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A striking feature of non-Hermitian systems is the presence of two different types of topology. One generalizes Hermitian topological phases, and the other is intrinsic to non-Hermitian systems, which are called line-gap topology and point-gap topology, respectively. Whereas the bulk-boundary correspondence is a fundamental principle in the former topology, its role in the latter has not been clear yet. This Letter establishes the bulk-boundary correspondence in the point-gap topology in non-Hermitian systems. After revealing the requirement for point-gap topology in the open boundary conditions, we clarify that the bulk point-gap topology in open boundary conditions can be different from that in periodic boundary conditions. On the basis of real space topological invariants and the K theory, we give a complete classification of the open boundary point-gap topology with symmetry and show that the nontrivial open boundary topology results in robust and exotic surface states.

Organic-inorganic hybrid perovskite solar cells have attracted much attention as important next-generation solar cells. Their solar cell performance is known to change during operation, but the root cause of the instability remains unclear. This report describes an investigation using electron spin resonance (ESR) to evaluate an improvement mechanism for the open-circuit voltage, V OC , of inverted perovskite solar cells at the initial stage of device operation. The ESR study revealed electron transfer at the interface from the perovskite layer to the hole-transport layer not only under dark conditions but also under light irradiation, where electrons are subsequently trapped in the hole-transport layer. An electron barrier is enhanced at the perovskite/hole-transport-layer interface, improving field-effect passivation at the interface. Thereby, the interface recombination velocity is reduced, and thus the V OC improves. These findings are crucially important for elucidating the mechanisms of device performance changes under operation. They reveal a relation between charge transfer and performance improvement, which is valuable for the further development of efficient perovskite solar cells.

Breast cancer is a complex heterogeneous disease with unique molecular subtypes, which limits the development of optimized treatment strategies for each subtype. Cancer gene therapy and potential therapeutics for advanced/refractory cancers can be promising for breast cancer. Combining tumor-tropic lipid nanoparticles (LNPs) and inducible caspase-9 (iC9) mRNA, we aimed to develop a novel treatment strategy for refractory breast cancer. LNP's anti-tumor effects were tested in vitro in three breast cancer cell lines: MDA-MB231, SKBR3, and MCF-7. Tumor cells were treated with LNPs encapsulated with eGFP or iC9 mRNA and chemical inducers of dimerization (CID). Apoptosis-related genes were evaluated by reverse transcriptase quantitative PCR. LNPs could efficiently deliver encapsulated GFP mRNA to all three cancer cell lines (>80% GFP expression. in target cells). Furthermore, LNPs encapsulated with iC9 mRNA (iC9-LNPs) and CID showed cytotoxic activity against all cancer cell lines in vitro. Interestingly, susceptibility to iC9 gene therapy was heterogeneous among cancer cell lines. iC9-LNPs with CID-induced potent cytotoxic effects against SKBR3 and MDA-MB231 cells, but only a mild cytotoxic effect on MCF7 cells. Quantification of apoptosis-related genes suggested that a high BAX/Bcl-2 ratio might be associated with iC9-LNP + CID susceptibility. Thus, cancer gene therapy using iC9-LNPs and CID could be a promising alternative for the treatment of breast cancers, especially for aggressive breast cancers., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yozo Nakazawa reports financial support was provided by Toshiba Corporation. Yozo Nakazawa reports a relationship with Toshiba Corporation that includes: funding grants. Mitsuko Sugano-Ishihara has patent #PCT/IB2020/058307 pending to Shoji Saito, Eiichi Akahoshi, and Yozo Nakazawa. Eiichi Akahoshi and Mitsuko Sugano-Ishihara are employees of Toshiba Corporation., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Learning is a fundamental component of creating intelligent machines. Biological intelligence orchestrates synaptic and neuronal learning at multiple time scales to self-organize populations of neurons for solving complex tasks. Inspired by this, we design and experimentally demonstrate an adaptive hardware architecture Memristive Self-organizing Spiking Recurrent Neural Network (MEMSORN). MEMSORN incorporates resistive memory (RRAM) in its synapses and neurons which configure their state based on Hebbian and Homeostatic plasticity respectively. For the first time, we derive these plasticity rules directly from the statistical measurements of our fabricated RRAM-based neurons and synapses. These "technologically plausible" learning rules exploit the intrinsic variability of the devices and improve the accuracy of the network on a sequence learning task by 30%. Finally, we compare the performance of MEMSORN to a fully-randomly-set-up spiking recurrent network on the same task, showing that self-organization improves the accuracy by more than 15%. This work demonstrates the importance of the device-circuit-algorithm co-design approach for implementing brain-inspired computing hardware., (© 2022. The Author(s).)

