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The mTOR inhibitor temsirolimus has antitumor and antiangiogenic activity against several carcinomas, yet few reports document the efficacy of temsirolimus against malignant pleural mesothelioma (MPM). Therefore, we evaluated the efficacy of temsirolimus and the antiangiogenic effect of temsirolimus in the treatment of MPM. We examined the efficacy of temsirolimus alone and the efficacy of the combination of temsirolimus and cisplatin or pemetrexed against four MPM cell lines using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The effect of temsirolimus on the production of proangiogenic cytokines by MPM cell lines was examined by enzyme-linked immunosorbent assay (ELISA). Expression of mTOR and proangiogenic cytokines in clinical specimens from MPM patients was determined by immunohistochemistry. Temsirolimus inhibited cell viability and suppressed cell proliferation of all MPM cell lines. Combined treatment with temsirolimus and cisplatin inhibited the viability of all MPM cell lines more effectively than temsirolimus alone. Temsirolimus strongly inhibited the phosphorylation of p70s6k, a downstream molecule of mTOR, in all MPM cell lines and led to an increase in the levels of cleaved caspase-3 in the H226 and Y-meso14 cells. Temsirolimus also inhibited the production of vascular endothelial growth factor (VEGF) and platelet-derived growth factor-AA (PDGF-AA). Phosphorylated mTOR and high expression of VEGF and PDGF were detected in 2 and 3, respectively, out of the 5 MPM specimens. These results suggest that temsirolimus has activity against MPM cells by inhibition of cell proliferation and angiogenesis, and may be beneficial for a subset of MPM patients with high mTOR expression.

In this paper, we aim to elucidate whether effects related to supply or demand contributed to the Japanese “credit crunch” in the 1990s. Using prefectural panel data, we estimate loan supply and demand functions and calculate their shifts. Our analysis reveals that demand-side effects contributed to the Japanese credit crunch to an equal or greater degree than supply-side effects. Further, we show that the credit crunch was not uniform across Japan, but was more severe in urban relative to rural prefectures. These findings suggest that traditional countermeasures in the banking sector that similarly affect all prefectures may not induce economic recovery. Given this, we assert that region-specific policies may be more appropriate.

MnSi1.7 layers have been successfully grown using a molten salt method. It was found that homogeneous MnSi1.7 layers with columnar domain structure can be grown on MnSi substrates. The dependence of the thickness and domain structure of the layers on the growth conditions was investigated. It was found that the deposited atoms, namely Si, were the dominant diffusion species, and the formation of Kirkendall voids was avoided for the silicidation reaction based on interdiffusion. The layer thickness could be controlled by the growth temperature and time, and was diffusion controlled. The interdiffusion coefficient was approximately 5 × 10−10 cm2/s for growth temperature of 900°C. The activation energy of interdiffusion was deduced to be approximately 1.1 eV for growth of the MnSi1.7 layers. This growth technique provides a simple and controllable method to grow large-area, high-quality MnSi1.7 layers.

A variety of nanostructured silicide bundles using abundant, non-toxic materials have been prepared. The CrSi2 nanowire, Mg2Si/MgO composite nanowire and Mg2Si nanowire bundles were synthesized using a Si substrate, a SiOx nanofiber bundle, and a Si nanowire array, respectively. The hexagonal MoSi2 nanosheet bundles were also synthesized using a MoS2 layered material as the template. The growth phenomena and the structural properties of the nanostructured materials have been investigated. In addition, the preparation of the CrSi2/SiOx radial nanowire structures is examined.

Acquired resistance to epidermal growth factor receptor–tyrosine kinase inhibitors (EGFR–TKIs), such as gefitinib and erlotinib, is a critical problem in the management of patients with EGFR mutant lung cancer. Several mechanisms have been reported involved in this acquired resistance, including hepatocyte growth factor (HGF) activation of an alternative pathway. PI3K and mTOR are downstream molecules of receptor tyrosine kinases, such as EGFR and Met, and are thought to be ideal targets for controlling various tumor types. We assessed whether BEZ235, a dual inhibitor of PI3K and mTOR, could overcome the EGFR–TKI resistance induced by HGF in an EGFR mutant lung cancer model. Exogenous and endogenous HGF triggered resistance to erlotinib in the PC-9 and HCC827, EGFR mutant lung cancer cell lines. BEZ235 alone inhibited the viability of PC-9 and HCC827 cells in vitro, irrespective of the presence or the absence of HGF. Using a xenograft model of severe combined immunodeficient mice with HGF-gene-transfected PC-9 cells (PC-9/HGF), we found that BEZ235 inhibited tumor growth, whereas erlotinib did not. BEZ235 monotherapy also inhibited the phosphorylation of Akt and p70S6K/S6RP, downstream molecules of PI3K and mTOR, respectively, as well as suppressing tumor-cell proliferation and angiogenesis of PC-9/HGF tumors. These results suggest that BEZ235, even as monotherapy, may be useful in managing HGF-induced EGFR–TKI resistance in EGFR mutant lung cancer.

