This was the author’s claim—thanks for the counter-evidence!
sarahconstantin
Karma: 8,421
Book Review: Affective Neuroscience
links 02/27/25: https://roamresearch.com/#/app/srcpublic/page/02-27-2025
https://blog.sentinel-team.org/p/sentinel-minutes-for-week-82025 blog of Sentinel, a team of forecasters concerned about catastrophic risks; might be a good news digest for straightforward politics/war/etc
https://eristicstest.com/ everyone’s favorite new personality test
https://benexdict.io/p/empathy-hardware Benedict Hsieh personal essay
https://www.shinzen.org/resources/articles/ Shinzen Young on meditation
https://www.ben-evans.com/benedictevans/2025/2/17/the-deep-research-problem OpenAI’s Deep Research spot-check; it’s error prone. sources don’t always say what the bot says they say.
https://www.nature.com/articles/s41586-024-08508-4 is this a mRNA cancer vaccine that works? on pancreatic cancer???
not so much. this is examining the difference in survival between vaccine responders and nonresponders. It’s substantial! but only 8⁄16 treated patients responded. not clear how it stacks up to other pancreatic cancer treatments.
but there are lovely single-cell sequencing techniques to see that the vaccine can induce long-lived T cells
endometriosis only occurs spontaneously in primates
https://www.sciencedirect.com/science/article/abs/pii/S0021997512000072 mandrill
https://pb.copernicus.org/articles/4/77/2017/ rhesus monkey
https://academic.oup.com/humrep/article-abstract/27/8/2341/712472 olive baboon (this one is induced)
https://academic.oup.com/humrep/article-abstract/10/3/558/648290#google_vignette baboons with endometriosis have reduced NK activity
https://academic.oup.com/humrep/article-abstract/22/1/272/2939374 it can get into the colon in baboons
https://academic.oup.com/humrep/article-abstract/11/9/2022/616104 baboons with endometriosis have more retrograde menstruation (but not all baboons with retrograde menstruation get endometriosis)
what works on endometriosis in primate studies?
https://www.sciencedirect.com/science/article/abs/pii/S1642431X17302498 Icon immunoconjugate
https://academic.oup.com/endo/article-abstract/151/4/1846/2456726 pioglitazone
https://academic.oup.com/biolreprod/article-abstract/97/1/32/3869077 simvastatin
https://www.sciencedirect.com/science/article/pii/S0015028212024338 aromatase inhibitors
can you selectively kill ectopic endometrial cells in endometriosis?
https://journals.sagepub.com/doi/abs/10.1177/1933719113485298 the endometrial stromal cells are CD10+
more on this: https://en.wikipedia.org/wiki/Neprilysin
https://link.springer.com/article/10.1007/s10815-023-02772-5 yes they’re thinking about cell therapies
https://www.publicbenefitinnovationfund.org/ Public Benefit Innovation Fund, accepting applications for AI projects that benefit social services
links 2/25/25: https://roamresearch.com/#/app/srcpublic/page/02-25-2025
https://en.m.wikipedia.org/wiki/Cherenkov_radiation blue glow from particles moving faster than the speed of light in a medium (like water)
https://dsq-sds.org/index.php/dsq/article/view/5824/4684
https://en.m.wikipedia.org/wiki/Muir_Woods_National_Monument Muir Woods, home of the old-growth coast redwoods, was originally preserved by politician William Kent. But when a water company planned to build a dam (which would flood the woods) and threatened to use eminent domain when Kent objected, he had to donate the park to the federal government in order to actually preserve it as a place of natural beauty.
https://www.osv.llc/our-fellows O’Shaunessy Ventures fellows
surrogate endpoints in clinical trials are generally evaluated with a meta-analysis, in which the trial-level correlation between the surrogate and “gold standard” endpoint is compared. Do trials that find a larger treatment vs. control effect on the surrogate endpoint also find greater effects on the “gold standard” endpoint? Mostly these are done in only a handful of diseases, primarily cancer where things like response rate or progression-free survival are compared to the “gold standard” of overall survival.
https://open.library.ubc.ca/soa/cIRcle/collections/ubctheses/24/items/1.0072082 lesion count as a surrogate for relapse rate in [MS
https://www.sciencedirect.com/science/article/abs/pii/S0895435608001698 LDL as a surrogate in statin trials
https://onlinelibrary.wiley.com/doi/abs/10.1111/bjh.18217 PET complete response as a surrogate in follicular lymphoma
https://www.sciencedirect.com/science/article/abs/pii/S0003496724224262 serum urate is a poor surrogate for gout flares!
https://ascopubs.org/doi/abs/10.1200/jco.2005.08.156 PSA is a poor surrogate for survival in prostate cancer
https://www.sciencedirect.com/science/article/abs/pii/S0272638616002146 protein urea as a surrogate in kidney disease
https://www.thelancet.com/journals/landia/article/PIIS2213-8587(18)30314-0/abstract albuminuria isn’t great as a surrogate in kidney disease
https://www.sciencedirect.com/science/article/pii/S2666168322026842 progression-free survival is ok as a surrogate in metastatic urothelial cancer
https://www.bmj.com/content/bmj/375/bmj-2021-066381.full.pdf pathological complete response is a terrible surrogate for survival in early breast cancer
https://www.thelancet.com/pdfs/journals/eclinm/PIIS2589-5370(21)00010-9.pdf event-free survival is a much better surrogate in early breast cancer
https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools list of FDA-cleared companion diagnostics for determining who should use a therapeutic. these are almost all genetic tests for cancer mutations.
https://research.manjarinarayan.org/ Manjari Narayan’s personal website
https://etherospharma.com/our-team/ Laura Dugan, whom I funded for her work on carboxyfullerene SOD mimetics extending lifespan and preventing neurodegeneration, has a biotech company now; and Jack Scannell, the predictive validity guy, is the CEO!
