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Trust and attention allocation are pivotal determinants in human-automation interaction. However, there are scarce empirical findings regarding the relationship between trust and attention allocation. Observations from our previous work suggested there may be a negative correlation between trust in automation and eye movement towards automation, though no formal analysis of these data had been conducted to quantify this relationship. The present meta-analysis examined the relationship between three dimensions of trust in automation (performance, process, and purpose) and visual attention allocation to the automation. Specifically, we applied Cumming’s (2014) meta-analysis technique to combine evidence across three experiments. Results indicated a negative correlation between trust in automation and visual sampling of the automated system monitoring task for performance-based trust, but not for process- or purpose-based trust. These findings suggest that operators scanned the automation’s behavior less frequently when indicating higher performance-based trust towards the automation.

A model that introduces surface tension as a pressure boundary condition, named the surface tension as pressure (STP) model, was developed for free surface flow analyses by the moving particle simulation (MPS) method. The STP model assigns to surface particles the liquid pressure of Laplace’s formula. The model is an alternative to previous models that apply surface tension as volume force such as the continuum surface force model. Problems that appeared when using the volume force models, such as the dependencies of calculation results on particle resolution and pressure gradient accuracy, were solved by using the STP model. Calculations predicted the theoretical values of the internal pressure of a 3D spherical droplet and the oscillation period of a 2D elliptic droplet over a wide range of surface tension coefficients and droplet sizes with errors less than 10%. Since the STP model is easy to implement, does not increase computation cost from previous models, and does not require surface reconstruction or additional marker particles, the model is suitable for practical and large-scale free surface flow problems that involve violent deformation of the liquid surface such as liquid atomization.

Trust is expected to be a critical construct that drives successful use of advanced air mobility technologies. As yet, though, the role of trust in human-autonomy interaction is underexplored. Kaber (2018) argues that autonomy requires the highest level of three independent dimensions – viability, independence, and self-governance. The present study examined whether trust varies across the three dimensions of autonomy under varying levels of risk. Participants in the high-risk group read a series of vignettes on a drone that delivers medical supplies over a city where the current study was conducted. Participants in the low-risk group read a series of vignettes on a drone that delivers fast food over a fictitious city. Each vignette described a drone that is either autonomous (i.e., possesses all dimensions) or automated (i.e., one of the dimensions is compromised). Results imply that the three dimensions of autonomy do not equally influence human-technology trust and behavior.

This study considers the sphericity test, a specific test of variance-covariance matrix under monotone missing data for a one-sample problem. We provide the likelihood ratio (LR) and derive an asymptotic expansion of the likelihood ratio test (LRT) statistic and modified LRT statistic for the null distribution. We also derive the upper percentiles of the LRT statistic and modified LRT statistic when the null hypothesis holds, and provide approximate upper percentiles. Furthermore, we prove that the LR under monotone missing data is affine invariant under the null hypothesis. For complete data, we provide an asymptotic expansion of the LRT statistic and modified LRT statistic for the null distribution. Furthermore, we numerically evaluate the actual type I error rates for the approximate upper percentiles using Monte Carlo simulation and provide examples of the LRT statistic and modified LRT statistic and approximate upper percentiles under monotone missing data.

Pathfinder networks are a method to represent mental models from empirically generated pairwise relatedness ratings. This study examined the effects of training exposure on mental model structures based on relatedness ratings collected using the Target Rating method. Forty-eight participants read instruction slides with or without explicit information on the functionality of an autopilot system (Advanced Mental Model or Basic Mental Model groups, respectively). Participants provided relatedness ratings and completed a comprehension test. The Advanced Mental Model group had more common links with the expected model, higher within-group network similarity scores, and higher mental model assessment questionnaire scores than the Basic Mental Model group. Both groups had coherence scores above the minimum threshold for internal consistency. Pathfinder network analysis was sensitive to changes produced by a simple exposure training intervention. In practice, a simple training program may effectively influence operator mental models in novel technological environments such as Advanced Air Mobility.

