Search

BACKGROUND: Extended-spectrum β-lactamase (ESBL)-producing Escherichia coli has been increasingly recognized as the cause of upper urinary tract infection (UTI) in children. We have been using flomoxef at our department since 2017 as the first-line empiric therapy for children diagnosed with UTIs, and we avoid using carbapenems, which are considered the first-line treatment for ESBL-producing E. coli. However, reports on the use of flomoxef for UTIs are limited, especially for pediatric patients. The presence of vesicoureteral reflux at the onset of pyelonephritis is a concern. Severe vesicoureteral reflux can lead to repeated UTI and future deterioration of renal function, but the indication for voiding urethrography, which closely examines the presence of vesicoureteral reflux complications, is controversial. METHODS: We retrospectively reviewed the laboratory findings, treatment, and clinical course of 96 pyelonephritis cases experienced at our department over a 7-year period from April 2014 to March 2021. RESULTS: ESBL-producing E. coli were identified as the cause of pyelonephritis in 51% of cases, and this value was significantly higher (88%) in 2017. No significant differences were found in the febrile period or recurrence rate between the flomoxef-initiated group and other antibiotics groups. We also examined clinical indicators to predict vesicoureteral reflux and found no significant differences in ultrasonographic findings of hydronephrosis. CONCLUSION: In the present series, 51% of all pyelonephritis cases were found to be caused by ESBL-producing E. coli, with a significant increase in recent years. Flomoxef may be a useful alternative to carbapenem for ESBL-producing E. coli and the initial antibiotic of choice for upper UTIs in children. The indication for voiding cystourethrography should be carefully determined.

Uncertainty in hydrological statistics estimated with finite observations, such as design rainfall, can be quantified as a confidence interval using statistical theory. Ensemble climate data also enables derivation of a confidence interval. Recently, the database for policy decision making for future climate change (d4PDF) was developed in Japan, which contains dozens of simulated extreme rain-fall events for the past and 60 years into the future, allowing the uncertainty of design rainfall to be quantified as a confidence interval. This study applies an order statistics distribution to evaluate uncertainty in the order statistics of extreme rainfall from the perspective of mathematical theory, while a confidence interval is used for uncertainty evaluation in the probability distribution itself. An advantage of the introduction of an order statistics distribution is that it can be used to quantify the goodness-of-fit between observation and ensemble climate data under the condition that the extreme value distribution estimated from observations is a true distribution. The order statistics distribution is called the control density distribution, which is derived from characteristics that order statistics from standard uniform distribution follows beta distribution. The overlap ratio of the control density distribution and frequency distributions derived from ensemble climate data is utilized for evaluation of the degree of goodness-of-fit for both data.

Pneumatic artificial muscles (PAMs), also known as McKibben artificial muscles, are used in a variety of applications owing to its many positive features, such as simple and lightweight structure and high force to weight ratio. Sensing is essential to precisely control PAMs. Previous studies have proposed various embeddings of PAMs with sensors. However, these often require sophisticated fabrication processes and dedicated setups, which can cause production to be laborious and costly. This letter presents a method to create sensorized PAMs using a dielectric elastomer sensor (DES). In these self-sensing actuators, which we call PAM-DES, the sensor is consisting of a thin, highly compliant dielectric and conductive membranes, which allow the length of the actuator to be detected by reading the capacitance. The sensor directly wraps around the inner tube of the actuator. Therefore, the entire structure remains simple. This feature allows the fabrication of actuators to be relatively effortless and inexpensive. As a proof of concept, a PAM-DES with a length of 100 mm and diameter of 9 mm is fabricated. An analytical model is constructed to design and predict the sensor response. Characterization results show that the sensor properly detects actuator deformation, and low hysteresis and high robustness are observed. The prediction model shows good agreement with the experimental data. Furthermore, the presence of the sensor has almost no influence on the actuator performance. These results validate the concept and suggest that PAM-DES is a highly effective strategy to sensorize actuators of the same type.

