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Given the demographic challenges of an ageing population combined with rising patient expectation and the growing emphasis placed on cost containment by healthcare providers, economic regenerative medicine approaches for regeneration of damaged and diseased organs and tissues are a major clinical and socio-economic need. The scope of this chapter is to use skeletal regeneration as the exemplar to discuss classical and high-throughput screening approaches to biomaterials development for regenerative medicine, including choice and design of materials based on clinical need, biological assessment and regulatory issues.
Basic principles: development of materials for regenerative medicine
The increase in an ageing population in developed countries is accompanied by a growing need for replacement and repair of damaged organs and tissues. Transplantation of the patient’s own tissue is still considered the gold standard in many applications, but limited availability, and complications associated with harvesting of the so-called autograft, are becoming an important drawback. Tissues and organs from human or animal donors present issues of disease transmission and functional failure. Alternative strategies, based on biological growth factors, cell therapy and tissue-engineered constructs, are being explored as alternatives to the patient’s own tissue, but their use is hampered by biological instability and high costs. These issues demonstrate the need for strategies based on biomaterials, which are often synthetic, and thus less prone to instability problems. In addition, the fact that (synthetic) biomaterials can often be produced in large quantities and thus be available off-the-shelf is an important advantage when coping with an increasing need for regenerative approaches.
During a series of submersible surveys of the Shiribeshi Seamount, northern Sea of Japan, by the remotely-operated vehicle (ROV) ‘Dolphin 3K’ and the human-occupied vehicle (HOV) ‘Shinkai 2000’ in July 2001, dense patches of golden skate eggs were observed. Given the lack of information for this species, an analysis was performed to estimate the abundance of the eggs and to ascertain if any patterns could be determined from the distribution of eggs on the sea-floor as recorded by the ROV and HOV video cameras. Eggs, including some with viable embryos, were found on only one of four ROV benthic transect surveys and one crewed submersible dive in the same location. The site where eggs were laid was relatively small and appeared to have been revisited through time. This work is part of an ongoing collaborative effort between East Stroudsburg University and the Marine Biodiversity Research Programme at the Japan Agency for Marine–Earth Science and Technology to characterize the midwater and benthic deep-sea faunas around Japan.
Modern in situ survey technologies such as crewed submersibles, remotely-operated vehicles (ROVs), towed camera arrays, and visual/video plankton recorders (VPRs) were used to characterize the dominant anthomedusan species off the eastern seaboard of Japan. Notes on the taxonomy, distribution, behaviour and interspecies interactions are presented for the four observed species: Euphysa japonica, E. flammea, Calycopsis nematophora and Pandea rubra. A new generic definition for the genus Calycopsis is proposed. The possibility of run-on, cascading detrimental effects of oceanic acidification on midwater ecosystems was identified from observations made during the present study.
This paper presents the results of a juxtaposition of archaeological findings on Hohokam irrigation and ethnographic research on the social organization of irrigation. There are no ethnographic or historic records pertaining to the Hohokam, so the comparative ethnographic approach is perhaps more productive than in other situations. Several forms of canal irrigation organization are considered, including politically centralized, acephalous, private, and several forms of communal. We find that politically centralized, acephalous, and private forms are implausible in the Hohokam context. Several of the communal forms are plausible. We find no ethnographic basis for positing a valley-wide management system.
Biodiversity of cnidarian and ctenophore forms in Toyama Bay, Japan Sea, was lower than that in Sagami Bay, north-western Pacific, according to all the indices investigated. Highest richness of forms occurred in the 400—600 m depth layer in Sagami Bay, while in Toyama Bay richness was low in most layers. New forms continued to occur with increasing depth in Sagami Bay but not in Toyama Bay and species composition differed remarkably between the two bays. Putative secondary deep-sea gelatinous forms were identified. Horizontal patchiness in normalized abundances was the rule rather than the exception and for accurate calculations of biodiversity indices incorporating evenness or equitability, the necessity for multiple submersible dives in a single area and survey period was noted. Vertical migration and predation were identified as possible factors contributing to the higher diversity in the 400—600 m depth layer in Sagami Bay.
The defect formation in surface modified TiO2 has been studied. Anatase TiO2 structures in the 3-20 nm range formed by a wet chemical technique were surface modified and nitridation of the highly reactive TiO2nanocolloid surface was achieved by a quick and simple treatment in alkyl ammonium compounds. The nitriding process was also accompanied by a metal surface coating process using electroless plating techniques, resulting in a thin metal surface layer on the modified TiO2 nanostructures. The crystal structure of the resultant TiO2-xNx nano-colloids remained anatase and the freshly prepared samples exhibited a strong light emission near 560nm (2.21 eV), which red shifted to 660 nm (1.88 eV) and dropped in intensity with aging in the atmosphere. This behavior was also evident in some of the combined nitridized and metal coated TiO2 nano-colloids. Electron Spin Resonance performed on these samples identified a resonance at g = 2.0035, which increased significantly with nitridation. This resonance is attributed to an oxygen hole center created near the surface of the nanocolloid, which correlates well with the observed optical activity.
