sarahconstantin

Karma: 9,225

sarahconstantin 27 Jan 2026 17:46 UTC
14 points
0
on: sarahconstantin’s Shortform
links 1/27/26: https://roamresearch.com/#/app/srcpublic/page/01-27-2026
- https://en.wikipedia.org/wiki/Insurrection_Act_of_1807 last invoked in the 1990s LA riots
- https://www.sluggish.xyz/p/are-we-all-just-having-understandable
  - one annoying thing about anti-psychiatry people is that they equivocate between “the person labeled insane is behaving in a valid fashion, and deserves acceptance/respect rather than pathologization” and “the person labeled insane is causing their own problems and ought to stop; they deserve criticism rather than therapeutic treatment”
  - either of these can, imo, sometimes be true, but it’s weird when someone is trying to pose as both the defender of the misunderstood and the teller of hard truths to malingerers.
- https://www.darioamodei.com/essay/the-adolescence-of-technology not a lot of news in here; Dario Amodei lays out “Anthropic-ism”, the summary of their research & policy programs of the past several years.
  - he and Paul Christiano deserve credit as the architects and prophets of the age we’re living in. things did, after all, turn out their way. i was always critical of their theories as basically blurring boundaries between “real intelligence” and the thing LLMs do, but in their defense, that boundary has turned out to be blurrier than I expected.
  - i think i might be at least sympathetic to Anthropic-ism. it turns out that a world with these kinds of gradually-and-quickly-improving AI tools is pretty nifty, and also involves all kinds of novel risks that are short of the “everyone dies instantly” scenario but are still quite worrying. sure, if they had listened to Eliezer they could simply have not chosen to go down this path, and there’s more than a hint of vainglory in the motivations of people who want to build powerful AI, but all in all I’d rather the 2020s had these tools than not. it’s not like the “end of the end of history” wouldn’t have happened anyway, and at least this way we have some powerful opportunities as well as depressing developments.
- https://oll.libertyfund.org/titles/bagehot-lombard-street-a-description-of-the-money-market 1873 classic about central banking
- https://steve-yegge.medium.com/welcome-to-gas-town-4f25ee16dd04 this sounds quite complicated but interesting. multi-agent management system.
- https://marginalrevolution.com/marginalrevolution/2026/01/a-more-intelligent-comment-than-most-of-the-emotional-reactions-we-are-seeing.html why do comments have to be “intelligent” per se? you can just say the obvious thing that expresses your values! simple things can be correct.
- https://epirium.com/wp-content/uploads/2025/11/GSA2025_Poster_Epirium_MF-300_Phase-1.pdf that sure is a drug for sarcopenia in phase 1 trials
- https://www.axios.com/2026/01/24/ice-cbp-shooting-minneapolis-democrats-reaction imagine, congress actually putting checks on the executive branch!
- https://writing.antonleicht.me/p/how-ai-safety-is-getting-middle-powers too much inside baseball for me, but probably a useful pointer to what experts think
- https://corticallabs.com/ sounds like a joke? you do not want to do any computation on neurons, they are slow and fragile. (you might want to run brain-inspired algorithms, but on semiconductors!)
- https://centuryofbio.com/p/sid extreme personalized medicine approach to cancer—it worked! after the standard of care failed, single-cell sequencing exposed a fibroblast-like phenotype, and an anti-fibroblast radiotherapy shrank the tumor enough to be operable.
- https://www.sam-rodriques.com/post/the-humanity-project this sounds entirely desirable but insanely expensive. sure, i’d like this, and a pony too. and world peace. can you just do that these days? i’d be delighted if so.
- https://defenseanalyses.org/work/the-maha-pentagon/ ehhh like so much DARC stuff it’s hard to tell if they’re serious. biohacking for soldiers?
  - what I’d really like to see in the health/military space is to take advantage of the DOD’s truly massive biobank resources & make more data accessible to researchers from modern omics techniques.
- https://en.wikipedia.org/wiki/Hanfu_Movement historical costume is big in China.
- https://www.humanlayer.dev/blog/writing-a-good-claude-md keep it simple, stupid (one perspective)

