#workable space

[luc1d17y-ffxiv]

Been busy between work, MSQ, and grinding out this and the new crafting set.

Raex is pretending to be a sexy bun who wasn't so bothered by how big and bulky the gloves looked that he glammed them over

[shroomsnail]

fixed a little thing that i believed only i noticed or cared about in the lab then a day later a lab mate points it out and says its great

[whentherewerebicycles]

.

[essenceofarda]

ugh does anyone else find that Clip Studio Paint's UI/interface is wayyyy too big on MacOS? It's not the resolution of my display tablet, because the icons are also blown up on my higher resolution macbook screen. It's driving me crazy bc i have a pretty large display tablet and I can only use like 3 inches of it -.- Anyway,,, I've been googling and searching for answers for three hours now, if any fellow mac users out there has any tips,,, I'd very much appreciate it,,,

[mumblesplash]

hot(?) take the witch in the alps lost cat story is in fact unsalvageable because it’s not a story. it’s an absence of one. it is a shadow in the negative space of a thing with actual substance and there is nowhere to take this premise that would not turn it into something else entirely by the time it was fleshed out into a workable game plot. it cannot meaningfully exist in a way that would not render it unrecognizable.

[skylordhorus]

like i can get him off skyhold it’s just.. accounting for the out of character mood swings and also that there are now reports of a large beast going after the livestock around mistral after finnigan comes back early from travel because he was attacked by a strange aggressive Creature

still tryin to figure out how to finagle werewolf!finnigan au so that it’s not immediately obvious to everyone that finnigan is. yknow. a werewolf

[fandomtrumpshate]

Totals Time!

It's been a year of records and record-breaking. Of reaching new fandom spaces and building new community ties. It's been wild. And absolutely fantastic.

When we closed the auction signup window we had 981 offers —nearly 150 more than we'd ever had before. When we re-opened it for 4 more hours, hoping to find another 19 folks (because we wondered what an auction with 1000 offers would look like) you all came through in spades, boosting the auction everywhere and bringing back 100 new offers in 15 new fandoms, bringing us to 1081 offers this year - a 33% increase over our previous record.

And you all weren't done breaking records. Shattering them.

This is the first year that any of our supported nonprofit orgs has received a 5-digit sum. And? TWO of them did.

So. Are you ready to see what our community has done? Are you ready for the numbers?

This year

thanks to all of you

FTH raised…

$67,931.28

The breakdown of donations to orgs looks like this -

This brings our eight-year total to

$307,439.14

Huge thanks to our 797 creators offering 1081 auctions in more than 400 different fandoms and subfandoms, and to everyone who bid! And to our 17 fan crafters who brought in $4,127 of that total —60% more than our previous crafting record!

So, what's next?

Contact deadlines:

Creators, be sure you contact your bidders by April 1, and bidders, on your end please respond to their communication by April 15!

Bidders need to provide their creator with a workable prompt by June 30 (unless you've worked out a different timeline together) to ensure they have plenty of time to finish their fanwork.

Once the fanwork is posted, let us know via our form (can you believe FOURTEEN creators have already finished??) and if you’re posting it on AO3 be sure to add it to the Fandom Trumps Hate 2024 collection. If you’re writing a fic for FTH and need help from our Regiment of Fan Laborers, email us! As always, the deadline for completed fanworks is December 31.

We hope that for at least some people, your involvement in FTH will lead to continued action throughout the year. Sign up for our organizations’ email lists, check out their volunteer opportunities, and help boost their signals on social media!

And if you’d like to run your own fanworks auction for a good cause, we can help get you started!

We have a packet of organizational materials we’ve been sharing with other auction organizers since 2017; we’re planning to spend the month of April overhauling and updating these materials to incorporate many of the improvements we’ve implemented since then. If you’re thinking about organizing an auction or fanworks exchange in your fandom to raise money for a good cause, we would love to share those materials with you. Contact us at fandomtrumpshate at gmail.com and we can send you our auction playbook, as well as answer any questions you have about our process.

Your mods (@porcupine-girl, @captainbunnicula, @tiltedsyllogism, @anyawen, @renjunbabygirl, @trickybonmot, and @a-still-small-vox) are going to be going into post-auction hibernation mode (or, for most of us, post-auction deal-with-all-this-other-stuff mode) for a little while. So if you email us, don’t panic if we don’t get back to you immediately! We will start actively monitoring the inbox again by April 15 at the latest.

