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Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive carcinoma with poor prognosis. Its poor prognosis is ascribed to the extensive fibrotic stroma. Pancreatic stellate cells (PSCs) are major contributors to PDAC fibrosis. Type 2 diabetes (T2D) is an established risk factor for PDAC. The common mechanistic link might be the accumulation of advanced glycation end-products (AGEs) and the signaling through receptor for advanced glycation end-products (RAGE), the receptor for AGEs. Nevertheless, the role of RAGE in PSCs activation was not evaluated in PDAC with T2D. First, PSCs were isolated from male obese T2D model, db/db (db) and db/m (C) mice at 12 weeks of age. mRNA expression of the makers for PSCs activation like TGF-β1, αSMA and collagen type1A1 were significantly increased in PSCs isolated from db compared to C (p Disclosure C. Uchida: None. H. Mizukami: None. K. Kudo: None. Y. Yamamoto: None. Funding Japan Society for the Promotion of Science (JP17K17579)

Cyclin D2 (CCND2) is an essential cell cycle regulator of rodent pancreatic β cells, while its expression in human islets is still controversial in the past studies. It may be because few proliferative β cell is generally present in human adult islets. In contrast, expansion of β cell population mainly depends on a cell proliferation in human perinatal islets. Therefore, CCND2 is expected to be implicated in β cell proliferation in human perinatal islets. The aim of this study is to explore the implication of CCND2 in proliferation of human perinatal β cells. We evaluated pancreata of 39 autopsy cases from prenatal 24 weeks old to postnatal 19 years old. The subjects were divided into fetus (F: prenatal 24-31 weeks), infant (I: 0-1 years), child (C: 2-12 years) and adolescence (A: 13-19 years). Quintuple-immunohistochemistry (IHC) for glucagon, insulin, somatostatin, pp and Ki-67 was performed for the measurement of islet cell volume density (V) and cell replication status. Double-IHC for insulin with CCND2, 5-hydroxy tryptophan (5-HT) and p16 were performed. Double positive cells for each staining were counted. Morphometric analysis revealed that Vα and Vβ were increased with maturation. Ki-67 positivity for α and Δ cells was the highest in F (p90%) and I (>90%). Thereafter, its expression was dramatically declined in C and A (2.25±1.4%). 5-HT was highly expressed in perinatal subjects but not in C and A. Conversely, p16 expression was minimum before adolescence and its expression was evident in A. Our results clearly suggested that CCND2 could be implicated in the development of human β cell population in perinatal stage. The expression of CCND2 might be independently regulated by 5-HT and p16, while other factors may be implicated in the expression mechanism. To elucidate the regulation mechanism of CCND2 in human islets may lead to develop a novel strategy for diabetes treatments. Disclosure S. Osonoi: None. H. Ichinohe: None. K. Kudo: None. S. Yagihashi: None. H. Mizukami: None.

Xanthine oxidase (XO), a potent inducer of reactive oxygen species, catalyzes purine metabolism. XO is expected to be implication of the macrophage activation. XO is also expressed in the peripheral nerve system, while its role in diabetic polyneuropathy (DPN) has not been clarified. We explored the implication of XO in DPN of db/db mice (db/db) treating with XO-inhibitor, topiloxostat (To). C57BL6 mice (C57) and db/db (5 wks of age) were daily treated with 1mg/kg (dbT1) and 2mg/kg (dbT2) To (per os) for 8 wks. During experimental period, peripheral nerve function was monitored. At end, serum and dissected sciatic nerves and dorsal root ganglia (DRG) served for evaluation of uric acid metabolism. Primary culture of DRG neuron was performed to evaluate the effects of To on neurite outgrowth in vitro. To improved significant delay of nerve conduction velocities and elevation of threshold for tail flick test in db/db in a dose dependent manner (p As a conclusion, increase in XO activity in serum and DRG may be implicated in the pathophysiology of DPN in db/db. Activation of XO in serum may directly exacerbate neuronal injury for DRG in DPN. To has a beneficial effect on DPN through its specific property to suppress serum XO activity. Disclosure H. Ichinohe: None. H. Mizukami: None. S. Osonoi: None. K. Kudo: None. S. Yagihashi: None.

