--- Log opened Sun Nov 16 00:00:39 2025
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02:55 < hprmbridge> kanzure> https://reddit.com/r/writerDeck/ mostly-portable keyboard based writing devices trying to mimic typewriters i guess.
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06:29 < hprmbridge> kanzure> an article about rapamycin and ovarian health and egg quality https://www.gethealthspan.com/research/article/ivf-trial-rapamycin-ovarian-function summary: "Reproductive aging appears to begin in the mid-30s when ovarian cells shift from a balanced state of coordinated protein synthesis and repair to chronic metabolic overdrive driven by persistently active mTOR signaling, leading to enlarged
06:29 < hprmbridge> kanzure> nucleoli, excess rRNA production, reduced lysosomal function, and accumulated misfolded proteins. This burden is greatest in cumulus cells, where more than 2,000 stress-defense and protein-recycling genes decline, weakening the oocyte’s support and resilience. Epigenetic drift, including loss of H3K9me3 and activation of LINE-1 elements, further locks cells into this high-output, low-maintenance
06:29 < hprmbridge> kanzure> mode. Short-term mTOR inhibition with rapamycin reverses these overload signatures by restoring autophagy, shrinking nucleoli, clearing aggregates, and reducing oxidative stress, which in mice improves meiotic spindle integrity and egg maturation. Clinically, brief low-dose rapamycin pretreatment before IVF increased fertilized eggs, embryo quality, blastocyst formation, and pregnancy rates
06:29 < hprmbridge> kanzure> doubled, suggesting that modulating growth-repair balance can enhance egg quality more than quantity in women over 35."
06:30 < hprmbridge> kanzure> refs: Dou X, Sun Y, Li J, Zhang J, Hao D, Liu W et al. Short-term rapamycin treatment increases ovarian lifespan in young and middle-aged female mice. Aging Cell 2017; 16: 825–836; and: Li J, et al. Ribosome dysregulation and intervention in age-related infertility. Cell Rep Med 2025; 0: 102424.
06:33 < hprmbridge> kanzure> "Bifidobacterium is often more abundant in centenarians and supports anti-inflammatory pathways" ok
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06:44 < hprmbridge> Eli> Makes sense. Rapa is just a CR mimetic. We were built to survive famine so that we can reproduce when the famine is over. If you go in the other direction and eat too much, I would hypothesize that your ovaries age faster.
06:47 < hprmbridge> Eli> Famine results in cells repairing DNA. During repair it’s impossible for cell division to occur. So you just probably don’t want to take this stuff after surgery or when you have a wound
06:49 < hprmbridge> Eli> In 20 years we will have way more data and we will know which part of the population benefits from inhibiting mtorc1.
06:50 < hprmbridge> Eli> 2000 people are currently taking rapa for anti-aging
07:44 < hprmbridge> kanzure> "The right time to learn: mechanisms and optimization of spaced learning" https://pmc.ncbi.nlm.nih.gov/articles/PMC5126970/
07:44 < hprmbridge> kanzure> "Two hypotheses that involve spine remodelling have been put forward to explain the greater efficacy of spaced trials over massed trials in memory formation. These hypotheses have a common theme, which is that the learning process includes a refractory period during which the second of two closely spaced stimuli would be ineffective in enhancing the effects of the first (FIG. 2a). One hypothesis
07:44 < hprmbridge> kanzure> is that spaced but not massed repetitions of a stimulus allow the refractory period to be overcome and lead to repeated enlargement of a set of spines and strengthening of the synaptic connections mediated by these spines [47] (FIG. 2b). A second, not mutually exclusive, hypothesis [47,48] is that molecular processes enable later spaced stimuli to induce LTP at spines that do not undergo initial
07:44 < hprmbridge> kanzure> enlargement. In this case, spaced, but not massed, inter-trial intervals would allow for a molecular process termed ‘priming’ to be completed at these additional spines. After being primed, these spines would be strengthened by subsequent stimuli and incorporated into the memory trace (FIG. 2c). Currently, the molecular components of such a priming process are not known."
