91 research outputs found
Simulation studies of transition metal and actinide oxides
This thesis reports the results of several studies carried out using the technique of atomistic computer simulation. First, an investigation of the behaviour of several important fission products in UO2±x is discussed. With the aid of a simple statistical mechanical model of defect equilibria, the favoured location for single Xe atoms in UO2 is found to display a marked dependence on the Xe concentration. A predicted change in the preferred location of Xe as the Xe concentration is increased, is shown to coincide with a well known reduction in the diffusion coefficient of this fission product. Using similar techniques, the charge state and location of Mo atoms in UO2±x is then investigated. A computed estimate of the solubility of Mo in UO2±x is found to agree with the generally insoluble nature for this important fission product. Mo atoms dispersed in the lattice are calculated to have a charge state of no greater than 3+. Results are also given concerning the behaviour of atoms of the closely related fission products Ru, Rh and Pd. Finally, as a test of our model for fission product solubility, the behaviour of Sr and Ba in UO2 is investigated and the results compared with experiment. The clustering of defects in the highly non-stoichiometric transition metal oxides Mn1-xO, Fe1-xO, Co1-XO and Ni1-XO is a well studied phenomenon. In the final part of this thesis the effect of the dopants Mn, Fe, Co and Ni on the stability of several important defect structures in these oxides is investigated. If crystal field effects are included in the analysis, Fe is found to enhance the stability of {4:1} defect clusters in Mn1-XO, Co1-XO and Ni1-XO
Hydrostatic Pressure Differentially Regulates Outer and Inner Annulus Fibrosus Cell Matrix Production in 3D Scaffolds
Mechanical stimulation may be used to enhance the development of engineered constructs for the replacement of load bearing tissues, such as the intervertebral disc. This study examined the effects of dynamic hydrostatic pressure (HP) on outer and inner annulus (OA, IA) fibrosus cells seeded on fibrous poly(glycolic acid)-poly(L-lactic acid) scaffolds. Constructs were pressurized (5 MPa, 0.5 Hz) for four hours/day from day 3 to day 14 of culture and analyzed using ELISAs and immunohistochemistry (IHC) to assess extracellular matrix (ECM) production. Both cell types were viable, with OA cells exhibiting more infiltration into the scaffold, which was enhanced by HP. ELISA analyses revealed that HP had no effect on type I collagen production while a significant increase in type II collagen (COL II) was measured in pressurized OA constructs compared to day 14 unloaded controls. Both OA and IA dynamically loaded scaffolds exhibited more uniform COL II elaboration as shown by IHC analyses, which was most pronounced in OA-seeded scaffolds. Overall, HP resulted in enhanced ECM elaboration and organization by OA-seeded constructs, while IA-seeded scaffolds were less responsive. As such, hydrostatic pressurization may be beneficial in annulus fibrosus tissue engineering when applied in concert with an appropriate cell source and scaffold material
Induction of osteoblast differentiation markers in human dermal fibroblasts: potential application to bone tissue engineering.
Tissue engineered constructs have the potential to be used as replacements for current bone graft technologies. One component necessary for bone tissue engineering is a readily available, osteogenic cell source. Human dermal fibroblasts may have the potential to differentiate along an osteoblastic lineage, making them a candidate for use in bone tissue engineering applications. The objective of this study was to validate the ability of dermal fibroblasts to express gene and protein markers of osteoblastic differentiation and to explore their potential, in combination with biomaterial scaffolds and signaling factors, for use in bone tissue engineering
Carboxymethylcellulose hydrogels support cns-derived tumor cell chemotactic migration
The local microenvironment plays an important role in maintaining the dynamics of the extracellular matrix (ECM) and the cell-ECM relationship. ECM is a complex network of molecules with distinct mechanical and biochemical characteristics. When the mechanisms that are in place to maintain ECM homeostasis are deregulated, most likely, this is the onset of cancer. The ECM becomes highly disorganized and the cell-matrix relationship changes, thus promoting alternations in cell mechanisms and metastasis. Medulloblastoma (MB) is one of the most common, malignant pediatric brain tumors in the United States. In order to gain a better understanding between the cell-ECM relationship and cell migratory responses in tumors we investigate 7 different types of ECM proteins via a MB-derived cell line: Poly-D-Lysine (PDL), Matrigel, Laminin, Collagen-1, Fibronectin, a 10% blend of Laminin-Collagen1, a 20% blend of Laminin-Collagen 1 and a new cellulose derived hydrogel, carboxymethylcellulose (CMC). Over time, the average changes in cell morphology, in 2D and 3D, are quantified. Data reveals CMC allows for a cell-ECM relationship typically believed to present