Readit News....what does this say about DRM enforcement?
Pharma companies care very much about off target effects. Molecules get screened against tox targets, and a bad tox readout can be a death sentence for an entire program. And you need to look at the toxicity of major metabolites too.
One of the major value propositions of non small molecule modalities like biologics is specificity, and alternative metabolism pathways; no need to worry about the CYPs.
Another thing they fail to account for is volume of distribution. Does it matter if it hits some receptor only expressed in microglia if it can’t cross the blood brain barrier?
Also the reason why off targets for a lot of FDA approved drugs are unknown is because they were approved in the steampunk industrial era.
To me this whole article reads like an advertisement for a screening assay.
Of course we've thought of all these things. But it's typically fragmented, and oftentimes out of scope. One of the hardest parts of any R&D project is honestly just doing a literature search to the point of exhaustion.
How does one become a microscopist as a profession? It seems like a specialized field with a narrow entry point and a lot of hoops.
1) Cold field emission guns. The big challenge of an electron source is producing a coherent beam - that is a beam that comes off the tip one electron at a time, at the same location, the same angle, and with the same energy. The cooler the tip runs, the more coherent it tends to be. This has made a big difference and is just now widely commercially available.
2) Narrow pole-piece gap. The sample on most TEMs sits sandwiched between two objective lenses that operate in tandem - these are typically called twin objectives. The upper one ensures the beam is parallel, which primarily results in uniform defocus (or focus if one so desires) across the image. The lower one is responsible for image formation and initial magnification (actually, all of your resolution essentially). The gap between them is responsible for your primary aberrations: spherical and chromatic. Reducing this gap reduces the total aberrations in the image.
I will side bar that the physics of a microscope are not really holding it back from what I'm doing - generating structures of biomolecules. Really, I'm more limited by the camera technology than anything, because the cameras simply aren't performant enough to dose the images to the level I'd like, to collect as many images as possible in as short a time as possible. Fundamentally, I tend to be limited by number of observations.
For the really cutting edge stuff...check out ptychography:
https://en.wikipedia.org/wiki/Ptychography
>How does one become a microscopist as a profession? It seems like a specialized field with a narrow entry point and a lot of hoops.
There are basically two routes for TEM - material science, or biochemistry. The way to become a microscopist for me was to show up at a University that had a grant for a microscope, but no one to operate it. :)
In general, universities operate TEM cores, frequently called bioimaging or something. (Structural biology if it's newer although that's just one application among many). Frequently there are positions for all education levels - bachelor's through PhD, depending on what one wants to do. Training is a mix of hands on (interfacing with complicated systems) and theoretical (physics and image formation). Typically the operators aren't the most theoretical, but have a lot of very niche practical knowledge you only get from being around broken microscopes.
(Also have done Xray crystallography)
Even more than that, dosing hundreds of millions of Americans for life is one insanely expensive and ridiculous solution.
Side note, is there good research on the effects of microplastics on the body? I'm holding out adding that to my plate of concerns until this is the case, and last I heard we were pretty in-the-dark on the topic.
There are two factors here:
1) Vaccine-derived immunity is a function of the individual's immune response, which in general, weakens significantly with age. It is not unrealistic for a vaccine to simply fail to elicit any response in someone old enough.
2) It is very, very difficult to recruit folks without HPV that are over 40 for a clinical trial. Most people of that age, who were never immunized, most likely have had it. This significantly convolutes the signal.
3) This is all especially confounded once something becomes "standard of care". Every year there are fewer and fewer people age 40+ with HPV.
For these reasons, the vaccine is currently officially ??? in people over 40. Most doctors will prescribe it anyways if you ask. It may or may not infer immunity. It almost certainly will not harm you.
This is interesting because of "supposed" cardiovascular effects of the vaccine that many folks were worried about. Even more confounding is the gender differences. You'd think skewing women would skew away from cardiovascular issues.
An alternate interpretation is that the at risk cardio unvaccinated died of COVID for some reason.