Your friend
Canada
Joined April 2018
- Tweets34K
- Following79
- Followers418
- Likes499K
Morgoth was the secondmost powerful being in the universe, and was described as being more powerful than *all* of the other ainur combined.
It's not said directly but Tolkien's dragons are possibly dead matter given structure by magic and animated by evil spirits. No food needed
If Ancalagon was really this massive, how did Morgoth even feed him during his growth phase without causing a full ecosystem collapse across Middle-earth?
Readers added context they thought people might want to know
Tolkien never specified Ancalagon's exact size; the video is fan-made exaggeration. The Silmarillion calls him only the mightiest winged dragon whose fall broke Thangorodrim's towers, in mythic fantasy unbound by real-world ecology or feeding needs.
tolkiengateway.net/wiki/Ancalagon
learningelvish.com/blog/ancalagon…
en.wikipedia.org/wiki/Ancalagon…
scifi.stackexchange.com/questions/2066…
The answer is "not enough information to say".
If the question said she bought red fish and blue fish, or asked how many fish weren't red, then the answer would be 3, but as asked we have no idea how many of the remaining fish are blue.
Bad logic in schoolwork is a real problem!
Boys like Hatchet, girls don't, somehow this isn't just boys and girls having different interests generally.
Who is reading these huge AI generated texts and why are they being generated in 4chan greentezt format
>be 2003, Cambridge MA
>company called Phoenix Pharma because of course it is
>renamed to Acceleron because too much on the nose
>founders are literally the guy who discovered activin and the guy who figured out TGF-β receptors
>thesis: the body has a whole family of proteins whose job is to tell tissues "that's enough, stop growing"
>bone, muscle, blood, blood vessels
>all of them braking
>what if we just. cut the brake line
>be me, protein engineer
>boss wants a drug that mops up activin
>but can't block a receptor with a small molecule, it's a protein handshake
>idea.jpg
>take the receptor
>chop off the part that grabs the ligand
>glue it to an antibody tail so it lives longer than four minutes
>it's not a blocker it's a *decoy*
>soluble fake receptor floating around catching ligands before the real receptor sees them
>ship it, we'll do it live
>be me, 2006-2008, clinical ops
>first in human
>indication is osteoporosis, boring, safe, big market
>48 postmenopausal women
>bone formation markers go *up*
>bone resorption markers go *down*
>FSH drops, proving we're actually hitting activin
>everything working exactly as designed
>we are going to cure bone loss
>feelsgoodman
>hold on
>reviewing labs
>hemoglobin is up
>hemoglobin is up again
>hematocrit climbing
>red cell count climbing
>white cells normal. platelets normal. ONLY red cells
>"did we accidentally make an erythropoietin"
>no. it's not even working like erythropoietin
>one patient's blood gets so thick she goes hypertensive a week after dose two
>three patients at 1 mg/kg need actual phlebotomy
>we are bleeding our own trial subjects to undo our bone drug
>terminate dose escalation
>mfw the side effect is more interesting than the drug
>be Celgene, 2008
>these nerds have a molecule that makes red blood cells by a mechanism nobody understands
>hand them $50 million up front
>buy $5 million of stock
>dangle $510 million in milestones
>also grab options on three more things in the pipeline because why not
>tell them to develop it for cancer-related bone loss
>we're obviously here for the blood
>be Acceleron, 2011-2019
>Celgene asks for the sibling molecule
>built off the OTHER activin receptor
>hand it over
>it becomes luspatercept
>it becomes Reblozyl
>it becomes Celgene's whole thing
>our lead program is now the understudy to its own little brother
>2017: renegotiate
>"fine, you keep every indication"
>"we keep pulmonary hypertension"
>everyone at the table thinks we got the scraps
>pulmonary hypertension. the rare lung thing. sure. whatever
>be PAH researcher, Brigham
>this disease makes no sense
>vessels in the lung thicken, narrow, close
>heart strains, patient dies
>five-year mortality ~43%
>genetics scream BMPR2 gene
>BMP signaling protective, loss of function causes the heritable form
>everyone spends 20 years asking how to put BMP signaling BACK
>can't. it's broken. it's a receptor, it's gone
>staring at pathway diagram at 2am
>BMP goes through SMAD1/5/9
>activin and GDFs go through SMAD2/3
>they share receptors
>they push opposite directions
>it's a SEESAW
>its_all_connected.jpg
>you don't have to add weight to the empty side
>you can take weight OFF the heavy side
>be same guy
>stain lung tissue from PAH patients
>GDF8 elevated
>GDF11 elevated
>activin A elevated
>exactly the ligands the bone drug eats
>nobody expected these to matter here
>call Acceleron
>"do you still have that bone drug"
>test the mouse version
>smooth muscle cells stop proliferating
>endothelial cells stop proliferating
>give it to rats AFTER they already have severe disease
>not just better than placebo
>better than a vasodilator
>hemodynamics improve
>right ventricular hypertrophy REVERSES
>vessel wall cells start apoptosing
>mfw every PAH drug for 30 years just relaxed the pipe
>and ours remodels the pipe
>be Merck, September 2021
>Keytruda is 40% of our revenue and the patent cliff is 2028
>need cardiovascular assets. need them yesterday
>tiny Cambridge biotech has one molecule with good Phase 2 lung data