Chromium disilicide (CrSi 2 ) nanostructures were grown by the exposure of Si substrates to CrCl 2 vapor at atmospheric pressure, and the growth condition dependence on the morphological and structural properties of CrSi 2 was systemically investigated. The various structures of CrSi 2 , such as microrods, nanowire bundles along with microrods and dendritic nanowire structures, have been grown. It was found that the Si substrate temperature and the quantity of the CrCl 2 source materials significantly affect the morphological and structural properties of the CrSi 2 structures. The structural evolution of CrSi 2 has been discussed on the basis of thermodynamic reactions, vapor deposition growth and dendritic growth phenomena. This growth process provides a simple and controllable method to grow novel nano-scaled structures of transition metal silicides for technological use.

The inhibition of fibril formation of amyloid β (Aβ) and the disaggregation of Aβ fibrils are the promising approaches for a medical treatment of Alzheimer's disease (AD) therapy. In this study, we investigated the effects of liposomes on dopamine-induced disaggregation of Aβ fibrils by using the variety of liposomes. The used liposomes were normal liposomes, raft-forming liposomes, charged liposomes and oxidized liposomes. Those liposome could accelerate the disaggregation rate of fibrils. From the comparison of normal and charged liposomes, a certain contribution of dopamine via an electrostatic interaction to the disaggregation was confirmed. From raft-forming and oxidized liposomes, we revealed a significant contribution of bound water to liposomes, which could assist the formation of the quinine-form of dopamine by a removal of its proton. It is, therefore, concluded that the membrane surface of liposomes is considered to be an adequate environment for the dopamine-induced disaggregation of fibrils.

Reversible dynamic control of structure is a significant challenge in molecular nanotechnology. Previously, we have reported a mechanically induced continuous (analog) conformational variation in an amphiphilic binaphthyl, where closing of molecular pliers was achieved by compression of a molecular monolayer composed of these molecules at the air-water interface. In this work we report that a phase transition induced by an applied mechanical stress enables discontinuous digital (1/0) opening of simple binaphthyl molecular pliers. A lipid matrix at the air-water interface promotes the formation of quasi-stable nanocrystals, in which binaphthyl molecules have an open transoid configuration. The crystallization/dissolution of quasi-stable binaphthyl crystals with accompanying conformational change is reversible and repeatable.

Experimental determination of VP of hcp-Fe can show potential candidates for major light elements in Earth’s inner core., Hexagonal close-packed iron (hcp-Fe) is a main component of Earth’s inner core. The difference in density between hcp-Fe and the inner core in the Preliminary Reference Earth Model (PREM) shows a density deficit, which implies an existence of light elements in the core. Sound velocities then provide an important constraint on the amount and kind of light elements in the core. Although seismological observations provide density–sound velocity data of Earth’s core, there are few measurements in controlled laboratory conditions for comparison. We report the compressional sound velocity (VP) of hcp-Fe up to 163 GPa and 3000 K using inelastic x-ray scattering from a laser-heated sample in a diamond anvil cell. We propose a new high-temperature Birch’s law for hcp-Fe, which gives us the VP of pure hcp-Fe up to core conditions. We find that Earth’s inner core has a 4 to 5% smaller density and a 4 to 10% smaller VP than hcp-Fe. Our results demonstrate that components other than Fe in Earth’s core are required to explain Earth’s core density and velocity deficits compared to hcp-Fe. Assuming that the temperature effects on iron alloys are the same as those on hcp-Fe, we narrow down light elements in the inner core in terms of the velocity deficit. Hydrogen is a good candidate; thus, Earth’s core may be a hidden hydrogen reservoir. Silicon and sulfur are also possible candidates and could show good agreement with PREM if we consider the presence of some melt in the inner core, anelasticity, and/or a premelting effect.

Phonons in iron pnictide materials were predicted to show large effects from magnetic ordering that had not been observed, and, indeed, the overall phonon dispersion has been in poor agreement with \textit{ab initio} calculations. By carefully detwinning a sample of SrFe${}_{2}$As${}_{2}$, clear phonon splitting was observed below ${T}_{N}$, allowing the authors to suggest an improved model for the phonon response for both the antiferromagnetically ordered phase below ${T}_{N}$ and the paramagnetic phase above ${T}_{N}$.

