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Although tyrosine kinase inhibitors markedly improve the clinical outcome of chronic myeloid leukemia (CML), blast crisis in CML (CML-BC) still has a poor prognosis. Many chromosomal abnormalities have been reported in CML-BC and may contribute to therapeutic resistance, disease progression, and prognosis. Herein, we report a rare chromosome abnormality with der(16)t(1;16)(q12;q11.2) in CML-BC. It has been demonstrated that this chromosomal abnormality is associated with disease progression and poor prognosis in other malignancies, such as Ewing sarcoma. A 70-year-old man with CML who had been treated with imatinib and dasatinib was admitted to our hospital after complaining for several weeks of fatigue and dyspnea and diagnosed with CML-BC. His tumor cells presented additional chromosomal abnormality with der(16)t(1;16)(q12;q11.2), which has never been reported in CML cases. We successfully treated him using cytotoxic agents combined with ponatinib, and this chromosome abnormality was detected via G-banding. Our patient has lived for over 8 months without any progression with ponatinib treatment alone. Although the biological function of this chromosomal abnormality remains unclear, the satellite DNA of 1q12, which induces genomic instability in other malignancies, and the loss of 16q may contribute to the disease progression of CML in this case. In conclusion, this paper is the first to report on the case of CML-BC with der(16)t(1;16)(q12;q11.2).

Troponin (Tn) is composed of three subunits (TnI, TnC and TnT) that bind Ca2+ and regulate striated muscle contraction in vertebrates. TnT’s function has been extensively described in vertebrates, but its role has been obscure in molluscan muscles. Our previous work indicated that the TnC and TnI subunits work in adductor phasic muscle, but not in catch muscle. Here, we have characterized TnT from the Japanese bivalve pearl oyster Pinctada fucata to start to explain the function of Tn in molluscan muscle contraction. We determined the primary structure of the full-length TnT protein from the P. fucata adductor muscle (Pifuc-TnT), and found that it is composed of 316 amino acid residues with a predicted molecular mass of 37.4 kDa. Multiple sequence alignment showed that Pifuc-TnT has an extension of >60 residues at the C-terminus that are not present in vertebrate TnTs, including known TnTs from other mollusks. Pifuc-TnT gene structure predictions using Splign alignment of the cDNA generated in this study and genome sequences indicated that Pifuc-TnT consists of 13 exons. Start and stop codons are located in exons 2 and 12, respectively. Quantitative real-time PCR revealed that the Pifuc-TnT gene was predominantly expressed in adductor phasic muscle, weakly in adductor catch muscle, slightly in gill, and not at all in mantle and foot. These findings suggest that TnT plays a regulatory role in adductor phasic muscle contraction, but not in catch contraction. Isothermal titration calorimetry revealed that unlike vertebrate TnTs, Pifuc-TnT does not interact with P. fucata tropomyosin-1 nor with tropomyosin-2. These findings in P. fucata imply that Tn functions differently in molluscan muscle than it does in vertebrates.

