135 research outputs found
Wasting Breath in Hamlet
This is the final version. Available on open access from Palgrave via the DOI in this recordThis chapter draws on instances of disordered breathing in
Hamlet in order to examine the cultural signifcance of sighs in the early
modern period, as well as in the context of current work in the feld
of medical humanities. Tracing the medical history of sighing in ancient
and early modern treatises of the passions, the chapter argues that sighs,
in the text and the performance of the tragedy, exceed their conventional
interpretation as symptoms of pain and disrupt meaning on the page and
on stage. In the light of New Materialist theory, the air circulating in
Hamlet is shown to dismantle narratives of representation, posing new
questions for the future of medical humanities
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
Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas
Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN
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
Imatinib for Melanomas Harboring Mutationally Activated or Amplified KIT Arising on Mucosal, Acral, and Chronically Sun-Damaged Skin
Amplifications and mutations in the KIT proto-oncogene in subsets of melanomas provide therapeutic opportunities
The JWST Early Release Science Program for Direct Observations of Exoplanetary Systems IV: NIRISS Aperture Masking Interferometry Performance and Lessons Learned
We present a performance analysis for the aperture masking interferometry
(AMI) mode on board the James Webb Space Telescope Near Infrared Imager and
Slitless Spectrograph (JWST/NIRISS). Thanks to self-calibrating observables,
AMI accesses inner working angles down to and even within the classical
diffraction limit. The scientific potential of this mode has recently been
demonstrated by the Early Release Science (ERS) 1386 program with a deep search
for close-in companions in the HIP 65426 exoplanetary system. As part of ERS
1386, we use the same dataset to explore the random, static, and calibration
errors of NIRISS AMI observables. We compare the observed noise properties and
achievable contrast to theoretical predictions. We explore possible sources of
calibration errors, and show that differences in charge migration between the
observations of HIP 65426 and point-spread function calibration stars can
account for the achieved contrast curves. Lastly, we use self-calibration tests
to demonstrate that with adequate calibration, NIRISS AMI can reach contrast
levels of mag. These tests lead us to observation planning
recommendations and strongly motivate future studies aimed at producing
sophisticated calibration strategies taking these systematic effects into
account. This will unlock the unprecedented capabilities of JWST/NIRISS AMI,
with sensitivity to significantly colder, lower mass exoplanets than
ground-based setups at orbital separations inaccessible to JWST coronagraphy.Comment: 20 pages, 12 figures, submitted to AAS Journal
The JWST Early Release Science Program for Direct Observations of Exoplanetary Systems V: Do Self-Consistent Atmospheric Models Represent JWST Spectra? A Showcase With VHS 1256 b
The unprecedented medium-resolution (R~1500-3500) near- and mid-infrared
(1-18um) spectrum provided by JWST for the young (140+/-20Myr) low-mass
(12-20MJup) L-T transition (L7) companion VHS1256b gives access to a catalogue
of molecular absorptions. In this study, we present a comprehensive analysis of
this dataset utilizing a forward modelling approach, applying our Bayesian
framework, ForMoSA. We explore five distinct atmospheric models to assess their
performance in estimating key atmospheric parameters: Teff, log(g), [M/H], C/O,
gamma, fsed, and R. Our findings reveal that each parameter's estimate is
significantly influenced by factors such as the wavelength range considered and
the model chosen for the fit. This is attributed to systematic errors in the
models and their challenges in accurately replicating the complex atmospheric
structure of VHS1256b, notably the complexity of its clouds and dust
distribution. To propagate the impact of these systematic uncertainties on our
atmospheric property estimates, we introduce innovative fitting methodologies
based on independent fits performed on different spectral windows. We finally
derived a Teff consistent with the spectral type of the target, considering its
young age, which is confirmed by our estimate of log(g). Despite the
exceptional data quality, attaining robust estimates for chemical abundances
[M/H] and C/O, often employed as indicators of formation history, remains
challenging. Nevertheless, the pioneering case of JWST's data for VHS1256b has
paved the way for future acquisitions of substellar spectra that will be
systematically analyzed to directly compare the properties of these objects and
correct the systematics in the models.Comment: 32 pages, 16 figures, 6 tables, 2 appendice
The \textit{JWST} Early Release Science Program for Direct Observations of Exoplanetary Systems III: Aperture Masking Interferometric Observations of the star HIP\,65426 at
We present aperture masking interferometry (AMI) observations of the star HIP
65426 at as a part of the \textit{JWST} Direct Imaging Early
Release Science (ERS) program obtained using the Near Infrared Imager and
Slitless Spectrograph (NIRISS) instrument. This mode provides access to very
small inner working angles (even separations slightly below the Michelson limit
of for an interferometer), which are inaccessible with the
classical inner working angles of the \textit{JWST} coronagraphs. When combined
with \textit{JWST}'s unprecedented infrared sensitivity, this mode has the
potential to probe a new portion of parameter space across a wide array of
astronomical observations. Using this mode, we are able to achieve a contrast
of \,mag relative to the host star at a separation
of {\sim}0.07\arcsec but detect no additional companions interior to the
known companion HIP\,65426\,b. Our observations thus rule out companions more
massive than 10{-}12\,\rm{M\textsubscript{Jup}} at separations
from HIP\,65426, a region out of reach of ground or
space-based coronagraphic imaging. These observations confirm that the AMI mode
on \textit{JWST} is sensitive to planetary mass companions orbiting at the
water frost line, even for more distant stars at 100\,pc. This result
will allow the planning and successful execution of future observations to
probe the inner regions of nearby stellar systems, opening essentially
unexplored parameter space.Comment: 15 pages, 9 figures, submitted to ApJ Letter
The JWST Early Release Science Program for Direct Observations of Exoplanetary Systems II: A 1 to 20 Micron Spectrum of the Planetary-Mass Companion VHS 1256-1257 b
We present the highest fidelity spectrum to date of a planetary-mass object.
VHS 1256 b is a 20 M widely separated (8\arcsec, a =
150 au), young, planetary-mass companion that shares photometric colors and
spectroscopic features with the directly imaged exoplanets HR 8799 c, d, and e.
As an L-to-T transition object, VHS 1256 b exists along the region of the
color-magnitude diagram where substellar atmospheres transition from cloudy to
clear. We observed VHS 1256~b with \textit{JWST}'s NIRSpec IFU and MIRI MRS
modes for coverage from 1 m to 20 m at resolutions of 1,000 -
3,700. Water, methane, carbon monoxide, carbon dioxide, sodium, and potassium
are observed in several portions of the \textit{JWST} spectrum based on
comparisons from template brown dwarf spectra, molecular opacities, and
atmospheric models. The spectral shape of VHS 1256 b is influenced by
disequilibrium chemistry and clouds. We directly detect silicate clouds, the
first such detection reported for a planetary-mass companion.Comment: Accepted ApJL Iterations of spectra reduced by the ERS team are
hosted at this link:
https://github.com/bemiles/JWST_VHS1256b_Reduction/tree/main/reduced_spectr
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