CharonY

If you want your product to be biotinylated, you need to attach a biotin. This can be done directly during synthesis (i.e. order it if you get them commercially), but there are also labelling kits if for some reasons you want to do it on your own. If you want to get a new restriction enzyme site, you need to add it to your oligo upstream of your priming site. I think "Molecular Cloning" (Green and Sambrook) should have chapter about it, but it is fairly common nowadays and I would think that many suppliers (e.g. NEB) will have information about that (though of course they also want to peddle their specific products, you can ignore that).

And that is precisely why we did not manage to stamp out the disease in the first place and why the chances of stamping it out is diminishing. I wished I could say I was surprised but I really am just disappointed. In addition what has already been mentioned, one can get more details from state/provincial data as well from COVID-Net (USA). Looking at the cumulative values, about 20% of all recorded COVID-19 related hospitalizations in the US were folks below 40 years. Also, being fit is is not confer magic protection. There have been plenty of hospitalizations of folks who had no known comorbidities. The data in papers are pretty broad (as they are all over the world with different cohorts), but we can see among folks in the 40s without comorbidities about 15% develop severe symptoms, including death. I.e. while there is a correlation with worse outcomes in cases of certain risk factors, thinking that you are safe just because you have no (known) issues is very risk (and again, at minimum you would be likely become a spreader and incubator). Also when it comes to background monitoring of effects, COVID-19 vaccines are administered as a much higher rate than other vaccines (influenza, for example is typically only as high as 40% among the target age group). So we do not have good apples to apples comparisons here. However, there is clinical data from the trials and if we look at e.g. the Pfizer documents, about 0.6% of the vaccine group had at least one serious adverse event compared to 0.5% in the placebo group. Adverse effects in case of COVID-19 in the 30s age bracket (minimum hospitalization) is somewhere around 14-20%. So if the question is not between two different vaccines but between vaccines and COVID-19 the answer is clear, even if one ignores the public health need of vaccinations (which at this point one really, really shouldn't).

Polio is still endemic in Afghanistand and Pakistan and I believe there have been irregular detections elsewhere. To OP, at this point it is not clear. If vaccination was available early in the pandemic and/or if the infection levels where kept at a low level until now, and if everyone was getting vaccinated, then the answer would have been a yes. However, one should take a step back in understanding how eradication works. It is not necessarily just a matter of vaccination, but it is about creating a situation where an infected person is unable to infect enough folks to sustain pathogen spread. Herd immunity could be achieved by a combination of vaccination, immunity, as well as social measures (e.g. distancing) for example. But right now we have still over 14.8 million detected infections (and likely many more undetected) which is a huge reservoir for the virus and has a high risk of the creation of new variants. I have lost track of how many variants there are now in circulation, though only relatively few are classified to be of concern. Nonetheless, there is a big risk that for at least some of the variants, the vaccine will be less effective. We have already observed across the world that the UK variant (B.1.1.7) has displaced the wildtype. And this also affects how we should interpret vaccine efficacy data. Pfizer/BioNTech and Moderna efficacy data were generated earlier in the pandemic where mostly the wildtype was around. However, AstraZeneca already included data from patients with the B.1.351 (South African) strain, against which the vaccines might not work as well. Some smaller data sets indicate for example that the Pfizer/BioNTech vaccine is about 89.5% effective against any infection with the B.1.1.7 variant and only 75% against B.1.351 in some groups (DOI: 10.1056/NEJMc2104974). However, they still protected with over 90% against severe diseases. The issue there is that while it prevents hospitalizations, it is still possible that folks get infected and may potentially transmit it to vulnerable persons. Aside from variants we got the issue that in many (most) populations we will not achieve anything close 100% compliance. Surveys in various countries, including the US, UK and Canada, indicate that up to 35% of those surveyed indicated that they won't get the vaccine. Another big issue is worldwide-timing. If vaccines are only provided in richer countries, then those who cannot afford it are basically a reservoir for the virus. If we take another year to vaccinate them, it will be a full year where new variants can rise. But even if just focus on local issues (and I want to emphasize that this would be really stupid to address a pandemic), we can do a little bit of a back-of-the-envelope calculation here. Let's focus on vaccination as the sole measure and let's assume we need ~80% immunity in the population to reach herd immunity. Let us further assume that the vaccines have an effectiveness of 90%. In order to achieve 80% immunity, it would be necessary to vaccinate 89% of the population to reach the herd immunity target. Only few countries (according to polls) are at that level of theoretical compliance. If we use US polls as an estimate of vaccine willingness (~75%), we can estimate that with a 90% effective vaccine we will have ~68% immunity, lower than almost all current estimated requirement for herd immunity. If the vaccine effectiveness goes down to 80% (due to variants for example) we would need to vaccinate every single person. So even if there are no barriers to providing vaccines to folks, it is tricky to rely on it alone to push down viral numbers to a degree that there is no net transmission. So no, based on the current situation I actually do not think that the current rollout in practice is likely going to eradicate the virus completely. The more likely scenario (I believe) for now is that it will become endemic. However, the optimistic scenario is that it will be better controlled via regular vaccines (and treatments) and won't have the same horrible death toll in the future. It might indeed become something like a flu, which, I want to emphasize has regularly costed many lives and is not really harmless either (though compared to COVID-19 it is comparatively tame). And as a minor sidenote, I would like to emphasize how behavioral changes have affected flu-related deaths. In the years prior 20-50k folks are estimated to have died each year from influenza in the US. Last year it was a few hundred reported so far.

