ChristianKl

Orexin and the quest for more waking hours

A week ago I was skeptical about the prospect of radically reducing human sleep needs. After reading John Boyle’s Cause area: Short-sleeper genes, I decided to research the area more deeply and updated to believe that it’s more likely that we can reduce human sleep needs without significant negative side effects. It might increase risk-taking which has both positive and negative effects. The one friend I have that has short-sleeper genes is a startup founder. Boyle suggested that one of the best actions to attempt would be using orexin or an orexin agonist as a drug, but that there’s currently a lack of funding for doing so. Given the way the FDA and EMA work, drugs only get approved when they are able to cure illnesses, with an illness being anything that has an ICD code. According to that notion, people who suffer from having to sleep more than four hours don’t have an illness and thus drugs can’t be approved for that purpose. In practice, this results in the NIH not being interested to fund the research of Ying-Hui, about people who need a lot less sleep and are still well rested, that Boyle discussed. DEC2-P384R and orexin biology The DEC2 gene produces prepro-orexin, which is 131 amino acids long. People with the DEC2-P384R mutation produce more prepro-orexin and have a reduced need for sleep. From prepro-orexin our body generates orexin A, which is 33 amino acids long, and orexin B, which is 28 amino acids long. Orexin A is highly conserved and has the same molecular structure in humans, mice, rats, and cows, while human orexin B differs from rodent orexin B. While orexin B doesn’t cross the blood-brain barrier, orexin A does. I didn’t find information on whether or not prepro-orexin passes the barrier, but it likely doesn’t given its size. According to Uniprot: > Orexin-A binds to both OX1R and OX2R with a high affinity, whereas orexin-B binds only to OX2R with a similar high affinity. The literature is sometimes unclear when they use the term orexi

132Sep 24, 2022

ChristianKl

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Rank: #10 out of 4859 in peer accuracy at Metaculus for the time period of 2016-2020.

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Why is Anthropic is okay with being used for disinformation?

> First they came for the epistemology, we don't know what happened afterwards - Michael Vassar In it's current conflict with the Department of War, Anthropic public position is that it has only two red lines, domestic surveillance and being used to kill people without human input. Previously, Anthropic also...

Feb 2610

Should we consider Meta to be a criminal enterprise?

Meta's estimates of money they earn due to fraudulent ads was $16 billion in 2024. In contrast total value of property stolen in burglaries in the US is around $3 billion per year. Unfortunately, 2019 is the last year with good numbers but should still be around that amount. If...

Feb 1042

Why do LLMs so often say "It's not an X, it's a Y"?

There seem to be common patterns of how LLMs write text that's shared by the LLMs of different companies and where the language patterns the LLM uses are different from usual human writing. How much do we know about why LLMs pick certain patterns? Do we know why they use...

Dec 16, 202526

Did Tyler Robinson carry his rifle as claimed by the government?

The FBI uploaded a video of their suspected shooter running over the roof after the shoot on Charlie Kirk was made. The Utah County Attorney writes in their charging document: > Immediately after the shot was fired, a camera captures the suspect running across the roof carrying an item whose...

Oct 6, 20252

The next wave of model improvements will be due to data quality

When talking about why the models improve, people frequently focus on algorithmic improvements and on hardware improvements. This leaves out improvements in data quality. DeepResearch provides a huge quantity of high quality analysis reports. GPT5 will almost certainly be trained on all the DeepResearch requests (where there are no reason...

Jun 28, 202517

Does BPC-157 work for healing and tissue repair?

BPC-157, a peptide frequently marketed as a breakthrough for healing and tissue repair, has attracted substantial attention in wellness and performance communities. It’s discussed in forums, recommended by biohackers, and even offered in clinics—despite lacking FDA approval or broader clinical recognition. The challenge is personal: we all want healing when...

May 22, 202517

There's more low-hanging fruit in interdisciplinary work thanks to LLMs

I'm right now doing conceptual theoretical work about how the human fascia system works. While I do rely on some original conceptual insights that I have e come up with on my own, Gemini 2.5 Pro massively speeds up my conceptual work. Being able to formulate a principle or analogy...

May 7, 202526

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ChristianKl

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ChristianKl

Orexin and the quest for more waking hours

Prediction-based medicine (PBM)

What happened to the OpenPhil OpenAI board seat?

Why aren't we all using Taffix?

ChristianKl

Why is Anthropic is okay with being used for disinformation?

Should we consider Meta to be a criminal enterprise?

Why do LLMs so often say "It's not an X, it's a Y"?

Did Tyler Robinson carry his rifle as claimed by the government?

The next wave of model improvements will be due to data quality

Does BPC-157 work for healing and tissue repair?

There's more low-hanging fruit in interdisciplinary work thanks to LLMs

Orexin and the quest for more waking hours

Prediction-based medicine (PBM)

What happened to the OpenPhil OpenAI board seat?

Why aren't we all using Taffix?

Why is Anthropic is okay with being used for disinformation?

Should we consider Meta to be a criminal enterprise?

Why do LLMs so often say "It's not an X, it's a Y"?

Did Tyler Robinson carry his rifle as claimed by the government?

The next wave of model improvements will be due to data quality

Does BPC-157 work for healing and tissue repair?

There's more low-hanging fruit in interdisciplinary work thanks to LLMs