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Doing something novel is incredibly difficult through LLM work alone. Dreaming, hallucinating, might eventually make novel possible but it has to be backed up be rock solid base work. We aren't there yet.

The working memory it holds is still extremely small compared to what we would need for regular open ended tasks.

Yes there are outliers and I'm not being specific enough but I can't type that much right now.


Feature request: Combine book series into a single entity. Bummer getting recommendations for another book in the same series as one I already liked and read.

Feature request: Exclude books already in shelf. This is harder I'm sure. I've got 1146 books in my Read shelf.


I know a couple folks that do a ton of phone only reading now. I haven't read for pleasure in over a decade but I've listened to ~1300 different audiobooks. Seems like this isn't well thought out.


Listening to audiobooks is included in the survey (but they also mention that most people who listen to audiobooks also read print books; you are likely an outlier in that regard).


I don't know what I'm talking about but when I first asked your question this https://gist.github.com/Artefact2/b5f810600771265fc1e3944228... helped start me on a path to understanding. I think.

But if you don't already know the question your asking is not at all something I could distill down into a sentence or to that would make sense to a lay-person. Even then I know I couldn't distill it at all sorry.

Edit: I found this link I referenced above on quantized models by bartowski on huggingface https://huggingface.co/bartowski/Qwen2.5-Coder-14B-GGUF#whic...


No huggingface models or did I just miss them? Edit: they mention doing open models at some point at the bottom of the page


  Location: Austin, TX
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  Technologies: JavaScript, TypeScript, Node, GIT, NPM, React, Web Components, Webpack, Build configuration, Jest, Mocha, ESLint, CSS, SASS, Storybook, Monorepo configuration, TestCafe, Unit testing, End-to-end testing, Integration testing, Backbone, Marionette, jQuery, Bootstrap, Google MUI React UI Components, MySQL, Postgres SQL, SQL Server, C#, Python, Ruby, Rake, Docker, TeamCity, Jenkins, Amazon Web Services, Terraform, PowerShell, Visual Studio, EC2, S3, DynamoDB, Lambda, API Gateway, Cloud Development Kit, EC2 Image Builder, HTML, Internationalization i18n, Localization l10n, Visual Diff testing, Bash scripting, Objective-C, Android Java, Cordova, KendoUI, Flash, Flex, ActionScript
  Résumé/CV: https://barrettsonntag.com/Sonntag_Barrett_resume.pdf
  Email: barrett@sosuke.com
Is it better that I list everything or just a few things? I'm always conflicted. What if I said TypeScript and React but left out JavaScript? That could mean I never worked with JavaScript right? Which sounds crazy but code camps produce React developers that have no experience outside that framework.


Imagine three other possibilities:

You have a dozen people who would give you emotional support but you don't ask for any because you aren't sure you could give emotional support in return.

You have a dozen people you think might give you emotional support but you don't want to burden them with your problems.

You have a dozen people that would give you emotional support, maybe once, but you are too afraid to burn the single emotional support coupon until its more important.


i have one friend that i can trust to be able to talk to with challenges in my life and especially with challenges in my relationship. i know that because he has been open and sharing many of his personal challenges for by now decades with a group of friends that i am privileged to have been invited to.

for everyone else it is pretty much like you describe. i have probably over time met people from each of those categories. and some of them may actually have turned into real friends that i could trust like this one friend above. but moving around meant that we didn't keep in touch. (and it's worth mentioning that almost none of them are from my home, so without moving around i would not have even met them)


> You have a dozen people that would give you emotional support, maybe once, but you are too afraid to burn the single emotional support coupon until its more important.

This is real. I went through an emotional crisis last year and reached out to a few friends and family for support. My choice to do that has left those relationships more distant, if not permanently damaged.


Yeah, that makes sense. I guess I just don't worry about it that much these days. What you're describing - the fear of overburdening or burning bridges, the uncertainty about what I can give back - I dunno. I had that, at one point, too. A LONG time ago. Middle school, high school maybe. But many years of being shown I can count on the people around me, and that I'm better at giving support in kind than I think, has made it less of a serious worry.

Of course there are limits, and they have to be respected. "Do not discuss rope in the house of a hanged man." But that's why there's so much breadth. If I can't talk about it with my partner, or my close friends are involved, I can almost always find someone willing to hear me out. Someone it's appropriate to go to support for.


It’s awesome they try to define those terms. But I wouldn’t call that well defined at all. https://www.lexology.com/library/detail.aspx?g=6a4c20dc-594d...

I would say that math is unambiguous.

Measurements are becoming more unambiguous. The accepted measurement of a kilogram equalling s Avogadro’s constant. Something like the number of silicon atoms in a 93mm sphere?

But the definitions of best and reasonable are only accepted based off precedent and we’ve seen in recent history precedent in law isn’t as reliable or defined as we may have thought.

Is there any language or any level of language that can remain defined across time and culture?

So long as legalese requires interpretation to determine intent and outcome it can be expected be incomprehensible.


For the sake of my question let’s assume this is legit and magically works for a wide range of autoimmune conditions. How many years away are we from being able to sign up for this treatment? 10 years? 20? 30?