For the most part it is used semi-quantitatively by measuring and comparing inhibition zones. It is in principle possible to try to estimate concentration, but it is a bit tricky. As the process is diffusion, the concentration decreases with the square of the distance. But then you also need the diffusion coefficient of the compound and also consider that diffusion happens also in three dimensions. But often the theoretical values or simulation are going to bit off unless you spend a lot of time to make the assay very accurate. However that is counter the typical benefit of such assays, i.e. being quick. There are quite a few other issues with quantifying antimicrobial activities (e.g. factors that influence MICs) but that is not specific to disk diffusion assays.

The use if siRNA itself to knock down genes is universal and been discussed as an antiviral for quite some time. The tricky bit is the delivery to target sites. In this case, they took advantage of the fact that certain lipid nanoparticle compositions have been shown earlier to accumulate in lungs, so when delivered intravenously they were able enrich the siRNA in lung tissues. For other tissues and cell targets (which include HIV) it may be more difficult to deliver the siRNA there. Difficult to tell, normally they need a controlled trial on humans first to make sure that it is safe. One issue of the paper is the use of a mouse model, which might have rather different results than in humans. The target of SARS-CoV-2 spike protein is the ACE2 protein, but the one in mice is sufficiently different to have reduced binding efficiency. Folks have expressed human ACE2 in mice (and the authors of the paper used such a mouse line) to improve their use as model. While on the symptomatic side they are closer to human infections than the wildtype mice, the transgenic mouse line has a few issues which and differences, which makes transferring treatments directly to humans without trials quite difficult. However, there are other therapeutics in play, such as Plitidepsin which are already in trials (Phase 3) and have been established in similar animal models.

I only glanced through it so may have missed some dinner points. It seems interesting, but considering the end points measured, the cohort is too small and needs to be much more age stratified. Titer and disease severity correlate with age.

Well, you do also have to add the fact that we still have a historic association with markers of race. Even if things like critical race theory are dismantling these notions, it would be silly to assume that they suddenly have gone. Plus, many political parties are still using it as a wedge issue, so in other words race assumptions still permeate and influence society beyond just individual experiences. While that is true, there are also big differences depending on where you grow up, when folks have immigrated and so on. There can be a big difference between immigrants now, who are living in a generally more welcoming and accepting environment compared to, say First Nations folks or African Americans, who have experienced continued erasure of their identity and culture. It is easy to overlook those those issues if one does not experience them (heck, my immigration experience to Germany in the 80s was vastly different to what I am experiencing now), but they will still colour individual interactions. Terms like white (or dominant culture) behaviour usually arises if folks create an identity in an area which they can control, i.e. which feels like themselves than something the dominant culture forces them to do. It happens usually if society is less inclusive and on the one hand forces an adherence to norms, but at the same time always finds gaps in the adherence to criticize (i.e. using the framework from OP one could say by being of certain ethnicity one might not be white enough). Again, on the individual level it is fairly easy to resolve, but projecting it on a societal level things get complicated.