Troponin is a thin filament-associated regulator of vertebrate striated muscle contraction. Troponin changes its structure upon Ca2+ binding to troponin C, one of the subunits of troponin, allowing myosin to interact with actin. We recently elucidated the molecular characteristics of the Japanese pearl oyster Pinctada fucata troponin C (Pifuc-TnC), revealing the possibilities that Pifuc-TnC and vertebrate muscle TnC play dissimilar roles in muscle contraction. Pifuc-TnC has four EF-hand motifs, but, unlike vertebrate TnC, only one (site IV) was predicted to bind Ca2+. To confirm the number of Ca2+-binding sites in Pifuc-TnC and whether Ca2+ binding induces a conformational change, we purified the full-length protein and a variant, Pifuc-TnC-E142Q (that has a mutation in the predicted Ca2+-binding site of site IV), following their expression in laboratory E. coli. Isothermal titration calorimetry demonstrated Ca2+ binding to Pifuc-TnC, whereas Pifuc-TnC-E142Q was unable to bind Ca2+, confirming that site IV is the only Ca2+-binding site in Pifuc-TnC. Pifuc-TnC eluted in a later fraction from a gel filtration column in the presence of Ca2+ compared with the condition when Ca2+ was absent. In contrast, the elution profiles of Pifuc-TnC-E142Q were equivalent in both the presence and absence of Ca2+, suggesting that Ca2+ binding to Pifuc-TnC induces a conformational change that delays its elution from the column. UV-absorption spectral analysis revealed that binding of Ca2+ to Pifuc-TnC caused an increase in absorption at a wavelength of approximately 250 nm, possibly because phenylalanine residues had been exposed on the surface of the molecule as a result of a conformational change. Differential scanning calorimetric analyses of Pifuc-TnC showed aggregation in the presence of Ca2+ in accordance with an increase of temperature, but no aggregation was seen in the absence of Ca2+. In combination, these findings suggest that Ca2+ binding to site IV induces a conformational change in Pifuc-TnC.

New amphiphilic transition metal complexes with helical structures self-assembled to form disk-like units in 20 wt % EtOH/water. d–d transition bands in the visible-near IR region were used to prob...

Heterodyne-detected vibrationally electronically doubly resonant chiral sum-frequency generation (HD-DR chiral SFG) spectra were observed for the first time on monolayers. Langmuir monolayers of R- and S-binaphthyl amphiphiles on water exhibited complex chiral vibrational sum frequency generation (VSFG) spectra whose amplitudes were approximately the same, but whose phases were different by π. By comparing the electronic resonance profiles of the chiral VSFG signal amplitude and phase with simulations based on a nonadiabatic resonance Raman theory, we concluded that the chiral VSFG signals from the monolayers originated not from the antisymmetric Raman tensor but from the symmetric one. This is the first experimental evidence that the symmetric Raman tensor indeed contributes to the chiral VSFG signals from oriented monolayer systems.

We report an “ionic liquid state” substance composed of superoxide radical anions (O₂⁻) and crownether-coordinated potassium cations. A binary mixture of 18-crown-6-ether (18C6) and potassium superoxide (KO₂) becomes liquid above ca. 38°C. The coordination of 18C6 to K⁺ and the presence of O₂⁻ were confirmed in the liquid state by Raman spectroscopy measurements. Below 38°C, however, the 18C6-KO₂ mixture does not form a complex but undergoes phase separation to parent phases of solid 18C6 and KO₂, because the ion-dipole interaction between K⁺ and 18C6 is overwhelmed by the ion-ion interaction between K⁺ and O₂⁻. In other words, the pair of O₂⁻ and 18C6-coordinated K⁺ only appears above the melting point of pure 18C6, to form an “ionic liquid state”. Among radical-containing ionic liquids, the liquid 18C6-KO₂ mixture has high fluidity and comparable conductivity. The findings show stabilization of superoxide radical anions at liquid state with high concentration, which could be used for many radical reactions., This was Paper 1417 presented at the Cancun, Mexico, Meeting of the Society, October 5–9, 2014. This paper is part of the JES Focus Issue on Progress in Molten Salts and Ionic Liquids.

This study introduces a novel monoclonal anti-α9 integrin antibody (MA9-413) with human variable regions, isolated by phage display technology. MA9-413 specifically binds to both human and mouse α9 integrin by recognizing a conserved loop region designated as L1 (amino acids 104–122 of human α9 integrin). MA9-413 inhibits human and mouse α9 integrin-dependent cell adhesion to ligands and suppresses synovial inflammation and osteoclast activation in a mouse model of arthritis. This is the first monoclonal anti-α9 integrin antibody that can react with and functionally inhibit both human and mouse α9 integrin. MA9-413 allows data acquisition both in animal and human pharmacological studies without resorting to surrogate antibodies. Since MA9-413 showed certain therapeutic effects in the mouse arthritis model, it can be considered as a useful therapy against rheumatoid arthritis and other α9 integrin-associated diseases.