Tibial plateau fractures (TPFs) are one of the most challenging intra-articular fractures to treat. Along with reconstruction of the articular surfaces, appropriate alignment of the knee joints must be obtained and maintained after open reduction and internal fixation (ORIF) for TPFs because loss of alignment (LA) is associated with worse clinical outcomes. We aimed to investigate and clarify the risk factors related to LA after ORIF for TPFs.This multicenter, retrospective cohort study used data of hospitals of the Trauma Research Group (TRON group) from January 1, 2011, to December 31, 2020. Among 293 TPFs extracted from the database, we evaluated the alignment of the articular surface to the anatomical axis of the tibia in the immediate postoperative and last follow-up radiographs. We defined a change of alignment from the immediate postoperative radiograph as LA. We evaluated the risk factors of LA using univariate and multiple logistic regression analyses.LA was observed in 27 fractures (9.2%). In multiple logistic regression analyses, preoperative articular step-off and postoperative condylar widening were statistically associated with LA (OR = 1.1, 95% CI: 1.02-1.19 and P = 0.012; OR = 1.04, 95% CI: 1.00-1.08, P = 0.045, respectively). We calculated the threshold by drawing a receiver operating characteristic curve using the final regression model. The threshold of postoperative widening was 8.2 mm. We divided the 293 TPFs into two groups according to this threshold and determined differences between the two groups using Fisher's exact test. The two groups were statistically significantly different (P = 0.00502).Preoperative articular step-off and postoperative condylar widening could be associated with LA after ORIF for TPFs. We suggest that intraoperative restoration of condylar widening is important for the prevention of malalignment following ORIF for TPF.

application/pdf

The Hokkaido Eastern Iburi earthquake in 2018 induced the largest landslide over the Azuma River basin in Hokkaido, the north island of Japan. This study estimated the sediment erosion rate over the Azuma River basin using the universal soil loss equation (USLE) for the pre- and post-earthquake conditions. The results showed that the potential sediment erosion rate from the entire basin increased by 8–29 times more than the pre-earthquake condition. The primary cause of the increase in sediment erosion rate was deforestation due to the landslide, which generated 13% of the bare land area in the entire basin. In addition, the influence of interannual variability of rainfall on sediment erosion rate was calculated from observed rainfall data. As a result, the minimum annual sediment erosion rate after the earthquake exceeded the maximum before the earthquake, indicating that the post-earthquake sediment erosion rate is substantially higher than the pre-earthquake rate. These findings suggest that in order to assess the sediment erosion risk over the Azuma River basin, it is necessary to predict and monitor the vegetation recovery, considering the interannual variability of rainfall.

Dielectric elastomer actuators (DEAs) are one of the promising actuation technologies for soft robotics. This study proposes a fiber-shaped DEA, namely dielectric elastomer fiber actuators (DEFAs). The actuator consisted of a silicone tube filled with the aqueous electrode (sodium chloride solution). Furthermore, it could generate linear and bending actuation in a water environment, which acts as the ground side electrode. Linear-type DEFA and bending-type DEFA were fabricated and characterized to prove the concept. A mixture of Ecoflex 00–30 (Smooth-On) and Sylgard 184 (Dow Corning) was employed in these actuators for the tube part, which was 75.0-mm long with outer and inner diameters of 6.0 mm and 5.0 mm, respectively. An analytical model was constructed to design and predict the behavior of the devices. In the experiments, the linear-type DEFA exhibited an actuation strain and force of 1.3% and 42.4 mN, respectively, at 10 kV (~20 V/µm) with a response time of 0.2 s. The bending-type DEFA exhibited an actuation angle of 8.1° at 10 kV (~20 V/µm). Subsequently, a jellyfish-type robot was developed and tested, which showed the swimming speed of 3.1 mm/s at 10 kV and the driving frequency of 4 Hz. The results obtained in this study show the successful implementation of the actuator concept and demonstrate its applicability for soft robotics.

