The optical fiber geometry is known for rugged, high power laser sources that are preferred for many applications, but is typically limited to the visible and near-infrared regions of the electromagnetic spectrum due to the transmission limits of silica (< 2 µm). This wavelength range could be extended into the mid-infrared using transition metal doped, crystalline II-VI optical gain media, but these materials cannot be fabricated into optical fibers using conventional glass drawing methods. An in-situ high pressure chemical vapor deposition method for the fabrication of silica-cladded ZnSe fiber cores uniformly doped with Cr 2 + is reported. Optical pumping experiments reveal that these doped fibers exhibit threshold behavior and thus function as mid-infrared optical fiber lasers. Finite element calculations show that undesirable thermal effects common in bulk II-VI crystals are mitigated in the fiber geometry.

Evaporation from a surface under atmospheric conditions can be difficult to characterize because the process involves both thermodynamics and kinetics. Thermogravimetric analysis was used to study the evaporation of D-limonene under several nitrogen flow rates above the surface. Instead of the common thermodynamic analysis, a kinetic treatment resulted in an activation energy of evaporation that is mostly composed of the enthalpy of vaporization with a smaller, additional energy due to the diffusion of molecules through the laminar boundary layer above the evaporating surface. As the flow rate over the sample increased from 60 to 200 mL/min, the activation energy decreased from 57.3 to 49.7 kJ mol −1 and approached reported enthalpy of vaporization values. Thus thermogravimetric analysis can be used to quantitatively characterize both the kinetic and thermodynamic aspects of nonequilibrium evaporation processes.

Purpose: DNMT3A mutations confer a poor prognosis in acute myeloid leukemia (AML), but the molecular mechanisms downstream of DNMT3A mutations in disease pathogenesis are not completely understood, limiting targeted therapeutic options. The role of microRNA in DNMT3A-mutant AML pathogenesis is understudied. Experimental Design: DNA methylation and miRNA expression was evaluated in human AML patient samples and in Dnmt3a/Flt3-mutant AML mice. The treatment efficacy and molecular mechanisms of TLR7/8-directed therapies on DNMT3A-mutant AML were evaluated in vitro on human AML patient samples and in Dnmt3a/Flt3-mutant AML mice. Results: miR-196b is hypomethylated and overexpressed in DNMT3A-mutant AML and is associated with poor patient outcome. miR-196b overexpression in DNMT3A-mutant AML is important to maintain an immature state and leukemic cell survival through repression of TLR signaling. The TLR7/8 agonist Resiquimod induces dendritic cell-like differentiation with co-stimulatory molecule expression in DNMT3A-mutant AML cells and provides a survival benefit to Dnmt3a/Flt3-mutant AML mice. The small molecule Bryostatin-1 augments Resiquimod-mediated AML growth inhibition and differentiation. Conclusions: DNMT3A loss-of-function mutations cause miRNA locus-specific hypomethylation and overexpression important for mutant DNMT3A-mediated pathogenesis and clinical outcomes. Specifically, the overexpression of miR-196b in DNMT3A-mutant AML creates a novel therapeutic vulnerability by controlling sensitivity to TLR7/8-directed therapies.

Supplementary Table from miR-196b–TLR7/8 Signaling Axis Regulates Innate Immune Signaling and Myeloid Maturation in <i>DNMT3A</i>-Mutant AML