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Supplementary Figure 1 Legend from Down-regulation of PU.1 by Methylation of Distal Regulatory Elements and the Promoter Is Required for Myeloma Cell Growth

Supplementary Figure 1 Legend from Development of Gastric Tumors in ApcMin/+ Mice by the Activation of the β-Catenin/Tcf Signaling Pathway

Although several lines of evidence suggest the involvement of the Wnt pathway in the development of gastric cancers, the functional significance of the pathway in gastric carcinogenesis is still poorly defined. To examine the role of the Apc/β-catenin signaling pathway in the development of gastric cancers, we investigated the gastric mucosa of the ApcMin/+ mouse, which is a murine model for familial adenomatous polyposis, carrying a germ-line mutation at codon 850 of Apc. We found that aged ApcMin/+ mice spontaneously develop multiple tumors in the stomach, which are accompanied by loss of heterozygosity of Apc. Such tumors consisted of adenomatous glands with strong nuclear accumulation of β-catenin. Even a single adenomatous gland already showed nuclear accumulation of β-catenin, suggesting that Apc/β-catenin pathway is an initiating event in gastric tumorigenesis in ApcMin/+ mice. Myc and cyclin D1 expressions, which are transcriptional targets of β-catenin/Tcf, increased in the adenomatous lesions. Furthermore, β-catenin/Tcf reporter transgenic mice with ApcMin allele showed higher levels of the transcriptional activity of β-catenin/Tcf in the gastric tumors. We also treated ApcMin/+ and wild-type mice with N-methyl-N-nitrosourea (MNU), an alkylating agent that induces adenomas and adenocarcinomas in the stomach. Consequently, MNU-treated ApcMin/+ mice significantly enhanced the tumor development in comparison with ApcMin/+ mice or MNU-treated wild-type mice. Several gastric tumors in MNU-treated ApcMin/+ mice showed invasion into the submucosal layer. These results indicate that the Apc/β-catenin pathway may play an important role in at least subset of gastric carcinomas. In addition, ApcMin/+ mice combined with MNU could be a useful short-term model to investigate multistage carcinogenesis in the stomach. [Cancer Res 2007;67(9):4079–87]

β cells have a limited capacity for regeneration, which predisposes towards diabetes. Here, we show that, of the MYC family members, Mycl plays a key role in proliferation of pancreatic endocrine cells. Genetic ablation of Mycl causes a reduction in the proliferation of pancreatic endocrine cells in neonatal mice. By contrast, the expression of Mycl in adult mice stimulates the proliferation of β and α cells, and the cells persist after withdrawal of Mycl expression. A subset of the expanded α cells give rise to insulin-producing cells after this withdrawal. Transient Mycl expression in vivo is sufficient to normalize the hyperglycaemia of diabetic mice. In vitro expression of Mycl similarly provokes active replication in islet cells, even in those from aged mice. Finally, we show that MYCL stimulates the division of human adult cadaveric islet cells. Our results demonstrate that the induction of Mycl alone expands the functional β-cell population, which may provide a regenerative strategy for β cells.

A coherent Ising machine (CIM) is known to deliver the low-energy states of the Ising model. Here, we investigate how well the CIM simulates the thermodynamic properties of a two-dimensional square-lattice Ising model. Assuming that the spin sets sampled by the CIM can be regarded as a canonical ensemble, we estimate the effective temperature of the spins represented by degenerate optical parametric oscillator pulses by using maximum likelihood estimation. With the obtained temperature, we confirmed that the thermodynamic quantities obtained with the CIM exhibited a phase-transition-like behavior that better matches the analytical and numerical results than the mean field one., 6 pages, 3 figures

X-ray photoelectron spectroscopy (XPS) is among the most utilized analytical methods for nitrogen-doped carbon materials. Clarifying the assignments of nitrogen-doped carbon materials with different degrees of carbonization, which relates to conjugated systems, is essential to correlate structures with the performance of various applications, but such precise assignments were challenging. In this work, precise analyses were conducted to overcome the difficulty to assign the peaks of carbon materials with different degrees of carbonization, different edges, and various nitrogen-containing functional groups in graphene nanoribbons (GNRs), such as nitrile, pyridinic, primary with/without charges, secondary with/without charge, tertiary without charges (graphitic nitrogen), and quaternary nitrogen. Electrons donated from hydrogen and Madelung potentials showed a higher correlation to the peak shift of C1s and N1s XPS spectra than Mulliken charges on nitrogen. Zigzag edges showed a greater influence on the peak shift of tertiary amine (graphitic nitrogen) than armchair edges on XPS spectra. Besides, as the degree of carbonization is increased from aromatic compound-like structures to GNRs, the peak positions of C–N in C1s and N1s XPS spectra shifted to higher binding energies. This research proved that XPS could be applied to the precise structural analyses of nitrogen-containing carbon materials.