Transcription factor RUNX1 plays key roles in the establishment and maintenance of the hematopoietic system. Although RUNX1 has been considered a beneficial tumor suppressor, several recent reports have described the tumor-promoting role of RUNX1 in a variety of hematopoietic neoplasms. In this study, we assessed the effect of RUNX1 depletion in multiple human leukemia cell lines using the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 system, and confirmed that RUNX1 is in fact required for sustaining their leukemic proliferation. To achieve efficient RUNX1 inhibition in leukemia cells, we then examined the effect of lipid nanoparticle (LNP)-mediated delivery of RUNX1-targeting small interfering (si)RNA using two tumor-tropic LNPs. The LNPs containing RUNX1-targeting siRNA were efficiently incorporated into myeloid and T-cell leukemia cell lines and patient-derived primary human acute myeloid leukemia (AML) cells, downregulated RUNX1 expression, induced cell cycle arrest and apoptosis, and exhibited the growth-inhibitory effect in them. In contrast, the LNPs were not efficiently incorporated into normal cord blood CD34 + cells, indicating their minimum cytotoxicity. Thus, our study highlights RUNX1 as a potential therapeutic target to inhibit leukemogenesis, and provides the LNP-based siRNA delivery as a promising approach to deplete RUNX1 specifically in leukemia cells., Competing Interests: Conflicts of interest disclosure SK and MS work for Toshiba Corporation. S.G. received a research grant from Toshiba Corporation. Other authors declare that they have no conflicts of interest with respect to the contents of this article., (Copyright © 2022 ISEH -- Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the disintegration of wet- and dry-compressed orally disintegrating (OD) tablets, with synchrotron radiation as the X-ray source., Significance: Pharmaceutical tablets are vital for the treatment of various diseases. Therefore, they are constantly developed to ensure desirable characteristics. In particular, OD tablets need to disintegrate immediately after absorbing saliva. How these tablets absorb saliva is key to enhancing rapid product development. Recently, absorption processes have been investigated using various noninvasive techniques, including X-ray radiography and X-ray computed tomography. However, X-ray radiography studies on how water without a contrast agent is absorbed, moves, and causes a tablet to swell are scarce. The use of a contrast agent is associated with some shortcomings, including complex data analysis in some instances, alterations in the viscosity of water, and potential influence on fluid transport inside the tablet, thus possibly affecting the disintegration process., Methods: Real-time X-ray radiography was used to monitor the disintegration of various tablets, while X-ray computed tomography and software were used to create 3 D images., Results: We demonstrated how pure water penetrated the wet-compressed tablet faster than inside the dry-compressed tablet, and how the latter swelled more. X-ray computed tomography showed the presence of voids in the tablets following water absorption., Conclusion: Our methods are promising for nondestructive fluid absorption and transport investigations inside OD tablets.

Deep learning has been widely used for inferring robust grasps. Although human-labeled RGB-D datasets were initially used to learn grasp configurations, preparation of this kind of large dataset is expensive. To address this problem, images were generated by a physical simulator, and a physically inspired model (e.g., a contact model between a suction vacuum cup and object) was used as a grasp quality evaluation metric to annotate the synthesized images. However, this kind of contact model is complicated and requires parameter identification by experiments to ensure real world performance. In addition, previous studies have not considered manipulator reachability such as when a grasp configuration with high grasp quality is unable to reach the target due to collisions or the physical limitations of the robot. In this study, we propose an intuitive geometric analytic-based grasp quality evaluation metric. We further incorporate a reachability evaluation metric. We annotate the pixel-wise grasp quality and reachability by the proposed evaluation metric on synthesized images in a simulator to train an auto-encoder-decoder called suction graspability U-Net++ (SG-U-Net++). Experiment results show that our intuitive grasp quality evaluation metric is competitive with a physically-inspired metric. Learning the reachability helps to reduce motion planning computation time by removing obviously unreachable candidates. The system achieves an overall picking speed of 560 PPH (pieces per hour)., Competing Interests: PJ, JOa, YI, JOo, HH, AS, ST, HE, KK, and AO were employed by Toshiba Corporation., (Copyright © 2022 Jiang, Oaki, Ishihara, Ooga, Han, Sugahara, Tokura, Eto, Komoda and Ogawa.)

In computer science, clustering is a technique for grouping data. Ising machines can solve distance-based clustering problems described by quadratic unconstrained binary optimization (QUBO) formulations. A typical simple method using an Ising machine makes each cluster size equal and is not suitable for clustering unevenly distributed data. We propose a new clustering method that provides better performance than the simple method, especially for unevenly distributed data. The proposed method is a hybrid algorithm including an iterative process that comprises solving a discrete optimization problem with an Ising machine and calculating parameters with a general-purpose computer. To minimize the communication overhead between the Ising machine and the general-purpose computer, we employed a low-latency Ising machine implementing the simulated bifurcation algorithm with a field-programmable gate array attached to a local server. The proposed method results in clustering 200 unevenly distributed data points with a clustering score 18% higher than that of the simple method. The discrete optimization with 2000 variables is performed 100 times per iteration, and the overhead time is reduced to approximately 20% of the total execution time. These results suggest that hybrid algorithms using Ising machines can efficiently solve practical optimization problems., (© 2022. The Author(s).)