Real-space motions of molecules and ions in an aqueous solution of sodium chloride are studied with high-resolution inelastic x-ray scattering. We focus on the correlated dynamics of water molecules and salt ions, instead of the instantaneous structure and the rotational and reorientation dynamics that have been studied using scattering techniques and optical spectroscopy, respectively. The real-space analysis in terms of the Van Hove function illustrates the effect of salt ions to slow down the local correlated dynamics of surrounding water in the hydration shells.

Journal article Gradual and reversible tuning of the torsion angle of an amphiphilic chiral binaphthyl, from −90° to −80°, was achieved by application of a mechanical force to its molecular monolayer at the air–water interface. This 2D interface was an ideal location for mechanochemistry for molecular tuning and its experimental and theoretical analysis, since this lowered dimension enables high orientation of molecules and large variation in the area. A small mechanical energy (50 %) in the area of the monolayer and modification of binaphthyl conformation. Single-molecule simulations revealed that mechanical energy was converted proportionally to torsional energy. Molecular dynamics simulations of the monolayer indicated that the global average torsion angle of a monolayer was gradually shifted. "This work was partly supported by World Premier International Research Center Initiative (WPI Initiative), MEXT (Japan), the Core Research for Evolutional Science and Technology (CREST) program of Japan Science and Technology Agency (JST) (Japan), and JSPS KAKENHI Grant Number 26104541, 26790003, and 259503." peer-reviewed 2016-06-12

Spontaneous neuronal activity is present in virtually all brain regions, but neither its function nor spatiotemporal patterns are fully understood. Ex vivo organotypic slice cultures may offer an opportunity to investigate some aspects of spontaneous activity, because they self-restore their networks that collapsed during slicing procedures. In hippocampal networks, we compared the levels and patterns of in vivo spontaneous activity to those in acute and cultured slices. We found that the firing rates and excitatory synaptic activity in the in vivo hippocampus are more similar to those in slice cultures compared to acute slices. The soft confidence-weighted algorithm, a machine learning technique without human bias, also revealed that hippocampal slice cultures resemble the in vivo hippocampus in terms of the overall tendency of the parameters of spontaneous activity.

