Structural study of epitaxial LiCoO2 films grown by pulsed laser deposition on single crystal SrTiO3 substrates.

Epitaxial LiCoO2 (LCO) thin films of different orientations were fabricated by pulsed laser deposition (PLD) in order to model single-crystal behavior of intercalation cathodes during electrochemical reactions. This paper demonstrates that (1) epitaxial growth of LCO on a single crystal Nb-doped SrTiO3 (Nb:STO) of different orientations occurs with a single orientation relationship; (2) surface morphology of the LCO films is established by the morphology of coalescing grains during island growth mode, whereas morphology of the grains can be visualized as different cuts from a cube with low-energy {104}R-LCO surfaces; (3) the films consist of predominately trigonal R-LiCoO2 phase, with a small fraction of the occasionally present cubic c-LixCoO2 phase; (4) cyclic voltammetry measurements have determined rectification at interface between LCO and Nb:STO causing bias on the oxidation part of cycling, thus preventing full cycling.

High-throughput determination of structural phase diagram and constituent phases using GRENDEL.

Advances in high-throughput materials fabrication and characterization techniques have resulted in faster rates of data collection and rapidly growing volumes of experimental data. To convert this mass of information into actionable knowledge of material process-structure-property relationships requires high-throughput data analysis techniques. This work explores the use of the Graph-based endmember extraction and labeling (GRENDEL) algorithm as a high-throughput method for analyzing structural data from combinatorial libraries, specifically, to determine phase diagrams and constituent phases from both x-ray diffraction and Raman spectral data. The GRENDEL algorithm utilizes a set of physical constraints to optimize results and provides a framework by which additional physics-based constraints can be easily incorporated. GRENDEL also permits the integration of database data as shown by the use of critically evaluated data from the Inorganic Crystal Structure Database in the x-ray diffraction data analysis. Also the Sunburst radial tree map is demonstrated as a tool to visualize material structure-property relationships found through graph based analysis.

In situ observation of reversible nanomagnetic switching induced by electric fields.

We report direct observation of controlled and reversible switching of magnetic domains using static (dc) electric fields applied in situ during Lorentz microscopy. The switching is realized through electromechanical coupling in thin film Fe(0.7)Ga(0.3)/BaTiO(3) bilayer structures mechanically released from the growth substrate. The domain wall motion is observed dynamically, allowing the direct association of local magnetic ordering throughout a range of applied electric fields. During application of approximately 7-11 MV/m electric fields to the piezoelectric BaTiO(3) film, local magnetic domains rearrange in the ferromagnetic Fe(0.7)Ga(0.3) layer due to the transfer of strain from the BaTiO(3) film. A simulation based on micromagnetic modeling shows a magnetostrictive anisotropy of 25 kPa induced in the Fe(0.7)Ga(0.3) due to the strain. This electric-field-dependent uniaxial anisotropy is proposed as a possible mechanism to control the coercive field during operation of an integrated magnetoelectric memory node.

Japanese civilian and US military interaction in the evacuation of casualties from Camp Fuji.

Historically, if US soldiers at Camp Fuji become severely ill or suffer trauma, they are transported by the ground ambulance, as the doctor-led air ambulance in eastern Shizuoka has never been permitted to land at Camp Fuji. However, it is widely recognised that severely ill or traumatised patients require time-dependent medical management. It was therefore agreed to undertake a joint exercise between the US medical assets of Camp Fuji and the doctor helicopters in eastern Shizuoka prefecture in evacuating a simulated severely ill or traumatised US soldier. The aim of this article is to describe the background and rationale between this collaboration between the civilian Japanese air ambulance and the US medical assets in Camp Fuji.

Tuning the hysteresis of a metal-insulator transition via lattice compatibility.

Structural phase transitions serve as the basis for many functional applications including shape memory alloys (SMAs), switches based on metal-insulator transitions (MITs), etc. In such materials, lattice incompatibility between transformed and parent phases often results in a thermal hysteresis, which is intimately tied to degradation of reversibility of the transformation. The non-linear theory of martensite suggests that the hysteresis of a martensitic phase transformation is solely determined by the lattice constants, and the conditions proposed for geometrical compatibility have been successfully applied to minimizing the hysteresis in SMAs. Here, we apply the non-linear theory to a correlated oxide system (V1-xWxO2), and show that the hysteresis of the MIT in the system can be directly tuned by adjusting the lattice constants of the phases. The results underscore the profound influence structural compatibility has on intrinsic electronic properties, and indicate that the theory provides a universal guidance for optimizing phase transforming materials.