Jack Scannell’s thesis: we have more and more ways to screen targets and drug candidates, but they have lower predictive validity, so more drugs fail in the clinic and the cost per successful drug keeps rising.
solution: care more about what screens, animal models, etc you use! just because it’s “industry standard” doesn’t mean it doesn’t suck!
melanocortin/leptin-related hereditary obesity
https://pubs.rsna.org/doi/abs/10.1148/radiology.168.2.3393649 you can measure liver iron overload with imaging in thalassemia
James M. Wilson discovered the AAV, the family of viruses most used in gene therapy
discoveries of cancer genes/mutations:
https://onlinelibrary.wiley.com/doi/full/10.1111/j.1349-7006.2008.00972.x a chromosomal translocation with ALK in solid tumors (which was unknown before 2008)
Monica Hollstein discovered TP53 mutations and EGFR amplification in cancer
Robert A. Weinberg seems to have done a LOT of discoveries of oncogenes
Michael Stratton discovered BRAF and RAS and BRCA2 mutations in cancer; also established the Cancer Genome Project
Mary-Claire King discovered the BRCA1 susceptibility mutation for breast cancer
Mark Skolnick, founder of Myriad Genetics, sequenced BRCA1 and BRCA2
Jose Baselga developed Herceptin
John Mendelsohn developed cetuximab
Garth Powis discovered KRAS
https://www.appliedinvention.com/ Danny Hillis’s company
https://gsb-faculty.stanford.edu/benoit-monin/topics/do-gooder-derogation-moral-social-comparison/ people are especially eager to derogate “do-gooders” to alleviate feelings of comparative inadequacy. These are the sorts of studies that don’t replicate but I find the theory plausible.
https://en.wikipedia.org/wiki/John_Bull symbol of the UK
https://en.wikipedia.org/wiki/Brother_Jonathan precursor of Uncle Sam, symbol of New England
https://en.wikipedia.org/wiki/Tiny_Broadwick pioneering female aviator and parachutist
https://www.panoramaortho.com/wp-content/uploads/2017/09/History-of-DXA-2107-PDF.pdf bone density DXA scans date back to the 1980s
https://www.nature.com/articles/s41390-022-02101-z Claude Bachmann discovered NAGS deficiency, a genetic disease
https://everythingstudies.com/2022/05/24/the-political-is-personal/
links 1/21/2025: https://roamresearch.com/#/app/srcpublic/page/02-21-2025
https://en.wikipedia.org/wiki/Neurofilament_light_polypeptide a marker of axonal degeneration in Alzheimer’s, Huntington’s, ALS, MS
https://onlinelibrary.wiley.com/doi/abs/10.1046/j.1471-4159.1996.67052013.x study linking levels of NfL to ALS: 1996
https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1468-1331.2012.03777.x study linking levels of NfL to ALS severity/progression: 2012
https://www.nature.com/articles/312757a0 sequencing the HIV-1 virus -- 1984
https://www.nature.com/articles/324691a0 same group at the Pasteur Institute sequenced the HIV-2 virus in 1986
xhttps://www.thelancet.com/journals/lancet/article/PIIS0140-6736(96)05283-X/fulltext earliest trial (1996) I could find using viral load as an endpoint for HIV vaccines
https://en.wikipedia.org/wiki/Sitosterolemia lipid metabolic disorder
https://en.wikipedia.org/wiki/Fibrodysplasia_ossificans_progressiva rare disease that turns muscle and tendons to bone
https://www.nature.com/articles/ng1783 gene for fibrodysplasia ossificans progressiva
https://www.pennmedicine.org/news/publications-and-special-projects/the-research-legacy-of-penn-medicine/orthopaedics/fop history of research on the disease
https://en.wikipedia.org/wiki/Michael_Houghton discovered hepatitis C
https://en.wikipedia.org/wiki/Louis_M._Kunkel discovered dystrophin, the protein deficient in muscular dystrophy
https://www.discoverymedicine.com/Eric-P-Hoffman/2013/11/08/orphan-drug-development-in-muscular-dystrophy-update-on-two-large-clinical-trials-of-dystrophin-rescue-therapies/ trials using dystrophin as a biomarker in trials for muscular dystrophy
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)60756-3/fulltext?keepThis=true&width=850&height=650&rss=yes&TB_iframe=true dystrophin used as a surrogate endpoint in muscular dystrophy trial
https://www.tandfonline.com/doi/abs/10.3109/10425179109008433 cytomegalovirus sequenced in 2009
https://www2.mrc-lmb.cam.ac.uk/bart-barrell-1944-2023/ Bart Barrell
https://profiles.ucl.ac.uk/1277-stephan-beck Stephan Beck
https://academic.oup.com/cid/article/62/9/1154/1745383 first study I could find (2016) using viral load as an endpoint for CMV antivirals
https://pmc.ncbi.nlm.nih.gov/articles/PMC2730307/ standard anthrax immunoassay, from 2002
https://www.nejm.org/doi/10.1056/NEJMoa2003715 SOD1 used as an endpoint in a trial for ALS
https://www.science.org/doi/abs/10.1126/science.1243292 first description of activated PI3K-δ syndrome, 2013
https://ashpublications.org/blood/article/130/21/2307/36662/Effective-activated-PI3K-syndrome-targeted-therapy lymph node size and naive B cells as endpoints in activated PI3K-δ syndrome trial
https://en.wikipedia.org/wiki/Activated_PI3K_delta_syndrome
https://www.nejm.org/doi/abs/10.1056/NEJM197911223012102 IGF-1 as a biomarker for acromegaly, 1979
more on IGFs in acromegaly: https://www.sciencedirect.com/science/article/abs/pii/0026049594901996
https://jamanetwork.com/journals/jama/article-abstract/257810 Niemann-Pick first described in 1928
https://www.fda.gov/drugs/development-resources/table-surrogate-endpoints-were-basis-drug-approval-or-licensure list of surrogate endpoints that the FDA accepted for drug approval/licensing
https://charlesyang.substack.com/p/2-years-at-doe what it’s really like at DOE
https://www.ams.org/journals/bull/2022-59-02/S0273-0979-2022-01759-4/S0273-0979-2022-01759-4.pdf this is the closest I could find to an exposition of the Bellman function method
https://en.wikipedia.org/wiki/Berl_Katznelson early Zionist; does not appear to be related to the mathematician
people often claim that the “female orgasm” is exclusive to humans, or cannot be detected in animals, but this is false
https://kinseyinstitute.org/pdf/womens%20orgasm%20annual%20review.pdf female orgasm has numerous objectively verifiable signs, from characteristic changes in breathing/heart rate to rhythmic vaginal contractions.
