Ezku

An interesting piece featured in the article: “Concept and Location Neurons in the Human Brain Provide the ‘What’ and ‘Where’ in Memory Formation”, Nature Communications 2024 (https://doi.org/10.1038/s41467-024-52295-5)

This wasn’t in the article, but I feel it makes for good background reading: “Universal Principles Justify the Existence of Concept Cells”, Scientific Reports 2020 (https://doi.org/10.1038/s41598-020-64466-7)

This book is probably about a very different kind of ”engineering” than what you had in mind, but it’s been highly influential to my thinking:

“The Social Construction of Reality: A Treatise in the Sociology of Knowledge.” Berger & Luckmann 1966.

Perhaps the core insight to me is that not only does every practice of engineering exist as embedded in the context of a socially constructed reality, but the practice of engineering itself also fundamentally involves the continual construction of such realities. In other words, for a software engineer to be able to do their job, they must among other things be a kind of applied social epistemologist.

I expect this framing doesn’t make much sense to many readers — I’m hoping the following articles might serve to illustrate:

“Programming as Theory Building.” Peter Naur, Microprocessing and Microprogramming 1985 (https://doi.org/10.1016/0165-6074(85)90032-8)

> … suggests that programming properly should be regarded as an activity by which the programmers form or achieve a certain kind of insight, a theory, of the matters at hand. This suggestion is in contrast to what appears to be a more common notion, that programming should be regarded as a production of a program and certain other texts.

“Interpretation, Interaction and Reality Construction in Software Engineering: An Explanatory Model.” Kari Rönkkö, Information and Software Technology 2007 (https://doi.org/10.1016/j.infsof.2007.02.014)

> Floyd’s paper Outline of a Paradigm Change in Software Engineering requested that we move from a product oriented paradigm to a process oriented paradigm.

> Naur’s paper Programming as Theory Building made it painfully clear to us that exemplary resources in the form of material and available support are not enough when modifying others’ programs. In fact, if Floyd’s claims had been taken seriously by the software developers in Naur’s study, and if the same developers had access to an explanatory model … their difficulties could have been both anticipated and prevented.

> This article … explains from a natural language point of view, how interpretation takes place, and discusses the consequences of this in relation to interaction and reality construction in software engineering practice.

Research citation & abstract, for other PDF-challenged individuals:

Braddy, Jon. “Utilizing the Octothorpe (#).” Exchanges: The Interdisciplinary Research Journal, April 2022. https://doi.org/10.31273/eirj.v9i2.837.

”Felix Guattari’s ‘Schizoanalytic Cartographies’ acts as a methodological blueprint and can be used to explain a subject’s lack of expressivity when confronted by Foucauldian systems of discipline and punishment. Understanding mechanisms of regulation and control within a closed or open system is the purpose of cybernetics. This communication studies tradition emerged from the artificial intelligence work of Norbert Wiener’s data flows with the intentional purpose of steering people, thought, societies, and the cosmos towards—becoming. Using the analogy of the octothorpe (#) as a roadmap explaining the four cartographies (Flows, Phyla, Territories, Universes) as outlined by Guattari, this manuscript will analyze the film, ‘War Games,’ demonstrating schizoanalytic technique. Another layer of power over humanity is not a panacea, rather it ushers forth civilisation’s speedier, and predicted, demise.”

Here’s also a web version of the PDF, as processed by Readwise Reader: https://readwise.io/reader/shared/01hjkgjb3qb9408fk8pg8xap3x

Your point is a very important one. Do we check the interactions of a tentative drug molecule against every single molecular target in the body, and do we track what happens as a result of all those interactions? It’s quite common that a group of ”usual suspects” on the researchers’ radar get checked for — but by necessity, a lot of ground goes uninvestigated.

  > Consider valproic acid: For many decades, its only use was in laboratories as a "metabolically inert" solvent for organic compounds

Speaking of ”inert” solvents:

  > Dimethyl sulfoxide (DMSO) is the most common organic solvent used in biochemical and cellular assays during drug discovery programs.
  > Despite its wide use, the effect of DMSO on several enzyme classes, which are crucial targets of the new therapeutic agents, are still unexplored.
  > 1-4% (v/v) DMSO, the commonly used experimental concentrations, showed ∼37-80% inhibition of human acetylcholine-degrading enzyme, acetylcholinesterase (AChE)

(DMSO: A Mixed-Competitive Inhibitor of Human Acetylcholinesterase. ACS Chem Neurosci. 2017 https://pubmed.ncbi.nlm.nih.gov/29017007/)

Oops! How many investigations on specific drugs were in fact showing mostly the results of what happens when interfering with one of the most ubiquitous-yet-underappreciated signalling systems, the cholinergic system?

