Nesco (u/Nesco) - Readit News

Nesco commented on Ozempic shows anti-aging effects in trial trial.medpath.com/news/5c... · Posted by u/amichail

cthalupa · 17 days ago

Losing weight through any method will make your metabolism slow down - fat is metabolically active. Uncouplers won't change this. Even if 100% of your weight loss is fat, your BMR is going to drop. The amount of metabolic adaptation from caloric deficits is grossly overstated by many people, and the "starvation mode" adaptation is temporary. Just reaching a maintenance level of calories for a relatively short period of time is enough to reset it - but this change is minor to begin with. The majority of any metabolism slowing will occur purely as a function of weight loss.

The issue with regaining weight after coming off these drugs is that people don't change their habits, and once they are off, they no longer have the limited appetite, and return to eating like they did before, which just results in the problem reoccurring. Uncouplers won't change this.

If people want to sustain their weight loss, they either need to change their lifestyle and eating habits, or they need to stay on the drugs, and potentially even both.

Nesco · 16 days ago

Let’s be real: both of us have no idea of how it would play out. Pharma companies will try to add them to their stack at some point, and then the real world data we currently lack will decide for everyone

Nesco commented on Ozempic shows anti-aging effects in trial trial.medpath.com/news/5c... · Posted by u/amichail

cthalupa · 17 days ago

I would agree, personally - I won't go near DNP, and even the newer stuff like BAM15 that is supposed to be incredibly selective I am quite suspicious of.

But you still see people losing tons of weight on GLP-1s wanting it to go faster, drop more pounds, etc.

I'm a big proponent of them - and I have enough risk tolerance that I'm on grey market retatrutide - but I see a lot of people that want to just keep adding more and more chemicals to the equation to solve the issue. I've taken the time to significantly modify my food and exercise habits, and believe that I'll be able to maintain my weight loss if I were to go off of the GLP-1. But a lot of people haven't. They eat the same bad food, just in lower quantities, don't increase their protein and fiber intake, don't exercise, and just up the dose or add a new compound when their rate of weight loss doesn't satisfy them.

There's tons of interest in BAM15, clenbuterol, and all sorts of experimental substances. Tons of people taking things like tesamorelin and ipamorelin too.

I think the GLP-1s are basically miracle drugs that have allowed a lot of people, including myself, to totally revamp their approaches to diet and fitness. But there's a lot of people that are going to be more than happy to increase their cocktail with anything they think will get them skinny faster.

Nesco · 17 days ago

Uncouplers are particularly useful to make sure your metabolism doesn’t slow down, which makes getting off those drugs when reaching the right body fat percentage without regaining everything way easier

Nesco commented on Ozempic shows anti-aging effects in trial trial.medpath.com/news/5c... · Posted by u/amichail

nkmnz · 18 days ago

looking for this, hu? https://en.wikipedia.org/wiki/HU6

Nesco · 18 days ago

Yes, but also BAM15 and mRNA based UCPs overexpression

Longer term if it works more research in the domain, including variations of the other well known ones (DNP, XCT-790, mitoCCCP, …)

I firmly believe that combined with:

- additional progress on the current targets (GLP-1, GIP, …)

- compounds to counteracts muscle loss like myostatin inhibitors

- food options being shaped by more health conscious consumers

Having a slow metabolism will stop being an disadvantage by midcentury

Nesco commented on Ozempic shows anti-aging effects in trial trial.medpath.com/news/5c... · Posted by u/amichail

strken · 18 days ago

"No free lunch" is a reasonable question to ask when evaluating medication, if it would improve the evolutionary fitness of the majority of people. I think this is behind some of the skepticism. If Ozempic is so great then how come our bodies don't just produce more GLP-1? How come we aren't like chimps, with eternally shredded bodies and cheese grater abs, provided we get the protein to support them?

I would guess that getting fat in times of plenty was a feature and not a bug in the ancestral environment, and that's why we get fat today, which is obvious if you think about it. Still, it means GLP-1 agonists are smacking into quick "is it bullshit?" heuristics for a lot of people.

The second point I haven't seen discussed is that weight loss drugs prior to GLP-1 agonists include cigarettes, which (worst case) give you cancer; stimulants, which cause your heart to fail; parasitic intestinal worms, which can kill you but more importantly are just plain gross; and mitochondrial uncouplers, which set you on fire at a cellular level. That's a long history of miracle weight loss drugs which turn out to have horrible side effects. It's not reasonable to think GLP-1 is bad just because of other drugs with different mechanisms, but it certainly causes some skepticism anyway.