https://onlinelibrary.wiley.com/doi/abs/10.1002/ajp.1350010104 females of many species of primates make facial expressions and noises associated with pleasure during sex, and also show the characteristic vaginal contractions of female orgasm when stimulated
https://www.tandfonline.com/doi/pdf/10.3402/snp.v6.31883 evidence that female rats experience sexual pleasure
https://en.wikipedia.org/wiki/Leroy_Hood nvented the DNA sequencer, the protein sequencer, the peptide synthesizer, and many other methods
https://en.wikipedia.org/wiki/Eleftherios_Diamandis biochemist who first skeptically investigated Theranos’s claims and prompted John Carreyrou to do his famous investigative expose
links 02/19/2025
https://hyperphor.com/ammdi/How-to-be-less-agentic Michael Traven
I don’t exactly agree or disagree with this
https://aok.heavengames.com/cgi-bin/aokcgi/display.cgi?action=st&fn=22&tn=44725&st=10#post11
very funny! internet personalities as factions in various strategy games
https://asteriskmag.com/issues/09/automating-math good post by Adam Marblestone on AI-for-math
links 2/17/2025: https://roamresearch.com/#/app/srcpublic/page/02-17-2025
https://en.m.wikipedia.org/wiki/Giant_panda
the word “panda” is not Chinese for panda. it came to English through French; nobody knows where it came from originally.
https://marginalrevolution.com/marginalrevolution/2025/02/emergent-ventures-winners-40th-cohort.html Emergent Ventures winners
https://journals.aps.org/prapplied/abstract/10.1103/PhysRevApplied.14.011002 portable outdoor magnetometry—could we get around the need for shielding in magnetoencephalography?
links 02/14/25: https://roamresearch.com/#/app/srcpublic/page/02-14-2025
https://en.m.wikipedia.org/wiki/Vomeronasal_organ
organ in the nasal septum of many animals that helps them “smell” non-volatile compounds like pheromones
it’s supposed to be “vestigial” in humans, but I’ve also heard claims that it’s still functional! intriguing!
https://en.m.wikipedia.org/wiki/Flehmen_response when animals “sneer” or flare their lips, it’s to expose their vomeronasal organ and pick up pheromones.
https://en.m.wikipedia.org/wiki/Cholecystokinin hormone used in bile release, satiety, and fear. very reliably induces fear/panic in humans and animals.
https://en.m.wikipedia.org/wiki/Cholecystokinin_antagonist can you treat anxiety by blocking CCK receptors? looks like this line of research was abandoned because peptides are hard to get into the brain. i think we may have better ways around this problem now?
https://pubmed.ncbi.nlm.nih.gov/12789687/ more on CCK antagonists
https://en.m.wikipedia.org/wiki/Adrenocorticotropic_hormone ACTH is a hormone involved in the HPA axis, including anxiety. but not something you want to inhibit across the board.
https://en.m.wikipedia.org/wiki/Hypopituitarism this is what would happen, giving results kind of like:
https://en.m.wikipedia.org/wiki/%CE%91-Melanocyte-stimulating_hormone?searchToken=d8yek3asorql89td1t0fy80ay alpha-MSH is what makes some reptiles and fish turn dark when frightened, and is chemically related to ACTH, but in mammals is less a fear thing, more related to pigmentation, appetite, and sexuality.
https://www.complexsystemspodcast.com/episodes/zeke-faux-stablecoins-tether/ Patrick McKenzie on his usual crypto-skeptic beat
https://docs.google.com/forms/d/e/1FAIpQLSfZf8MsW31eer-VruxpNmVGjiwZAdPk_akKVA-owo8DQqwgPA/viewform apply to intern at Alexandria AI, translating public domain books into as many languages as possible.
https://makesunsets.com/blogs/news/climate-outlaws Make Sunsets’ case that their solar radiation management geoengineering is legal and safe.
https://en.m.wikipedia.org/wiki/Louis_Lewin I <3 this guy. this is what made the Long Nineteenth Century great. his accomplishments range from:
characterizing the traditional use, psychoactive effects, and active compounds of ayahuasca, peyote, kava, betel, and possibly others
exposing the causal connection between dental amalgam fillings and mercury poisoning
analyzing the effect of aconite on the heart
various medical and toxicological works
https://en.m.wikipedia.org/wiki/%CE%92-Carboline some of the beta-carboline alkaloids are anxiogenic
some other beta-carbolines function as MAOIs in ayahuasca, allowing the DMT to be active when taken orally
https://en.m.wikipedia.org/wiki/Harmine
also is a fluorescent pH indicator!
https://en.m.wikipedia.org/wiki/9-Methyl-%CE%B2-carboline does things to the brain maybe. also MAOI.
https://jamanetwork.com/journals/jama/article-abstract/334068 “bubble bath cystitis”, paper from 1967 -- not that interesting, just that some ingredient in a bubble bath soap led to irritation of the urethra in several diabetic women.
https://acsjournals.onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(196904)23:4%3C791::AID-CNCR2820230408%3E3.0.CO;2-Y instead of mammograms, xerox your breast! 1969 paper
old papers on cheaply testable electrical properties of tumors:
https://journals.sagepub.com/doi/abs/10.3181/00379727-15-174 1918, tumors are lower in resistance than healthy tissue, and fast-growing tumors more so than slow-growing ones; this is true both for plants and animals!
https://pmc.ncbi.nlm.nih.gov/articles/PMC2599246/pdf/yjbm00323-0079.pdf electrical potential across a mouse tumor (in millivolts) is quite a bit higher than across healthy tissue, and more so for fast-growing than slow-growing tumors
https://pmc.ncbi.nlm.nih.gov/articles/PMC2246588/pdf/brjcancer00131-0037.pdf rat tumors generally have a more acidic pH than healthy tissue, but malignant vs. benign tumors have similar pH. the more epithelial tissue there is in a tumor, whether malignant or benign, the more acidic it is.
https://aacrjournals.org/jcancerres/article/10/3/340/449670/The-Electric-Capacity-of-Tumors-of-the-Breast1 1926 paper, human malignant breast cancer tumors have about 2-3x the capacitance of normal breast tissue or benign tumors—about 2000-3000 microfarads vs 1000 microfarads.