[probablyasocialecologist]

Making worlds is not limited to humans. We know that beavers reshape streams as they make dams, canals, and lodges; in fact, all organisms make ecological living places, altering earth, air, and water. Without the ability to make workable living arrangements, species would die out. In the process, each organism changes everyone’s world. Bacteria made our oxygen atmosphere, and plants help maintain it. Plants live on land because fungi made soil by digesting rocks. As these examples suggest, world-making projects can overlap, allowing room for more than one species. Humans, too, have always been involved in multispecies world making. Fire was a tool for early humans not just to cook but also to burn the landscape, encouraging edible bulbs and grasses that attracted animals for hunting. Humans shape multispecies worlds when our living arrangements make room for other species. This is not just a matter of crops, livestock, and pets. Pines, with their associated fungal partners, often flourish in landscapes burned by humans; pines and fungi work together to take advantage of bright open spaces and exposed mineral soils. Humans, pines, and fungi make living arrangements simultaneously for themselves and for others: multispecies worlds.

Anna Lowenhaupt Tsing, The Mushroom at the End of the World: On the Possibility of Life in Capitalist Ruins

[nevertheless-moving]

unable to stop dwelling on the discworld trouser leg of time where, in the penultimate fight scene in Nightwatch, Carcer manages to kill teenage Sam Vimes.

Which means that the future that Duke Vimes came from can no longer exist, which means he can’t go home. Meanwhile you’ve got a bunch of history monks with stored up temporal energy, a prepared space outside of time, and the need to do some desperate damage control before the Auditors get involved. Death shows up, reality is unweaving, Sam is reading Carcer his discworld miranda rights because what else is he supposed to do.

and finally, with little other option, the monks de-age Sam so he fits the time period and send him back out into the fray.

(they didn't call it deageing of course. His memory is hazy, splintered during that terrible in between moment, They....took the time out of him? Sanded away the edges of his self for a terrible, workable fit? It...wasn't a good feeling.)

Just—damn. Sam Vimes having to live his whole crapsack life over again, but this time as his disillusioned-reillusioned, unwillingly-character-developed, noir-epic, Duke of Ankh, Commander Sir Samuel Vimes self. 

Younger (Older? He's never felt so Old, His steps so Childlike, reality twisting in his gut like one of Dibbler's pies) Sam Vimes walking around in a haze after the revolution. Desperate to go home, knowing he can’t. Wanting to drink. Knowing he can’t.

The whole precinct feels pity, he really took Keel’s death hard, hardly speaks except to do his job. Eventually he has to grit his teeth and start being present, because what else is there to do?

Resists the urge to drink until Colon takes the whole watch out to celebrate because -he’s going to be a father!

Come on Sammy, one drink won’t kill you— and after the first drink he’s cracking jokes and after the second hes smiling and after the third hes honestly the life of the party and sometime after that he’s crying about how he was going to be a father and my wife would be ashamed if she saw me drinking like this and— 

Oh shit, Did anyone else know he had a wife?? A PREGNANT wife??? What—aren’t you like 12—no you're 17 now aren't you but when did—

You guys n’ver met ’er—oh gods none if you ev’n know ‘er, is jus’ me...

What—when did you lose—

I lost her the same damn day I los’ ev’rythin else, whadya think...bleeding Carcer...the fuckin revolution...

So! That! Sam only vaguely remembers the night, but rumors travel faster than light on the disc, so by the next day the whole damn city knows about poor Sam brung low by the loss of his poor, tragic, pregnant wife, so young to be a widower, and the Seamstresses nod because they already knew, don’t ask them how, somethings you just have to know in that trade.

And his mother—I don’t know, sue me, I’m a time travel fiend but there’s something deeply intriguing about a man meeting his dead parent, who is somewhat younger than him, and stepping into the old relationship like a badly fitting thing that's supposed to fit well. She would know, right? How would she deal with her son’s impossible grief? Maybe she wouldn’t know—he spent most of the time out of the house, running with different street gangs, maybe he avoids her until she dies and lives with the guilt twice over. God, we don’t even know her name. There’s just so much narrative and emotional potential that I don’t even know where to start.

