The 7th biggest airplane manufacturer is Embraer, a Brazilian company. How did that happen?
it came out of a state aeronautical institute founded by aviation pioneer Casimiro Montenegro Filho in the 1940s; military-run, well-funded, and famously competitive as an engineering school.
Embraer was founded in 1969 as a state-run spinout company using a prototype developed by a student. They focused on a specific niche: small commuter planes for the local market.
Brazil is very big and has bad roads; there’s high demand for domestic air travel.
Embraer was privatized in 1994 as part of an overall economic liberalization strategy in response to the hyperinflation and falling GDP of the early 1990s. At this point, Embraer got more investment from the private markets and branched out to regional jets and exports.
“classic industrial policy” playbook: strong government support at first, which was later taken away; focus on exports and keeping up with the technological frontier.
“Death-seq”—identify dead or dying cells as those which have detached from the surrounding tissue, and do RNA-seq on dead vs. live cells to identify the expression properties characteristic of cell death.
Then do a genome-wide CRISPR knockout screen on cultured fibroblasts, induce senescence with doxorubicin, and see which gene knockouts make senescent cells more or less susceptible to being killed by the senolytic compound ABT-263. then Death-seq the lot.
they find hits, particularly SMAC/DIABLO, a mitochondrial protein whose knockout inhibits senolysis with multiple BCL-inhibiting senolytics. Going the other way, SMAC mimetic drugs promote senolysis.
Senescent but not proliferating cells get their cell membranes depolarized during senolytic treatment.
systemic SMAC] mimetic + senolytic combination therapy in a mouse model of idiopathic pulmonary fibrosis reduces senescent cell markers & reduced the histological severity of pulmonary fibrosis.
the combo also helps with liver function in a mouse model of NASH
what about doing Death-Seq with no drug? what gene knockouts predispose to all sorts of cell death (apoptotic or not)?
they get 13 markers of senescent cell death. most are novel. one is expected (BCL2L1)
bad news for senescence markers: the Tabula Muris Senis (single-cell sequencing atlas of mice at different ages) simply does not contain cells with multiple genetic markers of senescence in the aged animals!
“Despite an increase in both the percent of cells expressing Cdkn2a and expression levels of Cdkn2a increasing when pooling cells across 23 organs, we were unable to find cells with multiple markers of senescence in physiologically aged mice in either atlas, in accordance with another recent independent cell atlas dataset.”
“When she told a CBP officer who questioned her that she feared political persecution if she returned to Russia, the agency decided to detain her instead, according to one of the petitions filed by her lawyer, Gregory Romanovsky.”
https://www.lesswrong.com/posts/JFWiM7GAKfPaaLkwT/the-vision-of-bill-thurston Legendary topologist Bill Thurston, famous for his extraordinary abilities to visualize in 4 and 5 dimensions, had no visual depth perception, due to strabismus. He said that he did high-dimensional visualization exactly the same way he had to do 3D visualization—by reconstructing it from 2D projections.
links 3/31/25: https://roamresearch.com/#/app/srcpublic/page/03-31-2025
https://www.noahpinion.blog/p/how-brazil-built-a-world-beating
The 7th biggest airplane manufacturer is Embraer, a Brazilian company. How did that happen?
it came out of a state aeronautical institute founded by aviation pioneer Casimiro Montenegro Filho in the 1940s; military-run, well-funded, and famously competitive as an engineering school.
Embraer was founded in 1969 as a state-run spinout company using a prototype developed by a student. They focused on a specific niche: small commuter planes for the local market.
Brazil is very big and has bad roads; there’s high demand for domestic air travel.
Embraer was privatized in 1994 as part of an overall economic liberalization strategy in response to the hyperinflation and falling GDP of the early 1990s. At this point, Embraer got more investment from the private markets and branched out to regional jets and exports.
“classic industrial policy” playbook: strong government support at first, which was later taken away; focus on exports and keeping up with the technological frontier.
https://www.cell.com/cell-metabolism/pdf/S1550-4131(23)00303-0.pdf
“Death-seq”—identify dead or dying cells as those which have detached from the surrounding tissue, and do RNA-seq on dead vs. live cells to identify the expression properties characteristic of cell death.
Then do a genome-wide CRISPR knockout screen on cultured fibroblasts, induce senescence with doxorubicin, and see which gene knockouts make senescent cells more or less susceptible to being killed by the senolytic compound ABT-263. then Death-seq the lot.
they find hits, particularly SMAC/DIABLO, a mitochondrial protein whose knockout inhibits senolysis with multiple BCL-inhibiting senolytics. Going the other way, SMAC mimetic drugs promote senolysis.
Senescent but not proliferating cells get their cell membranes depolarized during senolytic treatment.
systemic SMAC] mimetic + senolytic combination therapy in a mouse model of idiopathic pulmonary fibrosis reduces senescent cell markers & reduced the histological severity of pulmonary fibrosis.
the combo also helps with liver function in a mouse model of NASH
what about doing Death-Seq with no drug? what gene knockouts predispose to all sorts of cell death (apoptotic or not)?
they get 13 markers of senescent cell death. most are novel. one is expected (BCL2L1)
bad news for senescence markers: the Tabula Muris Senis (single-cell sequencing atlas of mice at different ages) simply does not contain cells with multiple genetic markers of senescence in the aged animals!
“Despite an increase in both the percent of cells expressing Cdkn2a and expression levels of Cdkn2a increasing when pooling cells across 23 organs, we were unable to find cells with multiple markers of senescence in physiologically aged mice in either atlas, in accordance with another recent independent cell atlas dataset.”
https://www.chicagotribune.com/1994/02/08/sour-note-metropolitan-opera-dumps-soprano-kathleen-battle Operatic soprano Kathleen Battle got fired from the Met for being unprofessional and “nasty”, which is really saying something.
https://957benfm.com/2025/02/18/timothee-chalamet-method-a-complete-unknown/ Timothee Chalamet sang and played his own songs as [[Bob Dylan]] in “A Complete Unknown”, got a dialect coach and movement coach, didn’t use a cell phone, and gained 20 pounds for the role.
https://www.thecrimson.com/article/2025/3/28/hms-researcher-detained/ Kseniia Petrova, a bioinformatician at Harvard Medical School, is currently detained by ICE in Louisiana after her visa was revoked because she didn’t declare some biological samples at customs when reentering the country.
“When she told a CBP officer who questioned her that she feared political persecution if she returned to Russia, the agency decided to detain her instead, according to one of the petitions filed by her lawyer, Gregory Romanovsky.”
https://www.lesswrong.com/posts/JFWiM7GAKfPaaLkwT/the-vision-of-bill-thurston Legendary topologist Bill Thurston, famous for his extraordinary abilities to visualize in 4 and 5 dimensions, had no visual depth perception, due to strabismus. He said that he did high-dimensional visualization exactly the same way he had to do 3D visualization—by reconstructing it from 2D projections.
https://en.m.wikipedia.org/wiki/Jharkhand
heavily forested state in India
https://hbd.gg/play/
very tricky “guess where these people originated from their faces” quiz