Even discounting everything about the ethics, feasibility, state of our conceptual knowledge of brain function, has anyone demonstrated how a six-figure hardware suite like this https://plexon.com/plexon-systems/ is going to be miniaturized into a smartphone sized device mass produced for consumer purchase in the timetable laid out by Neuralink?
The hardware in that system is from Blackrock Microsystems. You can call them up and buy it right now (if you’ve got the cash...It’s not cheap!) It’s currently intended for research, so you’ll need ethics approval and the decoder isn’t included (but that’s the fun part anyway).
Ripple Neuro sells similar gear (better, even, maybe) and Neuralynx and some smaller companies also have competing products. It’s not in every corner store, but you could have a similar setup this month if you really wanted to.
You are correct. The researchers here sequenced each vaccine starting with the bit of vaccine left in the vial after administration. The goal was to get a raw sequence of the Moderna mRNA component so it can be easily filtered out as being a signal of therapeutic origin. Pfizer's sequence has already been published; it's incldued here to confirm that the result achieved experimentally matches the published sequence.
The human-octopus most recent common ancestor was an ancient organism from hundreds of million years ago. It would have been one of the earlier organisms to have bilateral symmetry and an embryonic development characterized by the three germ layers we have today.
If you have a dog and have been to the aquarium you're likely to already intuit that octopuses do something that looks a lot like sleeping and that animals all the way down the family tree have periods of quiet and active sleep as well. The researchers here use a combination of observational techniques to suggest that the octopus sleep states observed are analogous to sleep in the vertebrate.
The research paper as published does not explicitly mention dreaming, rather it is one of a host of processes implied when the researchers analogize the 'active sleep' behavior observed in the octopus to animal REM sleep patterns. The conclusion spells out the possible connection to the 'metabolic detoxification' and 'cognitive processing' functions of vertebrate REM sleep but does not state them definitively.
The general media news article and the research paper have some slight differences because of their different intended audiences, but litigating that divide is best left to those already doing it: the esteemed scholars of the Dunning-Krueger Institute at Wikipedia University.
>Recent evidence suggests neurogenesis is on-going throughout life but the relevance of these findings for neurodegenerative disorders such as Parkinson’s disease (PD) is poorly understood.
They are misrepresenting the state of knowledge in that field. It has indeed been known -- since the 90s -- that there is ongoing neurogenesis in the human brain after birth. However, it is also well-known that these new neurons are produced in regions of the brain that are not relevant to Parkinson's. The specific neurons that are lost in this disease, from a region of the brain known as the substantia nigra, are not normally replaced by ongoing neurogenesis.
(I say "not normally" because redirecting neurogenesis to supply new neurons to the substantia nigra, as a treatment for Parkinson's disease, has been an ongoing area of research for decades.)
Note also that this research study was done with zebrafish, whose neurobiology is dramatically different from humans.
"Zebrafish are a particularly valuable tool to study neurogenesis in vertebrates. Basal levels of neurogenesis occur at higher levels than in mammals, and additional proliferative zones are found throughout the brain"
In the zebrafish model, which yes, is different from the human brain, the researchers specifically demonstrate that neurogenesis is occurring in dopaminergic regions throughout life:
"... we demonstrate that ascending TPp DA neurons and local-projecting PVO neurons, but not magnocellular ascending DA neurons, are each generated into adulthood in wild type animals at a rate that decreases with age."
PINK1 deficiency slows the rate of the generation of DA neurons in zebrafish. Following this result, they then turned to the question of applicability to human systems by testing PINK1 deficiency on a culture of human midbrain organoids and successfully showed that this gene downregulated the size these organoids reached, demonstrating that this gene has an effect on neurogenesis of human dopaminergic neurons from the substantia nigra.
"Isolated observations in animal models of PD always raise concerns about the applicability of any results to human patients with this condition. However, the observation of impairment of DA neurogenesis in a PINK1-deficient, human tissue derived organoid model confirmed the initial observations."
> demonstrating that this gene has an effect on neurogenesis of human dopaminergic neurons from the substantia nigra.
But there is no neurogenesis of human dopaminergic neurons in the adult substantia nigra.
To create the organoid model, they used fibroblasts to generate induced pluripotent stem cells, and then differentiated these into neurons in culture. As an experimental model, this is fine, but it is not particularly indicative of actual human biology.
The most you could probably infer from this paper is that IF there were dopaminergic progenitors in the human substantia nigra (there aren't), they MIGHT respond this way if you deleted PINK1.
