The mitochondria in many cancer cell behave abberantly. For example, in many cases, they can start promoting glycolysis, in process known as the Warburg effect. They're also involved in other processes such as apoptosis and cell migration. I'd hypothesize that these drugs target pathways or processes that are dysregulated in the mitochondria of those cancers.
I think this is a very cynical take. Patients with gastric cancer are often in a dire situation: many of them have had their stomach removed and have generally significant difficulties with digestion, which makes consuming specific foods very difficult. The therapeutically effective doses of ATRA are also high compared to what you'd get from foods, meaning that injections are nearly the only solution for these patients. Finally, naturally derived compounds generally have the weakest patents, so if anything, we should thank these researchers for looking into the therapeutic potential of these drugs. I can assure you that few pharmaceutical companies would research this, as the commercial incentives are really weak to do so.
I work in drug discovery (including in oncological indications), so it's always great to see new research with early, promising results!
To summarize the paper: some gastric cancer models are sensitive to all-trans retinoic acid (ATRA). ATRA is an active metabolite of vitamin A, and is already used clinically to treat some hematological cancers. The researchers tested the compound at several concentrations on a number of gastric cancer cell lines, where they show moderate to significant reductions in growth (from 30% to 60% reduction). Next, they tested ATRA on xenografted tumor cells on immuno-compromised mice, where they also show a reduction in tumor size. They hypothesize that ATRA exerts its effects through immuno-modulation.
Firstly, very cool, and congrats to the authors - I definitely see first evidence of the potential of ATRA to treat gastric cancer.
While I might have misunderstood some parts, I do think there are some elements that warrant precautions here: 1. we can see that some of the untreated mice also show reduction in tumor size, albeit less significant, meaning there could be issues with the cells or protocol, 2. I find it hard to conclude anything about ATRA exerting its effect through the immune system in a study of cell models and immuno-compromised mice.
Nevertheless, given the frankly poor prognosis of gastric cancer (many patients in early stages of the disease now get their stomach removed, and more often than not, these tumors metastize aggressively), and the well known safety profile of ATRA, I think the study is very welcome, and should warrant further investigation. Given the hypothesized mechanism of action, I think testing on humanized mice, using more and more distinct patient-derived cells would bring convincing proof to move ATRA forward to clinical trials.
While I agree with the general sentiment of your message, there are quite a few meta-analyses on pubmed on the long-term safety and efficacy of gastric bypass surgery. They mostly show that while some patients do end up back obese, the majority do improve on many markers of health (weight, diabetes, ...).
Here's an example of a study if you're interested [1]!
I just tested the model [1] using an RTX3090, trying to translate a french text I found here [2].
Some observations:
- The full translation of the 6:22 minute video takes about 22 seconds (17x real time)
- It recognizes the language by default (and did a good job to recognize it was french audio)
- MIT License [3]!
- The quality of the transcription is good, but not perfect.
- The quality of the translation (if you don't consider transcription errors as a translation error) is generally very good.
---
The transcription:
> Bonjour à tous, <error>j'suis</error> espère que vous allez bien, c''est ENTI. Et aujourd', <error>aujourd',</error> on se retrouve <error>un peu physique</error> pour parler de la termo dynamique. Vous ne vous inquiétez pas, ça va bien se passer. On va y aller ensemble, <error>être à par exemple,</error> je vous accompagne à travers une série de vidéos pour vous expliquer les principes de base en termo dynamique. Et bah, c''est parti, on va y aller tranquillement. Lidée, c''est vous puissiez comprendre la termo dynamique dans son ensemble. Donc, je vais vraiment prendre mon temps pour <error>couplisser</error> bien comprendre les notions,
The translation:
> Hello everyone, I hope you're doing well, it's NT and today we find ourselves a little physical to talk about the thermo dynamic. Don't worry, it's going well, we're going to go together and be the same. I'm going to accompany you through a series of videos to explain the basic principles in thermo dynamic. Well, let's go, <error>we're going to go quietly</error>. The idea is that you can understand the thermo dynamic <error>in sound together</error>. So I'm really going to take my time to understand the notions,
---
All in all very happy that OpenAI is publishing their models. If Stable Diffusion is any guide, people will hack some crazy things with this.
It also runs well on a CPU and seems to have proper memory management. Wonderful timing because I was using DeepSpeech for some audio recordings and it required me to script up a splitter to make the files into .wav and then do snippets of 10 seconds each. Everything about this just works out of the box. On a core i5 I'm getting about 30 seconds every minute. Transcriptionist jobs just turned into editor jobs. I love how it drops the inflections in the audio as well, because it was trained on transcription work, and that is one of the first things you learn to do (drop the uhs and ums and huhs etc, unless it is a strictly verbose transcription).
That's hilarious and honestly, incredibly bad. "Dans son ensemble" is a very common idiom (meaning "as a whole") while "in sound together" has to be pretty rare. "Son" means "his/hers/its" as well as "sound", and the former meaning is probably more common in general so I have no idea how this result could arise.
"Termo" also doesn't exist in French, it's "thermo", so the transcript even makes orthographic errors.
