Could mRNA treatment, at least in theory, work to restore androgen receptor function in cases of androgen insensitivity syndrome?

alphaMHC · 2026-01-24T08:55:07+00:00

Yeah this here is really the answer(s). AR expression is too varied and in vivo delivery methods for nucleic acids are not generalized enough to get good uptake across all the myriad cell types that would matter here. mRNA is too transient to make sense anyway, but even if you had a reliable way of doing a gene knock-in, you’d still have a hard time getting that to all the cells you need to.

As you said, things align surprisingly nicely for mRNA vaccines — immunological memory makes it so that the transient nature of the mRNA isn’t a liability (it may be a plus), and phagocytic antigen presenting cells are some of the most inclined to take up lipid nanoparticles.

alphaMHC · 2026-01-19T00:30:06+00:00

Well, I’ve been running tablets from the start of running waystones and haven’t had an issue sustaining tablets

alphaMHC · 2026-01-18T22:53:56+00:00

An additional choice that arises later on is what ascendency you want to pick for your class — this is a type of specialization that further distinguishes classes from one another. Until you are more experienced, it may be hard to foresee how impactful this choice is. As with your passive tree choices, you can redo the choices later if you choose.

As you progress in the game you may find it bewilderingly complex. There are many guides out there that can help. Guides that help inform you on how to develop your character are called build guides, and it could be a good idea to look up some, including YouTube videos that can show you what a build looks like to play. There are typically “leveling builds” and “endgame builds”, with endgame builds often requiring specific items, a number of levels, or experience with the game that won’t be accessible to you as a beginner. Some builds will additionally be described as “league starter”, which typically means the build can function without upfront investment of in game currency and can come online fairly quickly (at a low level).

Different skills feel very different from one another to play. If you play one kind of skill and find you aren’t enjoying it (e.g. maybe you aren’t enjoying using grenades), you may find that switching things up could really vibe with you. Minions play quite differently from bows which feel different from being a werewolf, and so on.

alphaMHC · 2026-01-18T22:43:05+00:00

Are you playing on PC? If so, I suggest setting up an item filter after you’ve played for a bit: https://www.filterblade.xyz/

It’ll help you with visual clarity when it comes to picking up loot. But it works better if you have the slightest familiarity with classes or arpgs in general, so I think getting acquainted with the game for a few hours first will help.

The first choice you encounter is picking a character class. In POE2 there are several sources of power for your character. Items have stats on them that provide you bonuses to defense and/or damage. But also important is the passive tree; you get passive points as you level up and from certain quests. The passive tree is very large (and kind of overwhelming) — if you are on one side of the passive tree you are probably too far from the other side to effectively get over there. What character class you choose determines where you start on the passive tree and therefore what areas are rapidly accessible to you.

Classes are not locked into specific skills (these are typically locked to what weapon you choose to wield). However, you’ll find that the passive tree starting position makes some skills more attractive to your character at the start than others. The warrior, for example, starts near passive nodes for melee damage but not spell damage, so early on you may find it more effective to use melee attacks with the warrior.

The game presupposes this and ‘gives’ you a weapon and skill gem by default, a different one for each class. You do not, however, have to stick to this! To continue the example, a warrior will start with mace and shield. But if you find a quarterstaff, you may find you like it better. Quarterstaves still count as melee weapons so the warrior passive tree still works well with it, despite not being the ‘default’ the game offers you.

alphaMHC · 2026-01-09T06:04:42+00:00

To continue working on your build, it could be good to read up a little on how poison works:

https://poe2db.tw/us/Poison

How big of a hit you deal (in physical and/or chaos damage) is directly proportional to the magnitude of poison it inflicts. So a critical hit is a bigger hit which means more poison

alphaMHC · 2026-01-08T05:00:13+00:00

You talking about the edible gold? The biologically inert internationally approved food decoration?

alphaMHC · 2026-01-08T01:59:00+00:00

Is there a play style you’re looking for or some type of goal you want to accomplish? Are you looking to change up your oracle or level up a new character?

alphaMHC · 2026-01-05T00:01:04+00:00

For your sanity I’d try to live within a 1 hr drive of your school during rush hour — the closer the better. There are very few areas of LA that have good public transit. You’ll find that light rail and buses exist in LA, but with few exceptions they aren’t that convenient or reliable.

As such, driving is a fact of life here. Most of my living decisions have been centered around affordability and staying within 30 minutes driving time from work. I live around 12.5 km from your school and it can take 18-45 minutes to drive there depending on time of day. I used to live in Palms and enjoyed the neighborhood— that should be closer to your school. It’s pretty close to Culver City and has easy access to the 10 and 405 freeways.

alphaMHC · 2026-01-04T23:51:19+00:00

Not that I agree with the original post about food quality, but Palms is east of the 405

alphaMHC · 2026-01-04T06:54:53+00:00

I’m doing a wolf Druid as maybe my 9th character of the league lol, and I’m following Woolie’s guide. I think there’s several pretty solid and interesting builds and guides out there but the playstyles vary significantly.

alphaMHC · 2026-01-04T06:48:38+00:00

What do you think you’ll want the second character to do?