Previous studies have shown that phosphorylation of the retinoid X receptor-α (RXRα) is associated with the development of hepatocellular carcinoma (HCC). However, these findings were revealed using HCC cell lines that express phosphorylated-RXRα (p-RXRα) proteins; therefore, it remains unclear whether p-RXRα affects hepatocarcinogenesis in vivo. Therefore, to investigate the biological function of p-RXRα in vivo, we developed a doxycycline-inducible ES cell line and transgenic mouse, both of which overexpress the phosphomimetic mutant form of RXRα, T82D/S260D, in a doxycycline-dependent manner. We found that the development of liver tumors, especially high-grade adenoma and HCC, was enhanced in diethylnitrosamine (DEN)-treated T82D/S260D-inducible mice. Moreover, the increased incidence of liver tumors in the transgenic mice was attributable to the promotion of cell cycle progression. Interestingly, the expression of β-catenin protein and its target gene cyclin D1 was elevated in the liver tumors of DEN-treated T82D/S260D-inducible mice, concurrent with increased cytoplasmic and nuclear β-catenin protein expression, indicating its stabilization and transcriptional activation. These results indicate that p-RXRα promotes DEN-induced hepatocarcinogenesis in mice through the activation of the β-catenin signaling pathway, suggesting that p-RXRα may serve as a possible therapeutic target for HCC.

A metal-free covalent triazine framework (CTF) was synthesized from 2,4,6-tricyano-1,3,5-triazine (TCT) through open-system and liquid-phase synthesis using trifluoromethanesulfonic acid as both a ...

Preoperative assessment of surgery using high-quality images can help surgeons to achieve best result of treatment. With the advances in computer technology, interactive multimodality fusion images have been developed. The use of fusion images as a preoperative planning tool is described with its examples in illustrative cases of trigeminal neuralgia and hemifacial spasm microvascular decompression (MVD). Interactive computer graphics such as multimodality fusion method is a useful tool to preoperatively predict the need of bone exposure and configuration of blood vessels with its correlation to cranial nerves in MVD.

Oxygen-containing carbon materials have been studied extensively because of their excellent dispersibility, absorptivity, separability, and supportability of catalysts. However, structural control by existing top-down methods is almost impossible. Our group has demonstrated that phloroglucinol (PG, 1,3,5-trihydroxybenzene) can be a promising raw material to synthesize structurally controlled oxygen-containing carbon materials. In this study, in addition to PG, hexahydroxybenzene (HHB), which has more oxygen and high symmetry, was used as the raw material, and a Lewis acid catalyst, tris (pentafluorophenyl) borane (TPB), was used to enhance the structural control rate and the removability of catalysts from the carbonized samples. The solubility of heat-treated HHB was lower than that of heat-treated PG, but the oxygen content of heat-treated HHB was higher than that of heat-treated PG even at 673 K. By adding TPB to PG, dibenzofuran-like structures formed, and the structural control rate increased up to 93.6%. Besides, the content of fluorine in the catalyst was reduced to 0%, indicating that TPB can be a promising recyclable catalyst to promote the structural control rate of carbonized PG.

X-ray photoelectron spectroscopy (XPS) is among the most powerful techniques to analyse structures of nitrogen-doped carbon materials. However, reported assignments of (1) graphitic nitrogen (N)/substitutional N, quaternary N (Q–N), or tertiary amine (T–N) and (2) pyrrolic N/secondary amine or T–N are questionable. Most reports assign peaks at ca. 401 eV as Q–N or graphitic N, whereas raw materials in most of those works contain neither counter anion nor halogen. Besides, the peak at ca. 400 eV has been assigned as pyrrolic N, but the presence of N–H is generally not confirmed. In this work, it was clarified that one of the reasons for the prevailing ambiguous assignments is the presence of N in heptagonal and pentagonal rings. The peaks at 400.1–401.2 eV were determined to be T–N, but not Q–N by analyzing graphitized polyimide (with the oxygen content of 0.01 at% or lower and the hydrogen content of 0 at%) using Raman spectroscopy, XPS, X-ray diffraction, total neutron scattering, elemental analysis, and molecular dynamics simulation. Besides, it was revealed that the peak at 400.1 eV originated from T–N on 5-membered rings or 7- and 5-membered rings, but not pyrrolic N because graphite including no hydrogen was used for analysis.

The vapor-phase dehydration of 1,3-butanediol (1,3-BDO) to produce 1,3-butadiene (BD) was investigated over yttrium zirconate, Y2Zr2O7, which was prepared through a hydrothermal aging process. 1,3-...