Superoxide anion O2 – is obtained by one electron reduction reaction of the oxygen molecule (O2 + e → O2 –)[1]. Since O2 – has one unpaired electron it is also used for the radical polymerization initiator for organic synthesis[1]. Generally O2 – is dissolved in aprotic solvents because it decomposes in the presence of H2O or protic solvents (e.g. 2O2 − + H2O → O2 + HO2 − + OH− and 2HO2 − → O2 + 2OH−). It is known that potassium superoxide (KO2) has little solubility even in dimethylsulfoxide, a highly polar aprotic organic solvent. Researcher has demonstrated that the solubility of KO2 in aprotic solvents increases dramatically by adding 18-crown-6-ether[1]. Nevertheless, the maximum solubility of superoxide is only about 20 mmol dm–3 in aprotic solvents. Spectacularly improving the concentration of superoxide anion, it could be one method that we synthesize novel superoxide compounds in the liquid state at room temperature while the reported quaternary alkylammonium superoxides are all solid at room temperature[4]. In this work, we tried to synthesize superoxide ionic liquids by complexation of K+ cation to decrease charge density of cations substantially. KO2, a yellow solid at room temperature, was chosen as an O2 − source and mixed with two kinds of chain ethers i.e. diethylene glycol dimethyl ether (G2) and tetraethylene glycol dimethyl ether (G4), and a macrocyclic ether i.e. 18-crown-6-ether. Mixture of KO2 and each ether was stirred at 500 rpm and heated under several situations in a glove box of Ar atmosphere (H2O, O2 < 1 ppm). Molar ratio of KO2 : ether was 2 : 1 for G2, 1 : 1 for G4, and 1 : 1 for 18-crown-6-ether. It was visually judged from the absence of discoloration and precipitation of the mixture if these two substances chemically reacted without substantial decomposition of O2 –. The coordination of 18-crown-6-ether to K+cation was checked with Raman spectrometry. Figure 1 schematically illustrates possible states of K+ cation complxed with three kinds of ethers : (a) G2, (b) G4, and (c) 18-crown-6-ether (K+ : G2 = 1 : 2, K+ : G4 = 1 : 1, K+ : 18-crown-6-ether = 1 : 1 in molar). KO2 and G2 or G4 did not result in a liquid state even at 60 °C. By contrast, the mixture of KO2 and 18-crown-6-ether became clear yellow liquid at 50 °C (see Figure 2 (b)). The melting point was 41 ~ 42 °C. We speculate that the strong coordination ability of 18-crown-6-ether to K+cation contributed to the sizable decrease in charge density of cations and thereby the melting point of the superoxide became near room temperature. Figure 3 demonstrates the Raman spectra for (a) uncomplexed liquid 18-crown-6-ether and (b) liquid [(18-crown-6)K]O2 measured at 50 °C. For the latter case we observed evolution of sharp peaks between 860 and 900 cm–1 in comparison of the former case. It is attributed to the conformation change of 18-crown-6-ether from Ci conformation to D3d conformation[5]. This strongly suggersts that 18-crown-6-ether coordinates K+to form much weaker Lewis acidic cation. [1] D. T. Sawyer et al., Acc. Chem. Res., 14, 393 (1981). [2] K. Yamaguchi et al., Inorg. Chem., 25, 1289 (1986). [3] K. Fukuhara et al., J. Mol. Struct., 224, 203 (1990).

Because superoxide anion is easily decomposed by the presence of proton, it is known that superoxide anion only dissolves in specific highly polar aprotic solvents such as dimethylsulfoxide. Organic solvents are dangerous due to their high volatility and flammability, while ionic liquids possess inflammability, nonvolatility, and high ion conductivity. Additionally, in the area of organic synthesis, there is a potential for a new reaction media different from existing organic reaction media. Therefore, it would be attractive to use ILs as a new reaction media and an electrolyte of batteries. In this study, we studied solubility and stability of superoxide anion in five kinds of ILs. It was found that P14,6,6,6Cl was the most suitable solvent in terms of the solubility and stability of superoxide anion.

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.

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.

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]

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.

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.

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.

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.

X-ray diffraction measurements for expanded fluid mercury have been carried out in a wide density region from the liquid to dense vapour region using synchrotron radiation at SPring-8. We have developed a new high-pressure vessel with seven windows to collect the scattered X-rays for energy-dispersive X-ray diffraction measurements under high temperature and high pressure, and present the new data. It was found that the reliability of the structure factors, S(k), and the accuracy of the pair distribution functions, g(r), are much better. Reliable relations of the coordination number and the correlation distance with the density of fluid Hg were obtained. Structural changes with decreasing density are discussed in relation to the metal–non-metal transition in fluid Hg based on the new results.

Small angle X-ray scattering measurements for supercritical fluid metals such as selenium and mercury have been carried out using synchrotron radiation at SPring-8 to study density fluctuations near the liquid–vapor critical points. The absolute value of the scattering intensity was estimated from measurements on compressed He gas, a method developed using the in-house X-ray source at Hiroshima University. The observed scattering intensity of fluid selenium increases when one approaches the isochore of the critical density with decreasing pressure. The correlation length of the density fluctuations and the long wave length limit of the structure factor, S (0), are deduced to be 16.5 A and 31 at 1680 °C and 459 bar using the Ornstein–Zernike formula. Based on these data, the density fluctuations in fluid selenium are discussed.