AIMS Parasympathetic nerve (PN) signaling plays a crucial role in the maintenance of pancreatic β-cell volume density (Vβ). PN may be pathologically affected in diabetic polyneuropathy (DPN). However, the association between the reduction of PNs in islets and Vβ and the therapeutic effects of a DPP4 inhibitor (DPP4i) and an SGLT2 inhibitor (SGLT2i) in nonobese type 2 diabetes mellitus (T2DM) Goto-Kakizaki rats (GK) have not been investigated. MATERIALS AND METHODS We divided 5-week old male GK and Wistar rats (W) into a DPP4i-treated group (GKTe), SGLT2i-treated group (GKCa), and combination-treated group (GKCaTe). After 25 weeks, the pancreata was pathologically evaluated. RESULTS Vβ in GK was significantly decreased (p < 0.01 vs. W), whereas Vβ was the most well preserved in GKCaTe (p < 0.05 vs. GKTe), followed by GKTe (p < 0.05 vs. GK). The decreased amount of PNs in the islets and intraepidermal nerve fiber density (IENFD) in GK was significantly improved in the treated groups compared with GK (p < 0.05 vs. GKCa and GKTe and p < 0.01 vs. GKCaTe). PN density and IENFD were significantly correlated with Vβ (r = 0.55, p < 0.01 and r = 0.54, p < 0.01, respectively). IENFD was identified as a surrogate marker for the prediction of Vβ (cutoff value, 16.39). CONCLUSIONS The combination therapy of DPP4i and SGLT2i improved Vβ accompanied by PNs density and IENFD. IENFD was proportionally correlated with Vβ. Therefore, the prevention of DPN development may be concurrently beneficial for the preservation of Vβ in nonobese T2DM.

Alveolar rhabdomyosarcoma (ARMS) is a type of primitive round cell tumor that mainly develops in adolescents and young adults. Immunohistochemically, the expression of myogenic markers is a key clue for pathological diagnosis, and an aberrant expression of neuroendocrine markers and/or cytokeratin has also been reported. Therefore, an unusual clinical course complicated with aberrant neuroendocrine expression may make the diagnosis of ARMS difficult. In this report, we present a case of ARMS that developed in the skin of the abdominal wall in an elderly patient; the tumor cells expressed neuroendocrine markers. ARMS should be considered as a differential diagnosis of primitive round cell tumors in elderly patients and it is essential to confirm concurrent myogenic differentiation and PAX3/PAX7–FOXO1 fusion gene expression to make a pathological diagnosis. Keywords: Alveolar rhabdomyosarcoma, Primitive round cell tumor, Neuroendocrine marker, PAX3/PAX7–FOXO1 fusion gene, High-sensitivity RT-PCR

In this work, a thermal molding technique is proposed for the fabrication of plastic electronics on curved surfaces, enabling the preparation of plastic films with freely designed shapes. The induced strain distribution observed in poly(ethylene naphthalate) films when planar sheets were deformed into hemispherical surfaces clearly indicated that natural thermal contraction played an important role in the formation of the curved surface. A fingertip-shaped organic thin-film transistor array molded from a real human finger was fabricated, and slight deformation induced by touching an object was detected from the drain current response. This type of device will lead to the development of robot fingers equipped with a sensitive tactile sense for precision work such as palpation or surgery.

For more than four decades, issues pertaining to the development of intercultural relationships between international and domestic students in university settings have received scholarly attention. However, there appears to be lack of research exploring the extent to, and the manner in which the individual and environmental dimensions interact with one another to co-create this development. This review addresses this gap by scrutinising English-language refereed journal articles from an ecological and person-in-context perspective. The review, involving a constructionist thematic analysis of systematically searched and screened papers, identified the few empirical studies from that perspective, the vague operationalisation of intercultural relationship development, and the methodological limitations of the empirical work. It also generated content-related themes of the individual–environmental interactions in the development of intercultural relationships. The review concludes by suggesting multiple areas of inquiry that warrant further empirical investigations, and by calling for the amplification and refinement of the research methodologies.

Pancreatic branch of vagus nerve (pvn) signaling plays a pivotal role in the maintenance of islet β cell volume density (Vβ). In type 2 diabetes (T2D), small fibers in the epidermis is decreased by diabetic insult. It is not still uncovered yet, however, that the reduction of terminal pvn fibers is associated with Vβ in T2DM. Herein, we explored the association between islet pvn fiber density and Vβ. We recruited non-obese spontaneous T2D Goto-Kakizaki (GK) rats and control Wistar rats (W) at 5 weeks of age. GK was divided into DPP-4 inhibitor (DPi)-treated group (GTe) (10mg/kg teneligliptine), SGLT2 inhibitor (SGi)-treated group (GCa) (10mg/kg canagliflozin) and both treated group (GTeCa). During experimental period, 2g/kg oral glucose tolerance test (OGTT) and glucose-stimulated insulin secretion test (GSIS) was performed. At end, pancreata were underwent for the pathological evaluation. OGTT in GK was attenuated (p Disclosure H. Mizukami: None. D. Guo: None. K. Takahashi: None. S. Osonoi: None. K. Kudo: None. S. Yagihashi: None.