sarahconstantin 21 Jan 2026 18:20 UTC
5 points
0
on: sarahconstantin’s Shortform
links 1/21/26: https://roamresearch.com/#/app/srcpublic/page/01-21-2026
- safety of BPC-157:
  - https://www.sciencedirect.com/science/article/abs/pii/S027323002030091X good results in animals
  - https://clinicaltrials.gov/study/NCT02637284 Phase I trial never published results
- efficacy of BPC-157:
- Shaun Tan’s art: https://www.npr.org/2022/11/03/1131598819/shaun-tan-creature-the-lost-thing-the-arrival
- https://merge.io/blog Merge Labs, the successor to Sumner Norman’s Forest Neurotech. Sam Altman is involved.
  - “entirely new technologies that connect with neurons using molecules instead of electrodes, transmit and receive information using deep-reaching modalities like ultrasound, and avoid implants into brain tissue.”

sarahconstantin 21 Jan 2026 18:18 UTC
5 points
0
in reply to: sarahconstantin’s comment on: What comes after Roam’s renaissance?
as of now, i’m using a Claude Code-generated app for the same logging and diary functions as my private Roam. I had no compelling reason to switch to a different app, but a natural-language-queryable, endlessly reconfigurable interface? yes please. it can do everything I wanted out of Roam plus anything else I want!

sarahconstantin 15 Jan 2026 13:02 UTC
2 points
0
in reply to: papetoast’s comment on: sarahconstantin’s Shortform
no, sometimes it’s short

sarahconstantin 14 Jan 2026 21:41 UTC
5 points
0
on: sarahconstantin’s Shortform
links 1/14/26: https://roamresearch.com/#/app/srcpublic/page/01-14-2026
- https://www.destroyallsoftware.com/screencasts/catalog/functional-core-imperative-shell
- https://blog.spec.tech/p/spectech-lessons-and-updated-hypotheses-d9f Ben Reinhardt on lessons learned at SpecTech in 2025.
- https://www.corememory.com/p/exclusive-fridge-magnet-medicine-nonfiction-labs-cancer drugs whose binding affinity is magnetosensitive—so you can target to tumors and not other organs

