HN user
Related, I recently read an article about staghorn corals surviving in Miami of all places [1]. They resisted bleaching, pollution and inundations with fresh water. The origin of this resistance is apparently colonization by a different species of algae that is otherwise native to the western Pacific and Indian Oceans.
[1] https://www.biographic.com/the-corals-that-shouldnt-exist/
I can't imagine that the same factors aren't at play in the scientific research community
I can't speak for the entire scientific research community, but I can say that for basic biomedical research (not clinical research), LLMs are mostly ignored. They simply don't have the ability to parse most raw wet lab data.
This obviously has not stopped the creation of a legion of startups, new Asst Profs, etc, claiming that they are using "AI" to crack new frontiers. In practice, the most effective of these use machine learning, rather than LLMs.
“We can do neuroscience on A.I. systems in a way that we kind of can’t with humans,” Mr. Long said, in that they “don’t have skulls.” The three jobs Eleos was hiring for would all be machine-learning research scientists who could design and perform experiments.
This is pretty interesting! I wouldn't know how easy such "surgery" on LLMs would be to do, if if they do have "knowledge" or "consciousness" as their proponents claim, there could be some profound outcomes from this.
I would have thought that the right to privacy as a fundamental human right would have been sufficient. But apparently not....
Equally, there is abundant precedent for forbidding interference with old-fashioned postal communications, that seemingly doesn't translate to electronic communications...
There's a risk of echos of Theranos here. A paper apparently describing this ultrasound approach has been uploaded to arXiv [0]. If so, the resolution demonstrated is nowhere near sufficient to detect small changes to anatomy, let alone monitor them over time. Future developments could obviously improve on that.
[0] “Whole Cross-Sectional Human Ultrasound Tomography” https://arxiv.org/pdf/2307.00110
This prompted me to check out rental rates in my old haunt of Inner Sunset. I remember the Craigslist offices on 9th and Judah...
It's shocking that a 1 bedroom apartment now rents for $4-5k/month....
You will notice that the criticism this judgement receives if not for finding Song guilty, even if the sentence is inordinately long for a non-lethal crime with minor wider repercussions.
The criticism this judgement receives is the fact that the prosecutors and judge drew these lines of association into a "terrorist organization" so much that even merely possessing literature tangentially related to this non-existent "organization" was deemed a crime worthy of 30 years imprisonment. This is the sort of thinking that sent people to the Soviet Gulags.
It's kind of fact-based that "antifa" is not an organization in the real world.
It's as real as claiming that "pro-gun" is an organization, or "anti-pollution" is an organization.
The zines are only evidence of Rueda's political opinions, not of intent to carry out a crime.
First, there's no "terrorist organization". Antifa doesn't exist as an organization.
Second, the zines cannot be evidence of the crimes committed, i.e. setting off fireworks, and injuring an officer.
The crimes here are the injuring of an officer, and causing a disturbance near the ICE facility.
How could the zines be evidence for those crimes?
At worst, the zines are evidence of Rueda's political opinions. They are not evidence of conspiracy to set off fireworks near the compound, nor shoot an officer.
I noticed the prominence of celery, which might surprise a modern diner. I had reason some years ago to look into this and the history is interesting. Celery was at one time difficult to cultivate, growing only in select marshlands. In the absence of refrigeration it was also difficult to transport to city diners, so was considered a delicacy.
This also lead to the production of specific table items intended to display celery such as the vase shown in the menus above.
This is referred to as shifting the Overton window. If voices from the extreme are not heard, the Overton window moves away from their position, so protests help their cause even if only a minority completely agree with them.
Very well-written!
I wonder if the inaccurate representation of colors by screens, etc, in any way underlies the distinctive color palette of many AI image generators?
Twitter can make a "Kid's Twitter" (Kitter? Kidder?) if it wants. It's far less oppressive than forcing people to reveal their identity to Twitter.
A system as above would matter only to sites that want children among their audience.
Those that don't, or don't care, would not seek a rating, and would not be accessible to devices that parents control. Otherwise they would be free to host whatever legal content they wish.