The implementation of automation will enable Advanced Air Mobility (AAM), which could alter the human's responsibilities from those of an active controller to a passive monitor of vehicles. Mature AAM operations will likely rely on both experienced and novice operators to supervise multiple aircraft. As AAM constitutes a complex and increasingly autonomous system, the human operator's set of responsibilities will transition from those of a controller, to a manager, and eventually to an assistant to highly automated systems. The development of AAM will require system designers to characterize these three sets of human responsibilities. The present work proposes different human responsibilities across various roles (i.e., pilot in command, system operator, system assistant) in the context of AAM along with pertinent attention-related constructs that could contribute to each of the three identified roles of AAM operators including situation awareness, workload, complacency, and vigilance.

The joint committee of the Japanese Society of Intensive Care Medicine/Japanese Respiratory Society/Japanese Society of Respiratory Care Medicine on ARDS Clinical Practice Guideline has created and released the ARDS Clinical Practice Guideline 2021.

Studies of the chemical properties of the elements at the uppermost end of the Periodic Table are extremely challenging both experimentally and theoretically. One of the most important and interesting subjects is to clarify the basic chemical properties of these elements as well as to elucidate the influence of relativistic effects on their electronic configuration. Isotopes of these elements produced at accelerators, however, are short-lived, and the number of produced atoms is so small; any chemistry to be performed must be done on an atom-at-a-time basis that imposes stringent limits on experimental procedures. Here we describe our recent achievements in the effective production of low-energy ion-beams of the elements at the end of the actinide series, fermium (Fm, atomic number Z= 100), mendelevium (Md, Z= 101), nobelium (No, Z= 102), and lawrencium (Lr, Z= 103), using a surface ionization ion-source installed in the ISOL (Isotope Separator On-Line) at the Tandem accelerator facility of JAEA (Japan Atomic Energy Agency). Then the successful measurements of the first ionization potentials (IP1) of these elements with the ISOL setup are reviewed. The measured IP1values increased up to No via Fm and Md, while that of Lr was the lowest among the actinides. Based on the variation of the IP1values of the heavy actinides with the atomic number in comparison with those of the heavy lanthanides, the results clearly demonstrated that the 5forbitals are fully filled at No, and the actinide series ends with Lr. Furthermore, the IP1value of Lr provoked controversy over its position in the Periodic Table, so a short introduction to this issue is presented. The feasibility of the extension of chemical studies to still heavier elements with their ion-beams generated by ISOL is briefly discussed.

In 2014 the first synthesis of a transactinide carbonyl complex – seaborgium hexacarbonyl – was reported. This was achieved in gas-phase chemical experiments in a beam-free environment behind the recoil separator GARIS. Extending this work to heavier elements requires more efficient techniques to synthesize carbonyl complexes as production rates of transactinide elements drop with increasing atomic number. A novel approach was thus conceived, which retains the benefit of a beam-free environment but avoids the physical preseparation step. The latter reduces the yields for products of asymmetric reactions such as those used for the synthesis of suitable isotopes of Sg, Bh, Hs and Mt. For this a series of experiments with accelerator-produced radioisotopes of the lighter homologues W, Re and Os was carried out at the tandem accelerator of JAEA Tokai, Japan. A newly developed double-chamber system, which allows for a decoupled recoil ion thermalization and chemical complex formation, was used, which avoids the low-efficiency physical preseparation step. Here, we demonstrate the feasibility of this newly developed method using accelerator-produced short-lived radioisotopes of the 5d homologues of the early transactinides.

The sensitive analysis of 90Sr with accelerator mass spectrometry (AMS) was developed to advance environmental radiology. One advantage of AMS is the ability to analyze environmental samples with 90Sr/88Sr atomic ratios of 10−14in following a simple chemical separation. Three different IAEA samples with known 90Sr concentrations (moss-soil, animal bone, Syrian soil: 1 g each) were analyzed to assess the validity of the chemical separation and the AMS measurement. The 90Sr measurements were conducted on the AMS system VERA combined with the Ion Laser InterAction Mass Spectrometry (ILIAMS) setup at the University of Vienna, which has excellent isobaric separation performance. The isobaric interference of 90Zr in the 90Sr AMS was first largely removed by chemical separation. The separation factor of Zr in two-step column chromatography with Sr resin and anion exchange resin was 106. The 90Zr remaining in the sample was effectively suppressed by ILIAMS. This procedure achieved a limit of detection <0.1 mBq in the 90Sr AMS, which is lower than typical β-ray detection. The agreement between AMS measurements and nominal values for the 90Sr concentrations of IAEA samples indicated that the new highly-sensitive 90Sr analysis in the environmental samples with AMS is reliable.

