mobilejdral
> Why It Happens: The Mechanics Underneath the Reaction
And then don't talk about Mechanics, but instead no citations just guess. For anyone that actually wants something to go learn more about checkout the frequency of NCAH and the resulting blunted cortisol response as one thing that is influencing this.
https://www.nature.com/articles/s42003-024-06102-y#MOESM3 Plasmalogen, B5, 12-HETE, Androsterone sulfate, etc are all related to the functioning of the HPA-Axis.
https://pubmed.ncbi.nlm.nih.gov/19598235/ <- CYP11B1 specifically here
Anecdotally: I worked at a software company that had free snacks in the office kitchen and would always chuckle how the salt snacks would run out first. The connection being NCAH can result in less aldosterone which helps regulate salt in the body.
1. The article presents that calling out to a tool like python is "expensive" because of the overhead of forking a process, loading up the python env etc, but why not just eliminate that overhead and embed WebAssembly so this "tool call" is near zero? This feels very similar to the discussion in the 90's around the overhead of threads v.s. processes or kernel space v.s. user space. Could even go further and have a running beam vm so the LLM can write elixir which is ideal for LLM's that stream out code? Elixir programs will be a lot shorter than webassembly.
2. The core argument stated is "A system that cannot compute cannot truly internalize what computation is." The idea being that it could write a program, execute it and by seeing all of the steps maybe even part way through stop and change its mind or when writing new programs write them better, aka be able to debug on the fly?
3. Not mentioned, but there is a 3rd x factor that LLM's will use this new found computation engine to do overall better at "thinking". Computing in very unexpected ways and to unexpected problems. Maybe it would do dramatically better at some benchmark because of this?
Unfortunately these are not explored and it is just an execution engine even resulting in the conclusion stating "arbitrary programs can be compiled directly into the transformer weights, bypassing the need to represent them as token sequences at all." which goes to point number 1 of if we are compiling to weights why not just optimize the tool calling?
Go back to your desk and work on a PR that is going to go through a 20 step process that is constantly changing before a hopefully semi-regular release goes out to customers and tell me how you ignoring all of knowledge on how to do this well is good for your career.
For a long time I assumed folks like you were simply uneducated, but know I see it for what it is, elitism.
Natto-serrazime is probably an excellent complement as it is on the other side and is a dissolver. (Noteworthy: Pterostilbene + Glucosamine similar to EPA reduces fibrosis)
The interesting connection is how this is needed when we are older, but not younger. When younger ERa activates more which does this all on its own. This is the connection to why 2/3 of alzheimer's are post-menopausal women and why HRT is important.
Edit: and to tie this to APOE as it is the gene most associated with Alzheimer's. e4/e4 requires more choline so someone with e4/e4 is more likely to be choline deficient. EPA/DHA usually attach to Phosphatidylcholine (PC) when in the blood/brain. PEMT is a gene controlled by ERa to make choline, but from the above less ERa activation and we make less PEMT so less choline and less PC. Choline is the precursor to Acetylcholine (primary neurotransmitter for memory and focus and essential for REM sleep). This is why Choline is known to help with Alzheimer's.
So this is one of those standard poor estrogen signaling downstream things and simply improving the estrogen signaling and you get improved cartilage. Anyone can do this today along with getting all of the other positive effects. Those with EDS who have say variants on their TNXA/B have poor production ability to start and so we do everything we can to improve their cartilage production as they can only make so much which include doing stuff like this.
One needs to also dive into neurogenesis. Elevated HPA Axis activation which brought us the oxy-androgens also gives use higher cortisol and lower α-MSH which promote neurogenesis. This elevated cortisol is one of the classic hallmarks of Alzheimer's. Estrogen signaling is also an important part of neurodevelopment. So someone with Alzheimer's usually has low α-MSH and low estrogen signaling and overall reduced neurodevelopment. Need to fix these to prevent dementia.
The various stuff that has been found to reduces dementia also improve estrogen signaling. Estrogens are an incredibly old hormone used in regulating a ton of basic cell function. Keep ERa functioning well and you get not only better amyloid plaque clearance, but healthier DNA repair, immune system, etc and better neurogenesis. A lot of stuff that improves longevity ultimately just keeps this going.
There is a Alzheimer's Choline camp which is where we know that Choline supplements is associated with improved Alzheimer's. With low estrogen signaling you have lower N-methyltransferase so less Choline in the body as it is how the body makes it. Less Choline, less SAM via BHMT, less SAM, less clearance of 2-OHE1, less ERa activation, and ... less choline in a loop. Supplement with Choline and it helps not only with the APOE e4 which consumes more Choline, but undoes this is what this theory is about.
As we are having fun with this, decrease the BHMT from less Choline and it shifts from BHMT-mediated methionine synthesis to MTR-mediated pathways, consuming 5-MTHF resulting in slower THF regeneration. Slower THF regeneration impairs the folate cycle, increasing reliance on serine as a one-carbon donor. Elevated serine flux upregulates PHGDH, which promotes IKKα-HMGB1 signaling which drives amyloid pathology and neuron death! Which brings us to probably my favorite paper from this year. "Transcriptional regulation by PHGDH drives amyloid pathology in Alzheimer’s disease" https://www.cell.com/cell/fulltext/S0092-8674(25)00397-6
I myself don't put myself in the Choline camp, but more see Alzheimer's simply as one failure mode on the metabolic estrogen axis of which is induce in certain genetic or diet configurations. In this mode it results in a number of cascading failures until death. Some genetics/diet are fairly easy to halt/undo the spiral of death which is seen in how there are some things that are known to improve Alzheimer's in some, but not all patients. I can induce Alzheimer's via the gut, diet, inflammation, adrenals, sleep, a whole host of ways, anything that starts the cascade.
