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Posts

  • Fuzzy Cumulonimbus CloudFuzzy Cumulonimbus Cloud Registered User regular
    The periodontal strep hypothesis is very enticing in that it doesn't involve tau or abeta at all which would be novel. There is 0 mechanism for how the strep bacteria infiltrate the brain and I suspect that it will turn out that general cerebrovascular breakdown that is 100% concomitant with alzheimer's progression will be responsible for the post-mortem correlation and it won't be causative. I could be pleasantly surprised though! But also a periodontal mechanism doesn't explain familial Alzheimer's in the slightest. But since AD and PD and ALS and FTLD are all on a spectrum, it could help explain sporadic AD to some degree since it is obvious that there could just be environmental hits regardless of denovo mutations in sporadic patients.

  • override367override367 ALL minions Registered User regular
    edited February 2019
    emnmnme wrote: »
    i hadnt actually watched sterling's video but activision's CEO is gross all these CEOs are gross eat the rich

    how can any intelligent sane animal person have a business plan of "Make exponentially more money every year or declare utter disaster"

    If you buy a AAA game, you are supporting capitalism.

    im pretty sure im supporting capitalism when I buy a hentai game about anime girls as different houseplants or whatever as well, but I doubt their developer is upset when their games only have a 1000% profit margin

    but I'm totes down with abolishing capitalism where do I sign

    override367 on
  • Fuzzy Cumulonimbus CloudFuzzy Cumulonimbus Cloud Registered User regular
    Chanus wrote: »
    I don't see much difference between fans of Overwatch and fans of Zelda/Smash/etc

    well those properties have been around a long time at least

    this seemed to spring up as soon as overwatch existed

    it confused me

    A big part of this was just how well designed and animated all the characters are. For reasons COMPLETELY unrelated to the discussion further up this page I immediately fell in love with both Roadhog and Junkrat because you could play them for ten minutes and have a very strong idea of who they are as characters; they did a fantastic job with subtle visual storytelling. And that's a very good way to inspire fan artists to pick up and run with those characters.

    """unrelated"""
    there is one on GIS where junkrat is giving roadhog the old 1-2 with his peg leg and he's using vegemite as lube
    definitely a subtle visual storytelling

  • VishNubVishNub Registered User regular
    The periodontal strep hypothesis is very enticing in that it doesn't involve tau or abeta at all which would be novel. There is 0 mechanism for how the strep bacteria infiltrate the brain and I suspect that it will turn out that general cerebrovascular breakdown that is 100% concomitant with alzheimer's progression will be responsible for the post-mortem correlation and it won't be causative. I could be pleasantly surprised though! But also a periodontal mechanism doesn't explain familial Alzheimer's in the slightest. But since AD and PD and ALS and FTLD are all on a spectrum, it could help explain sporadic AD to some degree since it is obvious that there could just be environmental hits regardless of denovo mutations in sporadic patients.

    They do talk about this a little, in a purely speculative manner, admittedly.
    Here, we have not addressed how P. gingivalis infection might relate to apolipoprotein E4 (APOE4), the greatest genetic risk factor for sporadic AD (77). Studies in mice deficient in APOE proteins demonstrated an impaired innate immune response to the bacterial pathogen Listeria monocytogenes (78), implicating APOE in normal innate immune function in vivo. It was recently reported that human APOE is a target of gingipain proteolysis, and the authors suggested that this mechanism could generate neurotoxic APOE fragments in the AD brain (79). We propose that APOE4 may be more susceptible to gingipain cleavage than APOE3 or APOE2 due to the presence of more arginine residues, resulting in decreased innate immune function and the generation of neurotoxic fragments (80). The distinct role of APOE in relation to P. gingivalis infection and targeting by gingipains remains a focus of future studies.

  • Evil MultifariousEvil Multifarious Registered User regular
    Eliminate CEOs

  • ChanusChanus Harbinger of the Spicy Rooster Apocalypse The Flames of a Thousand Collapsed StarsRegistered User regular
    Chanus wrote: »
    I don't see much difference between fans of Overwatch and fans of Zelda/Smash/etc

    well those properties have been around a long time at least

    this seemed to spring up as soon as overwatch existed

    it confused me

    A big part of this was just how well designed and animated all the characters are. For reasons COMPLETELY unrelated to the discussion further up this page I immediately fell in love with both Roadhog and Junkrat because you could play them for ten minutes and have a very strong idea of who they are as characters; they did a fantastic job with subtle visual storytelling. And that's a very good way to inspire fan artists to pick up and run with those characters.