Metal oxynitride two-dimensional (2D) crystals prepared by the delamination of layered compounds have attracted attention as photocatalysts, electrode catalysts, and electrolyte materials. However, the preparation of such materials is a significant challenge because of the difficulty related to producing chemically stable layered oxynitrides. In this study, oxynitride 2D crystals having triple perovskite units (A site: Ca, B site: Ta) were successfully prepared via the perfect delamination of the chemically stable Ruddlesden–Popper phase layered oxynitrides, Na2Ca2Ta3O9N. The layered compound was found to be stable during proton exchange in 6 M HNO3and a subsequent delamination process, and the resulting oxynitride 2D crystals (herein [Ca2Ta3O9.5N0.5]−1.5) were observed to have a yellow coloration along with a band gap of 2.58 eV. The [Ca2Ta3O9.5N0.5]−1.52D crystals modified with RhCrOxand CoOxcocatalysts restacked with alkali ions exhibited photocatalytic activity for H2and O2evolution from pure water under UV light and visible light illumination. A transparent, free-standing oxynitride 2D-crystal film having a thickness of around 1 μm was prepared from the 2D-crystal suspension. This film was perfectly oriented in the [001] direction, which resulted in flexibility, mechanical strength, and airtightness due to face-to-face lamination of the 2D crystals. The proton conductivity of the oxynitride 2D-crystal film was around 10–3–10–4S/cm at 25–50 °C (RH: 90–100%). The cell exhibited a power density of 9 mW/cm2at 25 mA/cm2. This type of free-standing, flexible oxynitride film is expected to provide a new possibility and to enable the use of oxynitride materials in various applications.

Acute myeloid leukemia (AML) is a heterogenous malignancy characterized by distinct lineage subtypes and various genetic/epigenetic alterations. As with other neoplasms, AML cells have well-known aerobic glycolysis, but metabolic variations depending on cellular lineages also exist. Lysine-specific demethylase-1 (LSD1) has been reported to be crucial for human leukemogenesis, which is currently one of the emerging therapeutic targets. However, metabolic roles of LSD1 and lineage-dependent factors remain to be elucidated in AML cells. Here, we show that LSD1 directs a hematopoietic lineage-specific metabolic program in AML subtypes. Erythroid leukemia (EL) cells particularly showed activated glycolysis and high expression of LSD1 in both AML cell lines and clinical samples. Transcriptome, chromatin immunoprecipitation–sequencing, and metabolomic analyses revealed that LSD1 was essential not only for glycolysis but also for heme synthesis, the most characteristic metabolic pathway of erythroid origin. Notably, LSD1 stabilized the erythroid transcription factor GATA1, which directly enhanced the expression of glycolysis and heme synthesis genes. In contrast, LSD1 epigenetically downregulated the granulo-monocytic transcription factor C/EBPα. Thus, the use of LSD1 knockdown or chemical inhibitor dominated C/EBPα instead of GATA1 in EL cells, resulting in metabolic shifts and growth arrest. Furthermore, GATA1 suppressed the gene encoding C/EBPα that then acted as a repressor of GATA1 target genes. Collectively, we conclude that LSD1 shapes metabolic phenotypes in EL cells by balancing these lineage-specific transcription factors and that LSD1 inhibitors pharmacologically cause lineage-dependent metabolic remodeling.

