Gefitinib induction followed by chemoradiotherapy in EGFR-mutant, locally advanced non-small-cell lung cancer: LOGIK0902/OLCSG0905 phase II study.

BACKGROUND: The role of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) induction coupled with standard concurrent chemoradiotherapy (CRT) is unclear in unresectable, stage III, EGFR-mutant non-small-cell lung cancer (NSCLC). Therefore, a phase II trial was conducted to evaluate the efficacy and safety of gefitinib induction followed by CRT in this disease setting. PATIENTS AND METHODS: Patients with unresectable, EGFR-mutant, stage III NSCLC were administered gefitinib monotherapy (250 mg/day) for 8 weeks. Subsequently, patients without disease progression during induction therapy were administered cisplatin and docetaxel (40 mg/m2 each) on days 1, 8, 29, and 36 with concurrent radiotherapy at a total dose of 60 Gy. The primary endpoint was the 2-year overall survival (OS) rate, which was hypothesized to reach 85%, with a threshold of the lower limit of 60%. RESULTS: Twenty patients (median age: 66 years; male/female: 9/11; histology: 20 adenocarcinoma; stage IIIA/IIIB: 9/11; and exon 19/21: 10/10) were enrolled. The 2-year OS rate was 90% (90% confidence interval: 71.4% to 96.8%), indicating that this trial met the primary objective. The overall response rate and 1- and 2-year progression-free survival rates were 85.0%, 58.1%, and 36.9%, respectively. Grade ≥3 adverse events (>10%) included hepatic toxicity during the induction phase and neutropenia and febrile neutropenia in the CRT phase. Radiation pneumonitis grade ≥3 or treatment-related death did not occur. CONCLUSIONS: This is the first prospective study to demonstrate the favorable efficacy and safety of EGFR-TKI induction followed by standard CRT in EGFR-mutant, stage III NSCLC. Further confirmatory studies are needed.

Structural investigation of Ru/Pt nanocomposite films prepared by plasma-enhanced atomic layer depositions.

We have fabricated Ru and Pt nanocomposite films using plasma-enhanced atomic layer deposition (PE-ALD), and characterized their structure by means of analytical electron microscopy. Pt and Ru were deposited in Ar/O(2) plasma using trimethyl(methylcyclopentadienyl) platinum(IV) and bis(cyclopentadienyl)Ru(II) or bis(ethylcyclopentadienyl)Ru(II) as precursors, respectively. The resistivity of a Pt film deposited on a Si substrate at 300°C was 16.2µΩcm, and that of a Ru film was as low as 11µΩcm, showing the film to be metallic and not oxidized. It was revealed that the film prepared by successive PE-ALDs of Pt and Ru on a thin amorphous carbon substrate for electron microscopy analysis is a nanocomposite of Ru ribbons and PtRu (7:3) alloy ribbons with 2-3 nm in width. The Ru ribbon comprised small particles with poor crystallinity of the hcp A3 structure and the PtRu ribbon comprised crystallites with good crystallinity of the fcc Al structure. The atomic layer deposition would be one of potential techniques to produce Ru/Pt nanocomposites for fuel cell catalysts.

Electron microscopy investigations of V defects in multiple InGaN/GaN quantum wells and InGaN quantum dots.

The mechanism of high emission of InGaN-based multiple quantum wells, which exhibit exceptionally high light emission efficiency despite their high defect density, is still not fully understood. Here, we deal with this problem, showing the details of structure and formation of V defects in the multiple quantum wells and reviewing interpretations proposed so far. Then, we show a structural investigation of three-dimensional high-density quantum dots, fabricated instead of quantum wells in the active layer. The shape and size of the InGaN quantum dots and the SiN(x) masks for the growth of the dots have been revealed using high-angle annular dark field scanning transmission electron microscopy, energy dispersive X-ray spectroscopy nanoanalysis and high-resolution transmission electron microscopy.

Fine structures of wing scales in Sasakia charonda butterflies as photonic crystals.

