Investigation on the Initial Stage of the Dehydration Process in Mg(OH)2 by Density Functional Theory Calculations.

Mg(OH)2/MgO has been attracting considerable interest as a viable candidate for thermochemical heat storage materials, particularly within the temperature range of 200-400 °C. Nonetheless, the typical dehydration temperature of Mg(OH)2, which occurs within the 300-400 °C range, needs to be reduced to enhance its effectiveness in various applications for thermal energy storage. While several studies have shown that heterospecies doping can lower the dehydration temperature, the fundamental mechanism underlying this effect still remains unclear. Here, we employed density functional theory calculations to elucidate the dehydration mechanism of Mg(OH)2, with a particular focus on the initial stage of the dehydration that determines the temperature beginning the reaction. Our findings indicate that the formation of water molecules on the (001) surface is critical in the early stages of the dehydration. This discovery provides a comprehensive explanation for the role of dopants (Na, Li, or LiCl) in reducing the dehydration temperature by decreasing the formation energy of paired H and OH defects and the migration barrier of H on the surface. The present study will significantly advance the development of novel dopants for Mg(OH)2, facilitating a lower dehydration temperature and, thereby, increasing its suitability for heat storage applications.

Bacterial TLR2/6 Ligands Block Ciliogenesis, Derepress Hedgehog Signaling, and Expand the Neocortex.

Microbial components have a range of direct effects on the fetal brain. However, little is known about the cellular targets and molecular mechanisms that mediate these effects. Neural progenitor cells (NPCs) control the size and architecture of the brain and understanding the mechanisms regulating NPCs is crucial to understanding brain developmental disorders. We identify ventricular radial glia (vRG), the primary NPC, as the target of bacterial cell wall (BCW) generated during the antibiotic treatment of maternal pneumonia. BCW enhanced proliferative potential of vRGs by shortening the cell cycle and increasing self-renewal. Expanded vRGs propagated to increase neuronal output in all cortical layers. Remarkably, Toll-like receptor 2 (TLR2), which recognizes BCW, localized at the base of primary cilia in vRGs and the BCW-TLR2 interaction suppressed ciliogenesis leading to derepression of Hedgehog (HH) signaling and expansion of vRGs. We also show that TLR6 is an essential partner of TLR2 in this process. Surprisingly, TLR6 alone was required to set the number of cortical neurons under healthy conditions. These findings suggest that an endogenous signal from TLRs suppresses cortical expansion during normal development of the neocortex and that BCW antagonizes that signal through the TLR2/cilia/HH signaling axis changing brain structure and function. IMPORTANCE Fetal brain development in early gestation can be impacted by transplacental infection, altered metabolites from the maternal microbiome, or maternal immune activation. It is less well understood how maternal microbial subcomponents that cross the placenta, such as bacterial cell wall (BCW), directly interact with fetal neural progenitors and neurons and affect development. This scenario plays out in the clinic when BCW debris released during antibiotic therapy of maternal infection traffics to the fetal brain. This study identifies the direct interaction of BCW with TLR2/6 present on the primary cilium, the signaling hub on fetal neural progenitor cells (NPCs). NPCs control the size and architecture of the brain and understanding the mechanisms regulating NPCs is crucial to understanding brain developmental disorders. Within a window of vulnerability before the appearance of fetal immune cells, the BCW-TLR2/6 interaction results in the inhibition of ciliogenesis, derepression of Sonic Hedgehog signaling, excess proliferation of neural progenitors, and abnormal cortical architecture. In the first example of TLR signaling linked to Sonic Hedgehog, BCW/TLR2/6 appears to act during fetal brain morphogenesis to play a role in setting the total cell number in the neocortex.

A multicomponent equimolar proton-conducting quadruple hexagonal perovskite-related oxide system.

