Hi HN! There's been lots of note-taking / personal knowledge tools developed in the past few years. But there's a big difference between working with people you already know and collaborating with anyone on the internet.Right now, if you're interested in, say DIY air purifiers[1], you could throw up a document or webpage. But there's no good way for people you don't already know to work on it,...
There's been lots of note-taking apps and personal knowledge sharing tools developed in the past few years. But there's a big difference between working with people you already know and collaborating with anyone on the internet.
Right now, if you're interested in, say DIY air purifiers[3], you could throw up a document or webpage. But there's no good way for people you don't already know to work on it, to make it their own. If you're writing software, the answer is obvious: publish a Git repository on GitHub/GitLab.
With Encycla, we're building a sort of "GitHub for knowledge": a place where you can create simple, topical webpages that others can fork and asynchronously push & pull changes from (without knowing about Git or anything technical).
On the backend, every page on Encycla is a git repository containing Markdown that you can clone, edit independently of the Encycla website, push to other services (such as GitHub, GitLab), etc.
Despite the fact soluble ACE2 is not looking like it'll be developed in time to impact the pandemic, there is a silver lining:
If you look at the original paper (https://www.thelancet.com/journals/lanres/article/PIIS2213-2...), you'll note they include details on angiotensin peptide levels in the patient.
Interestingly, in this n=1 case report, it looks like the soluble ACE2 is unlikely to have worked as an antiviral; the patient already had a high level of antibodies, as you can see in the Lancet paper above. So /if/ the patient's improvements can be ascribed to the soluble ACE2 treatment, it's likely the improvement was because of the effect the soluble ACE2 had on the person's renin-angiotensin system.
And if this holds, then it's likely many of these same improvements would be possible using a common class of widely-available blood pressure medications called ARBs.
This approach would not neutralize the virus, but instead stop the body from damaging itself. That's the theory, at least.
There are ~20 trials of ARBs for COVID-19 in progress now, though almost all are underdosed.
1. SARS1 spike protein itself, without any virus, causes ACE2 downregulation which leads to severe lung damage: https://twitter.com/__philipn__/status/1237588716236898304
2. When mice are engineered to be deficient in ACE2, the otherwise non-severe RSV causes severe disease: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4728398/
(This may be why COVID is bad. Check out my twitter above for a lot on this)
Other studies on Vitamin D are retrospective cohort / observational studies which are heavily biased with possible confounders with respect to Vitamin D.
My personal opinion is that Vitamin D may help in COVID-19 but this trial does not 'confirm' that. Someone should run a similar trial with more participants and/or a fully blinded trial / a trial with more outcomes (biomarkers, etc).
For instance, there are 137 current smokers. 108 are listed as non-severe. 29 are listed as severe. This means 108/137 = 79% non-severe, 29/137 21% severe.
Never smoked: 927 total, 793/927 non-severe (86%), 134/927 severe (14%).
Hope that makes sense. That table confused me too. Don't start smoking!
https://twitter.com/__philipn__/status/1235756671852589056
It may be the other way around: ACEi/ARB may be protective. HTN without ACEi/ARB would be non-protective, potentially so much so that it skews the group fatality numbers. This is because people with HTN have a different renin-angiotensin system profile: more AT1R, less AT2R, more ACE, potentially less ACE2.
This is being looked at now. But the key is that in every study ever done on viral lung disease, etc, AT1R blockade was highly beneficial, and we know that ACE2-knockout basically screws up lungs, makes viral lung disease way worse, etc. Please see my twitter posts.
The virus eats up ACE2, downregulating it as it binds. This would have delirious effects. Check out the linked "essential reading" twitter post.
Will be posting a summary to my twitter soon.
Review of small molecule therapies (not comprehensive): https://blogs.sciencemag.org/pipeline/archives/2020/03/06/co...
If anyone is reading this with connections to the Gates Foundation: Please contact Dr. Robert Kruse at John Hopkins. https://twitter.com/RobertLKruse. I have been trying to get in touch with people at Gates. This announcement unfortunately features no contact email address :(
Dr. Kruse is developing an extremely promising therapeutic, ACE2-fc, which will both neutralize the virus and treat the symptoms of the disease. It has been shown to work in vitro; variants have been tested in animals models; and its been through Phase II human trials for a different indication. A variant of the therapy, soluble ACE2, is being trialed in humans now in China.
Details on the approach can be found in his paper here:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7029759/ see "ACE2 immunoadhesin strategy"
E.g. can they ask google.com for $1B to renew and mygrandmascookiecompany.com for $20 to renew?
https://www.fairvote.org/how_ranked_choice_voting_survives_t...
https://www.fairvote.org/_ranked_choice_voting_reaffirmed_in...
If it's used for a multi-winner election, it gives results that are proportional in representation. For instance, this is how it's used in the city council elections in Cambridge, MA. Sometimes it's referred to as "Single Transferable Vote" when used for multi-winner elections.
"Ranked Choice Voting" is an umbrella term that refers to the ranked ballots, round-by-round elimination of candidates, etc.
"..There was zero overlap between the provers and the bulldogs. I was expecting at least some overlap: somebody who mocked me but also provided a valid solution, or even tried but failed. But that didn’t happen.
I normally assume these people are “brilliant jerks”: they’re assholes online, but I still have to listen to them in case they say something important. This really cracked that assumption: none of the “brilliant jerks” were willing to put any skin in the game. You don’t have to listen if they have nothing to say."
I'm not sure, but iOS's anti-ad tracking function(s) may have an effect as well (https://support.apple.com/en-us/HT202074)
Of course, you could buy one of these services and have access, too.
My rough summary: given there is no known second-preimage attack on SHA1, this is not an immediate danger to Git security because of the way Git works. The Git developers do want to move to a non-SHA1 hash at some point in the future.
Linus, from thread:
"I think that's a no-brainer, and we do want to have a path to eventually move towards SHA3-256 or whatever.
But I'm very definitely arguing that the current attack doesn't actually sound like it really even _matters_, because it should be so easy to mitigate against."
Why not include the cost of your time to maintain and improve the service? Without including the cost of your own time it seems hard to make budget decisions (e.g. the tradeoff between a PaaS and using a provisioned VPS). Even if you're not paying yourself anything, it seems important to include what you could be making if you were doing something else with your time.
E.g. see https://twitter.com/SFElections/status/534405668258594816 and https://twitter.com/SFElections/status/535541022915186688
San Francisco's election process has many distinct pieces, some of which currently involve software. For instance, the optical scanning machines that scan paper ballots run software. With this proposal, these machines will run open-source software.
The proposal isn't for a new electronic voting system (e.g. electronic voting machines), or to rid the city of paper ballots. It's just to improve the existing process.