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For pulse energies between 10 and 30 mJ, the ablation product yield increases linearly, reaching approximately 1012 salt molecules per 30 mJ pulse. Using mass spectrometry, we observe Li+, Na+, and K+ in the plumes of ablated NaCl, KCl, and LiCl, which implies dissociation of the volatilized material. We do not observe salt ions (e.g., NaCl+). However, with 800 nm femtosecond laser pulses, the triatomic ion clusters Li2Cl+, Na2Cl+, and K2Cl+ are produced. Finally, we observe incomplete volatilization with the nanosecond pulses some of the ejecta are liquid droplets. The insights about ablation plume physics gleaned from these experiments should guide future implementations of the laser-volatilization technique.pH-Switchable, self-assembling materials are of interest in biological imaging and sensing applications. Here we propose that combining the pH-switchability of RXDX (X = Ala, Val, Leu, Ile, Phe) peptides and the optical properties of coumarin creates an ideal candidate for these materials. This suggestion is tested with a thorough set of all-atom molecular dynamics simulations. We first investigate the dependence of pH-switchabiliy on the identity of the hydrophobic residue, X, in the bare (RXDX)4 systems. Increasing the hydrophobicity stabilizes the fiber which, in turn, reduces the pH-switchabilty of the system. This behavior is found to be somewhat transferable to systems in which a single hydrophobic residue is replaced with a coumarin containing amino acid. In this case, conjugates with X = Ala are found to be unstable at both pHs, while conjugates with X = Val, Leu, Ile, and Phe are found to form stable β-sheets at least at neutral pH. The coumarin-(RFDF)4 conjugate is found to have the largest relative entropy value of 0.884 ± 0.001 between neutral and acidic coumarin ordering distributions. Thus, we posit that coumarin-(RFDF)4 containing peptide sequences are ideal candidates for pH-sensing bioelectronic materials.Fatty acid esters of 3-monochloropropane 1,2-diol (3-MCPD esters) are processing-induced food toxicants, with the kidney as their major target organ. For the first time, this study treated Sprague Dawley (SD) rats with 3-MCPD 1-monooleate at 10 and 100 mg/kg BW/day and 1-monostearate at 15 and 150 mg/kg BW/day for 90 days and examined for their potential semi-long-term nephrotoxicity and the associated molecular mechanisms. No bodyweight difference was observed between groups during the study. Both 3-MCPD 1-monooleate and 1-monostearate resulted in a dose-dependent increase of serum urea creatinine, uric acid and urea nitrogen levels, and histological renal impairment. The proteomic analysis of the kidney samples showed that the 3-MCPD esters deregulated proteins involved in the pathways for ion transportation, apoptosis, the metabolism of xenobiotics, and enzymes related to endogenous biological metabolisms of carbohydrates, amino acids, nitrogen, lipids, fatty acids, and the tricarboxylic acid (TCA) cycle, providing partial explanation for the nephrotoxicity of 3-MCPD esters.Cryo-electron tomography maps often exhibit considerable noise and anisotropic resolution, due to the low-dose requirements and the missing wedge in Fourier space. These spurious features are visually unappealing and, more importantly, prevent an automated segmentation of geometric shapes, requiring a subjective and labor-intensive manual tracing. We developed a novel computational strategy for objectively denoising and correcting missing-wedge artifacts in homogeneous specimen areas of tomograms, where it is assumed that a template repeats itself across the volume under consideration, as happens in the case of filaments. In our deconvolution approach, we use a template and a map of corresponding template locations, allowing us to compensate for the information lost in the missing wedge. We applied the method to tomograms of actin-filament bundles of inner-ear stereocilia, which are critical for the senses of hearing and balance. In addition, we demonstrate that our method can be used for cell membrane detection.Double proton transfer (DPT) in guanine-cytosine (GC) base pairs and adenine-thymine (AT) base pairs produces tautomeric forms, denoted G*C* and A*T*. To examine DPT, (i) intrinsic reaction coordinates for DPT, (ii) probabilities of change from GC to G*C* and from AT to A*T*, and (iii) infrared absorption intensities of GC and G*C* were investigated on the basis of density functional theory and Eyring’s chemical kinetics. The probabilities of change from GC to G*C* were 3 × 10-8, and those from AT to A*T* were 2 × 10-10. These values are consistent with the rate of mutation previously reported by Drake et al. (Proc. Natl. Acad. Sci. U.S.A. 1991, 88, 7160-7164). G*C* exhibited two vibrational modes around 3000 cm-1, whereas GC exhibited no vibrational modes around the same frequency. The infrared intensity calculated for G*C* showed that the strong absorption obtained around 3000 cm-1 was caused by one of the two modes.We describe the development and implementation of a quasi-equilibrium hydration shell model of biomolecular solvation with adaptive boundaries. Applying the model to microsecond-long molecular dynamics simulations of several protein systems of varying complexity, we find that the model simulation results are of comparable quality to those obtained from simulations of fully solvated systems, but at a reduced computational cost. We discuss the dominant sources of error in the model and outline directions for future improvements.The effective treatment of adenovirus (HAdV) infections in immunocompromised patients still poses great challenges. Herein, we reported our continued efforts to optimize a series of salicylamide derivatives as potent inhibitors of HAdV infection. Of these, nine compounds (11, 13, 14, 17, 20, 58, 60, 62, and 70) showed significantly improved anti-HAdV activities with nanomolar to submicromolar IC50 values and high selectivity indexes (SI > 100), indicating better safety windows, compared to those of the lead compound niclosamide. Our mechanistic assays suggest that compounds 13, 62, and 70 exert their activities in the HAdV entry pathway, while compounds 14 and 60 likely target the HAdV DNA replication, and 11, 17, 20, and 58 inhibit later steps after DNA replication. selleck chemical Given the broad anti-viral activity profile of niclosamide, these derivatives may also offer therapeutic potential for other viral infections.