N3+ Watcher or Tracker is kind of a shitty role. N3+ Cop has legs…
once in qbcord a cop waited to out their reds until they had three
this is what we would normally call bad gameplay but i guess it worked
(wolves still won)
You coulda nightkilled yourself
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- Players may not target themselves with abilities and Evils can’t target their teammates.
nk was also mandatory
and yes: the nk is explicitly referred to as an ability
A teammate
oh
I diidnt read
nightkill yourself
Is this the weebfia game where town basically almost reverse swept bc of donut’s “weak” cop checks
no this is unrelated
if mountainous is pure mafia it’s like you’re drinking rubbing alcohol, sure you can but too much of it and you’re vomiting all over the place
roles are like watering down that alcohol so it doesn’t like poison you and becomes somewhat more pleasant to drink
does this metaphor make sense
and too many roles you’re just drinking lemonade… ishmael hates rolemadness…
yea
- Drug development is risky and has a high failure rate because of the difficulty of conducting in-vivo assays; binding screens are typically conducted with an isolated protein where it is impossible to determine effects of everything else
- In-cell NMR allows for the assessment of the interactions a drug has within a living cell without the ordeal of dosing a candidate compound to a creature and measuring its binding there. Can find off-target interactions, metabolism, membrane impermeability, etc. Previously, in-cell ^1H-^{15}N HMQC NMR has been used to assess binding to targets (show HMQC from the paper)
- Problem: the cell is a messy environment. Target proteins are very large and frequently interact with everything else in the cell, slowing molecular tumbling and increasing transverse spin relaxation rates. That means no more signal! Some protein signals can only be viewed after cell lysis (breaking the cell open)
- Solution: ^{19}F NMR. Fluorine is great: ^{19}F has 100% isotopic abundance, high gyromagnetic ratio, is naturally absent in living cells (so no issue with background), and is commonly used in drugs. This allows us to tag the ligand instead of the protein and simplifies detection greatly
- Problem: what if your ligand doesn’t have fluorine in it? Changing out anything will modify its affinity. Solution: Use a fluorinated ‘spy’ ligand of known binding affinity, which binds to the target and then is gradually displaced as the ‘test’ ligand is added (show displacement reaction) – by fitting the curve of this displacement over time, affinity constant can be calculated exactly, regardless of ligand fluorination
- A flow bioreactor is used to achieve this (show diagram of the bioreactor from the figure), which allows the cells to be kept alive through a flow of fresh nutrients and removal of waste.
- Here, cancer cells which overexpress the \text{Hsp90}_\text{N} domain were treated with a set of potential fluorinated inhibitor (as well as control cells which did not overexpress this domain). Signals were compared, the most effective ligand was determined
- Interestingly, we can see that compound 4 (show NMR signals) shows this broad peak which is present both in the cancer cells and control cells, indicating off-target interactions, something we couldn’t see in an out-of-cell assay! It doesn’t show up in the lysate!
Hm I don’t fully agree I think it’s less akin to “active ingredient (social deduction) watered down by mechanics (which decrease the amount of social deduction)” I think it’s more akin to mixing different alcohols. It’s different kinds of deduction with different flavors
yeah that’s probably a better way of putting it
rubbing alcohol was just the first thing i came up with
honestly it’s my least liked version of fm so yeah