That is an excellent point. And just to support that point, the work on animal and most human coronavirus isolates is BSL-2. If they unknowingly isolated SARS-CoV-2 (which is considered BSL-3) then yes, it would be dramatically increase the risk of infection, but as John said, it would have to come from the outside. Perhaps somewhat ironically, they technically might have violated law before their system actually worked to a certain degree. The system they had was unfortunately specific to SARS so it did not trigger properly and while warnings were sent, they were ignored (mix of maliciousness and ineptness would be my guess). If they hadn't anything built up as a response to SARS, however, they would likely not have identified it in the first place (a situation that might have happened in Europe based on newer research). I.e. in a way they would have been in compliance if they simply hadn't identified the clusters in the first place and could then have claimed ignorance. So in other words failing at monitoring diseases would allow folks not to run afoul of reporting requirements (and again, it seems that before the WHO rang the alarm bells there were already cases elsewhere which were not identified and where we generally do not assign maliciousness to their motives.

Even if the organization is charged, it does not mean that anything will come back to the Trumps. Also white collar crime often does not see much jail time. But all is very much speculation at this point.

Well, that is the role of the UN, they can propose things but it is up to folks to take it up or not. However, at least they provide a basis for discussion. The idea of a two-state solution has been kicking around since the beginning and has been basically the working plan from the UN. Support came and went from either side of the conflict and has been e.g. part of the Palestinian Declaration of Independence. At least after the Annapolis Conference it is at least in principle agreed upon by Israel and the Palestinian Authority. In most recent times, Netanyahu has become a major obstacle with pushing settlements on the West Bank. He is also explicitly against a one-state solution seemingly favoring status quo (a cynical view could be that this is the only move to preserve his power). Similarly, during many times a two-state solution was favoured among Palestinians and Israelis, often fueled by threat of conflict. Again, it almost seems like the hardliners on each side are feeding each other at the cost of the citizens. Right, so historically how well did it work? What would be the body count where you think folks would be ready to submit? Especially in the last few years (2008-2020; Statista data) the death toll are already 20x among Palestinians over Israelis (not counting injuries and associated death due to loss of medical supply, hospitals etc.). So is the region more peaceful now? Since we have passed your highest levels, how far should they go? In contrast, I think it is wrong to have plans that focus on outbreak of violence. When the rockets are flying, it is already too late. Rather I would ask why were the Palestinian families evicted? Wasn't there a way to mitigate? How about strengthening the rights of Palestinians living under occupation to undermine the argument of Hamas? Was storming of the Mosque necessary? And so on. If the whole picture (rather than isolated events) paint the picture of a suppressive regime that clearly favors one group of the population, it is small wonder that there is an ample feeding ground for resentment.

Yes and that is what Israel is doing and obviously we have seen how well that worked. Other than a net increase of human suffering what are the positives? Also what would be the endgame? There is a whole range of other issues beside the attacks on either side, but it is clear that hardliners in Israel only bolster hardliners among Palestinians. Actually the tunnels are also used to smuggle food and medication, but profit margins are likely lower and the volume to value ratio probably too. Also there is that: Also the blockade is not only limiting influx of goods, but also efflux, which has devastated Palestinian economy. I.e. even if they smuggled food it would do little to improve the quality of life in Gaza. There are many reports on this issue see a recent one here https://unctad.org/news/israeli-occupation-cost-gaza-167-billion-past-decade-unctad-estimates

Eh, I am not sure that I would like smart fascists over dumb ones, though.

! Moderator Note As OP has not established that the discussion is based on accepted biological knowledge, the thread has been moved to speculations. As such it follows the usual speculation rules and requires some support to allow a proper discussion.

I am aware of Dr. Shi's work. But it is one thing to use the moniker in an article or perhaps a social media post, whereas in press interview and especially if accusations are made one would expect something to be a bit more specific. To be fair, she may actually be fond of the moniker and I suspect I am projecting a bit but I am personally not fond of these kind of nicknames, especially when they are used without the actual name.

