Expression in Aromatase Inhibitor Responder vs. Non-Responder HR+ Breast Cancer Cohorts

Hormone receptor positive (HR+) breast cancer patients have an excellent prognosis with over 85% cure rates. However, 20,000 women with HR+ breast cancer die annually from tumor recurrence. Those at highest risk for recurrence are those women whose tumors continue to proliferate through estrogen blockade (Figure 4). Addition of chemotherapy for these patients failed to improve outcomes. We retrospectively identified women with HR+ breast cancer treated neoadjuvantly with aromatase inhibitors (AI), and selected matched patient cohorts for responders and non-responders determined by post-AI Ki67 o

Generating Stable Bioluminescent Cell Lines by Retroviral Transduction

This project focuses on improving tumor in vivo imaging techniques. It is difficult to accurately in vivo image orthotopic tumors using CT scans alone. Muriglo provides the capability to visualize in vivo bioluminescent signals emanating from intact tissues. We can coregister CT scans captured with the SARRP with luciferase signals captured with the Muriglo and locate tumor isocenters for image-guided radiation. We may then direct radiation to neoplastic tissue while also sparing the maximum amount of healthy tissue. To do this we must genetically engineer cells to express luciferase. We propose a protocol to use a retrovirus to create stable cell lines that express firefly luciferase for bioluminescence. We will also determine the optimal dosage of the G418 antibiotic for selection

Data Reduction Pipeline for the CHARIS Integral-Field Spectrograph I: Detector Readout Calibration and Data Cube Extraction

We present the data reduction pipeline for CHARIS, a high-contrast integral-field spectrograph for the Subaru Telescope. The pipeline constructs a ramp from the raw reads using the measured nonlinear pixel response, and reconstructs the data cube using one of three extraction algorithms: aperture photometry, optimal extraction, or $\chi^2$ fitting. We measure and apply both a detector flatfield and a lenslet flatfield and reconstruct the wavelength- and position-dependent lenslet point-spread function (PSF) from images taken with a tunable laser. We use these measured PSFs to implement a $\chi^2$-based extraction of the data cube, with typical residuals of ~5% due to imperfect models of the undersampled lenslet PSFs. The full two-dimensional residual of the $\chi^2$ extraction allows us to model and remove correlated read noise, dramatically improving CHARIS' performance. The $\chi^2$ extraction produces a data cube that has been deconvolved with the line-spread function, and never performs any interpolations of either the data or the individual lenslet spectra. The extracted data cube also includes uncertainties for each spatial and spectral measurement. CHARIS' software is parallelized, written in Python and Cython, and freely available on github with a separate documentation page. Astrometric and spectrophotometric calibrations of the data cubes and PSF subtraction will be treated in a forthcoming paper.Comment: 18 pages, 15 figures, 3 tables, replaced with JATIS accepted version (emulateapj formatted here). Software at https://github.com/PrincetonUniversity/charis-dep and documentation at http://princetonuniversity.github.io/charis-de

Affine su(2) fusion rules from gerbe 2-isomorphisms

We give a geometric description of the fusion rules of the affine Lie algebra su(2)_k at a positive integer level k in terms of the k-th power of the basic gerbe over the Lie group SU(2). The gerbe can be trivialised over conjugacy classes corresponding to dominant weights of su(2)_k via a 1-isomorphism. The fusion-rule coefficients are related to the existence of a 2-isomorphism between pullbacks of these 1-isomorphisms to a submanifold of SU(2) x SU(2) determined by the corresponding three conjugacy classes. This construction is motivated by its application in the description of junctions of maximally symmetric defect lines in the Wess-Zumino-Witten model.Comment: 41 pages, 1 figure (the published version

Patterns of Lumbar Disc Degeneration: Magnetic Resonance Imaging Analysis in Symptomatic Subjects

