New Synthesis Method for the Growth of Epitaxial Graphene

As a viable candidate for an all-carbon post-CMOS electronics revolution, epitaxial graphene has attracted significant attention. To realize its application potential, reliable methods for fabricating large-area single-crystalline graphene domains are required. A new way to synthesize high quality epitaxial graphene, namely "face-to-face" method, has been reported in this paper. The structure and morphologies of the samples are characterized by low-energy electron diffraction, atomic force microscopy, angle-resolved photoemission spectroscopy and Raman spectroscopy. The grown samples show better quality and larger length scales than samples grown through conventional thermal desorption. Moreover the graphene thickness can be easily controlled by changing annealing temperature.Comment: 16 pages and 7 figure

Norcantharidin Induces Human Melanoma A375-S2 Cell Apoptosis through Mitochondrial and Caspase Pathways

Norcantharidin (NCTD) is the demethylated form of cantharidin, which is the active substance of mylabris. To examine the pathway of NCTD-induced A375-S2 cell death, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-dipheyltetrazolium bromide (MTT) assay, photomicroscopical observation, DNA agarose gel electrophoresis, caspase activity assay and Western blot analysis were carried out. A375-S2 cells treated with NCTD exhibited several typical characteristics of apoptosis. The inhibitory effect of NCTD on human melanoma, A375-S2 cells, was partially reversed by the inhibitors of pan-caspase, caspase-3 and caspase-9. The activities of caspase-3 and -9 were significantly increased after treatment with NCTD at different time. The expression of inhibitor of caspase-activated DNase was decreased in a time-dependent manner, simultaneously, the ratio of Bcl-2/Bax or Bcl-xL/Bax was decreased and the expression ratio of proteins could be reversed by caspase-3 inhibitor. The expression of cytochrome c in cytosol was increased after NCTD treatment and caspase-3 inhibitor had no significant effect on the up-regulation of cytochrom c. These results suggest that NCTD induced A375-S2 cell apoptosis and the activation of caspase and mitochondrial pathway were involved in the process of NCTD-induced A375-S2 cell apoptosis

Zoledronic acid inhibits pulmonary metastasis dissemination in a preclinical model of Ewing's sarcoma via inhibition of cell migration

Background: Ewing’s sarcoma (ES) is the second most frequent primitive malignant bone tumor in adolescents with a very poor prognosis for high risk patients, mainly when lung metastases are detected (overall survival <15% at 5 years). Zoledronic acid (ZA) is a potent inhibitor of bone resorption which induces osteoclast apoptosis. Our previous studies showed a strong therapeutic potential of ZA as it inhibits ES cell growth in vitro and ES primary tumor growth in vivo in a mouse model developed in bone site. However, no data are available on lung metastasis. Therefore, the aim of this study was to determine the effect of ZA on ES cell invasion and metastatic properties. Methods: Invasion assays were performed in vitro in Boyden’s chambers covered with Matrigel. Matrix Metalloproteinase (MMP) activity was analyzed by zymography in ES cell culture supernatant. In vivo, a relevant model of spontaneous lung metastases which disseminate from primary ES tumor was induced by the orthotopic injection of 106 human ES cells in the tibia medullar cavity of nude mice. The effect of ZA (50 μg/kg, 3x/week) was studied over a 4-week period. Lung metastases were observed macroscopically at autopsy and analysed by histology. Results: ZA induced a strong inhibition of ES cell invasion, probably due to down regulation of MMP-2 and −9 activities as analyzed by zymography. In vivo, ZA inhibits the dissemination of spontaneous lung metastases from a primary ES tumor but had no effect on the growth of established lung metastases. Conclusion: These results suggest that ZA could be used early in the treatment of ES to inhibit bone tumor growth but also to prevent the early metastatic events to the lungs

Severe Compromise of Preosteoblasts in a Surgical Mouse Model of Bisphosphonate-Associated Osteonecrosis of the Jaw.

