Combinatorial synthesis of heteroepitaxial, multi-cation, thin-films via pulsed laser deposition coupled with in-situ, chemical and structural characterization.

Combinatorial synthesis via a continuous composition spread is an excellent route to develop thin-film libraries as it is both time- and cost-efficient. Creating libraries of functional, multicomponent, complex oxide films requires excellent control over the synthesis parameters combined with high-throughput analytical feedback. A reliable, high-throughput, in-situ characterization analysis method is required to meet the crucial need to rapidly screen materials libraries. Here, we report on the combination of two in-situ techniques-(a) Reflection high-energy electron diffraction (RHEED) for heteroepitaxial characterization and a newly developed compositional analysis technique, low-angle x-ray spectroscopy (LAXS), to map the chemical composition profile of combinatorial heteroepitaxial complex oxide films deposited using a continuous composition spread method via pulsed laser deposition. This is accomplished using a unique state-of-the-art combinatorial growth system with a fully synchronized four-axis mechanical substrate stage without shadow masks, alternating acquisition of chemical compositional data using LAXS at various different positions on the [Formula: see text] 41 mm [Formula: see text] 41 mm range and sequential deposition of multilayers of SrTiO[Formula: see text] and [Formula: see text] on a 2-inch (50.8 mm) [Formula: see text] wafer in a single growth run. Rutherford backscattering spectrometry (RBS) is used to calibrate and validate the compositions determined by LAXS. This study shows the feasibility of combinatorial synthesis of heteroepitaxial, functional complex oxide films at wafer-scale via two essential in-situ characterization tools-RHEED for structural analysis or heteroepitaxy and LAXS for compositional characterization. This is a powerful technique for development of new films with optimized heteroepitaxy and composition.

Structural "δ Doping" to Control Local Magnetization in Isovalent Oxide Heterostructures.

Modulation and δ-doping strategies, in which atomically thin layers of charged dopants are precisely deposited within a heterostructure, have played enabling roles in the discovery of new physical behavior in electronic materials. Here, we demonstrate a purely structural "δ-doping" strategy in complex oxide heterostructures, in which atomically thin manganite layers are inserted into an isovalent manganite host, thereby modifying the local rotations of corner-connected MnO_{6} octahedra. Combining scanning transmission electron microscopy, polarized neutron reflectometry, and density functional theory, we reveal how local magnetic exchange interactions are enhanced within the spatially confined regions of suppressed octahedral rotations. The combined experimental and theoretical results illustrate the potential to utilize noncharge-based approaches to "doping" in order to enhance or suppress functional properties within spatially confined regions of oxide heterostructures.

Spatial control of functional properties via octahedral modulations in complex oxide superlattices.

Control of atomic structure, namely the topology of the corner-connected metal-oxygen octahedra, has emerged as an important route to tune the functional properties at oxide interfaces. Here we investigate isovalent manganite superlattices (SLs), [(La(0.7)Sr(0.3)MnO(3))n/(Eu(0.7)Sr(0.3)MnO(3))n] × m, as a route to spatial control over electronic bandwidth and ferromagnetism through the creation of octahedral superstructures. Electron energy loss spectroscopy confirms a uniform Mn valence state throughout the SLs. In contrast, the presence of modulations of the MnO(6) octahedral rotations along the growth direction commensurate with the SL period is revealed by scanning transmission electron microscopy and X-ray diffraction. We show that the Curie temperatures of the constituent materials can be systematically engineered via the octahedral superstructures leading to a modulated magnetization in samples where the SL period is larger than the interfacial octahedral coupling length scale, whereas a single magnetic transition is observed in the short-period SLs.

Evaluation of dietary multiple enzyme preparation (natuzyme) in laying hens.

The current experiment was designed to evaluate the efficacy of adding the multi-enzyme mixture (Natuzyme) into layers' diets with different levels of energy and available phosphorus in relation to laying performance, egg qualities, blood cholesterol level, microflora and intestinal viscosity. Two hundred and fifty 43-wk-old Hy-Line commercial layers were divided into five groups with five replicates per group (10 birds per replicate) and fed one of five experimental diets. A corn and soybean meal-based control diet was formulated and used as a control diet. Two experimental control diets were formulated to reduce energy and crude protein contents (rE) or energy, crude protein and phosphorus contents (rEP). In addition, Natuzyme was added into either rE (rE-Natu500) or rEP (rEP-Natu500) diet to reach a concentration of 500 mg per kg of diet. The experiment lasted 8 weeks. There were no significant differences in feed intake, egg production, egg weight, egg qualities such as eggshell color or Haugh unit, total cholesterol, relative organ weights and cecal microflora profiles between any dietary treatments. Natu500 supplementation into the rE diet, but not rEP diet significantly increased egg mass and eggshell qualities such as strength and thickness, but it decreased cecal ammonia concentration and intestinal viscosity in laying hens. In conclusion, the present study shows that adding multiple enzyme preparation could improve performance of laying hens fed energy and protein restricted diets.