Dielectric elastomer actuators (DEAs) are a promising actuator technology for soft robotics. As a configuration of this technology, stacked DEAs afford a muscle-like contraction that is useful to build soft robotic systems. In stacked DEAs, dielectric and electrode layers are alternately stacked. Thus, often a dedicated setup with complicated processes or sometimes laborious manual stacking of the layers is required to fabricate stacked actuators. In this study, we propose a method to monolithically fabricate stacked DEAs without alternately stacking the dielectric and electrode layers. In this method, the actuators are fabricated mainly through two steps: 1) molding of an elastomeric matrix containing free-form microfluidic channels and 2) injection of a liquid conductive material that acts as an electrode. The feasibility of our method is investigated via the fabrication and characterization of simple monolithic DEAs with multiple electrodes (2, 4, and 10). The fabricated actuators are characterized in terms of actuation stroke, output force, and frequency response. In the actuators, polydimethylsiloxane (PDMS) and eutectic gallium–indium (EGaIn) are used for the elastomeric matrix and electrode material, respectively. Microfluidic channels are realized by dissolving a three-dimensional printed part suspended in the elastomeric structure. The experimental results show the successful implementation of the proposed method and the good agreement between the measured data and theoretical predication, validating the feasibility of the proposed method.

This paper studies a static hedging problem of derivatives when the model risk exists. When the payoff of derivative depends on one asset, Matsumoto (Int J Financ Eng 4(4):1750042, 2017b) solves the problem. We extend his result to derivatives on two assets. Though the optimal solution is more complicated, we show that the problem can be solved numerically in an algebraic way. Further we give some simple numerical examples to show our method works well.

We report on pneumatic artificial muscles (PAMs), also known as McKibben artificial muscles, that are integrated with a tubular dielectric elastomer sensor (DES). PAMs are usually composed of a rubber tube surrounded by a sleeve. When pressurized, the deformations of the rubber tube are conformed by the sleeve such that the actuator shrinks in the length direction and expands in the radial direction. To precisely control PAMs, a sensor is required to detect the deformations. DES is suitable for this purpose because it is highly compliant and thin, minimizing the influence on the configuration and performance of the actuators. In order to prove the concept, a sensorized PAM is fabricated by adhering a tubular DES onto the outside of the rubber tube, followed by placing the sleeve. A natural rubber tube with an outer diameter of 6 mm is employed. DES is made of an acrylic elastomer (3M, VHB4905) sandwiched between two compliant electrodes (Adhesives Research, ARcare 90366). When injecting air, the surface of the actuator increases therefore the capacitance of DES. This relationship enables the sensing of the actuator length by measuring the change in capacitance. We characterize the actuators in terms of capacitance as a function of the actuator displacement at different applied pressure.

Nonstationarity in hydrological variables has been identified throughout Japan in recent years. As a result, the reliability of designs derived from using method based on the assumption of stationary might deteriorate. Non-stationary hydrological frequency analysis is among the measures to counter this possibility. Using this method, time variations in the probable hydrological quantity can be estimated using a non-stationary extreme value distribution model with time as an explanatory variable. In this study, we build a new method for constructing the confidence interval regarding the non-stationary extreme value distribution by applying a theory of probability limit method test. Furthermore, by introducing a confidence interval based on probability limit method test into the non-stationary hydrological frequency analysis, uncertainty in design rainfall because of lack of observation information was quantified, and it is shown that assessment pertaining to both the occurrence risk of extremely heavy rainfall and changes in the trend of extreme rainfall accompanied with climate change is possible.