Prostate squamous cell carcinoma (pSCC) rarely develops as a secondary cancer after treatment with low-dose-rate brachytherapy (LDR-BT). There is no established effective treatment for the disease condition. Herein, we present a 78-year-old man who developed pSCC 8 years after LDR-BT. He was subsequently selected to receive a combined multimodal treatment with high-dose-rate interstitial brachytherapy (HDR-ISBT), external beam radiation therapy, and chemotherapy for his pSCC. Eleven months later, he displayed no biochemical failure nor clinical radiographic recurrence. However, MRI detected a newly developed prostatic-rectal fistula (grade 4), and a colostomy was performed to relieve pain and inflammation. To our knowledge, this is the first report to perform a combined multimodal treatment with HDR-ISBT for pSCC suspected as a secondary cancer due to LDR-BT.

Carbonization process of pyromellitic dianhydride (PMDA)-4,4′-diaminodiphenyl ether (ODA)-type polyimide has been studied for decades. However, various reaction mechanisms have been proposed and the detailed mechanisms are still controversial. It is essential to understand the carbonized structures of PMDA-ODA-type polyimide before analyzing the defect structures in graphite. In this work, the carbonization mechanisms of polyimide heated at 1273 K or lower were unveiled and the methodology to analyze carbon materials containing nitrogen, oxygen, pentagons, and heptagons using computational spectral analysis combined with molecular dynamics simulation (ReaxFF) are exhibited. For example, the formations of isoimide and cyclic ether were estimated by ReaxFF, and the presence was supported by experimental and calculated X-ray photoelectron spectroscopy (XPS) and carbon-13 nuclear magnetic resonance (13C NMR) spectra of polyimide heated between 813 and 873 K. The formations of pentagons and heptagon, suggested by ReaxFF, were also supported by Raman and 13C NMR spectra of polyimide heated between 833 and 1273 K. This work also revealed that the previously reported structures were unstable and that amine in the basal plane was the most plausible structure in polyimide heated at 1073 K or higher, as clarified by XPS, ReaxFF, and the energy calculation.

The bromination reactivity of various types of polycyclic aromatic hydrocarbons (PAHs) with oxygen atoms and graphene with oxygen atoms was estimated by density functional theory calculation and experimentally clarified by analyzing bromination of PAHs using gas chromatography–mass spectrometry. In the experimental and theoretical bromination reactivity of PAHs, the presence of hydroxyl group increased the reactivity of PAHs because of electron-donating nature of the hydroxyl group but the other oxygen-containing functional groups such as lactone, ether, and ketone decreased the reactivity due to the electron-withdrawing nature of those groups. These effects of functional groups on the reactivity were also confirmed in graphene. The tendency of theoretical bromination reactivity of graphene was graphene with hydroxyl group > graphene with no group > graphene with lactone group > graphene with ether group > graphene with ketone group. Our study on the estimation of bromination reactivity of graphene edges provides the groundwork for the bromination of graphene edges.

For more than half a century, exploring a complete sequence of the oceanic crust from the seafloor through the Mohorovičić discontinuity (Moho) and into the uppermost mantle has been one of the most challenging missions of scientific ocean drilling. Such a scientific and technological achievement would provide humankind with profound insights into the largest realm of our planet and expand our fundamental understanding of Earth's deep interior and its geodynamic behavior. The formation of new oceanic crust at mid-ocean ridges and its subsequent aging over millions of years, leading to subduction, arc volcanism, and recycling of some components into the mantle, comprise the dominant geological cycle of matter and energy on Earth. Although previous scientific ocean drilling has cored some drill holes into old (> 110 Ma) and young (< 20 Ma) ocean crust, our sampling remains relatively shallow (< 2 km into intact crust) and unrepresentative of average oceanic crust. To date, no hole penetrates more than 100 m into intact average-aged oceanic crust that records the long-term history of seawater–basalt exchange (60 to 90 Myr). In addition, the nature, extent, and evolution of the deep subseafloor biosphere within oceanic crust remains poorly unknown. To address these fundamentally significant scientific issues, an international workshop “Exploring Deep Oceanic Crust off Hawai`i” brought together 106 scientists and engineers from 16 countries that represented the entire spectrum of disciplines, including petrologists, geophysicists, geochemists, microbiologists, geodynamic modelers, and drilling/logging engineers. The aim of the workshop was to develop a full International Ocean Discovery Program (IODP) proposal to drill a 2.5 km deep hole into oceanic crust on the North Arch off Hawai`i with the drilling research vessel Chikyu. This drill hole would provide samples down to cumulate gabbros of mature (∼ 80 Ma) oceanic crust formed at a half spreading rate of ∼ 3.5 cm a−1. A Moho reflection has been observed at ∼ 5.5 km below the seafloor at this site, and the workshop concluded that the proposed 2.5 km deep scientific drilling on the North Arch off Hawai`i would provide an essential “pilot hole” to inform the design of future mantle drilling.