A right to privacy is one of the fundamental human rights.
Kids don't need Twitter.
There would obviously arise a market for a moderated, or more regulated, version of this type of social media.
Social media doesn't deserve an exemption from the efforts society makes to protect children in other domains.
Mixed content would have to be tagged as such.
Mixed content isn't a problem for broadcast TV or newspapers. They simply avoid publishing material not appropriate for children, e.g. broadcast news programs don't show gore, even when a place has been bombed and is littered with body parts.
How many 10 yr olds are going to read a academic article on transgender studies?
And if they are curious about the question, it would be better if they found sources that frame the issue appropriately for their age.
It would be a ban only to children. "Addictive" sites without certification could still be accessed by those who are no longer their parent's responsibility.
The same problem exists for almost any product that might be a risk to children, from cleaning products to "adult" literature.
Parents would be much more able to restrict the devices a child has access to (or its controls) than the websites they visit (absent website certification).
Surveillance of who by whom? Requiring identity disclosure guarantees surveillance.
Even when cigarettes were smoked by ~50% of the adult population, there were restrictions on sales to children. Why can we not accept the same for websites?
Would someone be able to comment on this:
Why is it not possible to require websites that wish to market to children to be certified as "child safe". Such sites would be audited by an independent entity that would grant them some form of encrypted key. These could be in age bands, e.g. <6yr, <12 yrs, <16 yrs, etc. also also possibly geographically.
We do this for many other things, from toys to public venues.
Parents could then set their child's device to only allow access to sites with the appropriate certification.
This way the children are as safe as their parents allow them to be, without sharing their child's identity, and the rest of the population also doesn't have to share their identity with dubious authentication service or the government.
There's probably something wrong with this idea, if so I'd be glad to hear it!
Thanks for the article.
I actually read your article some time ago, having found it via SSC. One comment I would make is that the pathology and genetics of AD implicate APP without much doubt. In the field, there isn't much argument against it, even by those who work on tau. Divergences in opinion more often focus on which is the better target for drug therapy.
For example, Derek Lowe's articles on AD do not argue against an APP-tau-neurodegeneration pathway (I am a regular reader of his blog), but argue that targeting amyloid is unlikely to work as a drug therapy. This argument is sometimes extended by Lowe and others to questioning whether Aβ per se is the agent that triggers the downstream effects of either mutating APP or otherwise disrupting its biology. It is possible that Aβ is a by-product of the "true" APP-triggered pathway, see the arguments in favor of C-terminal fragments I linked to earlier.
A fundamental problem the field faces is that it is difficult to experimentally induce actual AD in animals, and so it is difficult to scientifically test hypotheses as to what might cause it. Compare perhaps to something like diabetes. Exactly why mice do not develop realistic AD is unknown.
In addition, there have been literally hundreds of publications (minimum 300) claiming to reverse "Alzheimer's disease" in mice, and the only ones that have lead to any kind of meager success are those using the antibodies. The arguments made in the 2010 review below by Zahs and Ashe [0] remain mostly true sixteen years later.
The recent clinical trials, e.g. Lecanemab, are of interest not only because they might provide at least some benefit, but also because they might represent the first actual scientific experiments showing that removing Aβ can ameliorate the disease, even if only slightly because of the late stage at which they have so far been tested.
Currently ongoing trials using anti-Aβ antibodies and targeting earlier phases of the disease in those with inherited mutations are of keen interest. If these demonstrate clear prevention of disease progression, then the Aβ hypothesis can be considered tested and proven. If not, then the Aβ hypothesis should be abandoned. This would however still not disprove an APP-focused hypothesis.
[0] 'Too much good news' - are Alzheimer mouse models trying to tell us how to prevent, not cure, Alzheimer's disease? https://alzped.nia.nih.gov/sites/default/files/2022-09/zahs....
P.S.
As you have demonstrated an interest in this topic, but are not an active researcher, I suggest that you become familiar with Alzforum [www.alzforum.org]. It provides reputable summaries and comments from leading researchers on topical issues and papers in Alzheimer's and related neurodegenerative diseases.
