Model for growth hormone receptor activation based on subunit rotation within a receptor dimer

Growth hormone is believed to activate the growth hormone receptor (GHR) by dimerizing two identical receptor subunits, leading to activation of JAK2 kinase associated with the cytoplasmic domain. However, we have reported previously that dimerization alone is insufficient to activate full-length GHR. By comparing the crystal structure of the liganded and unliganded human GHR extracellular domain, we show here that there is no substantial change in its conformation on ligand binding. However, the receptor can be activated by rotation without ligand by inserting a defined number of alanine residues within the transmembrane domain. Fluorescence resonance energy transfer ( FRET), bioluminescence resonance energy transfer (BRET) and coimmunoprecipitation studies suggest that receptor subunits undergo specific transmembrane interactions independent of hormone binding. We propose an activation mechanism involving a relative rotation of subunits within a dimeric receptor as a result of asymmetric placement of the receptor-binding sites on the ligand.

Phase equilibria in high MgO ferro-manganese and silico-manganese smelting slags

Liquidus isotherms and phase equilibria have been determined experimentally for a pseudo-ternary section of the form MnO-(CaO+MgO)-(SiO2+Al2O3) with a fixed Al-2,O-3,/SiO2, weight ratio of 0.17 and MgO/CaO weight ratio of 0.17 for temperatures in the range 1473-1673 K. The primary phase fields present for the section investigated include manganosite (Mn,Mg,Ca)O; dicalcium silicate alpha-2(Ca,Mg,Mn)O (.) SiO2; merwinite 3CaO(.) ((Mg,Mn)O.2SiO(2); wollastonite [(Ca,Mg,Mn)(OSiO2)-Si-.]; ;tephroite [2(Mn,Mg)O.SiO2]; rhodonite [(Mn,Mg)O. diopside [(CaO,MgO,MnO,Al2O3)(SiO2)-Si-.]; tridymite (SiO2), SiO2] and melilite [2CaO (.) (MgO,MnO,Al2O3).2(SiO2,Al2O3)]. The liquidus temperatures relevant to ferro-manganese and silico-manganese smelting slags have been determined. The liquiclus temperature is shown to be principally dependent on the modified basicity weight ratio (CaO+Mgo)/(SiO2+Al2O3) at low MnO concentrations, and dependent on the mole ratio (CaO+ MgO+MnO)/(SiO2+Al2O3) at higher MnO concentrations.

The effect of manganese on the grain size of commercial AZ31 alloy

The effect of manganese on gain refinement of a commercial AZ31 alloy has been investigated using an Al-60%Mn master alloy splatter as an alloying additive at 730 degrees C in aluminium titanite crucibles. It is shown that grain refinement by manganese is readily achievable in AZ31. Electron microprobe analyses reveal that prior to the addition of extra manganese the majority of the intermetallic particles found in AZ31 are of the AL(8)Mn(5) type. However, after the addition of extra manganese in the range from 0.1% to 0.8%, the predominant group of intermetallic particles changes to the metastable AlMn type. This leads to a hypothesis that the metastable AlMn intermetallic particles are more effective than Al8Mn5 as nucleation sites for magnesium grains. The hypothesis is supported by the observation that a long period of holding at 730 degrees C leads to an increase in grain size, due probably to the transformation of the metastable AlMn to the stable Al8Mn5. The hypothesis has also been used to understand the mechanism of grain refinement by superheating.

Effect of manganese on grain refinement of Mg-Al based alloys

Manganese is a grain refiner for high purity Mg-3%Al, Mg-6%Al, Mg-9%Al, and commercial AZ31 (Mg-3%Al-1%Zn) alloys when introduced in the form of an Al-60%Mn master alloy splatter but the use of pure Mn flakes and ALTAB (TM) Mn75 tablets shows no grain refinement. Long time holding of the melt at 730 degrees C leads to an increase in grain size. The mechanism is attributed to the presence of all epsilon-AlMn phase (hexagonal close-packed) in the master alloy splatter. (c) 2006 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Interactions between iron, manganese, and the Al-Si eutectic in hypoeutectic Al-Si alloys

Sand-cast plates were used to determine the effect of iron and manganese concentrations on porosity levels in Al-9 pet Si-0.5 pet Mg alloys. Iron increased porosity levels. Manganese additions increased porosity levels in alloys with 0.1 pet Fe, but reduced porosity in alloys with 0.6 and I pet Fe. Thermal analysis and quenching were undertaken to determine the effect of iron and manganese on the solidification of the Al-Si eutectic. At high iron levels, the presence of large beta-Al5FeSi was found to reduce the number of eutectic nucleation events and increase the eutectic grain size. The preferential formation of alpha-Al15Mn3Si2 upon addition of manganese reversed these effects. It is proposed that this interaction is due to beta-Al5FeSi and the Al-Si eutectic having common nuclei. Porosity levels are proposed to be controlled by the eutectic grain size and the size of the iron-bearing intermetallic particles rather than the specific intermetallic phase that forms.

Phase equilibria in high MgO ferro- and silico-manganese smelting slags

Phase equilibria have been determined experimentally for pseudo-ternary sections of the form “MnO”- (CaO+MgO)-(SiO2+Al2O3) with a fixed Al2O3/SiO2 weight ratio of 0.17 and MgO/CaO weight ratios of 0.25 and 0.17 respectively for temperatures in the range 1473-1673 K. The primary phase fields present for the MgO/CaO weight ratio of 0.17 include manganosite (Mn,Mg,Ca)O; dicalcium silicate α-2(Ca,Mg,Mn)O·SiO2; merwinite 3CaO⋅(Mg,Mn)O⋅2SiO2; wollastonite [(Ca,Mg,Mn)O·SiO2]; diopside [(CaO,MgO,MnO,Al2O3)·SiO2]; tridymite (SiO2); tephroite [2(Mn,Mg)O·SiO2]; rhodonite [(Mn,Mg)O·SiO2] and melilite [2CaO·(MgO,MnO,Al2O3)·2(SiO2,Al2O3)]. For the section with MgO/CaO weight ratio of 0.25 the anorthite phase (CaO⋅Al2O3⋅2SiO2) is also present. The liquidus temperatures of ferro- and silico-manganese smelting slags have been determined. The liquidus temperatures at low MnO concentrations are shown to be principally dependent on the modified basicity weight ratio (CaO+MgO)/(SiO2+Al2O3).