31 research outputs found
Ground and In-Flight Calibration of the OSIRIS-REx Camera Suite
The OSIRIS-REx Camera Suite (OCAMS) onboard the OSIRIS-REx spacecraft is used to study the shape and surface of the missionâs target, asteroid (101955) Bennu, in support of the selection of a sampling site. We present calibration methods and results for the three OCAMS camerasâMapCam, PolyCam, and SamCamâusing data from pre-flight and in-flight calibration campaigns. Pre-flight calibrations established a baseline for a variety of camera properties, including bias and dark behavior, flat fields, stray light, and radiometric calibration. In-flight activities updated these calibrations where possible, allowing us to confidently measure Bennuâs surface. Accurate calibration is critical not only for establishing a global understanding of Bennu, but also for enabling analyses of potential sampling locations and for providing scientific context for the returned sample
Gene Fusion Characterization of Rare Aggressive Prostate Cancer Variants â Adenosquamous Carcinoma, Pleomorphic Giant Cell Carcinoma, and Sarcomatoid Carcinoma: An Analysis of 19 Cases
Aims
We evaluated the molecular underpinnings of rare aggressive prostate cancer variants adenosquamous, pleomorphic giant cell, and sarcomatoid carcinomas.
Methods and Results
We retrieved 19 tumors with one or more variant(s) and performed ERG immunohistochemistry, a nextâgeneration sequencing assay targeting recurrent gene fusions, and fluorescence in situ hybridization (FISH) for ERG and BRAF. Divergent differentiation included: sarcomatoid (n=10), adenosquamous (n=7), and pleomorphic giant cell carcinoma (n=7). Five patients had more than one variant. Four had variants only in metastases. ERG rearrangement was detected in 9 (47%, 7 via sequencing, showing TMPRSS2âERG and one GRHL2âERG fusion, and 2 via FISH, showing rearrangement via deletion). Of these, ERG immunohistochemistry was positive in the adenocarcinoma for 8/9 (89%) but only 5/9 (56%, typically decreased) in the variant. One patient had falseâpositive ERG immunohistochemistry in the sarcomatoid component despite negative FISH. Two (11%) harbored BRAF fusions (FAM131AâBRAF and SND1âBRAF).
Conclusions
ERG gene fusions are present in these rare prostate cancer variants with a close frequency to conventional prostate cancer (9/19, 47%). ERG immunohistochemistry usually detects rearrangement in the adenocarcinoma but is less sensitive for the variant histology with weak to negative staining. Adenosquamous and sarcomatoid variants particularly can occur together. Molecular assessment may be an additional tool in select cases to confirm prostatic origin of unusual tumors. The presence of 2 BRAF gene rearrangements suggests that this gene fusion may be enriched in this setting, as RAF kinase fusions have been previously reported in 1â2% of prostate cancers
Development of PolyHIPE Grafts for Guided Bone Regeneration
A pressing need exists to develop an improved bone replacement to treat the millions of non-union fractures that occur each year as a result of severe trauma, tumor resection, spinal fusions, and joint replacements. Current bone grafts are often hindered by a lack of biodegradability, porosity or innate ability to promote regeneration. This work employs tissue engineering to design a novel bone replacement that combines the regenerative potential of autologous tissue with the tunability of synthetic grafts. This is accomplished by engineering a biodegradable scaffold with physical and mechanical properties emulating those of cancellous bone and combining this scaffold with technologies that allow for the controlled delivery of stem cells and osteoinductive factors.
In this work, polymerized high internal phase emulsions (polyHIPEs) were developed as an injectable, high porosity bone graft. Thiol-methacrylate polyHIPEs were investigated to increase resistance to oxygen inhibition and improve scaffold function under clinically relevant conditions. Methods were established to modulate and characterize scaffold porosity, cure rate, compressive properties, and degradation rates. Furthermore, cell-laden poly(ethylene glycol)-dithiothreitol hydrogels were developed to improve loading and distribution of human mesenchymal stem cells (hMSCs) within 3D printed polyHIPEs. This approach allowed for increased cell retention and supported critical markers of osteoblastic differentiation. Finally, to confer additional osteoinductive character, porous microspheres with tunable release kinetics and requisite compressive properties were fabricated using a solvent-free, in-line loading approach. Bioactivity retention of encapsulated bone morphogenetic protein-2, along with its ability to promote osteoblastic differentiation of hMSCs, was explored.