Since the high configurational entropy-driven structural stability of multicomponent oxide system was proposed Rost et al. in 2015, many experiments and simulations have been done to develop new multicomponent oxides. Although many notable findings have shown unique physical and chemical properties, high configurational entropy oxide systems that have more than 3 distinct cation sites are yet to be developed. By utilizing atomic-scale direct imaging with scanning transmission electron microscopy and AC-impedance spectroscopy analysis, we demonstrated for the first time that a multicomponent equimolar proton-conducting quadruple hexagonal perovskite-related Ba5RE2Al2ZrO13 (RE = rare earth elements) oxide system can be synthesized even when adding eight different rare earth elements. In particular, as the number of added elements was increased, i.e., as the configurational entropy was increased, we confirmed that the chemical stability toward CO2 was improved without a significant decrement of the proton conductivity. The findings in this work broaden the use of the crystal structure to which the multicomponent model can be applied, and a systematic study on the correlation between the configurational entropy and proton conductivity and/or chemical stability is noteworthy.

Primary cilia control translation and the cell cycle in medulloblastoma.

The primary cilium, a signaling organelle projecting from the surface of a cell, controls cellular physiology and behavior. The presence or absence of primary cilia is a distinctive feature of a given tumor type; however, whether and how the primary cilium contributes to tumorigenesis are unknown for most tumors. Medulloblastoma (MB) is a common pediatric brain cancer comprising four groups: SHH, WNT, group 3 (G3), and group 4 (G4). From 111 cases of MB, we show that primary cilia are abundant in SHH and WNT MBs but rare in G3 and G4 MBs. Using WNT and G3 MB mouse models, we show that primary cilia promote WNT MB by facilitating translation of mRNA encoding ß-catenin, a major oncoprotein driving WNT MB, whereas cilium loss promotes G3 MB by disrupting cell cycle control and destabilizing the genome. Our findings reveal tumor type-specific ciliary functions and underlying molecular mechanisms. Moreover, we expand the function of primary cilia to translation control and reveal a molecular mechanism by which cilia regulate cell cycle progression, thereby providing new frameworks for studying cilium function in normal and pathologic conditions.

Strategies for the use of Ginkgo biloba extract, EGb 761® , in the treatment and management of mild cognitive impairment in Asia: Expert consensus.

BACKGROUND: Mild cognitive impairment (MCI) is a neurocognitive state between normal cognitive aging and dementia, with evidence of neuropsychological changes but insufficient functional decline to warrant a diagnosis of dementia. Individuals with MCI are at increased risk for progression to dementia; and an appreciable proportion display neuropsychiatric symptoms (NPS), also a known risk factor for dementia. Cerebrovascular disease (CVD) is thought to be an underdiagnosed contributor to MCI/dementia. The Ginkgo biloba extract, EGb 761® , is increasingly being used for the symptomatic treatment of cognitive disorders with/without CVD, due to its known neuroprotective effects and cerebrovascular benefits. AIMS: To present consensus opinion from the ASian Clinical Expert group on Neurocognitive Disorders (ASCEND) regarding the role of EGb 761® in MCI. MATERIALS & METHODS: The ASCEND Group reconvened in September 2019 to present and critically assess the current evidence on the general management of MCI, including the efficacy and safety of EGb 761® as a treatment option. RESULTS: EGb 761® has demonstrated symptomatic improvement in at least four randomized trials, in terms of cognitive performance, memory, recall and recognition, attention and concentration, anxiety, and NPS. There is also evidence that EGb 761® may help delay progression from MCI to dementia in some individuals. DISCUSSION: EGb 761® is currently recommended in multiple guidelines for the symptomatic treatment of MCI. Due to its beneficial effects on cerebrovascular blood flow, it is reasonable to expect that EGb 761® may benefit MCI patients with underlying CVD. CONCLUSION: As an expert group, we suggest it is clinically appropriate to incorporate EGb 761® as part of the multidomain intervention for MCI.

MgO-Template Synthesis of Extremely High Capacity Hard Carbon for Na-Ion Battery.

