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The detection of vertical and lateral forces at the nanoscale by atomic force microscopy (AFM) reveals various mechanical properties on surfaces. The qPlus sensor is a widely used force sensor, which is built from a quartz tuning fork (QTF) and a sharpened metal probe, capable of high-resolution imaging in viscous liquids such as lubricant oils. Although a simultaneous detection technique of vertical and lateral forces by using a qPlus sensor is required in the field of nanotribology, it has still been difficult because the torsional oscillations of QTFs cannot be detected. In this paper, we propose a method to simultaneously detect vertical and lateral force components by using a qPlus sensor with a long probe. The first three eigenmodes of the qPlus sensor with a long probe are theoretically studied by solving a set of equations of motion for the QTF prong and probe. The calculation results were in good agreement with the experimental results. It was found that the tip oscillates laterally in the second and third modes. Finally, we performed friction anisotropy measurements on a polymer film by using a bimodal AFM utilizing the qPlus sensor with a long probe to confirm the lateral force detection.

Water structuring on the outer surface of protein molecules called the hydration shell is essential as well as the internal water structures for higher-order structuring of protein molecules and their biological activities in vivo. We now show the molecular-scale hydration structure measurements of native purple membrane patches composed of proton pump proteins by a noninvasive three-dimensional force mapping technique based on frequency modulation atomic force microscopy. We successfully resolved the ordered water molecules localized near the proton uptake channels on the cytoplasmic side of the individual bacteriorhodopsin proteins in the purple membrane. We demonstrate that the three-dimensional force mapping can be widely applicable for molecular-scale investigations of the solid–liquid interfaces of various soft nanomaterials.

Surfactants play a critical role in bottom-up nanotechnologies due to their peculiar nature of controlling the interfacial energy. Since their operational mechanism originates from the molecular-scale formation and disruption processes of molecular assemblies (

Solvation structures formed by ions and solvent molecules at solid/electrolyte interfaces affect the energy storage performance of electrochemical devices, such as lithium-ion batteries. In this study, the molecular-scale solvation structures of an electrolyte, a solution of lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) in propylene carbonate (PC) at the electrolyte–mica interface, were measured using frequency-modulation atomic force microscopy (FM-AFM). The spacing of the characteristic force oscillation in the force versus distance curves increased with increasing ion concentration, suggesting an increase in the effective size of molecules at the interface. Molecular dynamics simulations showed that the effective size of molecular assemblies, namely, solvated ions formed at the interface, increased with increasing ion concentrations, which was consistent with the experimental results. Knowledge of molecular-scale structures of solid/electrolyte interfaces obtained by a combination of FM-AFM and molecular dynamics simulations is important in the design of electrolytes for future energy devices and in improving their properties., リチウムイオンが溶媒や負イオンに包まれている様子を可視化！ --リチウムイオン電池用電解質の固液界面における溶媒和構造の可視化--. 京都大学プレスリリース. 2022-12-22.

Understanding the sub-nanoscale solvation structures of ionic liquids is crucial for the development of innovative functional "devices" across numerous fields. We previously demonstrated the atomic-scale solvation measurements using an ultralow noise 3D frequency-modulation atomic force microscopy combined with molecular dynamics simulations. However, to facilitate practical applications, the molecular distribution on a heterosurface must be verified. Here, we unveil the local solvation structures on a heterogeneously charged phyllosilicate surface in an ionic liquid solution and pure liquid. By identifying adsorbed ion species from the molecular sizes and orientations, we experimentally demonstrate that anions and cations preferentially adsorbed onto the positive and negative surfaces exhibit different orientations and water miscibility. Moreover, we reveal that neutral intermediate regions are formed at the boundary region in ionic liquid media as well as a KCl solution. In the future, this technique will be essential for the evolution of ionic-liquid functional "devices".