Although the EGF receptor tyrosine kinase inhibitors (EGFR-TKI) erlotinib and gefitinib have shown dramatic effects against EGFR mutant lung cancer, patients become resistant by various mechanisms, including gatekeeper EGFR-T790M mutation, Met amplification, and HGF overexpression, thereafter relapsing. Thus, it is urgent to develop novel agents to overcome EGFR-TKI resistance. We have tested the effects of the mutant-selective EGFR-TKI WZ4002 and the mutant-selective Met-TKI E7050 on 3 EGFR mutant lung cancer cell lines resistant to erlotinib by different mechanisms: PC-9/HGF cells with an exon 19 deletion, H1975 with an L858R mutation, and HCC827ER with an exon 19 deletion, with acquired resistance to erlotinib because of HGF gene transfection, gatekeeper T790M mutation, and Met amplification, respectively. WZ4002 inhibited the growth of H1975 cells with a gatekeeper T790M mutation, but did not inhibit the growth of HCC827ER and PC-9/HGF cells. HGF triggered the resistance of H1975 cells to WZ4002, whereas E7050 sensitized HCC827ER, PC-9/HGF, and HGF-treated H1975 cells to WZ4002, inhibiting EGFR and Met phosphorylation and their downstream molecules. Combined treatment potently inhibited the growth of tumors induced in severe-combined immunodeficient mice by H1975, HCC827ER, and PC-9/HGF cells, without any marked adverse events. These therapeutic effects were associated with the inhibition of EGFR and Met phosphorylation in vivo. The combination of a mutant-selective EGFR-TKI and a Met-TKI was effective in suppressing the growth of erlotinib-resistant tumors caused by gatekeeper T790M mutation, Met amplification, and HGF overexpression. Further evaluations in clinical trials are warranted. Mol Cancer Ther; 11(10); 2149–57. ©2012 AACR.

Cortical synaptic strengths vary substantially from synapse to synapse and exhibit a skewed distribution with a small fraction of synapses generating extremely large depolarizations. Using multiple whole-cell recordings from rat hippocampal CA3 pyramidal cells, we found that the amplitude of unitary excitatory postsynaptic conductances approximates a lognormal distribution and that in the presence of synaptic background noise, the strongest fraction of synapses could trigger action potentials in postsynaptic neurons even with single presynaptic action potentials, a phenomenon termed interpyramid spike transmission (IpST). The IpST probability reached 80%, depending on the network state. To examine how IpST impacts network dynamics, we simulated a recurrent neural network embedded with a few potent synapses. This network, unlike many classical neural networks, exhibited distinctive behaviors resembling cortical network activity in vivo. These behaviors included the following: 1) infrequent ongoing activity, 2) firing rates of individual neurons approximating a lognormal distribution, 3) asynchronous spikes among neurons, 4) net balance between excitation and inhibition, 5) network activity patterns that was robust against external perturbation, 6) responsiveness even to a single spike of a single excitatory neuron, and 7) precise firing sequences. Thus, IpST captures a surprising number of recent experimental findings in vivo. We propose that an unequally biased distribution with a few select strong synapses helps stabilize sparse neuronal activity, thereby reducing the total spiking cost, enhancing the circuit responsiveness, and ensuring reliable information transfer.

The hexagonal phase MoSi2 was grown using MoS2 powder as the source material by the molten salt method. The structural and morphological properties of the resultant silicides are characterized. As a comparison, the structural and compositional characterizations were made for the Mo-silicides grown on a Mo substrate and a Mo-Ti alloy compact. It was revealed that the homogeneity of the chemical composition of the silicides grown using MoS2 is improved, except for the existence of the Si source powders, though a small amount of S remained in the powder. The layered structure of MoS2 with a hexagonal crystalline structure would affect the growth morphology and enhance the formation of the hexagonal MoSi2. A simple growth procedure to fix the crystalline structure using an appropriate starting material under a preferable growth environment is proposed. [DOI: 10.1380/ejssnt.2012.55]

We have determined the density evolution of the sound velocity of dhcp-FeHx (x ≈ 1) up to 70 GPa at room temperature, by inelastic X-ray scattering and by X-ray diffraction. We find that the variation of VP with density is different for the ferromagnetic and nonmagnetic dhcp-FeHx, and that only nonmagnetic dhcp-FeHx follows Birch's law. Combining our results with Birch's law for iron and assuming an ideal two-component mixing model, we obtain an upper bound of the hydrogen content in the Earth's inner core, 0.23(6) wt.% H, corresponding to FeH0.13(3). The iron alloy with 0.23(6) wt.% H can satisfy the density, and compressional and shear sound velocities of the PREM inner core, assuming that there are no other light elements in the inner core.