> But there is no neurogenesis of human dopaminergic neurons in the adult substantia nigra.
Two regions of the mature mammalian brain generate new neurons: (a) the border of the lateral ventricles of the brain (subventricular zone) and (b) the subgranular zone (SGZ) of the dentate gyrus of the hippocampus. [0]
In adult humans, neural progenitors migrate from the early postnatal SVZ into neocortical and striatal areas [1].
Indeed, as I wrote elsewhere. (I can't directly respond to your other comment, with which I also agree).
But there are two relevant questions: first, does this constitute orthotopic neurogenesis in any meaningful way? The progenitors are specified as interneurons in both the olfactory bulb or the dentate gyrus, certainly in the absence of any factors that encourage transition to a dopaminergic phenotype. Second, is there enough neurogenesis in the adult human brain for any purpose? Probably the most careful scientist in this space is Arturo Alvarez-Buylla, and his two Nature papers on postnatal neurogenesis in humans [0, 1] paint a fairly bleak picture.
> his two Nature papers on postnatal neurogenesis in humans [0, 1] paint a fairly bleak picture.
Science is neither bleak nor joyous. Science is just a process for uncovering facts, which may or may not hint at mechanisms that may or may not yield future possibilities.
The future is not writ yet.
Exercise-Mediated Neurogenesis in the Hippocampus via BDNF
In neurobiology, human in vivo studies are prohibitive from a cost, logistical, and ethical standpoint. But to anyone who can successfully parse a neurobiology paper this is assumed knowledge.
To return the goal posts to their original location, my premise was that the title "Parkinson's gene may impair how new neurons are made throughout our lifetime" is misleading, as the neurons in question are not actually made throughout our lifetimes. The referenced paper, which uses zebrafish and a somewhat contrived cell culture model, does not provide any new evidence about actual dopaminergic neurogenesis in humans. It is fair to say that if they'd actually demonstrated such neurogenesis actually occurs, with or without PINK1, the paper wouldn't have been published in just Scientific Reports.
Okay man, cool. Let me know when your open-brain Dr. Mephisto trials disproving adult DA neurogenesis are written up in Nature
Edit: the title’s not even misleading; “Parkinson’s” modifies “gene,” not “neurons” so it’s not even saying anything about the location of these neurons or when they are being created!
This has been a topic of intensive research for several decades [0]. In a nutshell, people have looked, repeatedly, and have failed to find very much.
There are two main stem cell populations in the brain, which produce new neurons in two discrete regions. One stem cell population is adjacent to the substantia nigra, but produces neurons which migrate to an entirely different region of the brain (involving a "cell highway" known as the rostral migratory stream). There are experimental ways to "misdirect" these new neurons towards the substantia nigra, but there have been no durable experimental or clinical successes. Furthermore, it is relatively straightforward to look for neural stem cells in brain tissue, and to my knowledge, none have been found in the substantia nigra per se.
In spite of the efforts, it is true that finding new neurons in the brain is very challenging, if for no other reason than that there are very few of them. One fascinating study from a few years ago actually used the elevated levels of atmospheric carbon-14 during the Cold War as a label with which to identify new neurons from the second stem cell population [1]. It's now considered that they greatly overestimated the number of new neurons, but it is still a seminal paper in the field.
> One stem cell population is adjacent to the substantia nigra, but produces neurons which migrate to an entirely different region of the brain (involving a "cell highway" known as the rostral migratory stream).
However, the migration can be demand driven, in response to disease conditions.
I've been taking magnesium l-threonate and l-theanine before bed, I seem to have more dreams and more intense dreams. I've seen both linked to neurogenesis.
Mg threonine/ate usually is taken in the morning because it crosses the brain barrier causing an active response. I can see why you have active dreams. Try changing your mg type for less active nights.
I see the "geopolitical" angle again and it's still not vindicated by this announcement. Nothing that Gelsinger said indicated he came to those decisions by seeing what was cookin' on the threat board:
> We are committed to ensuring this capacity will support commercial customers, as well as address unique government and security requirements in the U.S.
Geographic distribution makes a certain amount of business sense and getting those nice DoD contracts makes even more.
What doesn't make sense is China having Wing Attack Plan R ready to go against TSMC and Samsung.
Or possibly merely that high schoolers are incompletely socialised adolescents? Your own comments, e.g. "Teenagers love being edgy" show that you know this.
No need for the rebound accusation. If you're a teenager trying to be "edgy" it's not working.