Early detection and treatment are crucial for increasing the five-year survival rates of various cancers. Low-cost and convenient cancer screening tests are also critically important. Circulating microRNAs are reported as potential biomarkers for various cancers. Recently, miR-1307-3p was found to be a cancer-related microRNA. We evaluated the expression levels of miR-1307-3p in sera obtained from 254 patients with thirteen types of cancer (colon cancer, lung cancer, gastric cancer, liver cancer, bladder cancer esophageal cancer, breast cancer, ovarian cancer, prostate cancer, pancreatic cancer, biliary tract cancer, brain cancer, sarcoma) and 27 non-cancer samples using isothermal amplification and microRNA chip. The expression levels of miR-1307-3p in sera obtained from cancer patients were clearly different from those obtained from non-cancer samples and differentiated the validation cohort into cancer patients and non-cancer control with high accuracy (AUC: 0.98; sensitivity: 0.98; specificity: 0.85). These results showed the potential relevance of miR-1307-3p in serum for the development of new diagnostic examination tools for cancer patients., Competing Interests: The authors declare the following conflict of interests: ​Koji Hashimoto and Mika Inada are employees of Toshiba Corporation and the technologies reported in this paper are patent pending. Yusuke Yamamoto and Takahiro Ochiya received research funding from Toshiba Corporation., (© 2021 The Authors.)

Shapelets are discriminative segments used to classify time-series instances. Shapelet methods that jointly learn both classifiers and shapelets have been studied in recent years because such methods provide both interpretable results and superior accuracy. The partial area under the receiver operating characteristic curve (pAUC) for a low range of false-positive rates (FPR) is an important performance measure for practical cases in industries such as medicine, manufacturing, and maintenance. In this article, we propose a method that jointly learns both shapelets and a classifier for pAUC optimization in any FPR range, including the full AUC. In addition, we propose the following two extensions for shapelet methods: (1) reducing algorithmic complexity in time-series length to linear time and (2) explicitly determining the classes that shapelets tend to match. Comparing with state-of-the-art learning-based shapelet methods, we demonstrated the superiority of pAUC on UCR time-series data sets and its effectiveness in industrial case studies from medicine, manufacturing, and maintenance.

Purpose: For patients with localized pancreatic cancer (PC) with vascular involvement, prediction of resectability is critical to define optimal treatment. However, the current definitions of borderline resectable (BR) and locally advanced (LA) disease leave considerable heterogeneity in outcomes within these classifications. Moreover, factors beyond vascular involvement likely affect the ability to undergo resection. Herein, we share our experience developing a model that incorporates detailed radiologic, patient, and treatment factors to predict surgical resectability in patients with BR and LA PC who undergo stereotactic body radiation therapy (SBRT)., Methods and Materials: Patients with BR or LA PC who were treated with SBRT between 2010 and 2016 were included. The primary endpoint was margin negative resection, and predictors included age, sex, race, treatment year, performance status, initial staging, tumor volume and location, baseline and pre-SBRT carbohydrate antigen 19-9 levels, chemotherapy regimen and duration, and radiation dose. In addition, we characterized the relationship between tumors and key arteries (superior mesenteric, celiac, and common hepatic arteries), using overlap volume histograms derived from computed tomography data. A classification and regression tree was built, and leave-one-out cross-validation was performed. Prediction of surgical resection was compared between our model and staging in accordance with the National Comprehensive Care Network guidelines using McNemar's test., Results: A total of 191 patients were identified (128 patients with LA and 63 with BR), of which 87 patients (46%) underwent margin negative resection. The median total dose was 33 Gy. Predictors included the chemotherapy regimen, amount of arterial involvement, and age. Importantly, radiation dose that covers 95% of gross tumor volume (GTV D95), was a key predictor of resectability in certain subpopulations, and the model showed improved accuracy in the prediction of margin negative resection compared with National Comprehensive Care Network guideline staging (75% vs 63%; P < .05)., Conclusions: We demonstrate the ability to improve prediction of surgical resectabiliy beyond the current staging guidelines, which highlights the value of assessing vascular involvement in a continuous manner. In addition, we show an association between radiation dose and resectability, which suggests the potential importance of radiation to allow for resection in certain populations. External data are needed for validation and to increase the robustness of the model.

Bovine mastitis causes significant economic losses in the dairy industry. Effective prevention of bovine mastitis requires an understanding of the infection status of a pathogenic microorganism in a herd that has not yet shown clinical signs of mastitis and appropriate treatment specific for the pathogenic microorganism. However, bacterial identification by culture has drawbacks in that the sensitivity may be low and the procedure can be complex. In this study, we developed a genetic detection method to identify mastitis pathogens using a simple and highly sensitive electrochemical DNA chip which can specifically detect bacterial DNA in milk specimens. First, we selected microorganisms belonging to 12 families and/or genera associated with mastitis for which testing should be performed. Next, we optimized the conditions for amplifying microorganism DNA by loop-mediated isothermal amplification (LAMP) using 32 primers and the use of a DNA chip capable of measuring all pathogens simultaneously. Sample detection could be completed in just a few hours using this method. Comparison of the results obtained with our DNA chip method and those obtained by bacterial culture verified that when the culture method was set to 100%, the total positive concordance rate of the DNA chip was 85.0% and the total negative concordance rate was 86.9%. Furthermore, the proposed method allows both rapid and highly sensitive detection of mastitis pathogens. We believe that this method will contribute to the development of an effective mastitis control program.

We study hole spin resonance in a p-channel silicon metal-oxide-semiconductor field-effect transistor. In the subthreshold region, the measured source-drain current reveals a double dot in the channel. The observed spin resonance spectra agree with a model of strongly coupled two-spin states in the presence of a spin-orbit-induced anticrossing. Detailed spectroscopy at the anticrossing shows a suppressed spin resonance signal due to spin-orbit-induced quantum state mixing. This suppression is also observed for multiphoton spin resonances. Our experimental observations agree with theoretical calculations.