Genome-wide analysis of DNA copy number alterations and gene expression in gastric cancer.

Genomic copy number aberrations (CNAs) are believed to play a major role in the development and progression of human cancers. Although many CNAs have been reported in gastric cancer, their genome-wide transcriptional consequences are poorly understood. In this study, to reveal the impact of CNAs on genome-wide expression in gastric cancer, we analysed 30 cases of gastric cancers for their CNAs by array comparative genomic hybridization (array CGH) and 24 of these 30 cases for their expression profiles by oligonucleotide-expression microarray. We found that with the application of laser microdissection, most CNAs were detected at higher frequency than in previous studies. Notably, gain at 20q13 was detected in almost all cases (97%), suggesting that this may play an important role in the pathogenesis of gastric cancer. By comparing the array CGH data with expression profiles of the same samples, we showed that both genomic amplification and deletion strongly influence the expression of genes in altered genomic regions. Furthermore, we identified 125 candidate genes, consisting of 114 up-regulated genes located in recurrent regions (>10%) of amplification and 11 down-regulated genes located in recurrent regions of deletion. Up-regulation of several candidate genes, such as CDC6, SEC61G, ANP32E, BYSL and FDFT1, was confirmed by immunohistochemistry. Interestingly, some candidate genes were localized at genomic loci adjacent to well-known genes such as EGFR, ERBB2 and SMAD4, and concordantly deregulated by genomic alterations. Based on these results, we propose that our list of candidate genes may contain novel genes involved in the pathogenesis of advanced gastric cancer.

Rapid structural mapping of ternary metallic alloy systems using the combinatorial approach and cluster analysis.

We are developing a procedure for the quick identification of structural phases in thin film composition spread experiments which map large fractions of compositional phase diagrams of ternary metallic alloy systems. An in-house scanning x-ray microdiffractometer is used to obtain x-ray spectra from 273 different compositions on a single composition spread library. A cluster analysis software is then used to sort the spectra into groups in order to rapidly discover the distribution of phases on the ternary diagram. The most representative pattern of each group is then compared to a database of known structures to identify known phases. Using this method, the arduous analysis and classification of hundreds of spectra is reduced to a much shorter analysis of only a few spectra.

Development and analysis of patient-derived xenograft mouse models in intravascular large B-cell lymphoma.

Intravascular large B-cell lymphoma (IVLBCL) is a distinct disease entity with the peculiar characteristic that tumor cells proliferate within vessels. Despite recent advances in understanding the disease from clinical aspects, the underlying pathogenesis remains unknown. Here we demonstrate analyses of IVLBCL biology using four xenograft mouse models established from primary IVLBCL samples. In all four models, the main characteristic of IVLBCL tumor cell proliferation within vessels was retained. Time-lapse engraftment analyses revealed that the tumor cells initially engrafted and proliferated in the sinusoids and vessels in the liver and then engrafted and proliferated in multiple organs. Intriguingly, serial passage of tumor cells from the adrenal gland of a transplanted mouse developed from primary patient bone marrow cells into a second mouse showed that the tumor cells mainly distributed into the adrenal gland in the second mouse, implying the existence of clonal selection and/or evolution at engraftment of a specific organ. Gene expression profiling analyses demonstrated that the gene set associated with cell migration was enriched for normal peripheral blood B cells, indicating that inhibition of cell migration might be involved in IVLBCL pathogenesis. In conclusion, the mouse xenograft models described here are essential tools for uncovering IVLBCL biology.

Repression of rRNA synthesis induced by disaggregation in Dictyostelium discoideum.

