100ideas

I’m going to take an extreme position in the hopes it “stimulates” conversation: the best course is $6k direct citizen payments. Business that fail create new niches some of the gritty but solvent ex-employed can try to exploit with new startups.

Also, if the stimulus in the scenario was $4 trillion total, each citizen could be given/loaned ~$12000; by pooling their stimuli payments, tens of individuals and/or large families could potentially have enough capital to take a risky shot on a startup / small biz.

On the eve of passing the first $2 trillion stimulus package, final deliberations in the US Congress about the "best" way to use the funds devolve into partisan deadlock:

One side insists that the only rational policy is for approximately 100% of the funds to be used to prevent business failures, arguing that "1) citizens need businesses to employ them so they can earn the monies they need to avoid starvation and homelessness with enough leftover (or at least a line of credit) for consumer consumption to collectively drive 70% of the economy; 2) the economy is literally made out of businesses and if too many die, then by definition so will economy; and 3) failed businesses take longer and are more costly (in capital investments) to repair/replace than are the jobs/homes/lives of the employees that must be sacrificed to save the company.

"On the contrary!", says the almost-equally-sized other half of the legislature, "Approx 100% of the funds to be distributed directly to citizens, $6000 each, thus 'cutting out the the middleman employers' and maximizing the number of citizens saved from homelessness and starvation due to unemployment. THIS is the optimal policy, both economically AND morally!"

To break the deadlock, Congress selects YOU as stimulus policy czar: your job is to decide and justify how best to distribute the stimulus funds - primarily distributed to businesses, primarily distributed directly to citizens, or some compromise between?

100%

For those out there interested in DIY molecular diagnostics, in addition to qPCR, also check out this new technique:

"SHERLOCK-based one-step test provides rapid and sensitive COVID-19 detection: New CRISPR-based research tool delivers results in an hour in a one-step reaction, advancing the technology closer to a point-of-care or at-home testing tool." - https://mcgovern.mit.edu/2020/05/05/sherlock-based-one-step-...

"STOPCovid is an effort to develop point-of-care and at-home tests for COVID-19. Developed by scientists at MIT, the McGovern Institute, and the Broad Institute, our test relies on a number of enzyme innovations to enable rapid detection in less than an hour without any complex instrumentation. We are committed to providing simple and easy-to-use tests that can be used in any setting so that society can reopen. On our website, we will provide updates as well as live clinical data from within our collaborator network. We are committed to working with partners to validate and distribute test kits. Please reach out to us (STOPcovid@mit.edu) if you are interested in working with us!" https://www.stopcovid.science

No no, thank YOU for "refuting" my "refutation"! I do stand corrected, I did not internalize your "total antibody-based immunity will last a few years" sentance, and was focused on the following "memory B cell / T cell based immunity is likely lifelong".

It's estimated that ~14% of common cold cases are caused by coronaviruses (HCoV-OC43, HCoV-229E, HCoV-NL63)... so although it seems particularly difficult, if we do manage to discover how to develop effective vaccines against Covid19, perhaps the silver lining is that vaccines against the related viruses responsible for a significant fraction of the common cold will be in reach.

https://en.wikipedia.org/wiki/Human_coronavirus_OC43

What’s your approach for getting covid19 template dna for the positive control reaction?

Just to spell it out: herd immunity depends on sustained immunity postinfection. It seems possible, perhaps probable, that covid19 "immunity" may have an unusually short duration or attenuated response, resulting in an effective herd population that is a fraction of the theoretical herd population. I.e. if 60% of Americans have been infected and recovered after 12 months, but antibody levels drop 25% after 12 months, the true number of immune americans comprising the herd will be less than 60%.

If so, we may need to consider pursuing a relatively slow and steady relaxation of lockdown to tune the rate of new infections such that herd immunity is kept as stable as possible - i.e. flatten curve into truly flat-but-nonzero line

As @tpnCC and @seppin said, there is significant clinical & scientific uncertainty about covid19 antibody response and duration, partly because there hasn't been enough time to collect the relevant data (for covid19) and partly because of prior resarch indicating reduced human antibody response to SARS.

Lower in this thread I commented about a 2011 resarch paper that demonstrated anti-SARS antibody levels fell by half 2 years postinfection and were undetectable 6 years postinfection in 21 of 23 SARS patients tested.

see this chart https://www.jimmunol.org/content/186/12/7264.long#sec-7

Here's the reference: Liu 2020 "Anti-spike IgG causes severe acute lung injury by skewing macrophage responses during acute SARS-CoV infection." https://doi.org/10.1172/jci.insight.123158

here are my highlights of the article and other articles I cited https://twitter.com/100ideas/status/1255671725112659969

Correct - there was a long-term memory T cell response. However, see sentance immediately preceeding the one you quoted - basically SARS-CoV IgG antibodies ("IgG Ab" below) were totally absent 6 years after infection. So, antibodies against SARS are not produced long-term, unlike many other types of viral infections, and unlike the desired mechanism of most vaccines.

