parallel response between Lys36 methylation of histone H3 and occupancy of either Tip60 or Mof in a region-dependent manner. We also found that Brg1 is another key player involved in the response. Our results uncover a novel regulatory cascade orchestrated by Ash1l with RAR and provide insights into mechanisms underlying the establishment of the transcriptional activation that counteracts Polycomb silencing. [ABSTRACT FROM AUTHOR]

NKT cells demonstrate antitumor activity when activated to produce Th1 cytokines by DCs loaded with alpha-galactosylceramide, the prototypic NKT cell-activating glycolipid antigen. However, most patients do not have sufficient numbers of NKT cells to induce an effective immune response in this context, indicating a need for a source of NKT cells that could be used to supplement the endogenous cell population. Induced pluripotent stem cells (iPSCs) hold tremendous potential for cell-replacement therapy, but whether it is possible to generate functionally competent NKT cells from iPSCs has not been rigorously assessed. In this study, we successfully derived iPSCs both from embryonic fibroblasts from mice harboring functional NKT cell-specific rearranged T cell receptor loci in the germline and from splenic NKT cells from WT adult mice. These iPSCs could be differentiated into NKT cells in vitro and secreted large amounts of the Th1 cytokine IFN-gamma. Importantly, iPSC-derived NKT cells recapitulated the known adjuvant effects of natural NKT cells and suppressed tumor growth in vivo. These studies demonstrate the feasibility of expanding functionally competent NKT cells via an iPSC phase, an approach that may be adapted for NKT cell-targeted therapy in humans. [ABSTRACT FROM AUTHOR]

A critical step during intrathymic T-cell development is the transition of CD4+ CD8+ double-positive (DP) cells to the major histocompatibility complex class I (MHC-I)-restricted CD4- CD8+ and MHC-II-restricted CD4+ CD8- single-positive (SP) cell stage. Here, we identify a novel gene that is essential for this process. Through the T-cell phenotype-based screening of N-ethyl-N-nitrosourea (ENU)-induced mutant mice, we established a mouse line in which numbers of CD4 and CD8 SP thymocytes as well as peripheral CD4 and CD8 T cells were dramatically reduced. Using linkage analysis and DNA sequencing, we identified a missense point mutation in a gene, E430004N04Rik (also known as themis), that does not belong to any known gene family. This orphan gene is expressed specifically in DP and SP thymocytes and peripheral T cells, whereas in mutant thymocytes the levels of protein encoded by this gene were drastically reduced. We generated E430004N04Rik-deficient mice, and their phenotype was virtually identical to that of the ENU mutant mice, thereby confirming that this gene is essential for the development of SP thymocytes. [ABSTRACT FROM AUTHOR]

Mutations in IFIH1 gene encoding viral RNA sensor MDA5 have been reported responsible for many interferonopathies, including Aicardi-Goutières syndrome (AGS) and monogenic lupus, however, the pathological link between IFIH1 mutations and various autoimmune symptoms remains unclear. Here, we generated transgenic mice expressing human MDA5 R779H mutant (R779H Tg), reported in AGS and monogenic lupus patient. Mice spontaneously developed myocarditis and nephritis with upregulation of type I IFNs in the major organs. R779H Tg Mavs −/− and R779H Tg Ifnar −/− showed no phenotypes, indicating direct MDA5-signaling pathway involvement. Rag-2 deficiency and bone marrow cells transfer from wild type to adult mice did not prevent myocarditis development, while mice with cardiomyocyte-specific expression of hMDA5 R779H showed cardiomegaly and high expression of inflammatory cytokines. Taken together, our study clarifies that type I IFNs production and chemokines from cardiomyocytes starts in neonatal period and is critical for the development of myocarditis. Activated lymphocytes and auto-antibodies exacerbate the pathogenesis but are dispensable for the onset. • We generated transgenic mice expressing human MDA5 R779H mutant (R779H Tg mice) commonly identified in AGS patients and a case of monogenic lupus. • R779H Tg mice developed spontaneous myocarditis with fibrotic remodeling of the epicardium and lupus-like nephritis, while R779H Tg Mavs −/- and R779H Tg Ifnar1 −/− mice showed no phenotype. • R779H Tg mice showed high mortality rate (50% of the R779H Tg mice died within 30 weeks after birth). • R779H Tg Rag2 −/− mice showed decreased myocarditis and nephritis scores, but R779H Tg μMT mice still developed lethal myocarditis. • Mice with cardiomyocyte-specific expression of hMDA5 R779H showed cardiomegaly, indicating a major role of cardiomyocytes in the development of heart phenotype. [ABSTRACT FROM AUTHOR]