MRI measurements of carotid plaque in the atherosclerosis risk in communities (ARIC) study: Methods, reliability and descriptive statistics

To measure carotid plaque components using MRI and estimate reliability in the population-based Atherosclerosis Risk in Communities (ARIC) study

Combining asteroid models derived by lightcurve inversion with asteroidal occultation silhouettes

Asteroid sizes can be directly measured by observing occultations of stars by asteroids. When there are enough observations across the path of the shadow, the asteroid's projected silhouette can be reconstructed. Asteroid shape models derived from photometry by the lightcurve inversion method enable us to predict the orientation of an asteroid for the time of occultation. By scaling the shape model to fit the occultation chords, we can determine the asteroid size with a relative accuracy of typically ~ 10%. We combine shape and spin state models of 44 asteroids (14 of them are new or updated models) with the available occultation data to derive asteroid effective diameters. In many cases, occultations allow us to reject one of two possible pole solutions that were derived from photometry. We show that by combining results obtained from lightcurve inversion with occultation timings, we can obtain unique physical models of asteroids.Comment: 33 pages, 45 figures, 4 tables, accepted for publication in Icaru

An Evolutionarily Conserved Enhancer Regulates Bmp4 Expression in Developing Incisor and Limb Bud

To elucidate the transcriptional regulation of Bmp4 expression during organogenesis, we used phylogenetic footprinting and transgenic reporter analyses to identify Bmp4 cis-regulatory modules (CRMs). These analyses identified a regulatory region located ∼46 kb upstream of the mouse Bmp4 transcription start site that had previously been shown to direct expression in lateral plate mesoderm. We refined this regulatory region to a 396-bp minimal enhancer, and show that it recapitulates features of endogenous Bmp4 expression in developing mandibular arch ectoderm and incisor epithelium during the initiation-stage of tooth development. In addition, this enhancer directs expression in the apical ectodermal ridge (AER) of the developing limb and in anterior and posterior limb mesenchyme. Transcript profiling of E11.5 mouse incisor dental lamina, together with protein binding microarray (PBM) analyses, allowed identification of a conserved DNA binding motif in the Bmp4 enhancer for Pitx homeoproteins, which are also expressed in the developing mandibular and incisor epithelium. In vitro electrophoretic mobility shift assays (EMSA) and in vivo transgenic reporter mutational analyses revealed that this site supports Pitx binding and that the site is necessary to recapitulate aspects of endogenous Bmp4 expression in developing craniofacial and limb tissues. Finally, Pitx2 chromatin immunoprecipitation (ChIP) demonstrated direct binding of Pitx2 to this Bmp4 enhancer site in a dental epithelial cell line. These results establish a direct molecular regulatory link between Pitx family members and Bmp4 gene expression in developing incisor epithelium

Remodeling of Carotid Arteries Detected with MR Imaging: Atherosclerosis Risk in Communities Carotid MRI Study1

We observed compensatory remodeling of the internal carotid artery associated with greater maximum wall thickness, without a reduction in lumen area, below a wall thickness of 1.38 mm, which was the 69th percentile in a population-based sample of older adults

Effect of neoadjuvant chemotherapy on tumor-infiltrating lymphocytes and PD-L1 expression in breast cancer and its clinical significance

Abstract Background The effects of neoadjuvant chemotherapy on immune markers remain largely unknown. The specific aim of this study was to assess stromal tumor-infiltrating lymphocytes (TILs) and programmed death ligand 1 (PD-L1) protein expression in a cohort of breast cancer patients treated with neoadjuvant chemotherapy. Methods Using quantitative immunofluorescence, we investigated stromal TILs and PD-L1 protein expression in pre-treatment and residual breast cancer tissue from a Yale Cancer Center patient cohort of 58 patients diagnosed with breast cancer from 2003 to 2009 and treated with neoadjuvant chemotherapy. We compared the TIL count and PD-L1 status in paired pre-treatment and residual cancer tissues and correlated changes and baseline levels with survival. Results Of the 58 patients, 46 (79.3%) had hormone-positive and 34 (58.6%) had node-positive breast cancer. Eighty-six percent of residual cancer tissues had TIL infiltration and 17% had PD-L1 expression. There was a trend for higher TIL counts in postchemotherapy compared to prechemotherapy samples (p = 0.09). Increase in TIL count was associated with longer 5-year recurrence-free survival (p = 0.02, HR = 3.9, 95% CI = 1.179–15.39). PD-L1 expression (both stromal and tumor cells) was significantly lower in post-treatment samples (p = 0.001). Change in PD-L1 expression after therapy or TILs and PD-L1 expression in the posttreatment samples did not correlate with survival. Conclusions Increase in stromal TILs in residual cancer compared to pretreatment tissue is associated with improved recurrence-free survival. Despite a trend for increasing TIL counts, PD-L1 expression decreased in residual disease compared to pretreatment samples