Ezku (u/Ezku) - Readit News

Ezku commented on Concept cells help your brain abstract information and build memories quantamagazine.org/concep... · Posted by u/headalgorithm

Ezku · a year ago

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)

Ezku commented on Ask HN: Good books on philosophy of engineering? · Posted by u/s3micolon0

Ezku · 2 years ago

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.

Ezku commented on Deploying the Octothorpe (#) exchanges.warwick.ac.uk/i... · Posted by u/jruohonen

Ezku · 2 years ago

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

Ezku commented on Schizophrenia drugs may have been off target for decades, study finds msn.com/en-us/health/medi... · Posted by u/thedday

A_D_E_P_T · 3 years ago

Situation normal.

Consider the discovery of valproic acid:

"Valproic acid is a carboxylic acid, a clear liquid at room temperature. For many decades, its only use was in laboratories as a "metabolically inert" solvent for organic compounds. In 1962, the French researcher Pierre Eymard serendipitously discovered the anticonvulsant properties of valproic acid while using it as a vehicle for a number of other compounds that were being screened for antiseizure activity. He found it prevented pentylenetetrazol-induced convulsions in laboratory rats. It was approved as an antiepileptic drug in 1967 in France and has become the most widely prescribed antiepileptic drug worldwide. Valproic acid has also been used for migraine prophylaxis and bipolar disorder."

To this day, nobody knows exactly how it works, apart from the fact that it hits more than a few targets. (And it's a particularly potent inhibitor of the epigenetic modulator histone deacetylase.)

Apart from a subset of very clear-cut cases -- steroid hormones, peptide hormones, and certain aggressive chemotherapeutic drugs -- there's no clear model for most small molecule drugs. Even really mundane ones like metformin and paracetemol are very imperfectly understood.

Ezku · 3 years ago

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.

Ezku commented on Thinking hard makes the brain tired economist.com/science-and... · Posted by u/gyre007

Ezku · 3 years ago

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/

Ezku commented on JavaScript and TypeScript features of the last 3 years medium.com/@LinusSchlumbe... · Posted by u/Killusions

Ezku · 3 years ago

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.

Ezku commented on Vitamin D supplementation and incident dementia alz-journals.onlinelibrar... · Posted by u/bookofjoe

Ezku · 3 years ago

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/

Ezku commented on Vitamin D supplementation and incident dementia alz-journals.onlinelibrar... · Posted by u/bookofjoe

underdeserver · 3 years ago

I dove deep into Vitamin D supplementation research during Covid. The tl;dr as I understand it - and bear in mind I'm a layperson in this - is that while Vitamin D deficiency correlates to many bad things, taking Vitamin D doesn't help. It does raise your level as it shows up in blood tests, but the bad things still happen.
Except for some very specific issues.

I have a mild deficiency and used to take Vitamin D. I stopped taking it after consulting with a doctor on the meaning of the VITAL study results [1]. I also recommend [2], from a practicing surgeon who deals with Vitamin D related medical issues in patients.

[1] https://pubmed.ncbi.nlm.nih.gov/35939577/ [2] https://www.devaboone.com/post/vitamin-d-part-3-the-evidence

Ezku · 3 years ago

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.

Ezku commented on Gut microbes could drive brain disorders nature.com/articles/d4158... · Posted by u/pella

shagie · 3 years ago

Serotonergic Mechanisms Regulating the GI Tract: Experimental Evidence and Therapeutic Relevance (2017) - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5526216/

> Serotonin (5-hydroxytryptamine; 5-HT) is best known as a neurotransmitter critical for central nervous system (CNS) development and function. 95% of the body’s serotonin, however, is produced in the intestine where it has been increasingly recognized for its hormonal, autocrine, paracrine, and endocrine actions.

--

Here's this chemical that we use to run our brain... where is it produced? Not in the brain, but rather in the gut.

Ezku · 3 years ago

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/

Ezku commented on Almost monospaced: the perfect fonts for writing blakewatson.com/journal/a... · Posted by u/blakewatson

delta_p_delta_x · 3 years ago

> iA Writer

The typeface is a modification of IBM Plex Mono[0][1]. I'd recognise that 'a' glyph anywhere.

[0]: https://github.com/IBM/plex

[1]: https://www.ibm.com/plex/

Ezku · 3 years ago

Well spotted!

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

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