Overall, these studies highlight the strong potential of polyHIPE scaffolds to serve as an improved bone replacement with the ability to actively guide bone regeneration. Key technologies have been developed that allow for fabrication of a bone graft with improved function in a clinically relevant setting, efficient seeding with mesenchymal stem cells, and targeted delivery of osteoinductive factors. Fundamentally, this work will be an invaluable tool in identifying and evaluating critical design requirements for future bone graft design
Estimating the Economic, Social and Environmental Value of Tourism to Protected Areas
This project provides series of detailed assessments of tourism values and costs in localities adjacent to protected
areas in Tasmania, Victoria and Western Australia. The project demonstrates a range of techniques for
respectively measuring social, environmental and economic impacts of tourism activity. It involved tourists,
townspeople, natural area managers and government authorities. The project draws together recent work on
economic valuation of protected area tourism by Carlsen and Wood (2004), social values of tourism by Fredline,
Deery and Jago (2006) and environmental values of tourism based on work by Michael Lockwood at the
University of Tasmania and David Wood in Western Australia..
As a final stage, the project identified the costs of tourism activity to a region based on a case study of
Exmouth. The project aims to provide methods for identifying monetary and non-monetary values for tourism
across a range of study areas using methods that may be replicated across regions. While not currently fully
integrating social, economic and environmental measures, the methods will inform the development of toolkits
for the assessment of these values of protected areas, which will be made widely available for use. The process
of creating toolkits has begun with the existing Valuing Places Toolkit, which is based on the economic
valuation methods detailed in this report
Prevention of Oxygen Inhibition of PolyHIPE Radical Polymerization Using a Thiol-Based Cross-Linker
Polymerized
high internal phase emulsions (polyHIPEs) are highly
porous constructs currently under investigation as tissue engineered
scaffolds. We previously reported on the potential of redox-initiated
polyHIPEs as injectable bone grafts that space fill irregular defects
with improved integration and rapid cure. Upon subsequent investigation,
the radical-initiated cure of these systems rendered them susceptible
to oxygen inhibition with an associated increase in uncured macromer
in the clinical setting. In the current study, polyHIPEs with increased
resistance to oxygen inhibition were fabricated utilizing a tetrafunctional
thiol, pentaerythritol tetrakisÂ(3-mercaptoproprionate), and the biodegradable
macromer, propylene fumarate dimethacrylate. Increased concentrations
of the tetrathiol additive provided improved oxygen resistance as
confirmed by polyHIPE gel fraction while retaining the requisite rapid
cure rate, compressive properties, and pore architecture for use as
an injectable bone graft. Additionally, thiol-methacrylate polyHIPEs
exhibited increased degradation under accelerated conditions and supported
critical markers of human mesenchymal stem cell activity. In summary,
we have improved upon current methods of fabricating injectable polyHIPE
grafts to meet translational design goals of improved polymerization
kinetics under clinically relevant conditions without sacrificing
key scaffold properties
Osteoinductive PolyHIPE Foams as Injectable Bone Grafts
We have recently fabricated biodegradable polyHIPEs as injectable bone grafts and characterized the mechanical properties, pore architecture, and cure rates. In this study, calcium phosphate nanoparticles and demineralized bone matrix (DBM) particles were incorporated into injectable polyHIPE foams to promote osteoblastic differentiation of mesenchymal stem cells (MSCs). Upon incorporation of each type of particle, stable monoliths were formed with compressive properties comparable to control polyHIPEs. Pore size quantification indicated a negligible effect of all particles on emulsion stability and resulting pore architecture. Alizarin red calcium staining illustrated the incorporation of calcium phosphate particles at the pore surface, while picrosirius red collagen staining illustrated collagen-rich DBM particles within the monoliths. Osteoinductive particles had a negligible effect on the compressive modulus (âŒ30 MPa), which remained comparable to human cancellous bone values. All polyHIPE compositions promoted human MSC viability (âŒ90%) through 2 weeks. Furthermore, gene expression analysis indicated the ability of all polyHIPE compositions to promote osteogenic differentiation through the upregulation of bone-specific markers compared to a time zero control. These findings illustrate the potential for these osteoinductive polyHIPEs to promote osteogenesis and validate future in vivo evaluation. Overall, this work demonstrates the ability to incorporate a range of bioactive components into propylene fumarate dimethacrylate-based injectable polyHIPEs to increase cellular interactions and direct specific behavior without compromising scaffold architecture and resulting properties for various tissue engineering applications