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Why do humans search for better alternatives when a familiar trained procedure is sufficient to solve the problem? Such a question is important in explaining the flexibility of human thinking. This study investigated whether the finder of an alternative procedure intentionally seeks to access information irrelevant to the trained procedure while solving a problem using the trained procedure. The results show that finders intentionally sought more information irrelevant to the trained procedure, even when solving a problem using the procedure. In addition, differences in intentional search may be caused by resistance to the reinforcement of fixation on the trained procedure. This study provides evidence that the discovery of alternatives involves the tendency to intentionally search for information irrelevant to a familiar solution.

It is essential to consider the fluidity of a debris-flow front when calculating its impact. Here, we flume-tested monogranular and bigranular debris flows, and compared the results to those of numerical simulations. We used sand particles with diameters of 0.29 and 0.14 cm at two mixing ratios, of 50% and 50% (5:5), and 30% and 70% (3:7), respectively. Particle segregation was recorded using a high-speed video camera. We evaluated the fronts of debris flows at 0.5-s intervals. We then numerically simulated one- dimensional debris flows under the same conditions, and we used the mean particle diameter when simulating mixed-diameter flows. For monogranular debris flows, the experimental and simulated results were in good agreement in terms of flow depth, front velocity, and flux, but the bigranular debris flows were not well-simulated; the simulated flow depth was less than that found experimentally, and the front velocity and flux were greater. The differences may be attributable to the fact that the dominant shear stress was caused by the concentration of smaller sediment particles in the lower flow layers; such inverse gradations were detected in the debris flow bodies. In this situation, most shear stress is supported by smaller particles in the lower layers; the debris-flow characteristics become similar to those of monogranular flows. Consequently, the calculated front velocities were underestimated; particle segregation at the front of bigranular debris flows did not affect fluidity either initially or over time.

Table S1. Sequences of siRNA oligonucleotides. Table S2. Sense and antisense primers for real-time PCR (DOCX 29Â kb)

Doripenem (DRPM) is a relatively new drug belonging to the carbapenem antibiotic group. We hypothesized that the pharmacological characteristics of DRPM could make it useful in the treatment of severe acute pancreatitis (SAP). We investigated the usefulness of continuous regional arterial infusion (CRAI) with DRPM and protease inhibitors for SAP. Two hundred and forty-two patients with SAP were admitted to Showa University Hospital between November 2002 and June 2013. Of these, 53 patients were treated with CRAI with carbapenem antibiotics and nafamostat mesilate (NM), a serine protease inhibitor, via the celiac and superior mesenteric arteries. Clinical outcomes were evaluated retrospectively in 34 patients treated with DRPM and 19 patients undergoing non-DRPM therapy (meropenem n=11, imipenem n=6; biapenem n=2). The median time to commencement of oral intake was significantly shorter in the DRPM than non-DRPM group (9 vs 14 hospital days, respectively; P

Cell viability in C-MSC and C-MSCγ. TUNEL staining for apoptotic cells was performed using the DeadEnd™ Fluorometric TUNEL System (Promega, Madison, WI, USA). (A) Confocal immunofluorescence images of TUNEL (green) and nuclei (blue) in C-MSC or C-MSCγ. Upper panel shows lower magnification (bar = 200 μm) and the lower panels indicates higher magnification (bar = 50 μm). (B) The graphs show the percentage of TUNEL-positive apoptotic cells. Values represent means ± S.D. of three cultured C-MSCs. Similar results were obtained from three independent experiments. C-MSC clumps of a mesenchymal cell/extracellular matrix complex (C-MSC) cultured in growth medium for 3 days, C-MSCγ (50) C-MSC stimulated with 50 ng/mL of IFN-γ for 24 h, TUNEL TdT-mediated dUTP nick-end labeling. Figure S2. IFN-γ increased IL-10 mRNA expression, but not its protein production in C-MSC. (A)Time course study. C-MSCs were exposed to IFN-γ (10 ng/ml) for the indicated time. (B and C) Dose course study. C-MSCs were treated with or without various doses of IFN-γ (10, 50, 100 ng/ml) for 24 h. (A and B) IL-10 mRNA expression level was evaluated by real-time PCR as described in the “Methods” section. Sequence of primers for IL-10 was 5’-TCAAACTCACTCATGGCTTTGT-3’ (forward) and 5’-GCTGTCATCGATTTCTTCCC-3’ (reverse). The plot shows the ratio of IL-10 mRNA to GAPDH mRNA. Values represent means ± S.D. of four cultures. (C) The IL-10 protein production in culture supernatant was measured by IL-10 ELISA kit (Peprotech) following the manufacturer’s instruction. Data are the means ± S.D. of four cultures. GAPDH glyceraldehyde-3-phosphate dehydrogenase, IDO indoleamine 2,3-dioxygenease, IFN interferon, IL interleukin (PDF 378 kb)