in tumors, with cell exhibiting amoeboidal morphology that is believed to indicate the ready-ness of a cell to migrate within a given environment. Further investigation into the CMC hydrogels reveal a polysaccharide that allows for chemotactic study of MB-derived Daoy cells enabling minimal haptotactic migration conducive in the mechanistic study of the cellsâ chemotactic behavior. Understanding the cell-ECM relationship provides insight into their interactions and the information obtained can be utilized in studying the natural migratory patterns of cells. CMC allows for such a behavior to be studied along with testing the motility of Daoy cells because the hydrogel provides minimal integrin interaction between the cells and the ECM. This study provides insights into understanding the mechanisms behind tumor-associated migratory patterns via chemokines. The data reflects a new possibility of tackling central nervous system (CNS) diseases by utilizing a platform of natural hydrogels to generate therapies inhibiting metastasis
Genipin-Crosslinked Fibrin Hydrogels Modified With Collagen or Fibronectin as an Annulus Fibrosus Sealant
Cellular Models of Aggregation-Dependent Template-Directed Proteolysis to Characterize Tau Aggregation Inhibitors for Treatment of Alzheimer's Disease
Copyright © 2015, The American Society for Biochemistry and Molecular Biology. Acknowledgements-We thank Drs Timo Rager and Rolf Hilfiker (Solvias, Switzerland) for polymorph analyses.Peer reviewedPublisher PD
Carboxymethylcellulose hydrogels support central nervous system-derived tumor-cell chemotactic migration: comparison with conventional extracellular matrix macromolecules
The local microenvironment plays an important role in maintaining the dynamics of the extracellular matrix and the cell-extracellular matrix relationship. The extracellular matrix is a complex network of macromolecules with distinct mechanical and biochemical characteristics. Disruptions in extracellular matrix homeostasis are associated with the onset of cancer. The extracellular matrix becomes highly disorganized, and the cell-matrix relationship changes, resulting in altered cell-signaling processes and metastasis. Medulloblastoma is one of the most common malignant pediatric brain tumors in the United States. In order to gain a better understanding of the interplay between cell-extracellular matrix interactions and cell-migratory responses in tumors, eight different matrix macromolecule formulations were investigated using a medulloblastoma-derived cell line: poly-D-lysine, matrigel, laminin, collagen 1, fibronectin, a 10% blend of laminin-collagen 1, a 20% blend of laminin-collagen 1, and a cellulose-derived hydrogel, carboxymethylcellulose. Over time, the average changes in cell morphology were quantified in 2D and 3D, as was migration in the presence and absence of the chemoattractant, epidermal growth factor. Data revealed that carboxymethylcellulose allowed for a cell-extracellular matrix relationship typically believed to be present in tumors, with cells exhibiting a rounded, amoeboid morphology consistent with chemotactic migration, while the other matrices promoted an elongated cell shape as well as both haptotactic and chemotactic motile processes. Therefore, carboxymethylcellulose hydrogels may serve as effective platforms for investigating central nervous system-derived tumor-cell migration in response to soluble factor
Composite biomaterial repair strategy to restore biomechanical function and reduce herniation risk in an ex vivo large animal model of intervertebral disc herniation with varying injury severity
Back pain commonly arises from intervertebral disc (IVD) damage including annulus fibrosus (AF) defects and nucleus pulposus (NP) loss. Poor IVD healing motivates developing tissue engineering repair strategies. This study evaluated a composite injectable IVD biomaterial repair strategy using carboxymethylcellulose-methylcellulose (CMC-MC) and genipincrosslinked fibrin (FibGen) that mimic NP and AF properties, respectively. Bovine ex vivo caudal IVDs were evaluated in cyclic compression-tension, torsion, and compression-to-failure tests to determine IVD biomechanical properties, height loss, and herniation risk following experimentally-induced severe herniation injury and discectomy (4 mm biopsy defect with 20% NP removed). FibGen with and without CMC-MC had failure strength similar to discectomy injury suggesting no increased risk compared to surgical procedures, yet no biomaterials improved axial or torsional biomechanical properties suggesting they were incapable of adequately restoring AF tension. FibGen had the largest failure strength and was further evaluated in additional discectomy injury models with varying AF defect types (2 mm biopsy, 4 mm cruciate, 4 mm biopsy) and NP removal volume (0%, 20%). All simulated discectomy defects significantly compromised failure strength and biomechanical properties. The 0% NP removal group had mean values of axial biomechanical properties closer to intact levels than defects with 20% NP removed but they were not statistically different and 0% NP removal also decreased failure strength. FibGen with and without CMC-MC failed at super-physiological stress levels above simulated discectomy suggesting repair with these tissue engineered biomaterials may perform better than discectomy alone, although restored biomechanical function may require additional healing with the potential application of these biomaterials as sealants and cell/drug delivery carriers