Liquid As2Se3 undergoes the semiconductor-metal transition with increasing temperature when pressure is applied to avoid evaporation of the liquid. To investigate the atomic dynamics of liquid As2Se3, we have carried out inelastic x-ray scattering experiments of this system at 1073 K and 6 MPa and obtained the dynamic structure factor S(Q,E), from approximately 1.6 nm−1 to 11 nm−1, where Q and E are momentum and energy transfer, respectively. The excitation energy in the semiconducting state at 1073 K disperses as fast as the ultrasonic sound velocity at Q 2.9 nm−1 it disperses approximately 1.8 times faster. We analyzed S(Q,E) at 1073 K using a simple viscoelastic model and discussed Q dependence of the propagation of the acoustic mode.

Ubiquitylation of membrane proteins triggers their endocytosis at the plasma membrane and subsequent lysosomal degradation through multivesicular bodies (MVBs). A dominant-negative mutant SKD1/Vps4B caused an accumulation of ubiquitylated membrane proteins in MVBs. We have identified 22 membrane proteins whose trafficking is potentially regulated by ubiquitylation. Nine of them, including transferrin receptor (TfR), are indeed ubiquitylated and/or accumulated in MVBs in the cells expressing mutant Vps4. While the recycling route and iron-regulated expression of TfR are well characterized, the mechanism by which the degradation of TfR is regulated is largely unknown. We show that an excess of iron enhances both TfR's ubiquitylation and degradation in lysosomes. Probably, the up-regulated expression of ferritin, an endogenous iron-chelating molecule, attenuated the iron-induced degradation of TfR. Exogenously introduced lysine-less TfR, compared to the wild-type one, showed resistance to the iron-induced ubiquitylation and degradation, when endogenous TfR, which most certainly heterodimerizes with exogenous ones, was depleted with siRNA. These data suggest that the iron-induced ubiquitylation and degradation of TfR along with MVB pathway physiologically plays an important role in iron homeostasis.

In this paper, we discuss the structure of a forward-looking model of the Japanese economy, which has been jointly developed by the Institute of Economic Research, Kyoto University, and the Policy Research Institute, Ministry of Finance, and use the model to simulate policies for fiscal consolidation. In the simulation, we compared our results with those from the IMF fs MULTIMOD model (whose data and equation list are open to the public) as thoroughly as possible and verified the appropriateness of the simulation results of our macroeconomic model. The overall results are similar to those from the IMF model, and we confirmed that our model can grasp the mechanism in which an economic agent will smooth out economic activities in anticipation of any future shock.

コミュニティ型質問応答サイト(CQA) は，ユーザが自身の状況に応じた回答を得ることができる新たな情報獲得手段である．しかしCQA サイトに投稿された回答の質は様々であるため，そこから良質な回答を効果的に取り出す方法が必要である．そこで本研究は，Yahoo!知恵袋データを用いて複数判定者によって手動で良質回答を分析し，判定者らが良質回答の評価に用いた判定基準を特定した．

コミュニティ型質問応答サイト(CQA)は，ユーザが自身の状況に応じた情報を得ることができる新たな手段である．しかし投稿された回答の質は様々であるため，その中から良質な回答を選択する方法が求められている．そこで本研究は，まず Yahoo!知恵袋データにおける良質回答を人手で分析し，その結果に基づいて良質回答自動予測システムを構築した．具体的には，「恋愛相談」「パソコン」「一般教養」「政治」の4つのカテゴリからそれぞれ無作為に50問の質問を抽出し，判定者2名によって手作業で良質回答を決定した．次に，その結果を分析し，良質回答の特徴として「詳しさ」「根拠」「丁寧さ」に基づく機械学習システムを構築した．機械学習システムの評価結果は，「パソコン」と「一般教養」カテゴリでは判定者らを上回った．「恋愛相談」と「政治」カテゴリでは，機械学習システムの評価結果は判定者らとほぼ同じであった．以上の結果から，CQAアーカイブから自動的に良質回答を発見するシステムの可能性が示唆される．

Spike-timing dependent plasticity (STDP), a synaptic modification depending on a relative timing of presynaptic and postsynaptic spikes, has fascinated researchers in the fields of neurophysiology and computational neuroscience, because it is not only conceptually simple or biologically reasonable but is also versatile in neural network simulations. The STDP rule may be valid only under specific conditions, however. We propose herein a method that could find more natural and potent rules of synaptic plasticity.

Atomic motions and, especially, correlations in atomic motion over angstrom length scales are a sensitive probe of material properties: phonons in single crystals respond to the detailed interactions between atoms, including both short- and long-range forces, and screening thereof, while the atomic dynamics of liquids is intimately connected with nearly all aspects of liquid behavior. Scientific questions associated with measuring dynamics include the detailed nature of phase transitions, correlations of atomic motions with electronic or magnetic properties (superconductivity, ferro-electric behavior, magnetoelastic coupling, etc.), and also very practical issues, such as investigating elasticity. Not surprisingly, both from the point of view of basic science and for applications such as geology, there is strong desire to extend studies of atomic dynamics throughout material phase diagrams, into extreme conditions.