In recent years, due to global climate change, flood disaster has become more frequent and intense. Along with this, many researchers in different fields are working on researches to reduce the damage caused by these severe water-related disasters. This study focusses on weather radars, which are mainly used for a countermeasure against flood damage in Japan. Our purpose is to examine the validity of weather radars currently set such as X band multi-parameter radars and C band radars in flood disasters which may cause serious damage in Japan.The targeted flood disaster is one of the largest water-related disasters which caused severe damages to Japan, the typhoon Hagibis in 2019. It caused floods in more than 140 rivers. We used the observed data from weather radars of Chikuma and Abukuma river which are severely damaged in this disaster. Also, the Tama River in the Tokyo metropolitan area was flooded because of the heavy rainfall caused by Hagibis. we compared the accuracy of the multi-parameter radar and the single-parameter radar. thus, the issues of the current weather radar were extracted.As a result, the accumulated rainfall of the single-parameter radars was larger than that of the multi-parameter radars. This may cause by the fact that radio wave of the multi-parameter radars will get attenuated when it passesthrough areas with strong rainfall so that it is difficult to observe some area if there is strong rainfall area between the radar and targeted area. In addition, the values observed by multi-parameter weather radars are fitted with the values by the ground rain gauges.In conclusion, it was found that the multi-parameter weather radars have better accuracy of precipitation observation than that of the single parameter weather radars. Furthermore, it is necessary to consider the optimal position of multi-parameter weather radars to improve accuracy of the observation.

The shortage of extreme rainfall data gives substantial uncertainty to design rainfalls and causes predictions for torrential rainfall to deviate strongly from adopted probability distributions used in river planning. These torrential rainfalls are treated as outliers which existing studies do not evaluate. However, probability limit method test which its acceptance region expresses with high accuracy the range where observed ith order statistics could realize. Confidence interval which quantifies uncertainty of adopted distributions can be constructed by assuming that these critical values in both sides of the adopted region follow the same function form applied to actual observed data. Furthermore, its validity is proved through comparison of confidence interval derived from ensemble downscaling calculations. In addition, these critical values are almost in accordance with outliers in samples from the ensemble downscaling calculations. Therefore, prediction interval which expresses the range that an unknown observed datum can take is constructed by extrapolating the critical values for limit estimation of a future datum. In this paper, quantification method of uncertainty of design rainfall and occurrence risk of outliers in the traditional framework, using the proposed confidence interval and prediction interval, is shown. Moreover, their application to future climate by using Bayesian statistics is explained.

In this paper, we study the dynamics of the Bose-Hubbard model with the nearest-neighbor repulsion by using time-dependent Gutzwiller methods. Near the unit filling, the phase diagram of the model contains density wave (DW), supersolid (SS) and superfluid (SF). The three phases are separated by two second-order phase transitions. We study "slow-quench" dynamics by varying the hopping parameter in the Hamiltonian as a function of time. In the phase transitions from the DW to SS and from the DW to SF, we focus on how the SF order forms and study scaling laws of the SF correlation length, vortex density, etc. The results are compared with the Kibble-Zurek scaling. On the other hand from the SF to DW, we study how the DW order evolves with generation of the domain walls and vortices. Measurement of first-order SF coherence reveals interesting behavior in the DW regime., 10 pages, 13 figures, Version to appear in Phys.Rev.A

In this paper, we study the nonequilibrium dynamics of the Bose-Hubbard model with the nearest-neighbor repulsion by using time-dependent Gutzwiller (GW) methods. In particular, we vary the hopping parameters in the Hamiltonian as a function of time, and investigate the dynamics of the system from the density wave (DW) to the superfluid (SF) crossing a first-order phase transition and vice-versa. From the DW to SF, we find scaling laws for the correlation length and vortex density with respect to the quench time. This is a reminiscence of the Kibble-Zurek scaling for continuous phase transitions and contradicts the common expectation. We give a possible explanation for this observation. On the other hand from the SF to DW, the system evolution depends on the initial SF state. When the initial state is the ground-state obtained by the static GW methods, a coexisting state of the SF and DW domains forms after passing through the critical point. Coherence of the SF order parameter is lost as the system evolves. This is a phenomenon similar to the glass transition in classical systems. When the state starts from the SF with small local phase fluctuations, the system obtains a large-size DW-domain structure with thin domain walls., 21 pages, 13 figures, Version to appear in New J. Phys, typos corrected

A concise synthesis of anserine and related compounds was accomplished by Et-DuPhos-Rh-catalyzed asymmetric hydrogenation of dehydrohistidine derivatives in 2,2,2-trifluoroethanol, which played a key role in improving the yield and selectivity.