Cells disaggregated from the slugs of Dictyostelium discoideum continued to incorporate [3H]uridine or [3H]uracil, though at a lower rate than interphase amoebae. Disaggregation brought about a marked increase in the proportion of labeled poly(A)-containing RNA to labeled total RNA. The proportion reached the maximum in disaggregated cells after 1 h of incubation, but remained high even after 5 h of incubation. Reconstruction of slugs from the disaggregated cells did not bring about a decrease but a further increase in the proportion. The real proportion estimated from the minimum period of labeling reached almost 100% in the disaggregated cells, in contrast to about 30% in the interphase amoebae. The increase in the proportion is attributed to the disaggregation-induced repression of rRNA synthesis, which was supported by sucrose density gradient analyses of RNA synthesized in the disaggregated cells. The possibility that rRNA synthesis in this organism is regulated by the loss of cell contact is discussed.

Structural requirements of salicylanilides for uncoupling activity in mitochondria: quantitative analysis of structure-uncoupling relationships.

The uncoupling activities of more than 20 salicylanilides were measured in rat liver mitochondria. The activities, expressed as the minimum concentrations required for full release of state-4 respiration, ranged over three orders of magnitude. The acid dissociation constant, pKA, and the partition coefficient between octanol and water (Poct) of some of the salicylanilides were determined. These two parameters were found to be well expressed in terms of the Hammett constant, sigma, and the hydrophobic substituent coefficient, II, respectively. The pKA and log Poct values of all the salicylanilides were predicted according to these relationships. Furthermore, the capacity factor, k', on high-performance liquid chromatography was determined on glyceryl-coated-controlled pore glass (gly-CPG). Values of log k' correlated well with those of log Poct. The uncoupling activities of the salicylanilides were analyzed in terms of these three parameters. Both hydrophobic and electron-withdrawing properties were found to be essential for induction of potent uncoupling activity. The correlations using log k' were better than those using log Poct.

Very low density lipoprotein binding to adipocytes.

Human very low density lipoprotein (VLDL) has been found to interact with both isolated adipocytes and adipocyte membranes in a manner which is saturable, reversible and dependent on time and temperature. Except for a difference in maximum binding capacity, a similar pattern is seen with both rat epididymal adipocytes and human omental adipocytes. The capacity of rat cells is 0.04 micrograms VLDL per 2 x 10(5) cells. For human cells the capacity is 0.321 micrograms VLDL per 2 x 10(5) cells. Scatchard plots of the competition data are linear. This, and dissociation studies conducted in the presence or absence of unlabelled VLDL suggest that there is no cooperative interaction between the binding sites. Unlabelled VLDL and HDL each compete equally with 125I-labelled VLDL for binding sites. LDL is 25 times weaker as a competitor. Intralipid and unrelated peptides have no effect. These data suggest that the ligand is not apolipoprotein B and not apolipoprotein A. The competitive effect of HDL is not dependent on its apolipoprotein E content. A preparation of C apolipoproteins (75% C-11) is as potent as unlabelled VLDL in competing with 125I-labelled VLDL for binding sites. These data indicate that VLDL can bind to adipocytes. The receptor can interact with other lipoproteins. If differs from the LDL receptor as it does not interact with apolipoprotein B or apolipoprotein E, but binds to a C apolipoprotein.

Secretion of chondroitin 6-sulfotransferase and chondroitin 4-sulfotransferase from cultured chick embryo chondrocytes.

We found that chondroitin 6-sulfotransferase and chondroitin 4-sulfotransferase were released into the culture medium from the cultured chick embryo chondrocytes. Since the release of the sulfotransferases was observed not only in serum-supplemented medium but also in serum-free medium, the released sulfotransferases were unlikely to be derived from serum. Addition of ascorbate to the serum-free medium supported the continuous release of the sulfotransferases. Monensin, which is known to cause dilatation of the Golgi apparatus and to inhibit sulfation of proteoglycan, was found to affect the release of the sulfotransferases. In the presence of 10(-6) M monensin, chondroitin 6-sulfotransferase activity in the cell layer was decreased to less than one tenth of the control, and the rate of the release of the activity became much smaller than the control after the initial rapid release. The activity of chondroitin 4-sulfotransferase was also affected by monensin, but the reduction of the chondroitin 4-sulfotransferase activity in the cell layer was not so great as the reduction of chondroitin 6-sulfotransferase activity. Unlike to the microsomal sulfotransferases, both chondroitin 6-sulfotransferase and chondroitin 4-sulfotransferase released into the culture medium were retained in the soluble fraction after centrifugation at 100,000 x g for 60 min, and were not activated by detergent. pH optimum and requirements for sulfhydryl compounds of the released sulfotransferases were similar to those observed previously in the chondroitin sulfotransferases from chick embryo cartilage and from cultured chick embryo chondrocytes. These results suggest that chondroitin sulfotransferases, which are localized in the Golgi apparatus, may be secreted to the extracellular space in a soluble form under the culture conditions.

