4,054 research outputs found
Joint single-cell DNA accessibility and protein epitope profiling reveals environmental regulation of epigenomic heterogeneity.
Here we introduce Protein-indexed Assay of Transposase Accessible Chromatin with sequencing (Pi-ATAC) that combines single-cell chromatin and proteomic profiling. In conjunction with DNA transposition, the levels of multiple cell surface or intracellular protein epitopes are recorded by index flow cytometry and positions in arrayed microwells, and then subject to molecular barcoding for subsequent pooled analysis. Pi-ATAC simultaneously identifies the epigenomic and proteomic heterogeneity in individual cells. Pi-ATAC reveals a casual link between transcription factor abundance and DNA motif access, and deconvolute cell types and states in the tumor microenvironment in vivo. We identify a dominant role for hypoxia, marked by HIF1α protein, in the tumor microvenvironment for shaping the regulome in a subset of epithelial tumor cells
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Physiological, behavioral and subjective sadness reactivity in frontotemporal dementia subtypes.
Frontotemporal dementia (FTD), a neurodegenerative disease broadly characterized by socioemotional impairments, includes three clinical subtypes: behavioral variant FTD (bvFTD), semantic variant primary progressive aphasia (svPPA) and non-fluent variant primary progressive aphasia (nfvPPA). Emerging evidence has shown emotional reactivity impairments in bvFTD and svPPA, whereas emotional reactivity in nfvPPA is far less studied. In 105 patients with FTD (49 bvFTD, 31 svPPA and 25 nfvPPA) and 27 healthy controls, we examined three aspects of emotional reactivity (physiology, facial behavior and subjective experience) in response to a sad film. In a subset of the sample, we also examined the neural correlates of diminished aspects of reactivity using voxel-based morphometry. Results indicated that all three subtypes of FTD showed diminished physiological responding in respiration rate and diastolic blood pressure; patients with bvFTD and svPPA also showed diminished subjective experience, and no subtypes showed diminished facial behavior. Moreover, there were differences among the clinical subtypes in brain regions where smaller volumes were associated with diminished sadness reactivity. These results show that emotion impairments extend to sadness reactivity in FTD and underscore the importance of considering different aspects of sadness reactivity in multiple clinical subtypes for characterizing emotional deficits and associated neurodegeneration in FTD
Three Dimensional Structure and Energy Balance of a Coronal Mass Ejection
The Ultraviolet Coronagraph Spectrometer (UVCS) observed Doppler shifted
material of a partial Halo Coronal Mass Ejection (CME) on December 13 2001. The
observed ratio of [O V]/O V] is a reliable density diagnostic important for
assessing the state of the plasma. Earlier UVCS observations of CMEs found
evidence that the ejected plasma is heated long after the eruption. We have
investigated the heating rates, which represent a significant fraction of the
CME energy budget. The parameterized heating and radiative and adiabatic
cooling have been used to evaluate the temperature evolution of the CME
material with a time dependent ionization state model. The functional form of a
flux rope model for interplanetary magnetic clouds was also used to
parameterize the heating. We find that continuous heating is required to match
the UVCS observations. To match the O VI-bright knots, a higher heating rate is
required such that the heating energy is greater than the kinetic energy. The
temperatures for the knots bright in Ly and C III emission indicate
that smaller heating rates are required for those regions. In the context of
the flux rope model, about 75% of the magnetic energy must go into heat in
order to match the O VI observations. We derive tighter constraints on the
heating than earlier analyses, and we show that thermal conduction with the
Spitzer conductivity is not sufficient to account for the heating at large
heights.Comment: 40 pages, 16 figures, accepted for publication in ApJ For associated
mpeg file, please see https://www.cora.nwra.com/~jylee/mpg/f5.mp
In silico and in vitro drug screening identifies new therapeutic approaches for Ewing sarcoma.