I’m hoping widespread & systematic application of modern methods like in-silico molecular docking studies will lead to much fewer such oversights.

Is it really considered acceptable not to link to the scientific research you are basing your news on?

Pubmed link (with abstract); full text is paywalled:

> A neuro-metabolic account of why daylong cognitive work alters the control of economic decisions. Curr Biol. 2022 https://pubmed.ncbi.nlm.nih.gov/35961314/

From the comments here, I was expecting to find myself hopelessly out of date, and to end up with a migraine trying to parse through a mindnumbing list of changes. Turned out I was mistaken.

  > Me: oh, cool, they fixed so many tiny things I had bumped up against
  > Some others: oh no, why are things changing

I'm not getting it. Maybe I'm reading this wrong, but to me these seem pretty obvious small issues to smooth over.

Perhaps not many in this audience are dealing with having to mitigate the prospect of dementia. How about something close to the horizon for almost all of us?

> Vitamin D deficiency can cause over‐activation of the pulmonary renin‐angiotensin system (RAS) leading to the respiratory syndrome. RAS is regulated in part at least by angiotensin‐converting enzyme 2 (ACE2), which also acts as a primary receptor for SARS‐CoV‐2 entry into the cells. Hence, vitamin D deficiency can exacerbate COVID‐19, via its effects on ACE2.

— Vitamin D and COVID-19: Role of ACE2, age, gender, and ethnicity. J Med Virol. 2021 https://pubmed.ncbi.nlm.nih.gov/33990955/

> Angiotensin-converting enzyme 2 (ACE2), a part of the renin-angiotensin system (RAS), serves as the major entry point into cells for SARS-CoV-2 which attaches to human ACE2, thereby reducing the expression of ACE2 and causing lung injury and pneumonia. Vitamin D, a fat-soluble-vitamin, is a negative endocrine RAS modulator and inhibits renin expression and generation… Therefore, targeting the unbalanced RAS and ACE2 down-regulation with vitamin D in SARS-CoV-2 infection is a potential therapeutic approach to combat COVID-19.

— A brief review of interplay between vitamin D and angiotensin-converting enzyme 2: Implications for a potential treatment for COVID-19. Rev Med Virol. 2020 https://pubmed.ncbi.nlm.nih.gov/32584474/

Here’s a caveat to remember when taking vitamin D:

> Majority of the adults are deficient in both vitamin D and magnesium but continue to go unrecognized … Mg is essential in the metabolism of vitamin D, and taking large doses of vitamin D can induce severe depletion of Mg. Adequate magnesium supplementation should be considered as an important aspect of vitamin D therapy.

— Magnesium Supplementation in Vitamin D Deficiency. Am J Ther. 2019 https://pubmed.ncbi.nlm.nih.gov/28471760/

FWIW, I think the article agrees.

> vitamin D effects were significantly greater in females versus males and in normal cognition versus mild cognitive impairment.

> vitamin D effects were significantly greater in apolipoprotein E ε4 non-carriers versus carriers.

Translation: If you’re already cognitively impaired, vitamin D can do little to fix that. Same goes for if you’re at high risk for Alzheimer’s genetically (ApoEε4), or generally at higher risk for neurovascular diseases (male).

However, as I’m sure others in the comments will point out — supplementing vitamin D will at least ensure you’re not getting cognitive impairment due to vitamin D deficiency, which seems to absolutely be a thing.

Peripheral and central serotonergic systems are both relevant:

> Because 5-HT cannot cross the blood-brain barrier, the peripheral 5-HT system is functionally separate from the central 5-HT system. — Diabetes Metab J. 2016 https://pubmed.ncbi.nlm.nih.gov/27126880/

Well spotted!

> This is a modification of IBM's Plex font.

https://github.com/iaolo/iA-Fonts/tree/master/iA%20Writer%20...

Great information & a good summary, thank you! If I’m looking to get more in-depth with the known mechanisms of locus coeruleus and episodic memory, would you be able to recommend any sources of yours?

To try and tickle your interest, here’s why I’m looking into it: I have no episodic memory. I have aphantasia. I have hypotheses for explanations that I’m looking to correlate with different pieces of research, and locus coeruleus interactions is one area I have yet to look sufficiently deeply into.

I do often share this sentiment, even if I’m not in agreement with your tone. But I’m curious —

  > Specific qualia have a higher cortical resonance, due to overarching reinforcement over time, and they are picked out.  
  > The more a single stream of information is focused on, the greater degree of resonance that may occur with less endowed qualia (slow down, notice more shit due to neuro-satiation).