X-ray diffraction measurements for expanded fluid selenium have been carried out in a wide density region from the liquid to the dense vapor using synchrotron radiation at SPring-8. We have developed a new high pressure vessel with seven windows to measure scattered X-rays and the reliability of the structure factors becomes much better. The measurements were made in the semiconductor–metal (SC–M) transition region from 600 to 1500 °C near 800 bar. The structure factors in the dense vapor region from 300 to 441 bar at 1650 °C are obtained for the first time. Structural changes in the SC–M transition region and the structure of the dense selenium vapor are discussed, based on these new results.

We investigated transverse acoustic (TA) phonons in iron-bearing magnesium oxide (ferropericlase) up to 56 GPa using inelastic x-ray scattering (IXS). The results show that the energy of the TA phonon far from the Brillouin zone center suddenly increases with increasing pressure above the spin transition pressure of ferropericlase. Ab initio calculations revealed that the TA phonon energy far from the Brillouin zone center is higher in the low-spin state than in the high spin state; that the TA phonon energy depend weakly on pressure; and that the energy gap between the TA and the lowest-energy-optic phonons is much narrower in the low-spin state than in the high-spin state. This allows us to conclude that the anomalous behavior of the TA mode in the present experiments is the result of gap narrowing due to the spin transition and explains contradictory results in previous experimental studies.

Energy-dispersive X-ray diffraction measurements using synchrotron radiation at SPring-8 for fluid Se have been carried out at temperatures up to 1650 °C and pressures up to 878 bar, including the dense vapour region, to investigate the structural change in the semiconductor-to-metal (SC–M) transition in expanded fluid Se. We obtained the structure factors, S ( k ), and the pair distribution functions, g ( r ), with a fairly good accuracy. Besides confirming the preservation of twofold-co-ordinated structure, the contraction of nearest co-ordination distance and the existence of asymmetry of the first peak in the g ( r ) in the metallic fluid region, it was found that the line shape of the first peak in the g ( r ) changes as well as the value of the first minimum in the g ( r ) increases obviously with increasing metallic properties. These results indicate that both the existence of different intrachain bonds and the interchain interaction are important for the mechanism of SC–M transition in fluid Se.

We report on the selective binding of 2-amino-5,6,7-trimethyl-1,8-naphthyridine (ATMND) to C-C mismatch present in the hairpin structures of (CCG)(n) trinucleotide repeats that are associated with neurological diseases; this binding is accompanied by significant fluorescence quenching of ATMND.

The eukaryotic small-subunit (SSU) ribosomal RNA (rRNA) has two evolutionarily conserved acetylcytidines. However, the acetylation sites and the acetyltransferase responsible for the acetylation have not been identified. We performed a comprehensive MS-based analysis covering the entire sequence of the fission yeast, Schizosaccharomyces pombe, SSU rRNA and identified two acetylcytidines at positions 1297 and 1815 in the 3' half of the rRNA. To identify the enzyme responsible for the cytidine acetylation, we searched for an S. pombe gene homologous to TmcA, a bacterial tRNA N-acetyltransferase, and found one potential candidate, Nat10. A temperature-sensitive strain of Nat10 with a mutation in the Walker A type ATP-binding motif abolished the cytidine acetylation in SSU rRNA, and the wild-type Nat10 supplemented to this strain recovered the acetylation, providing evidence that Nat10 is necessary for acetylation of SSU rRNA. The Nat10 mutant strain showed a slow-growth phenotype and was defective in forming the SSU rRNA from the precursor RNA, suggesting that cytidine acetylation is necessary for ribosome assembly.

e18553 Background: Platinum-based combination is the mainstay of chemotherapy for ES-SCLC, with limited recent fruit of new agent development. In terms of treatment modality, dose-intensive chemoth...