Extremely high capacity hard carbon for Na-ion battery, delivering 478 mAh g-1 , is successfully synthesized by heating a freeze-dried mixture of magnesium gluconate and glucose by a MgO-template technique. Influences of synthetic conditions and nano-structures on electrochemical Na storage properties in the hard carbon are systematically studied to maximize the reversible capacity. Nano-sized MgO particles are formed in a carbon matrix prepared by pre-treatment of the mixture at 600 °C. Through acid leaching of MgO and carbonization at 1500 °C, resultant hard carbon demonstrates an extraordinarily large reversible capacity of 478 mAh g-1 with a high Coulombic efficiency of 88 % at the first cycle.

A band-gap database for semiconducting inorganic materials calculated with hybrid functional.

Semiconducting inorganic materials with band gaps ranging between 0 and 5 eV constitute major components in electronic, optoelectronic and photovoltaic devices. Since the band gap is a primary material property that affects the device performance, large band-gap databases are useful in selecting optimal materials in each application. While there exist several band-gap databases that are theoretically compiled by density-functional-theory calculations, they suffer from computational limitations such as band-gap underestimation and metastable magnetism. In this data descriptor, we present a computational database of band gaps for 10,481 materials compiled by applying a hybrid functional and considering the stable magnetic ordering. For benchmark materials, the root-mean-square error in reference to experimental data is 0.36 eV, significantly smaller than 0.75-1.05 eV in the existing databases. Furthermore, we identify many small-gap materials that are misclassified as metals in other databases. By providing accurate band gaps, the present database will be useful in screening materials in diverse applications.

Lanthanum Doping Enabling High Drain Current Modulation in a p-Type Tin Monoxide Thin-Film Transistor.

Effects of lanthanum (La) loading on the structural, optical, and electrical properties of tin monoxide (SnO) films were examined as a p-type semiconducting layer. La loading up to 1.9 atom % caused the texturing of the tetragonal SnO phase with a preferential orientation of (101), which was accompanied by the smoother surface morphology. Simultaneously, the incorporated La cation suppressed the formation of n-type SnO2 in the La-doped SnO film and widened its optical band gap. These variations allowed the 1.9 atom % La-loaded SnO film to have a high hole mobility and carrier density, compared with the La-free control SnO film. The superior semiconducting property was reflected in the p-type thin-film transistor (TFT). The control SnO TFTs exhibited the field-effect mobility (µSAT) and ION/OFF ratio of 0.29 cm2 V-1 s-1 and 5.4 × 102, respectively. Enhancement in the µSAT value and ION/OFF ratio was observed for the TFTs with the 1.9 atom % La-loaded SnO channel layer: they were improved to 1.2 cm2 V-1 s-1 and 7.3 × 103, respectively. The reason for this superior performance was discussed on the basis of smoother morphology, suppression of disproportionation conversion from Sn2+ to Sn + Sn4+, and reduced gap-state density.

Material Design of New p-Type Tin Oxyselenide Semiconductor through Valence Band Engineering and Its Device Application.

This paper reports a new p-type tin oxyselenide (SnSeO), which was designed with the concept that the valence band edge from O 2p orbitals in the majority of metal oxides becomes delocalized by hybridizing Se 4p and Sn 5s orbitals. As the Se loading increased, the SnSeO film structures were transformed from tetragonal SnO to orthorhombic SnSe, which was accompanied by an increase in the amorphous phase portion and smooth morphologies. The SnSe0.56O0.44 film annealed at 300 °C exhibited the highest Hall mobility (µHall), 15.0 cm2 (V s)-1, and hole carrier density (nh), 1.2 × 1017 cm-3. The remarkable electrical performance was explained by the low hole effective mass, which was calculated by a first principle calculation. Indeed, the fabricated field-effect transistor (FET) with a p-channel SnSe0.56O0.44 film showed the high field-effect mobility of 5.9 cm2 (V s)-1 and an ION/OFF ratio of 3 × 102. This work demonstrates that anion alloy-based hybridization provides a facile route to the realization of a high-performance p-channel FET and complementary devices.

