2,935 research outputs found
The single cell transcriptional landscape of esophageal adenocarcinoma and its modulation by neoadjuvant chemotherapy
Immune checkpoint blockade has recently proven effective in subsets of patients with esophageal adenocarcinoma (EAC) but little is known regarding the EAC immune microenvironment. We determined the single cell transcriptional profile of EAC in 8 patients who were treatment-naive (n = 4) or had received neoadjuvant chemotherapy (n = 4). Analysis of 52,387 cells revealed 10 major cell subsets of tumor, immune and stromal cells. Prior to chemotherapy tumors were heavy infiltrated by T regulatory cells and exhausted effector T cells whilst plasmacytoid dendritic cells were markedly expanded. Two dominant cancer-associated fibroblast populations were also observed whilst endothelial populations were suppressed. Pathological remission following chemotherapy associated with broad reversal of immune abnormalities together with fibroblast transition and an increase in endothelial cells whilst a chemoresistant epithelial stem cell population correlated with poor response. These findings reveal features that underlie and limit the response to current immunotherapy and identify a range of novel opportunities for targeted therapy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12943-022-01666-x
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Polymorphism in M(H2PO2)3 (M = V, Al, Ga) compounds with the perovskite-related ReO3 structure.
Trivalent metal hypophosphites with the general formula M(H2PO2)3 (M = V, Al, Ga) adopt the ReO3 structure, with each compound displaying two structural polymorphs. High-pressure synchrotron X-ray studies reveal a pressure-driven phase transition in Ga(H2PO2)3 that can be understood on the basis of ab initio thermodynamics
Direct measurement of antiferromagnetic domain fluctuations
Measurements of magnetic noise emanating from ferromagnets due to domain
motion were first carried out nearly 100 years ago and have underpinned much
science and technology. Antiferromagnets, which carry no net external magnetic
dipole moment, yet have a periodic arrangement of the electron spins extending
over macroscopic distances, should also display magnetic noise, but this must
be sampled at spatial wavelengths of order several interatomic spacings, rather
than the macroscopic scales characteristic of ferromagnets. Here we present the
first direct measurement of the fluctuations in the nanometre-scale spin-
(charge-) density wave superstructure associated with antiferromagnetism in
elemental Chromium. The technique used is X-ray Photon Correlation
Spectroscopy, where coherent x-ray diffraction produces a speckle pattern that
serves as a "fingerprint" of a particular magnetic domain configuration. The
temporal evolution of the patterns corresponds to domain walls advancing and
retreating over micron distances. While the domain wall motion is thermally
activated at temperatures above 100K, it is not so at lower temperatures, and
indeed has a rate which saturates at a finite value - consistent with quantum
fluctuations - on cooling below 40K. Our work is important because it provides
an important new measurement tool for antiferromagnetic domain engineering as
well as revealing a fundamental new fact about spin dynamics in the simplest
antiferromagnet.Comment: 19 pages, 4 figure
IκBβ acts to inhibit and activate gene expression during the inflammatory response
The activation of pro-inflammatory gene programs by nuclear factor-κB (NF-κB) is primarily regulated through cytoplasmic sequestration of NF-κB by the inhibitor of κB (IκB) family of proteins1. IκBβ, a major isoform of IκB, can sequester NF-κB in the cytoplasm2, although its biological role remains unclear. Although cells lacking IκBβ have been reported3, 4, in vivo studies have been limited and suggested redundancy between IκBα and IκBβ5. Like IκBα, IκBβ is also inducibly degraded; however, upon stimulation by lipopolysaccharide (LPS), it is degraded slowly and re-synthesized as a hypophosphorylated form that can be detected in the nucleus6, 7, 8, 9, 10, 11. The crystal structure of IκBβ bound to p65 suggested this complex might bind DNA12. In vitro, hypophosphorylated IκBβ can bind DNA with p65 and c-Rel, and the DNA-bound NF-κB:IκBβ complexes are resistant to IκBα, suggesting hypophosphorylated, nuclear IκBβ may prolong the expression of certain genes9, 10, 11. Here we report that in vivo IκBβ serves both to inhibit and facilitate the inflammatory response. IκBβ degradation releases NF-κB dimers which upregulate pro-inflammatory target genes such as tumour necrosis factor-α (TNF-α). Surprisingly, absence of IκBβ results in a dramatic reduction of TNF-α in response to LPS even though activation of NF-κB is normal. The inhibition of TNF-α messenger RNA (mRNA) expression correlates with the absence of nuclear, hypophosphorylated-IκBβ bound to p65:c-Rel heterodimers at a specific κB site on the TNF-α promoter. Therefore IκBβ acts through p65:c-Rel dimers to maintain prolonged expression of TNF-α. As a result, IκBβ^(−/−) mice are resistant to LPS-induced septic shock and collagen-induced arthritis. Blocking IκBβ might be a promising new strategy for selectively inhibiting the chronic phase of TNF-α production during the inflammatory response
Random repeated quantum interactions and random invariant states
We consider a generalized model of repeated quantum interactions, where a
system is interacting in a random way with a sequence of
independent quantum systems . Two types of randomness
are studied in detail. One is provided by considering Haar-distributed
unitaries to describe each interaction between and
. The other involves random quantum states describing each copy
. In the limit of a large number of interactions, we present
convergence results for the asymptotic state of . This is achieved
by studying spectral properties of (random) quantum channels which guarantee
the existence of unique invariant states. Finally this allows to introduce a
new physically motivated ensemble of random density matrices called the
\emph{asymptotic induced ensemble}
New Particles Working Group Report of the Snowmass 2013 Community Summer Study
This report summarizes the work of the Energy Frontier New Physics working
group of the 2013 Community Summer Study (Snowmass)
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