FebA: a gene for eukaryotic translation initiation factor 4E-binding protein (4E-BP) in Dictyostelium discoideum.

We have identified a gene encoding a eukaryotic initiation factor 4E-binding protein (4E-BP) in the EST database of the Dictyostelium cDNA project. The Dictyostelium 4E-BP, designated febA (four e-binding), showed significant similarity to mammalian 4E-BPs. Northern blot analysis revealed that febA was expressed at a high level in the vegetative growth phase but the level of expression decreased during late development. The gene was shown to be non-essential since disruption of the gene had no severe effect; the null mutant proliferated normally and formed normal fruiting bodies. However, strains overexpressing the gene could not be established, suggesting that an excess of FebA protein may have a lethal effect on the cells.

Cooperation of positively and negatively acting promoter elements determines prespore-specific transcription of Dp87 gene in Dictyostelium.

Dp87 gene in Dictyostelium is a novel prespore-specific gene, whose expression is first observed when the aggregation stream is formed, the earliest among prespore-specific genes so far isolated. By 5'-sequential deletion analyses, we had previously indicated that the region between -447 and -356 is important for transcription. Here we show by detailed analyses that the regulatory mechanism of the gene is more complex in that multiple positive and negative regulatory regions including the previously identified region act cooperatively. In addition, we show that the region including the putative TATA box and the transcriptional start site is required for proper negative regulation of the gene.

Protein binding and DNase-I-hypersensitive sites in the cis-acting regulatory region of the spore-coat SP96 gene of Dictyostelium.

The spore-coat protein gene (SP96) of Dictyostelium discoideum is transcribed only in prespore cells. To identify the cis-acting region of this gene, mutant mini-genes which contained different lengths of 5' upstream region, the partially deleted SP96 coding region and ca. 600 bp of 3' flanking sequence were transformed into D. discoideum cells. Expression of the mini-genes was analysed by Northern hybridization. Our results indicate that the 5' upstream region from -686 to -494 contains an important cis-acting element for the temporal and cell type-specific transcription. A nuclear factor which specifically bound the cis-acting region was identified by gel retardation assay. DNase-I-hypersensitivity of the 5' upstream region was examined and it was shown that the appearance of two new hypersensitive sites correlates with transcriptional activation of the gene. One of the two sites maps to the TATA region and the other was located in the cis-acting region identified by deletion analysis. Our results suggest that gene activation occurs by conformational changes in the chromatin structure of the cis-acting region followed by subsequent binding of regulatory factors and the TATA-binding protein.

Regulation of cell differentiation and pattern formation in Dictyostelium development.

Free-living cells of Dictyostelium discoideum aggregate to form a slug-shaped cell mass and differentiate into prestalk and prespore cells. The differentiation of prespore cells is characterized by expression of Dp87 gene, the earliest event of prespore differentiation. It encodes a protein which first appears in ER of aggregating cells in a precursor form, is then translocated to prespore vacuoles and modified to a mature form and finally exocytosed to constitute the sorus matrix. The transcription of Dp87 is regulated by the cis-acting region consisting of positive, prespore-specific, negative, non-prespore-specific and positive, cell-type-non-specific elements. Cells expressing Dp87 appear at random in early aggregation streams and centers and then sort out to the posterior part of the slug. Intercellular signals required for prestalk and prespore differentiation were investigated by incubation at a low cell density of disaggregated cells. cAMP is inhibitory at the first and second stages of prespore differentiation, while it is required at the third stage. The stalk differentiation is divided into four stages: cAMP is required at the second stage and differentiation inducing factor (DIF) at the third stage, where a low molecular weight secretory substance is also required. At the third stage, cAMP inhibits both ecmA and ecmB expression, while 8-Br-cAMP specifically induces ecmB and maturation of prestalk to stalk cells. The relationship between the differentiation tendency of preaggregative cells and the cell-cycle phase at the initiation of development was studied by the use of cells synchronized for growth by a temperature-shift method.(ABSTRACT TRUNCATED AT 250 WORDS)

Anomalous magnetoresistance in the spinel superconductor LiTi2O4.