Room-temperature ionic liquids are promising media for next-generation energy devices because of their various superior characteristics. Because device performance is often dictated by the solvation structures at the solid-liquid interfaces, particularly at the local reactive sites, their atomistic pictures are in great demand. However, there has been no experimental technique for their three-dimensional solvation structures. Here, we first demonstrate the measurement of the atomic-scale ionic liquids using a recently established ultralow-noise three-dimensional frequency-modulation atomic force microscopy technique supported by molecular dynamics simulations. We conducted the experiments in protic and aprotic aqueous solutions and reveal that the aprotic solvation structure exhibits the higher site specificity, which resolves atomic-scale surface charge distribution on mica because of the absence of the H-bonding network. Our methodology is also applicable to pure liquids and would be a breakthrough for expanding their future applications.

Summary Purpose We examined the feasibility, efficacy, and safety of TS-1 add-on therapy (TAT) in Japanese patients with triple-negative breast caner (TNBC). Methods TAT (TS-1, 80 mg/m2/day, BID, PO), consisting of the 21-day cycles of 14-day consecutive administration followed by 7-day drug holiday, was conducted for 365 days. The median follow-up was 75.2 months (range, 7.3–103.3 months). The primary endpoint was the feasibility of TAT. The secondary endpoints included relapse-free survival (RFS), overall survival (OS), and safety. Results 63 Japanese patients with TNBC (median age, 52.5 years; range, 23.7–68.6 years) were examined. Among them, 34 (54.0%) were postmenopausal, 54 (93.7%) had TNBC of common histological type, 51 (81.0%) had T1 to 3 tumors, 63 (100%) had undergone standardized surgery, and 44 (69.8%) and 19 (30.2%) had undergone neoadjuvant chemotherapy and adjuvant chemotherapy, respectively. The 365-day cumulative rate of TS-1 administration was 68.3% (95% confidence interval, 55.3–79.4), being comparable to 65.8% previously reported for gastric cancer. The 5-year RFS rates were 52.3% and 84.2% in the neoadjuvant and adjuvant chemotherapy groups, respectively, and the 5-year OS rates were 68.0% and 89.5%, respectively. The most common adverse events (AEs) were leucocyte count decreased (50.8%), total bilirubin decreased (44.4%), and pigmentation (42.9%). AEs were manageable clinically, and any grade 4 AEs did not develop. Conclusions The 365-day cumulative rate of TS-1 administration in TNBC patients was comparable to that in gastric cancer patients despite previous chemotherapy with anthracyclines and/or taxanes. TAT was feasible for TNBC patients after standard primary therapy.

Background Fulvestrant 500 mg has been an option for endocrine therapy for advanced or recurrent breast cancer after prior endocrine treatment since November 2011 in Japan. This study aimed to clarify the effectiveness and safety of fulvestrant 500 mg in clinical settings. Methods This was a multicenter, both prospective and retrospective, observational study of 132 postmenopausal women (median age 66) with locally advanced or metastatic breast cancer, who had been treated with fulvestrant. Information from medical records was retrospectively obtained from 9 hospitals (Saitama Breast Cancer Clinical Study Group: SBCCSG) in Saitama prefecture, Japan, from October 2012 to April 2014. The primary end point was time to treatment failure (TTF). The secondary end points were overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR), and adverse events (AE) (CTCAE ver. 4). The choice of subsequent therapy after fulvestrant was also evaluated. Results The median TTF was 6.1 months. Median OS was 28.5 months (the starting date was the first day of fulvestrant). ORR was 12.9% and CBR was 45.5%. The most common AEs were injection site reactions (9.1%). The rate of grade 3 AE was only 2.3% (3/132). The number of patients who underwent subsequent therapy after fulvestrant were 54 (55.7%) receiving chemotherapy, 42 (43.3%) receiving non-fulvestrant endocrine therapy, and 1 (1%) receiving mammalian target of rapamycin inhibitor (mTORi) + endocrine therapy (ET). Conclusion Fulvestrant 500 mg is an effective and safe treatment for patients with advanced or recurrent breast cancer after prior endocrine treatment.

