Infrequent expression of the cancer-testis antigen, PASD1, in ovarian cancer

Ovarian cancer is very treatable in the early stages of disease; however, it is usually detected in the later stages, at which time, treatment is no longer as effective. If discovered early (Stage I), there is a 90% chance of five-year survival. Therefore, it is imperative that early-stage biomarkers are identified to enhance the early detection of ovarian cancer. Cancer-testis antigens (CTAs), such as Per ARNT SIM (PAS) domain containing 1 (PASD1), are unique in that their expression is restricted to immunologically restricted sites, such as the testis and placenta, which do not express MHC class I, and cancer, making them ideally positioned to act as targets for immunotherapy as well as potential biomarkers for cancer detection where expressed. We examined the expression of PASD1a and b in a number of cell lines, as well as eight healthy ovary samples, eight normal adjacent ovarian tissues, and 191 ovarian cancer tissues, which were predominantly stage I (n = 164) and stage II (n = 14) disease. We found that despite the positive staining of skin cancer, only one stage Ic ovarian cancer patient tissue expressed PASD1a and b at detectable levels. This may reflect the predominantly stage I ovarian cancer samples examined. To examine the restriction of PASD1 expression, we examined endometrial tissue arrays and found no expression in 30 malignant tumor tissues, 23 cases of hyperplasia, or 16 normal endometrial tissues. Our study suggests that the search for a single cancer-testes antigen/biomarker that can detect early ovarian cancer must continue

A Digital X-Ray Tomosynthesis Coupled Near Infrared Spectral Tomography System for Dual-Modality Breast Imaging

A Near Infrared Spectral Tomography (NIRST) system has been developed and integrated into a commercial Digital Breast Tomosynthesis (DBT) scanner to allow structural and functional imaging of breast in vivo. The NIRST instrument uses an 8-wavelength continuous wave (CW) laser-based scanning source assembly and a 75-element silicon photodiode solid-state detector panel to produce dense spectral and spatial projection data from which spectrally constrained 3D tomographic images of tissue chromophores are produced. Integration of the optical imaging system into the DBT scanner allows direct co-registration of the optical and DBT images, while also facilitating the synergistic use of x-ray contrast as anatomical priors in optical image reconstruction. Currently, the total scan time for a combined NIRST-DBT exam is ~50s with data collection from 8 wavelengths in the optical scan requiring ~42s to complete. The system was tested in breast simulating phantoms constructed using intralipid and blood in an agarose matrix with a 3 cm x 2 cm cylindrical inclusion at 1 cm depth from the surface. Diffuse image reconstruction of total hemoglobin (HbT) concentration resulted in accurate recovery of the lateral size and position of the inclusion to within 6% and 8%, respectively. Use of DBT structural priors in the NIRST reconstruction process improved the quantitative accuracy of the HbT recovery, and led to linear changes in imaged versus actual contrast, underscoring the advantages of dual-modality optical imaging approaches. The quantitative accuracy of the system can be further improved with independent measurements of scattering properties through integration of frequency or time domain data

Integrated natural resource planning

Deciding upon management strategies and use of natural resources becomes more challenging as urban areas expand and human population and consumption levels continue to increase. Given that a larger urban population, interestingly, seems to demand both more resources (products) and greater environmental protection, there will no doubt be a coincident heightening of conflicts over natural resource management in the next century. Making decisions on natural resource allocation and use under such circumstances will become even more complex and difficult than they are today. Skilled people will be needed who can develop an integrated approach to natural resource management that sheds light on the tradeoffs and implications of their decisions. To help address this need, we developed a course in integrated natural resource management with funding received from the Cooperative State Research Service Higher Education Challenge Grants Program. This interdisciplinary course is team-taught and uses a combination of case studies and computerized models

Application of the pMHC array to characterise tumour antigen specific T cell populations in leukaemia patients at disease diagnosis