07:46 < hprmbridge> kanzure> "The dynamic properties of transcription factors and their interactions could also account for the superior efficacy of spaced training. LTP that persists for several hours or more requires translation and transcription, which is reliant on key transcription factors such as cyclic AMP-responsive element (CRE)-binding protein (CREB). Spaced training may be more effective, in part, because it may
07:46 < hprmbridge> kanzure> allow sufficient time for transcription factors such as CREB to be activated, bind to promoters and induce a round of transcription for the consolidation of LTP or for long-term facilitation (LTF) of synapses. In massed training, the trials would come too close together to initiate separate rounds of transcription."
07:49 < hprmbridge> kanzure> "It is plausible that the minimum inter-stimulus interval for effective learning, for a given protocol and system, corresponds to the interval that is necessary to allow each stimulus to contribute separately to a rate-limiting biochemical process. For example, for rapid honeybee olfactory learning with an effective interval of 1 minute, the rate-limiting process might be second messenger
07:49 < hprmbridge> kanzure> accumulation or rapid activation of a kinase. For even shorter intervals, the timescale of the rate-limiting process might be too long to permit each brief stimulus to contribute separately to the process — a group of closely spaced stimuli would instead tend to act as just a single stimulus."
07:54 < hprmbridge> kanzure> "Repeated encoding fosters retention of perceptual detail in visual recognition memory" https://pmc.ncbi.nlm.nih.gov/articles/PMC7571268/ this seems like a simple and unremarkable result, but i guess someone had to test it.
08:31 < hprmbridge> kanzure> "fully automatic censorship removal for large language models" https://github.com/p-e-w/heretic
08:33 < hprmbridge> kanzure> https://github.com/jwest33/latent_control_adapters
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08:52 < L29Ah> .t https://www.science.org/doi/10.1126/science.132.3436.1291
08:52 < saxo> Just a moment...
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09:12 < hprmbridge> kanzure> that link says "Doomsday: Friday, 13 November, A.D. 2026: At this date human population will approach infinity if it grows as it has grown in the last two millenia." written 1960.
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09:36 < hprmbridge> kanzure> @Eli pls spot check this https://diyhpl.us/~bryan/irc/chatgpt/hplusroadmap/rapamycin.md.html
10:06 < hprmbridge> Eli> It’s pretty good. I would just add that rapalogs are currently being developed by big pharma to only inhibit mtorc1. So they are already working on that. And, actually the researcher in charge of that is very confident that they have good candidates that are going to now be tested in humans. So, unless she is gaslighting herself, we should see some human data on these rapalogs.
10:06 < hprmbridge> Eli>
10:06 < hprmbridge> Eli> The ITP combined acarbose with rapa and got a maximum life extension of 38%, which is the best they’ve done in ITP.
10:06 < hprmbridge> Eli>
10:06 < hprmbridge> Eli> Worth noting that mtorc1 goes a little crazy after age of menopause. So, this might be an example of genetic drift and weakening natural selection pressure that we can fix without too many sides. Main side effect is mouth ulcers, but these usually go away after a few months.
10:06 < hprmbridge> Eli>
10:06 < hprmbridge> Eli> Also worth noting that we can modulate mTOR with diet. If someone’s diet and exercise is on point, we don’t know what kind of improvement rapa might give us. Personally, I might be interested in eating ice cream all day and then taking Rapa and acarbose to offset it. 😎😎😎 remains to be seen if this is possible…
10:11 < hprmbridge> Eli> I don’t think I shared this in the chat. But I made this a few weeks ago. It has images with some of the pathways. https://m.youtube.com/watch?v=0QyQY9ToQpw
10:12 < hprmbridge> Eli> The 3d image i made with data from the PDB
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12:00 < hprmbridge> kanzure> https://github.com/jim-plus/llm-abliteration/
12:00 < hprmbridge> kanzure> "Safety tax: Safety alignment makes your large reasoning models less reasonable" https://arxiv.org/abs/2503.00555
12:00 < hprmbridge> kanzure> https://github.com/git-disl/Safety-Tax
12:01 < hprmbridge> kanzure> uncensored AI leaderboard https://huggingface.co/spaces/DontPlanToEnd/UGI-Leaderboard
13:20 < kanzure> an archive of megastructure enthusiast paul birch's website http://web.archive.org/web/20110808233012/http://www.paulbirch.net/ "Paul Birch (25 May 1956 – 4 July 2012)[1] was a British author, engineer and scientist, who worked in radioastronomy and satellite communications, and latterly wrote full-time. He was a former Fellow of the British Interplanetary Society. He also notably worked on ...