A molecular dynamics study on the interface morphology of vapor-deposited amorphous organic thin films.

The interfaces between amorphous organic layers play an important role in the efficiency and lifetime of organic light emitting diodes (OLEDs). However, an atomistic understanding of the interface morphology is still poor. In this study, we theoretically investigate the interfacial structure of amorphous organic films using molecular dynamics simulations that mimic vapor-deposition processes. We find that molecularly sharp interfaces are formed by the vapor-deposition process as the interface thickness spans only a mono- or double-layer in terms of lie-down geometry. Interestingly, the interface is more diffusive into the upper layer due to asymmetric interdiffusion during the vapor-deposition process, which is well described by a simple random-walk model. Additionally, we investigate the change in the molecular orientation of interdiffused molecules, which is crucial for device performance.

Incidence and Risk Factors of Recurrent Falls in the Elderly Visiting the Emergency Department after a Fall

BACKGROUND: Several studies have evaluated risk factors for falls; however, the risk factors for recurrent falls are poorly understood. Therefore, this study evaluated the prevalence and factors associated with recurrent falls.METHODS: This study included 250 patients aged over 65 years, all of whom visited the emergency department (ED) at Seoul Medical Center following a fall from January 2016 to December 2017. We reviewed the patients' medical records for demographic data and medical history. Previous fall history, use of gait-aids, residence type, and fall recurrence were assessed via individual telephone calls.RESULTS: During the follow-up period, 21.6% (n=54) of the 250 subjects experienced recurrent falls. Logistic regression analyses showed that fall recurrence was significantly associated with a previous fall history and the residence type. Subjects who lived in basement-level residences had a significantly higher risk of fall recurrence compared to those who lived in ground-level residences (odds ratio, 8.910; 95% confidence interval, 1.082–73.366).CONCLUSION: This study revealed a high incidence of fall recurrence in older adults who visited the ED due to falls. Our results suggest that careful evaluation and intervention are essential, especially in elderly individuals with fall histories and those who live in residences associated with ncreased risk of falls.

High-throughput ab initio calculations on dielectric constant and band gap of non-oxide dielectrics.

High-k dielectrics, materials having a large band gap (Eg) and high dielectric constant (k) simultaneously, constitute critical components in microelectronic devices. Because of the inverse relationship between Eg and k, materials with large values in both properties are rare. Therefore, massive databases on Eg and k will be useful in identifying optimal high-k materials. While experimental and theoretical data on Eg and k of oxides are accumulating, corresponding information is scarce for non-oxide dielectrics with anions such as C, N, F, P, S, and Cl. To identify promising high-k dielectrics among these material groups, we screen 869 compounds of binary carbides, nitrides, sulfides, phosphides, chlorides, and fluorides, through automated ab initio calculations. Among these compounds, fluorides exhibit an Eg-k relation that is comparable to that of oxides. By further screening over ternary fluorides, we identify fluorides such as BiF3, LaF3, and BaBeF4 that could serve as useful high-k dielectrics.

Primary Cilia in Brain Development and Diseases.

The primary cilium, a sensory appendage that is present in most mammalian cells, plays critical roles in signaling pathways and cell cycle progression. Mutations that affect the structure or function of primary cilia result in ciliopathies, a group of developmental and degenerative diseases that affect almost all organs and tissues. Our understanding of the constituents, development, and function of primary cilia has advanced considerably in recent years, revealing pathogenic mechanisms that potentially underlie ciliopathies. In the brain, the primary cilia are crucial for early patterning, neurogenesis, neuronal maturation and survival, and tumorigenesis, mostly through regulating cell cycle progression, Hedgehog signaling, and WNT signaling. We review these advances in our knowledge of primary cilia, focusing on brain development, and discuss the mechanisms that may underlie brain abnormalities in ciliopathies.

mTORC1-Mediated Inhibition of 4EBP1 Is Essential for Hedgehog Signaling-Driven Translation and Medulloblastoma.

