FACILE SYNTHESIS OF 2,3-DISUBSTITUTED PYRROLES FROM 2-SUBSTITUTED 1-PYRROLINES

2-Substituted-1-pyrrolines react with various arylaldehyde acetals in the presence of a Lewis acid and base to give 2-substituted 3-arylmethylidene-1-pyrrolines, which are transformed to 2,3-disubstituted pyrroles by base-catalyzed double-bond isomerization.ArticleHETEROCYCLES. 85(5):1187-1195 (2012)journal articl

Density fluctuations and confinement in the Nagoya Bumpy Torus (NBT-1M)

The stabilization of low-frequency density fluctuations is evidenced in the Nagoya Bumpy Torus (NBT-1M) [Plasma Physics and Controlled Nuclear Fusion Research (IAEA, Vienna, 1985), Vol. 2, p. 551] in the presence of microwave-heated hot-electron rings. Flute-type fluctuations, which are considered to be stabilized by the charge-uncovering effect of the rings, are found to cause large plasma losses, and to affect radial density profiles in the way that the lower fluctuation level yields the steeper density gradient. The particle confinement is, therefore, improved by the hot-electron rings to some extent, but is mainly determined by the plasma convection, which is expected from the discrepancy between density and potential profiles. It is also found that fluctuations in a toroidal plasma inside the ring grow when a weak negative ambipolar potential and a steep density gradient are formed, and are reduced to a low level when a deep potential well is achieved

Modulating effect of the PI3-kinase inhibitor LY294002 on cisplatin in human pancreatic cancer cells

<p>Abstract</p> <p>Background</p> <p>Chemoresistance is a serious problem in pancreatic cancer, but the mechanism of resistance and strategies against the resistance have not been elucidated. We examined the potential of the phosphatidylinositol 3-kinase (PI3K)/Akt inhibitor LY294002 to enhance the anti-tumor effect of cisplatin and investigated the mechanism of chemoresistance in pancreatic cancer cells using a combination therapy of cisplatin and LY294002, both <it>in vitro </it>and <it>in vivo</it>.</p> <p>Methods</p> <p>Cisplatin and LY294002, individually or in combination, were given to AsPC-1 and PANC-1 cell lines. Tumor growth, DNA fragments, and Akt phosphorylation were examined <it>in vitro</it>. To examine the therapeutic effect of cisplatin and LY294002, individually or combination an AsPC-1 tumor xenograft model was prepared for <it>in vivo </it>study.</p> <p>Results</p> <p>Cisplatin induced growth inhibition and Akt phosphorylation in pancreatic cancer cells. LY294002 also inhibited cell proliferation but without showing Akt phosphorylation. However, the combination therapy markedly increased cleavage of caspase-3 and cytoplasmic histone-associated DNA fragments compared to the results with cisplatin alone. In the <it>in vivo </it>study, blocking the PI3K/Akt cascade with LY294002 increased the efficacy of cisplatin-induced inhibition of tumor growth in nude mice, suppressing half the tumor growth with cisplatin alone. There were no detectable side effects in mice treated with combination therapy.</p> <p>Conclusion</p> <p>Our studies suggest that the PI3K/Akt pathway plays an important role in cisplatin resistance of pancreatic cancer cells. The augmentation of cisplatin with PI3K/Akt inhibitor may resolve the chemoresistance problem of cisplatin, and this might be a plausible strategy for achieving tolerance for chemotherapeutic agents in pancreatic cancer therapy.</p

Nuclear spin relaxation in ordered bimetallic chain compounds

A theoretical interpretation is given to recent proton spin relaxation-time (T_1) measurements on NiCu(C_7H_6N_2O_6)(H_2O)_3$\cdot$2H_2O, which is an ideal one-dimensional ferrimagnetic Heisenberg model system of alternating spins 1 and 1/2. The relaxation rate T_1^{-1} is formulated in temrs of the spin-wave theory and is evaluated by the use of a quantum Monte Carlo method. Calculations of the temperature and applied-field (H) dependences of T_1^{-1} are in total agreement with the experimental findings. T_1 behaves as $T_1^{-1}\propto H^{-1/2}$, which turns out an indirect observation of the quadratic dispersion relations dominating the low-energy physics of quantum ferrimagnets.Comment: 5 pages, 4 figures embedded, to appear in Phys. Lett.