>Phase 3 still running
>bid $11.5 BILLION
>for one drug
>for the goddamn bone drug
>for a decoy receptor originally designed for osteoporosis that failed into hematology and got traded away as a consolation prize
>board asks if we're sure
>close November 19
>be Merck, March 2023, ACC New Orleans
>STELLAR readout, late breaker
>everyone already knows topline from October, we announced it
>crowd applauds anyway, loudly
>8 of 9 secondary endpoints significant
>risk of clinical worsening or death down 84%
>and this is ON TOP of maximum therapy
>61% already on triple therapy
>40% on infused prostacyclin
>these patients were supposed to have nothing left
>NEJM editorial calls it impressive
>$11.5 billion starting to look cheap
>be FDA
>approve. first activin signaling inhibitor for PAH
>August 2024: EU
>September 2024: Switzerland
>June 2025: Japan
>drug named Winrevair
>twenty-one years after a company called Phoenix Pharma
>be Merck clinical, ZENITH
>sickest patients. functional class III and IV. high risk of death
>first PAH Phase 3 where the primary endpoint is nothing but death, transplant, hospitalization
>no walk tests. no surrogate. just outcomes
>interim analysis comes in
>76% reduction
>DSMB says stop
>first PAH trial in history stopped early for efficacy
>everyone gets offered open label
>be Merck clinical, HYPERION, same week
>testing it EARLY, within a year of diagnosis
>trial still running, patients still on placebo
>ZENITH interim lands on the desk
>mfw you can no longer ethically give anyone a placebo
>clinical equipoise is dead, we killed it
>stop that one too
>76% reduction in clinical worsening
>goes on the label September 2026
>three Phase 3 trials on one label
>two of them stopped early
>one of them stopped BY the other one
>be Merck, Q3 2026
>Winrevair does $694 million in one quarter
>up 93% year over year
>ERS guidelines give it the only strong add-on recommendation in PAH
>CADENCE reads out positive in heart failure, Phase 3 next
>open the label
>scroll to warnings
>monitor hemoglobin
>monitor platelets
>watch for bleeding
>watch for telangiectasia
>mfw it's the exact same pharmacology that blew up the osteoporosis trial in 2008
>the side effect never left
>it just waited eighteen years for the right disease
130% of the thrust of the BE-4 and it has a better name, nice
I wonder what BE-4s future looks like
Our new booster engine, Northstar, was built from the ground up by a scrappy team focused on weight, cost, manufacturability, and performance. More than 65% of the engine is additively manufactured using our in-house 3D printing capability. Northstar can be assembled in less than a day and produces 715,000 pounds of thrust.
I cannot think about the fact that a huge number of children have horrible evil abusive parents, it's too sad. That poor innocent baby girl
Lovely question!
Apart from the leisure activities of flying around, hiking, and generally exploring the planet as it currently exists (both in person and via a fleet of research probes presenting me with scientific papers), I think I'd enjoy gardening the planet & building stuff
Maybe this is arrogance but I feel like my current knowlege and acceptance of the fact that all "matter" in the universe is excitations in quantum fields would translate pretty well into maintaining my sense of self in this scenario.
"The substrate is different!" Yet I think.
CHIM
The entire Elder Scrolls universe is the multi-layered dream of a cosmic entity known as the Godhead.
If a being within the dream realizes the truth of their existence, a profound existential crisis beings to take hold that only has two real solutions.
1. Those who lose their sense of self as a result of this realization immediately cease to exist, like the Dwarves.
2. Those who face this reality head on and assert “I AM” in spite of what they now know achieve CHIM, like the once Imperial Emperor Tiber Septim.
CHIM effectively makes you a god unbound by the limits of the Godhead’s dream.
This technology brings us closer to the minimum viable self replicating spacecraft/Astrochicken
Firing a proton beam at an asteroid to simultaneously extract, ionize, separate and refine the regolith into pure metals or their hydrides:
youtu.be/8fbjrFmClKU
You need big ships. Big ships can carry enough industrial equipment to repair, maintain, & make copies of every part of the ship (industry included). Big ships also carry entire communities, so no homesickness.
Nukes can propel ships to another star in <100 yrs.
You want a low gravity target because you already live in a comfy 1g space habitat & want to mine materials to build more habitats. These could just be stations or outright vehicles themselves. Once at least one full copy of the industrial base has been made the ship can depart.
Wash airlock volumes and suits with a water hose after an EVA. Collect the mud in a sump tank and periodically blow down the tank through a filter pack, and periodically remove the filter pack.
We can just solve problems, everyone.
Mars is toxic to human life.
RIP trillionaire dreams
Readers added context they thought people might want to know
Mars dust ultrafine particles and perchlorates pose inhalation risks that require mitigations for astronauts, but NASA and lead researchers describe this as a manageable design challenge that can be prepared for and overcome, not evidence that Mars is toxic to human life.
nasa.gov/missions/mars-…
source.washu.edu/2026/10/washu-…