It would be nice to dream of it happening sometime soon.


In the US, my "back of the napkin" estimate tends to be 8-15 years, if it passes trials.


Is there a way to speed up trials without compromising quality?


Only for orphan and ultra orphan diseases where there are so few patients that it’s not economically viable to do full clinical trials.

There is also a breakthrough therapy designation where the clinical evidence is solid enough to release the drug while they finish full trials but that’s only in exceptional cases.


Possible to use surrogate endpoints, which is used for slower evolving diseases. But then the claims need to be associated with the new endpoints.

FDA can fast track certain drugs, but it really needs to show amazing efficacy.


Not really, the process gets shortcut when the benefits of moving fast are dramatic enough.

So sure we could speed things up by killing more people undergoing medical experiments. But the current approach of validating safety in humans then efficacy in humans is inherently serial. Further a lot more stuff is going into the pipeline than actually ends up working.



Only for gene therapies unfortunately


Maybe not long at all. Scroll down to the section that says "Our Approach : Building a Designer Immune System" on this site[0]

[0]https://orcabio.com/what-we-do/


amen. I've tried 3 tnf inhibitors that have not worked (and had negative side effects). Cosentyx (il 17a inhibitor) kinda scares me. I always like to keep my hopes that some better autoimmune treatments could come soon


Out of curiosity I'm curious why it scares you?

For context, I had been on Taltz before for psoriasis, and it worked very well. It seems like il17 inhibitors specifically are extremely targeted in what they affect.

In comparison, I was also on otezla at one point (tnf-a inhibitor) and it didnt work for me either, and the side effects were terrible.


It's the few instances of new onset IBD and generally the GI side effects. I'm lucky enough to have a pretty solid GI system that I don't want to risk messing with. I get very anxious with medicine, and my ankylosing spondylitis is sufficiently slow moving on MRI and tolerable enough that I prefer not to use the medicines. I had too many strange side effects whilst on Humira/Remicade such that it scares the crap out of me.


Understandable. I'll just say that for a sample size of n=1 I've seen no GI side effects with il17 blockers.

Which was not the case with otezla. But tnfa blockers - yeah those are bad times.

In any case, good luck with your treatment!


thank you and thanks for your n=1, wish you the best with your treatment as well


You had a skin fungal infection dumbass not some unknown mystery condition psoriasis they came up with


Wow, kid, you really have no clue about the world.


Depends. Do you want to be a patient, or a trial test subject?


I would assume they primarily would like to suffer less.

My uncle has developed an autoimmune respiratory disease over twenty years ago, and I know he would give a whole lot to improve his condition.


Probably less long if you are prepared to go to China where the research in the paper took place. The FDA seems to be a bit slow.


In Mexico, maybe a year?

(Please don’t downvote me because you don’t like the tone of that. Europe banned artificial food colors and Japan is using self-replicating RNA vaccines. There is a wide spectrum of risk tolerance and healthcare does not revolve around the USA)


I'm not sure about Mexico, but here in Argentina I think we wait until the drug gets a the FDA or EMA approval and ask for a copy, well we probably ask for all the paperwork but I don't remember cases of weird fast local approvals. It's possible to buy Metamizole/Dipyrone here https://en.wikipedia.org/wiki/Metamizole . Anyway, we have special cases, like a vaccine for a local illness https://es.wikipedia.org/wiki/Virus_Jun%C3%ADn that I guess is not approved anywhere else.

Every few years, there is an scandal for illegal medicine, but I think most of the case it's about using industrial silicone in human cosmetic surgery or something as stupid like that, not cutting edge new drugs. Perhaps it's possible to get tourist-illegal-medicine, but I strongly advice against that.

---

> Japan is using self-replicating RNA vaccines

Do you have a source for that? I can try to take a look. I suspect it's very bad journalism reporting.

Self-replicating RNA are just https://en.wikipedia.org/wiki/Viroid but they only survive in plants, not animals. If they make their own coating, they are retrovirus. Writing a retrovirus from scratch is too difficult, some vaccines use edited virus, where they add the interesting part but also remove another part to the virus can't reproduce outside the lab. And there are vaccines with "live" attenuated virus, like the oral polio vaccine, but they are more difficult to make.


https://www.prnewswire.com/news-releases/japans-ministry-of-...

Your characterization is inaccurate, of both the reporting and the technology


Thanks. Very interesting. From the research paper:

> The ARCT-154 study vaccine consists of sa-mRNA encapsulated in lipid nanoparticles. The RNA comprises a replicon based upon Venezuela equine encephalitis virus (VEEV) in which RNA coding for the VEEV structural proteins has been replaced with RNA coding for the full-length spike (S) glycoprotein of the SARS-CoV-2 D614G variant.

IIUC the RNA makes copies of itself inside the cell, but it does not get a capsule of proteins to travel and invade other cells. Is this correct?

(A few more details in https://en.wikipedia.org/wiki/MRNA_vaccine#Amplification but not enough for my curiosity level.)


I’d like a small phone with the newest screen and camera features. The phones with the features keep growing in size,


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