Effect of interfacial octahedral behavior in ultrathin manganite films.

We investigate structural coupling of the MnO6 octahedra across a film/substrate interface and the resultant changes of the physical properties of ultrathin La2/3Sr1/3MnO3 (LSMO) films. In order to isolate the effect of interfacial MnO6 octahedral behavior from that of epitaxial strain, LSMO films are grown on substrates with different symmetry and similar lattice parameters. Ultrathin LSMO films show an increased magnetization and electrical conductivity on cubic (LaAlO3)0.3(Sr2AlTaO6)0.7 (LSAT) compared to those grown on orthorhombic NdGaO3 (NGO) substrates, an effect that subsides as the thickness of the films is increased. This study demonstrates that interfacial structural coupling can play a critical role in the functional properties of oxide heterostructures.

Asymmetric orbital-lattice interactions in ultrathin correlated oxide films.

Using resonant x-ray spectroscopies combined with density functional calculations, we find an asymmetric biaxial strain-induced d-orbital response in ultrathin films of the correlated metal LaNiO3 which are not accessible in the bulk. The sign of the misfit strain governs the stability of an octahedral "breathing" distortion, which, in turn, produces an emergent charge-ordered ground state with an altered ligand-hole density and bond covalency. Control of this new mechanism opens a pathway to rational orbital engineering, providing a platform for artificially designed Mott materials.

Controlled self-organization of atom vacancies in monatomic gallium layers.

Ga adsorption on the Si(112) surface results in the formation of pseudomorphic Ga atom chains. Compressive strain in these atom chains is relieved via creation of adatom vacancies and their self-organization into meandering vacancy lines. The average spacing between these line defects can be controlled, within limits, by adjusting the chemical potential mu of the Ga adatoms. We derive a lattice model that quantitatively connects density functional theory (DFT) calculations for perfectly ordered structures with the fluctuating disorder seen in experiment and the experimental control parameter mu. This hybrid approach of lattice modeling and DFT can be applied to other examples of line defects in heteroepitaxy.

Dental restorative composites containing 2,2-bis-[4-(2-hydroxy-3-methacryloyloxy propoxy) phenyl] propane derivatives and spiro orthocarbonates.

Various dental restorative composite resins containing 2,2-bis-[4-(2-hydroxy-3-methacryloyloxy propoxy) phenyl] propane (Bis-GMA) derivatives and spiro orthocarbonates (SOCs) were explored for minimizing the volumetric shrinkage that generally occurs during polymerization. Previous reports suggested mixing Bis-GMA with its derivative TMBis-GMA (2,2-bis[3,5-dimethyl-4-(2-hydroxy-3-methacryloyloxy propoxy) phenyl] propane) to obtain a dental composite with low volumetric shrinkage. It was hypothesized that spiro orthocarbonates would expand volumetrically during polymerization, because of their sophisticated ring-opening reactions; therefore several of them were added to the mixture of Bis-GMA and TMBis-GMA to bring about further reductions in volumetric shrinkage. It was indeed possible to reduce the extent of volumetric shrinkage of dental composites containing SOCs, and to do so without compromising these resins' mechanical properties.

Histone deacetylases induce angiogenesis by negative regulation of tumor suppressor genes.

Low oxygen tension influences tumor progression by enhancing angiogenesis; and histone deacetylases (HDAC) are implicated in alteration of chromatin assembly and tumorigenesis. Here we show induction of HDAC under hypoxia and elucidate a role for HDAC in the regulation of hypoxia-induced angiogenesis. Overexpressed wild-type HDAC1 downregulated expression of p53 and von Hippel-Lindau tumor suppressor genes and stimulated angiogenesis of human endothelial cells. A specific HDAC inhibitor, trichostatin A (TSA), upregulated p53 and von Hippel-Lindau expression and downregulated hypoxia-inducible factor-1alpha and vascular endothelial growth factor. TSA also blocked angiogenesis in vitro and in vivo. TSA specifically inhibited hypoxia-induced angiogenesis in the Lewis lung carcinoma model. These results indicate that hypoxia enhances HDAC function and that HDAC is closely involved in angiogenesis through suppression of hypoxia-responsive tumor suppressor genes.