sarahconstantin 11 Jan 2026 16:12 UTC
2 points
0
on: sarahconstantin’s Shortform
links 1/11/26: https://roamresearch.com/#/app/srcpublic/page/01-11-2026
- https://www.science.org/doi/full/10.1126/sciadv.aaw7243 TRPM7 is involved in mechanosensing
  - https://karger.com/cpb/article-abstract/19/1-4/1/207934/Direct-Mechano-Stress-Sensitivity-of-TRPM7-Channel
- https://link.springer.com/article/10.1007/s12032-017-0987-1 TRPM7 is involved in the epithelial-mesenchymal transition in multiple tumor types
  - https://journals.sagepub.com/doi/full/10.3233/CBM-190666
  - https://aacrjournals.org/cancerres/article/72/16/4250/575870/TRPM7-Is-Required-for-Breast-Tumor-Cell
  - https://www.sciencedirect.com/science/article/pii/S0006295223004483
- pharmacologically targeting TRPM7 https://www.nature.com/articles/s41467-023-38362-3
- DRP1 and mitochondrial fission in cancer https://www.sciencedirect.com/science/article/abs/pii/S0304419X25001957
- DNML1 in cancer https://pmc.ncbi.nlm.nih.gov/articles/PMC11540555/
- the anti-apoptotic protein FLIP as a cancer target https://febs.onlinelibrary.wiley.com/doi/pdfdirect/10.1111/febs.14523
  - https://www.tandfonline.com/doi/full/10.2147/JIR.S519885
  - https://www.tandfonline.com/doi/abs/10.1517/14728222.2013.736499
- GUK1 and cancer: https://pmc.ncbi.nlm.nih.gov/articles/PMC12148050/
- ELL, involved in the elongation phase in transcription, in cancer: https://www.nature.com/articles/nrc2915
- SEPHS2 & selenium metabolism in cancer: https://www.sciencedirect.com/science/article/pii/S0006497118585554
  - https://link.springer.com/article/10.1007/s00109-025-02563-8
  - https://www.nature.com/articles/s42255-020-0224-7
  - https://www.nature.com/articles/s41598-019-52718-0
- trial of transferrin receptor drug in cancer: https://ashpublications.org/blood/article/144/Supplement%201/1496/531990/Results-of-a-Phase-1-First-in-Human-Study-of-INA03
  - more on transferrin & cancer: https://www.sciencedirect.com/science/article/abs/pii/S0304416511001826
- NMT1, myristoylation, and cancer: https://www.nature.com/articles/s41598-025-13529-8
  - and phase 1 trial of drug with this target: https://link.springer.com/article/10.1007/s10637-024-01448-w
- ADSL and cancer
  - https://onlinelibrary.wiley.com/doi/pdf/10.1002/hep.31685
- PH5A and cancer: https://www.nature.com/articles/s41598-023-44899-6
  - https://link.springer.com/content/pdf/10.1186/s12885-024-12620-z.pdf
  - https://link.springer.com/content/pdf/10.1186/s12967-022-03821-w.pdf
- YRDC and cancer: https://onlinelibrary.wiley.com/doi/full/10.1002/cnr2.70325
  - https://www.nature.com/articles/s43018-024-00748-7
- https://platform.opentargets.org/ Open Targets Platform, info about many drug targets
- https://depmap.org/portal/ DepMap, cancer dependency database
- https://www.hyperdimensional.co/p/among-the-agents how Dean Ball uses Claude Code
- https://marginalrevolution.com/marginalrevolution/2026/01/the-tyranny-of-the-complainers.html most complaints to government agencies come from a few very active complainers
- https://x.com/mollycantillon/status/2008918474006122936?s=20 account (AI-written?) of how someone uses Claude Code for everything. seems potentially appealing
- https://www.alexkesin.com/p/a-better-proxy-than-the-rat-and-dog foundation models for toxicology
- https://www.asimov.press/p/research-forms metascience
- https://archive.ph/20260108173745/https://www.washingtonpost.com/opinions/2026/01/07/ice-minneapolis-shooting-deportaitons-escalation/ this is scary
- https://backofmind.substack.com/p/the-myth-of-merit-in-the-managerial this is probably the best defense of affirmative action—‘you weren’t that good at picking the best anyway, it’s mostly biases and vibes, so you may as well decide to correct historical inequities’. i think even to the extent this is true you could argue that the policies actually enacted were unwise, but i do think it’s a point worth addressing.

Cancer-Selective, Pan-Essential Targets from DepMap

sarahconstantin9 Jan 2026 20:50 UTC

21 points

0 comments11 min readLW link

(sarahconstantin.substack.com)

Self-Help Tactics That Are Working For Me

sarahconstantin8 Jan 2026 18:00 UTC

51 points

2 comments11 min readLW link

(sarahconstantin.substack.com)