"Six years postinfection, specific IgG Ab to SARS-CoV became undetectable in 21 of the 23 former patients. No SARS-CoV Ag-specific memory B cell response was detected in either 23 former SARS patients or 22 close contacts of SARS patients."

here is HTML version of article https://www.jimmunol.org/content/186/12/7264.long (DOI 10.4049/jimmunol.0903490)

Furthermore it seems as if mutations to the spike gene unique to hCov-2019 somehow is involved in suppression of immune systems’ ability to properly regulate its inflammation response; specifically, it seems to mess with the correct functioning of “M2” macrophages that act in a wound-healing mode to regulate the activity of proinflammatory “M1” macrophages. This leads to a runaway inflammation response.

The antibodies described here need to be tested en vivo (monkeys perhaps) to make sure they don’t actually lead to worse pathology (which for hCov-2019 seems to be immune mediated rather than directly caused by virus)

See my Twitter feed for references, I’ve been tweeting an immuno lit review (@100ideas).

Your personal belief about medium-to-long-term immunity is contradicted by research on same with SARS; see “Lack of Peripheral Memory B Cell Responses in Recovered Patients with Severe Acute Respiratory Syndrome: A Six-Year Follow-Up Study" [pdf] https://www.jimmunol.org/content/jimmunol/186/12/7264.full.p...

Some friends recently pointed me at:

https://covidbase.com/

the following article, published 13 Feb 2020, provides an exhaustive list of potential covid19 therapeutics, including remdesivir and a variety of other antivirals.

Zhang, L, Liu, Y. Potential interventions for novel coronavirus in China: A systematic review. J Med Virol. 2020; 1– 12. https://doi.org/10.1002/jmv.25707

open access via publisher: https://onlinelibrary.wiley.com/doi/full/10.1002/jmv.25707)

Very cool article summarizing potential of remdesivir as potential therapeutic vs Covid19. Submitted 16-Feb-2020, published 6-Mar-2020, and as of today 15-Mar-2020, it is the third-most-recently published article about remdesivir vs covid19 as indexed by google scholar [1].

interesting notes: remdesivir was given to the first reported covid19 patient in the usa under a compassionate use exception. Impossible to say if it helped, but the patient's condition did improve the next day.

> "Treatment with intravenous remdesivir (a novel nucleotide analogue prodrug in development) was initiated on the evening of day 7 (illness day 11), and no adverse events were observed in association with the infusion." [2]

Also see "Therapeutic options for the 2019 novel coronavirus (2019-nCoV)" [3]

[1] https://scholar.google.com/scholar?hl=en&as_sdt=0,5&q=remdes...

[2] https://www.nejm.org/doi/10.1056/NEJMoa2001191

[3] https://www.nature.com/articles/d41573-020-00016-0

You might find io-ts useful [1].

“io-ts introduces the concept of a runtime type (an instance of the Type class) which represents a runtime validator for a typescript (static) type. [2]”

See:

[1] https://gcanti.github.io/io-ts/

[2] https://lorefnon.tech/u2018/03/25/typescript-and-validations...

Are there phage therapy options for persistant lyme disease? Lyme disease is caused by the pathogen Borrelia burgdorferi. A quick pubmed search ([1],[2]) turned up two papers describing phage that interact with Borrelia.

Neither discussed their suitability for phage therapy. The most recent investigated phages as a potential mechanism for horizontal gene transfer b/w Borrelia burgdorferi: https://www.ncbi.nlm.nih.gov/pubmed/27811049

More searching led me to a page titled "Chronic Lime Disease" at the "Phage Therapy Center": https://www.phagetherapycenter.com/pii/PatientServlet?comman...

They seem to have developed phages for clinical treatment of chronic infections (perhaps biofilm mediated) of typical pathogens, and suggest that patients suffering from chronic lyme disease may actually be testing false-positive for Borrelia, and if so, may actually be suffering from chronic biofilm-mediated infection of a more common pathogen. In their words:

>>>> quote <<<<

Sometimes patients who have a legitimate, or otherwise, diagnosis of Chronic Lyme Disease, fibromyalgia or chronic fatigue are actually suffering from a toxin overload that is produced by a particular strain of bacteria. By clearing the treatable bacterial infections and utilizing various techniques to help reduce the toxin loads, there can be much improvement in the patient's overall condition.

