Zr alloy protection against high-temperature oxidation: Coating by a double-layered structure with active and passive functional properties

In this work, a new concept of metal surface protection against degradation caused by high-temperature oxidation in water environment is presented. We were the first to create a double-layered coating consisting of an active and passive part to protect Zr alloy surface against high-temperature oxidation in a hot water environment. We investigated the hot steam corrosion of ZIRLO fuel cladding coated with a double layer consisting of 500 nm nanocrystalline diamond (NCD) as the bottom layer and 2 m chromium-aluminum-silicon nitride (CrAlSiN) as the upper layer. Coated and noncoated ZIRLO samples were exposed for 4 days at 400 °C in an autoclave (working water-cooled nuclear reactor temperature) and for 60 minutes at 1000 °C (nuclear reactor accident temperature) in a hot steam furnace. We have shown that the NCD coating protects the Zr alloy surface against oxidation in an active way: carbon from NCD layer enters the Zr alloy surface and, by changing the physical and chemical properties of the Zr cladding tube surface, limits the Zr oxidation process. In contrast, the passive CrAlSiN coating prevents the Zr cladding tube surface from coming into physical contact with the hot steam. The advantages of the double layer were demonstrated, particularly in terms of hot (accident-temperature) oxidation kinetics: in the initial stage, CrAlSiN layer with low number of defects acts as an impermeable barrier. But after a longer time (more than 20 minutes) the protection by more cracked CrAlSiN decreases. At the same time, the carbon from NCD strongly penetrates the Zr cladding surface and worsen conditions for Zr oxidation. For the double-layer coating, the underlying NCD layer mitigates thermal expansion, reducing cracks and defects in upper layer CrAlSiN

Cancer targeting with biomolecules: a comparative study of photodynamic therapy efficacy using antibody or lectin conjugated phthalocyanine-PEG gold nanoparticles

The functionalisation of therapeutic nanoparticle constructs with cancer-specific biomolecules can enable selective tumour accumulation and targeted treatment. Water soluble gold nanoparticles (ca. 4 nm) stabilised by a mixed monolayer of a hydrophobic zinc phthalocyanine photosensitiser (C11Pc) and hydrophilic polyethylene glycol (PEG) have been prepared. The C11Pc-PEG gold nanoparticle constructs were further functionalised with jacalin, a lectin specific for the cancer-associated Thomsen–Friedenreich (T) carbohydrate antigen, or with monoclonal antibodies specific for the human epidermal growth factor receptor-2 (HER-2). The two biofunctionalised nanoparticle conjugates produced similar levels of singlet oxygen upon irradiation at 633 nm. Importantly, both nanoparticle conjugates demonstrated extensive, yet comparable, phototoxicity in HT-29 colorectal adenocarcinoma cells (80–90%) and in SK-BR-3 breast adenocarcinoma cells (>99%). Non-conjugated C11Pc-PEG gold nanoparticles were only minimally phototoxic. Lysosomal colocalisation studies performed with the HT-29 colon cancer cells and the SK-BR-3 breast cancer cells revealed that both nanoparticle conjugates were partially localised within acidic organelles, which is typical of receptor-mediated endocytosis. The similarity of the targeted PDT efficacy of the two biofunctionalised C11Pc-PEG gold nanoparticles is discussed with respect to targeting ligand binding affinity and cell surface antigen density as key determinants of targeting efficiency. This study highlights how targeting small cell-surface molecules, such as the T antigen, can mediate a selective photodynamic treatment response which is similar to that achieved when targeting overexpressed protein receptors, such as HER-2. The high prevalence of the T antigen present on the cellular surface of primary tumours emphasises the broad potential applications for lectin-targeted therapies

Microstructure and precipitates in annealed Co38Ni33Al29 ferromagnetic shape memory alloy