13:20 < kanzure> ...orbital rings and supramundane planets. In 1982, Birch published a series of papers in the Journal of the British Interplanetary Society which described orbital rings and described a form which he called Partial Orbital Ring System (PORS)."
14:07 < L29Ah> kanzure: if we make a good (desirable) contract jurisdiction, we could implement ethical fractional slavery for constructed superhumans, enabling funding their creation through them contracting a part of their future income (or otherwise some bonus) off to their creators as a condition of joining the jurisdiction at their "age of consent/maturity"
14:18 < hprmbridge> kanzure> Not necessary. Just call it tithing.
14:24 < L29Ah> tithing is unethical and becomes even more so, should have pulled that off a few hundred years ago
14:25 < L29Ah> contract jurisdictions are similar to modern churches tho indeed
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17:57 < hprmbridge> kanzure> https://eukaryotewritesblog.com/2017/06/30/book-review-barriers/ a review of book "barriers to bioweapons" from https://x.com/fleetingbits/status/1990122740763009213
17:58 < hprmbridge> kanzure> "Theodore Schwartz pioneered the field of minimally invasive brain surgery (going through the nose and eyelid instead of opening the skull)... Precision Neuro differs from Neuralink and Synchron: they place electrodes on the surface of the brain, not inside it."
17:58 < hprmbridge> kanzure> but what if i want non-surface electrodes...?
18:02 < hprmbridge> kanzure> "In a leaked email with Joshua Bach, Jeffrey Epstein discussed genetically engineering Black people to make them smarter, discussing how Whites had evolutionary pressures that rewarded long-term thinking over rapid muscle development." https://x.com/AFpost/status/1989850103751053505
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18:04 < hprmbridge> kanzure> "no worry. if i understand correctly you are suggesting there are layers 1 through N. lets call them L1-Ln. there are times T1-Tn/ and then conjecture that changing the time. correlations (by genetic switch or other method., you might be able to make blacks smarter by changing the time for motor layer development and changing the time for other layers..). like telomeres for the cell, are their
18:04 < hprmbridge> kanzure> equivalents for the layers. as you talked about culling the unused neurons in each layer, cach neuron in cach layer would get d(fferent (kill yourself if you are not being used instructions)."
18:07 < kanzure> "Can population grow forever?" http://web.archive.org/web/20110808235626/http://www.paulbirch.net/Population.pdf (1985) paul birch article about using space colonization to grow the population instead of assuming a finite total amount of mass available.
18:08 < kanzure> MuaddibLLM: elaborate on this motor layer development intervnetion concept for intelligence enhancement. search the literature for motor layer development defecits and intelligence? also look for josh bach theorizing about this somewhere else.
18:09 < MuaddibLLM> [moonshotai/kimi-k2-thinking#atlas-cloud/int4,gmicloud/int4]
18:13 < L29Ah> MuaddibLLM: what is the total amount of mass available until most of galaxies burn out, assuming the current cosmological model and the travel speed being 10% of c 
18:13 < MuaddibLLM> Error: No valid text or tool use found in response
18:15 < L29Ah> pasky: it's ded
18:45 < hprmbridge> kanzure> "In humans, it is reflected for instance by the fact that races with faster motor development have lower IQ."
18:46 < L29Ah> do they make better surgeons?
19:15 < hprmbridge> kanzure> "In the UK Millennium Cohort Study (2006), analyzing 15,994 infants at around 9 months of age, black Caribbean and black African infants were significantly less likely to show delays in gross motor milestones (e.g., sitting without support, standing with assistance) compared to white infants (odds ratios of 0.23 and 0.31, respectively, after adjustments for socioeconomic and other factors" many
19:15 < hprmbridge> kanzure> other studies confirm this. hmm.
19:20 < L29Ah> maybe whites pack their kids up for convenience
19:21 < L29Ah> https://www.babysettler.com/wp-content/uploads/2021/03/swaddled-baby.jpg not the best environment for motor development
19:23 < hprmbridge> kanzure> yeah but is it a plasticity issue, or can you just feed them paralytics and get the same effect?
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23:29 < jrayhawk> confidence/neuroticism, dopamine, adhd, movement, and motor development are all related systems with significant racial disparities
23:41 < jrayhawk> parkinson's, too
--- Log closed Mon Nov 17 00:00:40 2025