Patients who have or who have had Lyme and Lyme co-infections may have serious damage to their immune systems, making them more susceptible to infection. Chronic infections are biofilms, they are colonies of a number of bacteria that together form colonies in various parts of the body - the sinuses, urinary tract, prostate and elsewhere that are inherently more resistant to antibiotics. While in-vitro lab tests may show sensitivity to various antibacterials, such infections typically do not respond to antibiotics. Dr. Tim Lu (MIT), a professor at MIT, explains why biofilms are antibiotic resistant, and why bacteriophage therapy can be effective:

"A classic example of a patient who had a Western Blot test that detected antibodies for Borrelia bergdorferi: Laura Roberts nearly died from her "non-Lyme co-infection", due to a deadly strain of MRSA which was detected by the lab. There are other similar cases." - Dr. Tim Lu - Biofilms and Phage Therapy

To reiterate, if your infection is a biofilm containing Borrelia or any of the Lyme co-infections, phage therapy from our clinic is NOT going to help you. If the infection is caused by one of the treatable genuses (Staphylococcus spp., Streptococcus spp., Enterococcus spp., E. coli, Proteus spp., Pseudomonas aeruginosa, Salmonella spp., Shigella spp., Clostridium difficile (C.Diff), Klebsiella spp., Morganella spp. and several others) there is a good chance we can - but NO GUARANTEE. You will need to test for the presence of these treatable pathogens and even if they are cleared, sometimes symptoms will persist.

>>>>> endquote <<<<<

[1] https://www.ncbi.nlm.nih.gov/pubmed/?term=%22Borrelia%22%5BM...

[2] https://www.ncbi.nlm.nih.gov/pubmed?term=%22Borrelia%2Fvirol...

Let’s talk virtual particles...

The universe appears to have expanded or be expanding faster than the speed of light: the diameter of the observable universe is ~42 billion light-years but best estimates of age of universe is ~14 billion years.

So these fields can’t interact with everything everywhere, only the portion of the universe In the field’s lightcone. if the universe keeps this up there’s a chance some day Everything will be so stretched out that the fields will be basically redshifted to null, so not interacting with anything anywhere. That’d be lame.

What, you don’t think the Hylaean Theoric World is realer that reality?

How does spacetime know to curve?

Ok, thanks for bringing precision to my comment. It makes sense that any photons reaching an observer who is inside a BH event horizon must also already be trapped inside the EH.

I think what I find confusing is that I thought outside observers would never see the infalling observer reach or cross the EH due to time dilation.

I’ve read that an observer falling into a black hole would notice extreme time compression in the external universe (observing millions or billions of years pass in the external reference frame), and conversely external observers would notice extreme time dilation of people and redshifting of photons falling into the black hole. Infalling particles from their external perspective appear frozen and smeared into a blur outside the EH, fading away but never optically appearing to “enter” into the BH, even though physically these particles indeed have/will.

So I think I had it backwards, the external observers would see infalling objects redshift, and those falling in would see the universe blueshift (I guess getting fried by high energy photons before being torn up by tidal forces).

I like your elegant thought experiment!

Quarks have -1/3 or +2/3 charge in the standard model and presumably(?) at high enough energies they separate out into a quark-gluon plasma thus exposing the universe to their unholy fractional charges. Above 2 trillion Kelvin according to wikipedia.

Well in the beginning there was just the one electro-strong-weak-gravity field... until inflation cooled everything down enough for the four “fundamental” forces to freeze out.

Edit: ok so really there is only theoretical evidence of an electroweak field at the beginning (electromagnetic field and weak field are not independent at high energy) and everyone is currently hard at work trying to 1) figure out the “Grand Unified Theory” that will putatively integrate the strong force with the electroweak force, and 2) figure out how to rethink either gravity/spacetime in a quantum context to integrate it with the quantum GUT, or unquantize the GUT (not likely) so it can be combined with spacetime...

A handy rule of... thumb I like to keep in mind is that it takes about 1 ns for light to travel from your hand to your eye...

(... and then 10,000,000 ns for your brain to process it...)

If you were further in the black hole’s gravity well than the photons in the photon sphere, you would see them redshift and eventually freeze, right? I.e. from inside the photons don’t appear to escape

Is it ok to mentally replace the word/concept “gravitational field” with “energy density field”?

If so it resolves the mysterious central relationship this field has for all the others.

“Electromagnetic waves” are the manifestation of relative motion between an electric charge and an observer’s reference frame. A detector inside a cryogenic ion trap would detect much lower energy EM radiation from the contained cloud of ions vs a sensor speeding towards the trap at 10% c. If this second detector slowed towards the inertial reference frame of the ions, the apparent EM radiation emanating from them would decay towards zero from the second detectors point of view as it became stationary relative to the charges.

Are gravity waves similarly observer-reference-frame-dependent? I.e. the gravitation of a given object is not intrinsic but rather dependent on the energy difference between the object and a given observer’s frame?

That’s a good question!

I wouldn’t be surprised if the academic team in this case developed something relatively simple. Let’s try to find out how they dispatched the synthesis orders they made over the two years.

Was it excel or csv at the end of the day?

If they were an enterprise biotech I would bet the would have a much more elaborate in-house data & design toolchain + Lims. But academic teams rarely have the resources or drive necessary to engineer digital tools approaching that level of sophistication.

Other software academics might use - benching - teselagen - maaaaybe antha-lang - ???

Alternatively, perhaps the synthesis vendor supplied their own optimized design and inventory tool. Who did they buy from - gen9?