Objectives: This study describes the feasibility and accuracy of a novel computed tomography (CT) fractional flow reserve (FFR) technique based on alternative boundary conditions., Background: Techniques used to compute FFR based on images acquired from coronary computed tomography angiography (CTA) are described. Boundary conditions were typically determined by allometric scaling laws and assumptions regarding microvascular resistance. Alternatively, boundary conditions can be derived from the structural deformation of coronary lumen and aorta, although its accuracy remains unknown., Methods: Forty-two patients (78 vessels) in a single institution prospectively underwent 320-detector coronary CTA and FFR. Deformation of coronary cross-sectional lumen and aorta, computed from coronary CTA images acquired over diastole, was used to determine the boundary conditions based on hierarchical Bayes modeling. CT-FFR was derived using a reduced order model performed using a standard desktop computer and dedicated software. First, 12 patients (20 vessels) formed the derivation cohort to determine optimal CT-FFR threshold with which to detect functional stenosis, defined as FFR of ≤0.8, which was validated in the subsequent 30 patients (58 vessels)., Results: Derivation cohort results demonstrated optimal threshold for CT-FFR was 0.8 with 67% sensitivity and 91% specificity. In the validation cohort, CT-FFR was successfully computed in 56 of 58 vessels (97%). Compared with coronary CTA, CT-FFR at ≤0.8 demonstrated a higher specificity (87% vs. 74%, respectively) and positive predictive value (74% vs. 60%, respectively), with comparable sensitivity (78% vs. 79%, respectively), negative predictive value (89% vs. 88%, respectively), and accuracy (area under the curve: 0.88 vs. 0.77, respectively; p = 0.22). Based on Bland-Altman analysis, mean intraobserver and interobserver variability values for CT-FFR were, respectively, -0.02 ± 0.05 (95% limits of agreement: -0.12 to 0.08) and 0.03 ± 0.06 (95% limits: 0.07 to 0.19). Mean time per patient for CT-FFR analysis was 27.07 ± 7.54 min., Conclusions: CT-FFR based on alternative boundary conditions and reduced-order fluid model is feasible, highly reproducible, and may be accurate in detecting FFR ≤ 0.8. It requires a short processing time and can be completed at point-of-care. Further validation is required in large prospective multicenter settings., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Purpose: To directly compare the capability of three reconstruction methods using, respectively, forward projected model-based iterative reconstruction (FIRST), adaptive iterative dose reduction using three dimensional processing (AIDR 3D) and filter back projection (FBP) for radiation dose reduction and accuracy of computer-aided volumetry (CADv) measurements on chest CT examination in a phantom study., Materials and Methods: An anthropomorphic thoracic phantom with 30 simulated nodules of three density types (100, -630, and -800 HU) and five different diameters was scanned with an area-detector CT at tube currents of 270, 200, 120, 80, 40, 20, and 10mA. Each scanned data set was reconstructed as thin-section CT with three methods, and all simulated nodules were measured with CADv software. For comparison of the capability for CADv at each tube current, Tukey's HSD test was used to compare the percentage of absolute measurement errors for all three reconstruction methods. Absolute percentage measurement errors were then compared by means of Dunett's test for each tube current at 270mA (standard tube current)., Results: Mean absolute measurement errors of AIDR 3D and FIRST methods for each nodule type were significantly lower than those of the FBP method at 20mA and 10mA (p<0.05). In addition, absolute measurement errors of the FBP method at 20mA and 10mA was significantly higher than that at 270mA for all nodule types (p<0.05)., Conclusion: The FIRST and AIDR 3D methods are more effective than the FBP method for radiation dose reduction, while yielding better measurement accuracy of CADv for chest CT examination., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Given the complex morphologic nature of the right ventricle, three-dimensional (3D) approaches would be more appropriate for assessing right ventricular (RV) function than two-dimensional approaches. Thus, the investigators have developed a novel 3D speckle-tracking echocardiographic (STE) system specialized for the right ventricle. The aim of this study was to assess the characteristics of RV global and regional deformation as well as changes on stress tests using the 3D STE system in experimental studies., Methods: In 10 sheep, sonomicrometry crystals were implanted to validate 3D STE data in the RV endocardium of seven RV segments, including the basal and mid anterior, lateral and inferior wall, and outflow free wall. Full-volume 3D STE data sets and sonomicrometric data were acquired at baseline, during pulmonary artery banding (PAB)-induced moderate (peak RV pressure > 40 mm Hg) and severe (peak RV pressure > 60 mm Hg) RV pressure increases, and during propranolol infusion. The 3D STE area change ratio (ACR), longitudinal strain (LS), and circumferential strain (CS) were measured, and RV global and all segmental deformation data were compared between baseline and stress tests. To assess clinical feasibility, 30 control subjects and 11 patients with pulmonary arterial hypertension were enrolled., Results: All combined 3D STE data were significantly correlated with the sonomicrometric data (ACR, R(2) = 0.88; LS, R(2) = 0.84; CS, R(2) = 0.82; P < .001). In all seven segments, the 3D STE data correlated with the sonomicrometric data (R(2) = 0.72-0.90, P < .001). Global ACR and LS data showed significant differences among baseline, moderate PAB, and severe PAB; however, CS differed only between baseline and severe PAB. The magnitudes of segmental deformation in the free wall were larger than those in the septum and apex under all conditions (P < .05) except LS during severe PAB. Segmental analyses also showed similar responses during stress tests; the ACR in each segment differed significantly between conditions. In all but the apical segments, LS showed significant reductions from moderate PAB; in contrast, CS was significantly reduced with severe PAB in all segments. In this clinical study, the acquisition rate of adequate images for analysis of the RV outflow tract was lower (75.6%) compared with the rate in other segments (from 85.4% to 100%). However, the pulmonary arterial hypertension group had lower RV global deformation values than the control group (ACR and LS, P < .001; CS, P = .003), the ACR and LS in basal and middle segments differed significantly between groups, and the outflow and apex did not differ., Conclusions: A novel 3D STE system specialized for the right ventricle is reliable for RV deformation analyses and may provide additional information about RV global and segmental function. The clinical feasibility of this system is acceptable., (Copyright © 2016 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Resistive pulse sensing with nanopores having a low thickness-to-diameter aspect-ratio structure is expected to enable high-spatial-resolution analysis of nanoscale objects in a liquid. Here we investigated the sensing capability of low-aspect-ratio pore sensors by monitoring the ionic current blockades during translocation of polymeric nanobeads. We detected numerous small current spikes due to partial occlusion of the pore orifice by particles diffusing therein reflecting the expansive electrical sensing zone of the low-aspect-ratio pores. We also found wide variations in the ion current line-shapes in the particle capture stage suggesting random incident angle of the particles drawn into the pore. In sharp contrast, the ionic profiles were highly reproducible in the post-translocation regime by virtue of the spatial confinement in the pore that effectively constricts the stochastic capture dynamics into a well-defined ballistic motion. These results, together with multiphysics simulations, indicate that the resistive pulse height is highly dependent on the nanoscopic single-particle trajectories involved in ultrathin pore sensors. The present finding indicates the importance of regulating the translocation pathways of analytes in low-aspect-ratio pores for improving the discriminability toward single-bioparticle tomography in liquid.