https://www.semanticscholar.org/paper/Bio-Electric-Properties-of-Cancer-Resistant-and-Burr-Smith/dd717f464d7eb79bbd1930ba6e83e6e8d3892826 1938 paper, also finding much higher electrical potential across spontaneous rodent mammary tumors vs. healthy tissue.
https://www.marinanitze.com/ works on reforming/solving tech problems in government.
https://sloan.org/programs/digital-technology/aipostdoc-rfp Sloan Foundation is looking for social science postdocs to study the implications of AI For Science.
https://arxiv.org/abs/2409.11654 Nico McCarty and others’ roadmap for an AI virtual cell.
links 02/13/2025: https://roamresearch.com/#/app/srcpublic/page/02-13-2025
https://theupheaval.substack.com/p/american-strong-gods
this isn’t my perspective at all but it is a solid descriptive account of how people seem to be thinking
https://www.isac.bio/about organization to prevent (cyber)attacks on biotech/pharma facilities
https://pepfarreport.org/ an excellent analysis of the cost-effectiveness of PEPFAR
https://www.kalzumeus.com/2025/02/10/retraction-request-denied/ Patrick McKenzie stands by his “debanking” piece against a crypto bank CEO’s request for him to “retract” it (that word is often a prelude to a libel lawsuit)
https://www.owlposting.com/p/how-do-you-make-a-250x-better-vaccine the story of PopVax, ultra-cheap developed-in-India vaccine
https://zoogle.arcadiascience.com/about search for model organisms whose genes are especially good matches for a given human gene after controlling for phylogeny (so it’s not all monkeys all the time)
the frog Xenopus tropicalis seems to make an especially strong showing
and some people think it should be used more often as a model for human genetic disorders. https://journals.biologists.com/dmm/article/17/5/dmm050754/352283/Modelling-human-genetic-disorders-in-Xenopus
https://www.argmin.net/p/the-department-of-frictionless-reproducibilty “frictionless reproducibility” as a valuable norm in quantitative/data-based research; idea due to David Donoho of compressed sensing fame
https://markusstrasser.org/extracting-knowledge-from-literature.html Markus Strasser on why it’s hard to build a business around extracting knowledge from the biomedical literature
https://calvinmccarter.substack.com/p/the-new-morality-by-paul-elmer-more essay by Paul Elmer More about leftism as a secular version of Christianity, from a conservative perspective. Early 20th century essay—its villain is Jane Addams!
https://marginalrevolution.com/marginalrevolution/2025/02/the-danger-of-trump-disobeying-court-orders.html Tyler Cowen isn’t worried about Donald Trump violating the Constitution because if there were a real problem markets would move.
I’m really not convinced that public markets do reliably move in the predictable (downward) direction in response to “bad news” (wars, coups, pandemics, etc).
Sometimes subsidies to big companies mask risks/damage to the real economy.
Sometimes the “bad news” was already priced in by the time it happens.
Would be good to research past examples of governments making sharp authoritarian turns and see what happened to markets then.
anecdotally, some professional risk evaluators *have* upgraded their risk estimates for the US recently.
https://en.m.wikipedia.org/wiki/NK1_receptor_antagonist Substance P is involved in fear, rage, and pain; can you treat anxiety or pain disorders by blocking it? ehh, so far we mostly seem to have gotten anti-vomiting meds.
https://en.m.wikipedia.org/wiki/Eltoprazine this serotonergic drug was claimed to have a specific effect against aggression; it seems to have failed in trials though.
miniaturized, low-cost mass spectrometry: where are we?
https://www.soci.org/chemistry-and-industry/cni-data/2012/5/mass-spec-for-the-masses in progress as of 2012
https://www.bayspec.com/product-category/mass-spectroscopy/ Bayspec will sell em, but you have to request a quote
https://www.asbmb.org/asbmb-today/industry/092121/nautilus-founder-unspirals-a-new-approach-to-prote Parag Mallick is doing proteomics with a benchtop and algorithms, which doesn’t necessarily mean you can do general-purpose chemical analysis with the same machine
https://www.pharmasalmanac.com/articles/bringing-mass-spectrometry-out-of-the-lab-and-to-the-point-of-need 908 Devices has a portable mass spec that gets around the need for a vacuum by using a “microscale ion trap”
https://www.vox.com/future-perfect/398696/degrowth-economy-trump-right-poverty indeed, tariffs are harmful
https://www.unbundle-the-university.com/ Ben Reinhardt’s manifesto on unbundling the university
https://convergentresearch.substack.com/p/how-to-build-essential-technology Adam Marblestone on building scientific technology—FROs, startup-like teams
https://en.m.wikipedia.org/wiki/Nuclear_magnetic_resonance_spectroscopy_of_proteins
i still don’t understand how this works but it’s what they use to analyze intrinsically disordered proteins
see also https://pubs.acs.org/doi/10.1021/jacs.3c11614
https://bindresearch.org/fro/2025/02/11/press.html new FRO for studying intrinsically disordered proteins
https://pubmed.ncbi.nlm.nih.gov/16734424/ transcription factors are overwhelmingly proteins with disordered regions
https://en.m.wikipedia.org/wiki/Alpha-synuclein alpha-synuclein, the key aggregate protein in Parkinson’s, is an intrinsically disordered proteins
https://stripe.com/guides/atlas/pitching this is sound advice but, like so many things, it only works if you’re, like, super good at your job.
https://www.medstarhealth.org/services/vascular-infections-complications
somebody said ChatGPT told her that pain and swelling in her lip indicated a vascular infection… pretty sure that’s crazy talk. vascular infections will have systemic symptoms.
links 2/4/25: https://roamresearch.com/#/app/srcpublic/page/02-04-2025
https://www.nature.com/immersive/d41586-025-00269-y/index.htmlmitochondria are thread-shaped not bean-shaped. I truly do not understand these critters.
things i learned while reading about Venice:
https://en.m.wikipedia.org/wiki/Benedetto_Pesaro brutal, successful admiral who held off the Turks for a bit
https://en.m.wikipedia.org/wiki/Vasco_da_Gama
John II, the king, set an objective for his admirals to find a route to India that bypassed the usual middlemen for the spice trade (the Mamluks & Venetians). 16 years later, Vasco da Gama did it. Nice example of “goals and plans can work”.
https://en.m.wikipedia.org/wiki/Matchlock there seems to be an unfortunate definitional overload where “handgun” in the early modern period refers to a gun held by a human as opposed to a cannon? but in the late 15th century all “handguns” were long guns, it seems.
https://drive.google.com/file/d/1iXda2NyGzKVWxkd02IlXj5Tq5cOM_gNd/view
a “verified” programming language would be cool!
this means verifying multiple things. the compiler, the parser, the debugger, etc. all relative to a formal specification of what they’re supposed to do.
do you write a different specification for each thing you’re checking? this introduces lots of wasted/duplicated/inconsistent work. maybe you should just have a single specification for the language.
this is what K is: a framework for writing language specifications.
symbolic execution—don’t plug in values, map out branches of how the program behaves with any possible input. good for testing and verification.