When he’s on duty, which is most time - it’s agonizing because at first he remembers cases, saves lives that would have been lost. But the more time passes, the hazier his memory because in the original timeline he was becoming an alcoholic. Fuck! A kid dies and he could have saved her if he hadn’t been such a drunk, if he had just remembered where the asshole lived, but it’s all a haze, and he wants to drown out his guilt, but that’s what caused this in the first place.

Good young Sammy, who spends his rare off-time in dusty libraries (and yes, the irony that he’s apparently Carrot now is not lost on him) reading gods-only-know.

It’s not like he can ask the wizards for help, cutthroat and vicious as they are now in the not-so-distant-past.

Good young Sam, who...talks to the Broken Drum’s pet Bouncer like he’s a real person and not a dumb rock? That’s a bit weird, but he’s a bit of a funny guy.

Good old Sam, who believed the testimony of the dwarf who said the humans were trying to rob him and let the dwarf go??

the PROBLEMS this man would cause, good grief. Can you imagine a moderately progressive middle aged man with some degree of begrudging diversity and equity training that he did, for all his sins, pay attention to, suddenly going back to like, 1990, going back just 30 years, and going...oh damn this is kind of fucked up, no man you can’t say that, holy shit.

Except Sam’s lived through even more rapidly shifting social moroes! There’s no seamstress guild, there’s no women allowed inside the university, there’s no black ribboner’s society. People hunted trolls for their teeth! But Sam can’t just unlearn everything, and he can’t shut up, and he has no real luck and anyway he would absolutely get himself (temporarily) fired.

FUCK. Sam has no idea what to do with that. None. Zero clue. Wanders around in a haze until that dwarf he saved from police brutality finds him and insists on repaying the debt. No, he insists, do you have any idea what debt means to a dwarf?

“Sort-of?” he replies hesitantly, and that honest admission of incomplete knowledge shows a hell of a lot more respect and understanding than any self proclaimed dwarf-expert ever did.

Gets a job as a surface man, hauling rocks into the city. It’s backbreaking work, but, in true Discworld fashion, it’s also one hell of a workout (again the irony of being Carrot is not lost him. he freezes for a minute while hauling a rock cart, when he remembers he's technically Lost Nobility too, in a strict sense, but someone curses at him in the street and he's comfortingly grounded)

And here is where this au slides into a SPECTACULAR romantic comedy, BEAR WITH ME. Because in his time on the Watch he’s already done noir, action adventure, war story, detective who dunnit, psychological horror, but guards guards only allowed him to be a romance protagonist in an extremely limited context.

Give me righteous, twenty-something-looking, can’t-say-he-doesn’t-have-style, young Sam Vimes, not an alcoholic,  being fed three square meals a day by his dwarven forced found family, hauling rocks. He is startled to find him bumping his head on a low hanging bar that he doesn’t think used to be there, eventually realizing that he’s an inch or two taller than he remembers. Huh. Guess all that bearhuggers really did stunt his growth.

Still doesn’t get what some of the looks from women he’s getting are about, sure, he’s dirty but so is everyone else. Fine, he took his shirt off, but it’s hot out, there’s far wrinklier than him hauling heavy loads, get a life. 

Happens to glance in the Ankh one day when it’s particularly slow and shiny and is startled to realize that he might be turning heads for a different reason. Oh. Right, not that he was ever a heartbreaker, but he did alright for himself... when he was a younger and his face hadn’t been broken so many times. Which...it isn't now.

Is mildly disturbed by the revelation.

Especially once things blow over at the precinct and what with high mortality rates, he ends up with getting hired again. The boys are delighted to have him back, nevermind that he’s an odd one, noone is ever quite in your corner like Vimsey, absence makes the heart fonder, no one else works that hard, and he’s not even competition for promotion. All around great guy, we should set him up with somebody and just, no.

It just keeps getting worse! He’s literate! He’s a feminist! He believes abuse victims! He’s got a tragic backstory! He’s unreasonably good in a fistfight! He’s kind to animals! Word gets around that there’s a good man on the watch and he’s just waiting for a good woman to come snap him up. The widower excuse doesn’t hold people off completely, and for some it’s its own sort-of appeal. 

Things REALLY become stressful after he rescues that carriage full of noblewoman.

What’s he supposed to do? Let them get robbed? Or worse? Chasing down and beating up 10 goons is as easy as beating up one, when they’re that stupid, getting separated like that, drunk and distracted, and he knows these streets better than anyone, really it’s nothing. And oh lord he’s Modest too.