We investigate the microstructure of scales in the wings of male Sasakia charonda charonda butterflies by scanning electron microscopy with the aid of optical microscopy. Six types of scales are identified: B1, W1 and R1 in brown background yellow spots and red spots, respectively; B2 in iridescent purple-blue and W2 in white pearl, both of which characterize the male and B3 in the wing edges. The B1, W1 and R1 scales are almost the same in structure and the B2 and W2 scales are almost the same. The difference among the B, W and R scales is in species and content of pigment. The B1, W1 and R1 scales have only two layers of cuticle lapped on the ridges. In contrast with them, the B2 and W2 scales have seven multilayers of cuticle piled on the ridge. The multiple interference of light that occurs among these cuticle layers, spaced with air layers, generates the significant iridescence of the B2 and W2 scales. Thus, the characteristic purple-blue of the male wings is ascribed to the combination of the structural and chemical colouration in the B2 scales with melanin. The photonic crystals of these scales may be applicable to fine light manipulators such as reflection elements in laser diodes. B3 has many holes between the ridges and no multilayers of cuticle on the ridges. These structures may play any role in aerodynamically easy flight and/or in drainage of wet wings.

Imaging of high-angle annular dark-field scanning transmission electron microscopy and observations of GaN-based violet laser diodes.

The first part of this paper is devoted to physics, to explain high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM) imaging and to interpret why HAADF-STEM imaging is incoherent, instructing a strict definition of interference and coherence of electron waves. Next, we present our recent investigations of InGaN/GaN multiple quantum wells and AlGaN/GaN strained-layer superlattice claddings in GaN-based violet laser diodes, which have been performed by HAADF-STEM and high-resolution field-emission gun scanning electron microscopy.

Quantitative high-resolution HAADF-STEM analysis of inversion boundaries in Sb(2)O(3)-doped zinc oxide.

[Formula: see text] -doped ZnO crystals including inversion boundaries were investigated by high-resolution high-angle annular-dark field (HAADF) scanning transmission electron microscopy (STEM). The images were analysed with the aid of the image simulation based on Bethe method and also the retrieval processing using deconvolution. Utility of these two approaches for the HAADF-STEM analysis is discussed.

Effect of small crystal tilt on atomic-resolution high-angle annular dark field STEM imaging.

Using a slightly tilted convergent electron beam, high-angle annular dark field scanning transmission electron microscopy observations have been performed of a [0 11]-oriented Si crystal. A small tilt of the crystal zone axis with respect to the coma-axis of the probe-forming lens causes a difference in intensity between bright spots of a Si dumbbell. The semiangle of the beam probe and the tilting angle with respect to the specimen hormal were determined by means of convergent beam micro-diffraction. The simulation using these parameters accounts for the image contrasts satisfactorily.

Deconvolution processing of HAADF STEM images.

A deconvolution processing of high-resolution high-angle annular dark field (HAADF) scanning transmission electron microscopy (STEM) images, combined with maximum entropy method, is applied to two experimental [0 11]-Si images; one having unresolved dumbbells and the other having resolved dumbbells and artificial bright spots. The deconvoluted images for these images show bright spots corresponding to the projected atomic columns and no artificial bright spots. Thus, the deconvolution processing provides almost a real projected atomic structure by eliminating effects of the probe function from HAADF STEM images.

Artificial bright spots in atomic-resolution high-angle annular dark field STEM images.

Artificial bright spots, which appear in some atomic resolution high-angle annular dark field scanning transmission electron microscope (HAADF STEM) images, have been accounted for by simulations based on Bloch wave description. This is illustrated with Si and SrTiO3 images. The simulation reveals that bright spots on no-atomic columns in [011]-orientated Si images are produced by thermal diffuse scattering from Si atoms on their surrounding atomic columns, which are under the subsidiary peaks in the incident convergent electron probe. Similarly, bright spots on oxygen columns in [001]-orientated SrTiO3 images are ascribed to Sr and Ti atoms in their surrounding atomic columns rather than O atoms in the O columns. The probe function, therefore, provides a simple explanation for the appearance of these artificial spots.

Electron microscopy analysis of the boundary layer structure of SrTiO3 semiconducting ceramic