sarahconstantin 6 Jan 2026 16:40 UTC
6 points
1
on: sarahconstantin’s Shortform
links 1/6/25: https://roamresearch.com/#/app/srcpublic/page/01-06-2026
- https://archive.ph/xGv5E rationales, stated and unstated, for US action in Venezuela
- https://www.asimov.press/p/nature how Nature became a prestigious science journal: first by publishing fast and, later, by courting lots of submissions so they became more selective by necessity. it wasn’t always considered “good”; its credibility waxed and waned under different editors.
- https://en.wikipedia.org/wiki/B%C3%A9zier_curve
  - “The Bézier curve is named after French engineer Pierre Bézier(1910–1999), who used it in the 1960s for designing curves for the bodywork of Renault cars”.
  - they’re a polynomial basis with the convenient property that you can define them by any number of points and they’ll form a smooth curve between them. Widely used in industrial design. those computer graphics programs where you can drag points and distort curves accordingly? Bézier curves.
- https://read.isabelunraveled.com/p/manifest-rationally decent article on “manifestation” without woo.
- https://en.wikipedia.org/wiki/Bloomsday it takes 30 hours to read Ulysses out loud.
- https://fly.io/blog/youre-all-nuts/ argument to AI-skeptic engineers that they should be using coding agents.
- https://en.wikipedia.org/wiki/Peter,_Peter,_Pumpkin_Eater he originally murdered his wife
- https://www.ribbonfarm.com/2015/05/20/pretending-to-care-pretending-to-agree/ VGR classic. very complicated; once again revolves around his dichotomy of “hotter” people with a lot of social feelings and involvements, vs “cooler” people like himself who are disengaged. I’m definitely the former, and as his model predicts, I sometimes experience the difficulty of having to hide how I feel (“pretending to agree”) and never experience the difficulty of having to hide that i don’t feel anything (“pretending to care”). And then he goes into technology having an individualist, “exit”, bias; anti-communitarian, anti-emotion. I have never really bought this dichotomy. I’m a believing individualist, a fan of technology, a thinker, and sometimes a loner who’s attached to my privacy and autonomy, but I literally never feel this blah indifference or detached un-involvement from social/emotional issues. I think that’s just a thing where temperaments differ.
- https://www.corememory.com/p/exclusive-retro-hopes-it-has-found-alzheimers-trial Retro Bio enters the clinic for Alzheimer’s! I know people there and I’m rooting for them.

sarahconstantin 30 Dec 2025 21:11 UTC
2 points
0
on: sarahconstantin’s Shortform
links 12/30/25: https://roamresearch.com/#/app/srcpublic/page/12-30-2025
- https://distill.pub/2018/differentiable-parameterizations/ CPPNs make beautiful image parametrizations
- https://towardsdatascience.com/reveling-what-neural-networks-see-and-learn-pytorchrevelio-a218ef5fc61f/ layer activations of image classification neural networks
- https://www.fda.gov/news-events/press-announcements/fda-explores-new-contracting-approach-advance-public-health-innovation not sure what to make of this
- https://reason.com/2025/12/29/the-trump-america-ai-act-is-every-bit-as-bad-as-you-would-expect-maybe-worse/ yep, it’s very over-broad.
- https://www.asimov.press/p/clinic-loop detailed information from “failed” clinical trials can be very useful in iterating therapies. worked for CAR-T!

sarahconstantin 29 Dec 2025 19:57 UTC
3 points
0
on: sarahconstantin’s Shortform
links 12/29/25: https://roamresearch.com/#/app/srcpublic/page/12-29-2025
- https://simonwillison.net/2025/Dec/26/slop-acts-of-kindness/ AI agents are sending unwelcome “thank you” emails
- https://en.wikipedia.org/wiki/Rob_Pike creator of the Go programming language and contributor to Unix. these days very anti-AI
- https://reactormag.com/for-he-can-creep-siobhan-carroll/ story inspired by “For I Will Consider My Cat Jeoffrey”
- https://newaesthetics.art/ i agree, we need a new 21st century aesthetic paradigm to rival the Bauhaus’s influence over the 20th century. “but we have...” no we don’t. every magazine is still laid out according to Bauhaus principles. your “modern” typeface is 100 years old.
  - you need a new visual design vocabulary from the ground up; as Art Nouveau derived curvilinear elements from Ernst Haeckel’s invertebrate illustrations, and the Bauhaus derived geometric elements from engineering diagrams, maybe today’s design movement needs to derive its primitives from DeepDream/DALL-E artifacts or something.
- https://www.reddit.com/r/AskHistorians/comments/eko05d/in_little_women_set_in_1860s_massachusetts_amy/ the “pickled limes” in Little Women were actually popular among schoolchildren at the time, and yes, they were salt-pickled limes.
- https://en.wikipedia.org/wiki/Robert_the_Bruce seems like a pretty standard medieval military leader
- https://en.wikipedia.org/wiki/Fried_milk yes, you can “fry milk” if you solidify it with cornstarch

