National Mesothelioma Virtual Bank: A standard based biospecimen and clinical data resource to enhance translational research

Background: Advances in translational research have led to the need for well characterized biospecimens for research. The National Mesothelioma Virtual Bank is an initiative which collects annotated datasets relevant to human mesothelioma to develop an enterprising biospecimen resource to fulfill researchers' need. Methods: The National Mesothelioma Virtual Bank architecture is based on three major components: (a) common data elements (based on College of American Pathologists protocol and National North American Association of Central Cancer Registries standards), (b) clinical and epidemiologic data annotation, and (c) data query tools. These tools work interoperably to standardize the entire process of annotation. The National Mesothelioma Virtual Bank tool is based upon the caTISSUE Clinical Annotation Engine, developed by the University of Pittsburgh in cooperation with the Cancer Biomedical Informatics Grid™ (caBIG™, see http://cabig.nci.nih.gov). This application provides a web-based system for annotating, importing and searching mesothelioma cases. The underlying information model is constructed utilizing Unified Modeling Language class diagrams, hierarchical relationships and Enterprise Architect software. Result: The database provides researchers real-time access to richly annotated specimens and integral information related to mesothelioma. The data disclosed is tightly regulated depending upon users' authorization and depending on the participating institute that is amenable to the local Institutional Review Board and regulation committee reviews. Conclusion: The National Mesothelioma Virtual Bank currently has over 600 annotated cases available for researchers that include paraffin embedded tissues, tissue microarrays, serum and genomic DNA. The National Mesothelioma Virtual Bank is a virtual biospecimen registry with robust translational biomedical informatics support to facilitate basic science, clinical, and translational research. Furthermore, it protects patient privacy by disclosing only de-identified datasets to assure that biospecimens can be made accessible to researchers. © 2008 Amin et al; licensee BioMed Central Ltd

Atrial-like cardiomyocytes from human pluripotent stem cells are a robust preclinical model for assessing atrial-selective pharmacology

Drugs targeting atrial-specific ion channels, K(v)1.5 or K(ir)3.1/3.4, are being developed as new therapeutic strategies for atrial fibrillation. However, current preclinical studies carried out in non-cardiac cell lines or animal models may not accurately represent the physiology of a human cardiomyocyte (CM). In the current study, we tested whether human embryonic stem cell (hESC)-derived atrial CMs could predict atrial selectivity of pharmacological compounds. By modulating retinoic acid signaling during hESC differentiation, we generated atrial-like (hESC-atrial) and ventricular-like (hESC-ventricular) CMs. We found the expression of atrial-specific ion channel genes, KCNA5 (encoding Kv1.5) and KCNJ3 (encoding K-ir 3.1), in hESC-atrial CMs and further demonstrated that these ion channel genes are regulated by COUP-TF transcription factors. Moreover, in response to multiple ion channel blocker, vernakalant, and K(v)1.5 blocker, XEN-D0101, hESC-atrial but not hESC-ventricular CMs showed action potential (AP) prolongation due to a reduction in early repolarization. In hESC-atrial CMs, XEN-R0703, a novel K(ir)3.1/3.4 blocker restored the AP shortening caused by CCh. Neither CCh nor XEN-R0703 had an effect on hESC-ventricular CMs. In summary, we demonstrate that hESC-atrial CMs are a robust model for pre-clinical testing to assess atrial selectivity of novel antiarrhythmic drugs

Sequencing three crocodilian genomes to illuminate the evolution of archosaurs and amniotes

The International Crocodilian Genomes Working Group (ICGWG) will sequence and assemble the American alligator (Alligator mississippiensis), saltwater crocodile (Crocodylus porosus) and Indian gharial (Gavialis gangeticus) genomes. The status of these projects and our planned analyses are described

Flame retardancy of some ethylene-vinyl acetate copolymer-based formulation

The combustion behaviour and thermal decomposition of ethylene-vinyl acetate copolymer (EVA) (26 wt% vinyl acetate content) formulations containing alumina trihydrate, ammonium polyphosphate, melamine, pentaerythritol and their co-mixtures, were studied using cone calorimetry and thermogravimetric analysis. Formulations containing ammonium polyphosphate burned with the formation of intumescent carbonaceous chars, with EVA acting as a carbonization agent. EVA materials containing ammonium polyphosphate (20 wt%), with a sufficient amount of alumina trihydrate or melamine, were superior to the non-intumescent alumina trihydrate and melamine containing formulations in terms of the heat release rate, mass loss rate and smoke production. Melamine showed some smoke suppressant effect and significant CO reducing properties. However, the melamine-EVA and melamine-alumina trihydrate-EVA showed a very high heat release rate. Thermogravimetric studies showed that oxygen played a favourable role in enhancing the char formation by encouraging active participation of the polymer matrix in the interaction with polyphosphoric acid

Experimental parameters affecting the performance of the Purser furnace: a laboratory-scale experiment for a range of controlled real fire conditions

Yields of toxic combustion products from burning materials vary considerably between different stages and types of fire, eg fully ventilated, vitiated. It is important that any laboratory studies of such phenomena be carried out as close as possible to real fire conditions. The Purser furnace has been developed to widen the range of fire types amenable to laboratory-scale investigation. This paper describes Salford?s Purser furnace and reports the findings of a systematic assessment of the experimental parameters that affect the performance of the Purser furnace