Imidazolium ion-terminated self-assembled monolayer (SAM)-modified electrodes achieve CO2 conversion while suppressing hydrogen evolution. Immobile imidazolium ion on gold (Au) electrodes reduce CO2 at low overpotential. The distance between electrode and imidazolium ion separated by alkane thiol affects CO2 reduction activity. CO2 reduction current depends on the tunnel current rate. Although the product of CO2 reduction at the bare Au electrode is CO, SAM-modified electrodes produce ethylene glycol in aqueous electrolyte solution without CO evolution. The faradaic efficiency reached a maximum of 87%. CO2 reduction at SAM-modified electrodes is unaffected by reduction activity of Au electrode. This phenomenon shows that the reaction field of CO2 reduction is not the electrode surface but the imidazolium ion monolayer.

Modifying the surface energetics, particularly the work function of advanced materials, is of critical importance for a wide range of surface- and interface-based devices. In this work, using in situ photoelectron spectroscopy, we investigated the evolution of electronic structure at the SrTiO3 surface during the growth of ultra-thin MoO3 layers. Because of the large work function difference between SrTiO3 and MoO3, the energy band alignment on the SrTiO3 surface is significantly modified. The charge transfer and dipole formation at the SrTiO3-MoO3 interface leads to a large modulation of work function and to apparent doping in SrTiO3. The measured evolutions of electronic structure and upward band bending suggest that the growth of ultra-thin MoO3 layers is a powerful tool with which to modulate the surface energetics of SrTiO3, and this surface engineering approach could be generalized to other functional oxides.

High prevalence of infection with high-risk human papilloma virus (HPV) ranging from 25 to 100% (average 31%) was observed in breast cancer (BC) patients in Singapore using novel DNA chip technology. Early stage of BC demonstrated higher HPV positivity, and BC positive for estrogen receptor (ER) showed significantly higher HPV infection rate. This unique association of HPV with BC in vivo prompted us to investigate a possible involvement of HPV in early stages of breast carcinogenesis. Using normal breast epithelial cells stably transfected with HPV-18, we showed apparent upregulation of mRNA for the cytidine deaminase, APOBEC3B (A3B) which is reported to be a source of mutations in BC. HPV-induced A3B overexpression caused significant γH2AX focus formation, and DNA breaks which were cancelled by shRNA to HPV18 E6, E7 and A3B. These results strongly suggest an active involvement of HPV in the early stage of BC carcinogenesis via A3B induction.

In order to get a better understanding of different types of cancers and to find the possible biomarkers for diseases, recently, many researchers are analyzing the gene expression data using various machine learning techniques. However, due to a very small number of training samples compared to the huge number of genes and class imbalance, most of these methods suffer from overfitting. In this paper, we present a majority voting genetic programming classifier (MVGPC) for the classification of microarray data. Instead of a single rule or a single set of rules, we evolve multiple rules with genetic programming (GP) and then apply those rules to test samples to determine their labels with majority voting technique. By performing experiments on four different public cancer data sets, including multiclass data sets, we have found that the test accuracies of MVGPC are better than those of other methods, including AdaBoost with GP. Moreover, some of the more frequently occurring genes in the classification rules are known to be associated with the types of cancers being studied in this paper.