The DNA in the left-handed conformation (Z-conformation) was first discovered by A. Rich, who revealed the crystalline structure of a DNA oligomer d(GC)3 by X-ray diffraction method. Later it was also found that DNA molecules change their conformations from typical right-handed form (B-DNA) to the left-handed form (Z-DNA) under specific conditions (B–Z transition). Furthermore, the detailed structures of the interface between B- and Z-DNAs, B-Z junction, was also determined with an atomic resolution. Recently it was found that some proteins have the Z-DNA binding domains, but the biological functions of Z-DNA are not well understood yet. Therefore the investigation of Z-DNA under physiological conditions is highly essential. In this study, we demonstrated the high-resolution real-space imaging of DNA molecules having the Z- and B-form conformations by frequency-modulation atomic force microscopy (FM-AFM), that has made a great progress in recent years, in an aqueous solution. The major and minor grooves of both DNA conformations were clearly visualized. Furthermore, the surface charge density was measured by three-dimensional (3D) force mapping method. We found that Z-form region was less negatively charged than the B-form region., 左巻きDNAの2重らせん構造の直接可視化に成功 --液中原子間力顕微鏡によるDNA高分解能観察とその電荷分布計測--. 京都大学プレスリリース. 2019-05-17.

Direct proton-knockout reactions of ^{55}Sc at ∼220 MeV/nucleon were studied at the RIKEN Radioactive Isotope Beam Factory. Populated states of ^{54}Ca were investigated through γ-ray and invariant-mass spectroscopy. Level energies were calculated from the nuclear shell model employing a phenomenological internucleon interaction. Theoretical cross sections to states were calculated from distorted-wave impulse approximation estimates multiplied by the shell model spectroscopic factors, which describe the wave function overlap of the ^{55}Sc ground state with states in ^{54}Ca. Despite the calculations showing a significant amplitude of excited neutron configurations in the ground-state of ^{55}Sc, valence proton removals populated predominantly the ground state of ^{54}Ca. This counterintuitive result is attributed to pairing effects leading to a dominance of the ground-state spectroscopic factor. Owing to the ubiquity of the pairing interaction, this argument should be generally applicable to direct knockout reactions from odd-even to even-even nuclei.

A 71-year-old woman with an abnormality detected during the mammography screening consulted a physician. The physician palpated a mass measuring approximately 2 cm in the left lower outer quadrant, with no abnormal skin findings. Ultrasonography revealed an 18 mm hypoechoic mass with irregular

Tip-enhanced Raman spectroscopy (TERS) is a nano-optical approach to extract spatially resolved chemical information with nanometer precision. However, in the case of direct-illumination TERS, which is often employed in commercial TERS instruments, strong fluorescence or far-field Raman signals from the illuminated areas may be excited as a background. They may overwhelm the near-field TERS signal and dramatically decrease the near-field to far-field signal contrast of TERS spectra. It is still challenging for TERS to study the surface of fluorescent materials or a bulk sample that cannot be placed on an Au/Ag substrate. In this study, we developed an indirect-illumination TERS probe that allows a laser to be focused on a flat interface of a thin-film waveguide located far away from the region generating the TERS signal. Surface plasmon polaritons are generated stably on the waveguide and eventually accumulated at the tip apex, thereby producing a spatially and energetically confined hotspot to ensure stable and high-resolution TERS measurements with a low background. With this thin-film waveguide probe, TERS spectra with obvious contrast from a diamond plate can be acquired. Furthermore, the TERS technique based on this probe exhibits excellent TERS signal stability, a long lifetime, and good spatial resolution. This technique is expected to have commercial potential and enable further popularization and development of TERS technology as a powerful analytical method.