I mean, they were genuinely greatful, as genuine as people like that are capable of being, the skill having grown rusty. And then there is something...magnetic about the man. An air of command.

So, soon enough you get Lady Marigold of Marigrave calling on Treckle Road for that gallant young officer who rescued them, she really needs to thank him. And Viscountess Elanor Thitzferal specifically requesting that he guard her at her next soiree. And Baroness Julieta van Shoeholten insisting that he come to her home while her husband’s away, for... manly protection.

Aaaah just zero sympathy from the guys. None. 'It’s become a competition, they’re just trying to see who can get me into bed first, it’s like I’m a piece of meat, you can’t send me sir, the Marquess greeted me in a nightee last time you made me go to—' and 'small gods Vimes are you even listening to yourself, shut the hell up'.

Simultaneous to this, (again this is several years into the timeline) swamp dragon accessories come into style. Which means abandoned swamp dragons scrounging on the street. Vimes takes one back to his apartment, blows his paycheck on dragon medicine, and eventually, heart in his chest, brings it to the Ramkin estate. The sunshine orphanage doesn’t even exist yet and he’s just standing outside the gates like an idiot, what is he thinking. Turns around, but her carriage is pulling up and—

well. they meet. it's cute. he's never felt so young. he's never felt so old, too old for her, too poor—

and certainly her thoughts linger too long on the awkward, kindly, handsome young commoner, but is it any wonder she doesn't quite connect it to the stern, dangerous, sexy young guard the ladies seem to be in some quiet, cuthroat competition over?

i have this gorgeous, absurd scene in my head in which Vimes is strong armed into standing guard at some high society soiree and one of the pushiest ladies insists he dance with here, or, if he prefers, if he's not confident about his skills, he can dance with her in-private at her home and he’s like [grinding teeth, looking for a way out, seeinf one] “I would be honored to dance with you.”

Steps right into some ultra-complex dance with multiple partner swaps (she never thought he'd pick this one, devilishly intimidating to one not strictly trained, and you barely spend anytime with your first partner).

But he does alright. Better than alright, for a common man, sometimes misstepping but his hands and feet always end up where they need to be. Raises several eyebrows part way into the song because he's throuwing in some slightly scandalous, no innovative, extra lifts and twirls that wouldn't become fashionable for another decade or two. Who even is that guy? Some out of towner? No, no he's in a guards uniform...how very strange.

Gets to Sybll and she's used to embarrassment during these dances, she tries to get out of them when she can... but can't always. Men awkwardly skipping the lifts, or worse, trying and failing. But him — oh it's him, the one who helped little Erold, and looked at her like—like—well like she was someone beautiful. And he's doing it again, and he's strong and there's a quiet moment where she's in the air, they lock eyes, and the rest of the room melts away.

And then the partners change again, the moment ended.

Just...living throught it all again. To the left, a dance he almost knows the steps to, throwing others off balance with erratic moves , honest mistakes, and delibrate stepping on toes. Improvising. Ruining. Improving. Getting far, far too much attention.

Hes almost excited when the first assassains start coming after him. It's like a hobby.

Everyone tells him he should get a hobby.

Interactions with young vetinari...I don't have the energy to write it all down, the slow circling in on each other, both burning with the need to fix the city, save it, their city.

needless to say he ends up fired again, life under real threat after offending some high lord.

Conveniently enough he has an employment opportunity- bodyguard to fucking Vetinari on his 'grand sneer.' The bastard knows vimes isn't what he seems, though sam is pretty sure that he doesnt know the exacts.

Vetinari hypothesis:(the ghost of keel? Keels son, with some hereditary curse? Or a larger spirit of justice possessing a string of unrelated souls? He knows things he shouldn't- mind reader? Fortune teller? Havelock once arranged for a wizard to bump into him on the street, the magical fool gave an odd double look and then muttered something about destiny looping in on itself giving him a headache. Destiny? Lost noble? And hes far too familiar with sybyl, one of the few bearable noblewomen in this city. And his thoughts on guilds, when havelock can trip him into speaking... Most of all, if hes reading him at all correctly (for all the mystery hes not that hard to read, unless thats a very clever cover) then it seems that behind those dark haunted eyes is Respect. Loyalty. For vetinari. What an interesting man. A puzzling asset. An intriguing threat. )

Did I mention the timeline is changing, healing slowly around the place where it was torn? Healing enough around scars to perhaps get some flexibility back, with some painful stretches and...massaging of said scar tissue?

