Exploring the properties and applications of nanoceria: is there still plenty of room at the bottom?

Nanoceria is an exceptionally versatile, commercially valuable catalytic material whose properties vary dramatically from that of the bulk material. Nanoceria's redox properties can be tuned by choice of method of preparation, particle size, nature and level of dopant, particle shape and surface chemistry. The two oxidation states of the cerium element in the lattice make possible the formation of oxygen vacancies which are essential to the high reactivity of the material, its oxygen buffering capability and thus its ability to act as a catalyst for both oxidation and reduction reactions. Ceria has important commercial utility in the areas of chemical mechanical polishing and planarization, catalytic converters and diesel oxidation catalysts, intermediate temperature solid oxide fuel cells and sensors. Its potential future uses include chemical looping combustion, photolytic and thermolytic water splitting for hydrogen production and as a therapeutic agent for the treatment of certain human diseases. We have seen that the method of synthesis, particle size, stabilizing corona, and purity dictate where it is used commercially. Finally, in regards to the prescient words of Dr. Feynman, we note that while there is indeed “plenty of room at the bottom”, there quite possibly exists an optimal nanoceria size of between 2–3 nm that provides maximal reactivity and thermodynamic stability

Ab initio identification of functionally interacting pairs of cis-regulatory elements

Cooperatively acting pairs of cis-regulatory elements play important roles in many biological processes. Here, we describe a statistical approach, compositionally orthogonalized co-occurrence analysis (coCOA) that detects pairs of oligonucleotides that preferentially co-occur in pairs of sequence regions, controlling for correlations between the compositions of the analyzed regions. coCOA identified three clusters of oligonucleotide pairs that frequently co-occur at 5′ and 3′ ends of human and mouse introns. The largest cluster involved GC-rich sequences at the 5′ ends of introns that co-occur and are co-conserved with specific AU-rich sequences near intron 3′ ends. These motifs are preferentially conserved when they occur together, as measured by a new co-conservation measure, supporting common in vivo function. These motif pairs are also enriched in introns flanking alternative “cassette” exons, suggesting a role in silencing of intervening exons, and we showed that these motifs can cooperatively silence splicing of an intervening exon in a splicing reporter assay. This approach can be easily generalized to problems beyond RNA splicing

Taking advantage of tumor cell adaptations to hypoxia for developing new tumor markers and treatment strategies

Cancer cells in hypoxic areas of solid tumors are to a large extent protected against the action of radiation as well as many chemotherapeutic drugs. There are, however, two different aspects of the problem caused by tumor hypoxia when cancer therapy is concerned: One is due to the chemical reactions that molecular oxygen enters intoin therapeutically targeted cells. This results in a direct chemical protection against therapy by the hypoxic microenvironment which has little to do with cellular biological regulatory processes. This part of the protective effect of hypoxia has been known for more than half a century and has been studied extensively. However, in recent years more focus has been put into the other aspect of hypoxia, namely the effect of this microenvironmental condition on selecting cells with certain genetical pre-requisites that are negative with respect to patient prognosis. There are adaptive mechanisms, where hypoxia induces regulatory cascades in cells resulting in a changed metabolism or changes in extra cellular signalling. These processes may lead to changes in cellular intrinsic sensitivity to treatment irrespective of oxygenation and furthermore, may also have consequences for tissue organization. Thus, the adaptive mechanisms induced by hypoxia itself may have a selective effect on cells with a fine-tuned protection against damage and stress of many kinds. It therefore could be that the adaptive mechanisms may be taken advantage of for new tumor labelling/imaging and treatment strategies. One of the Achilles’ heels of hypoxia research has always been exact measurements of tissue oxygenation as well as control of oxygenation in biological tumor models. Thus, development of technology that can ease this control is vital in order to study mechanisms and perform drug development under relevant conditions. An integrated EU Framework project 2004-2009, termed Euroxy, demonstrates several pathways involved in transcription and translation control of the hypoxic cell phenotype and evidence of cross talk with responses to pH and redox changes. The carbon anhydrase isoenzyme CA IX was selected for further studies due to its expression on the surface of many types of hypoxic tumors. The effort has lead to marketable culture flaks with sensors and incubation equipment and the synthesis of new drug candidates against new molecular targets. New labelling/imaging methods for cancer diagnosing and imaging of hypoxic cancer tissue now are being tested in xeno-graft models and also are in early clinical testing while new potential anticancer drugs are undergoing tests using xenografted tumor cancers. The present paper describes the above results in individual consortium partner presentations