The MHC class I peptide repertoire is molded by the transcriptome

Under steady-state conditions, major histocompatibility complex (MHC) I molecules are associated with self-peptides that are collectively referred to as the MHC class I peptide (MIP) repertoire. Very little is known about the genesis and molecular composition of the MIP repertoire. We developed a novel high-throughput mass spectrometry approach that yields an accurate definition of the nature and relative abundance of unlabeled peptides presented by MHC I molecules. We identified 189 and 196 MHC I–associated peptides from normal and neoplastic mouse thymocytes, respectively. By integrating our peptidomic data with global profiling of the transcriptome, we reached two conclusions. The MIP repertoire of primary mouse thymocytes is biased toward peptides derived from highly abundant transcripts and is enriched in peptides derived from cyclins/cyclin-dependent kinases and helicases. Furthermore, we found that ∼25% of MHC I–associated peptides were differentially expressed on normal versus neoplastic thymocytes. Approximately half of those peptides are derived from molecules directly implicated in neoplastic transformation (e.g., components of the PI3K–AKT–mTOR pathway). In most cases, overexpression of MHC I peptides on cancer cells entailed posttranscriptional mechanisms. Our results show that high-throughput analysis and sequencing of MHC I–associated peptides yields unique insights into the genesis of the MIP repertoire in normal and neoplastic cells

Geophysical monitoring of a laboratory‐scale internal erosion experiment

Earth dams are structures used worldwide for water management. Their failure over time is notably due to water seepage generating internal erosion. There is a growing need to detect the processes at work as early as possible. This study presents a controlled laboratory experiment aimed at detecting and monitoring water seepage into a soil sample. The experiment was monitored with electrical resistivity tomography, velocimeters and video recording. The video recording of the downstream side of the soil sample shows successive episodes of mass movements associated with a progressive water flow increase. The electrical resistivity tomography, limited by a low temporal resolution, shows an evolution of the resistivity in agreement with the evolution of the soil sample (e.g., saturation and mass movements), but with strong limitations regarding the robustness of the results. The continuous seismic recording reveals extra rupture episodes that occur inside the volume of the soil sample, which were not recorded by the video. Their distribution in time and energy illustrates strongly nonlinear changes in the soil sample, with several phases of acceleration. A controlled source monitoring using external repetitive events allows probing the medium with an enhanced temporal resolution compared to electrical resistivity tomography. The apparent seismic velocity of the soil sample reveals a nonlinear decrease, high at the beginning of the experiment, and then stalled until the different mass movements enlarge the amount of water inside the sample along with the water flow. The different techniques used, especially seismic monitoring, describe a complex and strongly nonlinear process of internal erosion centred around the coupling between water flow and internal damage. Finally, these findings suggest that seismic methods could be able to distinguish the four different phases of internal erosion (namely, initiation, continuation, progression and failure) discussed in the geotechnical literature

Synthesis of New [2,3′:6′,3′′]Terpyridines Using Iterative Cross-Coupling Reactions

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Focus on Microwaves Assisted Halogen-halogen Reaction Conditions on 2-Halopyridines

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An improved test of the strong equivalence principle with the pulsar in a triple star system

Accepted in A&AInternational audienceContext. The gravitational strong equivalence principle (SEP) is a cornerstone of the general theory of relativity (GR). Hence, testing the validity of SEP is of great importance when confronting GR, or its alternatives, with experimental data. Pulsars that are orbited by white dwarf companions provide an excellent laboratory, where the extreme difference in binding energy between neutron stars and white dwarfs allows for precision tests of the SEP via the technique of radio pulsar timing.Aims: To date, the best limit on the validity of SEP under strong-field conditions was obtained with a unique pulsar in a triple stellar system, PSR J0337+1715. We report here on an improvement of this test using an independent data set acquired over a period of 6 years with the Nançay radio telescope. The improvements arise from a uniformly sampled data set, a theoretical analysis, and a treatment that fixes some short-comings in the previously published results, leading to better precision and reliability of the test.Methods: In contrast to the previously published test, we use a different long-term timing data set, developed a new timing model and an independent numerical integration of the motion of the system, and determined the masses and orbital parameters with a different methodology that treats the parameter Δ, describing a possible strong-field SEP violation, identically to all other parameters.Results: We obtain a violation parameter Δ = ( + 0.5 ± 1.8) × 10-6 at 95% confidence level, which is compatible with and improves upon the previous study by 30%. This result is statistics-limited and avoids limitation by systematics as previously encountered. We find evidence for red noise in the pulsar spin frequency, which is responsible for up to 10% of the reported uncertainty. We use the improved limit on SEP violation to place constraints on a class of well-studied scalar-tensor theories, in particular we find ωBD > 140 000 for the Brans-Dicke parameter. The conservative limits presented here fully take into account current uncertainties in the equation for state of neutron-star matter

Simple and Reversible Transformation of an APCI/MS/MS Into an Aerosol Mass Spectrometer: Development and Characterization of a New Inlet

International audienceThe inlet of a commercial atmospheric pressure chemical ionization—mass spectrometer (APCI/MS/MS) has been modified to transform it into an aerosol mass spectrometer, named TD-API-AMS. The new inlet consists in a charcoal denuder (to trap gas phase VOCs and SVOCs) followed by the thermal-desorption unit of the APCI source. Thermal desorption and APCI were chosen because they avoid sample denaturizing while keeping good time resolution. The objectives of this paper are (1) to describe the simple and reversible modifications of the commercial APCI inlet allowing its use as an aerosol mass spectrometer and (2) to characterize the performances of this modified inlet. These performances are characterized in term of efficiency of (i) gas phase organic compounds removal, (ii) particle transmission, and (iii) particle volatilization in the thermal-desorption unit. The characterization was conduced with secondary organic aerosol (SOA) produced from the ozonolysis of -pinene and 2-buten-1-ol in a continuous flow reactor. The results show a denuder gas phase trapping efficiency higher than 93 ± 3% while the particle transmission efficiency was nearly 100% in particle number, but decreased to as little as 85% in total particle volume. This result highlights a shift of the particle distribution towards the fine particles occurring through the denuder, due to a modification of the gas-particle equilibrium. The inlets' characterization has also shown a particle volatilization efficiency higher than 90% (in volume)

Aromatic garlands, as new foldamers, to mimic protein secondary structure.

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Synthesis of new phenylpyridyl scaffolds using the Garlanding approach

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