Angiogenic activity of pyruvic acid in in vivo and in vitro angiogenesis models.

The excessive growth of a tumor requires high rates of glucose uptake and glycolysis and continuous recruitment of new blood vessels. Here, we provide several lines of evidence showing that pyruvic acid, the end product of glycolysis, exhibits strong angiogenic activity. Pyruvic acid promoted angiogenesis in chorioallantoic membrane assay and in vivo mouse Matrigel plug assay. Pyruvic acid also positively affects angiogenic cascade, DNA synthesis, migration, and tube formation in bovine aortic endothelial cells. Furthermore, mRNA expression of fibroblast growth factor receptor-2 and vascular endothelial growth factor was enhanced by pyruvic acid. These results strongly suggest that pyruvic acid plays an important role in angiogenesis for tumor growth and metastasis.

A Case of Well-differentiated Papillary Mesothelioma Developing Malignant Mesothelioma with Seeding Mass on the Trocar Insertion Site of Diagnostic Laparoscopy and Malignant Change.

Although well-differentiated papillary mesothelioma (WDPM) is usually classified as benign, the natural history of this lesion has not been clearly established. We present a case of WDPM in 60-year old woman developing malignant mesothelioma with seeding mass on the trocar insertion site over a period of 2 years. The initial symptom exhibited by the patient was abdominal distension from massive ascitic fluid. With an impression of peritoneal carcinomatosis, we performed a diagnostic laparoscopy. On the laparoscopic finding, a small whitish nodule was found on the liver surface and the pathologic result revealed reactive mesothelial hyperplasia. At exploro-laparotomy, multiple small nodules were found on the omentum and a biopsy revealed well-differentiated papillary mesothelioma of the peritoneum. The patient underwent pelvic lymphadenectomy and omentectomy of the colon and was followed for 2 years without any further treatment. Subsequently, she presented with abdominal distention with massive ascites and palpable abdominal wall mass at the previous trocar insertion site. Malignant mesothelioma was confirmed histologically via re- exploration. The rare transformation of well-differentiated papillary mesothelioma into a typically malignant diffuse mesothelioma and the unusual seeding on trocar insertion site prompted us to report this case.

Anti-angiogenic activity of torilin, a sesquiterpene compound isolated from Torilis japonica.

Torilin is a sesquiterpene compound purified from fruits of Torilis japonica (Umbelliferae). In this study, we demonstrated the anti-angiogenic activity of torilin using in vivo and in vitro assay systems. Torilin decreased both neovascularization of chick embryos in the chorioallantoic membrane assay and basic fibroblast growth factor-induced vessel formation in the mouse Matrigel plug assay. Torilin also reduced the proliferation and tube formation of human umbilical vein endothelial cells. In addition, the concentrated conditioned media obtained from torilin-treated HepG2 human hepatoblastoma cells blocked the angiogenic activation of torilin-untreated concentrated conditioned media, indicating that torilin may have an inhibitory effect on tumor-induced angiogenesis. To determine what molecules were involved in the anti-angiogenic activity, we examined the expression of hypoxia-inducible angiogenic factors in torilin-treated HepG2 cells. Torilin significantly down-regulated the expression of hypoxia-inducible vascular endothelial growth factor and insulin-like growth factor-II. Taken together, our data suggest that torilin may be a strong angiogenic inhibitor with the ability to decrease tube formation of vascular endothelial cells and to reduce expression of angiogenic factors of tumor cells.

Identification of angiogenic properties of insulin-like growth factor II in in vitro angiogenesis models.