Transmission electron microscopy was performed to investigate the microstructure and precipitates in the annealed Co38Ni33Al29 ferromagnetic shape memory alloy. Apart from the dendritic secondary phase in the austenite matrix, micron-sized (up to 100 μm) fcc-based precipitates with partial γ′ L12 ordering and containing none, one or three {1 1 1}p parallel twin planes were found. The orientation relationship between the precipitates and matrix was found to be Kurdjumov–Sachs. STEM–EDX analysis indicates that twinned and non-twinned precipitates are Co-rich and Al- and Ni-deficient with respect to the matrix and with a lower Co/Al ratio for the latter. The 3D morphologies of precipitates were reconstructed with focused ion beam/scanning electron microscope dual-beam slice-and-view imaging, showing that the single {1 1 1}p plane twinned precipitates have a plate-like shape while the non-twinned precipitates are lath-like and often bent

Ontology Based Strategies for Supporting Communication within Social Networks

In this paper, ontology based dialogue strategies are presented in connection with the concept of communicative images. Communicative images are graphical objects integrated with a dialogue interface and linked to an associated knowledge database which stores the semantics of the objects depicted. The relevant pieces of information can be linked to the external knowledge distributed in a social network. Exploiting a formal ontology approach facilitates the process of deriving information from relevant texts that can be found in the social network and it simultaneously forms a suitable framework for supporting dialogue communication in natural language. This approach is discussed and illustrated with various examples in this paper

Dynamics of new party formation in the Czech Republic 1996–2010: looking for the origins of a ‘political earthquake’

The stable and closed nature of the Czech party system and the failure of most new political parties have been among the most salient features of Czech democracy over the past two decades. The results of the 2010 parliamentary elections seemed to mark a break with this pattern: support for two main parties slumped to historically low levels and two new parties, TOP09 and Public Affairs (VV), entered parliament. This article seeks to put the ‘political earthquake’ of 2010 into perspective by mapping the development of new parties in the Czech Republic from the mid-1990s and relating them to comparative literature and typologies of new party emergence. It concludes that of the two successful new parties in 2010, Public Affairs was, by far, the more novel and important phenomenon

Targeting Angiogenesis-Dependent Calcified Neoplasms Using Combined Polymer Therapeutics

There is an immense clinical need for novel therapeutics for the treatment of angiogenesis-dependent calcified neoplasms such as osteosarcomas and bone metastases. We developed a new therapeutic strategy to target bone metastases and calcified neoplasms using combined polymer-bound angiogenesis inhibitors. Using an advanced "living polymerization" technique, the reversible addition-fragmentation chain transfer (RAFT), we conjugated the aminobisphosphonate alendronate (ALN), and the potent anti-angiogenic agent TNP-470 with N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer through a Glycine-Glycine-Proline-Norleucine linker, cleaved by cathepsin K, a cysteine protease overexpressed at resorption sites in bone tissues. In this approach, dual targeting is achieved. Passive accumulation is possible due to the increase in molecular weight following polymer conjugation of the drugs, thus extravasating from the tumor leaky vessels and not from normal healthy vessels. Active targeting to the calcified tissues is achieved by ALN's affinity to bone mineral.The anti-angiogenic and antitumor potency of HPMA copolymer-ALN-TNP-470 conjugate was evaluated both in vitro and in vivo. We show that free and conjugated ALN-TNP-470 have synergistic anti-angiogenic and antitumor activity by inhibiting proliferation, migration and capillary-like tube formation of endothelial and human osteosarcoma cells in vitro. Evaluation of anti-angiogenic, antitumor activity and body distribution of HPMA copolymer-ALN-TNP-470 conjugate was performed on severe combined immunodeficiency (SCID) male mice inoculated with mCherry-labeled MG-63-Ras human osteosarcoma and by modified Miles permeability assay. Our targeted bi-specific conjugate reduced VEGF-induced vascular hyperpermeability by 92% and remarkably inhibited osteosarcoma growth in mice by 96%.This is the first report to describe a new concept of a narrowly-dispersed combined polymer therapeutic designed to target both tumor and endothelial compartments of bone metastases and calcified neoplasms at a single administration. This new approach of co-delivery of two synergistic drugs may have clinical utility as a potential therapy for angiogenesis-dependent cancers such as osteosarcoma and bone metastases