How did you come upon these conclusions, or this framing? I’m surprised, because what you’re saying meshes well with some details of a model for the neurophysiological basis of conscious experience I’ve been working on… and I don’t think I’ve ever seen anyone else point out these exact connections before.

For all I know this could be general knowledge in some community; or something believed widely at one time, now discredited. I’m operating in a vacuum and have been putting things together from what to me appear to be first principles. I might be reconstructing common knowledge, or just unknowingly restating things I’ve unconsciously absorbed in the past… The potential for which bothers me now that I’m seeing your comment.

Where’s your perspective coming from? :) Pointers to your sources would be much appreciated.

Oh, this was a new one for me.

In case you like narrow but Victor’s not your thing, I can enthusiastically point you towards Iosevka. (That’s also available in Victor’s comparison picker. Nice!)

I’m thinking your reference to composing red functions doesn’t seem congruent with your desire to discuss algebraic effects. Composing arbitrarily many red functions, or blue functions, is a solved problem. (I won’t mention the lingo knowing many in the audience to be allergic.) Composing functions with heterogenous, or completely arbitrary, colors is much less so. That’s what the article is about, too, is it not - combining blue and red? But I might well be missing something deeper here, perhaps you’ll enlighten the reader :)

I would be really keen on seeing a mainstream-ish language that does algebraic effects or that can even implement them in a legitimate sense (discounting React’s implementation here, for instance). Purescript tried, but are doing something different these days. https://purescript-resources.readthedocs.io/en/latest/eff-to...

> the compact camera market is dying. > Olympus just sold off their camera division.

And someone _bought_ that camera division. With the intent to continue designing, manufacturing and selling cameras under the Olympus brand. Sure, Olympus wasn’t doing great, but someone paid money because they thought they could run the business better. And their consumer business is in selling compact cameras, right? There appears to be at least some faith in the market.

> We probably won't see many new models from Canon

Personally I sure hope so. Their less-than-full-frame offering has been pretty lackluster afaict, other companies are doing the job better. We’ve lately seen some surprisingly kickass tech innovation in the full frame market from Canon, though. I hope they continue to focus their efforts.

The paper explicitly states that it’s about Functional Relational Programming, so that’s verifiably correct. I’m not sure if I can agree, though.

> It actually doesnt have much to do with "reactive" programming model as we know it today

What would you say is the ”reactive” model as we know it today?

If you asked me what FRP is, I’d tell you about Functional Reactive Programming. Maybe I’d point you to Conal’s writings[0] or something like Your Mouse is a Database[1]. Andre Staltz did a nice writeup on how it’s useful to think of FRP in more broader terms than the original definition would require[2]:

> it would make sense to talk about "functional reactive programming" as a paradigm or an idea where you build applications using listenable event streams (or "signals"), creating and composing them using pure functions

For me, that’s the spirit of FRP. And when I read Out of the Tarpit, that’s exactly what jumps at me. The paper seems to describe data that’s changing over time, and other data being derived from those such that when the original data changes, so does the derived one. That’s pretty much precisely Functional Reactive Programming to me, even if the words are different.

You might have another sense of the words in mind; I’d like to understand what you think, and why.

  [0]: http://conal.net/papers/push-pull-frp/  
  [1]: https://queue.acm.org/detail.cfm?id=2169076  
  [2]: https://medium.com/@andrestaltz/why-i-cannot-say-frp-but-i-just-did-d5ffaa23973b

The author seems to be referencing a project of theirs with a Finnish name, so perhaps my intuition as a native Finnish speaker can help. In Finnish you’d likely pronounce pijul [pi-jul]. If I were to pronounce the word ”in English” starting from that basis, the smallest change is, I think, to make it [pi-zhul]. That is, ”pee-jewel” but with short vocals instead of long ones for both words.

My personal take is that io-ts _is_ typescript’s aeson, but if you’re scared of the baggage it comes with then how about giving zod a try? https://github.com/vriad/zod

I have a hypothesis that this condition and ADHD are related. ADHD researcher Dr Russell Barkley links Vygotsky’s theories of childhood development to the mechanism by which ADHD interferes with executive function [0]. An ADHD brain would be less capable of imagining things and holding those images, which would lead to failure in development of self-directed action via those imagined images. Is this ”aphantasia”? I’m not sure, but I find it plausible.

The prevalence for ADHD has been cited at 5% in children and half of that in adults. A commenter here says aphantasia has been guessed to be at 1-3% [1], which would be a rough match. Another commenter describes their ADHD and aphantasia [2], and I am under the impression this has been reported often. If there was a causal relation I would expect to see these kinds of overlaps in the data, but it’s really the researcher’s description of a failure of imagination that makes this hypothesis especially interesting to me.

