links 3/28/25: https://roamresearch.com/#/app/srcpublic/page/03-28-2025

• https://docs.google.com/forms/d/e/1FAIpQLSc5RvEk4ufotM52v5mKHF7iZOh0Ls_cMDLd5TXn7YOVa62VZQ/viewform Anna Gat offers free mentoring calls to women & immigrants
• https://chatgpt.com/share/67e6ae4a-2138-800f-8e33-f1c50857859f Deep Research report says that 19th-20th c metals companies (Rio Tinto, US Steel, Alcoa, Timet) could routinely make double-digit profits.
• https://www.science.org/content/blog-post/alkanes-mars there are alkanes -- big organic molecules -- on Mars. these can be produced by abiotic processes, but usually that makes shorter chains than these. so....life? We Shall See.
• https://archive.is/20250326022231/https://www.nytimes.com/2025/03/25/opinion/ezra-klein-podcast-santi-ruiz.html Ezra Klein and Santi Ruiz on DOGE.
  • these are reasonable people. it's clear to both of them that you do not solve the federal debt with workforce cuts -- most of the money is in entitlements.
  • Ruiz is a bit more hopeful than Klein that the conspicuous cuts to (small and sometimes even cost-effective) liberal-coded programs like PEPFAR are the necessary concession to Trump voters (who want to own the libs but may want to keep their Medicare) before serious budget cuts can begin.
  • Klein is suspicious that the whole program is just punishing Trump's political enemies, which, as a Democrat, even a moderate who accepts the need for fiscal discipline, he has no reason to support.

links 3/27/25: https://roamresearch.com/#/app/srcpublic/page/03-27-2025

• https://www.secondperson.dating/p/navigation-by-moonlight
  • essentialist? sure. but this seems like an approximately right version of what "feels natural" to me and gets missed by most men I know.
    • most self-help revolves around "if you have a problem, here's how to take action to fix it", and there's a frame from which every version of this is missing the point.
      • sometimes the thing that is needed is not solving the problem but encouragement & support in the existing situation, reassurance that it's a normal situation to be in and doesn't reflect poorly on you, hope that things will get better...
      • sometimes the real "need" isn't a solution to the alleged problem but sympathetic social support itself. the "problem" being complained about is just a pretext; if it were "solved" you'd pick another problem to complain about; the point is that you need friends who care about you. this is a real need! people suffer without it! yet another book of advice on how to solve today's problem yourself is not going to help you acquire friends who would take care of you if you were completely helpless.
    • obviously if you like a guy and you are following vaguely feminine social scripts your first option is going to be "make yourself conspicuously attractive and show interest in him" rather than "ask him out." it's not that asking is totally taboo, but it's not the default first move! most people start out by trying to execute the briefs assigned to them by society, and only reject those expectations if they find them intolerable.
• https://www.ggd.world/p/how-do-radical-ideas-go-mainstream
  • mostly, reforms to social mores (and IMO feminism was a good one) happen through a process of "mainstreaming" that sands off the radical rough edges and makes them palatable to the general public. IMO this is also a good thing; it's what makes social change a process of persuasion and winning-over rather than an arbitrary dictate.
    • the weirdness of the past 15 years or so is that a bunch of changes skipped straight from Tumblr to the boardroom, leaving everyone else puzzled and dismayed. For a lot of little social-mores things -- like "should we have people in videos describe their appearance for the benefit of the blind?" -- it's not clear what the objectively right answer is, but it is clear that persuading most people to agree (on virtually any halfway-sane policy) is better than springing a baffling new policy on them and then having predictably bitter conflict over it.
• https://www.startrek.com/news/shirts-and-skins-in-tos
  • the command uniforms in Star Trek were green, not gold. their shifting color is an artifact of lighting.
• https://thechinaproject.com/2023/06/15/chinas-war-on-drugs-from-incarceration-to-rehabilitation/ a laudatory piece on China's approach to drug addiction. it's described as "compassionate" and "humane" but the bottom line is that drug use is not treated as a crime but rehab is mandatory for all. outpatient first, and then in state-run facilities if the person isn't going to the outpatient rehab.
•  

links 3/26/25: https://roamresearch.com/#/app/srcpublic/page/03-26-2025

• https://scp-wiki.wikidot.com/antimemetics-division-hub 

• https://lawsen.substack.com/p/my-current-claude-projects 

   

