Miscibility Gap Closure, Interface Morphology, and Phase Microstructure of 3D Li(x)FePO4 Nanoparticles from Surface Wetting and Coherency Strain.

We study the mesoscopic effects which modify phase-segregation in LixFePO4 nanoparticles using a multiphysics phase-field model implement on a high performance cluster. We simulate 3D spherical particles of radii from 3 to 40 nm and examine the equilibrium microstructure and voltage profiles as they depend on size and overall lithiation. The model includes anisotropic, concentration-dependent elastic moduli, misfit strain, and facet dependent surface wetting within a Cahn-Hilliard formulation. We find that the miscibility gap vanishes for particles of radius ∼5 nm, and the solubility limits change with overall particle lithiation. Surface wetting stabilizes minority phases by aligning them with energetically beneficial facets. The equilibrium voltage profile is modified by these effects in magnitude, and the length and slope of the voltage plateau during two-phase coexistence.

The influence of acute resistance exercise on cyclooxygenase-1 and -2 activity and protein levels in human skeletal muscle.

This study evaluated the activity and content of cyclooxygenase (COX)-1 and -2 in response to acute resistance exercise (RE) in human skeletal muscle. Previous work suggests that COX-1, but not COX-2, is the primary COX isoform elevated with resistance exercise in human skeletal muscle. COX activity, however, has not been assessed after resistance exercise in humans. It was hypothesized that RE would increase COX-1 but not COX-2 activity. Muscle biopsies were taken from the vastus lateralis of nine young men (25 ± 1 yr) at baseline (preexercise), 4, and 24 h after a single bout of knee extensor RE (three sets of 10 repetitions at 70% of maximum). Tissue lysate was assayed for COX-1 and COX-2 activity. COX-1 and COX-2 protein levels were measured via Western blot analysis. COX-1 activity increased at 4 h (P < 0.05) compared with preexercise, but returned to baseline at 24 h (PRE: 60 ± 10, 4 h: 106 ± 22, 24 h: 72 ± 8 nmol PGH2·g total protein(-1)·min(-1)). COX-2 activity was elevated at 4 and 24 h after RE (P < 0.05, PRE: 51 ± 7, 4 h: 100 ± 19, 24 h: 98 ± 14 nmol PGH2·g total protein(-1)·min(-1)). The protein level of COX-1 was not altered (P > 0.05) with acute RE. In contrast, COX-2 protein levels were nearly 3-fold greater (P > 0.05) at 4 h and 5-fold greater (P = 0.06) at 24 h, compared with preexercise. In conclusion, COX-1 activity increases transiently with exercise independent of COX-1 protein levels. In contrast, both COX-2 activity and protein levels were elevated with exercise, and this elevation persisted to at least 24 h after RE.

Estrogen receptor beta dependent attenuation of cytokine-induced cyclooxygenase-2 by androgens in human brain vascular smooth muscle cells and rat mesenteric arteries.

Androgens may provide protective effects in the vasculature under pathophysiological conditions. Our past studies have shown that dihydrotestosterone (DHT) decreases expression of cyclooxygenase-2 (COX-2) during cytokine, endotoxin, or hypoxic stimulation in human vascular smooth muscle cells, in an androgen receptor (AR)-independent fashion. Classically DHT is regarded as a pure AR agonist; however, it can be endogenously metabolized to 5α-androstane-3ß, 17ß-diol (3ß-diol), which has recently been shown to be a selective estrogen receptor (ERß) agonist. Therefore, we hypothesized that DHT's anti-inflammatory properties following cytokine stimulation are mediated through ERß. Using primary human brain vascular smooth muscle cells (HBVSMC), we tested whether DHT's effect on IL-1ß induced COX-2 expression was mediated via AR or ERß. The metabolism of DHT to 3ß-diol is a viable pathway in HBVSMC since mRNA for enzymes necessary for the synthesis and metabolism of 3ß-diol [3alpha-hydroxysteroid dehydrogenase (HSD), 3ß-HSD, 17ß-HSD, CYP7B1] was detected. In addition, the expression of AR, ERα, and ERß mRNA was detected. When applied to HBVSMC, DHT (10nM; 18 h) attenuated IL-1ß-induced increases in COX-2 protein expression. The AR antagonist bicalutamide did not block DHT's ability to reduce COX-2. Both the non-selective estrogen receptor antagonist ICI 182,780 (1 µM) and the selective ERß antagonist PHTPP (1 µM) inhibited the effect of DHT, suggesting that DHT actions are ERß-mediated. In HBVSMC and in rat mesenteric arteries, 3ß-diol, similar to DHT, reduced cytokine-induced COX-2 levels. In conclusion, DHT appears to be protective against the progression of vascular inflammation through metabolism to 3ß-diol and activation of ERß.