K does this. (I don’t understand details)
https://arxiv.org/pdf/1804.11044 very interesting and ambitious concept!
biology is multiscale and multimodal. genes! proteins! cells! tissues!
in particular we have dynamical spatial systems that govern developmental processes:
cell division & microtubules
neurite branching
mitochondrial fission & fusion
plant organogenesis in shoot & root growth
neural tube closure.
what happens (over time) is a function of what’s going on nearby in space;
macro geometry (the shapes of organs, bodies, etc) is a consequence of micro, local dynamics
declarative modeling:
one example of a bio dynamical system is differential equations defined by diffusion operators on the concentrations of chemical species (as functions of spatial position and time).
an abstract syntax tree (AST) is a way of representing the symbols of a mathematical expression (tree depth corresponds to order of operations, nested functions, that thing)
you could define a declarative modeling language as a space of ASTs that define models, a mapping between ASTs and dynamical systems (the mathematical objects that correspond to the symbolic objects) and transformations between ASTs.
for example one transformation is: you start with a chemical reaction; you reverse the arrow to get the reverse reaction; or, you change the rate constant to get a different reaction rate.
now, when do these manipulations commute? there is a quantum-inspired “operator algebra” for chemistry
each chemical species is a “state”; there are transition probabilities between them
mass action laws define relationships between the equilibrium concentrations of each species (as a function of the chemical reaction & the reaction constant)
“operators” for each species destroy or create particles of that species; what happens if you hit the system with an “operator”? add these up and you get the “chemical master equation” that defines the dynamical system and the enforced probability preservation (probabilities must sum to 1)...(again i don’t totally get it)
now we can also add parameters to these models. for instance a model governing cell division might depend on the size of the cell.
now we can start talking about cell division as a function of things like position, cell type, concentrations of signaling molecules, and so on, with invariants (like “1d growth”)
and we can do similar operator stuff based on probability distributions of what values parameters can take...
ok so what’s the point of all this?
normally in mathematical modeling of biological processes, you pick out a priori which variables to care about.
but alternatively, you could start with a finer model that throws in everything and the kitchen sink, and automatically discern which variables don’t really affect the result much no matter what values you plug in, and then “reduce” to a coarser model.
...but you could also do that statistically? i hate to be the “but how is this practical” guy but this literally is applied mathematics...
it’s pretty though. wish i had time to go through more carefully.
https://openai.com/index/introducing-deep-research/ I don’t seem to have access yet but this is intriguing
https://qntm.org/devphilo i love his short stories; his “developer philosophy” also seems sensible, though might be hard to make work in a real business with customer/deadline pressure?
https://alicemaz.substack.com/p/commentary-on-xunzis-enriching-the Alice Maz on Xunzi. insightful political philosophy.
https://benjaminrosshoffman.com/si-no-se-puede/ Ben Hoffman seems straightforwardly correct here.
if some governmental policy seems Not Fair, to people like you and me, we don’t actually have much of a (perceived) affordance to change it through collective civic action.
conventional political activism is more like a zero-sum negotiation between interest groups.
“it’s not fair” doesn’t move the needle by itself, even if everybody you tell can see it’s true.
organized political violence to achieve goals isn’t much of a thing these days either; the closest thing is disorganized violence (rioting, lone shooters)
the courts sort of are an avenue to push back against unfair policies, but civil courts are declining drastically in use.
links 02/03/25:
Jasmine Sun on the Tech Right
I like this. she’s not a theorizer! she’s just Some Guy, actually expressing her thoughts on current events. do I agree with everything she says? maybe not.
But it’s normal-ass blogging rather than inhibited silence or sloppy thoughts packaged as a Grand Narrative, and I think that’s healthy. we need normal-ass blogging.
Scott Alexander is a normal-ass blogger who kept up a regular schedule and has a gift for puns and a fairly high appetite for books and research papers.
like, that’s all it is, it’s being yourself in public, consistently year over year, while having a healthy (but not extraordinary!) degree of interest in the world around you.
https://www.programmablemutter.com/p/why-did-silicon-valley-turn-right this is cited in her piece; i’m also not sure what i think of this, might be a piece of the puzzle
https://meetmeoffline.com/ nice, Shreeda Segan’s dating app is live
https://lambda.chat/ nice hosting platform for multiple models including the DeepSeek ones.
note that the DeepSeek phone app is reputed to have a keylogger and location tracker; web apps are preferable.
https://www.betonit.ai/p/trust_and_diverhtml Bryan Caplan close-reads the famous Robert Putman paper that purportedly shows that “more ethnic diversity leads to lower social trust.”
It doesn’t show that; it shows that black, Latino, and Asian people have lower “trust” than white people.
also correlated with lower trust: poor neighborhoods; high-crime neighborhoods; high-density neighborhoods; neighborhoods where most people moved in recently; neighborhoods with lots of renters; neighborhoods with few US citizens
also correlated with higher trust: individual income, bachelor’s degree, homeownership
this just reduces to socioeconomic status. there’s not a separate thing going on here about diversity.
obviously you can increase the average of many quality-of-life metrics in a community by restricting it to people of higher socioeconomic status. but then those same metrics would (mathematically) decline outside the elite community.
this does not support claims like “everybody on average would be better off under residential segregation”.
https://marginalrevolution.com/marginalrevolution/2025/02/sundry-observations-on-the-trump-tariffs.html Tariffs harm economies, news at 11.
https://www.complexsystemspodcast.com/episodes/the-landmines-buried-in-the-fine-print-of-chicagos-new-casino-deal/ Patrick McKenzie has details (lots of details) about the new casino being built in Chicago.
in order to meet requirements to be 25% woman-and-minority owned, they went around to black churches to offer an extremely misleading “investment deal” to working-class people who cannot afford it and won’t understand the fine print.
the financial structure includes saddling these “investors” with a surprise enormous tax bill that only kicks in years after purchase.
of course, anybody can get in on special “women and minorities only” financial opportunities, even if they’re a white man; set up a shell company “owned” by a woman and/or minority, who is your wife, or an associate of yours willing to serve as your front. this happens ALL THE TIME.
the inference is that someone in city government said “nope, not this time, no more shell games, when we say minority owned we mean you’re gonna have to funnel the profits into our actual community.” So, this time around, the casino people did go to the community! but what the community gets is not gonna be profit.
https://en.m.wikipedia.org/wiki/Advanced_Research_and_Invention_Agency ARIA was founded in 2021.