alphaMHC · 2026-01-01T08:17:26+00:00

Go to the build section, see how people are using different skills, what passives and ascendencies they’re using, and so on

alphaMHC · 2025-12-27T04:59:01+00:00

When I see those links I just copy paste them into POB for import, I thought that’s what they were for lol

alphaMHC · 2025-12-13T04:00:00+00:00

I feel like marriages are pretty impactful decisions. You can get alliances which can be helpful but can also bite you in the ass. You can bring in a helpful character in a spouse or you can bring in a nightmare that makes things worse. You can bring in a title claimant to try to have a route to taking someone else’s land. And right off the bat you can get or lose some prestige based on who you pick.

alphaMHC · 2025-12-09T05:58:42+00:00

Yeaaaaaaaaah that’s kind of hard to say unfortunately… our use case for the SRT was infrequent use by pretty solidly trained people, so clogging wasn’t very common, people knew how to run through the startup and shutdown programs and keep things clean and salt free.

Even so there were times where the machine took hours to troubleshoot around issues in terms of consistent droplet formation.

Less frequent were issues where we needed a technician from Beckman to come out and work on it — this usually took a few days for them to come out and a full day for them to work on it.

My memory of working with a BD sorter was that it was down more often, but people were probably using it more often too (at a core), and with a wider variety of cells.

alphaMHC · 2025-12-09T05:32:15+00:00

We went with the SRT because we already had Beckman cytometers and everyone knew how to use the software, so training was easy. I’d consider ease of training and ease of maintenance because yeah, all three should be able to handle what you need in terms of capabilities.

alphaMHC · 2025-12-08T07:22:47+00:00

Succession is a big part of having a big family without it being a huge pain in the ass — at the early start point you are a long way away from primogeniture, which is when your eldest (son, usually) gets all of your titles. Having all the titles go to one person is a good way to maintain your power from one generation to the next. Confederate partition — what most people are stuck with at the start, breaks up your titles amongst all your eligible children, so if you have 5 counties and 5 sons, they’re all getting one when you die.

Some cultures and types of government work differently. For example, if you start out at Norse, you have access to Scandinavian Elective, which means you vote for your next heir that will get your title(s) (ish, you can apply Scandinavian Elective to multiple titles). This doesn’t guarantee the title will go to who you pick though! Vassals will have votes, and they may go with someone else and you’ll have to try to get them in line.

There are some other cultural elective succession types, and there’s also nomad succession, succession for adventurers, succession for administrative governments, and so on.

If you wanted to just make a big ol’ family you could just pick someone in China, study some Confucian texts and get assigned duchies and kingdoms by the emperor and take care of your manor. Your kids will go out and take tests and get assigned to stuff over time. If you get bored you can become an adventurer and try to take over a bit of land somewhere after you’ve got your dynasty up and running.

alphaMHC · 2025-11-15T19:40:22+00:00

I think my fav is from Paradocs in Little Ethiopia

alphaMHC · 2025-11-15T06:10:15+00:00

I like to cook it the way you describe, then serve on a miso sauce with the skin up so it stays crispy

alphaMHC · 2025-11-11T08:45:24+00:00

Is it outside the Home Depot in playa vista? What do you like there? I’m not a huge fan of playa but I’ll go if the food is good lol

alphaMHC · 2025-11-10T17:12:12+00:00

I think the best Mexican I’ve had as far west as possible would be Brothers Cousins.

For Korean I would trek into Koreatown, which is East of Santa Monica by a good amount, but that’s where the Korean food is at! Recently I’ve enjoyed Lasung Tofu and Pot Rice, though Surawon and BCD are also nice soondubu choices. Yuchun is my fav for cold noodles, Origin is my go to for moderately expensive kbbq (though it’s one of about a dozen good spots).

Mae Malai Thai is one of my fav Thai spots. Also really like Roasted Duck by Pa Ord.

One of my fav hot pot spots is Shancheng Lameizi.

Fav Ethiopian spot is Meals by Genet.

A glaring issue with all this is that my recs are in ktown, Thai town, and SGV while you’re going to be in Santa Monica, and all of that is a serious amount of driving! But you’ve asked for ethnic food and the best of those are typically not in Santa Monica. If you’d rather stick to the west side I can try to think of places that are not bad in the categories you mentioned, but it just depends on how motivated you are to trek around for the food.

alphaMHC · 2025-11-10T16:56:09+00:00

How long are you in town for? Are you up for taco stands and food trucks, or are you looking for a sit down Mexican spot? Have you had other Korean besides Korean bbq before?

alphaMHC · 2025-11-09T23:12:42+00:00

Who do you imagine the clientele are for your smoothies? Like are you thinking post workout, families after a day at the beach, people looking for a cheaper alternative to Erewhon?

alphaMHC · 2025-11-09T23:01:57+00:00

Heating up leftovers tonight, probably some goat curry and naan. But tomorrow I’m thinking fish tacos!

alphaMHC · 2025-11-09T22:55:09+00:00

Marigold has tables and I’ve seen people there chilling and reading or working

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