links 3/25/25: https://roamresearch.com/#/app/srcpublic/page/03-25-2025

• low dose aripiprazole papers
  • https://www.psychiatrist.com/pcc/four-cases-chronic-pain-improved-dramatically-following/
    • 4 cases of chronic pain responding to 2mg/day aripiprazole
  • https://journals.sagepub.com/doi/abs/10.1345/aph.1R387
    • torsades de pointes after 5 days on 2.5 mg. (pt had diabetes, hypertension, and stroke history though)
• https://en.m.wikipedia.org/wiki/Polyethylene_glycol
  • ethylene glycol is antifreeze. many of them stacked together is polyethylene glycol, which is Miralax.
    • so why is antifreeze toxic but PEG not?
      • https://claude.ai/share/17d8e7b4-ffd5-4c96-9ca2-fe71c69d828a because the toxicity of ethylene glycol actually comes from the metabolites when it's broken down by alcohol dehydrogenase. if you make a big polymer of PEG, ADH no longer metabolizes it, so it passes through the digestive system harmlessly.
• https://www.thenewatlantis.com/publications/will-anyone-vote-for-abundance
  • yeah everybody reasonable likes Good Things, but in real life we don't have a Good Things party, we have Republicans and Democrats.
• https://thehumanist.com/magazine/fall-2024/features/the-distinction-between-imaginary-science-and-magic Ted Chiang's categorization seems pretty much right; science fiction or "imaginary science" is about processes in an impersonal universe, whereas magic & fantasy are about a universe that relates to people the way people relate to each other.
• https://en.m.wikipedia.org/wiki/Imipramine
  • did we have antidepressants in the 1950's? yes. came out 1957.

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

This was the author's claim -- thanks for the counter-evidence!

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!
    • https://www.nature.com/articles/s41573-022-00552-x
    • https://ora.ox.ac.uk/objects/uuid:a03f3f9a-c8d0-47b0-9ced-7473fdcf6ca8/files/r8336h262x
    • https://www.nature.com/articles/d41573-020-00059-3
    • https://goldlabfoundation.org/presentations/damn-compass-full-speed-ahead-quality-beats-quantity-drug-rd/
• melanocortin/leptin-related hereditary obesity
  • https://www.cell.com/trends/endocrinology-metabolism/abstract/S1043-2760(99)00213-1?large_figure=true
  • https://www.sciencedirect.com/science/article/abs/pii/S0304394098004017
• 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
  • https://www.med.upenn.edu/apps/faculty/index.php/g275/p9746
• 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
    • https://www.science.org/doi/10.1126/science.1905840
    • https://aacrjournals.org/cancerres/article/48/18/5119/492885/Amplification-of-Epidermal-Growth-Factor-Receptor
  • Robert A. Weinberg seems to have done a LOT of discoveries of oncogenes
    • https://biology.mit.edu/profile/robert-a-weinberg/
    • https://www.cell.com/cell/abstract/0092-8674(83)90017-X NRAS
    • https://www.nature.com/articles/312513a0 HER2
  • Michael Stratton discovered BRAF and RAS and BRCA2 mutations in cancer; also established the Cancer Genome Project
    • https://www.sanger.ac.uk/person/stratton-mike/
    • https://aacrjournals.org/cancerres/article/62/23/6997/509398/BRAF-and-RAS-Mutations-in-Human-Lung-Cancer-and
  • Mary-Claire King discovered the BRCA1 susceptibility mutation for breast cancer
  • Mark Skolnick, founder of Myriad Genetics, sequenced BRCA1 and BRCA2
    • https://en.wikipedia.org/wiki/Mark_Skolnick
  • Jose Baselga developed Herceptin
    • https://en.wikipedia.org/wiki/Jos%C3%A9_Baselga
  • John Mendelsohn developed cetuximab
    • https://en.wikipedia.org/wiki/John_Mendelsohn_(doctor)
  • Garth Powis discovered KRAS
    • https://academic.oup.com/jnci/article-abstract/104/3/228/973198#google_vignette
    •  
• https://www.appliedinvention.com/ Danny Hillis's company
  • https://en.m.wikipedia.org/wiki/Danny_Hillis
• 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/Harold_Washington
• https://en.wikipedia.org/wiki/The_Patriot_Game
• 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://link.springer.com/chapter/10.1007/978-1-4757-6903-6_6
  • https://link.springer.com/article/10.1186/s13023-016-0406-2 it's treatable!
  • https://en.wikipedia.org/wiki/N-Acetylglutamate_synthase_deficiency
• 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