The spatial distribution of functional groups causes a charge distribution that often has a close relationship with its biofunctions. To understand them of the protein molecules, measurements of the charge distribution under physiological conditions are desired. Atomic force microscopy (AFM) has been utilized to measure the surface charge density by measuring the electric double layer (EDL) force caused by the overlap of the EDLs on the surfaces of the AFM tip and the biomolecule. Here, we demonstrated the surface charge density measurement of a single streptavidin (SA) protein molecule by the three-dimensional force mapping method based on frequency modulation AFM (FM-AFM). The SA has a strong affinity to biotin because of the electrostatic interactions between the molecules. Therefore, the surface charge density measurements of the biotin-binding sites and other surface areas of the molecule have been anticipated. However, the surface charge density of the surfaces other than the biotin-binding side has never been measured. We demonstrate the surface charge density measurement of the top surface of the single SA molecule, which is perpendicular to the biotin-binding sides, with a controlled orientation using DNA origami as a template by FM-AFM in an electrolyte solution. The surface charge density of the top surface of the SA molecule was estimated by fitting the experimental force curves to the Derjaguin-Landau-Verwey-Overbeck theory. We found that the surface charge density of the top surface of the SA molecule is comparable to those reported earlier for the biotin-binding sides of the molecule. We expect that, by using the DNA origami technology, one can control the orientation of a biomolecule attached to the substrate and measure the surface charge density of the specific surface areas of the biomolecule to obtain information that will help us to understand the relationship between their structures and functions.

Now there is a widespread demand for human resources who can apply Artificial Intelligence (AI) to problem solving. Kanazawa Institute of Technology has a major goal of making it possible for students to naturally use AI to solve problems. Therefore, in 2019, the university opened “AI Basics” for first-year students. The authors tried to see how AI was applied to the problem solution of Project Based Learning (PBL) education in two subjects, Project Design I (PD I) and “AI Basics”, which the author was in charge of. The purpose of this study is to understand the current situation of AI utilization in the first year and to find out some reflections to subjects in 2020. In practice, many PD I students had not yet taken the AI Basics, so the author gave supplementary lectures on AI and encouraged the use of AI for solutions. Also, in “AI Basics”, in the group activity of the last lesson, the author asked students to use AI just learned as a problem solution. The correspondence between each solution and the AI utilization categories were summarized in tables for understanding the current situation. As a result, it was confirmed that AI was widely used for problem solving in both subjects. In particular, the students learned “AI Basics” could propose an appropriate solution in a short time. This means lesson effects of “AI Basics” exist in problem solutions.

8 pags., 4 figs., 3 tabs., The nuclear structure of 51Ar, an uncharted territory so far, was studied by the (p,2p) reaction using γ-ray spectroscopy for the bound states and the invariant mass method for the unbound states. Two peaks were detected in the γ-ray spectrum and six peaks were observed in the 50Ar+n relative energy spectrum. Comparing the results to our shell-model calculations, two bound and six unbound states were established. Three of the unbound states could only be placed tentatively due to the low number of counts in the relative energy spectrum of events associated with the decay through the first excited state of 50Ar. The low cross sections populating the two bound states of 51Ar could be interpreted as a clear signature for the presence of significant subshell closures at neutron numbers 32 and 34 in argon isotopes. It was also revealed that due to the two valence holes, unbound collective states coexist with individual-particle states in 51Ar., We are very grateful to the RIKEN Nishina Center accelerator staff for providing the stable beam and to the BigRIPS team for the smooth operation of the secondary beams. The development of the MINOS device has been supported by the European Research Council through the ERC Grant No. MINOS-258567. F. B. was supported by the RIKEN Special Postdoctoral Researcher Program. K. O. acknowledges the support by Grant-in-Aid for Scientific Research JP16K05352. Y. U. acknowledges the support by Grant-in-Aid for Scientific Research 20K03981. Y. L. S. acknowledges the support of Marie Skłodowska-Curie Individual Fellowship (H2020-MSCA-IF-2015-705023) from the European Union and the support from the Helmholtz International Center for FAIR. H. N. L. acknowledges the support from the Enhanced Eurotalents program (PCOFUND-GA-2013-600382) co-funded by CEA and the European Union. T. A., C. L., D. R., H. T., V. W., L. Z., H. N. L., V. W. and A. O. acknowledge the support from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) Project No. 279384907-SFB 1245. R. B. G. acknowledges the support from the DFG under Grant No. BL 1513/1-1. Y. L. S. and A. O. acknowledge the support from the Alexander von Humboldt Foundation. B. D. L. and L. X. C. acknowledge the support from the Vietnam Ministry of Science and Technology under Grant No. ĐTCB.01/21/VKHKTHN. I. G. has been supported by HIC for FAIR and HRZZ under project No. 1257 and 7194. K. I. H., D. K. and S. Y. P. acknowledge the support from the NRF grant funded by the Korea government (No. 2017R1A2B2012382 and 2019M7A1A1033186). F. B. acknowledge the support from the RIKEN Special Postdoctoral Researcher Program. D. S. and Z. E. were supported by projects No. GINOP-2.3.3-15-2016-00034 and No. K128947. V. V. acknowledges support from the Spanish Ministerio de Economía y Competitividad under Contract No. FPA2017-84756-C4-2-P. V. W. and P. K. acknowledge the support from BMBF grants 05P15RDFN1 and 05P19RDFN1. P. K. acknowledges support from HGS-HIRe. This work was also supported by NKFIH (114454).