This paper describes an object detection framework that learns the discriminative co-occurrence of multiple features. Feature co-occurrences are automatically found by Sequential Forward Selection at each stage of the boosting process. The selected feature co-occurrences are capable of extracting structural similarities of target objects leading to better performance. The proposed method is a generalization of the framework proposed by Viola and Jones, where each weak classifier depends only on a single feature. Experimental results obtained using four object detectors, for finding faces and three different hand gestures, respectively, show that detectors trained with the proposed algorithm yield consistently higher detection rates than those based on their framework while using the same number of features.

Recently, we have developed novel Eu(III) complexes with three beta-diketonates and one asymmetric bis(phosphine) oxide whose light emission intensity is drastically increased. In this paper, one of these complexes is investigated by the density functional theory calculation. Sixteen isomers of this complex have been considered. The ratio of the existence for the most stable isomer (B1&#95;1a) is found to be about 51%, and the sum of the ratio of the existence for the six most stable isomers (B1&#95;1a, B1&#95;3a, B1&#95;8a, B1&#95;2a, B1&#95;1b, and B1&#95;5a) is about 100%, assuming the Boltzmann distribution (T = 300 K). The coordination structures of the six most stable isomers in the ground states are similar, and we can expect asymmetric ligand fields for them, favorable for the efficient light emission. Vertical excitation energies and oscillator strengths for each isomer have been obtained by the time-dependent density functional theory. With the red-shift of the wavelength and the interpolation by Gaussian convolution, both the calculated absorption spectra for the most stable isomer B1&#95;1a and the calculated absorption spectra for the ensemble average of the isomers are found to be similar to the experimental fluorescence excitation spectra. The efficiency of energy transfer from the triplet excited state to the Eu(III) ion is considered by calculating DeltaEET (difference between the adiabatic excitation energy of the complex for the lowest triplet state and the emission energy of the Eu(III) ion for 5D0 to 7F2). The characters for the lowest triplet states for the isomers are investigated by the spin density distributions of the triplet states.

The effects of fine metal oxide particles, particularly those of high-density elements (7.7 to 9.7 x 10(3) kg/m3), on the acoustic properties of silicone rubber have been investigated in order to develop an acoustic lens with a low acoustic attenuation. Silicone rubber doped with Yb2O3 powder having nanoparticle size of 16 nm showed a lower acoustic attenuation than silicone rubber doped with powders of CeO2, Bi2O3, Lu2O3 and HfO2. The silicone rubber doped with Yb2O3 powder showed a sound speed of 0.88 km/s, an acoustic impedance of 1.35 x 10(6) kg/m2s, an acoustic attenuation of 0.93 dB/mmMHz, and a Shore A hardness of 55 at 37 degrees C. Although typical silicone rubber doped with SiO2 (2.6 x 10(3) kg/m3) shows a sound speed of about 1.00 km/s, heavy metal oxide particles decreased the sound velocities to lower than 0.93 km/s. Therefore, an acoustic lens of silicone rubber doped with Yb2O3 powder provides increased sensitivity because it realizes a thinner acoustic lens than is conventionally used due to its low sound speed. Moreover, it has an advantage in that a focus point is not changed when the acoustic lens is pressed to a human body due to its reasonable hardness.

An electrochemical DNA chip using an electrochemically active intercalator and DNA probe immobilized on a gold electrode has been developed for genetic analysis. In this study, N-acetyltransferase2 (NAT2) gene polymorphisms (C481T G590A G857A) were determined by the electrochemical DNA chip and the automated DNA detection system that performs hybridization reaction, washing, detection, and data analysis. Human genomic DNAs were extracted from blood and DNA fragments containing the three polymorphisms were amplified by the polymerase chain reaction (PCR) method. Double-stranded PCR products were treated with T7 exonuclease and single-stranded target DNAs were obtained. A sample containing the single-stranded target DNAs was injected into a cassette including the electrochemical DNA chip and set in an automated system. The turnaround time for genotyping with this system was 90 min. A total of 38 samples were automatically genotyped by an SNP determination algorithm. The results of genotype were completely consistent with those determined by the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis. Consequently, this method requires no labeling step and has the advantage of realizing a compact and automatic system, and so the system is expected to contribute to personalized medicine based on genotype.

We propose a method to efficiently generate cluster states in charge qubits, both semiconducting and superconducting, as well as flux qubits. We show that highly entangled cluster states can be realized by a "one-touch" entanglement operation by tuning gate bias voltages for charge qubits. We also investigate the robustness of these cluster states for nonuniform qubits, which are unavoidable in solid-state systems. We find that quantum computation based on cluster states is a promising approach for solid-state qubits.