Development and growth of islet endocrine cell volume are assumed to mainly depend on cell proliferation. In addition, the partial contribution of islet neogenesis and chromogranin A positive hormone negative cell (CPHN cell) is recently clarified. Detailed evaluation for the islet cell development and growth, however, is not well explored linking to the change of cell replication, neognesis and CPHN cell for each type of endocrine cells in human specimens. For this purpose, we recruited human autopsied pancreata, aged from 24 weeks old to 19 years old (n=32). Formalin-fixed paraffin embedded sections from pancreatic body were used for immunohistochemistry (IHC) and immunofluorescence (IF) analysis. The subjects were divided into 4 groups, Fetus (F: 24-31 weeks), Infant (I : 0-1 years), Child (C : 2-12 years) and Adolescence (A : 13-19 years). Quintuple-IHC with antibodies for glucagon, insulin, somatostatin, pp and Ki-67 was performed for the measurement of islet cell volume density (V) and replication status. Vαand Vβwere increased with age. Vβin A was more abundant than in F (p Disclosure S. Osonoi: None. H. Mizukami: None. K. Takahashi: None. K. Kudo: None. S. Yagihashi: None.

Activation of AGEs-RAGE signal at macrophage (Mφ) aggravates local inflammation in diabetic polyneuropathy (DPN). Mφ skewing toward pro-inflammatory phenotype (M1) is implicated in insulin resistance (IR) in fatty tissue, suggesting activation of RAGE at Mφ may similarly trigger IR in DPN. Generally, IR leads to axonal transport deficit in peripheral nerves. The aim of this study is to clarify the role of RAGE in the inflammation of DPN and its relationship to IR and axonal transport. Male C57BL/6 mice (W) and RAGE null mice (R) were recruited and rendered diabetic with streprozotocin (STZ) (D). DPN was confirmed by delay of nerve conduction velocities (NCVs) 8 weeks later of STZ injection. Polarization of Mφ in the sciatic nerve (SN) was determined by immunofluorescence (IF) and qPCR. IR of SN was evaluated by phospho (p)-AKT expression with stimulation of 5 unit insulin. Cell size of the dorsal root ganglia (DRG) neuron was morphometrically measured. For the retrograde axonal transport, DRG was quantitatively evaluated by IF for Fluoro-Gold (FG) 7 days after subcutaneous injection of FG into the hindlimb footpad. WD showed significant delay of NCVs (p Disclosure S. Osonoi: None. H. Mizukami: None. K. Takahashi: None. K. Kudo: None. K. Sango: None. S. Yagihashi: None. Funding Japan Society for the Promotion of Science

[Abstract] Carrier-injection and the succeeding pre-channel-formation dynamics in organic thin-film transistor was observed using time-domain reflectometry. Having previously analyzed the depth-wise variation in the initial carrier-injection from the contact electrode to the channel region, we focus here on the succeeding pre-channel-formation dynamics. We demonstrate that a hole concentration in the semiconductor/gate insulator interface increases until its electrical capacitance is filled through contact and access resistances. Thereafter, the injected-hole dis-tribution gradually spreads. A reduction in both contact and access resistances is crucial not only for the static characteristics of the field effect transistor but also the dynamical response.