They're still fairly technical, but not as dense as the original papers. Here is an example related to our discussion: https://www.alzforum.org/news/research-news/app-c-terminal-f...
No APP-alone mouse gets neurodegeneration resembling that seen in the human AD brain, i.e. with so-called "neuritic" plaques, tauopathy, spongiopathy and widespread neuronal death.
This is why researchers now most often use the 5XFAD mouse, which has APP with three mutations, and presenilin with two mutations (hence 5 FAD mutations) [0]. Note however that mutated presenilin alone is enough to cause neurodegeneration in mice, such mice however do not accumulate amyloid, which is why mutated APP in added to make the pathology more "realistic".
As to Aβ42, there are mutations in APP which cause familial AD, but produce exclusively Aβ40, e.g. APP A673V [1]. Note also that most studies report alterations in the ratio of Aβ42 to Aβ40, precisely because effects on the levels of Aβ production are inconsistent across APP mutations.
Nevertheless..... and despite my obvious skepticism towards the amyloid toxicity hypothesis, the mutations in APP that cause AD all cluster in or near the region of the protein that is Aβ. There must be a reason for that. It is also in contrast to presenilin, where the mutations are distributed throughout the molecule, indication a loss of presenilin function causes AD.
One alternate explanation to Aβ or oligomer toxicity is proposed toxicity of the immediate precursor to Aβ, i.e. the APP C-terminal fragment (CTF), see for example the recent paper below and references therein [2].
[0] https://www.alzforum.org/research-models/5xfad-b6sjl
[1] A Recessive Mutation in the APP Gene with Dominant-Negative Effect on Amyloidogenesis https://pmc.ncbi.nlm.nih.gov/articles/PMC2728497/
[2] APP β-CTF triggers cell-autonomous synaptic toxicity independent of Aβ https://pmc.ncbi.nlm.nih.gov/articles/PMC12017768/
These points still don't explain how mutations in APP cause AD.
Note that not all AD-causing mutations in APP also cause amyloid accumulation, for example APP-Osaka (loss of APP residue E693) results in familial AD without any accumulation of amyloid [0]. (One can ignore claims that this mutation increases Abeta oligomers, since the evidence is that Abeta oligomers are found at far too low concentrations in the human brain. They would have to be more toxic than ricin if they were etiological for AD). The oligomers seen on gels are an artefact, see the controversy surrounding Tessier-Lavigne).
As you state, and I agree, APP is upstream of tau in natural AD pathogenesis, but does not cause neurodegeneration in mice. So we still don't know from direct experimentation how APP leads to tauopathy and neuodegeneration. The evidence that this is through Abeta per se is tentative at best.
[0] A Second Pedigree with Amyloid-less Familial Alzheimer’s Disease Harboring an Identical Mutation in the Amyloid Precursor Protein Gene (E693delta) https://pubmed.ncbi.nlm.nih.gov/25743013/
Yes, there is a clear sequence of how AD pathology develops, starting with amyloidopathy and progressing to tauopathy, but 1) there is as yet no established molecular connection between the two, and 2) one should not conflate pathology with disease mechanisms.
So, taking the amyloid hypothesis itself (putting presenilin aside for the time being).
We know that mutations in APP do cause AD. How? And if amyloid is not the "proximate" cause of AD, how do mutations in APP cause AD? Include in this Down syndrome, where >90% of cases develop early onset AD by age 50. They have an extra copy of APP that is not mutated.
Furthermore, people can accumulate large amounts of amyloid in the brain without having any notable dementia.
Adding tau to the equation does not help much in explaining how APP mutations cause AD. All people have tau. Furthermore, mutations in tau do not cause AD, they cause different neurodegenerative diseases (e.g. frontotemporal dementia).
Combining APP mutations with presenilin mutation and/or tau mutations in mice does lead to worse outcomes, but the same could be said for combining any other random set of neurodegeneration-associated gene mutations.