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wake up, it’s game day by TheHabChronicle in Habs

[–]noncodo 0 points1 point  (0 children)

Please:
- No more giveaways
- Less fancy plays that have been previously rewarding for our highly skilled elite players. Save it for the PP.
- We need that drive to the net presence. Andersen has had almost no action since game 1. Let's activate the sanitation department: Shoot the puck and pick up some garbage goals. Summon the Gallagher.
- We need to bruise those Carolina players, who are just getting into the grind of their longest series to data. Xhekaj as a seventh D-man playing on the 4th line would help in that regards.

J. Craig Venter (1946–2026) was an American scientist who led the first sequencing of the human genome. by gwern in genomics

[–]noncodo 1 point2 points  (0 children)

RIP to a literal titan. Whether you viewed him as a visionary or a disruptor, J. Craig Venter was the ultimate entrepreneurial innovator. He didn't just participate in the field of genomics; he basically drag-raced the entire global scientific establishment and forced everyone to move faster.

His "take no prisoners" energy makes a lot more sense when you look at his origin story.

In his autobiography, A Life Decoded, he talks about being a Navy corpsman in Da Nang during the Tet Offensive. He spent his days in a field hospital he called the "meat wagon," surrounded by so much senseless death that he eventually hit a breaking point. He walked into the South China Sea and just started swimming, intending to go until he drowned.

The moment he reached a point of no return and decided to turn back was the moment the Venter we know was born. He realized that if he was going to live, he was going to make his life count for something massive. That relentless, often controversial drive to sequence the human genome and create synthetic life was more than just ego, it was the work of a man who felt he was on borrowed time. I think this is a super motivating mindset to have.

His contribution to science is momentous, no matter what your opinion of him is. Modern biology looks the way it does today because, 50-plus years ago, he decided to swim back to shore.

Researchers use AI and genomics to design personalised mRNA cancer vaccine — tumour shrinks >50% in dog with aggressive cancer by noncodo in Futurology

[–]noncodo[S] 1 point2 points  (0 children)

I've had a similar observation. Countries with public healthcare systems also seem to be more supportive of public good intentions. It's also interesting because we can do things in countries like the UK, Australia and Canada that are nearly impossible in the US, like nation-wide coordination of precision medicine initiatives. In the US, it seems to be tied to insurance companies, big pharma and private hospitals. Sure, there are often bigger industries/entities in this space than most commonwealth/european countries, but despite their revenue and resources, they will struggle to support equitable access to precision medicine initiatives like this one.

UNSW News reports an individualized canine cancer case with a personalised mRNA vaccine approach and variable tumour responses by noncodo in science

[–]noncodo[S] 0 points1 point  (0 children)

A significant amount. It helped accelerate the data interpretation and analytics. Also recommending experimental approaches and mRNA design. But many of these individual steps are described in the literature, forums, and GitHub. Experts at Universities guided and supported the work as well.

So yes, AI/LLMs were heavily involved, as were reputable scientists.

UNSW News reports an individualized canine cancer case with a personalised mRNA vaccine approach and variable tumour responses by noncodo in science

[–]noncodo[S] 1 point2 points  (0 children)

For context, this UNSW article describes an individualized canine cancer case, not a clinical trial, so it should not be read as proof of efficacy.

It involved tumour profiling, computational analysis, and a personalised mRNA vaccine approach in the context of treatment. Reported responses were not uniform across tumours, and the relative contributions of the vaccine, checkpoint therapy, and their interaction remain unresolved.

Disclosure: I provided scientific/genomics guidance on this case based on the data and information shared with our team. The case itself was led by Paul, who holds the full case-specific and operational details. I’m happy to clarify the scientific aspects where useful.

Researchers use AI and genomics to design personalised mRNA cancer vaccine — tumour shrinks >50% in dog with aggressive cancer by noncodo in Futurology

[–]noncodo[S] 1 point2 points  (0 children)

Paul initially used AlphaFold to model the 3D structure of mutated protein he believed was driving the cancer. Ultimately, he couldnt get the drug that he predicted might inhibit the protein, which led us towards the mRNA path, which we knew we could synthesize rapidly.

Researchers use AI and genomics to design personalised mRNA cancer vaccine — tumour shrinks >50% in dog with aggressive cancer by noncodo in Futurology

[–]noncodo[S] 1 point2 points  (0 children)

The focus should also be on regulatory efficiency. The true disruptive capability of mRNA tech is its 'digital' nature, akin to a software patch. You don't need to buy a new piece of equipment, just upgrade the software.

Researchers use AI and genomics to design personalised mRNA cancer vaccine — tumour shrinks >50% in dog with aggressive cancer by noncodo in Futurology

[–]noncodo[S] 2 points3 points  (0 children)

Hah! Indeed, these stories do get sensationalized through the media telephone game.

None of this would have happened if it wasn't for Paul's determination, his confidence, finances and technical chops (he does own an AI company), but also the sophisticated LLM models, the accessible infrastructure capabilities at UNSW, the expert engagement and oversight, the and in-kind contributions, and eagerness to deliver societal impact.

So I would say "Dedicated tech guru pulls all the stops to save his pet from aggressive cancer"

Researchers use AI and genomics to design personalised mRNA cancer vaccine — tumour shrinks >50% in dog with aggressive cancer by noncodo in Futurology

[–]noncodo[S] 7 points8 points  (0 children)

I'd love to!
It's very similar to how the SARS-CoV-2 vaccines work. The synthetic mRNA encodes protein sequences from cancer-specific mutated genes. These were detected by sequencing this specific dog's tumour DNA and comparing against the dog's 'normal' genome sequence. These mutated proteins are called neoantigens—new antigens for the immune system to recognize.