A friend asked me a good question: what was the UK’s DARPA-equivalent before?
UKRI https://en.m.wikipedia.org/wiki/UK_Research_and_Innovation was the older UK science-and-tech funding org, which ARIA is unaffiliated with; it brought together nine older funding bodies, most of which were founded in the 21st century, and none of which could plausibly be the bodies that funded the bulk of UK nationally-funded (non-medical) science and engineering through the mid-20th-century.
so...what was the UK’s DARPA, or for that matter its NSF, in 1945-1990?
https://trevorklee.substack.com/p/on-the-responsibility-of-size this is a nice, slightly oblique thought by Trevor Klee. do I agree? maybe. i don’t expect to form considered opinions on All This until years later, if at all.
things I learned while reading about Venice:
https://en.m.wikipedia.org/wiki/Sigismondo_Pandolfo_Malatesta amazing guy. mercenary. murdered two out of three wives. first person that the Pope explicitly “canonized into Hell.” patron of Piero della Francesca and Leon Battista Alberti. rehabilitated in literature several times, including by Ezra Pound, which figures.
https://www.palladiummag.com/2025/01/31/the-failed-strategy-of-artificial-intelligence-doomers/ critical take on the ineffectiveness of “AI safety” as a political strategy.
if you successfully convince the world that AI is potentially very powerful (and dangerous), this does not make people go “ok let’s not build AI then”, it makes people think “i want to be powerful and dangerous!!!”
i’m not on board with everything in this article but i think i largely agree.
when you’re an idealistic nerd who despises playing politics and isn’t very good at it, it will probably end badly if you dive enthusiastically into politics.
“so how can you do anything helpful at all?”
provide true information. don’t optimize too aggressively for mass appeal.
this doesn’t mean actively hide or be deliberately cryptic—i think that’s often going too far. i think clarity and open communication are, where possible, good practices.
but maybe don’t make it your full-time job to strategically maximize the number of humans who believe a given thing.
focus your efforts on goals that you’re quite confident will be beneficial and that can be done without coercion. beware of making your job about “what the government should do”.
do not develop an identity around being an expert at strategic adversarial thinking.
you may be a literal chessmaster (like, at the game of chess);
you may be very skilled at things that would be useful to a modern military;
but if you are, in the colloquial sense, “kind of aspie”, you are not an expert in detecting when somebody’s about to screw you over. do not be over-eager to swim in shark-infested waters.
agreed
links 1/31/25: https://roamresearch.com/#/app/srcpublic/page/01-31-2025
https://hareesh.org/blog/2016/2/5/the-real-story-on-the-chakras the pop-culture chakra model comes from modern Theosophical books, not ancient Indian scripture.
https://solarfoods.com/ solar-powered industrial-fermentation food? they have a microbial protein called Solein. it’s made from bacteria, probably Cupriavidus necator.
is this competitive with whey, legume, or fungal protein, from a cost or sustainability standpoint? haven’t checked yet
https://vetmed.illinois.edu/i-tick/2019/08/09/iceman-lyme-mummy-tattle-the-tick-blog/Otzi the iceman had Lyme disease??
https://en.wikipedia.org/wiki/Xanthan_gum is made from bacteria
the inventor https://en.wikipedia.org/wiki/Allene_Jeanes, also pioneered mass production of dextran (from industrial fermentation) which saved many lives as an ingredient in an emergency blood substitute in the Korean and Vietnam wars
there are lots of smaller, newer companies with varied business models, mostly “too early to tell” for sure if they have the potential to get huge, but I expect in principle many of them should be viable.
will fix
What’s Behind the SynBio Bust?
links 1/30/25: https://roamresearch.com/#/app/srcpublic/page/01-30-2025
https://www.astralcodexten.com/p/why-recurring-dream-themes Scott Alexander on recurring dreams
https://darioamodei.com/on-deepseek-and-export-controls Dario Amodei on DeepSeek and export controls
he’s right that efficiency improvements in AI training shouldn’t reduce demand for chips; In This House We Believe in Jevon’s Paradox
I believe him if he says he’s priced in efficiency improvements into his estimates for time and cost to human-level AI performance. it would be stupid not to, and he’s not stupid.
the case he’s making is “no, DeepSeek doesn’t show that export controls backfire by motivating Chinese AI researchers to pursue efficiency.”
I think I agree narrowly.
China’s top AI researchers aren’t stupid either; they’re pursuing efficiency anyhow. So is everyone.
I think it’s never wise to bet on the best people in a competitive field being complacent, even when they can “afford to be.”
Poverty is a cost, not a benefit. It’s not clear to me that China’s chip-poverty (or overall poverty) made DeepSeek more innovative than its American counterparts.
I know there are DeepSeek stans out there who think everything about American culture is toxic, but the world is big, you have not read every AI paper under the sun, and you simply do not have enough information to conclude that they are uniquely innovative.
also, whether we have export controls or not right now, it is Known that the US-China relationship is chilly and that it’s in both countries’ national interest to pursue independent tech stacks.
otoh, while I don’t think DeepSeek’s strong performance was caused by export controls, I also think we can’t make strong claims in the other direction like “if we have these export controls, Chinese AI will be such-and-such amount far behind American AI”. Progress towards more cost-efficient and compute-efficient models is something everyone expects, but it’s very hard to predict how fast it will happen, or whether it’ll be steady or bursty, or how it will be implemented.
if what we really care about, as Dario claims, is ensuring victory in a potential US-China war, rather than economically immiserating the Chinese, then I think it is also very questionable whether the AI that wins wars is the most “advanced” AI.
