Inamori Foundation

Abstract Acute myeloid leukemia (AML) is an aggressive hematologic cancer characterized by proliferation of immature myeloblasts 1 . It shows profound molecular heterogeneity, which has been primarily studied through genetic abnormalities, providing the basis for disease classification, prognostication, and therapeutic choice 2–8 . However, genetic factors alone may not fully explain AML pathogenesis and diversity, while leaving the role of abnormal epigenome, particularly chromatin state, largely unexplored in a large cohort of patients. Here we show that AML is classified into 16 subgroups with distinct chromatin accessibility profiles based on ATAC-seq in 1,563 AML cases, derived from the encyclopedia of chromatin in AML (eCHROMA AML) dataset, including novel AML subgroups not previously recognized in conventional genomic classifications. By integrating multi-omics analyses of genome, transcriptome, and major histone marks, we show that these epigenetic subgroups exhibit unique features in clinical presentation, gene mutations, differentiation states, gene expression, and super-enhancer profiles, which are validated across independent cohorts. Single-cell sequencing demonstrates the presence of subgroup-specific ATAC signatures that are shared by all leukemic cells, confirming the key role of the epigenome in the ATAC-based classification. Mechanistically, each subgroup is associated with a distinct gene regulatory network centered on key transcription factors, where subgroup-specific super-enhancers play a pivotal role. These ATAC subgroups also have prognostic significance independent of genomic classification, and help reveal unexpected drug sensitivities. In summary, ATAC-based chromatin profiling in this large sample set, combined with multi-omics data, provides new insights into AML pathogenesis beyond genomic profiling and also serves as an invaluable resource for AML research.

When designing a haptic interface, simplicity is crucial to avoid negative effects caused by excessive weight and complexity. Using multimodal information, haptic illusions, and providing context are known to create simpler interfaces. We have previously proposed the use of single overlapped vibrotactile stimulation (SOVS) for presenting spatiotemporal tactile perception, a method that simultaneously presents overlapped waveforms to multiple body parts. There, the acceleration measured from a person dribbling a basketball with an accelerometer positioned on the index finger and the floor was overlapped to present as stimuli. When the stimuli were presented simultaneously to the hand and the feet, it demonstrated a dribbling sensation, like an imaginary ball moving back and forth between the hand and the feet. This demonstrated the potential to eliminate the need for time synchronization and reduce the number of required channels, ultimately leading to the development of simple haptic interfaces that enhance an immersive experience. In this paper, we aim to investigate the key factor behind the perception of SOVS using simple vibrotactile stimuli. The first experiment measured the occurrence rate of the dribbling feeling for different combinations of prepared stimuli, and the results show that the combination of two different input amplitudes is crucial for the occurrence rate of the phenomenon. The second experiment assessed how realistic each stimulus, presented to the hand and the feet separately, felt to the participants. The results show that for the hand, the perceived reality corresponded to the strength of input amplitude, whereas the second-strongest input amplitude was perceived as most realistic for the feet. This suggests that when the combination consists of duplicate input amplitudes and/or those with low perceived reality, the occurrence rate tends to decrease.

Since the qubit’s performance of solid-state spin centers depends highly on the host material, spin centers using new host materials may offer new qubit applications. We investigate the optical properties of Ce-implanted MgO and MgAl2O4 as potential materials holding the optically accessible qubit. We find that the photoluminescence of Ce-implanted MgAl2O4 is more than 10 times brighter than that of Ce-implanted MgO and observe polarization-dependent emission of Ce center in MgAl2O4 with 2% at 4 K under 500 mT, suggesting that the properties required for initializing and reading the state of the spin qubit have been achieved.

In this paper, we present holographic descriptions of entanglement phase transition using AdS/BCFT. First, we analytically calculate the holographic pseudo entropy in the AdS/BCFT model with a brane localized scalar field and show the entanglement phase transition behavior where the time evolution of entropy changes from the linear growth to the trivial one via a critical logarithmic evolution. In this model, the imaginary valued scalar field localized on the brane controls the phase transition, which is analogous to the amount of projections in the measurement induced phase transition. Next, we study the AdS/BCFT model with a brane localized gauge field, where the phase transition looks different in that there is no logarithmically evolving critical point. Finally, we discuss a bulk analog of the above model by considering a double Wick rotation of the Janus solution. We compute the holographic pseudo entropy in this model and show that the entropy grows logarithmically.