Complex system ceramics Pb(Sc(1/2)Nb(1/2))O3-Pb(Mg(1/3)Nb(2/3))O3-Pb(Ni(1/2)Nb(1/2))O3-(Pb0.965,Sr0.035) (Zr,Ti)O3 (PSN-PMN-PNN-PSZT abbreviated PSMNZT) have been synthesized by the conventional technique, and dielectric and piezoelectric properties of the ceramics have been investigated for ultrasonic medical transducers. High capacitances of the transducers are desired in order to match the electrical impedance between the transducers and the coaxial cable in array probes. Although piezoelectric ceramics that have high dielectric constants (epsilon33t/epsilon0 > 5000, k'33 < 70%) are produced in many foundries, the dielectric constants are insufficient. However, we have reported that low molecular mass B-site ions in the lead-perovskite structures are important in realizing better dielectric and piezoelectric properties. We focused on the complex system ceramics PSMNZT that consists of light B-site elements. The maximum dielectric constant, epsilon33T/epsilon0 = 7, 200, was confirmed in the ceramics, where k'33 = 69%, d33 = 940 pC/N, and T(c) = 135 degrees C were obtained. Moreover, pulse-echo characteristics were simulated using the Mason model. The PSMNZT ceramic probe showed echo amplitude about 5.5 dB higher than that of the conventional PZT ceramic probe (PZT-5H type). In this paper, the electrical properties of the PSMNZT ceramics and the simulation results for pulse-echo characteristics of the phased-array probes are introduced.

The driving force dependence of photoinduced electron transfer rate constant in synthetic DNA hairpins in aqueous solutions has been analyzed by means of molecular dynamics simulations. The quantum energy gap law has thus been investigated from a fully atomistic point of view, well reproducing the experimental results with reduced ambiguities in the parameter fitting. Although the contribution from the high-frequency vibrational modes of DNA and water solvent to the reorganization energy is fairly small, their quantum effect on the electron transfer rate constant is significant, well accounting for the deviation from the Marcus parabola observed in the experiments.

Spin-polarized tunneling was studied on Co surfaces of exchange coupled Co/Cu/Co samples, using an Fe tip. A spin-polarized surface state of Co(0001) was found to exist at -0.43 eV relative to E(F), with FWHM of 0.23 eV in the spectra. The state exhibits negative magnetoresistance with an effective spin polarization of less than -23%, suggesting negatively high spin polarization of the surface state. Our first-principles calculations have supported the existence of the surface state. From the calculation, the state is identified as a minority spin Gamma-centered d(2)(z)-like surface state.

High quality piezoelectric single crystals, such as Pb(Zn(1/3)Nb(2/3))O3-PbTiO3 (PZNT) and Pb(Mg(1/3)Nb(2/3))O3-PbTiO3 (PMNT), have been investigated, and, because their piezoelectric properties are greatly superior to those of Pb(Zr(1-x)Ti(x))O3 (PZT) ceramics, they have been used for certain transducer applications since the late 1990s. The present situation for these relaxor-PT (lead titanate) single crystals is summarized. In this review, some possible high Tc > 200 degrees C single crystals are also introduced. Single crystals of Pb(In(1/2)Nb(1/2))O3-PbTiO3 (PINT) binary system and Pb(Mg(1/3)Nb(2/3))O3-Pb(Sc(1/2)Nb(1/2))O3-PbTiO3 (PSMNT) tertiary system have been synthesized, and their electrical properties are reported. In addition, a novel guiding principle for discovering excellent piezoelectric materials, namely the presence of low molecular mass B-site ions that can enter the lead-perovskite Pb(B'B'')O3 structure, is introduced.

The discrete-dipole approximation is applied to vector diffraction analysis in a system with large-numerical-aperture (NA) optics and subwavelength targets. Distributions of light diffracted by subwavelength dielectric targets are calculated in a solid angle that corresponds to a NA of 0.9, and their dependence on incident polarization, target shape, and target size is studied. Electric field distributions inside the target are also shown. Basic features of the vector diffraction are clearly demonstrated. This technique facilitates understanding of the vectorial effects in systems that are expected to be applied in the future to optical data storage.

For the supervised learning problem, error correcting memorization learning was proposed in order to suppress noise in teacher signals. In this paper, generalization capability of the learning method is discussed. Generalization capability is evaluated based on the projection learning criterion. We give a necessary and sufficient condition for error correcting memorization learning to provide the same level of generalization as projection learning, and suggest how to choose a training set so as to satisfy the obtained condition. Moreover, it is revealed that noise suppression based on the error correcting memorization learning criterion always has a good effect on improving generalization to the level of projection learning.

In order to avoid overfitting, we propose error correcting memorization learning. This method is derived from minimization of error between outputs of a trained neural network and correct values for noisy training examples, although the correct values are unknown. We show that noise is adequately suppressed by error correcting memorization learning. The noise suppression mechanism is theoretically clarified. It is found that redundancy plays an essential role for noise suppression and depends on a set of training inputs. We give the condition for the training inputs to provide the redundancy. Moreover, by clarifying the relationships between the proposed method and the weighted least squares estimation with the Mahalanobis norm, we reveal effectiveness of the weighted least squares estimation on noise suppression.

This paper presents an algorithm for extracting rules from trained neural networks. The algorithm is a decompositional approach which can be applied to any neural network whose output function is monotone such as sigmoid function. Therefore, the algorithm can be applied to multilayer neural networks, recurrent neural networks and so on. It does not depend on training algorithms, and its computational complexity is polynomial. The basic idea is that the units of neural networks are approximated by Boolean functions. But the computational complexity of the approximation is exponential, and so a polynomial algorithm is presented. The author has applied the algorithm to several problems to extract understandable and accurate rules. This paper shows the results for the votes data, mushroom data, and others. The algorithm is extended to the continuous domain, where extracted rules are continuous Boolean functions. Roughly speaking, the representation by continuous Boolean functions means the representation using conjunction, disjunction, direct proportion, and reverse proportion. This paper shows the results for iris data.