In a boundary layer (BL) semiconducting SrTiO3-based ceramic condenser, the BL structure has been investigated using high-resolution field-emission scanning electron microscopy (FE-SEM) and field-emission (scanning) transmission electron microscopy (FE-(S)TEM). In an initial TEM observation, a double layered structure was observed at the grain boundary region. It consisted of a grain boundary (second phase) and a pair of the metal diffusion layers of up to several nanometres in width across the grain boundary where the change of the crystal lattice distance was undetected by the high-resolution TEM image. A facet structure was often observed on the grain boundaries. It was particularly formed on (020) plane of the grain crystal. High resolution SEM showed a jagged striped structure on the surface of the bulk material and on the inside grain as revealed by fracture. Using the similarity in shape and size, it can be identified to correspond to the facet boundary structure. Its formation mechanism can be explained as that during the reoxidization process when the oxide flux of the mixture of Bi2O3, PbO and CuO, painted on the bulk material, surfaces migrates into the ceramic along the grain boundary. The oxide corrodes the grain surfaces including the bulk surfaces. This corrosion particularly occurs on (020) plane of the grain so that the facet structure is produced. In this paper, by using the atomic scale high angle annular dark field STEM, it has been determined that Bi atoms preferentially replace Sr atoms on (020) in the diffusion layers. The atom position displacement was also detected at the grain surfaces and this altered atomic assignment can be determined as an origin of production of Sr2Bi4Ti5O18 at the grain boundary. Also, it was observed that the layer width of the metal diffusion layers was often different between the both grains and changed locally so that the ribbon of the diffusion layers meandered around the straight grain boundary. Its possible mechanism is also proposed.

Quantitative intensity measurement of equal thickness fringes in Si and MgO crystal images with an energy-filtering transmission electron microscope using an imaging plate.

Quantitative measurement of intensity profiles of equal thickness fringes has been carried out in Si and MgO crystal images with an energy-filtering transmission electron microscope using an imaging plate. The crystals have a 90 degrees wedge-shape with [110] surfaces for Si and with [100] surfaces for MgO, and are observed under the exact axial incidence of a 200 keV electron beam along the [100] axis for Si and along the [110] axis for MgO. The intensities are measured in bright field and 022 and 040 dark field images for Si, and in bright field and 111, 002, 220, 113, 222, and 004 dark field images for MgO, with and without an energy slit having +/- 5 eV energy width for incident electrons. The intensity profiles obtained from the images are presented as standard experimental data for calculation of electron diffraction intensities. A few simulation programs for high-resolution transmission electron microscopy are checked by comparing the calculated diffraction intensities with the experimental data. The complex potential suitable for matching the data is discussed.

Simulation of atomic-scale high-angle annular dark field scanning transmission electron microscopy images.

Image simulations for high-angle annular dark field (HAADF) scanning transmission electron microscopy (STEM) based on the Bethe's eigen-value method are presented. The effects of aperture size and defocus of a probe-forming lens, both of which determine the shape of the probe, and the effect of the distortion, influencing the Bloch wave field on atomic columns channelled by electrons, on the HAADF-image intensity are discussed in terms of dynamical effect. These effects are illustrated by our experimental atomic-scale HAADF-STEM images, detected in a detector range of 50-110 mrad. It is emphasized that the image simulations are indispensable for quantification of experimental HAADF-STEM images and as such provide a valuable compositional analysis for every atomic column along the incident beam.

Morphology and structure of photosensitive dye J-aggregates adsorbed on AgBr microcrystals grown in gelatin.

Though the cyanine dye J-aggregates carry the role to sense the exposing light in the silver halide photographic system, little research on the morphology of the aggregates in adsorption has been made with modern surface analytical methods. In this paper, we describe the size, epitaxy, multi-layered array formation, nucleation and preferential adsorption, and irregular distribution of population between particles and the segregation on a particle, of J-aggregates adsorbed on AgBr grown in gelatin. We employed cathodoluminescence microscopy, low energy high resolution scanning electron microscopy, and atomic force microscopy. Dye molecules aggregate together near the surface of AgBr and adsorb on the surface. The growth of adsorbed aggregates is controlled by the diffusion of dye molecules from the surrounding solution. The population of J-aggregates adsorbed on an AgBr particle varies from almost none to full coverage. Each aggregate is about (20-30) x (30-50) nm in size and is 2.1 nm thick for thiacarbocyanine with sodium ion, 1.04 nm for thiacarbocyanine with tosyl ion, and 0.5 nm for an oxacarbocyanine. The aggregates connect their longer edges to each other to form arrays, and the arrays build up multi-layered stacks. The arrays align parallel and segregate to form terraces. The longer edges of J-aggregates align along [210] on AgBr (100) or [632] on AgBr (111).

Gene of rat Ca2+/calmodulin-dependent protein kinase II alpha isoform -- its cloning and whole structure.

The gene encoding the alpha isoform of rat Ca2+/calmodulin-dependent protein kinase II was cloned, and its exon-intron organization was analyzed. The coding region of cDNA consists of 18 exons spanning more than 50 kilobase pairs. Each of the discrete functional units, such as the ATP-binding site, the autophosphorylation site responsible for Ca2+-independent activity, the calmodulin-binding site, and link structure is encoded by a single exon. The largest and smallest exons consist of 229 and 41 base pairs, respectively. All splice junction sequences flanking the introns conform to the consensus splice junction sequence and the GT-AG splice rule.

