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The objectives of this proposed study are to (1) design and develop single BCC phase refractory high-entropy alloys (HEAs) for the high-temperature applications, (2) investigate the deformation mechanisms of refractory HEAs, (3) improve an integrated approach, coupling focused experiments and theoretical modeling, to design, discover, and develop HEAs, and (4) understand the alloy design-microstructure-property-performance links underlying the mechanical behavior of refractory HEA systems for gas-turbine applications A traditional alloy system generally includes one or two principal elements that form the matrix with other additional elements, e.g., iron or aluminum alloys, to strengthen some specific properties, such as strength and corrosion resistance. As a novel class of multicomponent materials, HEAs have recently stimulated the intensive study because of their large composition space and great properties. The definition of HEAs could be based on their chemical compositions or configurational entropy. According to their compositions, HEAs are typically composed of four or more principal elements in an equal or near-equal atomic percent between 5 to 35 atomic percent (at. %), which can crystallize as a single phase. According to their entropies, HEAs are defined as alloys that have configurational entropies larger or equal to 1.5R, where R is the ideal gas constant, no matter whether they are a single phase or multi-phases. A majority of HEAs reported so far have multiple phases (second phases, nanoparticles, element segregations and etc.), rather than a single solid-solution phase. However, specially-designed HEAs can possess single-phase structures, such as body-centered-cubic (BCC), face-centered-cubic (FCC), and hexagonal-close-packed (HCP) structures These single-phase and multiple-phase HEAs have desirable materials properties, such as high strength, reasonable ductility, high hardness, good fatigue and corrosion resistance, high thermal conductivity, low coefficient of thermal expansion, and great toughness for gas turbines. Thus, it is of critical importance to develop a fundamental knowledge and understanding of the mechanical characteristics at elevated temperatures. The microstructure, and elastic/plastic deformation behavior of the refractory HEAs will be investigated, using the integrated experimental (transmission-electron microscopy/scanning-transmission-electron microscopy, in-situ neutron diffraction, and atom-probe tomography) and theoretical (first-principles calculations, and crystal-plasticity finite-element modeling) approaches.

Binding of GnRH to its receptor (GnRHR) stimulates the synthesis and secretion of the gonadotropins, as well as up-regulation of GnRHR. Thus, the interaction between GnRH and GnRHR represents a central point for regulation of reproduction. Glucocorticoids alter reproduction by reducing GnRH responsiveness of gonadotropes within the anterior pituitary gland, potentially via transcriptional regulation of the GnRHR gene. Investigation into this mechanism, however, revealed that the murine GnRHR gene was stimulated by glucocorticoids. To determine the effect of glucocorticoids on porcine GnRHR gene expression, gonadotrope-derived αT3-1 cells were transiently transfected with a vector containing 5118 bp of 5’ flanking sequence for the porcine GnRHR gene fused to luciferase for 12 h and treated with increasing concentrations of the glucocorticoid agonist, dexamethasone (0, 1, 10, 100 and 1,000 nM) for an additional 12 h prior to harvest. Maximal induction of luciferase activity was detected at 100 nM of dexamethasone (2-fold over vehicle; P < 0.05). Deletion from 274 to 323 bp of proximal promoter eliminated glucocorticoid responsiveness, suggestive of a glucocorticoid response element (GRE). Electrophoretic mobility shift assays (EMSAs) using a radiolabeled oligonucleotide spanning -290/-270 bp of proximal promoter revealed increased binding of nuclear extracts from αT3-1 cells treated with 100 nM dexamethasone compared to vehicle. Mass spectrometry analysis of isolated proteins from a pull-down using a biotinylated oligonucleotide (-290/-270 bp) identified PARP-1 as the binding component. EMSAs with either GR or PARP-1 antibodies resulted in a supershift of the specific binding complex, whereas addition of both antibodies abolished the supershift. Inhibition of p38 and ERK1/2 mitogen-activated protein kinase (MAPK) pathways decreased dexamethasone-induced promoter activity (P < 0.05), indicating their involvement in glucocorticoid stimulation of the promoter. Thus, our working model for glucocorticoid responsiveness of the porcine GnRHR gene suggests that binding of glucocorticoid to its receptor (GR), triggers GR phosophorylation by p38 and ERK1/2 MAPK pathways, resulting in the recruitment of PARP-1 by phosphorylated, ligand-bound GR to a GRE located within -290/-270 bp of the porcine GnRHR promoter. Adviser: Brett R. White