We investigate the dynamic structure factor of the melt of the well known glass former, As2Se3, using inelastic x-ray scattering for temperatures, T, [Formula: see text] K and momentum transfers Q from [Formula: see text] nm-1. An anomaly was observed at Q = 2.7 nm-1 ([Formula: see text] K) with, in the context of a simple model, both an abrupt change in frequency and an increased linewidth reminiscent of an anti-crossing in a solid. Comparison with structural information from reverse Monte Carlo modeling of x-ray diffraction data allows us to associate the disappearance of the anomaly at higher temperatures with a drop in the number of mechanical constraints per atom, n mc, to [Formula: see text] reminiscent of the threshold applicable for glass formation in rigidity theory. It is inferred that the surprising jump in the dispersion in the liquid may be correlated with a stiffness transition in a network glass.

Functional multineuron calcium imaging (fMCI) is a large-scale technique used to access brain function on a single-neuron scale. It detects the activity of individual neurons by imaging action potential-evoked transient calcium influxes into their cell bodies. fMCI has recently been used as a high-throughput research tool to examine how neuronal activity is altered in animal models of brain diseases, for example stroke, Alzheimer's disease, and epilepsy, and to estimate how pharmacological agents act on normal and abnormal states of neuronal networks. It offers unique opportunities to discover the mechanisms underlying neurological disorders and new therapeutic targets.

Background and Aims: Crohn's disease (CD) is a chronic inflammatory bowel disease with relapse and remission. CD patients are admitted to hospital when bowel inflammation flares up severely, which lowers their quality of life. Enteral nutrition (EN) with an elemental diet plays an important role in the treatment for CD patients in Japan, because of its few adverse effects, and it is thought to be effective in maintaining remission. We investigated the effectiveness of EN with an elemental diet with regard to the avoidance of hospitalization. Methods: A total of 268 patients with CD who visited hospital from 2003–2008 were enrolled. The relationship between the caloric content of an elemental diet and hospitalization as an end-point was examined retrospectively using Cox regression analysis. Cumulative non-hospitalization rates were calculated by the Kaplan–Meier method. Results: Of the 268 patients, 155 received an elemental diet providing 900 kcal/day or more. Among 237 patients with ileal involvement, 135 patients receiving an elemental diet providing 900 kcal/day or more showed a statistically significant improvement in cumulative non-hospitalization rate. Among 31 patients without ileal involvement, in contrast, the cumulative non-hospitalization rate did not differ among those receiving an elemental diet of less or more than 900 kcal/day. Conclusion: The use of an elemental diet of 900 kcal/day may be effective in avoiding hospitalization in CD patients with ileal lesions. This diet may be useful in improving the long-term convalescence of these patients.

Microbial population dynamics were investigated during the formation of nitrifying granules in an aerobic upflow fluidized bed (AUFB) reactor fed ammonia as a sole energy source. Analyses of clone libraries of 16S rRNA gene and the ammonia monooxygenase subunit A gene (amoA) revealed that although the clones obtained from the seed sludge were widely distributed among the ammonia-oxidizing bacteria (AOB) isolates, the community structure of AOB shifted towards the Nitrosomonas mobilis lineage as granulation proceeded. Quantitative fluorescence in situ hybridization showed that changes in the bacterial population occurred concomitantly with changes in nitrification performance and the size of granules. AOB associated with the N. mobilis lineage were predominant in the early stages as nitrifying granules formed (average diameter, 126 mm). In mature granules (average diameter, 270 mm), at least three types of AOB, N. mobilis, Nitrosomonas oligotropha, and Nitrosomonas europaea, formed different niches and coexisted. Nitrite-oxidizing bacteria (NOB) affiliated with Nitrospira spp. were detected in the start-up period, but were replaced by NOB affiliated with Nitrobacter spp. after granules formed.

