Interaction of intense ultrashort laser pulses with solid targets: A systematic analysis using first-principles calculations

Intense ultrashort laser pulse irradiation of solid targets was systematically investigated at the first-principles level, both theoretically and computationally. In the method, the propagation of a pulsed light through a thin film is described by a one-dimensional Maxwell's equation, and the microscopic electronic motion at different positions in the film is described by employing first-principles time-dependent density functional theory (TDDFT). The method uses a coarse-graining approximation to couple light propagation and electronic motion, and is termed the multiscale Maxwell-TDDFT method. The reflectance, transmittance, and absorbance of pulsed light incident normally on thin films of 50-200 nm thickness were calculated for materials with different optical properties, such as aluminum (simple metal), graphite (semi-metal), silicon (small-gap dielectric), and quartz (wide-gap dielectric). Optical response transitions were explored as the light intensity shifted from the linear regime, represented by the dielectric function for weak light, to the extremely nonlinear regime, represented by plasma reflection under intense light conditions. Numerous mechanisms that depend on the laser pulse intensity and material type were found to contribute to these changes. These include multiphoton absorption, saturable absorption, sign change of the effective dielectric constant, and transition from quantum occupation to classical Boltzmann distribution. Thus, the calculations provide a unified understanding of the interaction of intense pulsed light with solids, occurring on an extremely short time scale

Synthesis of Sulfanylated Difluoroalkenes: Electrophilic Difluoromethylidenation of Dithioesters with Difluorocarbene

Electrophilic difluoromethylidenation of dithioesters was achieved in high yields via the reaction with difluorocarbene. When aryl or alkyl dithiocarboxylates were treated with trimethylsilyl 2,2-difluoro-2-fluorosulfonylacetate in the presence of 5 mol % of a Proton Sponge catalyst, the in situ generated difluorocarbene reacted with the dithioesters to afford 2-sulfanylated 1,1-difluoro-1-alkenes via difluorothiiranes. This reaction can be considered as an electrophilic counterpart of the Wittig-type difluoromethylidenation of carbonyl compounds with nucleophilic difluoromethylene ylides

Deleterious Effects of Exact Exchange Functionals on Predictions of Molecular Conductance

Kohn–Sham (KS) density functional theory (DFT) describes well the atomistic structure of molecular junctions and their coupling to the semi-infinite metallic electrodes but severely overestimates conductance due to the spuriously large density of charge-carrier states of the KS system. Previous works show that inclusion of appropriate amounts of nonlocal exchange in the functional can fix the problem and provide realistic conductance estimates. Here however we discover that nonlocal exchange can also lead to deleterious effects which artificially overestimate transmittance even beyond the KS-DFT prediction. The effect is a result of exchange coupling between nonoverlapping states of diradical character. We prescribe a practical recipe for eliminating such artifacts

Immunofluorescence analysis of E-cadherin, fibronectin, and α-SMA in A549 cells treated with low-dose PQ for 6 days.

<p>Following 6 days of exposure to 30 μM PQ with or without SB431542, the cells were double-stained with anti-E-cadherin (D-F; green) and anti-fibronectin (G-I; red), or stained with anti-α-SMA (P-R; green), and observed under fluorescence microscopy. Nuclei were counterstained with DAPI (A-C and M-O; blue). Merged images are also shown (J-L and S-U).</p

G-Protein/β-Arrestin-Linked Fluctuating Network of G-Protein-Coupled Receptors for Predicting Drug Efficacy and Bias Using Short-Term Molecular Dynamics Simulation

<div><p>The efficacy and bias of signal transduction induced by a drug at a target protein are closely associated with the benefits and side effects of the drug. In particular, partial agonist activity and G-protein/β-arrestin-biased agonist activity for the G-protein-coupled receptor (GPCR) family, the family with the most target proteins of launched drugs, are key issues in drug discovery. However, designing GPCR drugs with appropriate efficacy and bias is challenging because the dynamic mechanism of signal transduction induced by ligand—receptor interactions is complicated. Here, we identified the G-protein/β-arrestin-linked fluctuating network, which initiates large-scale conformational changes, using sub-microsecond molecular dynamics (MD) simulations of the β₂-adrenergic receptor (β₂AR) with a diverse collection of ligands and correlation analysis of their G protein/β-arrestin efficacy. The G-protein-linked fluctuating network extends from the ligand-binding site to the G-protein-binding site through the connector region, and the β-arrestin-linked fluctuating network consists of the NPxxY motif and adjacent regions. We confirmed that the averaged values of fluctuation in the fluctuating network detected are good quantitative indexes for explaining G protein/β-arrestin efficacy. These results indicate that short-term MD simulation is a practical method to predict the efficacy and bias of any compound for GPCRs.</p></div

EMT-like response to low-dose PQ exposure is dependent on TGF-β1 signaling and is involved in the suppression of apoptosis.