Spherical aberration corrected Atomic Number Contrast Scanning Electron Microscopy (Z-STEM) has recently demonstrated an amazing ability to not only obtain sub-angstrom levels of detail but also yield chemical information at that level as well. With an optimal probe size of 0.8 Å, extremely detailed images of CdSe nanocrystals were obtained showing the lattice structure and surface morphology. As an example of the usefulness of this technique, a sample of CdSe nanocrystals prepared using trioctylphosphine oxide (TOPO) as the surfactant was compared to a sample of CdSe prepared using a mixture of TOPO and hexadecylamine (HDA) as the surfactant. The TOPO/HDA nanocrystals exhibit a narrower size distribution and several orders of magnitude greater fluorescence compared to that of the TOPO only nanocrystals. Interestingly, the Z-STEM images show a striking difference in nanocrystal morphology as the result of the addition of HDA to the reaction mixture. This result suggests surface morphology can be tuned through judicious choice of surfactant. A second example of Z- STEM imaging involves the characterization of CdSe/ZnS core/shell nanocrystals. The mass contrast afforded by Z-STEM can easily distinguish between core and shell.
Surfaces of ceria (CeO2) particles have been studied by electron energy-loss spectroscopy in a field-emission gun scanning transmission electron microscope. All the ceria particles analyzed contained Ce3+ at the surface. Rare-earth impurities such as La were enriched at the surface and were observed for particles ranging from tens to hundreds of nanometers in size. The oxidation state of the cerium ion is measured from the Ce M5/M4white-line intensity ratio.
The aim of this study was to determine the effect of acute plasma volume expansion on arterial blood-gas status during 6.5 min strenuous cycling exercise comparing six athletes with and six athletes without exercise-induced arterial hypoxaemia (EIAH). We hypothesized that plasma volume expansion could improve arterial oxygen pressure in a homogeneous sample of athletes - those with EIAH. In this paper we have extended the analysis and results of our recently published surprising findings that lengthening cardiopulmonary transit time did not improve arterial blood-gas status in a heterogeneous sample of endurance cyclists. One 500 ml bag of 10 % Pentastarch (infusion condition) or 60 ml 0.9 % saline (placebo) was infused prior to exercise in a randomized, double-blind fashion on two different days. Power output, cardiac output, oxygen consumption and arterial blood gases were measured during strenuous exercise. Cardiac output and oxygen consumption were not affected by acute hypervolaemia. There were group × condition interaction effects for arterial oxygen pressure and alveolar-arterial oxygen pressure difference, suggesting that those with hypoxaemia experienced improved arterial oxygen pressure (+4 mmHg) and lower alveolar-arterial oxygen pressure difference (-2 mmHg) with infusion. In conclusion, acute hypervolaemia improves blood-gas status in athletes with EIAH. The impairment of gas exchange occurs within the first minute of exercise, and is not impaired further throughout the remaining duration of exercise. This suggests that arterial oxygen pressure is only minimally mediated by cardiac output. Experimental Physiology (2003) 88.4, 555-564.
The behaviour of Loligo opalescens as observed by a remotely operated vehicle (ROV) was analysed. Thirty-nine behavioural components were identified and classed into four categories: chromatic, postural, locomotory, and inking. The frequency with which components were expressed was correlated to whether or not an individual was schooling, shoaling, alone with the ROV, or in the presence of other species. Behaviours observed were compared to those reported for other Loligo species. Observations of schooling and feeding behaviour, and reactions to other species are included.
A family of quadratic maps of the plane has been found numerically for certain parameter values to have three attractors, in a triangular pattern, with ‘intermingled’ basins. This means that for every open set S, if the basin of attraction of one of the attractors intersects S in a set of positive Lebesgue measure, then so do the other two basins. In this paper we mathematically verify this observation for a particular parameter, and prove that our results hold for a set of parameters with positive Lebesgue measure.
IBS of buried α and β iron suicide layers was achieved by the implantation of 2 MeV 56Fe+ ions into (100) single crystal silicon substrates over a dose range of 3 × 1017 to 1 × 1018 cm“-2followed by a high temperature anneal. No photoluminescence was observed from the as-implanted samples which contained a discontinuous layer of βFeSi2 precipitates approximately 1.5 μm below the silicon surface. Upon annealing at 700°C, a 200 nm polycrystalline βFeSi2 layer was formed which gave a PL signal centred at 1.55 μm. After a 900°C anneal, the layer transformed to αFeSix with a resistivity of approximately 280μΩcm.
Three unusual cases of oropharyngeal lympho-proliferative lesions were seen in recipients of heart and heart-lung transplants. Two caused acute upper respiratory obstruction necessitating urgent ENT intervention. All patients were receiving immunosuppressive drugs including cyclosporin. The two obstructive cases were adenotonsillar enlargement in a 6-year-old, and a tumour of the tonsil and tongue base with cervical lymph node enlargement in a 32-year-old male. Both were caused by Epstein-Barr Virus-associated lymphoproliferative disorder. The third patient, a 32-year-old female, had a presumed low grade T-cell lymphoma that regressed spontaneously.
Histopathological diagnosis of these lympho-proliferative disorders after transplantation usually requires immunocytochemistry to distinguish polyclonal proliferative disorders from true lymphoma. Polyclonal lymphoproliferative disorders after transplantation do not usually require aggressive cytoreductive therapy, but respond to simple measures such as the reduction of immunosuppression.