And hes heading to unresting uberwald, a place where a werewolf pack still hunts humans and, truely unrelated but perhaps equally exhausting, an eldritch spirit of vengeance just might be looking to stretch its legs in a hapless vessel?

Opening drabble Vimes Vetinari Meta (Unwell) Scene from the Uberwald Grand Sneer

[batboyblog]

https://www.tumblr.com/batboyblog/767861339473510400/see-i-kind-of-get-the-idea-of-wanting-her-to-at

And frankly, if regular people had done THEIR job of voting in a Harris presidency (especially the more "informed" non-voters or anti-voters who prioritized their own ego), then McBride wouldn't have to make these kinds of difficult choices (at least to the same degree, since I don't doubt transphobes would still do their bullshit) in the first place.

yes.

Nancy Mace who's leading this charge just cares about being on TV, literally thats it. Back in 2021 she was selling herself as pro-LGBT, even saying she was in favor of "transgender equality" now she's screaming about trans women being really men. Why? well in 2021 it looked like there was space for Republicans to move on from Queer bashing and she wanted to get interviewed and be on TV for being part of a new breed of Republican. After this election many people agree transphobia was a useful wedge issue for Trump so she's gonna be the most transphobic of them all, again just to get on TV. So yes, if Kamala Harris had won Nancy Mace wouldn't be doing this because this is only motivated by her wanting to be on TV.

In a bigger sense, if Democrats had won the House this wouldn't be happening, Republicans might rage and stamp their feet about it, but a Democratic Speaker would tell them to kick rocks.

So yeah past McBride herself, the 2024 election was a test, "is transphobia a workable electoral issue" and the answer was "yes, yes it is" so transphobia is gonna be worse, it told Republicans that being transphobic and running on bullying trans people works so they're gonna do more of it, and for Democrats it showed there were few if any electoral rewards for sticking up for trans people. I remember when Harris very first became the candidate there were a series of huge organizing calls, so big they broke Zoom a few times, Women for Harris, black women, black men, white dudes for Harris, etc and I kept thinking "geez there really should be a trans people for Harris" there was a generalized LGBT one which had big names but if there ever was a trans one it was not well marketed. Point being the election did not see a big trans mobilization, which is very bad, you're seeing a few Democrats break ranks and ask "if we get hammered on this issue, and lose elections, and don't see any mobilization or support, should we moderate?" If Harris had won the narrative would be "voters don't care about trans issues, its a loser to run on transphobia" but she didn't so we're in this darker timeline

And being in this darker timeline a good starting point to clawing your way back is to have the ONE! trans member of Congress, the ONLY national trans figure's back at all times. Because beaming the message that even a trans Congresswoman doesn't have the support of the trans community will tell every jumpy Democrat that they're right to be thinking about ditching trans rights.

[autismlitmag]

essay finished! brief intro time

hello everyone who doesnt know me, i am wash librarycard @librarycard from tumblr.com (they/them) and i want to make a magazine/journal/art-thing by autistic people for whomever is curious about quite literally whatever they're autistic about.

a tl;dr from a large body of text i wont write is that im a library student with a research/professional focus on digital archives and the digital humanities. i have four years of experience in libraries and DH in particular. im published but have never published, if you know what i mean, so i will be using my resources (other librarians and friends who have published) as collaborators or guides to get the framework for this established.

this will be a free, community-oriented, autism-proud body of work that is intended to give people a space to infodump. there are going to be some important """rules""" (regarding citations, pre-formatting, and general approve/deny criteria based on if i think your stuff is discriminatory or whatever, not that i expect it to be much of an issue or plan to be incredibly picky about things)

the point is for us all to come together and talk about the things we love to people who genuinely like to learn. do not expect this to be incredibly stuffy or professional as it is for fun first and foremost. i dont want this to be super academic-forward (not that works in it cant be) but i want things to be fairly credited, accurate, etc and to maintain a minimum workload for people who will be working on this (hence the pre-formatting which i will be more detailed about). this will be multimedia supported because i dont believe in limitations.

i am going to open submissions as soon as i get some actually workable guidelines typed up so that we can get started ASAP. please keep this mag in mind and that right now im one little guy trying to connect with autistic people everywhere because i love autism. <3

-w

[excalculus]

I saw some mentions of rabies going around again and have no clue what's set it off this time, but given recent scientific developments I want to revisit the idea of curing symptomatic rabies.