And I forgot about "couplisser" which is also a hilarious made-up word that sounds like it could mean something, but doesn't! Edit Google finds exactly one reference of this, in a patent with a typo on the word "coulisser".
I'm still impressed by the transcript quality since it covers many languages, but the translation part is quite poor.
Was this with the `base` model? `large` is running ok on a P100 in colab, but is about 4% the speed of `base.en`. Certainly seems like some of these models will be fast enough for real-time.
I installed Whisper (and, I thought all the needed dependencies), and had it running on my M1 Max MacBook Pro with 64 GB ram, but it ran TERRIBLY slowly... taking an hour to do a couple of minutes...
I found this thread and wondered if Whisper was accessing all the cores or the gpu, so I've spent a couple of hours trying to get whisper to access the gpu - following the points made in this thread, and googling how to install via brew the various components.
Long story short, I keep getting an error message
"RuntimeError: Attempting to deserialize object on a CUDA device but torch.cuda.is_available() is False. If you are running on a CPU-only machine, please use torch.load with map_location=torch.device('cpu') to map your storages to the CPU."
or when I set --device to gpu, it get the error:
"RuntimeError: don't know how to restore data location of torch.storage._UntypedStorage (tagged with gpu)"
it's been a looong time since I wrote any code (remember basic?), so realise I may be missing a lot here!!
does anyone have any pointers?
thanks!
edit: I'm now trying it one more time after trying to set the cpu using this line:
map_location=torch.device('gpu')
and I get this message as whisper begins:
~/opt/anaconda3/lib/python3.9/site-packages/whisper/transcribe.py:78: UserWarning: FP16 is not supported on CPU; using FP32 instead
warnings.warn("FP16 is not supported on CPU; using FP32 instead")
then I wait for whisper to do it's magic ...tho it looks like it will remain very slow...
This [1] study was pretty thorough on different fasting lengths. They tested 1422 patients for fasting lengths between 4 and 21 days, with a maximum calorie consumption of 200-250kcal and a moderate-intensity lifestyle program.
It concludes that all fasting lengths are beneficial, and are likely going to result in a) reduction in weight and waist circumference, b) beneficial effects on blood lipids, regulation of sugar and other blood-related parameters, including lower blood sugars and higher ketone body levels, c) an increase in physical and emotional well-being and absence of hunger, d) a high probability of decrease of pre-existing health-complaints, e) very limited chance of side-effects.
To build on this post it is further beneficial to understand the importance of the interaction between clock genes and nutrient intake timing for optimal results
You can order these drugs in bulk from chemical vendors for research purposes (i.e. non-human use). Chemscene, to name just one, sells Rapamacyn at 1440 USD for 5g.
EDIT: I clearly don't recommend you buying this and taking it by the way. You're never quite sure about the purity nor about how to dose this effectively as a layperson without access to a lab. It's also possibly completely illegal, depending on your local laws.
Yeah. By the time you're looking at stuff in the milligram range it becomes quite problematic to ensure consistent doses. I would be confident that I could get an *average* of 1mg/day but I would not be confident I could ensure every day was in .9mg to 1.1mg.
- One of the strategies in drug development is to find a protein that is more present in people who have a disease versus those who don't (called "overexpressed" proteins), and attempt to stop this protein from work correctly (called "inhibition") by having a small molecule drugs that binds to a specific site of the protein (called the "allosteric site") in order to make it mechanically unable to execute its function.
- Cyclin-dependent protein kinases (CDKs) are a family of proteins that seem to play important roles in controlling cell division. CDK20 is overexpressed in a number of cancers.
Regarding the novelty:
- Discovering new inhibitors of proteins based on AI is definitely less novel than it was 5 years ago - while it's definitely still not the norm, AI is making big waves in the pharmaceutical industry. However, I think this might be the first publication validating the use of Alphafold for small molecule drug development, which is a major step forward.
- While it's interesting to see that it's possible to design a small-molecule CDK20 inhibitor, it's currently still very uncertain whether this is a promising drug: i. the compound could be insufficiently specific to CDK20 and could bind to other important proteins and cause unwanted and potentially serious side-effects, ii. the compound could have bad "drug-like" properties (e.g. bioaccumulate in the liver) or be toxic in some way, iii. the compound could interact badly with other drugs that cancer patients receive, iv. the compound could induce resistance (a common problem in small molecule drugs in oncology), and finally, and most importantly, v. the drug might just not be effective at treating cancer or any other diseases - it's not because a protein is over-expressed that it's the cause of a cancer, but rather a symptom of another biological dysregulation.
Still, it's definitely an achievement, and I applaud the efforts of the team and hope they'll find successful treatments.
Most NFTs are like a title to a house. Like a title to a house, you can:
1. Prove you own it;
2. Sell it to someone.
Unlike the title to a house:
1. The party certifying your ownership is not the government, but the consensus rules of a blockchain;
2. The thing you own is not physical, but digital in nature;
3. Your ownership does not prevent anyone from copying the file itself for their own uses.
Regarding your point that the object you own might not be consistent: because of the cost relative of storing data on a blockchain, the actual digital thing you own isn't usually stored on the blockchain, but a hash of that file (e.g. [1]). Unless hashing is broken, this is cryptographic proof that the object does remain consistent.