Objectives: The effect of amino-bisphosphonates on osteoblastic lineage and its potential contribution to the pathogenesis of bisphosphonate-associated osteonecrosis of the jaw (BONJ) remain controversial. We assessed the effects of zoledronic acid (ZOL) on bone and vascular cells of the alveolar socket using a mouse model of BONJ. Material and Methods: Thirty-two mice were treated twice a week with either 100 μg/kg of ZOL or saline for 12 weeks. The first left maxillary molar was extracted at the third week. Alveolar sockets were assessed at both 3 weeks (intermediate) and 9 weeks (long-term) after molar extraction by semi-quantitative histomorphometry for empty lacunae, preosteoblasts (Osterix), osteoclasts (TRAP), and pericyte-like cells (CD146). Also, the bone microarchitecture was assessed by micro-CT. Results: Osteonecrotic-like lesions were observed in 21% of mice. Moreover, a decreased number of preosteoblasts contrasted with the increased number of osteoclasts at both time points. In addition, osteoclasts display multinucleation and detachment from the endosteal surface. Furthermore, the number of pericyte-like cells increased at the intermediate time point. The alveolar bone mass increased exclusively with long-term ZOL treatment. Conclusion: The severe imbalance between bone-forming cells and bone-resorbing cells showed in this study could contribute to the pathogenesis of BONJ

Pharmacokinetic/pharmacodynamic modelling approaches in paediatric infectious diseases and immunology.

Pharmacokinetic/pharmacodynamic (PKPD) modelling is used to describe and quantify dose-concentration-effect relationships. Within paediatric studies in infectious diseases and immunology these methods are often applied to developing guidance on appropriate dosing. In this paper, an introduction to the field of PKPD modelling is given, followed by a review of the PKPD studies that have been undertaken in paediatric infectious diseases and immunology. The main focus is on identifying the methodological approaches used to define the PKPD relationship in these studies. The major findings were that most studies of infectious diseases have developed a PK model and then used simulations to define a dose recommendation based on a pre-defined PD target, which may have been defined in adults or in vitro. For immunological studies much of the modelling has focused on either PK or PD, and since multiple drugs are usually used, delineating the relative contributions of each is challenging. The use of dynamical modelling of in vitro antibacterial studies, and paediatric HIV mechanistic PD models linked with the PK of all drugs, are emerging methods that should enhance PKPD-based recommendations in the future

Technique for the Dry Transfer of Epitaxial Graphene onto Arbitrary Substrates

In order to make graphene technologically viable, the transfer of graphene films to substrates appropriate for specific applications is required. We demonstrate the dry transfer of epitaxial graphene (EG) from the C-face of 4H-SiC onto SiO2, GaN and Al2O3 substrates using a thermal release tape. We further report on the impact of this process on the electrical properties of the EG films. This process enables EG films to be used in flexible electronic devices or as optically transparent contacts.Comment: 8 pages, 4 figures and supplementary info regarding procedure for transfe

Identification of Genes under Positive Selection Reveals Differences in Evolutionary Adaptation between Brown-Algal Species

Brown algae are an important taxonomic group in coastal ecosystems. The model brown algal species Ectocarpus siliculosus and Saccharina japonica are closely related lineages. Despite their close phylogenetic relationship, they vary greatly in morphology and physiology. To obtain further insights into the evolutionary forces driving divergence in brown algae, we analyzed 3,909 orthologs from both species to identify Genes Under Positive Selection (GUPS). About 12% of the orthologs in each species were considered to be under positive selection. Many GUPS are involved in membrane transport, regulation of homeostasis, and sexual reproduction in the small sporophyte of E. siliculosus, which is known to have a complex life cycle and to occupy a wide range of habitats. Genes involved in photosynthesis and cell division dominated the group of GUPS in the large kelp of S. japonica, which might explain why this alga has evolved the ability to grow very rapidly and to form some of the largest sporophytes. A significant number of molecular chaperones (e.g., heat-shock proteins) involved in stress responses were identified to be under positive selection in both species, potentially indicating their important roles for macroalgae to cope with the relatively variable environment of coastal ecosystems. Moreover, analysis of previously published microarray data of E. siliculosus showed that many GUPS in E. siliculosus were responsive to stress conditions, such as oxidative and hyposaline stress, whereas our RNA-seq data of S. japonica showed that GUPS in this species were most highly expressed in large sporophytes, which supports the suggestion that selection largely acts on different sets of genes in both marcoalgal species, potentially reflecting their adaptation to different ecological niches

Stabilization of mid-sized silicon nanoparticles by functionalization with acrylic acid

We present an enhanced method to form stable dispersions of medium-sized silicon nanoparticles for solar cell applications by thermally induced grafting of acrylic acid to the nanoparticle surface. In order to confirm their covalent attachment on the silicon nanoparticles and to assess the quality of the functionalization, X-ray photoelectron spectroscopy and diffuse reflectance infrared Fourier spectroscopy measurements were carried out. The stability of the dispersion was elucidated by dynamic light scattering and Zeta-potential measurements, showing no sign of degradation for months