Focusing on intracellular targets, we propose a new cell separation technique based on a nanoneedle array (NNA) device, which allows simultaneous insertion of multiple needles into multiple cells. The device is designed to target and lift ("fish") individual cells from a mixed population of cells on a substrate using an antibody-functionalized NNA. The mechanics underlying this approach were validated by force analysis using an atomic force microscope. Accurate high-throughput separation was achieved using one-to-one contacts between the nanoneedles and the cells by preparing a single-cell array in which the positions of the cells were aligned with 10,000 nanoneedles in the NNA. Cell-type-specific separation was realized by controlling the adhesion force so that the cells could be detached in cell-type-independent manner. Separation of nestin-expressing neural stem cells (NSCs) derived from human induced pluripotent stem cells (hiPSCs) was demonstrated using the proposed technology, and successful differentiation to neuronal cells was confirmed.

Salivary hemoglobin (Hb) for screening of periodontitis is approved under the pharmaceutical affairs law of Japan. Two reagents are commercially available for the modified fecal occult blood test: Saliva Hemo Plus and OC-AUTO S Latex Reagent. We simultaneously measured split specimens from 561 samples by using these two methods and compared the differences and agreement between both methods. Moreover, saliva samples were collected from 10 subjects at five time points during the day for analysis of circadian variations and fluctuation. The Pearson's correlation coefficient for these two reagents was 0.794. The Bland-Altman plot of differences in salivary Hb levels measured by the two reagents indicated that the difference included fixed errors (0.55 μg/mL). On analysis of circadian variations, no statistically significant differences were observed using the Friedman test. However, fixed errors were observed between wake-up time and before dinner and before lunch and before dinner, and no random errors were observed by Bland-Altman analysis. In conclusion, the salivary Hb levels measured using OC-AUTO S Latex Reagent were lower than those measured using Saliva Hemo Plus, along with a tendency for higher levels in the morning. Thus, when performing salivary tests these observations must be considered.

In this paper, we study the dynamics of the Bose-Hubbard model by using time-dependent Gutzwiller methods. In particular, we vary the parameters in the Hamiltonian as a function of time, and investigate the temporal behavior of the system from the Mott insulator to the superfluid (SF) crossing a second-order phase transition. We first solve a time-dependent Schr\"odinger equation for the experimental setup recently done by Braun et.al. [Proc. Nat. Acad. Sci. 112, 3641 (2015)] and show that the numerical and experimental results are in fairly good agreement. However, these results disagree with the Kibble-Zurek scaling. From our numerical study, we reveal a possible source of the discrepancy. Next, we calculate the critical exponents of the correlation length and vortex density in addition to the SF order parameter for a Kibble-Zurek protocol. We show that beside the "freeze" time $\hat{t}$, there exists another important time, $t_{\rm eq}$, at which an oscillating behavior of the SF amplitude starts. From calculations of the exponents of the correlation length and vortex density with respect to a quench time $\tQ$, we obtain a physical picture of a coarsening process. Finally, we study how the system evolves after the quench. We give a global picture of dynamics of the Bose-Hubbard model., Comment: References added. Version to appear in Phy.Rev.A

The burden of health-care costs relative to gross domestic product in Japan is increasing. A large percentage (7.6% in 2009) of the Japanese gross domestic product has been spent on health care, and this percentage has been increasing annually. Soaring health-care costs have been recognised as a serious social problem. In this study, we attempted to estimate the relationship between periodontal disease and health-care costs. Subjects consisted of teachers and staff members (35 men, 26 women; mean age, 45 ± 9 years) from two high schools. The salivary levels of lactate dehydrogenase and haemoglobin were adopted as biomarkers to assess periodontal disease. After salivary tests, data for the health-care costs over the subsequent 6 months were provided by the mutual association of the public schools on an individual basis. Curve-fit estimations were then performed where health-care costs were used as a dependent variable and age or salivary levels of haemoglobin or lactate dehydrogenase were used as independent variables. However, no good fitness was obtained. Subsequently, multilayer perceptron neural networks were applied. With the neural networks, good fitness was obtained by using lactate dehydrogenase as an independent variable. The results of this study show that oral health, particularly periodontal disease, is correlated with total health-care costs. The data presented in this study suggests that, from the perspective of both oral and systemic health, oral health can be a signpost in well-being and health promotion.