Acute myeloid leukemia (AML) is a heterogenous malignancy characterized by distinct lineage subtypes and various genetic/epigenetic alterations. As with other neoplasms, AML cells have well-known aerobic glycolysis, but metabolic variations depending on cellular lineages also exist. Lysine-specific demethylase-1 (LSD1) has been reported to be crucial for human leukemogenesis, which is currently one of the emerging therapeutic targets. However, metabolic roles of LSD1 and lineage-dependent factors remain to be elucidated in AML cells. Here, we show that LSD1 directs a hematopoietic lineage-specific metabolic program in AML subtypes. Erythroid leukemia (EL) cells particularly showed activated glycolysis and high expression of LSD1 in both AML cell lines and clinical samples. Transcriptome, chromatin immunoprecipitation–sequencing, and metabolomic analyses revealed that LSD1 was essential not only for glycolysis but also for heme synthesis, the most characteristic metabolic pathway of erythroid origin. Notably, LSD1 stabilized the erythroid transcription factor GATA1, which directly enhanced the expression of glycolysis and heme synthesis genes. In contrast, LSD1 epigenetically downregulated the granulo-monocytic transcription factor C/EBPα. Thus, the use of LSD1 knockdown or chemical inhibitor dominated C/EBPα instead of GATA1 in EL cells, resulting in metabolic shifts and growth arrest. Furthermore, GATA1 suppressed the gene encoding C/EBPα that then acted as a repressor of GATA1 target genes. Collectively, we conclude that LSD1 shapes metabolic phenotypes in EL cells by balancing these lineage-specific transcription factors and that LSD1 inhibitors pharmacologically cause lineage-dependent metabolic remodeling.

The formation of carbonyl complexes using atom-at-a-time quantities of short-lived transition metals from fusion and fission reactions was reported in 2012. Numerous studies focussing on this chemical system, which is also applicable for the superheavy elements followed. We report on a novel two-chamber approach for the synthesis of such complexes that allows spatial decoupling of thermalization and gas-phase carbonyl complex synthesis. Neutron induced fission on 235U and spontaneous fission of 248Cm were employed for the production of the fission products. These were stopped inside a gas volume behind the target and flushed with an inert-gas flow into a second chamber. This was flushed with carbon monoxide to allow the gas-phase synthesis of carbonyl complexes. Parameter studies of the transfer from the first into the second chamber as well as on the carbonyl complex formation and transport processes have been performed. High overall efficiencies of more than 50% were reached rendering this approach interesting for studies of superheavy elements. Our results show that carbonyl complex formation of thermalized fission products is a single-atom reaction, and not a hot-atom reaction.

ABSTRACTWhile designing deuteron accelerator neutron sources for radioisotope production, nuclear data for light elements such as Li, Be, and C have been systematically measured in the deuteron energy range from a few MeV to around 50 MeV. Currently, the experimental data available on double-differential thick-target neutron yields (DDTTNYs) are insufficient, especially for deuteron energies between 18 and 33 MeV. In this study, we measured the DDTTNYs of (d,n) reactions on natC target for incident deuteron energies of 12, 20, and 30 MeV using the multiple-foil activation method to improve nuclear data insufficiency. The neutrons were detected at emission angles of 0°, 10°, 20°, 30°, and 45°. We applied the GRAVEL code for the unfolding process to derive the DDTTNYs. The results were compared with the calculation by the deuteron-induced reaction analysis code system (DEURACS), and the DEURACS calculation underestimated our results 12 and 20 MeV deuteron. The present data were also used to confirm the systematics of the differential neutron yields at 0° and total neutron yield per incident deuteron in 12–30 MeV of deuteron energy.

Automation is used to complete a variety of everyday and professional tasks. Trust has been shown to be a critical factor that contributes to successful human-automation interaction. Modern theories of automation trust adapted theories of interpersonal trust and have been tested in a variety of domains. Specifically, a triadic model of trust, with performance, process, and purpose as factors, has emerged. From this theory, Chancey et al. (2017) adapted Madsen and Gregor’s (2000) trust scale to align with Lee and See’s (2004) trust framework. Conversely, Jian et al. (2000) developed a scale empirically with trust and distrust as factors. This study aims to use questionnaire data from previous experiments to explore the relationship between the empirically driven Jian et al. trust scale and the theoretically driven Chancey et al. trust scale. We will perform a multilevel confirmatory factor analysis (CFA) to test the distinctiveness of the two trust measures, as well as their structures and the correlation between the measures. The findings of this work will help researchers understand the relationship between the two trust scales, assess if Jian et al.’s scale contains a three-factor structure, and provide more information about the psychological structure of automation trust.

