https://www.celinehh.com/aging-field Celine Halioua on what the aging field needs—notably, more biotech companies that are prepared to run their own clinical trials specifically for aging-related endpoints.
a typical new biotech company never runs its own clinical trials—they license, partner, or get bought by pharma. but pharma’s not that into aging (yet) and nobody really has expertise in running aging-focused clinical trials, so that may need to happen first in a startup context. which means some investors have to be willing to put up more cash than usual....
it’s a “brown-yellow” pigmented substance (first observed under the microscope in the 19th century) that accumulates in post-mitotic cells with age.
it’s not one substance; it’s a mixture of “garbage” (mostly protein and lipid) that accumulates around the lysosome but can’t be disposed of through exocytosis.
it’s “autofluorescent”—it fluoresces in various wavelengths of light without being stained.
it accumulates more under conditions of oxidative stress like high-oxygen environments or in the presence of iron (which catalyzes oxidation reactions); it accumulates less in the presence of antioxidants and under caloric restriction.
evidence that lipofuscin accumulation causes disease or dysfunction seems a lot shakier in this paper.
I was a little self-conscious about her dissatisfaction with “San Francisco courtier culture”—of course she’s much better at the hustle than I ever was, but I actually love it. If anything, I’ve more often felt hurt that so many people I know got sick of the game before I ever really figured out how to play it.
https://dafny.org/ ”Dafny is a verification-aware programming language that has native support for recording specifications and is equipped with a static program verifier.”
Dafny’s formal verification is based on automated SMT solvers; compared to proof assistants like Coq/Lean/etc it’s less powerful
Dafny can be compiled to familiar languages such as such as C#, Java, JavaScript, Go and Python
wow. this is a very close parallel (and historically contemporaneous) with the conquistadors and privateers of England, Spain, and Portugl in the Age of Exploration...except we don’t make movies and novels about it in the West. But the swashbuckling potential is amazing.
I’ll kind of give him Kipling and Cummings; those are genuine anti-communist, anti-monarchical-absolutism, and anti-war sentiments. Yeats is doing a different thing; I love him but he is Not Our Friend.
links 11/13/2024: https://roamresearch.com/#/app/srcpublic/page/11-13-2024
https://amaranth.foundation/bottlenecks-of-aging the Amaranth Foundation’s bottlenecks of aging
https://www.celinehh.com/aging-field Celine Halioua on what the aging field needs—notably, more biotech companies that are prepared to run their own clinical trials specifically for aging-related endpoints.
a typical new biotech company never runs its own clinical trials—they license, partner, or get bought by pharma. but pharma’s not that into aging (yet) and nobody really has expertise in running aging-focused clinical trials, so that may need to happen first in a startup context. which means some investors have to be willing to put up more cash than usual....
https://en.wikipedia.org/wiki/Rapid_eye_movement_sleep_behavior_disorder is the rare sleep disorder that almost always progresses to Parkinson’s about 20 years later
https://pubmed.ncbi.nlm.nih.gov/12208347/ lipofuscin = cross-links.
it’s a “brown-yellow” pigmented substance (first observed under the microscope in the 19th century) that accumulates in post-mitotic cells with age.
it’s not one substance; it’s a mixture of “garbage” (mostly protein and lipid) that accumulates around the lysosome but can’t be disposed of through exocytosis.
it’s “autofluorescent”—it fluoresces in various wavelengths of light without being stained.
it accumulates more under conditions of oxidative stress like high-oxygen environments or in the presence of iron (which catalyzes oxidation reactions); it accumulates less in the presence of antioxidants and under caloric restriction.
evidence that lipofuscin accumulation causes disease or dysfunction seems a lot shakier in this paper.
https://barnacles.substack.com/p/understanding-as-an-art Laura Deming on visualization and the spiritual side of science
I was a little self-conscious about her dissatisfaction with “San Francisco courtier culture”—of course she’s much better at the hustle than I ever was, but I actually love it. If anything, I’ve more often felt hurt that so many people I know got sick of the game before I ever really figured out how to play it.
https://genomebiology.biomedcentral.com/articles/10.1186/s13059-019-1824-y some critiques of methylation clocks; the first one actually seems to have been an artifact of different distributions of cell types between old and young samples.
https://www.science.org/content/article/scientific-showdown-seeks-biological-clock-best-tracks-aging a contest for the best aging clock at predicting future mortality.
https://www.exactsciences.com/ cancer prognostic/diagnostic biomarker company
https://arxiv.org/abs/2411.04872 Epoch AI’s new math benchmark of original, very hard problems
https://arxiv.org/abs/2406.08467 a new benchmark for formal verification “hint” generation in the Dafny programming language
https://dafny.org/ ”Dafny is a verification-aware programming language that has native support for recording specifications and is equipped with a static program verifier.”
Dafny’s formal verification is based on automated SMT solvers; compared to proof assistants like Coq/Lean/etc it’s less powerful
Dafny can be compiled to familiar languages such as such as C#, Java, JavaScript, Go and Python
https://www.reddit.com/r/rust/comments/1fs12l9/what_do_you_rustaceans_think_of_dafny_language/ Rust users don’t think Dafny is practical for programming “real” things in.
https://manifund.org/projects/hire-a-dev-to-finish-and-launch-our-dating-site Shreeda Segan’s OKC-clone dating site needs $10,000 to build an MVP
https://en.m.wikipedia.org/wiki/Eubulides the guy who brought you lists of paradoxes
https://en.m.wikipedia.org/wiki/Epimenides_paradox “Epimenides the Cretan says, all Cretans are liars”
as my 6-year-old son Simon pointed out, this is not actually a paradox; to be a “liar” doesn’t mean every statement you utter is a lie.
Epimenides himself didn’t intend it to be a paradox. Apparently he disagreed with his fellow Cretans about the immortality of the god Zeus.
They fashioned a tomb for thee, O holy and high one
The Cretans, always liars, evil beasts, idle bellies!
But thou art not dead: thou livest and abidest forever,
For in thee we live and move and have our being.
— Epimenides, Cretica
Wikipedia seems to trace the idea that this is a “paradox” to Bertrand Russell.
https://en.m.wikipedia.org/wiki/Peter_the_Great
this is really badly written for a Wikipedia page. i suspect some kind of nationalist vandalism.
https://en.wikipedia.org/wiki/Russian_conquest_of_Siberia most of the conquest of Siberia actually happened before Peter the Great
https://en.wikipedia.org/wiki/Yermak_Timofeyevich the Cossack ataman who began the conquest of Siberia, under the reign of Ivan the Terrible in the 1500s.
why conquer Siberia? the fur trade.
why did it work? the khans didn’t have firearms.
he was hired by a powerful merchant family, the Stroganovs
https://en.wikipedia.org/wiki/Stroganov_family
wow. this is a very close parallel (and historically contemporaneous) with the conquistadors and privateers of England, Spain, and Portugl in the Age of Exploration...except we don’t make movies and novels about it in the West. But the swashbuckling potential is amazing.
i mean there was also genocide, to be fair.
https://daviddfriedman.substack.com/p/libertarian-poems
I’ll kind of give him Kipling and Cummings; those are genuine anti-communist, anti-monarchical-absolutism, and anti-war sentiments. Yeats is doing a different thing; I love him but he is Not Our Friend.
https://www.pewresearch.org/short-reads/2024/10/24/majority-of-americans-arent-confident-in-the-safety-and-reliability-of-cryptocurrency/ wow—a full 17% of Americans have ever owned crypto.