Climatic changes and social transformations in the Near East and North Africa during the âlongâ 4th millennium BC: A comparative study of environmental and archaeological evidence
This paper explores the possible links between rapid climate change (RCC) and social change in the Near East and surrounding regions (Anatolia, central Syria, southern Israel, Mesopotamia, Cyprus and eastern and central Sahara) during the âlongâ 4th millennium (âŒ4500â3000) BC. Twenty terrestrial and 20 marine climate proxies are used to identify long-term trends in humidity involving transitions from humid to arid conditions and vice versa. The frequency distribution of episodes of relative aridity across these records is calculated for the period 6300â2000 BC, so that the results may be interpreted in the context of the established arid episodes associated with RCC around 6200 and 2200 BC (the 8.2 and 4.2 kyr events). We identify two distinct episodes of heightened aridity in the early-mid 4th, and late 4th millennium BC. These episodes cluster strongly at 3600â3700 and 3100â3300 BC. There is also evidence of localised aridity spikes in the 5th and 6th millennia BC. These results are used as context for the interpretation of regional and local archaeological records with a particular focus on case studies from western Syria, the middle Euphrates, southern Israel and Cyprus. Interpretation of the records involves the construction of plausible narratives of humanâclimate interaction informed by concepts of adaptation and resilience from the literature on contemporary (i.e. 21st century) climate change and adaptation. The results are presented alongside well-documented examples of climatically-influenced societal change in the central and eastern Sahara, where detailed geomorphological studies of ancient environments have been undertaken in tandem with archaeological research. While the narratives for the Near East and Eastern Mediterranean remain somewhat speculative, the use of resilience and adaptation frameworks allows for a more nuanced treatment of humanâclimate interactions and recognises the diversity and context-specificity of human responses to climatic and environmental change. Our results demonstrate that there is a need for more local environmental data to be collected âat sourceâ during archaeological excavations
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Soil Respiration in a Northeastern US Temperate Forest: A 22-Year Synthesis
To better understand how forest management, phenology, vegetation type, and actual and simulated climatic change affect seasonal and inter-annual variations in soil respiration (R), we analyzed more than 100,000 individual measurements of soil respiration from 23 studies conducted over 22 years at the Harvard Forest in Petersham, Massachusetts, USA. We also used 24 site-years of eddy-covariance measurements from two Harvard Forest sites to examine the relationship between soil and ecosystem respiration (R).
R was highly variable at all spatial (respiration collar to forest stand) and temporal (minutes to years) scales of measurement. The response of R to experimental manipulations mimicking aspects of global change or aimed at partitioning R into component fluxes ranged from â70% to +52%. The response appears to arise from variations in substrate availability induced by changes in the size of soil C pools and of belowground C fluxes or in environmental conditions. In some cases (e.g., logging, warming), the effect of experimental manipulations on R was transient, but in other cases the time series were not long enough to rule out long-term changes in respiration rates. Inter-annual variations in weather and phenology induced variation among annual R estimates of a magnitude similar to that of other drivers of global change (i.e., invasive insects, forest management practices, N deposition). At both eddy-covariance sites, aboveground respiration dominated R early in the growing season, whereas belowground respiration dominated later. Unusual aboveground respiration patternsâhigh apparent rates of respiration during winter and very low rates in mid-to-late summerâat the Environmental Measurement Site suggest either bias in R and R estimates caused by differences in the spatial scale of processes influencing fluxes, or that additional research on the hard-to-measure fluxes (e.g., wintertime R, unaccounted losses of CO from eddy covariance sites), daytime and nighttime canopy respiration and its impacts on estimates of R, and independent measurements of flux partitioning (e.g., aboveground plant respiration, isotopic partitioning) may yield insight into the unusually high and low fluxes. Overall, however, this data-rich analysis identifies important seasonal and experimental variations in R and R and in the partitioning of R above- vs. belowground.Organismic and Evolutionary Biolog
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