We report a precision measurement of the parity-violating asymmetry APV in the elastic scattering of longitudinally polarized electrons from 208Pb. We measure APV= 550 ± 16 (stat) ±8 (syst) parts per ...billion, leading to an extraction of the neutral weak form factor FW(Q2= 0.00616 GeV2) = 0.368 ± 0.013. Combined with our previous measurement, the extracted neutron skin thickness is Rn-Rp= 0.283 ± 0.071 fm. The result also yields the first significant direct measurement of the interior weak density of 208Pb: ρ$^0_W$ = -0.0796 ± 0.0036(exp) ± 0.0013(theo) fm-3 leading to the interior baryon density ρ$^0_b$ = 0.1480 ± 0.0036(exp) ± 0.0013(theo) fm-3. Finally, the measurement accurately constrains the density dependence of the symmetry energy of nuclear matter near saturation density, with implications for the size and composition of neutron stars.
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Despite the well-known detrimental effects of cigarette smoke (CS), little is known about the complex gene expression dynamics in the early stages after exposure. This study aims to investigate early ...transcriptomic responses following CS exposure of airway epithelial cells in culture and compare these to those found in human CS exposure studies.
Primary bronchial epithelial cells (PBEC) were differentiated at the air-liquid interface (ALI) and exposed to whole CS. Bulk RNA-sequencing was performed at 1 h, 4 h, and 24 h hereafter, followed by differential gene expression analysis. Results were additionally compared to data retrieved from human CS studies.
ALI-PBEC gene expression in response to CS was most significantly changed at 4 h after exposure. Early transcriptomic changes (1 h, 4 h post CS exposure) were related to oxidative stress, xenobiotic metabolism, higher expression of immediate early genes and pro-inflammatory pathways (i.e., Nrf2, AP-1, AhR). At 24 h, ferroptosis-associated genes were significantly increased, whereas PRKN, involved in removing dysfunctional mitochondria, was downregulated. Importantly, the transcriptome dynamics of the current study mirrored in-vivo human studies of acute CS exposure, chronic smokers, and inversely mirrored smoking cessation.
These findings show that early after CS exposure xenobiotic metabolism and pro-inflammatory pathways were activated, followed by activation of the ferroptosis-related cell death pathway. Moreover, significant overlap between these transcriptomic responses in the in-vitro model and human in-vivo studies was found, with an early response of ciliated cells. These results provide validation for the use of ALI-PBEC cultures to study the human lung epithelial response to inhaled toxicants.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We present new precision measurements of the elastic electron-proton scattering cross section for momentum transfer (Q^{2}) up to 15.75 (GeV/c)^{2}. Combined with existing data, these provide an ...improved extraction of the proton magnetic form factor at high Q^{2} and double the range over which a longitudinal or transverse separation of the cross section can be performed. The difference between our results and polarization data agrees with that observed at lower Q^{2} and attributed to hard two-photon exchange (TPE) effects, extending to 8 (GeV/c)^{2} the range of Q^{2} for which a discrepancy is established at >95% confidence. We use the discrepancy to quantify the size of TPE contributions needed to explain the cross section at high Q^{2}.
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We report precision determinations of the beam-normal single spin asymmetries (A_{n}) in the elastic scattering of 0.95 and 2.18 GeV electrons off ^{12}C, ^{40}Ca, ^{48}Ca, and ^{208}Pb at very ...forward angles where the most detailed theoretical calculations have been performed. The first measurements of A_{n} for ^{40}Ca and ^{48}Ca are found to be similar to that of ^{12}C, consistent with expectations and thus demonstrating the validity of theoretical calculations for nuclei with Z≤20. We also report A_{n} for ^{208}Pb at two new momentum transfers (Q^{2}) extending the previous measurement. Our new data confirm the surprising result previously reported, with all three data points showing significant disagreement with the results from the Z≤20 nuclei. These data confirm our basic understanding of the underlying dynamics that govern A_{n} for nuclei containing ≲50 nucleons, but point to the need for further investigation to understand the unusual A_{n} behavior discovered for scattering off ^{208}Pb.
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Abstract
Engineering single base edits using CRISPR technology including specific deaminases and single-guide RNA (sgRNA) is a rapidly evolving field. Different types of base edits can be ...constructed, with cytidine base editors (CBEs) facilitating transition of C-to-T variants, adenine base editors (ABEs) enabling transition of A-to-G variants, C-to-G transversion base editors (CGBEs) and recently adenine transversion editors (AYBE) that create A-to-C and A-to-T variants. The base-editing machine learning algorithm BE-Hive predicts which sgRNA and base editor combinations have the strongest likelihood of achieving desired base edits. We have used BE-Hive and TP53 mutation data from The Cancer Genome Atlas (TCGA) ovarian cancer cohort to predict which mutations can be engineered, or reverted to wild-type (WT) sequence, using CBEs, ABEs or CGBEs. We have developed and automated a ranking system to assist in selecting optimally designed sgRNA that considers the presence of a suitable protospacer adjacent motif (PAM), the frequency of predicted bystander edits, editing efficiency and target base change. We have generated single constructs containing ABE or CBE editing machinery, an sgRNA cloning backbone and an enhanced green fluorescent protein tag (EGFP), removing the need for co-transfection of multiple plasmids. We have tested our ranking system and new plasmid constructs to engineer the p53 mutants Y220C, R282W and R248Q into WT p53 cells and shown that these mutants cannot activate four p53 target genes, mimicking the behaviour of endogenous p53 mutations. This field will continue to rapidly progress, requiring new strategies such as we propose to ensure desired base-editing outcomes.
Graphical Abstract
Graphical Abstract
We report measurements of the exclusive neutral pion electroproduction cross section off protons at large values of $x_B$ (0.36, 0.48 and 0.60) and $Q^2$ (3.1 to 8.4 GeV$^2$) obtained from Jefferson ...Lab Hall A experiment E12-06-014. The corresponding structure functions $d\sigma_L/dt+\epsilon d\sigma_T/dt$, $d\sigma_{TT}/dt$, $d\sigma_{LT}/dt$ and $d\sigma_{LT'}/dt$ are extracted as a function of the proton momentum transfer $t-t_{min}$. The results suggest the amplitude for transversely polarized virtual photons continues to dominate the cross-section throughout this kinematic range. The data are well described by calculations based on transversity Generalized Parton Distributions coupled to a helicity flip Distribution Amplitude of the pion, thus providing a unique way to probe the structure of the nucleon.
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