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Showing content with the highest reputation on 03/17/20 in all areas
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Sorry, dimreepr, but most of the times I am missing concreteness in your reactions. I discovered that when I react to possible interpretations of vague arguments or questions I have to write a long reply, then I get another short reaction that at one side seems to show that I interpreted you wrong, and at the other side forces me to write another long reply, etc. And then you react you do not have the time/energy/intention to read long texts... If the topic interests you, I would suggest to illustrate your questions or arguments with examples, preferably taken from real life, that can give your reactions the clearness for a fruitful discussion. It is true, iNow and me are trained in scientific, resp philosophical discourse, and so we can meet (and cross swords...) on a pretty abstract level. But that in itself is not a sign of intelligence, it just means we are used to the words (I hesitate to write '.. and concepts ...'), and ways of thinking. But abstract thinking can also hide a lot of differences and nuances. Therefore I often ask for concrete, real life examples. If an abstract concept really means something to a speaker, shows itself if the person can still make the connection with concrete life. And that also reduces the chances that two people use the same word, but think different things by it.2 points
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Nah, folks don't panic, they just stock up on essentials, like toilet paper.. oh. But in all seriousness, the turnaround for vaccines is usually quite a bit faster as desired reaction is (i.e. showing immune responses) is fairly easy to measure (at least in principle). According to Pharm folks quite a few assume that the vaccine is not going to be used recurrently so there is a focus on cheap and easy. With the accelerated stream efficacy can also be tested faster which basically can allow a fast rollout of phase III. Essentially first a few hundred than a few thousand folks will be treated and tracked. There it will show whether there is a likely acquisition of immunity (i.e. in essence it is already a low roll out of vaccination and at least theoretically this could could happen this year). Say May/June first safety results, if all is well on accelerated Phase II say two months to ensure that titers are there and high enough to indicate immune response. While results roll in start recruiting and one might have the first rollout for III maybe as early as August (say a few hundred patients). If efficacy and safety is still alright at this step a next wave could roll out a few months later with a few thousand patients. While the vaccine is not available for the population as such, I am pretty sure some would claim at that point that success at this point already. However, in principle we would need more time to gather sufficient info from Phase III to evaluate how much protection the vaccine actually delivers. That could be tricky as at that time it is possible if not likely that the number of infections are already declining. Actual full production and rollout normally proceeds after it is known to offer at least some level of protection. One should also not neglect the psychological value of the development itself. It provides folks with a sense of potential control over the situation and even if it does not come out in time, at least it feels like someone is doing something. Oh, and I should add that the accelerate trials are (AFAIK) all sponsored by the respective governments, so it is not like the involved companies are hurting from doing it.1 point
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As usual, I am going to guess what you might mean. If the question is whether it is profitable if it gets developed but too late, the answer is how likely the disease is to become either endemic or perhaps seasonal. In these cases a working vaccination could be quite profitable. In a broader sense, many of these trials do not make money. This is part of the inefficiency of the pipeline and this is why most companies only commit after at least very promising pre-clinicals. In that respect these approaches are not very different from other biomedical pipelines. SARS vaccines were in development for a long time, but some shut down because there were no major outbreaks and money dried up, for example. Other than that, having more things in pipelines is generally a good thing, especially novel ones.1 point
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I asked a similiar question, in short, ribosomes start of in the cytosol, when translation starts a subpopulation of those ribosomes will move to the ER. by CharonY1 point
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Interesting, if I properly understand, there are two forms of the virus membrane proteins: the pre-fusion ones in virus have stored energy to enable fusion with cell membrane, the post-fusion in infected cell have lower energy ... and the problem is that they are a bit different from perspective of antibodies. While it is much easier to produce the lower energy form, vaccine based on it would not protect against free virus, only would allow to mark the infected cells - these molecular clamp polypeptides are claimed to allow to produce pre-fusion ones. It is aminoacid sequence self-assembling into double helix rod-like structure ... I don't understand how it can help forming meta-stable higher energy protein forms? I see that this higher energy meta-stable form is originally prepared in ER membrane, somehow encapsulated from inside - from https://en.wikipedia.org/wiki/Coronavirus : ps. It is usually assumed that there are nearly no ribosomes in cytosol (?) - that some viruses have these complex capsides e.g. using pH difference to get into the nucleus ... so is the above diagram correct, or does coronavirus RNA have to get to ER or nucleus first? Update: ok, it seems there are free ribosomes in cytosol: https://en.wikipedia.org/wiki/Ribosome#Free_ribosomes So the most questionable part in this Moderna vaccine - just mRNA if I properly understand (?), is getting it into a cell: So can free mRNA get into a cell? But generally it could only give this weaker (?) post-fusion protection (assuming they go also to external membrane - not only ER suggested by diagram above) ... and could be also made by just putting these proteins on a liposome - I have started this thread with. A related idea is just putting ACE2 on liposome - getting a trap for this virus, it couldn't resist with mutations ... ps2: Also, the diagram above suggests that fusion requires binding with multiple ACE2 receptors, hence their concentration is a critical parameter ... which is said to be modulated by some common medicines used e.g. by high blood pressure and diabetic patients - suggesting a hypothesis that this might be a reason for increased mortality for them. Good lecture with commentary:1 point
