From Newsgroup: comp.lang.mumps

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Background: Apo- (iron free) and holo- (iron bound) transferrin (Tf) participate in precise regulation of brain iron uptake at endothelial cells of the blood-brain barrier. Apo-Tf indicates an iron deficient environment and stimulates iron release, while holo-Tf indicates an iron sufficient environment and suppresses additional iron release. Free iron is exported through ferroportin, with hephaestin as an aid to the process. Until now, the molecular mechanism of apo- and holo-Tf's influence on iron release was largely unknown.
Methods: Here we use a variety of cell culture techniques, including co-immunoprecipitation and proximity ligation assay, in iPSC-derived endothelial cells and HEK 293 cells to investigate the mechanism of apo- and holo-Tf's influence over iron release. We placed our findings in physiological context by further deciphering how hepcidin played a role in this mechanism as well.
Results: We demonstrate that holo-Tf induces the internalization of ferroportin through the established ferroportin degradation pathway. Furthermore, holo-Tf directly binds to ferroportin, whereas apo-Tf directly binds to hephaestin. Only pathological levels of hepcidin disrupt the interaction between holo-Tf and ferroportin, and no amount of hepcidin disrupts the interaction between apo-Tf and hephaestin. The disruption of the holo-Tf and ferroportin interaction by hepcidin is due to hepcidin's ability to rapidly internalize ferroportin compared to holo-Tf.
Conclusions: These novel findings provide a molecular mechanism for apo- and holo-Tf regulation of iron release from endothelial cells. They further demonstrate how hepcidin impacts these protein-protein interactions, and offer a model for how holo-Tf and hepcidin corporate to suppress iron release. We have established a more thorough understanding of the mechanisms behind iron release regulation with great clinical impact for a variety of neurological conditions in which iron release is dysregulated.
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I only made feedback on Holosmith and i believe you guys can make a better feedback regarding scrapper's and Mech's weapons. I always loved scrapper's hammer playstyle and loved holo's holo mode and now soon i will be able to enjoy both of them at the same time.
Isn't elite spec the main important play? The spec holo it self has a special abilities and making sword a all round core weapon has changed everything. At the moment, the sword has no value outside of holosmith spec because the sword is created to work around the holo spec but if Anet makes weapons to work around different elite specs then i believe it will fix everything.
Holosmith has heat levels and giving other weapons the similer ability will only make holosmith a special spec. Same goes for other elite spec weapons. Scrapper or mech using sword seems totally pointless when hammer will be the go to weapon for everything now, so only elite spec weapons needs buffs to work around other elite specs designs.
The issue with making sword bonuses baseline Is that Anet will definitely nerf it to compensate. Which means everyone will get sword to be a little better, but holosmiths will get it a little worst. I still don't think baking the >50% heat bonuses into the baseline would be enough for you guys to use it effectively. Imo sword only really gets good with >100% heat bonuses, but making those the baseline would definitely force Anets hand to hard nerf it.
On the other hand, making other weapons get heat tiers is a massive win for holosmiths, which even as a holosmith player Idk if we should have. Imagine shield with >100% heat bonus, I don't even want to think about how much better it will be, and it's already quite good.
likewise for hammer. Now the builds that had to take a utility to Block will be able to put that into hammer instead... and there will be huge cries to nerf hammer because of its effectiveness in covering some of the inherent limitations of holo.
What I like about the hammer is the amount of might it gives but holosmiths can compensate for that, and picking hammer over sword means a big loss of quickness(at least in PvE) which is massive for people who don't always do Raids/Strikes and organized Fractals because self boons won't matter that much there.
Yeah I was PvP talking... no idea about other environments. The thunderclap, plus reflect, plus block of hammer, the build in leap (in lighting field) made my holo experiments with it .... well abusive. Because it covers for the natural trade offs of holo typically.
But when you say might generation, are you talking the third whack with auto attack? I almost never auto attack with hammer in PvP because of its range and speed. Only sometimes if I have swiftness and am projectile reflected against nades, and every other skill is on cooldown.
Yeah I was PvP talking... no idea about other environments. The thunderclap, plus reflect, plus block of hammer, the build in leap (in lighting field) made my holo experiments with it .... well abusive. Because it covers for the natural trade offs of holo typically.
I'd still try that build in PvP but yeah. Lightning field is not bad either, Holo Leap can work with that as well. Although I think hammer is a weapon that makes you feel like you need to stay on it, while sword for example because of it's increasing quickness and heat bonuses will prompt you to go in forge. That's why it just feels more natural for holo.
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