Background The field of structural dynamics of cytoskeletons in living cells is gathering wide interest, since better understanding of cytoskeleton intracellular organization will provide us with not only insights into basic cell biology but may also enable development of new strategies in regenerative medicine and cancer therapy, fields in which cytoskeleton-dependent dynamics play a pivotal role. The nanoneedle technology is a powerful tool allowing for intracellular investigations, as it can be directly inserted into live cells by penetrating through the plasma membrane causing minimal damage to cells, under the precise manipulation using atomic force microscope. Modifications of the nanoneedles using antibodies have allowed for accurate mechanical detection of various cytoskeletal components, including actin, microtubules and intermediate filaments. However, successful penetration of the nanoneedle through the plasma membrane has been shown to vary greatly between different cell types and conditions. In an effort to overcome this problem and improve the success rate of nanoneedle insertion into the live cells, we have focused here on the fluidity of the membrane lipid bilayer, which may hinder nanoneedle penetration into the cytosolic environment. Results We aimed to reduce apparent fluidity of the membrane by either increasing the approach velocity or reducing experimental temperatures. Although changes in approach velocity did not have much effect, lowering the temperature was found to greatly improve the detection of unbinding forces, suggesting that alteration in the plasma membrane fluidity led to increase in nanoneedle penetration. Conclusions Operation at a lower temperature of 4 °C greatly improved the success rate of nanoneedle insertion to live cells at an optimized approach velocity, while it did not affect the binding of antibodies immobilized on the nanoneedle to vimentins for mechanical detection. As these experimental parameters can be applied to various cell types, these results may improve the versatility of the nanoneedle technology to other cell lines and platforms. Electronic supplementary material The online version of this article (doi:10.1186/s12951-016-0226-5) contains supplementary material, which is available to authorized users.

In the present paper, the Bose-Hubbard model (BHM) with the nearest-neighbor (NN) repulsions is studied from the view point of possible bosonic analogs of the fractional quantum Hall (FQH) state in the vicinity of the Mott insulator (MI). First, by means of the Gutzwiller approximation, we obtain the phase diagram of the BHM in a magnetic field. Then, we introduce an effective Hamiltonian describing excess particles on a MI and calculate the vortex density, momentum distribution and the energy gap. These calculations indicate that the vortex solid forms for small NN repulsions, but a homogeneous featureless `Bose-metal' takes the place of it as the NN repulsion increases. We consider particular filling factors at which the bosonic FQH state is expected to form. Chern-Simons (CS) gauge theory to the excess particle is introduced, and a modified Gutzwiller wave function, which describes bosons with attached flux quanta, is introduced. The energy of the excess particles in the bosonic FQH state is calculated using that wave function, and it is compared with the energy of the vortex solid and Bose-metal. We found that the energy of the bosonic FQH state is lower than that of the Bose-metal and comparable with the vortex solid. Finally, we clarify the condition that the composite fermion appears by using CS theory on the lattice that we previously proposed for studying the electron FQH effect., Revised version, 14 pages, 8 figures

Background/Purpose The intracellular enzymes present in the saliva have been studied as markers of periodontal disease. The aim of this study was to establish procedures for using salivary biomarkers as an alternative to the Community Periodontal Index (CPI) for community-based screening for periodontal disease. Materials and methods The study included 101 adults aged between 19 and 77 years who were undergoing treatment for periodontal disease. We applied analysis of covariance (ANCOVA) to analyze the relationship between Community Periodontal Index (CPI) and levels of salivary factors for the 101 volunteers. Results Demographic characteristics, including age, number of remaining teeth, and smoking habits, showed a significant correlation with CPI. An overall correlation was shown between CP and both salivary lactate dehydrogenases (LD) and hemoglobin (Hb) levels, when analyzed using continuous demographic variables as covariates. Conclusion Results indicated that screening with statistical modeling can be an effective tool for detecting periodontal disease.