This paper describes a new programming education method using stickers and a scanner that combine the features of unplugged programming and physical programming. The new materials developed in this study offer superior features compared to commercial materials, such as low cost, use in lower grades class in elementary school, and no need for teacher’s ICT skills.

Hydration structures play crucial roles in a wide variety of chemical and biological phenomena. However, the key factors that determine a hydration structure remain an open question. Most recent studies have focused on the electrostatic interactions between the surface charges and dipoles of water molecules, which are determined by the atomic/ionic species of the outermost solid surface, as the dominating factor. The number of studies on the correlation between the hydration structure and the atomic-scale surface corrugation has been limited. In this study, we investigated the hydration structures of alkanethiol self-assembled monolayers terminated with a hydroxyl group using frequency-modulated atomic force microscopy. We observed two molecular structures, namely, the (√3 × √3) R30° structure and the c(4 × 2) superlattice structure, and found that their hydration structures are different mainly because of the slight differences in their molecular arrangements. This result suggests that a slight difference in the molecular/atomic arrangements as well as the atomic/ionic species in the outermost solid surface strongly influences the local hydration structures.

Understanding the relationship between the microscopic structures and the carrier transport properties in organic electronic materials is of fundamental interest to exploit the potential of the materials and thus to realize highly efficient organic devices. In this study, carrier ejection processes in polycrystalline organic thin film transistors are investigated by time-resolved Kelvin probe force microscopy (tr-KPFM) that is capable of visualizing time evolution of the surface potential triggered by the application of a voltage pulse with a temporal resolution of 3 ms. The obtained tr-KPFM images show that the spatial distribution of the diffusing charge carriers is mostly non-homogeneous, reflecting the complex resistivity distribution in the channel region formed by the crystalline grains. The trapped charges in some grains diffuse to the electrodes on a time scale of several tens of milliseconds due to the low contact resistance of the grain boundaries, while most of the trapped charges diffuse on a time scale of hundreds of milliseconds.

Understanding and controlling the mechanism of energy conversion related to the development of a sustainable society not only make our lives more convenient but also make them more meaningful and enrichens us. The physical properties at the interface between solid and liquid (solid/liquid interface) play a significant role in energy conversion. The solid/liquid interface is buried and spatially limited, and thus clarifying the physical properties at the interface at the atomic scale is challenging. In this review, we describe our achievements by using frequency modulation atomic force microscopy for studying the geometric structure, molecule distribution, and viscosity at the solid/liquid interface at the atomic scale.