Block copolymers (BCPs) are particularly effective in creating soft nanostructured templates for transferring complex 3D network structures into inorganic materials that are difficult to fabricate by other methods. However, achieving control of the local ordering within these 3D networks over large areas remains a significant obstacle to advancing material properties. Here, we address this challenge by directing the self-assembly of a 3D alternating diamond morphology by solvent vapor annealing of a triblock terpolymer film on a chemically patterned substrate. The hexagonal substrate patterns were designed to match a (111) plane of the diamond lattice. Commensurability between the sparse substrate pattern and the BCP lattice produced a uniformly ordered diamond network within the polymer film, as confirmed by a combination of atomic force microscopy and cross-sectional imaging using focused ion beam scanning electron microscopy. The successful replication of the complex and well-ordered 3D network structure in gold promises to advance optical metamaterials and has potential applications in nanophotonics.

The stochastic magnetic tunnel junction (MTJ), the resistance of which fluctuates in time between low and high states under thermal fluctuation, is expected to serve as a key element in probabilistic computers. For reliable operation and versatile application, one needs to address the challenge that the relaxation time in each state should be virtually independent of external magnetic fields in the range of, for example, several mT. In this research, we fabricate in-plane easy-axis elliptical stochastic MTJs with a synthetic antiferromagnetic (SAF) free layer and examine the robustness of their properties against external fields while comparing them with stochastic MTJs with a conventional single ferromagnetic structure. We show that the MTJ with a SAF free layer shows more robust relaxation times against fields applied along the easy- and hard-axis directions. The results are reproduced with a macrospin simulation, from which design guidelines for robust stochastic MTJs targeting probabilistic computers are discussed.

Three-dimensional organic structures containing sp3 carbons bearing four non-hydrogen substituents can provide drug-like molecules. Although such complex structures are challenging targets in synthetic organic chemistry, efficient synthetic approaches will open a new chemical space for pharmaceutical candidates. This review provides an account of our recent achievements in developing organocatalytic approaches to attractive molecular platforms based on optically active sp3 carbons integrating four different functional groups. These methodologies include asymmetric cycloetherification and cyanation of multifunctional ketones, both of which take advantage of the mild characteristics of organocatalytic activation. Enzyme-like but non-enzymatic organocatalytic systems can be used to precisely manufacture molecules containing complex chiral structures without substrate specificity problems. In addition, these catalytic systems control not only stereoselectivity but also site-selectivity and do not induce side reactions even from substrates with rich functionality.

Modulation of the energy landscape by external perturbations governs various thermally-activated phenomena, described by the Arrhenius law. Thermal fluctuation of nanoscale magnetic tunnel junctions with spin-transfer torque (STT) shows promise for unconventional computing, whereas its rigorous representation, based on the Néel-Arrhenius law, has been controversial. In particular, the exponents for thermally-activated switching rate therein, have been inaccessible with conventional thermally-stable nanomagnets with decade-long retention time. Here we approach the Néel-Arrhenius law with STT utilising superparamagnetic tunnel junctions that have high sensitivity to external perturbations and determine the exponents through several independent measurements including homodyne-detected ferromagnetic resonance, nanosecond STT switching, and random telegraph noise. Furthermore, we show that the results are comprehensively described by a concept of local bifurcation observed in various physical systems. The findings demonstrate the capability of superparamagnetic tunnel junction as a useful tester for statistical physics as well as sophisticated engineering of probabilistic computing hardware with a rigorous mathematical foundation.

The present study investigates the human leucocyte antigen (HLA) allele and haplotype frequencies in Japanese population. We carried out the frequency analysis in 5824 families living across Japanese archipelago. The studied population has mainly been typed for the purpose of transplant, especially the hematopoietic stem cell transplantation (HSCT). We determined HLA class I (A, B, and C) and HLA class II (DRB1) using Luminex technology. The haplotypes were directly counted by segregation. A total of 44 HLA‐A, 29 HLA‐C, 75 HLA‐B, and 42 HLA‐DRB1 alleles were identified. In the HLA haplotypes of A‐C‐B‐DRB1 and C‐B, the pattern of linkage disequilibrium peculiar to Japanese population has been confirmed. Moreover, the haplotype frequencies based on family study was compared with the frequencies estimated by maximum likelihood estimation (MLE), and the equivalent results were obtained. The allele and haplotype frequencies obtained in this study could be useful for anthropology, transplantation therapy, and disease association studies.