In the research of advanced materials based on nanoscience and nanotechnology, it is often desirable to measure nanoscale local electrical conductivity at a designated position of a given sample. For this purpose, multiple-probe scanning probe microscopes (MP-SPMs), in which two, three or four scanning tunneling microscope (STM) or atomic force microscope (AFM) probes are operated independently, have been developed. Each probe in an MP-SPM is used not only for observing high-resolution STM or AFM images but also for forming an electrical contact enabling nanoscale local electrical conductivity measurement. The world's first double-probe STM (DP-STM) developed by the authors, which was subsequently modified to a triple-probe STM (TP-STM), has been used to measure the conductivities of one-dimensional metal nanowires and carbon nanotubes and also two-dimensional molecular films. A quadruple-probe STM (QP-STM) has also been developed and used to measure the conductivity of two-dimensional molecular films without the ambiguity of contact resistance between the probe and sample. Moreover, a quadruple-probe AFM (QP-AFM) with four conductive tuning-fork-type self-detection force sensing probes has been developed to measure the conductivity of a nanostructure on an insulating substrate. A general-purpose computer software to control four probes at the same time has also been developed and used in the operation of the QP-AFM. These developments and applications of MP-SPMs are reviewed in this paper.

The conductivity of polydiacetylene thin films has been evaluated in the region below 20 µm using a newly constructed independently driven double-tip scanning tunneling microscope. The polydiacetylene thin films fabricated by means of the Langmuir-Blodgett method showed the formation of islands with sizes of 2-20 µm with the polydiacetylene backbone extended in one direction in each island. It was indicated that the resistance of the polydiacetylene thin films is proportional to the tip-tip distances, suggesting one-dimensional conduction along the polydiacetylene backbones, which was clearly different from that of two-dimensionally uniform conductive thin films of poly(3-octylthiophene). The conductivity of the polydiacetylene thin film was estimated to be (3-5) × 10 -6 S/cm, which is 5 orders of magnitude higher than that in the previous report.

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Currently 5-fluorouracil (5-FU) plays a central role in the chemotherapeutic regimens for colorectal cancers and thus it is important to understand the mechanisms that determine 5-FU sensitivity. The expression profiles of human colon cancer cell line DLD-1, its 5-FUresistant subclone DLD-1/FU and a futher 21 types of colon cancer cell lines were compared to identify the novel genes defining the sensitivity to 5-FU and to estimate which population of genes is responsible for 5-FU sensitivity. In the hierarchical clustering, DLD-1 and DLD-1/FU were most closely clustered despite over 100 times difference in their 50% inhibitory concentration of 5-FU. In DLD-1/FU, the population of genes differentially expressed compared to DLD-1 was limited to 3.3%, although it ranged from 4.8% to 24.0% in the other 21 cell lines, thus indicating that the difference of 5-FU sensitivity was defined by a limited number of genes. Next, the role of the cellular inhibitor of apoptosis 2 (cIAP2) gene, which was up-regulated in DLD-1/FU, was investigated for 5-FU resistance using RNA interference. The downregulation of cIAP2 efficiently enhanced 5-FU sensitivity, the activation of caspase 3/7 and apoptosis under exposure to 5-FU. The immunohistochemistry of cIAP2 in cancer and corresponding normal tissues from colorectal cancer patients in stage III revealed that cIAP2 was more frequently expressed in cancer tissues than in normal tissues, and cIAP2-positive patients had a trend toward early recurrence after fluorouracilbased chemotherapy. Although the association between drug sensitivity and the IAP family in colorectal cancer has not yet been discussed, cIAP2 may therefore play an important role as a target therapy in colorectal cancer. (Cancer Sci 2009; 100: 903-913) 5-fluorouracil (5-FU) is an anticancer drug that has been mainly used in the treatment of colorectal cancers. Recently, 5-FU has been combined with oxaliplatin or irinotecan as the first-line treatment for advanced colorectal cancers and these have significantly improved the response rates to 40-50% and prolonged overall survival.(1,2) Furthermore, novel biological agents including monoclonal antibodies such as cetuximab, which is an antibody against epidermal growth factor receptor (EGFR), and bevacizumab, which is an antibody against vascular endothelial growth factor, have been shown to provide additional clinical benefit for patients with metastatic colorectal cancers.(3-5) However, there are still a large number of patients who do not benefit from the present treatments because of anticancer drug resistance. Elucidating the mechanisms by which 5-FU resistance arises in colorectal cancer therefore remains an important issue for either overcoming or predicting such resistance.5-FU is an analog of uracil and is rapidly incorporated into the cells using the same transport system as uracil.(6) Subsequently, 5-FU is converted into active metabolites which disrupt the action of thymidylate synthetase (TS) and RNA synthesis. TS and 5-FUmetabolizing enzymes such as dihydropy...