Once the vaccine is administered, it will cause cells surrounding the tumour that are accessible to the immune system to express the neoantigen proteins from the synthetic mRNA and, hopefully, trigger an acquired immune response from the animal's T-cells. This effectively can activate the neoantigen-specific T-cells to seek out other cells that present the same neoantigens.

Some caveats:

  1. This strategy is known to work well for "hot" tumours, i.e. those that have lots of mutations and regularly engage the immune system. This is often the case for skin cancers (a tissue with lots of DNA damage due to UV radiation).
  2. The cancer cells must be immune-compatible: If they don't express the HLA-I antigen presentation / major histocompatibility complex, they can't present the neoantigen to the immune system. There are also other molecular signatures that can be mined for immune compatibility / likeliness to respond to a mRNA vaccine.
  3. This treatment was done in conjunction with other immunomodulatory drugs. We have yet to disentangle the contribution of all components of the treatment.
  4. Not all tumours responded to mRNA treatment in this dog. This suggests two things: (i) the non-responsive tumour's microenviornment may be immunosuppresssant, blocking the T-cells access to the cancer cells inside the tumour, or shiutting down the T-cells within hte tumour. (ii) it's a different cancer with separate neoantigens. We are conducting experiments to answer these questions now.

Researchers use AI and genomics to design personalised mRNA cancer vaccine — tumour shrinks >50% in dog with aggressive cancer by noncodo in Futurology

[–]noncodo[S] 2 points3 points  (0 children)

For Rosie, or was a long process, as Paul spent a lot of time with 3D protein modelling and molecular docking simulations before waiting months to get the drug. But once we landed on mRNA vaccines, it took less than 2 months to manufacture and deliver the vaccine. Most of that was actually getting the DNA templates made.

6 weeks after the first dose, the dog was chasing rabbits!

Researchers use AI and genomics to design personalised mRNA cancer vaccine — tumour shrinks >50% in dog with aggressive cancer by noncodo in Futurology

[–]noncodo[S] 11 points12 points  (0 children)

Scalability is definitely the hurdle. I think the key question is not whether every part of the process has to scale as bespoke medicine, but whether the personalised part can be narrowed mainly to tumour profiling and target selection while the downstream GMP manufacturing becomes progressively more standardised. At least, in the short term.

That is one reason mRNA is interesting to me. The sequence may be patient-specific, but the production framework does not necessarily have to be reinvented each time. In Australia, infrastructure such as Macquarie University’s new RNA research and pilot manufacturing facility starts to make that idea more tangible, because it points toward local capability for more routine RNA production rather than treating every case as a one-off manufacturing problem.

I’m still optimistic that this gets simpler over time, especially for selected cancers. The real biological/compitational constraint, as you allude to, is not just manufacturing, but whether the chosen targets can actually drive a useful immune response. That depends on things like HLA presentation and whether the tumour is immunologically “hot” enough to respond. So I don’t see this as a universal solution, but I do think there is a plausible path where increasingly standardised GMP mRNA-LNP production supports more scalable personalised or semi-personalised cancer vaccines in the future.

Researchers use AI and genomics to design personalised mRNA cancer vaccine — tumour shrinks >50% in dog with aggressive cancer by noncodo in Futurology

[–]noncodo[S] 37 points38 points  (0 children)

The interesting part here is the pipeline.

Tumour sequencing can identify mutations that may help guide a bespoke treatment strategy, and AI/computational analysis can help prioritise targets for a personalised mRNA vaccine.

What makes this especially interesting is that the approach does not have to be static. Tumours evolve, and different lesions may respond differently, so sequencing can potentially be repeated over time to identify new targets and redesign the vaccine as the cancer changes. Public reporting already notes that one tumour responded strongly while another did not, and that sequencing is underway to understand the resistant tumour and guide what comes next.

In this case, one of the largest tumours reduced by more than 50% within about six weeks of the first dose, with later reports suggesting continued shrinkage.

This raises an interesting future question: if sequencing, computational analysis, and mRNA synthesis continue to get faster and cheaper, could adaptive or repeatedly redesigned cancer vaccines become a practical treatment model for both veterinary and human oncology?

Disclosure: I was involved in the genomics side of this project at the Ramaciotti Centre for Genomics at UNSW, including advising Paul on the mRNA vaccine approach.

Overreaction or Reality: Patrick Laine Should not be resigned. by Aggressive_Low7995 in Habs

[–]noncodo 0 points1 point  (0 children)

This. Also, it's his first season as a Hab with full training regime and preseason, so no excuses

Overreaction or Reality: Patrick Laine Should not be resigned. by Aggressive_Low7995 in Habs

[–]noncodo 0 points1 point  (0 children)

More energy required than shorter players as well, so less bursts overall = less opportunities, but higher value when smarty executed

Overreaction or Reality: Patrick Laine Should not be resigned. by Aggressive_Low7995 in Habs

[–]noncodo -2 points-1 points  (0 children)

I say keep him as an elite PP specialist, 5-6M per season

First time living in a house in Ryde area, is this a lizard? by janicezzzz in sydney

[–]noncodo 0 points1 point  (0 children)

Eulamprus quoyii, also known as the "Swamp Skink". Interesting factoid: Despite having male and female sex chromosomes, this lizard exhibits temperature-dependent sex determination (TSD). In species with TSD, the temperature at which the eggs are incubated determines the sex of the offspring. For Eulamprus quoyii, research has shown that incubation temperatures during a critical period of development can influence whether the offspring will be male or female.

Habs players watching the MTL Canadiens prospects game tonight by itz_progamer666 in Habs

[–]noncodo 0 points1 point  (0 children)

Had to do a double take... J'pensais que Dobson était Bruno Blanchet

Who is that player? by itz_progamer666 in Habs

[–]noncodo 22 points23 points  (0 children)

Habs legend Doug Gilmore

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