本研究では，Q&A サイトにおけるベストアンサーを計算機が推定可能か検証した．まず最初に，人間の判定者によるベストアンサー推定実験を行った．ベストアンサー推定実験にはYahoo!知恵袋データを利用し，「恋愛相談」「パソコン」「一般教養」「政治」の4つのカテゴリからそれぞれ無作為抽出した50 問を使用した．判定者二人による推定結果の正解率(精度) は，「恋愛相談」では50%と52%(ランダム推定:34%)，「パソコン」では62%と58%(ランダム推定:38%)，「一般教養」では54%と56%(ランダム推定:37%)，「政治」では56%と60%(ランダム推定:35.8%) であった．次に，この実験結果を分析し，ベストアンサーを選ぶ要因として「詳しい」「根拠」「丁寧」を素性とする機械学習システムを構築した．判定者らと同じ50 問を用いた推定実験の結果，機械学習システムの精度は，「パソコン」では判定者らの結果を上回り(67%)，「恋愛相談」では判定者らの結果を下回った(41%)．「一般教養」と「政治」では機械学習システムと判定者らの結果はほぼ同等であった．

Nagata et al. recently developed high-impact polyketone/polyamide-6 (PK/PA) alloys and investigated their mechanical properties (Nagata et al. Polym. Prep. Jpn. 2006, 55, 4286−4287). This paper presents the results of investigations of their morphology, such as the domain size of PA and PK, features of crystalline phase of PK (the long period and thickness of lamellae are deduced), and the change in crystalline form of PA in the PK/PA alloys, using solid-state nuclear magnetic resonance (NMR), small-angle X-ray scattering (SAXS), and transmission electron microscopy (TEM). Solid-state 13C and 15N NMR results revealed that the γ crystalline phase of PA changes into a thermodynamically stable α crystalline phase after alloying with PK. The difference in the long period of lamellae of PK/PA alloys between dry and wet conditions is discussed. We conclude that the characteristic morphology of PK and humidity of the amorphous phase of PA in the wet condition are very important factors enabling the PK/PA alloys ...

Background/Aims: Ulcerative colitis (UC) mainly affects the colon and rectum, whereas the chronic inflammatory process in Crohn’s disease (CD) can affect any part of the gastrointestinal tract. Recently, however, upper gastrointestinal lesions have been reported in UC patients. In this study, we investigated the immunological status of the stomach in UC or CD patients. Methods: 26 patients each with UC, CD or functional dyspepsia (FD) underwent diagnostic upper gastrointestinal endoscopy, and biopsy specimens were obtained from the gastric antrum.The contents of interleukin (IL)-6 and IL-8 in the organ culture supernatants of antral mucosal tissues were measured with enzyme-linked immunosorbent assay. Results: Endoscopically abnormal findings in the stomach were more frequent in CD than in UC or FD patients. Mononuclear cell infiltration and IL-6 production in the gastric antrum did not significantly differ between UC and FD patients, but were higher in those with CD. There was no significant difference in neutrophil infiltration or IL-8 production between UC, CD, and FD patients. Conclusions: UC patients did not show the immunological abnormalities in the stomach seen in CD patients.

X-ray diffraction, small angle X-ray scattering and inelastic X-ray scattering measurements for fluid Hg in the wide density range up to the supercritical region have been carried out using synchrotron radiation at SPring-8. We obtained the static and dynamic structure factors as a function of temperature, pressure and density. Based on the results we found that there exist medium-range fluctuations accompanying the metal–non-metal transition in fluid Hg. The scale of the fluctuations was about 10 A in space and sub-picoseconds in time. We discuss the possibility that such structural instability induces the metal–non-metal transition in expanded fluid Hg.

The dynamic structure factor S ( Q , ω ) of liquid silicon has been measured using inelastic X-ray scattering. The data show that distinct longitudinal collective modes exist in this ‘non-simple’ liquid metal similar as in the so-called ‘simple’ metallic fluids as, e.g. the liquid alkalis. However, the Si-modes are considerably more strongly damped and in S ( Q , ω ) the corresponding excitation peaks cease to exist for momentum transfers of about half the structure factor maximum position. The degree of positive dispersion, in the Q - ω -relation of the modes is, however, similar as in the liquid alkalis, indicating that the microscopic viscosity is similar in l-Si and that the stronger damping may rather be related to the higher thermal diffusivity. Additionally, it is found that the shape of the quasielastic line close to the structure factor maximum deviates considerably from the shape found in simple liquid metals. This observation is related to the onset of short time correlations between colliding particles on the sub picosecond scale which is in accord with findings from ab initio computer simulations under similar conditions.

In this paper, we propose all-optical multifunctional logic gates for image information using photorefractive (PR) two-wave mixing. The optical setup is simply configured compared with the other all-optical logic gates for image information. The XOR-, OR-, and AND-operation are all-optically performed in the same optical setup through the transitional response of the PR medium. One can switch these logic operations simply by means of the on-off control of the signal and the pump beam illumination. We analyze the spatial distribution of beam intensity in these logic gates using a finite-difference beam propagation method (FD-BPM) and the crosstalk between adjoining pixels is examined from the result. We also experimentally verify that the XOR-, OR-, and AND-gates are realized in the same optical setup.