sarahconstantin 22 Dec 2025 17:04 UTC
2 points
0
on: sarahconstantin’s Shortform
links 12/22/25: https://roamresearch.com/#/app/srcpublic/page/12-22-2025
- https://en.wikipedia.org/wiki/Ewan_MacColl the founder of the folk music revival in England in the 1960s. their version of Alan Lomax. married to Peggy Seeger!
- https://en.wikipedia.org/wiki/Maddy_Prior Maddy Prior is from Blackpool in Lancashire
  - https://en.wikipedia.org/wiki/Lancashire basically ground zero for the English ballad tradition. also used to contain Liverpool, which is of course where lots of sailing songs come from or mention.
- https://arxiv.org/pdf/2512.13724 PROTON, a graph transformer model trained on neuroscience datasets and literature, produces in silico screens, ranking proteins by association with a disease or its biomarker (Parkinson’s and alpha-synuclein in one case) and finding they recapitulated experimental screens. also predicts drug hits in organoid models of bipolar and drug repurposing candidates for Alzheimer’s.
  - i’d have expected something like this to be able to produce these results; not a huge update for me, mostly useful as a marker for what people are doing in this space.

sarahconstantin 19 Dec 2025 21:03 UTC
5 points
0
in reply to: Karl Krueger’s comment on: Karl Krueger’s Shortform
It’s also surprising to me! 10 years ago I was convinced by the case made by a (now out of business) self driving truck company that long-haul trucking is a technically easier problem than city driving. That doesn’t seem to have mattered, and I don’t know why.

sarahconstantin 19 Dec 2025 21:01 UTC
9 points
0
on: sarahconstantin’s Shortform
links 12/19/25: https://roamresearch.com/#/app/srcpublic/page/12-19-2025
- https://arxiv.org/pdf/2512.16856 Seb Krier thinks about what AI safety would look like in a polycentric world of different AI agents interacting in markets
- https://www.technologyreview.com/2025/09/23/1123897/ai-models-are-using-material-from-retracted-scientific-papers/ AI research tools include retracted papers; it’s going to be important to evaluate paper quality and rule out or clearly label “bad” papers.
- https://www.statnews.com/2023/09/30/weight-loss-ozempic-nobel-prize-science/ story of GLP-1 discovery
  - more story: https://www.pnas.org/doi/10.1073/pnas.2415550121
- https://arxiv.org/abs/2311.12022 the GPQA AI benchmark
- https://www.futurehouse.org/research-announcements/hle-exam the Humanity’s Last Exam benchmark has a bunch of wrong answers
- https://www.futurehouse.org/research-announcements/demonstrating-end-to-end-scientific-discovery-with-robin-a-multi-agent-system how FutureHouse did “end to end scientific discovery” guided by a lit review AI tool
- https://www.mackenziemorehead.com/what-to-do-if-energy-gets-cheap/ analysis of trends in solar and other forms of energy
- https://github.com/sarah-quinones/faer-rs apparently there’s now a Rust-based BLAS/LAPACK competitor
- https://www.nmccarty.com/p/this-openai-wet-lab-blog-is-actually Nico McCarty reviewss OpenAI’s report of an AI-optimized molecular biology protocol

sarahconstantin 18 Dec 2025 10:38 UTC
6 points
0
in reply to: lillybaeum’s comment on: Measuring Drug Target Success
As I’ve said before, there’s an automatic link between LW and my substack, so every time i make a paid post, it shows up here. Happy to take it down or put up a free version, whatever the mods prefer.