Creating Classes for Developing the Concept of Functions : A System of Learning Activities for Drawing out Four Qualities Tied to Nurturing the Concept of Functions

本研究は，数・量・図形的要素を見出し，どのような関係があるのかを考え，そこにきまりを発見していく力を育成するために以下の研究を進めた。昨年度は，函数観念の育成につながる授業の中で引き出したい４つの姿である，①事象の中に数・量・図形的要素を見つけようとする姿，②どのような関係かを考えていこうとする姿，③関係の中にある法則を見つけようとする姿，④事象を関係で見ていこうとする姿を発達段階ごとに設定し，その４つの姿を引き出すことを目的とした学習活動を仕組む授業実践を積み重ねた。さらに，本年度は，「関数の考えの指導」の関数の考えの背景となる「物事を動的に見ようとする態度」に焦点をあて，４つの姿を引き出すこととする。それらの取り組みを小学校と中学校で統一して取り組むことで「中一ギャップ」や算数・数学への円滑な移行ができると考えた。その結果，単元の事前と事後，昨年と今年とでは４つの姿をについて，どの項目についても肯定的な回答であった。また，教師が意図的に関数の考えを授業の中で取り扱っていくことが，子どもに「関数の観念」を育んでいく上で効果的であり，小・中学校で統一した指導も可能であることが分かった。This study was conducted, as a means of nurturing the ability to discover set facts when seeking out numerical, volumetric, and graphical elements in pondering relationships. Last year, four of figure you want a drawer in the class, which leads to the development of the function concept has been pulled out. This year, the focus was placed on “attitudes for seeing things dynamically”, as a precursor to thinking about functions, and the instruction thereof. It was felt that unifying these efforts in elementary and junior high schools would relieve the “first-year gap”. The result of these efforts was a positive response to all four qualities in both years, before and after the teaching units. In addition, teachers’ deliberate treatment of the idea of functions in classrooms was effective in engendering the “concept of functions” in children, showing that it is possible to have a unified way of teaching in elementary and junior high schools

Oncolytic Virus-Mediated Targeting of the ERK Signaling Pathway Inhibits Invasive Propensity in Human Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDAC) cells have an exceptional ability to invade nerves through pronounced crosstalk between nerves and cancer cells; however, the mechanism of PDAC cell invasion remains to be elucidated. Here, we demonstrate the therapeutic potential of telomerase-specific oncolytic adenoviruses, OBP -301 and tumor suppressor p53-armed OBP-702, against human PDAC cells. Highly invasive PDAC cells exhibited higher levels of phosphorylated extracellular signal-regulated kinases 1 and 2 (ERK1/2) expression independent of KRAS expression; ERK1/2 inhibitor or small interfering RNA (siRNA) treatment significantly reduced the migration and invasion of PDAC cells, suggesting that the ERK signaling pathway is associated with the invasiveness of PDAC cells. OBP-702 infection suppressed ERK signaling and inhibited PDAC cell migration and invasion more efficiently than OBP-301. OBP-702 also effectively inhibited PDAC cell invasion even when invasiveness was enhanced by administration of motility stimulators, such as nerve and neurosecretory factors. Moreover, noninvasive whole-body imaging analyses showed that OBP-702 significantly suppressed tumor growth in an orthotopic PDAC xenograft model, although both viruses were equally effective against subcutaneous tumors, suggesting that OBP-702 can influence the orthotopic tumor microenvironment. Our data suggest that oncolytic virus-mediated disruption of ERK signaling is a promising antitumor strategy for attenuating the invasiveness of PDAC cells

Intrinsic double-peak structure of the specific heat in low-dimensional quantum ferrimagnets

Motivated by recent magnetic measurements on A3Cu3(PO4)4 (A=Ca,Sr) and Cu(3-Clpy)2(N3)2 (3-Clpy=3-Chloropyridine), both of which behave like one-dimensional ferrimagnets, we extensively investigate the ferrimagnetic specific heat with particular emphasis on its double-peak structure. Developing a modified spin-wave theory, we reveal that ferromagnetic and antiferromagnetic dual features of ferrimagnets may potentially induce an extra low-temperature peak as well as a Schottky-type peak at mid temperatures in the specific heat.Comment: 5 pages, 6 figures embedded, Phys. Rev. B 65, 214418 (2002