Colorectal cancer is one of the most malignant neoplasms worldwide. Fucoxanthin is a carotenoid present in the chloroplasts of brown seaweeds. In the present study, the anticancer effects of fucoxanthin and its metabolite, fucoxanthinol, on 6 colorectal cancer cell lines and 20 tissue samples from surgically resected clinical colorectal cancer specimens were examined using a collagen-gel droplet embedded culture drug sensitivity test (CD-DST). The in vitro sensitivity to fucoxanthin, fucoxanthinol and the anticancer drugs is expressed as T/C (%), where T is the absorbance of cells which stained by neutral red treated with carotenoids and C is the absorbance of non-staining cells. Fucoxanthin and fucoxanthinol decreased the T/C (%) of Caco-2, WiDr, HCT116, and DLD-1 cell lines at doses of 20 µM. Fucoxanthinol also decreased the T/C (%) of SW620 cells, while the T/C (%) of Colo205 cells was not reduced by treatment with either carotenoid. Specifically, the T/C (%) of Caco-2 and WiDr cells, which were incubated in carotenoid-free medium for 6 days following treatment with 20 µM fucoxanthinol for 24 h, was markedly decreased to 1.4±0.2 and 12.0±0.3%, respectively. Furthermore, fucoxanthin and fucoxanthinol decreased the T/C (%) in colorectal cancer tissue samples. Notably, 20 µM fucoxanthinol treatment resulted in a higher proportion of colorectal cancer samples with a T/C (%) of

[Abstract] Organic sensor array was fabricated on a curved plastic film substrate of which Gauss curvature was finite. In this work, we proposed soft robot finger as one of the test cases of curved surface device that has artificial tactile sense by detecting slight deformation induced by touching an object. We made curved surface sensor array by thermal molding of planer device array on thin plastic film. Observed electrical current in each sensor pixel reflected strain distribution and time response induced by external slight displacement applied.

A gate-induced thermally stimulated current (TSC) on β′-(BEDT-TTF)(TCNQ) crystalline FET were conducted to elucidate the previously observed ferroelectric-like behaviors. TSC which is symmetric for the polarization of an applied VPG and has a peak at around 285 K was assigned as a pyroelectric current. By integrating the pyroelectric current, temperature dependence of the remnant polarization charge was obtained and the existence of the ferroelectric phase transition at 285 K was clearly demonstrated. We have tentatively concluded that the phase transition between dimer Mott insulator and charge ordered phase occurred at around the interface of organic crystal and substrate.

Testis lymphoma (diffuse large B cell lymphoma) metastasized to the gallbladder. The gall bladder is rarely involved in cases of the malignant lymphoma, and lymphoma metastasis from the testis to the gallbladder has not been previously reported. These reports may possibly change by the introduction of PET/CT. Furthermore, although it was a struggle to diagnose this particular case, there is a possibility that we may have been able to recognize metastasis from the testis at an earlier stage if PET/CT had been conducted.

This paper aims to contribute to the introduction and promotion of the snow and ice energy in cold and heavy snowfall regions in the future. To achieve this goal, we have developed a new concept for improvement of the performance of a snow and ice energy system. We propose the high-density snow storage (HSS) system and the urban cold spring (UCS) for the purpose of efficient energy use and cost saving. The snow density of conventional snow storage systems is 450–550 kg/m 3 . The high construction cost of these systems has been caused by a large space for the snow storage. The snow density is heightened to 750–800 kg/m 3 for the HSS system. UCS is the large HSS system for cities and communities. In 2002, HSS was applied to an actual office building in Oshu, Japan. The mass of stored snow was approximately 450 tonnes. The thermal insulation of snow storage room is 100–200 mm in thickness. Melt water is gathered in the cool water tank and is pumped to the heat exchanger. In 2003, space cooling was operated by using this HSS system. We evaluated the efficiency of storing snow and space cooling.

目的 : 私達は中皮腫の細胞診に特徴的な所見をスコア化し, 中皮腫診断におけるその有用性を検討した.方法 : 病理組織診断により中皮腫であることが確認された 19 例の体腔液を検討した. 腫瘍の発生部位は胸膜 17 例, 腹膜 2 例で, 上皮型 11 例, 二相型 3 例, 肉腫型 5 例だった. 性別は男性 17 例, 女性 2 例だった. 対照として, 任意に選択した癌性胸・腹膜炎 30 例, ClassIIIと診断された反応性中皮 13 例を検討した. 中皮腫に特徴的と考えられている項目に配点をしてその合計点数を数えた. スコアリングの項目と配点は以下のとおりである. 細胞の大小不同性 1 点, 全周性絨毛, ウィンドウ, ブレブを 1 点, 核異型 1 点, 大型好酸性核小体 2 点, 8 核以上の多核細胞 2 点, 相互封入像 1 点, 細胞密度が高いシート状細胞集塊 1 点, ミラーボール様の細胞集塊 1 点で合計点数を 10 点とした.成績 : 中皮腫では 10 点が 4 例, 9 点が 6 例, 8 点が 3 例, 7 点が 3 例, 6 点が 1 例, 5 点が 2 例で 4 点以下はなかった. 一方, 反応性中皮細胞は腹膜由来乳頭状癌の 1 例が 7 点と OK432 を用いた胸膜炎の 1 例が 4 点であるのを除くと, 全例 3 点以下だった.結論 : 本スコアリングは中皮腫の診断に有用だった.