People like Dario whose bread-and-butter is model performance invariably over-index on model performance, especially on benchmarks. But practical value comes from things besides the model; what tasks you use it for and how effective you are at deploying it.
If you want to win a war, does it help to have an AI that can win math Olympiads? I dunno. All things equal, I’d bet on the country that’s three years behind on the benchmarks and has a functional military procurement system.
we should also note that this is a push from the CEO of a private company who wants to outlaw selling advanced chips to his competitors. there’s a self-interested motive here.
stuff I looked up while reading about Venice
https://en.m.wikipedia.org/wiki/Euboea
home of https://en.m.wikipedia.org/wiki/Georgios_Papanikolaou, father of the Pap smear. apparently, as with so many scientists, his wife was his unpaid lab tech.
https://en.m.wikipedia.org/wiki/History_of_Thessaloniki
https://en.m.wikipedia.org/wiki/History_of_Thessaloniki
former Salonika; second largest city in the Byzantine Empire; crucial port
https://en.m.wikipedia.org/wiki/Pietro_Loredan_(admiral)
https://explorer.globe.engineer/ AI tool for learning about topics; generates heavily nested, illustrated “intros”. I don’t love the workflow; it’s overwhelming rather than sequential. If I’m trying to learn something in earnest, I need to go through it systematically rather than bopping around.
https://www.emilybynight.com/p/why-makeup-works
frustratingly, not a detailed how-to.
https://www.sciencedirect.com/science/article/pii/S2213671118304776 I don’t know how to compare this to anything, but indeed surface microenvironment makes a big difference for mammalian cell culture & cell differentiation.
3D culture is hard; 2D culture can’t get big; solution: tuuuuuubes.
https://www.nature.com/articles/s41467-024-46314-8 possibly the solution to the high cost of cultured meat is by using edible fungi instead.
https://nintil.com/why-so-few-women-in-cs-the-google-memo-is-right Jose Luis Ricon back in 2017 on the Damore memo
links 01/29/25: https://roamresearch.com/#/app/srcpublic/page/01-29-2025
https://marginalrevolution.com/marginalrevolution/2025/01/its-time-to-build-the-peptidome.html link of a piece I’ve already read by Maxwell Tabarrok about the value of building a dataset of peptides and their sequences, structures, and properties, for training models that can discover peptides that can be used pharmacologically (for instance, as antimicrobials).
https://www.biorxiv.org/content/10.1101/2025.01.24.634830v1 using modified T-regulatory cells can be turned against the macrophage foam cells that produce atherosclerosis plaque, reducing heart disease (in mice).
how do they do it?
oxidized LDL is a marker of inflammation and atherosclerosis. It’s also a protein (the acronym is for Low Density Lipoprotein) so you can target it with an antibody!
regulatory T cells (Treg) genetically modified to contain one of these anti-OxLDL antibodies prevents the OxLDL from getting into macrophages and turning them into foam cells.
inject them into live mice on a high-fat diet and they also get less atherosclerosis than control mice
interestingly they make Tregs from CD4 (helper) T-cells by getting them to express FOXP3. this will be useful for human clinical application, since natural Tregs are rare and it can be difficult to extract them in sufficient quantity.
https://talentmarket.org/cato-psych-policy-analyst/ ugh. they basically have already written the bottom line on what they want a new hire to think about the “psychology of progress”, and it’s mostly talking points that have been made ad infinitum already.
surely if you were serious about overcoming psychological barriers in the general public that make them ill-disposed to objectively beneficial economic/technological changes, you’d want to look for new ideas (since clearly past ones haven’t worked). you’d also want to focus on starting with empathy and common ground, if the hope is to actually change minds. this is a job description that, ironically, guarantees stasis, not progress.
https://stephenmalina.com/post/2023-11-04-biologizing-the-stack/ I’m glad he admits this is a contrarian position because the straightforward lesson of the past several decades is that you want as few things to be biomanufactured as possible, living things make incredibly cost-inefficient factories and should be a last resort.
https://unstableontology.com/2022/05/02/on-the-paradox-of-tolerance-in-relation-to-fascism-and-online-content-moderation/ I like this post, but on the general topic, how could you possibly implement Popper’s standard of “we must not tolerate speech that incites people to not listen to arguments”? That would, itself, require an extensive censorship apparatus.
1st Amendment Law seems much more practical in protecting all political opinions and having exceptions only for “true threats” or narrow “incitement to violence”. Saying “don’t read this book, it’s by a fascist” is intolerance by Popper’s definition, but it’s straightforwardly protected speech under US law and I think it should be; we don’t trust a government agency to adjudicate questions of epistemic vice.
1st Amendment law has almost a refreshingly nihilistic attitude to discussion—all “opinion”, including iirc all discussion on social media, is assumed to be neither true or false, so it can’t be considered defamatory. basically, under the law, “this is all just yapping, people get to yap, call me when they make a false factual claim that costs you money, or make an actual plan to physically hurt someone”. sometimes, in addition to being a safer standard for one’s government to hold, this is a healthy attitude to adopt oneself!
Stephen Wolfram on machine learning: https://writings.stephenwolfram.com/2024/08/whats-really-going-on-in-machine-learning-some-minimal-models/
first, we visualize how values at the nodes of a neural network (during inference) change based on the inputs. complicated!
then we look at how weights on edges change as a neural network is trained. also complicated! though you can see the changes getting smaller as the network approaches convergence.
a mesh neural net—each node is only connected to its neighbors in a grid—is a cellular automaton. Cellular automata are a special case of neural networks, in other words.
you can do an analogue of “training a model to fit a function” with something called a “rule array”—you have a grid, and each square can have a local update rule relative to its neighbors, cellular-automata style, but the rule might be different for different squares. If your “input” is a black square at the top row, then “running” the automata rule repeatedly may propagate down a black-and-white pattern on the grid. you can then “adapt” the rule array iteratively to get a desired pattern, like “generate one that lasts for exactly 30 steps”. or a function: you want to get something that gives certain “outputs” on the bottom row, given an “input” at the top row. then “mutate” cells at random, keeping only the results where the distance from the “training examples” doesn’t change.
you can observe which cells mutate along the training runs; they seem to be the ones along the “ideal path” between x (at the top) and f(x) (at the bottom).
doing mutations at random is inefficient; you can do an equivalent of “steepest descent” in cellular automata too, but this tends to get stuck
there’s an equivalent of “backpropagation” in automata-land too
in general, why translate to automata? he says they’re easier to “inspect” because simpler, but I kinda don’t get it.
he even builds a discrete analog of a transformer!