Study Design: Cross-sectional study. Purpose: To evaluate lumbar disc degeneration (LDD) on magnetic resonance imaging (MRI) in symptomatic subjects to accumulate baseline data on the pattern of degeneration. Overview of Literature: LDD plays an important role in the diagnosis and treatment of low-back pain in patients. Few studies have focused on the pattern of LDD to understand how the lumbar spine ages. Methods: This study included 1,095 patients (mean age, 44.29 years; range, 16–85 years) who underwent upright lumbar MRI. LDD was graded into five categories (I–V). Positive LDD was defined as grade III or greater. The prevalence and pattern of LDD were ana-lyzed, and the correlations between age and total grade of LDD were evaluated. Results: The average number of LDD levels and the total grade of LDD increased with age. LDD moved cephalad with age. The rate of LDD increased rapidly during the decade before the prevalence of LDD and became \u3e 50%. In the single-level LDD group, the levels L5–S1 were the most common levels (60.3%). In the two-level group, L4–L5 and L5–S1 were the most common levels (53.5%). In the three-level group, L3–L4, L4–L5, and L5–S1 were the most common levels (55.7%). In the multilevel LDD group, contiguous multilevel disc degeneration (CMDD) was more common than the skipped level disc degeneration (SLDD). The levels L4–L5 were the most com-mon levels in the CMDD group, and L5–S1 were the most common levels among SLDD. Conclusions: LDD was found to correlate with age, and the specific patterns and rates of LDD depended on lumbar disc level and age. These LDD pattern data can be used before spinal procedures to predict the probability of natural LDD progression with age

Optical Structure and Proper-Motion Age of the Oxygen-rich Supernova Remnant 1E 0102-7219 in the Small Magellanic Cloud

We present new optical emission-line images of the young SNR 1E 0102-7219 (E0102) in the SMC obtained with the HST Advanced Camera for Surveys (ACS). E0102 is a member of the oxygen-rich class of SNRs showing strong oxygen, neon , and other metal-line emissions in its optical and X-ray spectra, and an absence of H and He. The progenitor of E0102 may have been a Wolf-Rayet star that underwent considerable mass loss prior to exploding as a Type Ib/c or IIL/b SN. The ejecta in this SNR are fast-moving (V > 1000 km/s) and emit as they are compressed and heated in the reverse shock. In 2003, we obtained optical [O III], H-alpha, and continuum images with the ACS Wide Field Camera. The [O III] image captures the full velocity range of the ejecta, and shows considerable high-velocity emission projected in the middle of the SNR that was Doppler-shifted out of the narrow F502N bandpass of a previous Wide Field and Planetary Camera 2 image from 1995. Using these two epochs separated by ~8.5 years, we measure the transverse expansion of the ejecta around the outer rim in this SNR for the first time at visible wavelengths. From proper-motion measurements of 12 ejecta filaments, we estimate a mean expansion velocity for the bright ejecta of ~2000 km/s and an inferred kinematic age for the SNR of \~2050 +/- 600 years. The age we derive from HST data is about twice that inferred by Hughes et al.(2000) from X-ray data, though our 1-sigma error bars overlap. Our proper-motion age is consistent with an independent optical kinematic age derived by Eriksen et al.(2003) using spatially resolved [O III] radial-velocity data. We derive an expansion center that lies very close to X-ray and radio hotspots, which could indicate the presence of a compact remnant (neutron star or black hole).Comment: 28 pages, 8 figures. Accepted to the Astrophysical Journal, to appear in 20 April 2006 issue. Full resolution figures are posted at: http://stevenf.asu.edu/figure

The MAD-Related Protein Smad7 Associates with the TGFβ Receptor and Functions as an Antagonist of TGFβ Signaling

AbstractTGFβ signaling is initiated when the type I receptor phosphorylates the MAD-related protein, Smad2, on C-terminal serine residues. This leads to Smad2 association with Smad4, translocation to the nucleus, and regulation of transcriptional responses. Here we demonstrate that Smad7 is an inhibitor of TGFβ signaling. Smad7 prevents TGFβ-dependent formation of Smad2/Smad4 complexes and inhibits the nuclear accumulation of Smad2. Smad7 interacts stably with the activated TGFβ type I receptor, thereby blocking the association, phosphorylation, and activation of Smad2. Furthermore, mutations in Smad7 that interfere with receptor binding disrupt its inhibitory activity. These studies thus define a novel function for MAD-related proteins as intracellular antagonists of the type I kinase domain of TGFβ family receptors