What do you think? Has anyone looked into this?

[0]: https://youtu.be/sPFmKu2S5XY

[1]: https://news.ycombinator.com/item?id=22810934

[2]: https://news.ycombinator.com/item?id=22811184

Thanks for the reply. So, careful application of mapped types and removing the ability to type a property as `foo: bar | undefined`. I understand this is desirable a lot of times especially if you can’t affect the format of what’s being parsed, but I’m not sure this is unambiguously better.

FWIW it’s made my life easier to say the keys will always be there, but the values are possibly undefined. Less room for ambiguous interpretation.

Very strongly agreeing with this assessment and hoping Colin will come to agree.

A zero-argument function is either a constant, or a side-effect. Given we don’t want a side-effect, exposing a constant instead of an effectful-looking function is preferable.

You mention creating object types with optional keys is cumbersome in io-ts. How is that solved in zod, exactly? What allows you to map `foo: union([bar, undefined])` to `foo?: bar | undefined` (note the question mark on the left hand side)? There’s nothing in the declaration to give away why this wouldn’t yield `foo: bar | undefined` which is what I believe you’d get out of io-ts.

Looks useful - I would have an easier time introducing this than io-ts.

Thanks for pointing that out! I wonder why that is :S

Appears to have goals similar to https://parceljs.org/, except parcel is under active maintenance and development whereas the latest release on this one is from a year ago. Am I missing something important? :)

Anecdotally, both of these were difficult to get to run at all and offered subpar developer experience on macos. :(

I guess this is an easy point of confusion. Are specific instances of functor algebras, then? (What about f-algebras?) What would be the more appropriate word for the category theoretical things the author is trying to refer to here, functor and monad and so on?

Wow, looks interesting. Will have to investigate. Looks more solid than any other ”instant graphql” solution I’ve seen.

This rarely gets a mention but totally deserves one: Iosevka[0], a programming font with great ligatures, multiple weights, and customizable character variants to tune it to your preferences. It’s more slender than most blocky monotypes which makes it stand apart especially from more traditional choices like Monaco and Consolas.

[0]: https://typeof.net/Iosevka/

Here are my versions. Every playlist has top 5 songs from the artists mentioned for each subgenre on the list.

https://open.spotify.com/playlist/4dAcwPZxCRk5V2ab3EFPZP?si=...

https://open.spotify.com/playlist/6WrCSyOd1UfrmaZJFXeqAF?si=...

https://open.spotify.com/playlist/3SfxYfyeBU1ph75Ed8mCpP?si=...

https://open.spotify.com/playlist/3tETCS8IwxJiz5XWHz8Kqp?si=...

https://open.spotify.com/playlist/0Y3IUHGeiOwkpuUhjW2ErM?si=...

https://open.spotify.com/playlist/3hRuECtfy9PKczpWPE0SRh?si=...

https://open.spotify.com/playlist/22tkk9pQIbGVqpBVY2996d?si=...

https://open.spotify.com/playlist/0W9ICmxCNPQzkknHa6CyKI?si=...

https://open.spotify.com/playlist/1lIeAjrLNrggjQmC8BNxh0?si=...

https://open.spotify.com/playlist/0O1gKw9KRYTUFS7WyywMoT?si=...

https://open.spotify.com/playlist/5S34tPfWB0q9s3f3fcHLh8?si=...

https://open.spotify.com/playlist/3k13QP7kaDvbxYyKo4CuZp?si=...

https://open.spotify.com/playlist/7sZ7YSdmZXb2ksze3bk3cS?si=...

https://open.spotify.com/playlist/2KxhKNBkrW47UfrpW4ezAO?si=...

https://open.spotify.com/playlist/5D9xAkuYC9cklxFXZUns8K?si=...

https://open.spotify.com/playlist/62XI14VIjqZxsA2CikNrBf?si=...

https://open.spotify.com/playlist/5kf1tVYouTxcJGbxV1lQny?si=...

https://open.spotify.com/playlist/4bBurOc5GGytLjnKPIExy9?si=...

https://open.spotify.com/playlist/5n6n7vNaBbRNelVzAD8UKw?si=...

https://open.spotify.com/playlist/3jPeGD6FKvEiYH4HP6m0Lv?si=...

Hope you enjoy. :)

> React-like experience

Can you elaborate on what you mean by this? As a user of both serverless and react I’m afraid I’m failing to see your point here.

Other than that - exciting stuff. I’ve been eagerly waiting for the ability to build some more powerful abstractions, preferably with as little yaml as possible. :)