Immunotherapy treatments for cancer are becoming increasingly successful, however to further improve our understanding of the T-cell recognition involved in effective responses and to encourage moves towards the development of personalised treatments for leukaemia immunotherapy, precise antigenic targets in individual patients have been identified. Cellular arrays using peptide-MHC (pMHC) tetramers allow the simultaneous detection of different antigen specific T-cell populations naturally circulating in patients and normal donors. We have developed the pMHC array to detect CD8+ T-cell populations in leukaemia patients that recognise epitopes within viral antigens (cytomegalovirus (CMV) and influenza (Flu)) and leukaemia antigens (including Per Arnt Sim domain 1 (PASD1), MelanA, Wilms’ Tumour (WT1) and tyrosinase). We show that the pMHC array is at least as sensitive as flow cytometry and has the potential to rapidly identify more than 40 specific T-cell populations in a small sample of T-cells (0.8–1.4 x 106). Fourteen of the twenty-six acute myeloid leukaemia (AML) patients analysed had T cells that recognised tumour antigen epitopes, and eight of these recognised PASD1 epitopes. Other tumour epitopes recognised were MelanA (n = 3), tyrosinase (n = 3) and WT1126-134 (n = 1). One of the seven acute lymphocytic leukaemia (ALL) patients analysed had T cells that recognised the MUC1950-958 epitope. In the future the pMHC array may be used provide point of care T-cell analyses, predict patient response to conventional therapy and direct personalised immunotherapy for patients

Field scale evaluation of biostimulation in the near source zone of the former S3 ponds at Oak Ridge

The primary objective of this report is to evaluate the rates and mechanisms of U(VI) reduction by microbial populations

Overview of Advanced LIGO Adaptive Optics

This is an overview of the adaptive optics used in Advanced LIGO (aLIGO), known as the thermal compensation system (TCS). The thermal compensation system was designed to minimize thermally-induced spatial distortions in the interferometer optical modes and to provide some correction for static curvature errors in the core optics of aLIGO. The TCS is comprised of ring heater actuators, spatially tunable CO$_{2}$ laser projectors and Hartmann wavefront sensors. The system meets the requirements of correcting for nominal distortion in Advanced LIGO to a maximum residual error of 5.4nm, weighted across the laser beam, for up to 125W of laser input power into the interferometer

Overview of Advanced LIGO Adaptive Optics

This is an overview of the adaptive optics used in Advanced LIGO (aLIGO), known as the thermal compensation system (TCS). The TCS was designed to minimize thermally induced spatial distortions in the interferometer optical modes and to provide some correction for static curvature errors in the core optics of aLIGO. The TCS is comprised of ring heater actuators, spatially tunable CO_2 laser projectors, and Hartmann wavefront sensors. The system meets the requirements of correcting for nominal distortion in aLIGO to a maximum residual error of 5.4 nm rms, weighted across the laser beam, for up to 125 W of laser input power into the interferometer

μ→eγ\mu \to e \gamma and μ→3e\mu \to 3e processes with polarized muons and supersymmetric grand unified theories

$\mu^{+} \to e^{+} \gamma$ and $\mu^{+} \to e^{+}e^{+}e^{-}$ processes are analyzed in detail with polarized muons in supersymmetric grand unified theories. We first present Dalitz plot distribution for $\mu^{+} \to e^{+}e^{+}e^{-}$ decay based on effective Lagrangian with general lepton-flavor-violating couplings and define various P- and T-odd asymmetries. We calculate branching ratios and asymmetries in supersymmetric SU(5) and SO(10) models taking into account complex soft supersymmetry breaking terms. Imposing constraints from experimental bounds on the electron, neutron and atomic electric dipole moments, we find that the T-odd asymmetry for $\mu^{+} \to e^{+}e^{+}e^{-}$ can be 15% in the SU(5) case. P-odd asymmetry with respect to muon polarization for $\mu^{+} \to e^{+} \gamma$ varies from -20% to -100% for the SO(10) model while it is $+100$ in the SU(5) case. We also show that the P-odd asymmetries in $\mu^{+} \to e^{+}e^{+}e^{-}$ and the ratio of $\mu^{+} \to e^{+}e^{+}e^{-}$ and $\mu^{+} \to e^{+} \gamma$ branching fractions are useful to distinguish different models.Comment: 52 pages, 15 figure