Thermal aging embrittlement of LWR components made of stainless cast (e.g. CF-8 and CF-8M) is a potential degradation issue, and careful attention has been paid on it. Although welds of austenitic stainless steels (SSs) have γ-δ duplex microstructure, which is similar to that of the stainless cast, examination on thermal aging characteristics of the SS welds is very limited. In order to evaluate thermal aging behavior of weld metal of austenitic stainless steel, the 316L SS weld metal has been prepared and changes in mechanical properties and in etching properties at isothermal aging at 335°C have been investigated. The hardness of the ferrite phase has increased with aging, while the hardness of austenite phase has stayed same. It has been suggested that spinodal decomposition has occurred in δ-ferrite by the 335°C aging. The etching rates of δ-ferrite at immersion test in 5wt% hydrochloric acid solution have been also investigated using an AFM technique. The etching rate of ferrite phase has decreased consistently with the increase in hardness of ferrite phase. It has been thought that this characteristic is also caused by spinodal decomposition of ferrite into chromium-rich (α') and iron-rich (α).

In this paper, we study a one-dimensional boson system in a superlattice potential. This system is experimentally feasible by using ultracold atomic gases, and attracts much attention these days. It is expected that the system has a topological phase called a topological Mott insulator (TMI). We show that in strongly-interacting cases, the competition between the superlattice potential and the on-site interaction leads to various TMIs with a non-vanishing integer Chern number. Compared to the hard-core case, the soft-core boson system exhibits rich phase diagrams including various non-trivial TMIs. By using the exact diagonalization, we obtain detailed bulk-global phase diagrams including the TMIs with high Chern numbers and also various non-topological phases. We also show that in adiabatic experimental setups, the strongly-interacting bosonic TMIs exhibit the topological particle transfer, i.e., the topological charge pumping phenomenon, similarly to weakly-interacting systems. The various TMIs are characterized by topological charge pumping as it is closely related to the Chern number, and therefore the Chern number is to be observed in feasible experiments.

We have been developed a technology to detect cytoskeletal proteins, such as actin microfilament (1), tubulin (2) and intermediate filaments (3) in living cells using antibody immobilized nanoneedle and AFM. The nanoneedle can be inserted into cells by penetrating membranes with minimal damage to cells due to the ultra-thin shape of 200 nm in diameter and aspect ratio over 50. In this in situprotein detection, force to rupture the interactions between antibodies and cytoskeletal proteins is evaluated. Even by using such thin material, there is a problem of low efficiency of penetration through plasma membrane owing to lipid bilayer’s high fluidity under the condition of normal cultivation temperature of 37°C. In this study, we investigated the effect of impact speed of nanoneedle and insertion under low temperature condition to improve the membrane-penetration efficiency. We chose vimentin, a member of intermediate filaments, as a target protein, which is expressed in variety of cell species, e.g. mesenchymal cell. We immobilized anti-vimentin antibodies onto nanoneedle surface via bionanocapsules displaying Fc-binding ZZ domains derived from protein A. HeLa cells and MCF-7 cells were utilized as vimentin-positive and vimentin-negative cells, respectively. Magnitude of peak forces to rupture antibody-vimentin complexes which appear during the evacuation process of the nanoneedle from the cell was analyzed to evaluate effect of impact speed and temperature on the nanoneedle penetration efficiency. Although the impact speed of nanoneedle higher than 10 µm/s (conventional speed) did not show increment of fishing force detection efficiency, medium temperature of 4°C lower temperature obviously contributed to increment of the average fishing force, from 23 nN to 57 nN. The rupture force of singe interaction between the antibody and vimentin at 4°C was almost same that at 37°C. The results indicated that the temperature of 4°C was presumably under phase transition of the plasma membrane and the condition could enhance penetration of the nanoneedle. (1) Silberberg, et al., Biosens. Bioelectron., 40, 3-9 (2013) (2) Silberberg, et al., J. Biosci. Bioeng., 117, 107-112 (2014) (3) Mieda, et al., Biosens. Bioelectron., 31, 323-329 (2012)