Resolved Millimeter-wavelength Observations of Debris Disks around Solar-type Stars

The presence of debris disks around young main-sequence stars hints at the existence and structure of planetary systems. Millimeter-wavelength observations probe large grains that trace the location of planetesimal belts. The Formation and Evolution of Planetary Systems Spitzer Legacy survey of nearby young solar analogues yielded a sample of five debris disk-hosting stars with millimeter flux suitable for interferometric follow-up. We present observations with the Submillimeter Array (SMA) and the Combined Array for Research in Millimeter-wave Astronomy at ~2'' resolution that spatially resolve the debris disks around these nearby (d ~ 50 pc) stars. Two of the five disks (HD 377, HD 8907) are spatially resolved for the first time and one (HD 104860) is resolved at millimeter wavelengths for the first time. We combine our new observations with archival SMA and Atacama Large Millimeter/Submillimeter Array data to enable a uniform analysis of the full five-object sample. We simultaneously model the broadband photometric data and resolved millimeter visibilities to constrain the dust temperatures and disk morphologies, and perform a Markov Chain Monte Carlo analysis to fit for basic structural parameters. We find that the radii and widths of the cold outer belts exhibit properties consistent with scaled-up versions of the Solar System's Kuiper Belt. All the disks exhibit characteristic grain sizes comparable to the blowout size, and all the resolved observations of emission from large dust grains are consistent with an axisymmetric dust distribution to within the uncertainties. These results are consistent with comparable studies carried out at infrared wavelengths

Shallow Ultraviolet Transits of WD 1145+017

WD 1145+017 is a unique white dwarf system that has a heavily polluted atmosphere, an infrared excess from a dust disk, numerous broad absorption lines from circumstellar gas, and changing transit features, likely from fragments of an actively disintegrating asteroid. Here, we present results from a large photometric and spectroscopic campaign with Hubble, Keck , VLT, Spitzer, and many other smaller telescopes from 2015 to 2018. Somewhat surprisingly, but consistent with previous observations in the u' band, the UV transit depths are always shallower than those in the optical. We develop a model that can quantitatively explain the observed "bluing" and the main findings are: I. the transiting objects, circumstellar gas, and white dwarf are all aligned along our line of sight; II. the transiting object is blocking a larger fraction of the circumstellar gas than of the white dwarf itself. Because most circumstellar lines are concentrated in the UV, the UV flux appears to be less blocked compared to the optical during a transit, leading to a shallower UV transit. This scenario is further supported by the strong anti-correlation between optical transit depth and circumstellar line strength. We have yet to detect any wavelength-dependent transits caused by the transiting material around WD 1145+017.Comment: 16 pages, 11 figures, 6 tables, ApJ, in pres

Targeting the LOX/hypoxia axis reverses many of the features that make pancreatic cancer deadly: inhibition of LOX abrogates metastasis and enhances drug efficacy

Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer‐related mortality. Despite significant advances made in the treatment of other cancers, current chemotherapies offer little survival benefit in this disease. Pancreaticoduodenectomy offers patients the possibility of a cure, but most will die of recurrent or metastatic disease. Hence, preventing metastatic disease in these patients would be of significant benefit. Using principal component analysis (PCA), we identified a LOX/hypoxia signature associated with poor patient survival in resectable patients. We found that LOX expression is upregulated in metastatic tumors from Pdx1‐Cre KrasG12D/+ Trp53R172H/+ (KPC) mice and that inhibition of LOX in these mice suppressed metastasis. Mechanistically, LOX inhibition suppressed both migration and invasion of KPC cells. LOX inhibition also synergized with gemcitabine to kill tumors and significantly prolonged tumor‐free survival in KPC mice with early‐stage tumors. This was associated with stromal alterations, including increased vasculature and decreased fibrillar collagen, and increased infiltration of macrophages and neutrophils into tumors. Therefore, LOX inhibition is able to reverse many of the features that make PDAC inherently refractory to conventional therapies and targeting LOX could improve outcome in surgically resectable disease

Inherent Curiosity and the Effect of Error Generation on the Ability to Learn German Words

A Research Methods Project supervised by Dr. Hilary Stebbins (Spring 2021)

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Isotopic and Geochemical Investigation of Two Distinct Mars Analog Environments Using Evolved Gas Techniques in Svalbard, Norway

The 2010 Arctic Mars Analog Svalbard Expedition (AMASE) investigated two distinct geologic settings on Svalbard, using methodologies and techniques to be deployed on Mars Science Laboratory (MSL). AMASErelated research comprises both analyses conducted during the expedition and further analyses of collected samples using laboratory facilities at a variety of institutions. The Sample Analysis at Mars (SAM) instrument suite on MSL includes pyrolysis ovens, a gas-processing manifold, a quadrupole mass spectrometer (QMS), several gas chromatography columns, and a Tunable Laser Spectrometer (TLS). An integral part of SAM development is the deployment of SAM-like instrumentation in the field. During AMASE 2010, two parts of SAM participated as stand-alone instruments. A Hiden Evolved Gas Analysis- Mass Spectrometer (EGA-QMS) system represented the EGA-QMS component of SAM, and a Picarro Cavity Ring Down Spectrometer (EGA-CRDS), represented the EGA-TLS component of SAM. A field analog of CheMin, the XRD/XRF on MSL, was also deployed as part of this field campaign. Carbon isotopic measurements of CO2 evolved during thermal decomposition of carbonates were used together with EGA-QMS geochemical data, mineral composition information and contextual observations made during sample collection to distinguish carbonates formation associated with chemosynthetic activity at a fossil methane seep from abiotic processes forming carbonates associated with subglacial basaltic eruptions. Carbon and oxygen isotopes of the basalt-hosted carbonates suggest cryogenic carbonate formation, though more research is necessary to clarify the history of these rocks

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment