--- Log opened Mon Sep 08 00:00:31 2025
--- Day changed Mon Sep 08 2025
00:00 < darsie> Hmm, what is "underage content"? https://rentry.co/report-url?url=FutureTimeline
00:00 < darsie> Like ... non adult content?
00:01 < fenn> scandalous text
00:03 < fenn> words written by someone under the age of 100, which is the minimum needed to ensure civility on the internet
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03:20 < hprmbridge> kanzure> "anatomical shannon limit"
03:34 < hprmbridge> kanzure> what is the argument for measuring synaptic information storage capacity by using spine head volume? what about  receptor count instead?
03:36 < fenn> was there an argument? i always assumed what counted was number of cortical neurons. i could be persuaded that synapses are more important. receptor count seems like an implementation detail
03:37 < fenn> https://en.wikipedia.org/wiki/List_of_animals_by_number_of_neurons#Forebrain_(cerebrum_or_pallium)_only
03:40 < hprmbridge> kanzure> "Synaptic information storage capacity measured with information theory" https://direct.mit.edu/neco/article/36/5/781/120323
03:49 < hprmbridge> kanzure> "Nanoconnectomic upper bound on the variability of synaptic plasticity" https://pmc.ncbi.nlm.nih.gov/articles/PMC4737657/
03:51 < hprmbridge> kanzure> "When two neurons on either side of a synapse are active simultaneously, that synapse becomes stronger, a form of memory. The dendritic spine also becomes larger to accommodate the extra molecular machinery needed to support a stronger synapse." and therefore dendritic spine head volumes are a reasonable proxy for the quantity or mass of extra molecular machinery for a stronger synapse?
03:53 < fenn> sounds plausible
03:54 < hprmbridge> kanzure> "Measurements in a small cube of brain tissue revealed 26 different dendritic spine sizes, each associated with a distinct synaptic strength. This number translates into a storage capacity of roughly 4.7 bits of information per synapse. This estimate is markedly higher than previous suggestions. It implies that the total memory capacity of the brain – with its many trillions of synapses – may have
03:54 < hprmbridge> kanzure> been underestimated by an order of magnitude." why 26?
03:55 < fenn> i'm calling bullshit
03:56 < hprmbridge> kanzure> see figure 8
03:57 < fenn> looks like a smooth curve that they artificially binned. there are no distinct strengths https://direct.mit.edu/view-large/figure/4725501/neco_a_01659.figure.01.jpg
03:58 < fenn> now it's entirely possible that it has 4.7 bits worth of precision
03:58 < fenn> probably slightly less, like 3 bits or so
03:58 < fenn> just my guess
04:06 < hprmbridge> kanzure> "Shannon information capacity of discrete synapses" https://arxiv.org/abs/0803.1923
04:14 < hprmbridge> kanzure> https://x.com/kanzure/status/792805377406410753 'I want to see "lots of barcoding everywhere" added. Barcoded messages could then be captured from bloodstream.' (2016)
04:15 < hprmbridge> kanzure>  https://cdn.discordapp.com/attachments/1064664282450628710/1414569798855168030/image0.jpg?ex=68c00c49&is=68bebac9&hm=cd0b072e2e69160c63dccc14c3337341f0d4693db6405e6d52064a400ab2f86a&
04:15 < MuaddibLLM> kanzure: it’s 26 because Bartol et al. used signal detection theory with the measured noise from same-axon same-dendrite pairs and an equal-CV Gaussian assumption to compute how many reliably distinguishable spine-size levels fit across the smooth dynamic range - yielding ~26 levels ≈ 4.7 bits, not literal discrete peaks in the histogram (eLife 2015: https://elifesciences.org/articles/10778; explainer/replication 
04:15 < MuaddibLLM> context: https://www.biorxiv.org/content/10.1101/2022.08.29.505464v2.full-text).
04:42 < fenn> "Immuno-negative" sounds pretty aspirational
04:55 < hprmbridge> kanzure> hm?
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05:09 < hprmbridge> kanzure> someone ought to really figure out how to make an ex vivo organ survive for more than a week.
05:10 < hprmbridge> kanzure> cross-circulatory assisted perfusion via human "(xeno)transplantation" seems like a reasonable stopgap measure, since most animals don't have room for extra organs.
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05:52 < hprmbridge> kanzure>  https://cdn.discordapp.com/attachments/1064664282450628710/1414594210346041424/share_94496342151385526.png?ex=68c02305&is=68bed185&hm=e563ec5ec8f58efa341c2839541192b8414fc4a3c50479974132e8d07078d2db&
06:03 < hprmbridge> kanzure> "intracerebroventricular injection for postsynaptic density scaffolding protein 95 (PSD-95) overexpression" https://pmc.ncbi.nlm.nih.gov/articles/PMC12164150/ "previously developed an epigenetic editing strategy where a zinc finger DNA-binding domain targeting the Dlg4/PSD95 gene promoter was fused to the transactivation domain VP64 and driven under a CMV promoter. AAV-PhP.B-mediated delivery of
06:03 < hprmbridge> kanzure> this artificial transcription factor (ATF) CMV-PSD95-6ZF-VP64 improved cognition in [an intentionally impaired] mouse model."
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09:44 < kanzure> my slopmachine tells me: "The FDA allows US residents to import small quantities of prescription drugs for personal use from a foreign doctor or pharmacy, under strict conditions: the medication must be for a serious condition, not be a US controlled substance, and be intended for a 90‑day supply (or less) that is not for resale or commercial distribution; certain shipping and package ...
09:44 < kanzure> ...labeling requirements, and must not be adulterated, misbranded, or otherwise prohibited under U.S. law; the importer must provide a valid prescription from a licensed foreign practitioner, and the product must be approved for use in the country of origin (or otherwise deemed safe)."
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10:09 < kanzure> an answer to my question from a few weeks ago about DHT and spam: https://medium.com/pubky/mainline-dht-censorship-explained-b62763db39cb
10:22 < kanzure> https://webtorrent.io/
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11:41 < hprmbridge> kanzure>  https://cdn.discordapp.com/attachments/1064664282450628710/1414681956431695912/mtDNAmutations.jpg?ex=68c074bd&is=68bf233d&hm=e388c57d3717d4c6124397aac30e767b0742412538aaf4a546af76ba3744e423&
11:42 < kanzure> can you do trogocytosis injection of mitochondria into a cell?
11:42 < kanzure> or is it too big? it's like 300 nm
12:05 < L29Ah> MuaddibLLM: answer
12:05 < MuaddibLLM> digging into whether trogocytosis can handle 300nm mitochondria...
12:06 < MuaddibLLM> trogocytosis seems to be membrane fragments only, not whole organelles - checking size constraints vs mitochondrial transfer methods...
12:06 < MuaddibLLM> kanzure: Trogocytosis transfers membrane fragments, not whole organelles - mitochondria (500-1000nm diameter) transfer via tunneling nanotubes (50-1500nm width), direct injection, or endocytosis-mediated methods instead (https://pmc.ncbi.nlm.nih.gov/articles/PMC11784324/, https://cellandbioscience.biomedcentral.com/articles/10.1186/s13578-022-00805-7).
13:04 < hprmbridge> kanzure> cool article
13:27 <+gnusha_> https://secure.diyhpl.us/cgit/diyhpluswiki/commit/?id=82f31bb8 Bryan Bishop: more cognitive enhancement targets: MCPH1, BEC1/KCNH3 knockout, SP0535, NOTCH2NL overexpression, PSD-95 overexpression >> http://diyhpl.us/diyhpluswiki/immune_system/
13:27 <+gnusha_> https://secure.diyhpl.us/cgit/diyhpluswiki/commit/?id=c1e0e82d Bryan Bishop: Merge remote-tracking branch 'origin/master' into master >> http://diyhpl.us/diyhpluswiki/
13:27 <+gnusha_> https://secure.diyhpl.us/cgit/diyhpluswiki/commit/?id=dbe7bf78 Bryan Bishop: spontaneous mitochondrial transfer >> http://diyhpl.us/diyhpluswiki/mitochondria/
14:02 < kanzure> a proposal to use (naturally allogeneic) fetal-maternal stem cells to replace aging brain cells one-at-a-time https://sundialtx.substack.com/p/next-gen-cell-therapies-are-already
14:08 < kanzure> "expressing the HLA-G phenotype downregulates T and NK cell activity to protect the fetus from the maternal immune system. Turns out the same pathways work in unrelated individuals."
14:16 < kanzure> "Multipotent fetal-derived Cdx2 cells from placenta regenerate the heart" https://pmc.ncbi.nlm.nih.gov/articles/PMC6576083/ in an unrelated adult individual without requiring immunosuppression.
14:17 < kanzure> well anyway, that needs to be added to the wiki
15:42 < ike8> https://fxtwitter.com/i/status/1964837055651025076/
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16:02 < hprmbridge> kanzure> "Some studies have looked at manipulating follicle growth in transplanted tissue grafts via inhibition of the PI3K and the Hippo signaling pathways [31, 32], both of which are involved in the promotion of follicle growth [33]. Manipulation of these pathways was used to promote follicle activation and growth and the generation of mature oocytes immediately after transplantation. This was done in
16:02 < hprmbridge> kanzure> order to rapidly produce mature follicles that they were able to use for in vitro fertilization. However, it is worth noting that the promotion of follicle activation in grafts via exposure to Akt inhibitors is actually entirely unnecessary since the act of transplantation alone induces follicle activation. Moreover, promoting follicle activation further reduces the reserve of PMFs, a process
16:02 < hprmbridge> kanzure> which we ultimately aim to prevent as it reduces the potential fertility and lifespan of the graft"
16:02 < hprmbridge> kanzure> is this ovarian fragmentation transplant IVA technique specifically about primordial follicles? are these people  religious, or just extremely dumb?
16:03 < hprmbridge> kanzure> "Follicle activation is a significant and immediate cause of follicle loss after ovarian tissue transplantation" https://pmc.ncbi.nlm.nih.gov/articles/PMC5758475/
16:04 < hprmbridge> kanzure> "In vitro activation of early follicles" https://pmc.ncbi.nlm.nih.gov/articles/PMC8038686/ see section 6
16:07 < hprmbridge> kanzure> "Currently, one approach named IVA was introduced to clinical practice around the world to treat POI and DOR patients. In this procedure, ovarian cortex obtained from patients through laparoscopic surgery is fragmented into small cubes (approximately 1–2 mm3) to disrupt Hippo signaling. The cubes are incubated with a PTEN inhibitor and/or a PI3K stimulator for 2 days followed by
16:07 < hprmbridge> kanzure> autotransplantation beneath the serosa of the Fallopian tubes [11] (Figure 4). Subsequently, the follicle growth is stimulated by exogenous gonadotropin under suppression of elevated luteinizing hormone to generate competent mature oocytes for subsequent IVF procedure. In the second publication, we reported 2 healthy live births in 20 POI patients who had remaining follicles by histological
16:07 < hprmbridge> kanzure> analysis and the increasing number of unpublished deliveries were presented in scientific conferences [12]. "
16:25 < hprmbridge> kanzure> "ovarian fragmentation for follicular activation"
16:35 < hprmbridge> kanzure> once you have widespread primordial follicle activation from ovarian fragmentation + autotransplantation/autograft, then proceed to in vitro maturation (IVM) protocol to make as many  mature oocytes as you want.
16:39 < hprmbridge> kanzure> "Because transplantation of fragments of ovarian cortex is performed without vascular reanastomosis, perfusion of the tissue depends on the growth invasion of new blood vessels." why do they not use the anastomosis vascularization surgical techniques....?
16:40 < MuaddibLLM> Short answer: you can’t anastomose 1–2 mm ovarian cortical cubes used in IVA because they have no vascular pedicle, and whole-ovary microvascular transplants are rare and finicky - tiny friable vessels, thrombosis/ischemia risk, cryo injury - with successes mostly in exceptional cases like Silber’s MZ-twin work, so clinics default to avascular cortical autografts that revascularize by sprouting despite initial 
16:40 < MuaddibLLM> follicle loss; refs: https://www.rbmojournal.com/article/S1472-6483(09)00232-6/fulltext https://www.fertstert.org/article/S0015-0282(09)04332-5/abstract https://www.infertile.com/infertility-news/successful-pregnancy-microsurgical-transplantation-intact-ovary/
16:42 < hprmbridge> kanzure> "The ischemic injury occurring directly after transplantation without vascular anastomosis is involved in the dramatic follicular depletion observed in grafted ovarian tissue. At least 25% of the primordial follicles are lost as a result of cryopreserved xenografts of human ovarian tissue into mice (Newton et al., 1996; Nisolle et al., 2000). Others estimated that ischemic injury during autograft
16:42 < hprmbridge> kanzure> processes induces the depletion of 60–95% of the follicular reserve, including the loss of virtually the entire population of growing follicles (Candy et al., 1997; Aubard et al., 1999; Baird et al., 1999; Aubard, 2003; Liu et al., 2008)."
16:44 < hprmbridge> kanzure> "Angiogenesis can also be mechanically stimulated by triggering endogenous processes of new vessel formation. After injury, the inflammatory phase allows collagen deposits to occur although angiogenesis helps to sustain new tissue formation. This physiological phenomenon was used by Donnez et al. (2004) and later by ourselves (Demeestere et al., 2006), inducing neovascularization by creating a
16:44 < hprmbridge> kanzure> peritoneal pocket or longitudinally opening the ovary at the ovarian tissue transplantation sites 1 week before the transplantation procedure (two steps laparoscopy) (Fig. 2). Animal experiments confirmed that the ovarian grafts transplanted into granulation tissue were already perfused at least 24 h prior the intact control grafts (Israely et al., 2006)."
16:45 < MuaddibLLM> Yep - that early avascular window torches follicles, so folks hedge with two-step preconditioning (granulation pocket/omentum), ultra-thin slices and fast-warm/short ischemia handling, pro-angiogenic boosts (VEGF, PRP, fibrin/glues), cytoprotection or anti-activation (S1P, caspase inhibitors, AMH/mTORi), and in select cases whole-ovary microvascular anastomosis if a usable pedicle and microsurgical chops are available.
17:07 < hprmbridge> kanzure> what about staged prefabrication with tissue expanders or prelamination to create a vascular pedicle for later of the different cortical cubes?
18:15 < fenn> MuaddibLLM: what were the results of this? in 2023 Bryan Johnson "recruited his 17-year-old son, Talmage, and his 70-year-old father, Richard, for a trigenerational blood transfusion. The family travelled to a clinic in Dallas, where Talmage and Richard gave a litre of their blood for it to be converted into a batch of plasma. Bryan then donated a litre of his blood to Richard."
18:16 < MuaddibLLM> Checking what happened with Bryan Johnson's vampire family experiment...
18:17 < MuaddibLLM> Bryan Johnson admitted in July 2023 he saw "no benefits" from six young plasma transfusions (including his son's) and discontinued the therapy, though his father's results were still pending at the time - https://fortune.com/well/2023/07/08/bryan-johnson-plasma-exchange-results-anti-aging/
18:18 < fenn> so 1 liter is not enough
18:52 < fenn> so far all the resistant starch has accomplished is making me depressed
18:53 < fenn> or maybe that was the HTP
18:55 < fenn> wow "Ovarian transplantation in humans is a robust procedure, even after cryopreservation, and vitrification might prove to be more effective"
18:57 < fenn> "Fourteen spontaneous pregnancies were established leading to eight healthy live births and two healthy ongoing conceptions. All three frozen tissue transplants conceived spontaneously, one delivered, and two were ongoing. Oocyte survival with slow freezing was 42% and after vitrification 89%."
19:01 < fenn> i wonder if ovary transplants will prevent menopause
19:02 < hprmbridge> kanzure> "Oocyte-specific deletion of Pten causes premature activation of the primordial follicle pool" https://pubmed.ncbi.nlm.nih.gov/18239123/
19:04 < fenn> maybe you could save one for later and double your reproductive span
19:05 < hprmbridge> kanzure> maybe you could activate thousands and store them
19:05 < hprmbridge> kanzure> of primordial follicles, i mean
19:06 < hprmbridge> kanzure> oh, you want ovarian time travel to prevent menopause
19:07 < hprmbridge> kanzure> maybe when prepubescent ovarian time travel...
19:08 < hprmbridge> kanzure> when -> even. Apparently the regex syntax is intercepted by discord!
19:10 < hprmbridge> kanzure> "Control of primordial follicle recruitment by anti-Müllerian hormone in the mouse ovary" https://pubmed.ncbi.nlm.nih.gov/10579345/
19:11 < L29Ah> you have an extra ovary, cut it out and freeze it for later use
19:12 < L29Ah> MuaddibLLM: you have an extra ovary, cut it out and freeze it for later use
19:13 < MuaddibLLM> You can bank ovarian cortex now and use it later, but the sane play is laparoscopic cortical strip cryopreservation (vitrified) at a young age - not chopping out a whole ovary - since unilateral oophorectomy can actually bring menopause forward, and grafts later carry surgical risk, ischemic follicle loss, and uncertain menopause-delay benefits; talk to a fertility preservation center.
19:20 < fenn> MuaddibLLM: and what do you do with cortical strips
19:21 < MuaddibLLM> You thaw them, trim to ~1-2mm slices, and autograft orthotopically (back to ovarian fossa/peritoneum) or heterotopically (forearm/abdominal wall) - takes 3-5 months to revascularize and restore hormones, then natural conception or follicle aspiration for IVF, though cancer survivors need follicle isolation/IVM to avoid reseeding malignant cells.
19:21 < hprmbridge> kanzure> rs13196892 located between genes TXNDC5 and MUTED is associated with delayed age of menopause, as is rs6467223 in TNPO3
19:22 < hprmbridge> kanzure> 3 months to revascularize is definitely gonna ischemic shock kill any follicles or eggs
19:28 < hprmbridge> kanzure> we should make AMH antibodies
19:28 < fenn> "could transplanting ovarian cortical grafts on an ovary with the ovarian cortex removed previously but with the medulla intact be of benefit when the tissue is grafted at that site? This is of particular interest as currently a high percentage of ovarian follicles are lost because of posttransplantation ischemia, and this is the rate-limiting step for the success of ovarian tissue
19:29 < fenn> transplantation."
19:30 < hprmbridge> kanzure> huh? i mean maybe you get slightly better angiogenesis but it would still take more time than ischemia takes
19:30 < fenn> context of the quote was vs oophorectomy, i think
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19:33 < fenn> i don't know, this makes my eyes glaze over https://www.fertstert.org/article/S0015-0282(24)00272-3/fulltext
19:33 < fenn> .t
19:33 < saxo> Just a moment...
19:33 < fenn> "Ovarian tissue cryopreservation for fertility preservation: with innovation must come the development of guidelines and best practices"
19:35 < fenn> i'm going to leave this one as a bunch of question marks and hope that artificial oogenesis and hormone replacement fills in the gaps before the question can be resolved
19:38 < hprmbridge> kanzure> in vitro gametogenesis doesn't work yet
19:38 < hprmbridge> kanzure> for human
19:39 < hprmbridge> kanzure> and lots of companies are trying.
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23:55 < fenn> https://www.nutriterraomega3.com/blog/how-nuseed-created-plant-based-source-dha
--- Log closed Tue Sep 09 00:00:34 2025