High-frequency oscillations (HFOs) in the range of 300-900 Hz have been shown to occur simultaneously with the primary response (N20) of the human somatosensory cortex following median nerve stimulation. We studied the effects of aging on somatosensory evoked HFOs. Somatosensory evoked potentials (SEPs) were recorded with a filter set at 10-2000 Hz following right median nerve stimulation in 15 normal young subjects and 15 normal aged subjects. The HFOs were obtained by digitally filtering the wide-band SEPs (10-2000 Hz) using a band-pass of 300-900 Hz. In the aged subjects, the number of negative peaks, amplitudes, duration and area of the HFOs between N20 peak and HFO endpoint were significantly larger than those of young subjects. However, those between N20 onset and N20 peak did not differ between the groups. These results suggest that the later part of HFOs is associated with aging.

Objective: We compared the high-frequency oscillations (HFOs) evoked by posterior tibial nerve (PTN) and median nerve (MN) stimulation., Methods: Somatosensory evoked potentials (SEPs) were recorded with a filter set at 10-2000 Hz to right PTN and to right MN stimulation in 10 healthy subjects. The HFOs were obtained by digitally filtering the wide-band SEPs with a band-pass of 300-900 Hz., Results: HFOs were recorded in 8 of the 10 subjects for PTN, and in all subjects for MN stimulation. The HFOs after both PTN and MN stimulation started approximately at or after the onset of the primary cortical response (P37 and N20) and ended around the middle of the second slope. HFO amplitudes and area after PTN stimulation were significantly smaller than those after MN stimulation. HFO duration after PTN stimulation was markedly longer than that after MN stimulation. However, HFO interpeak latencies did not differ between the two nerves., Conclusions: The present findings suggest that the HFOs after PTN and MN stimulation reflect a neural mechanism common to the hand and foot somatosensory cortex.

A novel 128-channel phased array probe for echocardiography with a center frequency of 3.7 MHz using 0.91Pb(Zn(1/3)Nb(2/3))O(3)-0.09PbTiO(3 ) (PZN-9%PT) single crystal has been fabricated to realize greater sensitivity and broader bandwidth properties. The echo amplitude of the PZN-9%PT single-crystal probe is about 5 dB higher than that of the conventional lead airconate titanate (PZT) ceramic probe, and the fractional bandwidth is about 25 percentage points broader. The quality of B mode images obtained by the PZN-9%PT probe satisfies the performance of the two types of conventional PZT ceramic probes that have center frequencies of 2.5 and 3.75 MHz. At the reference frequency of 3 MHz, the Doppler sensitivity of the PZN-9%PT probe is about 5 dB higher than that of the 3.75 MHz PZT probe; the blood flow of a pulmonary vein in a hard-to-image patient is much more clearly imaged than in the case of using the PZT probe. These superior images are attributable to the use of sufficiently large PZN-9%PT single crystals obtained by the self-flux method.

Clathrin assembly protein 3 (AP-3) is a neuron-specific component of clathrin coated vesicles. Because it promotes the assembly of uniform clathrin cages, AP-3 may play a regulatory role in synaptic vesicle recycling. Previously, using the monoclonal antibody MabR-18, we demonstrated that AP-3 expression starts from the embryonic stage and is maintained at high levels from the early postnatal stages through adult. In order to study the expression of AP-3 during early postnatal development at the mRNA level, RT-PCR analysis was performed. We divided the coding region of AP-3 into 10 regions and designed primers to amplify each region. As a result, developmentally regulated splicing sites were found in two regions. In one region, a PCR product with a 108-bp deletion was detected from postnatal day 10 (P10). In the other region, a product with a 15-bp deletion was increased compensating for the decrease of the undeleted product. The expression of isoforms changed mainly from around P7 to P10, whereas the level of AP-3 protein remained relatively constant throughout postnatal development. These results suggest that the expression of AP-3 isoforms with mRNA splicing is developmentally regulated in the brain and may be involved in the maturation of synaptic vesicle recycling.

A synthesized 20-mer DNA probe complementary to a part of an oncogene v-myc region having a mercaptohexyl group at the 5'-phosphate end was immobilized on a gold electrode by chemisorption. The immobilized DNA was detected voltammetrically using Hoechst 33258 with a DNA minor groove binder and an electrochemically active dye. The modified electrode was immersed into a 100 mumol/L Hoechst 33258 solution and washed with a phosphate buffer (pH 7.0). The anodic peak current (ipa) of Hoechst 33258 on the modified electrode was higher than that on a bare gold electrode (128 and 75 nA, respectively). It was considered that Hoechst 33258 was concentrated on the electrode surface due to its association with DNA. When the modified electrode was hybridized in a solution of a model targeted gene (10(-7) g/mL), single-stranded pVM623 containing the PstI fragment of a 1.5-kilobase pair of oncogene v-myc, the ipa was 192 nA. On the other hand, the ipa was 128 nA when the modified electrode was reacted in a solution of single-stranded pUC119 without a region complementary to v-myc in pVM623. The ipa was related to the concentration of the targeted DNA in the hybridization reaction. The use of Hoechst 33258 resulted in a sequence-specific detection of the targeted DNA quantitatively ranging from 10(-7) to 10(-13) g/mL in a buffer solution.