We propose a single crystallization and transfer technique of organic semiconductors using a hydrogel capillary (gel capillary crystallization method). Single crystals of the C8-BTBT thienoacene-based organic semiconductor were prepared by crystal growth in a glass capillary filled with C8-BTBT solution in the supersaturated condition. By adjusting the concentration and temperature, selective nucleation was induced only at the air/liquid interface in the capillary. From the multiple nuclei generated at the interface, polycrystalline C8-BTBT formed near the interface. Subsequent continuous crystal growth in the capillary allowed the polycrystals to transform to a single crystal, because crystal growth was regulated along one direction in the capillary. Single-crystal growth was also induced at the air–liquid interface in an agarose gel capillary, which was made by piercing with a plastic sheet, similar to that in the glass capillary. After formation of a single crystal in the gel capillary, the single crystal was removed from the capillary and transferred onto a solid substrate by dissolution of the capillary with NaI solution.

A comparative turnover frequency (TOF) study for structure-sensitive CO–NO reactions between overlayer (thin-film) and nanoparticle Rh catalysts was performed using a combined experimental and theoretical approach. Two types of honeycomb catalysts were prepared: one by the arc-plasma deposition of a 3 nm Rh overlayer having a (111) preferential orientation atop a 20-μm Fe–Cr–Al metal foil and the other by a conventional wet coating of Rh/ZrO2powders comprised of Rh nanoparticles onto a cordierite honeycomb. The reaction rate of the overlayer was found to be more superior to the nanoparticles, despite a smaller surface area, as the TOF was 14-fold greater on the overlayer than on the nanoparticle. In situinfrared spectroscopy suggested that a hollow-site NO formed onto the overlayer in contrast to the bridge- and on-top-NO adsorptions on the nanoparticles. The energy barriers for surface reactions of adsorbed NO molecules were analyzed using a density functional theory based molecular dynamics approach for a Rh(111) slab and a Rh55cluster to model the overlayer and the nanoparticle. The nanoparticle was more favorable to the dissociation of bridge NO compared with the hollow NO on the overlayer despite needing to overcome much greater barriers for N–N recombination, suggesting that the surface of the nanoparticles was predominately covered by N and O atoms, where N–N recombination was the rate-limiting step. Conversely, the Rh(111) overlayer, which offered not only moderate or comparable energy barriers for NO dissociation and N–N recombination but also a lower energy barrier migration for N atoms on the surface, enabled a high-TOF reaction. The proposed mechanism was rationalized by comparing the results with the empirical kinetics of CO–NO reactions.

A nanometric Rh overlayer formed on a metal foil substrate enables much higher turnover frequencies in NO reduction than the Rh nanoparticles used in conventional three-way catalysis. However, the thermal stability of the Rh overlayer structure needs to be improved for practical applications. In the present study, a Zr buffer layer inserted between the Rh overlayer and the foil substrate efficiently overcame the thermal deterioration at 900 °C for 25 h. A honeycomb catalyst consisting of a 7 nm-thick Rh overlayer, a 500 nm-thick Zr buffer layer and a 30 μm-thick Fe–Cr–Al metal (SUS) foil was prepared by pulsed arc-plasma deposition. After thermal ageing, the Rh/Zr/SUS demonstrated steep light-off characteristics in simulated NO–CO–C3H6–O2reactions. In contrast, the neat catalyst without the buffer layer (Rh/SUS) was totally deactivated by the Al2O3passivation layer that formed over the active Rh overlayer. The Zr buffer layer preserves the outermost surface of the Rh overlayer by blocking the interaction between the Rh and Al2O3layers. Consequently, the Rh surface coverage of Rh/Zr/SUS exceeded 80% after thermal ageing at 900 °C, versusalmost 0% for Rh/SUS.

Online gas-solid adsorption studies with single-atom quantities of Hg, Tl, and Pb, the lighter homologs of the superheavy elements (SHE) copernicium (Cn, Z=112), nihonium (Nh, Z=113), and flerovium (Fl, Z=114), were carried out using short-lived radioisotopes. The interaction with Au and SiO2surfaces was studied and the overall chemical yield was determined. Suitable radioisotopes were produced in fusion-evaporation reactions, isolated in the gas-filled recoil separator TASCA, and flushed rapidly to an adjacent setup of two gas chromatography detector arrays covered with SiO2(first array) and Au (second array). While Tl and Pb adsorbed on the SiO2surface, Hg interacts only weakly and reached the Au-covered array. Our results contribute to elucidating the influence of relativistic effects on chemical properties of the heaviest elements by providing experimental data on these lighter homologs.