Careful evaluation of the preoperative imaging for extracranial-intracranial bypass performed for conditions like intracranial stenosis and Moya disease is important. The traditional use of 2D imaging has a significant limitation for neurosurgeons, primarily to determine the optimal location of the recipient artery for performing the surgical bypass. Therefore, many neurosurgeons use 3D angiograms more frequently to overcome these shortcomings.We performed the preoperative evaluation of the possibility of performing an anastomosis between the superficial temporal artery and the middle cerebral artery (STA-MCA) bypass by synthesizing images of computerized tomography (CT), magnetic resonance imaging (MRI), and digital subtraction angiography (DSA) using AmiraThe 3D images prepared before surgery using this software showed good agreement with the intraoperative findings.Preoperative image processing using tools like Amira provide optimal information for good planning and communication for performing STA-MCA bypass and may become a helpful tool.

Background Little evidence surrounds the effectiveness of decision aids to encourage physicians’ understanding of patients’ subjective perceptions. This study aimed to evaluate the impact of using a patient-filled standard template to express patients’ views, preferences, or concerns to their physicians in a clinical decision-making setting, on patients’ perceived decisional conflict and post-decision regrets. Methods A pre-post quasi-experimental study with a six-month control period followed by a 12-month intervention period. Participants came from six teaching hospitals and two clinics in Japan. The target population included 150 patients affected by diabetes mellitus, hypertension, and/or dyslipidemia, whose physicians had recently suggested to start drug treatment as a medical option. In the control period, a booklet on general informed consent was distributed, while in the intervention period, a “template for shared decision-making” was also provided. Patients were asked to fill out the template, which was then attached to the electronic medical records. Results Two months after enrollment, the decision conflict and decision regret scales were mailed to the patients. Three months after enrollment, the decision status about starting drug treatment and the concordance between the patients’ decision status and initial medical recommendation were observed. Seventy-nine and seventy-one participants assigned to the control and intervention groups were enrolled. Fifty-five patient pairs generated by propensity score matching were analyzed. No significant difference was observed between both groups in the decision conflict scale’s subscale scores and decision regret scale scores. The relative risk of the patients with a decision status of “still considering” regarding starting drug treatment was 2.2 (95% CI, 1.02–4.9) in the intervention group. The concordance rate between the physicians’ recommendation for starting drug treatment at enrollment and the patients’ actual decision made was 78.2% and 90.9% in the control and intervention groups, respectively (relative risk = 1.5; 95% CI, 1.05–2.2). Conclusions Using a template document to express patients’ personal values and feelings to their physicians is associated with longer deliberation times in making decisions about starting drug treatment; this may lead to decisions that are closer to medical recommendations.

This multicenter and prospective study was performed to evaluate the efficacy of tadalafil on patient-reported bother for each symptom in men with lower urinary tract symptoms (LUTS).Men with LUTS received 5 mg of tadalafil daily for 4 weeks. We assessed change in symptom severity using both international prostate symptom score (IPSS), and overactive bladder symptom score (OABSS), as well as patient-reported quality of life (QOL: bother or satisfaction) for each symptoms using IPSS-visual analog scale (IPSS-VAS) and OABSS-VAS.We found significant improvements in total IPSS (P 0.001), including voiding symptoms (P 0.001), storage symptoms (P 0.001), and QOL (P 0.001). All VAS measures corresponding to symptoms in IPSS and OABSS also significantly improved (P 0.001). The most bothersome symptoms for each patient at baseline evaluated by VAS measures significantly improved (P 0.001). Patients whose most bothersome symptoms at baseline included IPSS-Q7 (nocturia) showed significantly smaller improvement of VAS measure after treatment than those without it (P = 0.024).Daily tadalafil significantly improved not only symptom severity of LUTS but also patient-reported QOL on each symptom.

Strong electron-phonon interactions are frequently considered the origin of the unique electrical and optical properties of lead halide perovskites. Electron-phonon interactions induce the formation of a polaron, which is a charge carrier dressed with a phonon cloud. The details of polaron formation are crucial for carrier transport since polaron formation leads to a larger effective mass of a carrier. Several mechanisms have been proposed regarding the physics of polaron formation in halide perovskites, but the details are still under active debate. While the Fröhlich interaction plays an essential role in ionic crystals, we also need to consider the strong phonon anharmonicity of halide perovskites that may lead to the formation of an unconventional polaron. In this review article, we discuss the uniqueness of perovskite semiconductors from the viewpoint of electron-phonon interactions. We review the experimental results and the proposed models concerning the effective carrier mass and carrier mobility. Finally, we briefly explain two physical phenomena related to strong electron-phonon interactions: strong anti-Stokes photoluminescence and slow hot-carrier cooling.