Porphyrins and related families of molecules are important organic modules as has been reflected in the award of the Nobel Prizes in Chemistry in 1915, 1930, 1961, 1962, 1965, and 1988 for work on porphyrin-related biological functionalities. The porphyrin core can be synthetically modified by introduction of various functional groups and other elements, allowing creation of numerous types of porphyrin derivatives. This feature makes porphyrins extremely useful molecules especially in combination with their other interesting photonic, electronic and magnetic properties, which in turn is reflected in their diverse signal input-output functionalities based on interactions with other molecules and external stimuli. Therefore, porphyrins and related macrocycles play a preeminent role in sensing applications involving chromophores. In this review, we discuss recent developments in porphyrin-based sensing applications in conjunction with the new advanced concept of nanoarchitectonics, which creates functional nanostructures based on a profound understanding of mutual interactions between the individual nanostructures and their arbitrary arrangements. Following a brief explanation of the basics of porphyrin chemistry and physics, recent examples in the corresponding fields are discussed according to a classification based on physical modes of detection including optical detection (absorption/photoluminescence spectroscopy and energy and electron transfer processes), other spectral modes (circular dichroism, plasmon and nuclear magnetic resonance), electronic and electrochemical modes, and other sensing modes.

We designed azobenzene alkyl disulfide to visualize molecular photoswitches in a monolayer system. Repeated changes in the surface nanostructure between a stripe-shaped structure and a smoother structure as a result of the reversible trans ↔ cisphotoisomerization of azobenzene units in phase-separated nanodomains were obviously observed using atomic force microscopy and UV-vis absorption spectroscopy.

The dynamic structure factor S(Q,W) of liquid Fe was measured near the melting point of 1570°C using high-resolution inelastic x-ray scattering spectrometer at BL35XU/SPring-8. Although liquid Fe has large values of the ratio of heat capacities γ and the viscosity η, the S(Q, W) spectra show well-defined collective excitations. The excitation energy WQ of the inelastic excitation modes was obtained within the generalized Langevin formalism. A positive dispersion of the sound velocity, as compared to the hydrodynamic value by about 20 %, was found as in other liquid metals. The η(Q) values decrease rapidly with Q, which may result in the well-defined collective excitations.

Introduction: Met activation by gene amplification and its ligand, hepatocyte growth factor (HGF), imparts resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in EGFR-mutant lung cancer. We recently reported that Met activation by HGF stimulates the production of vascular endothelial growth factor (VEGF) and facilitates angiogenesis, which indicates that HGF induces EGFR-TKI resistance and angiogenesis. This study aimed to determine the effect of triple inhibition of EGFR, Met, and angiogenesis on HGF- triggered EGFR-TKI resistance in EGFR-mutant lung cancer. Methods: Three clinically approved drugs, erlotinib (an EGFR inhibitor), crizotinib (an inhibitor of anaplastic lymphoma kinase and Met), and bevacizumab (anti-VEGF antibody), and TAS-115, a novel dual TKI for Met and VEGF receptor 2, were used in this study. EGFR-mutant lung cancer cell lines PC-9, HCC827, and HGF-gene- transfected PC-9 (PC-9/HGF) cells were examined. Results: Crizotinib and TAS-115 inhibited Met phosphorylation and reversed erlotinib resistance and VEGF production triggered by HGF in PC-9 and HCC827 cells in vitro. Bevacizumab and TAS-115 inhibited angiogenesis in PC-9/HGF tumors in vivo. Moreover, the triplet erlotinib, crizotinib, and bevacizumab, or the doublet erlotinib and TAS-115 successfully inhibited PC-9/HGF tumor growth and delayed tumor regrowth associated with sustained tumor vasculature inhibition even after cessation of the treatment. Conclusion: These results suggest that triple inhibition of EGFR, HGF/Met, and VEGF/VEGF receptor 2, by either a triplet of clini- cal drugs or TAS-115 combined with erlotinib, may be useful for controlling progression of EGFR-mutant lung cancer by reversing EGFR-TKI resistance and for inhibiting angiogenesis.