Reactions of substituted acetone derivatives with acrylic acid esters (200 mol %) in the presence of t-BuOK (200 mol %) in t-BuOH-THF (1:1 by volume) turned out to proceed as a cascade process consisting of the first Michael addition, the second Michael addition, and the last Claisen reaction to afford 4,4-disubstituted cyclohexane-1,3-diones. Only more substituted enolates play the role of a Michael donor in this cascade process, and therefore the ketone took up two alkoxycarbonylethyl groups on the same carbon bearing more substituents. Such intermediates were followed by intramolecular Claisen reactions leading to cyclohexane-1,3-diones bearing quaternary stereogenic centers at C(4), which bears an alkoxycarbonylethyl group and the substituent of the starting acetone derivatives. Thus-obtained 4,4-disubstituted cyclohexane-1,3-diones were successfully employed for total syntheses of intricate alkaloids of biological interest such as (+)-aspidospermidine, (+/-)-galanthamine, (+/-)-lycoramine, and (+/-)-mesembrine, all featuring quaternary stereogenic centers. DFT calculations provided us with clear-cut explanations for the observed chemoselectivity of the cascade process involving ketone-based enolates under thermodynamically controlled conditions.

Although adenocarcinoma represents the vast majority of neoplasms of the large intestine, small cell undifferentiated carcinoma (SCUC) also arises from the colorectum. SCUC of the colorectum is highly malignant and shares the similarities in histologic characteristics, behavior, and histochemistry with SCUC of the lung. We report herein a case of SCUC in the ascending colon with rapid enlargement after resection. A 70-year-old male, who presented to a nearby physician with chief complaints of pain in the right lower quadrant, was referred to our hospital. We found a tumor mass that was approximately 15 cm in size in the right lower quadrant. Computed tomography (CT) images showed an irregularly shaped tumor, located inferior to the lower border of the right kidney and in the area of the ascending colon. By colonoscopy, we found a circumferential tumor of the ascending colon. A biopsy indicated it to be SCUC. The patient underwent right hemicolectomy. Two weeks after the resection, we palpated a tumor mass in the same area. The abdominal CT images showed a tumor mass that was approximately 10 cm in size. The tumor rapidly enlarged, and the patient died of multiple organ failure. SCUC is a tumor with a high malignant potential. Radical treatment cannot be achieved by surgical therapy alone and hence further studies of effective adjuvant therapy would be required.

We propose a double heterojunction type organic light emitting diodes (OLED) using zinc oxide (ZnO) films, which works as a transparent and electron injection layer. The crystal structure of the ZnO films as a function of Ar/O2 flow ratio and the basic characteristics of the OLED depending on the ZnO sputtering conditions are investigated. Excellent characteristics of novel OLED were obtained as high as 470cd/m2at 22V and 7.6mA/cm2. The results obtained here demonstrate that the vertical type organic light emitting transistor (OLET) using ZnO layer as an electron injection layer is expected as a key element for flexible sheet displays.

Organic semiconductor transistors are expected for flexible displays, information tags, and the like. However, organic transistors have some disadvantages of current density and speed of operation, because of their high resistivity and low carrier mobility. To improve their performance, it is valuable to analyze the mechanism of operation. We have compared characteristics of lateral- and vertical-type transistors using pentacene evaporated films. The pentacene lateral-type FET characteristics showed large variation due to fabrication parameters such as deposition rate, substrate temperature, and film thickness. It was found that evaporated pentacene thin films have large grain gaps, which disturb carrier flow along the channel formed pentacene film/SiO2 interface direction and make FET characteristics unstable. It is assumed that pentacene films are not suitable lateral-type transistors. Accordingly, we have fabricated vertical-type organic static induction transistors (SITs) using pentacene evaporated films. The pentacene SITs show high-speed operation (cutoff frequency of 7.5 kHz) at relatively low voltages. Further optimization of SIT structure will improve the device performance. © 2004 Wiley Periodicals, Inc. Electr Eng Jpn, 149(2): 43–48, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.10500