How? A worm is a whole multicellular organism. A neuron's just a cell, one that's specialized into a single function.
All a single neuron does is pass a signal to the synaptic cleft in response to a chemical or electrical signal at the other end. It's a simple subunit of a larger system.
Saying a single neuron is more complex than a worm is like saying a cat6 ethernet cable is more complex than a blast furnace.
Just because a structure is larger and contains complex structures does not mean the larger system is more complex. For instance, I can create a logic gate with some friends. The logic gate is way simpler than the people composing it.
Neurons can have millions of mitochondria [1], which they dynamically move about the cell. Neurons are like amoeba with dozens of pseudopods when young. Amoeba are more complicated than worms, in terms of degrees of freedom, no?
> And in that planning the fact that TSMC’s foundries — and Samsung’s — are within easy reach of Chinese missiles is a major issue.
Are processor fabs analagous to auto factories and shipyards in World War II? Is the United States military's plan for a nuclear exchange with China dependent on a steady supply of cutting edge semiconductors? Even if it is, is that strategy really going to help?
This article is mostly concerened with Intel's stock price. Why bring this into it? Let's say Intel gets its mojo back and is producing cutting edge silicon at a level to compete with TSMC and supplying the Pentagon with all sorts of goodies... and then China nukes Taiwan? And now we cash in our Intel options just in time to see the flash and be projected as ash particles on a brick wall?
"The U.S. needs cutting edge fabs on U.S. soil" is true only if you believe the falied assumptions of the blue team during the Millenium Challenge, that electronic superiority is directly related to battlefield superiority. If semiconductors are the key to winning a war, why hasn't the U.S. won one lately?
And what does any of this have to do with Intel? Why are we dreaming up Dr. Strangelove scenarios? Is it just that some people are only comfortable with Keynesian stimulus if it's in the context of war procurement?
I don't feel that there is a meaningful TSMC alternative today. Samsung, Intel and GlobalFoundries are not suitable replacements for TSMC with regards to throughput or technology.
The world does need some meaningful fabs outside of Taiwan/South Korea. All of the <10nm semiconductor and most of the >10nm semiconductor fabrication takes place within a 750km/460mile radius circle today. That is risky.
Israel, Mexico, Germany, Canada, Japan (not that it would grow the circle much...) are all viable places to run a foundry. The fact that Intel is one of the few outside that circle doesn't inspire confidence in the security of the global supply chain.
One of the key misconceptions that I see repeated in the comments for this article is that lithography with sub-10nm feature size is somehow universally appropriate and preferable. This may be true for high-performance computing or other applications that are sensitive to the ratio of compute to price (or mobile consumer devices with a small thermal envelope), but it's not necessarily true for power electronics, automotive ICs, or missile control systems. Some of those chips aren't even made of silicon, instead being made of more expensive gallium nitride or gallium arsenide because of their thermal, high-frequency, radiation, and voltage properties.
I mostly agree that there isn't a great alternative to TSMC, but I would point out that the 2021 Qualcomm Snapdragon 888 processors are being made by Samsung with their 5nm process (in addition to their new Exynos 2100). Intel and GlobalFoundries aren't really replacements, but Samsung has been winning business for latest-generation flagship processors. Maybe it isn't as advanced as TSMC and maybe Samsung will have problems, but a lot of the 2021 flagship phones will be shipping with Samsung-manufactured 5nm processors.
It's still within that circle. Samsung is a great fab, probably the only real contender to TSMC. Samsung is 17% global semiconductor demand vs TSMC at 50%+. Included in that 17% is all of Samsung's demand (Exynos, SSD/storage, memory, etc).
Further agitating the issue, South-Korean SK-Hynix is buying Intel's nand business this year and will likely shift production out of intel's US fabs when it comes time.
> If semiconductors are the key to winning a war, why hasn't the U.S. won one lately?
Semiconductors aren’t going to help change people’s cultures or religion or tribal affiliations without decades of heavy investment in education and infrastructure, or other large scale wealth transfers.
But if “winning a war” means killing the opposing members while minimizing your own losses, surely electronic superiority will help.
>Some readers may ask why I am not considering the failures of the White House, and making the case that the President is also a joke.
Some readers implicitly understood why when the author presented the pricipal disaster of 2020 as the death of '1/4 of all small businesses' and bailed before 20k words of statue-avi rationalist faux-erudition gave them aneuryisms.
I believe the author was being ironic, as they essentially go on to make an argument based on intelligence (von Neuman, etc.). The tone here is also a light one.