Measuring Drug Target Success

sarahconstantin16 Dec 2025 21:00 UTC

19 points

3 comments2 min readLW link

(sarahconstantin.substack.com)

sarahconstantin 11 Dec 2025 19:43 UTC
2 points
0
on: sarahconstantin’s Shortform
links 12/11/25: https://roamresearch.com/#/app/srcpublic/page/12-11-2025
- example of AI report, evaluating preclinical validation of a drug target:
  - https://elicit.com/review/824f5bb9-bc8e-4c06-b277-a8c342b19bbd
- https://www.macroscience.org/p/to-get-more-effective-drugs-we-need Ruxandra Tesloianu and Jack Scannell make the case for clinical trial reform; I couldn’t agree more
- https://astera.org/neuroscientist-doris-tsao-joins-astera-to-lead-its-new-neuroscience-program/ Astera is doing neuro now. consciousness is a focus.
- https://www.averi.org/ Miles Brundage’s new AI safety verification org

sarahconstantin 11 Dec 2025 19:26 UTC
7 points
0
on: Eliezer’s Unteachable Methods of Sanity
I liked your account of:
looking in the internal direction of your motor plans, and writing into your pending motor plan the image of you getting out of bed in a few moments, and then letting that image get sent to motor output and happen.
I do a similar sort of thing myself sometimes, and similarly do not think it is the same as predictive processing theory, which I don’t believe in for several reasons.
I would call that “visualization”, and I’d say that it’s not hyperstition/woo because it’s not believing in a prediction, it’s forming a plan. (Except that the actually-effective way of forming a plan, the kind you’ll actually be significantly more likely to do than most “plans”, involves vividly simulating the actions you’re going to take.)
A part of this technique involves being really honest with yourself about whether you have any intention of doing the thing, and if you don’t, don’t even try to do the visualization exercise. You have to be able to feel the difference between “yeah I’m gonna do it” and “nope, don’t want to.”
So to the particular goal here, I have rarely ever seriously held an intention to be “sane”, to “cope well,” or to “avoid drama”. to the extent that I have seriously wanted to be a bit better on that axis, I succeeded. It’s not quite as simple as “anyone can do it just by wanting to”, but rather “if you don’t want to, it will definitely not happen, and at least some people, n=1, don’t particularly want to.”

sarahconstantin 9 Dec 2025 17:45 UTC
2 points
0
on: sarahconstantin’s Shortform
links 12/9/25: https://roamresearch.com/#/app/srcpublic/page/12-09-2025
- https://www.gleech.org/erect did walking erect lead to human intelligence?
  - he doesn’t seem to be aware that “behavioral modernity” is looking a lot older than 40,000 years ago
- https://www.poetryfoundation.org/poems/48417/high-windows I still can’t tell whether he’s in favor or against the “long slide”
- https://www.mcsweeneys.net/articles/the-new-yorkers-isaac-chotiner-interviews-santa-claus

sarahconstantin 3 Dec 2025 20:57 UTC
5 points
0
on: sarahconstantin’s Shortform
links 12/3/25: https://roamresearch.com/#/app/srcpublic/page/12-03-2025
- https://covalent.bio/ AI-based life science data extraction
- https://en.wikipedia.org/wiki/Fantasia_(1940_film)
- https://blog.spec.tech/p/150x donate to SpecTech!
- https://nonv.substack.com/p/what-is-yimby-for-healthcare some suggestions on what “abundance for healthcare” would look like: ending certificate of need laws, making state regulations compatible, removing tax and nonprofit advantages that give preference to incumbent hospitals, reforming laws that prevent data sharing and compensation between medical systems

sarahconstantin

Cancer-Selec­tive, Pan-Essen­tial Tar­gets from DepMap

Self-Help Tac­tics That Are Work­ing For Me

Mea­sur­ing Drug Tar­get Success

Cancer-Selective, Pan-Essential Targets from DepMap

Self-Help Tactics That Are Working For Me

Measuring Drug Target Success