65 research outputs found
scAmpi—A versatile pipeline for single-cell RNA-seq analysis from basics to clinics
Single-cell RNA sequencing (scRNA-seq) has emerged as a powerful technique to decipher tissue composition at the single-cell level and to inform on disease mechanisms, tumor heterogeneity, and the state of the immune microenvironment. Although multiple methods for the computational analysis of scRNA-seq data exist, their application in a clinical setting demands standardized and reproducible workflows, targeted to extract, condense, and display the clinically relevant information. To this end, we designed scAmpi (Single Cell Analysis mRNA pipeline), a workflow that facilitates scRNA-seq analysis from raw read processing to informing on sample composition, clinically relevant gene and pathway alterations, and in silico identification of personalized candidate drug treatments. We demonstrate the value of this workflow for clinical decision making in a molecular tumor board as part of a clinical study
JUNO Conceptual Design Report
The Jiangmen Underground Neutrino Observatory (JUNO) is proposed to determine
the neutrino mass hierarchy using an underground liquid scintillator detector.
It is located 53 km away from both Yangjiang and Taishan Nuclear Power Plants
in Guangdong, China. The experimental hall, spanning more than 50 meters, is
under a granite mountain of over 700 m overburden. Within six years of running,
the detection of reactor antineutrinos can resolve the neutrino mass hierarchy
at a confidence level of 3-4, and determine neutrino oscillation
parameters , , and to
an accuracy of better than 1%. The JUNO detector can be also used to study
terrestrial and extra-terrestrial neutrinos and new physics beyond the Standard
Model. The central detector contains 20,000 tons liquid scintillator with an
acrylic sphere of 35 m in diameter. 17,000 508-mm diameter PMTs with high
quantum efficiency provide 75% optical coverage. The current choice of
the liquid scintillator is: linear alkyl benzene (LAB) as the solvent, plus PPO
as the scintillation fluor and a wavelength-shifter (Bis-MSB). The number of
detected photoelectrons per MeV is larger than 1,100 and the energy resolution
is expected to be 3% at 1 MeV. The calibration system is designed to deploy
multiple sources to cover the entire energy range of reactor antineutrinos, and
to achieve a full-volume position coverage inside the detector. The veto system
is used for muon detection, muon induced background study and reduction. It
consists of a Water Cherenkov detector and a Top Tracker system. The readout
system, the detector control system and the offline system insure efficient and
stable data acquisition and processing.Comment: 328 pages, 211 figure
Les sépultures préhistorique et protohistorique en abri-sous-roche de la Corse dans le contexte méditerranéen (Analyse et identification des pratiques funéraires)
CORTE-BU (200962101) / SudocSudocFranceF
Visualizing odorant receptor trafficking in living cells down to the single-molecule level
Despite the importance of trafficking for regulating G protein-coupled receptor signaling, for many members of the seven transmembrane helix protein family, such as odorant receptors, little is known about this process in live cells. Here, the complete life cycle of the human odorant receptor OR17-40 was directly monitored in living cells by ensemble and single-molecule imaging, using a double-labeling strategy. While the overall, intracellular trafficking of the receptor was visualized continuously by using a GFP tag, selective imaging of cell surface receptors was achieved by pulse-labeling an acyl carrier protein tag. We found that OR17-40 efficiently translocated to the plasma membrane only at low expression, whereas at higher biosynthesis the receptor accumulated in intracellular compartments. Receptors in the plasma membrane showed high turnover resulting from constitutive internalization along the clathrin pathway, even in the absence of ligand. Single-molecule microscopy allowed monitoring of the early, dynamic processes in odorant receptor signaling. Although mobile receptors initially diffused either freely or within domains of various sizes, binding of an agonist or an antagonist increased partitioning of receptors into small domains of ≈190 nm, which likely are precursors of clathrin-coated pits. The binding of a ligand, therefore, resulted in modulation of the continuous, constitutive internalization. After endocytosis, receptors were directed to early endosomes for recycling. This unique mechanism of continuous internalization and recycling of OR17-40 might be instrumental in allowing rapid recovery of odor perception
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