<p>(A) SB431542 suppresses the increase in α-SMA but not the decrease in E-cadherin in PQ-treated cells. Following 12 days of exposure to 30 μM PQ with or without 10 μM SB431542, the cells were subjected to Western blot analysis. The levels of α-SMA and E-cadherin relative to GAPDH were determined by densitometric analysis (mean and SD, n = 3–4). The value of the control was set to 1. **<i>p</i> < 0.01 versus control. (B) Cytomorphology of A549 cells exposed to PQ with or without SB431542. (C) Increased activation of caspase9 in PQ+SB431542-treated cells. The cleaved form (35 kDa, indicated by the arrow) of caspase9 was detected by Western blot analysis. The levels of cleaved caspase9 relative to GAPDH are shown (mean and SD, n = 4). The value of the control was set to 1. **<i>p</i> < 0.01 versus control.</p

Plots of the mean ΔRMSF and ΔPCC against G protein efficacy.

<p>The mean ΔRMSF and ΔPCC using C_α atoms, ΔRMSF(C_α) and ΔPCC(C_α), were plotted against G protein efficacy (A, B, C) and β-arrestin efficacy (D, E, F). The 14 ligands are shown as circles. (A) Plot of the mean ΔRMSF(C_α) of helix 6, on which the fluctuating atoms^G-protein were particularly concentrated, against the G protein efficacy from a previous study [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0155816#pone.0155816.ref027" target="_blank">27</a>]. (B) Plot of the mean ΔPCC(C_α) between helix 3–helix 6, in which a large number of atom–atom couplings^G-protein were detected, against G protein efficacy. (C) Plot of the mean ΔRMSF(C_α) of helix 6 against the mean ΔPCC(C_α) between helix 3–helix 6. Red: Ligands with a strong G protein efficacy that have larger E_max values than isoprenaline; Blue: Ligands with a moderate G protein efficacy that have smaller E_max values than isoprenaline; Green: Ligands with no/weak efficacy. (D) Plot of the mean ΔRMSF(C_α) of specific residues in helix 1 and helix 7 against the β-arrestin efficacy from a previous study [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0155816#pone.0155816.ref027" target="_blank">27</a>]. (E) Plot of the mean ΔPCC(C_α) of specific residue pairs between helix 1 and helix 7 against β-arrestin efficacy. (F) Plot of the mean ΔRMSF(C_α) against the mean ΔPCC(C_α). Red: Ligands with a strong β-arrestin efficacy (E_max ≥50); Blue: Ligands with a moderate β-arrestin efficacy (E_max 10–50); Green: Ligands with no/weak β-arrestin efficacy (E_max <10).</p

Immunofluorescence analysis of E-cadherin, fibronectin, and α-SMA in A549 cells treated with low-dose PQ for 12 days.

<p>Following 12 days of exposure to 30 μM PQ with or without SB431542, the cells were double-stained with anti-E-cadherin (D-F; green) and anti-fibronectin (G-I; red), or stained with anti-α-SMA (P-R; green), and observed under fluorescence microscopy. Nuclei were counterstained with DAPI (A-C and M-O; blue). Merged images are also shown (J-L and S-U).</p

G-protein-linked fluctuating network of β₂AR.

<p>(A) Fluctuating atoms^G-protein, which have a Pearson’s correlation coefficient of more than 0.6 between their ΔRMSF and G protein efficacy, are indicated by blue spheres. (B) Atom–atom couplings^G-protein were extracted from any pairs containing at least one fluctuating atom^G-protein by correlation analysis between ΔPCC and G protein efficacy. The atom–atom pairs with more than a 0.6 Pearson’s correlation coefficient and within 12 Å are connected by lines. In the cases where both atoms are fluctuating atoms^G-protein, the lines are colored red. In cases where one of the two atoms is a fluctuating atom^G-protein, the lines are colored orange (see the <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0155816#sec002" target="_blank">Methods</a> section). The G-protein-binding site is shown with a dashed magenta ellipse.</p

Low-dose long-term exposure to PQ induces both a decrease in E-cadherin and an increase in α-SMA.

<p>A549 cells were treated with 0, 10, or 30 μM PQ for 6 days and examined for cell morphology as well as the levels of E-cadherin and α-SMA. (A) Cytomorphology of A549 cells exposed to PQ was observed under light microscopy. (B) The decrease in E-cadherin and the increase in α-SMA proteins in PQ-treated cells. The levels of the E-cadherin and α-SMA proteins were determined by Western blot analysis, and levels of these proteins relative to GAPDH were measured by densitometric analysis (mean and SD, n = 4). (C) The decrease in E-cadherin and the increase in α-SMA mRNAs in PQ-treated cells. The levels of E-cadherin and α-SMA mRNAs were determined by qPCR analysis. The levels of the mRNAs relative to GAPDH are shown (mean and SD, n = 3–4). The value of the control was set to 1. *<i>p</i> < 0.05, **<i>p</i> < 0.01 versus zero.</p