Flame retardance of poly(methyl methacrylate) modified with phosphorus-containing compounds

MMA has been copolymerised with pentavalent phosphorus-containing monomers and the flame retardance of the resulting copolymers has been assessed by limiting oxygen indicies (LOI) and cone calorimetry experiments. The thermal stability of the copolymers has also been assessed by conventional thermogravimetric analysis (TGA). Poly(methyl methacrylate) (PMMA) modified with phosphorus-containing additives have also been synthesised and the flame retardance assessed. All of the modified PMMA samples contain 3.5 wt.\%, allowing a comparison of the relative merits of an additive and a reactive approach to flame retardance. The chemical environment of the phosphorus in terms of flame retardance achieved is also considered in this paper. The incorporation of 3.5 wt.\% phosphorus in both reactive and additive approaches increases the limiting oxygen index of PMMA from 17.8 to over 21. However, cone calorimetry shows that the phosphorus-containing copolymers are inherently more flame retardant than PMMA and the PMMA modified with phosphorus-containing additives. The methyl methacrylate (MMA) copolymers have significantly reduced peak rates of heat release and leave substantial char residue during combustion, as compared to PMMA. Cone calorimetry has also shown that the phosphates are more effective flame-retardants for PMMA than are the phosphonates in both additive and reactive approaches. TGA of the polymers indicates that the copolymers are more thermally stable than PMMA whilst PMMA containing the additives are less thermally stable. A condensed phase mechanism in which diethyl(methacryloyloxymethyl)phosphonate reduces the flammability of PMMA has been identified

Laser pyrolysis/time-of-flight mass spectrometry studies pertinent to the behaviour of flame-retarded polymers in real fire situations

The Salford Laser Pyrolysis/Time-of-Flight Mass Spectrometry (LP/TOFMS) technique, which models the behaviour in the so-called dark flame region behind the flame front in a polymer fire, has been applied to investigate flame-retarded polymethylmethacrylate (PMMA), rigid polyurethane foam systems and phosphorus retarded rigid polyurethane foams and a model urethane compound. The laser pyrolysis of aluminium oxide trihydrate (ATH) retarded PMMA produces a large amount of water and carbon dioxide in the volatiles. Also, the amount of the monomer evolved is reduced significantly compared to that obtained from pure PMMA. The implication of these results is that in a real fire situation, ATH influences PMMA pyrolysis in such a manner as to bring about a reduction in the evolved 'fuel' whilst at the same time adding non-combustible gases (e.g. water) to the flame region. Thus is the PMMA flame retarded. The rigid polyurethane foams studied varied in isocyanate index and the molecular weight of the polyols applied. The flame retardance of these materials has been shown to increase with increasing isocyanate index and weight fraction of isocyanate. Laser pyrolysis experiments of these samples showed that the major volatiles evolved were dominated by monomer and oligomers of the polypropylene glycol used to produce the foam, plus lower molecular weight species of which carbon dioxide appeared to be a significant part. An increase in isocyanate index results in a reduction in the extent of monomer/oligomer evolution and an increase in the low molecular weight species. With reference to the behaviour of the foams in a real fire situation, it could be imagined that the monomer/oligomer components and their breakdown products would act as fuel in the flame region while the low molecular weight species dominated by carbon dioxide would be relatively non-flammable. An increase of isocyanate index is equivalent to making less fuel and more of the 'inert gases' available to the burning zone and hence improving the fire resistance of the rigid polyurethane foams. The flame retardant mechanism of phosphorus, introduced as low percentages of dimethyl methylphosphonate, is also attributed to a reduction in fuel evolution via pyrolysis of rigid polyurethane foams

Cone calorimetry studies of polymer systems flame retarded by chemically bonded phosphorus

The combustion behaviour of polystyrene flame retarded by the incorporation of phosphorus-containing compounds has been studied by LOI and cone calorimetry. Both ?reactive? and ?additive? approaches to the incorporation of the phosphorus have been applied and assessed. The data obtained show that the reactive approach results in enhanced char formation during combustion due to a condensed phase mechanism. Flame retardation by the additive systems occurred exclusively in the vapour phase via both chemical and physical interactions. The main advantage of the reactive approach was the maintenance of the physical and chemical properties similar to those of the homopolymer. The phosphorus environment was also a significant factor in terms of the level of flame retardance achieved. Phosphonate species were more effective than were phosphate species

Effect of different compatibilisers on nanoclay dispersion, thermal stability, and burning behavior of polypropylene-nanoclay blends

The combustion behaviour of polystyrene flame retarded by the incorporation of phosphorus-containing compounds has been studied by LOI and cone calorimetry. Both 'reactive' and 'additive' approaches to the incorporation of the phosphorus have been applied and assessed. The data obtained show that the reactive approach results in enhanced char formation during combustion due to a condensed phase mechanism. Flame retardation by the additive systems occurred exclusively in the vapour phase via both chemical and physical interactions. The main advantage of the reactive approach was the maintenance of the physical and chemical properties similar to those of the homopolymer. The phosphorus environment was also a significant factor in terms of the level of flame retardance achieved. Phosphonate species were more effective than were phosphate species