Mechanistic target of rapamycin (MTOR) cooperates with Hedgehog (HH) signaling, but the underlying mechanisms are incompletely understood. Here we provide genetic, biochemical, and pharmacologic evidence that MTOR complex 1 (mTORC1)-dependent translation is a prerequisite for HH signaling. The genetic loss of mTORC1 function inhibited HH signaling-driven growth of the cerebellum and medulloblastoma. Inhibiting translation or mTORC1 blocked HH signaling. Depleting 4EBP1, an mTORC1 target that inhibits translation, alleviated the dependence of HH signaling on mTORC1. Consistent with this, phosphorylated 4EBP1 levels were elevated in HH signaling-driven medulloblastomas in mice and humans. In mice, an mTORC1 inhibitor suppressed medulloblastoma driven by a mutant SMO that is inherently resistant to existing SMO inhibitors, prolonging the survival of the mice. Our study reveals that mTORC1-mediated translation is a key component of HH signaling and an important target for treating medulloblastoma and other cancers driven by HH signaling.

Identification of ground-state spin ordering in antiferromagnetic transition metal oxides using the Ising model and a genetic algorithm.

We identify ground-state collinear spin ordering in various antiferromagnetic transition metal oxides by constructing the Ising model from first-principles results and applying a genetic algorithm to find its minimum energy state. The present method can correctly reproduce the ground state of well-known antiferromagnetic oxides such as NiO, Fe2O3, Cr2O3 and MnO2. Furthermore, we identify the ground-state spin ordering in more complicated materials such as Mn3O4 and CoCr2O4.

The Interaction of Myc with Miz1 Defines Medulloblastoma Subgroup Identity.

Four distinct subgroups of cerebellar medulloblastomas (MBs) differ in their histopathology, molecular profiles, and prognosis. c-Myc (Myc) or MycN overexpression in granule neuron progenitors (GNPs) induces Group 3 (G3) or Sonic Hedgehog (SHH) MBs, respectively. Differences in Myc and MycN transcriptional profiles depend, in part, on their interaction with Miz1, which binds strongly to Myc but not MycN, to target sites on chromatin. Myc suppresses ciliogenesis and reprograms the transcriptome of SHH-dependent GNPs through Miz1-dependent gene repression to maintain stemness. Genetic disruption of the Myc/Miz1 interaction inhibited G3 MB development. Target genes of Myc/Miz1 are repressed in human G3 MBs but not in other subgroups. Therefore, the Myc/Miz1 interaction is a defining hallmark of G3 MB development.

Investigation of field effects in a solid-state nanopore transistor.

In order to calculate ion currents through solid-state nanopore transistors realistically, we propose a computational model based on the Poisson-Nernst-Plank equation. In the present model, we determine the surface charge density locally on the nanopore by imposing consistency between the ion distribution and the chemical reaction at the surface. The model can consider a non-uniform influence by the gate voltage on the inner surface of the nanopore membrane, which enables us to investigate ion currents depending on the gate geometry such as the thickness and vertical position within the nanopore. We verify the validity of the model by comparing the pH dependence of simulation results with the extant experimental results. We also investigate the transistor behaviour depending on the surface material, pore geometry and gate position. In particular, we propose an optimized system to enhance the on/off ratio of the nanopore transistor.

LIS1 controls mitosis and mitotic spindle organization via the LIS1-NDEL1-dynein complex.