7 pags., 4 figs., 1 tab., Excited states in the N=40 isotone Ti were populated via the V(p,2p)Ti reaction at ∼200 MeV/nucleon at the Radioactive Isotope Beam Factory and studied using γ-ray spectroscopy. The energies of the 2 →0 and 4 →2 transitions, observed here for the first time, indicate a deformed Ti ground state. These energies are increased compared to the neighboring Cr and Fe isotones, suggesting a small decrease of quadrupole collectivity. The present measurement is well reproduced by large-scale shell-model calculations based on effective interactions, while ab initio and beyond mean-field calculations do not yet reproduce our findings. The shell-model calculations for Ti show a dominant configuration with four neutrons excited across the N=40 gap. Likewise, they indicate that the N=40 island of inversion extends down to Z=20, disfavoring a possible doubly magic character of the elusive Ca., We thank the RIKEN Nishina Center accelerator staff and the Bi-gRIPS team for the stable operation of the high-intensity Zn beam and for the preparation of the secondary beam setting. K.O. ac-knowledges the support by Grant-in-Aid for Scientific Research of the Japan Society for the Promotion of Science (JSPS) JP16K05352. A.P. is supported in part by the Ministerio de Ciencia, Innovación y Universidades (Spain), Severo Ochoa Programme SEV-2016-0597 and grant PGC-2018-94583. F.B. is supported by the RIKEN Spe-cial Postdoctoral Researcher Program. L.X.C. and B.D.L. would like to thank the Vietnam Ministry of Science and Technology (MOST) for its support through the Physics Development Program Grant No. ÐTÐLCN.25/18. I.G. has been supported by HIC for FAIR and Croatian Science Foundation under projects no. 1257 and 7194. D. So. was supported by the the European Regional Develop-ment Fund contract No. GINOP-2.3.3-15-2016-00034 and the National Research, Development and Innovation Fund of Hungary via Project No. K128947. V.V. acknowledges support from the Span-ish Ministerio de Economía y Competitividad under Contract No. FPA2017-84756-C4-2-P. K.I.H., D.K. and S.Y.P. acknowledge the sup-port from the National Research Foundation of Korea grant No. 2018R1A5A1025563 and 2019M7A1A1033186. The development of MINOS was supported by the European Research Council through the ERC Grant No. MINOS-258567. This work was also supported by the JSPS KAKENHI Grant No. 18K03639, MEXT as “Priority is-sue on post-K computer” (Elucidation of the fundamental laws and evolution of the universe), the Joint Institute for Computational Fundamental Science (JICFuS), the CNS-RIKEN joint project for large-scale nuclear structure calculations, Natural Sciences and Engineering Research Council (NSERC) of Canada, the Deutsche Forschungsgemeinschaft – Projektnummer 279384907 – SFB 1245, the PRISMA Cluster of Excellence, and the BMBF under Contracts No. 05P18RDFN1 and 05P19RDFN1. TRIUMF receives funding via a contribution through the National Research Council Canada. Com-putations were performed at the Jülich Supercomputing Center (JURECA)

The first γ-ray spectroscopy of ^{52}Ar, with the neutron number N=34, was measured using the ^{53}K(p,2p) one-proton removal reaction at ∼210 MeV/u at the RIBF facility. The 2_{1}^{+} excitation energy is found at 1656(18) keV, the highest among the Ar isotopes with N>20. This result is the first experimental signature of the persistence of the N=34 subshell closure beyond ^{54}Ca, i.e., below the magic proton number Z=20. Shell-model calculations with phenomenological and chiral-effective-field-theory interactions both reproduce the measured 2_{1}^{+} systematics of neutron-rich Ar isotopes, and support a N=34 subshell closure in ^{52}Ar.

It has been demonstrated that the modification of electrodes with self-assembled monolayers (SAMs) reduces the contact resistance and improves the device performances of organic field-effect transistors (OFETs). However, it has been difficult to judge if the contact resistance was reduced by the change in the electronic properties or by the change in the morphology of the metal–organic interface caused by the SAM modification because they have been difficult to be separately assessed. We have directly investigated the local impedance and the potential difference at the electrode–channel interfaces of the OFETs with and without modification of the electrodes by a pentafluorobenzenethiol SAM using frequency-modulation scanning impedance microscopy (FM-SIM). The potential profile measurement and the FM-SIM measurement at the interface showed that the improvement of the field-effect mobility in the SAM-modified OFET was caused by the reduction of the energy level mismatch, namely, the hole injection barrier at the source–channel interface, presumably with the reduction of the hole trap sites at the source–channel interface.