Insulin-like growth factor II (IGF-II), highly expressed in a number of human tumours, has been recently known to promote neovascularization in vivo. Yet, the detailed mechanism by which IGF-II induces angiogenesis has not been well defined. In the present study, we explored an angiogenic activity of IGF-II in in vitro angiogenesis model. Human umbilical vein endothelial cells (HUVECs) treated with IGF-II rapidly aligned and formed a capillary-like network on Matrigel. In chemotaxis assay, IGF-II remarkably increased migration of HUVECs. A rapid and transient activation of p38 mitogen-activated protein kinase (p38 MAPK) and p125 focal adhesion kinase (p125FAK) phosphorylation was detected in HUVECs exposed to IGF-II. IGF-II also stimulated invasion of HUVECs through a polycarbonate filter coated with Matrigel. Quantitative gelatin-based zymography identified that matrix metalloproteinase-2 (MMP-2) activity generated from HUVECs was increased by IGF-II. This induction of MMP-2 activity was correlated with Northern blot analysis, showing in HUVECs that IGF-II increased the expression of MMP-2 mRNA, while it did not affect that of TIMP-2, a tissue inhibitor of MMP-2. These results provide the evidence that IGF-II directly induces angiogenesis by stimulating migration and morphological differentiation of endothelial cells, and suggest that IGF-II may play a crucial role in the progression of tumorigenesis by promoting the deleterious neovascularization.

Sphingosine 1-phosphate induces angiogenesis: its angiogenic action and signaling mechanism in human umbilical vein endothelial cells.

Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid metabolite abundantly stored in platelets and released upon platelet activation. Recently, S1P has been postulated for its potential roles in angiogenesis. In this study, we provided several lines of evidence showing that S1P has angiogenic activity. In vitro, S1P stimulated DNA synthesis and chemotactic motility of human umbilical vein endothelial cells (HUVECs) in a dose-dependent manner, reaching a near maximum at 1 microM. S1P also significantly induced tube formation of HUVECs on Matrigel. Matrigel plug assay in mice revealed that S1P promotes angiogenesis in vivo. In addition, exposure of HUVECs to S1P led to rapid activation of extracellular signal-regulated kinases (ERKs) and p38 mitogen-activated protein kinase (p38 MAPK) in a pertussis toxin (PTX)-sensitive manner. Notably, HUVEC migration and tube formation in response to S1P were completely blocked by pretreatment with PTX. Further, the MEK inhibitor U0126 markedly inhibited S1P-induced tube formation but S1P-induced migration was not affected by inhibition of ERK and p38 MAPK. Taken together, these results indicate that S1P induces angiogenesis predominantly via G(i) protein-coupled receptors in endothelial cells and suggest that S1P may act as an important modulator of platelet-induced angiogenesis.

The nitric oxide-producing activities of Scutellaria baicalensis.

Scutellaria baicalensis (SB) has antibacterial and antiviral activities. Nitric oxide (NO) as a potent macrophage-derived effector molecule against a variety of bacteria, viruses and tumors has received increasing attention. The objective of this study was to determine the effect of SB on the production of NO. Stimulation of mouse peritoneal macrophages with SB after the treatment of recombinant interferon-gamma (rIFN-gamma) resulted in the increased NO production. SB had no effect on NO production by itself. When SB was used in combination with rIFN-gamma, there was a marked cooperative induction of NO production in a dose-dependent manner. The optimal effect of SB on NO production was shown 6 h after treatment with rIFN-gamma. NO production by SB was inhibited by N(G)-monomethyl-L-arginine. The increased production of NO from rIFN-(gamma) plus SB-stimulated cells was decreased by the treatment of protein kinase C inhibitor such as staurosporin. In addition, synergy between rIFN-gamma and SB was mainly dependent on SB-induced tumor necrosis factor-alpha (TNF-alpha) secretion. All the preparations of SB were endotoxin free. These results suggest that the capacity of SB to increase NO production from rIFN-gamma-primed mouse peritoneal macrophages is the result of SB-induced TNF-gamma secretion.

A novel angiogenic factor derived from Aloe vera gel: beta-sitosterol, a plant sterol.

Aloe vera gel has a beneficial effect on wound healing. Because angiogenesis is an essential process in wound healing, we hypothesized that Aloe vera gel might contain potent angiogenic compounds. Here we demonstrate that Aloe vera gel and its extracts are angiogenic on the chorioallantoic membrane (CAM) of chick embryo. Out of the three compounds purified from the final fraction of Aloe vera gel, beta-sitosterol showed a potent angiogenic activity in the CAM assay. In the presence of heparin, beta-sitosterol stimulated neovascularization in the mouse Matrigel plug assay and the motility of human umbilical vein endothelial cells in an in vitro wound migration assay. Thus beta-sitosterol is a novel plant-derived angiogenic factor which may have potential pharmaceutical applications for the management of chronic wounds.