Insights into the Reaction Mechanism of Aromatic Ring Cleavage by Homogentisate Dioxygenase: A Quantum Mechanical/Molecular Mechanical Study

To elucidate the reaction mechanism of the ring cleavage of homogentisate by homogentisate dioxygenase, quantum mechanical/molecular mechanical (QM/MM) calculations were carried out by using two systems in different protonation states of the substrate C₂ hydroxyl group. When the substrate C₂ hydroxyl group is ionized (the ionized pathway), the superoxo attack on the substrate is the rate-limiting step in the catalytic cycle, with a barrier of 15.9 kcal/mol. Glu396 was found to play an important role in stabilizing the bridge species and its O–O cleavage product by donating a proton via a hydrogen-bonded water molecule. When the substrate C₂ hydroxyl group is not ionized (the nonionized pathway), the O–O bond cleavage of the bridge species is the rate-limiting step, with a barrier of 15.3 kcal/mol. The QM/MM-optimized geometries for the dioxygen and alkylperoxo complexes using the nonionized model (for the C₂ hydroxyl group) are in agreement with the experimental crystal structures, suggesting that the C₂ hydroxyl group is more likely to be nonionized

Effect of the Electric Double Layer (EDL) in Multicomponent Electrolyte Reduction and Solid Electrolyte Interphase (SEI) Formation in Lithium Batteries

Electrolytes, consisting of salts, solvents, and additives, must form a stable solid electrolyte interphase (SEI) to ensure the performance and durability of lithium(Li)-ion batteries. However, the electric double layer (EDL) structure near charged surfaces is still unsolved, despite its importance in dictating the species being reduced for SEI formation near a negative electrode. In this work, a newly developed model was used to illustrate the effect of EDL on SEI formation in two essential electrolytes, the carbonate-based electrolyte for Li-ion batteries and the ether-based electrolyte for batteries with Li-metal anodes. Both electrolytes have fluoroethylene carbonate (FEC) as a common additive to form the beneficial F-containing SEI component (e.g., LiF). However, the role of FEC drastically differs in these electrolytes. FEC is an effective SEI modifier for the carbonate-based electrolyte by being the only F-containing species entering the EDL and being reduced, as the anion (PF6–) will not enter the EDL. For the ether-based electrolyte, both the anion (TFSI–) and FEC can enter the EDL and be reduced. The competition of the two species within the EDL due to the surface charge and temperature leads to a unique temperature effect observed in prior experiments: the FEC additive is more effective in modulating SEI components at a low temperature (−40 °C) than at room temperature (20 °C) in the ether-based electrolyte. These collective quantitative agreements with experiments emphasize the importance of incorporating the effect of the EDL in multicomponent electrolyte reduction reactions in simulations/experiments to predict/control the formation of the SEI layer

Self-Reported Negative Emotion Ratings.

<p>Self-reported negative emotion ratings of choice in each loss condition. Losing T in TV was rated as the least negative, followed by T in TR and R in TR, with V in TV rated as the most negative (<i>ps</i><.01), even though the choice difficulty was controlled.</p

Self-Reported Negative Emotion Ratings and Response Times.

<p>a) Self-reported negative emotion ratings of choice in each loss decision condition. b) Self-reported difficulty ratings of choice in each loss decision condition. c) Mean response time (in milliseconds) in each loss decision condition.</p

Self-Reported Importance Ratings and Response Times.

<p>a) Self-reported importance ratings for alternatives in each loss decision condition. b) Self-reported choice difficulty ratings in each loss decision condition. c) Mean response time (in milliseconds) in each loss decision condition.</p

From Ab Initio Calculations to Multiscale Design of Si/C Core–Shell Particles for Li-Ion Anodes

The design of novel Si-enhanced nanocomposite electrodes that will successfully mitigate mechanical and chemical degradation is becoming increasingly important for next generation Li-ion batteries. Recently Si/C hollow core–shell nanoparticles were proposed as a promising anode architecture, which can successfully sustain thousands of cycles with high Coulombic efficiency. As the structural integrity and functionality of these heterogeneous Si materials depend on the strength and fracture energy of the active materials, an in-depth understanding of the interface and their intrinsic mechanical properties, such as fracture strength and debonding, becomes critical for the successful design of such and similar composites. Here, we first perform ab initio simulations to calculate these properties for lithiated a-Si/a-C interface structures and combine these results with linear elasticity expressions to model conditions that will avert fracture and debonding in these heterostructures. We find that the a-Si/a-C interface retains good adhesion even at high stages of lithiation. For average lithiated structures, we predict that the strong Si–C bonding averts fracture at the interface; instead, the structure ruptures within lithiated a-Si. From the calculated values and linear elastic fracture mechanics, we then construct a continuum level diagram, which outlines the safe regimes of operation in terms of the core and shell thickness and the state of charge. We believe that this multiscale approach can serve as a foundation for developing quantitative failure models and for subsequent development of flaw-tolerant anode architectures

Fixation results under the onset target condition of Experiment 1.

<p>Panel A illustrates the probability of fixating new objects under the onset target condition in Experiment 1; Panel B illustrates the probability of first look to onset for the three mask types under the onset target condition.</p

The effect of G668A, T596A, and R612Q mutations on the proteolytic processing and intracellular localization of ADAM12-L.

<p>(A) Proteolytic processing of the WT and mutant forms of human ADAM12-L in MCF10A cells. Cells with stable expression of ADAM12-L proteins or control empty vector (EV)-transduced cells were selected with puromycin after retroviral infection. Total cell lysates were analyzed by Western blotting using antibody specific for the cytoplasmic tail of ADAM12-L. Arrowhead indicates the nascent, full-length, catalytically inactive form, and arrow denotes the mature, processed, catalytically active form of ADAM12-L. (B) Cell surface localization of ADAM12-L was examined by flow cytometry. Live cells were trypsinized and stained with an antibody specific for the extracellular domain of ADAM12-L (red) or with isotype control antibody (black). (C) Intracellular localization of the WT and mutant ADAM12-L proteins. Cells were co-stained with anti-ADAM12 antibody (red), anti-KDEL antibody (endoplasmic reticulum marker; green), and DAPI (blue). Control represents cells expressing WT ADAM12-L, incubated with pre-immune serum instead of anti-ADAM12 antibody. Arrows indicate ADAM12 staining in post-ER compartments. Bar, 20 μm.</p

The average latencies of fixation on a new object and average number of trials in which onsets were fixated for all conditions in Experiment 2.

<p>The average latencies of fixation on a new object and average number of trials in which onsets were fixated for all conditions in Experiment 2.</p

Breast cancer cell lines express different levels of ADAM12-La and ADAM12-Lb.

<p>(A) A 100-bp region flanking the exon 4-exon 5 junction was PCR-amplified using duplicate cDNA samples isolated from Hs578T, MDA-MB-231, and MCF10DCIS.com cells and analyzed as in Fig. 3. Var-1a and Var-1b vectors served as controls. Exon 4a- and exon 4b-related bands are indicated with arrow and arrowhead, respectively. (B) Glycoprotein-enriched fractions from Hs578T, MDA-MB-231, and MCF10DCIS.com cells were analyzed by Western blotting using anti-ADAM12-L antibody. Full length ADAM12-La and ADAM12-Lb are indicated with solid and open arrowheads, respectively. The processed form of ADAM12-La is shown with arrow. (C) Cell surface localization of ADAM12-L was examined by flow cytometry. Live cells were trypsinized and stained with an antibody specific for the extracellular domain of ADAM12-L (red) or with isotype control antibody (grey).</p