類推によって仮説を生成する発想支援システムを構築するための基礎研究として，我々は因果関係に類推を適用して仮説を生成し，その仮説の検証を試みた．基となる因果関係は， 我々が以前の研究で薬学分野の特許文献から抽出したものであって，手段の用語と効果の用語から構成されている．類推は，その因果関係の用語を他の類似した用語に置き換えることによって行った．ペプチドによる創傷治療効果，厚朴による抗炎症作用，ラクトフェリンによる感染防除効果の3 つの因果関係を用いて類推を行い，227 件の仮説を生成した．この227 件の仮説をライフサイエンス辞書を用いて検証し，91 件の仮説は類推として適切な結果であることを確認した．さらに，91 件の仮説の中から9 件の仮説をPubMed Central 及びPubMed で検証した結果，8 件の仮説は文献で報告されている．これらの結果は，本研究の類推によって生成された仮説は有効であることを示している．

A 65-year-old woman with left chest pain, back pain, and palpitation that had persisted for 2 months was referred to our hospital. Computed tomography of her chest showed an anterior mediastinal tumor with mediastinal lymphadenopathy, left pleural effusion, and pericardial effusion. Endobronchial ultrasound-guided transbronchial needle aspiration of the subcarinal lymphadenopathy was performed. The pathological findings and other examinations such as bone scintigraphy suggested advanced thymic cancer (stage IV b according to the Masaoka classification of thymic epithelial tumors). The patient was treated with combination chemotherapy of carboplatin(area under the curve [AUC]=6, 656 mg/body, day 1) and weekly paclitaxel (70 mg/m², 100 mg/body, days 1, 8, and 15). After 4 cycles of chemotherapy, a partial response was achieved and the pericardial effusion disappeared. The patient did not experience any severe toxicity, except for grade 1 nausea, grade 2 anemia, and grade 2 alopecia. Weekly paclitaxel combined with carboplatin appears to be a useful regimen with minimal toxicity for advanced thymic cancer.

Inelastic X-ray scattering measurements at 25 MPa using synchrotron radiation were carried out for semiconducting liquid Se at high temperatures up to 1673 K. The excitation energy of the acoustic mode disperses approximately 10-50 % faster than the ultrasonic sound velocity in the observed temperature range while the ultrasonic sound rapidly slows down with increasing temperature. We carried out X-ray scattering measurements and found that the average coordination number at 1673 K is 1.3, indicating that the high temperature liquid consists of short chain molecules. These results suggest that weakening of the interatomic interaction is correlated with breaking of polymeric chain molecules.

ワンチップマイコンを用いて, 簡便な計測方法で筋の硬さを評価できる小型筋硬度計の開発を目的とする．本小型筋硬度計では，圧子によって筋を押し込むときの押し込み量を直線型ポテンショメータで，反力をフォースセンサで計測し，AD変換して数学モデルによる近似を行って硬さの指標を算出する．測定者による計測値のばらつきを調べたところ，有意水準5%で有意な差は認められなかった．衣服による影響は，Tシャツの上から計測しても皮膚を直接計測する場合と比較して有意な差は認められなかった．上腕二頭筋および僧坊筋を対象として，収縮レベルと筋の硬さの指標の関係を調べたところ，収縮レベルによって筋の硬さの指標は有意に変化した．

The participation of pharmacists in various aspects of cancer therapy is highly necessary, among them cancer pain relief, countermeasures against adverse drug reactions to anticancer drugs, and risk management. In the present study, we investigated the proposals made by pharmacists to physicians regarding the administration of opioids and adjuvant analgesics for the purpose of pain relief in cancer patients and questions from physicians on this subject.The subjects were 28 patients (14 males and 14 females) and 72 proposals on 7 matters were made to physicians, including 24 proposals on administration method, 20 on dose, and 12 on rescue dose. The physicians adopted 44 of the proposals (61.1%), and 34 of them (77.3%) were beneficial to the patients. The physicians asked 16 questions concerning 5 matters. Seven questions concerned converted dose, the most frequent topic of questions. Next came questions about rescue dose, rescue method, administration method and dose.In conclusion, the participation of pharmacists in cancer pain treatment could achieve more rapid pain relief and improve patients' QOL. Pharmacists should therefore make sure that they understand methods of treating cancer pain and actively participate in relieving it.

Small angle X-ray scattering (SAXS) measurements for expanded fluid Hg have been carried out in wide density region including the metal-non-metal (M-NM) transition region at 9.0g cm-3and the liquid-vapor critical region at 5.8g cm-3using synchrotron radiation at SPring-8. We could observe the liquid-vapor critical scattering intensity in fluid Hg with good statistics and also SAXS intensity in the M-NM transition region. The latter result suggests that characteristic fluctuations are induced in the M-NM transition in expanded fluid Hg.