    """unrelated"""
    there is one on GIS where junkrat is giving roadhog the old 1-2 with his peg leg and he's using vegemite as lube
    definitely a subtle visual storytelling

    i asked him do you speak-a my language

    Allegedly a voice of reason.
  • ElendilElendil Registered User regular
    my pawn actually learns as we play

    "wolves hunt in packs, arisen"

    holy shit they do hunt in packs

  • DemonStaceyDemonStacey TTODewback's Daughter In love with the TaySwayRegistered User regular
    Abdhyius wrote: »
    Abdhyius wrote: »
    Couscous wrote: »
    Pokemon but it is a game designed to be somewhat challenging for adults rather than being designed to be easily beatable by young children.

    honestly this is pokemon, but with no motherfucking hyper potions

    as a kid, the one and only approach to a fight was grind the fuck out of those pokeymans

    as an adult, I can't be arsed to do that, so now I'm using strategies and expending every pokemon I have to reduce stats a little and barely eke out a chance at victory and I have tons of fun in the battles because they're hard

    and then the gym leader goes haha nope hyper potion

    What pokemon game would this be?

    The modern ones require absolutely none of that.

    the latter GBA ones, last time

    I also barely pay attention to having the right types or the right pokemon, just have a bunch I like and work with that

    Ahh. Yea I mean I always just pick the pokemon I think are the cutest/coolest as well. I don't remember the GBA ones at this point but on the DS ones even that is enough to just steamroll on through.

    Heck people playing nuzlocke rules on those ones can even steamroll through all the way to the elite 4 (where things do tend to actually get rough).

  • ElendilElendil Registered User regular
    Eliminate CEOs

    really any three letter acronym that starts with a C can go

  • emnmnmeemnmnme Registered User regular
    emnmnme wrote: »
    i hadnt actually watched sterling's video but activision's CEO is gross all these CEOs are gross eat the rich

    how can any intelligent sane animal person have a business plan of "Make exponentially more money every year or declare utter disaster"

    If you buy a AAA game, you are supporting capitalism.

    im pretty sure im supporting capitalism when I buy a hentai game about anime girls as different houseplants or whatever as well, but I doubt their developer is upset when their games only have a 1000% profit margin

    but I'm totes down with abolishing capitalism where do I sign

    Except for BMX XXX on the Gamecube, Hentai games are all indies.

    https://www.penny-arcade.com/comic/2002/10/18/now-you-know

  • Fuzzy Cumulonimbus CloudFuzzy Cumulonimbus Cloud Registered User regular
    VishNub wrote: »
    The periodontal strep hypothesis is very enticing in that it doesn't involve tau or abeta at all which would be novel. There is 0 mechanism for how the strep bacteria infiltrate the brain and I suspect that it will turn out that general cerebrovascular breakdown that is 100% concomitant with alzheimer's progression will be responsible for the post-mortem correlation and it won't be causative. I could be pleasantly surprised though! But also a periodontal mechanism doesn't explain familial Alzheimer's in the slightest. But since AD and PD and ALS and FTLD are all on a spectrum, it could help explain sporadic AD to some degree since it is obvious that there could just be environmental hits regardless of denovo mutations in sporadic patients.

    They do talk about this a little, in a purely speculative manner, admittedly.
    Here, we have not addressed how P. gingivalis infection might relate to apolipoprotein E4 (APOE4), the greatest genetic risk factor for sporadic AD (77). Studies in mice deficient in APOE proteins demonstrated an impaired innate immune response to the bacterial pathogen Listeria monocytogenes (78), implicating APOE in normal innate immune function in vivo. It was recently reported that human APOE is a target of gingipain proteolysis, and the authors suggested that this mechanism could generate neurotoxic APOE fragments in the AD brain (79). We propose that APOE4 may be more susceptible to gingipain cleavage than APOE3 or APOE2 due to the presence of more arginine residues, resulting in decreased innate immune function and the generation of neurotoxic fragments (80). The distinct role of APOE in relation to P. gingivalis infection and targeting by gingipains remains a focus of future studies.
    APOE4 is the only known SNP associated with AD but familial AD is mutations to the precursor of A-beta, APP. I've read the paper several times.

  • The Escape GoatThe Escape Goat incorrigible ruminant they/themRegistered User regular
    Chanus wrote: »
    Chanus wrote: »
    I don't see much difference between fans of Overwatch and fans of Zelda/Smash/etc

    well those properties have been around a long time at least

    this seemed to spring up as soon as overwatch existed

    it confused me

    A big part of this was just how well designed and animated all the characters are. For reasons COMPLETELY unrelated to the discussion further up this page I immediately fell in love with both Roadhog and Junkrat because you could play them for ten minutes and have a very strong idea of who they are as characters; they did a fantastic job with subtle visual storytelling. And that's a very good way to inspire fan artists to pick up and run with those characters.