The first year (December 2015 to November 2016) of IR2 after Akatsuki's successful insertion to an elongated elliptical orbit around Venus is reported with performance evaluation and results of data acquisition. The single-stage Stirlingcycle cryo-cooler of IR2 has been operated with various driving voltages to achieve the best possible cooling under the given thermal environment. A total of 3091 images of Venus (1420 dayside images at 2.02 μm and 1671 night-side images at 1.735, 2.26, and 2.32 μm) were acquired in this period. Additionally, 159 images, including images of stars for calibration and dark images for the evaluation of noise levels, were captured. Low-frequency flat images (not available in pre-launch calibration data) have been constructed using the images of Venus acquired from near the pericenter to establish the procedure to correct for the IR2 flat-field response. It was noticed that multiple reflections of infrared light in the PtSi detector caused a weak but extended tail of the point-spread function (PSF), contaminating the night-side disk of Venus with light from the much brighter dayside crescent. This necessitated the construction of an empirical PSF to remove this contamination and also to improve the dayside data by deconvolution, and this work is also discussed. Detailed astrometry is performed on star-field images in the H-band (1.65 μm), hereby confirming that the geometrical distortion of IR2 images is negligible.

A scanning tunneling microscope dedicated to in situ experiments under the irradiation of highly brilliant hard-X-rays of synchrotron radiation has been developed. In situ scanning tunneling microscopy (STM) observation was enabled by developing an accurate alignment system in ultrahigh vacuum. Despite the noisy conditions of the synchrotron radiation facility and the radiation load around the probe tip, STM images were successfully obtained at atomic resolution. Tip-current spectra were obtained for Ge nano-islands on a clean Si(111) surface by changing the incident photon energy across the Ge absorption edge. A current modification was detected at the absorption edge with a spatial resolution of the order of 10 nm.

A 74-year-old man was hospitalized for the investigation of fever and severe general fatigue. Laboratory examinations revealed severe leukocytosis, with a leukocyte count of 29 500/mm(3). Computed tomography, ultrasonography, and endoscopic retrograde cholangiopancreatography showed a pancreatic tumor with a diameter of 70 mm. We performed distal pancreatectomy with splenectomy and gastrectomy because there was invasion of the posterior wall of the stomach. The leukocyte count decreased to 16 900/mm(3) immediately following the operation, but it began to increase again a week later, ultimately reaching 213 000/mm(3). We measured the serum granulocyte-colony stimulating factor (G-CSF) concentration and the G-CSF expressions in the resected specimens with immunohistochemistry, the findings of which confirmed the diagnosis of G-CSF-producing pancreatic cancer. G-CSF-producing tumors are considered to be in a category of rare malignant diseases originating in various organs, which carry a poor prognosis. However, G-CSF-producing pancreatic cancer is extremely rare. On postoperative day (POD) 35, an intraabdominal recurrence was detected with marked leukocytosis, and on POD 42 the patient died without receiving postoperative cancer therapy.

We construct an independently driven double-tip scanning tunneling microscope (STM) for evaluating electrical conduction within the micrometer scale under an ambient condition. Each independently driven STM unit has on atomic resolution and the tip approaches an intended position within 10 mm2 on the surface with three course driving stages and a piezoelectric device which has a maximum scan area of 10 µm. The current flow between the two tips through the material can be detected in the range from 0.1 pA to 100 nA. The measurement of the resistivity of regiorandom poly(3-octylthiophene) thin films was demonstrated using this system.