LiTi2O4 is a unique compound in that it is the only known spinel oxide superconductor. The lack of high quality single crystals has thus far prevented systematic investigations of its transport properties. Here we report a careful study of transport and tunnelling spectroscopy in epitaxial LiTi2O4 thin films. An unusual magnetoresistance is observed which changes from nearly isotropic negative to prominently anisotropic positive as the temperature is decreased. We present evidence that shows that the negative magnetoresistance likely stems from the suppression of local spin fluctuations or spin-orbit scattering centres. The positive magnetoresistance suggests the presence of an orbital-related state, also supported by the fact that the superconducting energy gap decreases as a quadratic function of magnetic field. These observations indicate that the spin-orbital fluctuations play an important role in LiTi2O4 in a manner similar to high-temperature superconductors.

The Dictyostelium developmental cDNA project: generation and analysis of expressed sequence tags from the first-finger stage of development.

In an effort to identify and characterize genes expressed during multicellular development ill Dictyostelium, we have undertaken a cDNA sequencing project. Using size-fractionated subsets of cDNA from the first finger stage, two sets of gridded libraries were constructed for cDNA sequencing. One, library S, consisting of 9984 clones, carries relatively short inserts, and the other, library L, which consists of 8448 clones, has longer inserts. We sequenced all the selected clones in library S from their 3'-ends, and this generated 3093 non-redundant, expressed sequence tags (ESTs). Among them, 246 ESTs hit known Dictyostelium genes and 910 showed significant similarity to genes of Dictyostelium and other organisms. For library L, 1132 clones were randomly sequenced and 471 non-redundant ESTs were obtained. In combination, the ESTs from the two libraries represent approximately 40% of genes expressed in late development, assuming that the non-redundant ESTs correspond to independent genes. They will provide a useful resource for investigating the genetic networks that regulate multicellular development of this organism.

Intracellular free calcium level and its response to cAMP stimulation in developing Dictyostelium cells transformed with jellyfish apoaequorin cDNA.

A new method is described for measuring intracellular free calcium concentrations, [(Ca2+)i], in the cells of Dictyostelium discoideum transformed with apoaequorin cDNA of the jellyfish, Aequorea victoria. Aequorin, a calcium-specific indicator, was regenerated in vivo from apoaequorin produced in the cells by incubation with coelenterazine. The results showed that [(Ca2+)i] in developing cells markedly increases at the aggregation stage and again at the culmination stage after a temporary drop at the migration stage. Except for the vegetative stage, the cells at all stages of development exhibit a sharp transient increase in [(Ca2+)i] upon stimulation with a cAMP (50 nM) pulse, high responses being observed at the migration and culmination stages. Separated prestalk cells of migrating slugs contain more than twice as much [(Ca2+)i] and show three times as large a response to cAMP stimulation as prespore cells.

Dose-dependent hypolipidemic effect of an inhibitor of HMG-CoA reductase, pravastatin (CS-514), in hypercholesterolemic subjects. A double blind test.

The hypolipidemic effect of a new HMG-CoA reductase inhibitor, pravastatin, was examined. The reductions of serum cholesterol and LDL-cholesterol were dose-dependent and significant differences were observed between placebo and 10 or 20 mg groups (P less than 0.01), and 10 and 20 mg (P less than 0.05) groups. The reduction rate of cholesterol after 8 weeks during medication was 16.1% in the 10 mg group, 20.5% in the 20 mg group compared to baseline serum cholesterol levels. LDL-cholesterol decreased by 23.9% in the 10 mg group, and 29.8% compared to baseline LDL-cholesterol in the 20 mg group. The lowering of total cholesterol was entirely attributed to a reduction in LDL-cholesterol.