An example of an unlucky genetic case is when someone has 3 CYP21A2 rather than 2, they end up with hypercortisolism and nearly always they will get Alzheimer's if there is no intervention. This is a rare genetic case, but simply a way to break the axis elsewhere with the same effect.
There is a recent study on this showing how this form can provide better results in the brain. https://www.sciencedirect.com/science/article/pii/S305047402...
In general: Omega-3, bcomplex with choline etc all have studies. Really it depends on the individual and what their genetic weakest issue is. Its old and boring, but eat healthy, don't eat before bed, exercise (dance!), and get good sleep always apply.
> He found that too much of YKL-40, which is linked to Alzheimer’s risk in humans, leads to amyloid build-up, an accumulation that is a hallmark of the neurodegenerative disease.
There are countless studies that highlight how genetics or lifestyle and other factors that result in a reduction of estrogen signaling are associated with Alzheimer's. Estrogen, primarily activated at night decreases the expression of the YKL-40 gene. All of the known interventions, from vitamin D, Mg, to gut, choline, etc all can improve estrogen signaling, decreasing YKL-40 gene. One can end up with Alzheimer's from many different routes so interventions depend on the person.
If there was a pill on the market today that would only increase the plaque-clearing all this really does is move the needle, they still have reduced estrogen signaling and the next weakest part of the system would fail such as from animpaired immune system and they will probably die of pneumonia.
But we could back up and say what is the most common cause of the global reduced estrogen signaling? Often increased oxy-androgens (which increase as we age), so for example 11-ketotestosterone (11-KT) which can't convert to its estrogen form results in upregulates HSD17B2. Why do we have so much inflammation causing increased oxy-androgens from the adrenals? Senescence cells releasing inflammatory factors SASP. More time more time spent on repair resulting in identity loss and mesenchymal drift. All a fancy way of saying we get older and will probably die from whatever weakest part of the system we have genetically. Fix one thing and something else breaks instead.
And for those that want to bring in the most well known genetic mutation APOE e4: APOE e4/e4 has elevated choline demands hindering estrogen signaling as well as raising HDL and lowering LDL. Low estrogen influences Cholesteryl Ester Transfer Protein, raising HDL and lowers LDL beyond what e4/e4 does by itself. With less choline and less phosphatidylcholine, it decreases GLUT1 transporters reducing glucose entering the brain. All of the above leads to an escalating amyloid plaque burden. Then reduced deep sleep and the glymphatic system cleaning is reduced too and you have Alzheimer's.
The above was just from memory probably had an error, but the point is Alzheimer's is not "simple" like this article pretends.
* one agent generate the main response
* one agent pointing out flaws
* one agent coming up with new ideas
PEMT (phosphatidylethanolamine N-methyltransferase) is what makes choline in the body, but it depends on estrogen.(https://pmc.ncbi.nlm.nih.gov/articles/PMC3020773/)
But a prompt I can share is simply "Come up with a plan to determine the location of Planet 9". I have received some excellent answers from that.
I would fall into the category of someone who does research as leisure. I have been slowly unraveling the genetics behind gender dysphoria. Yes I have borrowed a few biology books from libraries, but it has mostly been reading 70 years of research papers, piecing together all the evidence to make a hypothesis, comparing it to all the research data and iterating. In the last year I have also started getting a fair number of WGS (Whole Genome Sequenced) files, and I have a whole separate pile of anecdotal that just because it isn't published doesn't mean I can ignore it either. These are about as far from books as you can get. It is something I do for leisure, so my investigation has been somewhat random, following whatever I found interating at that time including dead ends. Been doing this very open ended research for years now and at this point we have a really solid understanding of it, so the edge cases are actually now the fun stuff. I never would have made anywhere near the progress I did if I had been forced to start with reading a bunch of random unrelated biology books.
As for my favorite EM field there is a nearby street with buried powers lines and transformer boxes at ground level. As you walk the street to the main street each box has a bigger EM sphere and I like to let my hand coast over each sphere. It isn't a sphere per say, but only in the sense that at at certain depth in the field the density (for lack of a better term) becomes high enough that I can feel it and it is like a boundary line
This was all formulaic and the more experienced directors and VP's back in 2022 knew this and immediately started playing the new corporate game to win in the long run.
Bupropion acts as a norepinephrine–dopamine reuptake inhibitor. Importantly it doesn't directly raise your serotonin. If you are a night owl, have trouble falling asleep etc you might have low serotonin to start and this could be bad for you.
Both of these are associated with suicidal thoughts. There is a reason HIMS requires your health info before suggesting drugs. I would flag the parent as providing dangerous information.
> Conclusions and relevance: In this cohort study, a history of upper gastrointestinal MD was associated with elevated risk of developing a clinical PD diagnosis. Increased vigilance among patients with MD for future PD risk may be warranted.
Associated is the key word. The washington post sensationalizes it to "may begin in the gut"