Ah but the government will enforce my claim on the house if I’m holding (rightfully) the title. And if someone steals the title, it doesn’t mean they own my house.
You can prove that you own it (the NFT, not something else), which could be used for authentication systems. You could rent/lend it out, could also be used for subscriptions or whatever. Or you could sell it.
Basically, imagine a certificate you have on your computer, except it's publicly known, then imagine use cases based on that.
Yeah, there's another top level thread that helped me understand that a bit better: not all NFTs are art NFTs.
Which is to say that I think the problem is less that NFTs are inherently worthless and more that the crypto community desperately needs to reclaim the brand from the speculators, if there's even anyone else left.
For all the cool applications that there might be for blockchain, the only ones that seem to gain traction are the ones that involve highly speculative investment machines. NFTs have been no different, and it's this tendency that makes many people very uncomfortable with anything involving crypto.
You have to realize that this is not a defense in NFTs as they are being discussed.
The discussion is art NFTs being worthless (or not). Coming in and saying “yeah, but not all NFTs are about art” it’s not helpful. If you think that art NFTs are stupid but the underlying tech has promise, then say that. Don’t defend “NFTs” because that looks like you’re defending the value of the current ones actually being discussed.
Engaging in a semantic argument just muddies the whole issue and looks like you’re defending something you are not.
What can you do with a bank account, a book you wrote, a patent you own, an image you shot? Immaterial objects and intellectual property is not new. And NFTs are not that innovative or special in that regard.
All of those examples are backed by the state, who has the authority and power to investigate, litigate, fine, and arrest those who violate their rules. NFTs don't provide that. There's just the promise that, eventually, people will respect other people's NFT ownership... for some reason.
The laws of the country you live in have answers to those questions. Usually, you are the only person legally allowed to use your bank account. Nobody else is legally allowed to publish your book under their name, etc. There are no laws protecting "ownership" of NFTs
Whether title to a house, or entry ticket to a concert, those give you a practical, real world ability to do something. You can live in the house (or allow someone else to and charge them rent), and the government will defend this right for you. You can do neither things if you don't own the house. (well maybe you can live in it if you pay rent to someone who does) You can attend the concert if you have a ticket.
If you own an NFT, you get no practical real world benefits.
You're taking a lot of flak here, but I think you're basically correct. (Even if cross-game NFTs never become a thing.)
The debate reminds me of when Napster looked, to many, like it would end the sales of pre-recorded music, since music can be copied identically for free. Obviously such predictions turned out to be wrong.
I think they would have turned out to be right if there was no such thing as copyright law. But there is. People were prosecuted, and over time the prosecutions made a difference. They helped it make sense to invest money in creating well-designed, easy-to-use streaming services. And in the end, for most people, it was more convenient and risk-free to get music from such services than to pirate it. It was worth the cost.
Over time, if people spend real money on NFTs, the legal system will evolve to better protect people's purchases. For now, if two people claim to be the creator of a given artwork which is the subject of an NFT, and create two NFTs, only one of them will have the actual copyright. That should provide a basis for legal action.
As I said, I'm not sure cross-game NFTs will ever get past the hype stage. But I have been to a museum where truly beautiful NFT art was on display. I haven't bought any art in many years but I can certainly imagine that my next art purchase could be that kind of NFT. By purchasing it, I am helping the creator in "1000 True Fans"[1] manner, and I am, in the creator's view, which is the only one with any legitimacy when it comes to digital art, the "owner". (Even if I am the second or third purchaser of an NFT, the fact that the original purchaser knew he could sell it to someone like me is part of why he purchased it, so I have helped create the environment where that original purchase could happen.)
While it's true that people can make copies that are identical, people can also make copies of the Mona Lisa that can't be distinguished by anyone but specialists. To the normal person, they would appear to be identical. It isn't what they look like that matters. It's the legitimacy: which is the legitimate Leonardo Da Vinci? It's the one he personally made (and/or was made in his studio by other people under his direction). It has nothing to do with how it looks to the average person.
To one degree or another, these issues of legitimacy and helping the artist will have an affect and give value to NFTs of real art.
I'd also be willing to bet that there will be a long-term market for "collectibles" for the same reason there is for baseball cards. If someone were to make an identical copy of an original Mickey Mantle baseball card, it would have no value. Only the original does, and only because the purchasers believes it is the original, and therefore legitimate, card. The mechanism for NFT legitimacy is different, but there is no reason to assume that that mechanism will not create persistent value over time. It is unclear now how much value it will create. But it would be wrong to just dismiss it at this early stage.
Took me a while to wrap my head around the `baseball card analogy` but I've come to the conclusion that if they can be used to perceptively represent NFT's then pragmatically, the `serial number of the card` (or the object's metadata) is what you own as recorded on the blockchain and not the object itself.
I worked in the same co-working space as Wietse, Aline and Koen, the three co-founders of Citizenlab, when they were launching their service. They're a super competent team with a fantastic vision and execution - I'm excited to see this new step in their story.