Observation of ZnO particles grown by electrochemical reaction of Zn.

The electrochemical reaction of Zn is investigated by scanning electron microscopy and transmission electron microscopy. Zn films are used as anodes, loaded at DC voltages of 10-200 V in distilled water at 20 degrees C. Zn ions diffuse from the anode and are coupled with OH ions to form spindle-like ZnO particles of 1-2 microns on the cathode or on a permeable paper barrier placed between the anode and cathode. Formless layers, which are composed of fine ZnO crystallites of several nanometers or less in size, form on the cathode in the water at lower OH ion density before the growth of the spindles. They become spindle-shaped after only a few minutes of water bath treatment at 60 degrees C.

Cross-sectional transmission electron microscopy of ZnO tetrapod-like particles.

ZnO tetrapod-like particles having legs as long as several tens of micrometers have been observed by cross-sectional electron microscopy. The specimen is prepared by a new method where a photo-resist suspension of the particles fills up holes of an electron microscopy grid and is solidified for the subsequent ion-milling. Electron diffraction and high-resolution electron microscopy of a section of a ZnO tetrapod reveal the orientation relationship among its four legs, which enables us to discuss on the growth mechanism of these particles.

High-resolution transmission electron microscopy of hexagonal and rhombohedral molybdenum disulfide crystals.

Natural (molybdenite) and synthesized molybdenum disulfide crystals have been studied by high-resolution transmission electron microscopy. The image simulation demonstrates that the [0001] and [0110] HRTEM images of hexagonal and rhombohedral MoS2 crystals hardly disclose their stacking sequences, and that the [2110] images can distinguish the Mo and S columns along the incident electron beam and enable one to determine not only the crystal structure but also the fault structure. Observed [0001] images of cleaved molybdenite and synthesized MoS2 crystals, however, reveal the strain field around partial dislocations limiting an extended dislocation. A cross-sectional image of a single molecular (S-Mo-S) layer cleaved from molybdenite has been observed. Synthesized MoS2 flakes which were prepared by grinding have been found to be rhombohedral crystals containing many stacking faults caused by glides between S/S layers.

Structures of grain boundaries in long-chain Te crystals observed by high-resolution transmission electron microscopy.

Vacuum-deposited Te crystals, composed of endless chains of the right-handed or left-handed spiral, have been investigated by high-resolution electron microscopy with the aid of image simulation. A (010) grain boundary, which accompanies edge dislocations having an extra layer of the width of one Te chain, has been observed. A through-focal series of images reveal that it is not a reflectional nor a rotational twin boundary but a small angle grain boundary in a single crystal or an inversion twin. The lattice on one side of the boundary is shifted from that on the other side by [001]c/3 + [120]a/8, and inclined at 1.1 degrees around the c-axis of the other side. Also found between crystallites of [100] and [011] orientation is a grain boundary which is built with the (011) facets on one side of the boundary and the (211) or (0,1,10) facets on another side.

High-resolution transmission electron microscopy of inorganic materials in cellular and topological random systems.

The structure of amorphous Se films, in the topological random system, has been studied by the computer-simulation, electron diffraction (ED), and high-resolution transmission electron microscopy (HRTEM). As an example of HRTEM of the cellular random system, our recent investigation on Ba-ferrites is reviewed beforehand. In HRTEM images of spin-glass BaTi2-xSnxFe4O11 (x less than 0.6), magnetic clusters or clusters of FeO6-octahedra surrounded by TiO6-octahedra have been found. The structure of BaSn2Fe4O11 (x = 2) has been determined. The ordering of Sn (Ti) and Fe ions increases with increasing x, which interprets the change from the spin-glass state to nonspin-glass state at x = 0.6. It is shown that a cluster of polarized lattice ions is detectable in images of polar-glass BaxK2-xFexTi6-xO13 (x greater than or equal to 1.2). The structure models of amorphous Se films forming on a substrate have been constructed on a computer, and their radial distribution function (RDF) and HRTEM images have been calculated. Experimental RDF and HRTEM images have been obtained from vacuum-deposited amorphous Se films and are compared with the calculated ones. It is concluded that in the as-deposited films most of Se molecules may be composed of Se atoms as small as three and that by the electron-beam irradiation the molecules link to form spiral chains in amorphous state and then arrange to have the hexagonal crystal structure.