“It could have been that machine learning would somehow “crack systems”, and find simple representations for what they do. But that doesn’t seem to be what’s going on at all. Instead what seems to be happening is that machine learning is in a sense just “hitching a ride” on the general richness of the computational universe. It’s not “specifically building up behavior one needs”; rather what it’s doing is to harness behavior that’s “already out there” in the computational universe.”
yep this is a convergent idea. the secret sauce in machine learning is just having a rich enough space of possible functions, and a means of variation and selection. you can get similar results using things like genetic algorithms or cellular automata that aren’t “neural networks” at all.
Stephen Wolfram on formal verification: https://writings.stephenwolfram.com/2025/01/who-can-understand-the-proof-a-window-on-formalized-mathematics/
Wolfram Language allows proof verification!
you can also visualize the dependency graph of lemmas.
sometimes the “high-degree nodes” are legible things like commutativity
but often they, and “commonly used lemmas” in randomly generated proofs, are weird elaborate non-human-interpretable things.
What about proof-to-proof equivalences?
this is where the “homotopy” metaphors come from. you could find a “path” from one proof to another...but what if there are “holes” in proof-space? “Then a “continuous deformation” of one proof into another will get stuck, and even if there is a much shorter proof, we’re liable to get “topologically stuck” before we find it.”
https://kmill.github.io/informalization/ucsc_cse_talk.pdf
nice explanation of formalization (in Lean), auto-formalization and auto-informalization
if you just throw ChatGPT at this, it sucks.
so let’s do a little ontology hard-coding.
https://moreisdifferent.blog/p/german-scientific-paternalism how Germany in the late 19th-early 20th century trained scientists
https://kordinglab.com/about/ an approach to figuring out what neurons do by mapping between simulations, electrophysiology data, and psychophysics. “what algorithm is being implemented here?”
https://www.hypothesisfund.org/ a Reid Hoffman project: funds breakthrough research, mostly life sciences.
this doesn’t “smell” aggressive enough to me—the projects look fine but i’m surprised they’d be unfundable elsewhere—but maybe it’s just an insufficiently pointed communication style.
https://en.wikipedia.org/wiki/Robert_Duggan_(venture_capitalist)trange fellow. apparently he’s a Scientologist and knows nothing about biology but has a knack for picking winners. picked up ibrutinib!!!
links 01/27/25: https://roamresearch.com/#/app/srcpublic/page/01-27-2025
https://asteriskmag.com/issues/09/where-the-wild-things-arent Agnes Callard is strange and unsettling here. I wonder what this is “really” about.
“Being a person is too hard a job to leave to a single person. We can’t do it on our own, not even as adults. Figuring out how to be a person is a group project, and we have to help each other. But the catch is that we don’t really know what we are doing, so sometimes we end up hurting each other instead. When you are weird, you experience this hurt. Social categories have been poorly constructed and fail to conduce to human happiness. The weird person is a record of the mistakes we have made.”
it sounds like her own “weirdness” is experienced as a source of pain, not as a stable and beloved personal identity. and that she’s uncomfortable with public celebration of “weirdness”.
admittedly it is a bit paradoxical that contemporary culture celebrates “weirdos” in a not-very-individualistic way. the nonconformists who are celebrated do, actually, conform to their own little club rules.
this never particularly bothered me, though!
if i find a club i want to be a member of, that’s fantastic. i’m not attached to being literally unique.
if i find that existing “labels” or “groups” don’t entirely suit me as an individual, that can be a bummer, but i don’t think i would be better off if no fine-grained identity categories existed and i was expected to conform with everyone in my geographical location.
there’s a very natural explanation about why children’s books star alienated weirdos: writers are not typical people!
beloved children’s book authors were writing to children like me, the children who read a lot of books and might grow up to be writers ourselves.
this isn’t some paradoxical thing.
what is “normal” (both common and normative) in the world of books is what is “normal” for text-native obligate readers and writers, which does in fact mean being different from the majority! Bookishness is a minority trait!
Bookish people, as a rule, are glad we are this way, and eager to acculturate potential kindred spirits into bookishness. This seems generally healthy to me.
sure, be a little thoughtful about not making depictions of alienation into self-fulfilling prophecies, but I think a little bit of care and taste suffices. no need to angst about “what if we are BAD ROLE MODELS”. it’s okay to like your own quirks.
https://www.ams.org/journals/notices/202502/noti3114/noti3114.html anatomy of a Lean proof
https://en.m.wikipedia.org/wiki/Marquis_de_Sade
he sounds genuinely awful, though i haven’t read his writing
links 3/24/25: https://roamresearch.com/#/app/srcpublic/page/03-24-2025
https://www.statecraft.pub/p/how-to-commit-a-coup Edward Luttwak’s thoughts on foreign policy and the CIA’s refusal to recruit people who know foreign languages (because people who travel abroad are thought too risky to clear)
pregnancy affects thyroid hormone levels.
TSH is typically lower during pregnancy, while T3 and T4 are higher. this means that using non-pregnant reference ranges may miss cases of hypothyroidism relative to “normal” pregnancy levels. https://pmc.ncbi.nlm.nih.gov/articles/PMC4758281/
https://pmc.ncbi.nlm.nih.gov/articles/PMC6358369/ study showing lower TSH and higher TF in first trimester pregnancy vs. nonpregnant controls
https://www.vox.com/future-perfect/405263/covid-media-coronvirus-masks-lab-leak-public-health Kelsey Piper on how the media screwed up the coronavirus
https://www.popehat.com/p/incomplete-primer-caselaw-appertaining-bigfoot-aka-sasquatch-lnu Ken White looks at legal cases related to Bigfoot or Sasquatch. (I miss his humor posts.)
https://www.complexsystemspodcast.com/episodes/gary-leff-frequent-flier-programs/ Patrick McKenzie interviews Gary Leff on the business of frequent flyer miles