We report the first ionization potentials (IP1) of the heavy actinides, fermium (Fm, atomic number Z= 100), mendelevium (Md, Z= 101), nobelium (No, Z= 102), and lawrencium (Lr, Z= 103), determined using a method based on a surface ionization process coupled to an online mass separation technique in an atom-at-a-time regime. The measured IP1values agree well with those predicted by state-of-the-art relativistic calculations performed alongside the present measurements. Similar to the well-established behavior for the lanthanides, the IP1values of the heavy actinides up to No increase with filling up the 5f orbital, while that of Lr is the lowest among the actinides. These results clearly demonstrate that the 5f orbital is fully filled at No with the [Rn]5f147s2configuration and that Lr has a weakly bound electron outside the No core. In analogy to the lanthanide series, the present results unequivocally verify that the actinide series ends with Lr.

Disseminated intravascular coagulations (DIC), acute respiratory distress syndrome (ARDS), and acute kidney injury (AKI) are major organ dysfunctions that occur in patients with sepsis. This study aimed to elucidate the impact of these organ dysfunctions on mortality in patients with severe sepsis.

The gene encoding the chromatin remodeler CHD8 is the most frequently mutated gene in individuals with autism spectrum disorder (ASD). Heterozygous mutations in CHD8give rise to ASD that is often accompanied by macrocephaly, gastrointestinal complaints, and slender habitus. Whereas most phenotypes of CHD8 haploinsufficiency likely result from delayed neurodevelopment, the mechanism underlying slender habitus has remained unknown. Here, we show that CHD8 interacts with CCAAT/enhancer-binding protein β (C/EBPβ) and promotes its transactivation activity during adipocyte differentiation. Adipogenesis was impaired in Chd8-deleted preadipocytes, with the upregulation of C/EBPα and peroxisome-proliferator-activated receptor γ (PPARγ), two master regulators of this process, being attenuated in mutant cells. Furthermore, mice with CHD8 ablation in white preadipocytes had a markedly reduced white adipose tissue mass. Our findings reveal a mode of C/EBPβ regulation by CHD8 during adipogenesis, with CHD8 deficiency resulting in a defect in the development of white adipose tissue.

We have developed new boron paste materials for the process of diffusing crystalline silicon solar cells. The boron paste promotes pattern-forming, long carrier lifetime, and allows good sheet resistance uniformity. The cell efficiency achieved when applying boron paste to an n-type PERT cell was practically excellent. A high efficiency was also obtained under a codiffusion process with POCl3 gas for a simplifying process. We reported on the diffusion characteristic and process details of the boron paste in this paper.

A heterogeneous catalyst incorporating an inorganic ion cofactor for electrochemical water oxidation was exploited using a CoO(OH) nanoparticle layer-deposited electrode. The significant catalytic current for water oxidation was generated in a Na2B4O7solution at pH 9.4 when applying 0.94 V versus Ag/AgCl in contrast to no catalytic current generation in the K2SO4solution at the same pH. HB4O7–and B4O72–ions were indicated to act as key cofactors for the induced catalytic activity of the CoO(OH) layer. The Na2B4O7concentration dependence of the catalytic current was analyzed based on a Michaelis–Menten-type kinetics to provide an affinity constant of cofactors to the active sites, Km= 28 ± 3.6 mM, and the maximum catalytic current density, Imax= 2.3 ± 0.13 mA cm–2. The Imaxvalue of HB4O7–and B4O72–ions was 1.4 times higher than that (1.3 mA cm–2) for the previously reported case of CO32–ions. This could be explained by the shorter-range proton transfer from the active site to the proton-accepting cofactor because of the larger size and more flexible conformation of HB4O7–and B4O72–ions compared with that of CO32–ions.