The long-term overall survival of Ewing sarcoma (EWS) patients remains poor; less than 30% of patients with metastatic or recurrent disease survive despite aggressive combinations of chemotherapy, radiation and surgery. To identify new therapeutic options, we employed a multi-pronged approach using in silico predictions of drug activity via an integrated bioinformatics approach in parallel with an in vitro screen of FDA-approved drugs. Twenty-seven drugs and forty-six drugs were identified, respectively, to have anti-proliferative effects for EWS, including several classes of drugs in both screening approaches. Among these drugs, 30 were extensively validated as mono-therapeutic agents and 9 in 14 various combinations in vitro. Two drugs, auranofin, a thioredoxin reductase inhibitor, and ganetespib, an HSP90 inhibitor, were predicted to have anti-cancer activities in silico and were confirmed active across a panel of genetically diverse EWS cells. When given in combination, the survival rate in vivo was superior compared to auranofin or ganetespib alone. Importantly, extensive formulations, dose tolerance, and pharmacokinetics studies demonstrated that auranofin requires alternative delivery routes to achieve therapeutically effective levels of the gold compound. These combined screening approaches provide a rapid means to identify new treatment options for patients with a rare and often-fatal disease
How Many CMEs Have Flux Ropes? Deciphering the Signatures of Shocks, Flux Ropes, and Prominences in Coronagraph Observations of CMEs
We intend to provide a comprehensive answer to the question on whether all
Coronal Mass Ejections (CMEs) have flux rope structure. To achieve this, we
present a synthesis of the LASCO CME observations over the last sixteen years,
assisted by 3D MHD simulations of the breakout model, EUV and coronagraphic
observations from STEREO and SDO, and statistics from a revised LASCO CME
database. We argue that the bright loop often seen as the CME leading edge is
the result of pileup at the boundary of the erupting flux rope irrespective of
whether a cavity or, more generally, a 3-part CME can be identified. Based on
our previous work on white light shock detection and supported by the MHD
simulations, we identify a new type of morphology, the `two-front' morphology.
It consists of a faint front followed by diffuse emission and the bright
loop-like CME leading edge. We show that the faint front is caused by density
compression at a wave (or possibly shock) front driven by the CME. We also
present high-detailed multi-wavelength EUV observations that clarify the
relative positioning of the prominence at the bottom of a coronal cavity with
clear flux rope structure. Finally, we visually check the full LASCO CME
database for flux rope structures. In the process, we classify the events into
two clear flux rope classes (`3-part', `Loop'), jets and outflows (no clear
structure). We find that at least 40% of the observed CMEs have clear flux rope
structures. We propose a new definition for flux rope CMEs (FR-CMEs) as a
coherent magnetic, twist-carrying coronal structure with angular width of at
least 40 deg and able to reach beyond 10 Rsun which erupts on a time scale of a
few minutes to several hours. We conclude that flux ropes are a common
occurrence in CMEs and pose a challenge for future studies to identify CMEs
that are clearly not FR-CMEs.Comment: 26 pages, 9 figs, to be published in Solar Physics Topical Issue
"Flux Rope Structure of CMEs
Computing Equilibria of Prediction Markets via Persuasion
We study the computation of equilibria in prediction markets in perhaps the
most fundamental special case with two players and three trading opportunities.
To do so, we show equivalence of prediction market equilibria with those of a
simpler signaling game with commitment introduced by Kong and Schoenebeck
(2018). We then extend their results by giving computationally efficient
algorithms for additional parameter regimes. Our approach leverages a new
connection between prediction markets and Bayesian persuasion, which also
reveals interesting conceptual insights
Steps in the bacterial flagellar motor
The bacterial flagellar motor is a highly efficient rotary machine used by
many bacteria to propel themselves. It has recently been shown that at low
speeds its rotation proceeds in steps [Sowa et al. (2005) Nature 437,
916--919]. Here we propose a simple physical model that accounts for this
stepping behavior as a random walk in a tilted corrugated potential that
combines torque and contact forces. We argue that the absolute angular position
of the rotor is crucial for understanding step properties, and show this
hypothesis to be consistent with the available data, in particular the
observation that backward steps are smaller on average than forward steps. Our
model also predicts a sublinear torque-speed relationship at low torque, and a
peak in rotor diffusion as a function of torque
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