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Although I don't understand half of it, I find the technology used to develop the vaccine fascinating: https://en.wikipedia.org/wiki/Molecular_clamp1 point
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That is why they allowed the phase I to proceed, there was a balance between need and risk. However, phase II is still needed. In this phase folks look into whether it actually has an effect. A harmless but useless vaccine can exposure folks to additional risk, as they think they are safe, while they are not. It is likely that Phase III can be cut short, essentially because there is nothing to compare it to. But again, the ~12-18 months time line is roughly what is needed to get the minimum information (and you also need to ramp up production) It does not really matter under which regulatory guideline you fall into. You always have to make sure that a) whatever you inject is not worse than the disease b) that it actually does something and c) figuring how and how much you need to apply to get and maintain the desired response. Just observing the responses even if you could inject everyone instantenously would take some time, otherwise you have no clue how you should deploy a potential vaccine. With regard to China I think I mentioned earlier that there are Chinese trials underway using a variety of approaches (inkl. using specific candidate antigens, most within Shenzhen). But as mentioned, I would be extremely surprised if someone somehow could bring anything to market by November (therapies would potentially be something, if only for severe cases). I should also add that having an immunogenic response does not mean that immunity has been acquired. On top there are international efforts in testing existing antiviral therapies some of which are intervention studies (i.e. they recruit sick folks as part of the cohort).1 point
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The capsid refers to the protein structure that encapsulates the nucleic acid (whether RNA or DNA). Some have additional lipids from their hosts. That latter part is what is considered the envelope.1 point
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Today at the supermarket and on the way by foot, I've worn a coffee filter for about 1.5h as a face mask. Observations: I was too lazy to put surgical tape across the whole rim, only a few pieces perpendicular to the rim. They held. Breathing through the paper wastes a manageable pressure, even when pressing the rim airtight. But the filter's volume stores exhaled air. Better a smaller volume. Walking with it was fine. A strong effort on a bicycle wouldn't. The other sapiens reacted about normally to it. Cats were afraid. Obviously, I ignore how much protection it brings. But it didn't hurt. The filter is useable for a longer time under dry weather. Two women, one being an identified governmental spook, told me spontaneously and loudly "Masks don't serve", which is the official propaganda despite masks are requisitioned for medics which are homo sapiens too. The least sly explanation is that masks are too scarce for the whole population in Europe, so governments allege they would be useless.1 point
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So the coating is the protein capsid? (In an earlier post of mine there was a spell correct that changed the word). In west and south coast Aus, the weather is drier and less humidity. On the east coast and the north it is the opposite - but we still get seasonal flu. Either way we can only expect approaching winter to impact while approaching su8mmer in the northern hemisphere hopefully gains benefits. Fascinating what we do and don't know. Zapatos - from what we are hearing the symptoms could be symptoms of many many things of which only one is CV-19. FWIW some statistics in NSW Australia - reference: https://www.health.nsw.gov.au/news/Pages/20200316_02.aspx Total number of tests: 26 964 Tested and excluded: 25 511 Under investigation: 1 282 Confirmed positive: 171 Every country will have a different experience based on how accurate they are with who gets tested, and where they are on the curve. But as above under 1% confirmed approx 95% excluded.1 point
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Sorry, mate. No offense intended. Didn't see a question, though. Thank you for the thoughtful reply. I'll need to think a bit more about this, preferably when I'm not plugged into the corporate hive mind of a 300+ person conference call in my ear.1 point
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Do you mean that because, in this case, it has no free will, in normal circumstance it does? @ others: I can’t moderate in this thread but there is no reason to suddenly get irrational and offensive just because someone mentions the “R word”. Grow up1 point
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I may not understand you correctly, but you may have a number of misconceptions regarding viral surfaces. A couple of points: - virus envelopes are typically formed by elaborate protein structures and they do not have a membrane as such - these proteins have complex three-dimensional structures (as other proteins) and often require additional proteins to be folded correctly and can be decorated - as such, the interplay between different viral proteins (and host mechanisms) are required to give viruses their final shapes - the immune response is dependent on the recognition of specific shapes (epitopes) - producing a viral part in vitro does not guarantee to provide the correct shape to recognize a life virus In addition, as mentioned you have to make sure that whatever you use as a vaccine does not induce harmful events. So again, just pulling proteins from a sequence and then releasing it into the bloodstream does not easily work, rather it would need quite a long process to make sure that it works and that it is not harmful. On the other points, eukaryotic cells do have free ribosomes but are also part of the rough ER. There are various options for RNA delivery including liposomes. That being said, I think while there are quite a few clinical trials for mRNA vaccines, they have not been approved yet (but some are fast-tracked).1 point
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-Maths is a concept developed by humans. -I don't think it existed before humans existed. -Math is a concept mostly used by humans (I don't know if animals can use it).-1 points