Approximate relational Hoare logic (apRHL) is a logic for formal verification of the differential privacy of databases written in the programming language pWHILE. Strictly speaking, however, this logic deals only with discrete random samplings. In this paper, we define the graded relational lifting of the subprobabilistic variant of Giry monad, which described differential privacy. We extend the logic apRHL with this graded lifting to deal with continuous random samplings. We give a generic method to give proof rules of apRHL for continuous random samplings. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) comprises a range of neurodevelopmental disorders characterized by deficits in social interaction and communication as well as by restricted and repetitive behaviours. ASD has a strong genetic component with high heritability. Exome sequencing analysis has recently identified many de novo mutations in a variety of genes in individuals with ASD, with CHD8, a gene encoding a chromatin remodeller, being most frequently affected. Whether CHD8 mutations are causative for ASD and how they might establish ASD traits have remained unknown. Here we show that mice heterozygous for Chd8 mutations manifest ASD-like behavioural characteristics including increased anxiety, repetitive behaviour, and altered social behaviour. CHD8 haploinsufficiency did not result in prominent changes in the expression of a few specific genes but instead gave rise to small but global changes in gene expression in the mouse brain, reminiscent of those in the brains of patients with ASD. Gene set enrichment analysis revealed that neurodevelopment was delayed in the mutant mouse embryos. Furthermore, reduced expression of CHD8 was associated with abnormal activation of RE-1 silencing transcription factor (REST), which suppresses the transcription of many neuronal genes. REST activation was also observed in the brains of humans with ASD, and CHD8 was found to interact physically with REST in the mouse brain. Our results are thus consistent with the notion that CHD8 haploinsufficiency is a highly penetrant risk factor for ASD, with disease pathogenesis probably resulting from a delay in neurodevelopment.

An isothermal vacuum chromatography setup for superheavy element chemistry studies was developed and tested online at the one-atom-at-a-time level. As a model system, the adsorption behavior of thallium on quartz was chosen with respect to a future chemical characterization of its superheavy homologue, element 113 (E113, Z= 113), using the described setup. Short-lived 184Tl (t1/2= 10.1(5) s) was produced in the reaction 152Gd(35Cl, 3n)184Tl and delivered as a mass-separated ion beam to the chemistry experiment: A subsurface implantation and a subsequent fast thermal release from a metal matrix was followed by isothermal vacuum chromatography as the chemical separation stage. Single atomic species passing this chromatographic separation were finally identified by time- and energy-resolved event-by-event α-spectroscopy using a diamond-based solid-state detector. The derived adsorption enthalpy of −ΔHadsSiO2(Tl) = 158 ± 3 kJ·mol–1significantly exceeds available data but correlates well with the adsorption of other elements studied on the same surface. The described technique enables chemical experiments with short-lived transactinide elements (t1/2< 1 s), surpassing the rapidity of today’s state-of-the-art gas-phase experiments by at least 1 order of magnitude.

Fetal and adult Leydig cells develop in mammalian prenatal and postnatal testes, respectively. In mice, fetal Leydig cells (FLCs) emerge in the interstitial space of the testis at embryonic day 12.5 and thereafter increase in number, possibly through differentiation from progenitor cells. However, the progenitor cells have not yet been identified. Previously, we established transgenic mice in which FLCs are labeled strongly with enhanced green fluorescent protein (EGFP). Interestingly, fluorescence-activated cell sorting provided us with weakly EGFP-labeled cells as well as strongly EGFP-labeled FLCs. In vitro reconstruction of fetal testes demonstrated that weakly EGFP-labeled cells contain FLC progenitors. Transcriptome from the 2 cell populations revealed, as expected, marked differences in the expression of genes required for growth factor/receptor signaling and steroidogenesis. In addition, genes for energy metabolisms such as glycolytic pathways and the citrate cycle were activated in strongly EGFP-labeled cells, suggesting that metabolism is activated during FLC differentiation.

External genitalia are prominent organs showing hormone-dependent sexual differentiation. Androgen is an essential regulator of masculinization of the genital tubercle, which is the anlage of external genitalia. We have previously shown that v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog B (MAFB) is an androgen-inducible regulator of embryonic urethral masculinization in mice. However, it remains unclear how androgen regulates Mafbexpression. The current study suggests that the Mafb3′ untranslated region (UTR) is an essential region for its regulation by androgen. We identified 2 functional androgen response elements (AREs) in Mafb3′UTR. Androgen receptor is bound to such AREs in 3′UTR during urethral masculinization. In addition to 3′UTR, Mafb5′UTR also showed androgen responsiveness. Moreover, we also demonstrated that β-catenin, one of genital tubercle masculinization factors, may be an additional regulator of Mafbexpression during urethral masculinization. This study provides insights to elucidate mechanisms of gene regulation through AREs present in Mafb3′UTR for a better understanding of the processes of urethral masculinization.