Heterozygous LIS1 mutations are responsible for the human neuronal migration disorder lissencephaly. Mitotic functions of LIS1 have been suggested from many organisms throughout evolution. However, the cellular functions of LIS1 at distinct intracellular compartments such as the centrosome and the cell cortex have not been well defined especially during mitotic cell division. Here, we used detailed cellular approaches and time-lapse live cell imaging of mitosis from Lis1 mutant mouse embryonic fibroblasts to reveal critical roles of LIS1 in mitotic spindle regulation. We found that LIS1 is required for the tight control of chromosome congression and segregation to dictate kinetochore-microtubule (MT) interactions and anaphase progression. In addition, LIS1 is essential for the establishment of mitotic spindle pole integrity by maintaining normal centrosome number. Moreover, LIS1 plays crucial roles in mitotic spindle orientation by increasing the density of astral MT plus-end movements toward the cell cortex, which enhances cortical targeting of LIS1-dynein complex. Overexpression of NDEL1-dynein and MT stabilization rescues spindle orientation defects in Lis1 mutants, demonstrating that mouse LIS1 acts via the LIS1-NDEL1-dynein complex to regulate astral MT plus-ends dynamics and establish proper contacts of MTs with the cell cortex to ensure precise cell division.

Global developmental gene expression and pathway analysis of normal brain development and mouse models of human neuronal migration defects.

Heterozygous LIS1 mutations are the most common cause of human lissencephaly, a human neuronal migration defect, and DCX mutations are the most common cause of X-linked lissencephaly. LIS1 is part of a protein complex including NDEL1 and 14-3-3ε that regulates dynein motor function and microtubule dynamics, while DCX stabilizes microtubules and cooperates with LIS1 during neuronal migration and neurogenesis. Targeted gene mutations of Lis1, Dcx, Ywhae (coding for 14-3-3ε), and Ndel1 lead to neuronal migration defects in mouse and provide models of human lissencephaly, as well as aid the study of related neuro-developmental diseases. Here we investigated the developing brain of these four mutants and wild-type mice using expression microarrays, bioinformatic analyses, and in vivo/in vitro experiments to address whether mutations in different members of the LIS1 neuronal migration complex lead to similar and/or distinct global gene expression alterations. Consistent with the overall successful development of the mutant brains, unsupervised clustering and co-expression analysis suggested that cell cycle and synaptogenesis genes are similarly expressed and co-regulated in WT and mutant brains in a time-dependent fashion. By contrast, focused co-expression analysis in the Lis1 and Ndel1 mutants uncovered substantial differences in the correlation among pathways. Differential expression analysis revealed that cell cycle, cell adhesion, and cytoskeleton organization pathways are commonly altered in all mutants, while synaptogenesis, cell morphology, and inflammation/immune response are specifically altered in one or more mutants. We found several commonly dysregulated genes located within pathogenic deletion/duplication regions, which represent novel candidates of human mental retardation and neurocognitive disabilities. Our analysis suggests that gene expression and pathway analysis in mouse models of a similar disorder or within a common pathway can be used to define novel candidates for related human diseases.

Genetic mosaic dissection of Lis1 and Ndel1 in neuronal migration.

Coordinated migration of newly born neurons to their prospective target laminae is a prerequisite for neural circuit assembly in the developing brain. The evolutionarily conserved LIS1/NDEL1 complex is essential for neuronal migration in the mammalian cerebral cortex. The cytoplasmic nature of LIS1 and NDEL1 proteins suggest that they regulate neuronal migration cell autonomously. Here, we extend mosaic analysis with double markers (MADM) to mouse chromosome 11 where Lis1, Ndel1, and 14-3-3ɛ (encoding a LIS1/NDEL1 signaling partner) are located. Analyses of sparse and uniquely labeled mutant cells in mosaic animals reveal distinct cell-autonomous functions for these three genes. Lis1 regulates neuronal migration efficiency in a dose-dependent manner, while Ndel1 is essential for a specific, previously uncharacterized, late step of neuronal migration: entry into the target lamina. Comparisons with previous genetic perturbations of Lis1 and Ndel1 also suggest a surprising degree of cell-nonautonomous function for these proteins in regulating neuronal migration.