This is a weasel tactic. Rand Paul did not provide any trackable information on: - the name of the researcher (installing calling them dismissively bat woman) - the specific grant he alludes to - any reference on the paper. This could just be sloppy, but more realistically it gives him and his ilk the ability to then continue to say that there is 'reasonable' doubt, or 'some' have said that and so on. If Fauci responds to that, there will be something else next week. It is not an honest inquiry. Rather the goal is to discredit the person and spin a narrative that suits their base.

One could change the wording a bit insofar that an engineer applies known principles to make things work rather than necessarily having a rigorous scientific framework (which is probably less applicable to modern engineering).

Also to emphasize that the article I linked also shows that the US private space sector has raised much more than the Chinese private sector.

It is not an either or question. China also has a fledgling private space industry (mostly involved in satellite delivery). https://www.technologyreview.com/2021/01/21/1016513/china-private-commercial-space-industry-dominance/ And looking at an apple-to-apple comparison the Chinese private sector has total lower volume in investments than their US counterparts. Also regarding unilateralism, the US congress has banned NASA from any bilateral agreements with China (with few exceptions). However, with respect to the Chinese space station, there are at least agreements with the Italian space agency and I have heard of some European universities involved in designing microgravity experiments.

In other words, all of them had at best a science-based education, but none of them worked in any capacity as scientists.

A new report has provided new estimates for COVID-19 deaths. Verified death numbers obviously are a lower estimate. By looking at excess deaths and accounting for non-COVID-19 related deaths the authors estimate a current death toll of 6.9 millions globally (more than double of verified cases). In the US the estimated total deaths are over 900k. In the UK both numbers are closer (209k vs 150k).

It got highlighted in the news for a while as fatal cases (often strokes) occurred also in younger (below 55) hospitalized patients. There are follow-up studies indicating that even after discharge COVID-19 patients were at a higher risk to suffer from thrombembolic events, so the numbers I provided above might actually underestimate the risk, if they only looked at the time during hospitalization (I honestly cannot recall the details, there is just so much being published and quite a bit of it is somewhat useless).

In addition to what Phi and exchemist said, there are folks who have lost loved ones or know of folks who did. The whole outbreak was perpetuated by the inability of us to pull together and do the right thing. The fact that even now, when the chance of herd immunity is slipping away, there are folks who cannot think beyond their own benefit is galling, to say the least.

We could shorten the discussion by simply stating that a) there is no age group where providing the vaccine does not benefit the population as a whole and b) with the potential exception of under 20 year olds there is no age group where vaccination does not significantly reduce the risk of adverse health outcomes. And even then in younger folks it would depend a lot on active case numbers and other factors, which goes back to a). I mean, theoretically you can avoid those risks altogether by isolating alone indefinitely in a bunker, but that likely carries other health risks.

There are values actually published and circulated in various news (I could try to find them, but it was maybe a few weeks ago). There is a bit of a problem with how the reporting should be done, as there are different thromboses risks. Looking at the published numbers The result was about a 10 fold higher level in COVID-19 patients. In the study the calculated rate was about 40 per million CVST (the form of thrombosis associated with AZ and J&J) in COVID-patients and about 7 per million for mRNA vaccines. However that study did not (to my knowledge) include AZ and J&J vaccines (i.e. adenovirus-vaccines). We cannot simply compare raw numbers as the cohort need to be matched and it appears that there is significant gender effect there. However, they also looked at PVT, which is a more frequent type of thrombosis found in COVID-19 patients (~400 per million), whereas the rate for the vaccinated group was again only ~7 per million. There is another pre-print out suggesting that CVST is actually not statistically significantly higher in a vaccinated cohort compared to baseline incidence.

This understanding is very wrong. As you mentioned the overall goal of vaccinations is to limit spread of the disease and thereby the creation of new variants that could increase morbidity in younger folks. This is happening right now, B.1.1.7 has resulted in much higher hospitalizations among younger folks. In many areas half the ICU cases are now under 40. However, even ignoring that, the risk of death drops with younger age, but even in the 30s it is still estimated at around 0.2%. This is way higher (orders of magnitudes) than any risk (i.e. not only counting death) from any vaccine. Taken together, individual as well as population risk suggest that vaccinations will improve both outcomes