    """unrelated"""
    there is one on GIS where junkrat is giving roadhog the old 1-2 with his peg leg and he's using vegemite as lube
    definitely a subtle visual storytelling

    i asked him do you speak-a my language

    just watch this video ya perverts

    https://youtu.be/7Dga-UqdBR8

    9uiytxaqj2j0.jpg
  • VishNubVishNub Registered User regular
    And it still invokes tau/Abeta as the direct cause of neurodegeneration, it just provides a trigger to explain why they might start accumulating other than time/genetics/bad luck.

  • override367override367 ALL minions Registered User regular
    Elendil wrote: »
    my pawn actually learns as we play

    "wolves hunt in packs, arisen"

    holy shit they do hunt in packs

    TIS A GOBLIN MASTER!

  • VishNubVishNub Registered User regular
    Ok. You clearly know more about this than me.

  • Evil MultifariousEvil Multifarious Registered User regular
    Elendil wrote: »
    Eliminate CEOs

    really any three letter acronym that starts with a C can go

    Except CBD

  • override367override367 ALL minions Registered User regular
    edited February 2019
    I love dragon's dogma, I love my derpy pawn who comments about the existence of harpies while being carried off into the clouds and dropped, managing to utter "It seems all roads lead to gran soren master" before their brains paint the rocks

    override367 on
  • TL DRTL DR Not at all confident in his reflexive opinions of thingsRegistered User regular
    desc wrote: »
    Peak 90s would be to include a spelling like “bad bwoy”

    Bad boyz

  • emnmnmeemnmnme Registered User regular
    https://www.penny-arcade.com/comic/2002/10/28/gabe-is-angry-again

    Tell the higher-ups this one needs to be updated for streamers in 2019.

  • bowenbowen How you doin'? Registered User regular
    I'm really concerned and mad at Pinecone's work; it's whiteout conditions outside and everyone knew there'd be a storm today starting around noon, and their job decided to still have people come in and work until 2:30!!! >:((((

    Our car sucks for snow driving and our street hasn't been plowed at all and it's already snowed almost two inches and Pinecone's gotta come home in this

    @Blameless Cleric I just got dismissed myself and if it's half as bad as it is here holy shit anyone without 4wd is screwed.

    not a doctor, not a lawyer, examples I use may not be fully researched so don't take out of context plz, don't @ me
  • FeralFeral MEMETICHARIZARD interior crocodile alligator ⇔ ǝɹʇɐǝɥʇ ǝᴉʌoɯ ʇǝloɹʌǝɥɔ ɐ ǝʌᴉɹp ᴉRegistered User regular
    I wanted Dragon's Dogma to have 50% more boss battles and 50% less everything else

    every person who doesn't like an acquired taste always seems to think everyone who likes it is faking it. it should be an official fallacy.

    the "no true scotch man" fallacy.
  • Fuzzy Cumulonimbus CloudFuzzy Cumulonimbus Cloud Registered User regular
    Sorry its been my field on and off for 10 years. I am basically kept up at night by what mechanisms actually and legitimately drive neurodegeneration. You are totally right that it still involves tau and a-beta.

  • The Escape GoatThe Escape Goat incorrigible ruminant they/themRegistered User regular
    Abdhyius wrote: »
    Abdhyius wrote: »
    Couscous wrote: »
    Pokemon but it is a game designed to be somewhat challenging for adults rather than being designed to be easily beatable by young children.

    honestly this is pokemon, but with no motherfucking hyper potions

    as a kid, the one and only approach to a fight was grind the fuck out of those pokeymans

    as an adult, I can't be arsed to do that, so now I'm using strategies and expending every pokemon I have to reduce stats a little and barely eke out a chance at victory and I have tons of fun in the battles because they're hard

    and then the gym leader goes haha nope hyper potion

    What pokemon game would this be?

    The modern ones require absolutely none of that.

    the latter GBA ones, last time

    I also barely pay attention to having the right types or the right pokemon, just have a bunch I like and work with that

    Ahh. Yea I mean I always just pick the pokemon I think are the cutest/coolest as well. I don't remember the GBA ones at this point but on the DS ones even that is enough to just steamroll on through.

    Heck people playing nuzlocke rules on those ones can even steamroll through all the way to the elite 4 (where things do tend to actually get rough).

    If your favorites happen to have decent type coverage you're good. I had a friend try to go through Moon with a six water type team (bc Alola is full of awesome water types) and that was rough. But that's a very specific hoop to jump through to make the game anymore more than "pretty easy".