SKD1 belongs to the AAA-ATPase family and is one of the mammalian class E Vps (vacuolar protein sorting) proteins. Previously we have reported that the overexpression of an ATPase activity-deficient form of SKD1 (suppressor of potassium transport growth defect), SKD1(E235Q), leads the perturbation of membrane transport through endosomes and lysosomes, however, the molecular mechanism behind the action of SKD1 is poorly understood. We have identified two SKD1-binding proteins, SBP1 and mVps2, by yeast two-hybrid screening and we assign them as mammalian class E Vps proteins. The primary sequence of SBP1 indicates 22.5% identity with that of Vta1p from Saccharomyces cerevisiae, which was recently identified as a novel class E Vps protein binding to Vps4p. In fact, SBP1 binds directly to SKD1 through its C-terminal region (198-309). Endogenous SBP1 is exclusively localized to cytosol, however it is redirected to an aberrant endosomal structure, the E235Q compartment, in the cells expressing SKD1(E235Q). The ATPase activity of SKD1 regulates both the membrane association of, and assembly of, a large hetero-oligomer protein complex, containing SBP1, which is potentially involved in membrane transport through endosomes and lysosomes. The N-terminal half (1-157) of human SBP1 is identical to lyst-interacting protein 5 and intriguingly, SKD1 ATPase activity significantly influences the membrane association of lyst protein. The SKD1-SBP1 complex, together with lyst protein, may function in endosomal membrane transport. A primary sequence of mVps2, a mouse homologue of human CHMP2A/BC-2, indicates 44.4% identity with Vps2p/Did4p/Chm2p from Saccharomyces cerevisiae. mVps2 also interacts with SKD1 and is localized to the E235Q compartment. Intriguingly, the N-terminal coiled-coil region of mVps2 is required for the formation of the E235Q compartment but not for binding to SKD1. We propose that both SBP1 and mVps2 regulate SKD1 function in mammalian cells.

The dynamic structure factor, S(Q,ω), of dense Hg vapour has been measured by high resolution inelastic x-ray scattering for densities of 3.0, 2.1 and 1.0 g cm−3 corresponding to 0.52, 0.36 and 0.17 times the critical density, respectively, and for momentum transfers between 2.0 and 48 nm−1. Analysis of the longitudinal current–current correlation function in the framework of generalized hydrodynamics reveals that the frequencies of the collective excitations increase faster with Q than estimated from the macroscopic speed of sound. The ratios of the frequencies were found to be 1.27 at 3.0 g cm−3, 1.12 at 2.1 g cm−3 and 1.10 at 1.0 g cm−3. The sound velocity obtained from the present experiments is well reproduced by a wavenumber dependent adiabatic sound velocity, which means that the collective modes remain in the spectra of dense Hg vapour.

We are the first group to succeed in measuring the dynamic structure factor S(Q,ω) of liquid Si close to melting using high-resolution inelastic x-ray scattering. The spectra clearly demonstrate the existence of propagating short wavelength modes in the melt with a Q–ω relation similar to those in other liquid metal systems. A specific variation of the quasi-elastic line shape with increasing Q is observed close to the structure factor maximum. This observation is related to the onset of atomic correlations on the sub-picosecond timescale in the vicinity of a metal-to-insulator transition. Such observations have been made previously only in computer simulations of metallic systems with increasing covalent character. Our data provide the first experimental evidence for these ultrashort density correlations.

Nitrate uptake rate was determined in the East China Sea by a simulated in situ 15 N incubation technique during four cruises representing different seasons in the period from 1993 to 1996. Stations were occupied on an observational line extending from the inner continental shelf to the adjacent oceanic water in the Pacific. The nitrate uptake rate integrated over the euphotic zone was higher on the average on the continental shelf (56 mg N m −2 d −1 ) than at the outer waters of the shelf-break and pelagic regions (21 mg N m −2 d −1 ). Both seasonal and spatial variations were larger on the shelf. Uptake rates were low in summer when the water columns were stratified. Nitrate in the summer surface waters was found to be almost completely depleted by determination with a chemiluminescence technique, and kinetic uptake experiments conducted concurrently suggested severe limitation of uptake due to the low nitrate concentrations. Uptake rates were also low in well-mixed water columns in winter and spring when the water temperature was low. High rates of uptake were observed in a spring bloom as well as at some of the inner-shelf stations in autumn. In the latter case, high phytoplankton biomass was accompanied by detectable amounts of nutrients and by lower salinity at the surface of the stratified water columns. Chlorophyll specific uptake capacity was higher and was significantly correlated with water temperature at a group of stations mostly on the shelf, while the capacity was lower and unaccountably varied at other stations. An empirical prediction model of nitrate uptake from chlorophyll concentration, temperature, light intensity, and nitrate concentration was developed and applied to these data.