Nesco · 18 days ago

I am pretty sure uncouplers will make a come back. Just something a little more targeted and safer than good ol’ DNP

Nesco commented on How to grow almost anything howtogrowalmostanything.n... · Posted by u/car

the__alchemist · 20 days ago

Warning to anyone who goes down this rabbit hole: If you set up a home lab, don't tell people who you're not close with. There's a very good chance they'll assume you're (if they're a normie) making coronavirus or meth, and (If they're a biologist or chemist) assume you're not disposing of reagents and cultures properly. I wish this wasn't the case, but as a society, we're not ready to talk about bio outside of institutions and universities.

Also, the costs are deceptive, even with used or Chinese parts: I estimate $10k USD for a usable molecular bio lab, including equipment and reagents.

Nesco · 20 days ago

Yeah, trying to create one right now to try to do some E Coli + Desnoyer’s style flower experiments.

I really underestimated the cost

Nesco commented on My 2.5 year old laptop can write Space Invaders in JavaScript now (GLM-4.5 Air) simonwillison.net/2025/Ju... · Posted by u/simonw

NitpickLawyer · a month ago

> Two years ago when I first tried LLaMA I never dreamed that the same laptop I was using then would one day be able to run models with capabilities as strong as what I’m seeing from GLM 4.5 Air—and Mistral 3.2 Small, and Gemma 3, and Qwen 3, and a host of other high quality models that have emerged over the past six months.

Yes, the open-models have surpassed my expectations in both quality and speed of release. For a bit of context, when chatgpt launched in Dec22, the "best" open models were GPT-J(~6-7B) and GPT-neoX (~22B?). I actually had an app running live, with users, using gpt-j for ~1 month. It was a pain. The quality was abysmal, there was no instruction following (you had to start your prompt like a story, or come up with a bunch of examples and hope the model will follow along) and so on.

And then something happened, LLama models got "leaked" (I still think it was a on purpose leak - don't sue us, we never meant to release, etc), and the rest is history. With L1 we got lots of optimisations like quantised models, fine-tuning and so on, L2 really saw fine-tuning go off (most of the fine-tunes were better than what meta released), we got alpaca showing off LoRA, and then a bunch of really strong models came out (mistrals, mixtrals, L3, gemmas, qwens, deepseeks, glms, granites, etc.)

By some estimations the open models are ~6mo behind what SotA labs have released. (note that doesn't mean the labs are releasing their best models, it's likely they keep those in house to use on next runs data curation, synthetic datasets, for distilling, etc). Being 6mo behind is NUTS! I never in my wildest dreams believed we'll be here. In fact I thought it would take ~2years to reach gpt3.5 levels. It's really something insane that we get to play with these models "locally", fine-tune them and so on.

Nesco · a month ago

Zuck wouldn’t have leaked it on 4chan of all the places

Nesco commented on Org tutorials orgmode.org/worg/org-tuto... · Posted by u/dargscisyhp

Nesco · a month ago

To people using org mode, how does it help you more than Markdown? Genuinely curious because I tried at some point and it felt too heavy.

Maybe because I am a vim user instead of eMacs?

Nesco commented on OpenICE: Open-Source US Immigration Detention Dashboard openice.org/... · Posted by u/supermaxman

allthedatas · a month ago

Seems more like a scoreboard -- this may have the opposite effect the creators intended? The top 10 virus lists published by some vendors became that for virus writers.

Nesco · a month ago

[flagged]

Nesco commented on Ask HN: What Are You Working On? (June 2025) · Posted by u/david927

Nesco · 2 months ago

I have been working on a symbolic solution to ARC-AGI: https://github.com/nesco/DPS

Shapes are converted into trees of paths, and those trees are compressed using a symbolic lookup table

A LLM can then use those symbols to reason about shapes, and a tree edit distance can be used to group them in categories

Nesco commented on Icônes icones.js.org/... · Posted by u/tambourine_man

jfengel · 4 months ago

What's with the hat on the o?

In French it's used to mark where an o was followed by an s in Latin, but that's not the case here. Icon comes from Greek word that never had an S.

Wiktionary reports an Esperanto iĉon, which means "male".

Perhaps this means something in some other language? Or is it a metal umlaut?

Nesco · 4 months ago

It’s the French spelling. Saying it’s only to indicate the disappearance of an “s” is reductive