We investigated the safety and utility of endoscopic removal of common bile duct stones (CBDS) in the elderly. In all, 253 patients with CBDS who underwent endoscopic retrograde cholangiopancreatography (ERCP) between January 2007 and December 2011 at Showa University Hospital were evaluated retorspectively. The median age of the patients was 75 years ; thus, we divided patients into two groups, those aged ≥ 75 years (Group A ; n ＝ 134) and those aged ＜75 years (Group B ; n ＝ 119). Patients in Group A had significantly higher rates of endoscopic sphincterotomy in palliative ERCP (24.8% vs. 10.7%; p ＝ 0.008) and palliative removal of CBDS (34.8% vs. 20.9%; p ＝ 0.015) than patients in Group B. However, the median dose of flunitrazepam was significantly lower for patients in Group A than Group B (1 vs. 1.4 mg, respectively ; p ＜ 0.001). The rate of use of pentazocine (18.5% vs. 54.7%; p ＜ 0.001) and scopolamine butylbromide (6.2% vs. 23.9%; p ＜ 0.01) was significantly lower in Group A patients, whereas the use of glucagon was significantly higher in this group (43.8 vs. 15.4%; p ＜ 0.001). There were no significant differences in the rate of successful endoscopic removal of CBDS, treatment time, complications, and the recurrence of CBDS between the two groups. Endoscopic removal of CBDS in the elderly is a safe procedure with good outcomes if the appropriate treatment is selected.

Diabetes mellitus (DM) is observed in patients with autoimmune pancreatitis (AIP). The development of DM in AIP is believed to be due to blood flow obstruction of the endocrine gland that accompanies pancreatitis, as well as injury to the islets caused by inflammation. The latter is called insulitis and the detailed mechanisms underlying its development are not yet clear. The aim of the present study was to elucidate the mechanisms involved in the development of insulitis in AIP using aly mice as an animal model of AIP: results in aly/aly male mice, as the AIP group, were compared with those inaly/+ male mice as a control group. Mice in both groups were killed between 16 and 48 weeks of age, and pancreatitis and insulitis were evaluated histologically. Inflammatory and endocrine cells were evaluated by immunofluorescence staining with anti-CD4, anti-CD8, anti-CD11b, and anti-CD11c antibodies, as well as immunohistochemical analyses using insulin and glucagon antibodies. Plasma levels and the pancreatic content of interferon (IFN)-γ (as a Th1-secreted cytokine) and interleukin (IL)-4 (as a Th2-secreted cytokine) were determined. Pancreatitis was seen in aly/aly mice from 16 weeks of age and it developed gradually thereafter. Insulitis also developed gradually and was seen in mice after 24 weeks of age in association with a decrease in the number of islets. CD11c+ cells and CD4+ T cells were seen to infiltrate into the islets. Although the number of β-cells decreased with time, the number of α-cells was maintained until mice were 48 weeks of age. IFN-γ content peaked in mice at 16 weeks of age and declined rapidly from 20 weeks. There were two peaks in IL-4 content, one at 16 weeks and the other at 32 weeks, suggesting an association between IL-4 content and advanced insulitis after 32 weeks. In conclusion, the results suggest that insulitis in AIP is induced predominantly by the infiltration of CD11c+ cells and CD4+ T cells into the islets, and progression is facilitated by the imbalance of the activation of Th2 rather than Th1. Furthermore, insulitis in AIP predominantly involves β-cells rather than α-cells.