    9uiytxaqj2j0.jpg
  • override367override367 ALL minions Registered User regular
    emnmnme wrote: »
    emnmnme wrote: »
    i hadnt actually watched sterling's video but activision's CEO is gross all these CEOs are gross eat the rich

    how can any intelligent sane animal person have a business plan of "Make exponentially more money every year or declare utter disaster"

    If you buy a AAA game, you are supporting capitalism.

    im pretty sure im supporting capitalism when I buy a hentai game about anime girls as different houseplants or whatever as well, but I doubt their developer is upset when their games only have a 1000% profit margin

    but I'm totes down with abolishing capitalism where do I sign

    Except for BMX XXX on the Gamecube, Hentai games are all indies.

    https://www.penny-arcade.com/comic/2002/10/18/now-you-know

    It's still capitalism when you're buying it from a small company

  • Evil MultifariousEvil Multifarious Registered User regular
    I would love a party-based action game where all your companions are Dragon's Dogma style learning AIs, but they're explicitly barely living homunculi and you have to train them to get past any difficult fights

  • override367override367 ALL minions Registered User regular
    Feral wrote: »
    I wanted Dragon's Dogma to have 50% more boss battles and 50% less everything else

    thats basically the expansion right?

  • VishNubVishNub Registered User regular
    I mostly read the paper looking for the structure (it's not there).

    I started reading the patents, then I remembered how much reading patents sucks.

  • Fuzzy Cumulonimbus CloudFuzzy Cumulonimbus Cloud Registered User regular
    FF12 is my favorite FF game because if you did it right you could just program your whole team and have them do everything for you.

  • VishNubVishNub Registered User regular
    Sorry its been my field on and off for 10 years. I am basically kept up at night by what mechanisms actually and legitimately drive neurodegeneration. You are totally right that it still involves tau and a-beta.

    All good

    :bro:

  • ElkiElki get busy Moderator, ClubPA mod
    @Sir Landshark it takes 30 to 60 minutes to get the 650 light weapon from Crimson Days.

    smCQ5WE.jpg
  • Fuzzy Cumulonimbus CloudFuzzy Cumulonimbus Cloud Registered User regular
    VishNub wrote: »
    I mostly read the paper looking for the structure (it's not there).

    I started reading the patents, then I remembered how much reading patents sucks.
    I would kill to know their phase 2 results.

  • P10P10 An Idiot With Low IQ Registered User regular
    you can't make pokemon actually hard without drastically redesigning the core gameplay
    you can make it grindy

    Shameful pursuits and utterly stupid opinions
  • syndalissyndalis Getting Classy On the WallRegistered User, Loves Apple Products regular
    edited February 2019
    FF12 is my favorite FF game because if you did it right you could just program your whole team and have them do everything for you.

    I liked 12 because it was basically Final Fantasy Star Wars with some fairly heavy inspiration from KOTOR. First FF I enjoyed post 8.


    edit: and honestly the last one I enjoyed at all.

    syndalis on
    SW-4158-3990-6116
    Let's play Mario Kart or something...
  • ElendilElendil Registered User regular
    the dragon's dogma expansion is 100% dungeon crawling and it slaps

    also i love the galaxy brain turn the last act of the story takes

  • P10P10 An Idiot With Low IQ Registered User regular
    also people only think they want hard games

    Shameful pursuits and utterly stupid opinions
  • VishNubVishNub Registered User regular
    I liked ff12 even if vaan is a moron.

  • Hahnsoo1Hahnsoo1 Make Ready. We Hunt.Registered User regular
    Kamiro wrote: »
    Elendil wrote: »
    Eliminate CEOs

    really any three letter acronym that starts with a C can go

    C

    O

    W

    oh no, wandering!
    If it will stop goddamn stoner hippies talking about their CBD oil...

    8i1dt37buh2m.png
  • emnmnmeemnmnme Registered User regular
    syndalis wrote: »
    FF12 is my favorite FF game because if you did it right you could just program your whole team and have them do everything for you.

    I liked 12 because it was basically Final Fantasy Star Wars with some fairly heavy inspiration from KOTOR. First FF I enjoyed post 8.


    edit: and honestly the last one I enjoyed at all.

    No one mentions FF13 or FF15 here at all anymore. They must have been duds with no staying power.

  • IlpalaIlpala Just this guy, y'know TexasRegistered User regular
    syndalis wrote: »
    FF12 is my favorite FF game because if you did it right you could just program your whole team and have them do everything for you.

    I liked 12 because it was basically Final Fantasy Star Wars with some fairly heavy inspiration from KOTOR. First FF I enjoyed post 8.


    edit: and honestly the last one I enjoyed at all.

    12 is v good and if they hadn't completely flubbed the last third and finished out Vayne's character arc properly, it could've been the best.

    FF XIV - Qih'to Furishu (on Siren), Battle.Net - Ilpala#1975
    Switch - SW-7373-3669-3011
    Fuck Joe Manchin
  • Fuzzy Cumulonimbus CloudFuzzy Cumulonimbus Cloud Registered User regular
    FF13 was absymal and I gave up at the end because it was just SO dumb in design and story
    FF15 is on my list

This discussion has been closed.