First things first: there is still no practical way to do this. The famous Milwaukee Protocol fails far more frequently than it succeeds, and even the successes are not making it out in anything like a normal state. It's been argued that it should no longer be considered a valid treatment [1] due to these issues; any continued use is because there's literally nothing else on the table.

However. There are now two separate studies showing it's possible to cure rabies in mice after the onset of symptoms. The lengths you have to go to in order to pull this off are drastic, to put it mildly, and couldn't really be adapted to humans even if you wanted to. But proof of concept is now on the board.

long post under the cut, warnings for animal experimentation and animal death. full bibliography at the end and first mention of each source links to paper.

Quick recap - rabies is a viral disease of mammals usually transmitted through the saliva of an infected animal. From a contaminated bite wound, it propagates slowly for anywhere from days to months until it reaches the central nervous system (CNS). Post-exposure vaccination can head it off during this phase, but once it reaches the CNS and neurological symptoms appear it's game over. There will typically be a prodromal phase where the animal doesn't act right - out at the wrong time of day, disoriented, abnormally friendly, etc. This will then progress to the furious (stereotypical "mad dog" disease) and/or paralytic phases, with death eventually caused by either seizures or paralysis of the muscles needed for breathing.

That's the course we're familiar with in larger animals. Mice, though, are fragile little creatures with fast metabolisms.

In the first study's rabies infection model, lab mice show rabies virus in the spinal cord by day 4 after infection and in the brain by day 5. Weight loss and slower movement start by day 7, paralysis starting from the hind limbs from day 8 on, and if not euthanized first they're dead by day 10-13. [2]

This study (fittingly conducted at the Institut Pasteur) had two human monoclonal antibodies, and wanted to see if there was any possibility they could be used to cure rabies after what we think of as the point of no return.

Injecting the antibodies into muscle saved some mice if done at days 2 or 4, and none if done later, even at high doses of 20 milligrams per kilogram of body weight of each. Conclusion: targeting the virus out in the rest of the body is no use if it's already replicating in the CNS.

Getting a drug past the blood-brain barrier is, to use a highly technical term, really fucking hard. It's the sort of problem that even the best-funded labs and biggest companies in the world routinely fail at. And that's for small molecule drugs, which are puny compared to antibodies.

But this isn't drug development for a clinical trial. This is a very, very early proof-of-concept attempt, which means you're willing to ignore practicality to see if this idea is even remotely workable. So you can do things like brute force the issue by cutting through the skull to implant a microinfusion pump, which lets you deliver the antibodies directly into the normally-protected space around the brain. Combine this with the normal injections, and you can treat both the CNS and the rest of the body at the same time. Here's a survival graph of treated mice. X axis is days, Y axis is percentage of mice in that group still alive.

Figure 2A from reference 2, accessed February 2024

The fact that the blue, green, and purple lines did anything other than sink horribly to zero is unheard of. When the combination treatment was started at day 6, 100% of the mice survived. Started at day 7 (prodromal phase), 5 out of 9 mice recovered and survived. Started at day 8 (solidly symptomatic, paralysis already starting to set in), 5 of 15 mice recovered and survived. And when they say "survived", they kept these mice all the way to day 100 to make sure. Some of them had permanent minor paralysis but largely they were back to being normal mice doing normal mouse things. So, success, but by pretty extreme means.

Enter the second paper [3]. This was a different approach using a single human monoclonal antibody against Australian bat lyssavirus (ABLV - closely related to rabies, similar symptoms in humans) to try for a cure without needing to deliver treatments directly into the CNS. They also made a luminescent version of ABLV that let them directly image viral activity, so they could see both where the virus was replicating and how much there was in a live mouse.

Figure 1 from reference 3, accessed February 2024

Mice infected with ABLV start showing symptoms around day 8. You can see in the figure that at day 3 there's viral replication in the foot at the site of infection, which has shifted into the spine and brain by day 10. So what happens if you give one of these doomed mice one single injection of the antibody into the body?

Done at day 3, the virus doesn't make it to the brain until day 14, and while disease does set in after that around 30% of the mice survive. Days 5 and 7 are much more interesting. Those mice still develop symptoms at day 8, but the imaging shows the amount of virus in their spines and brains never gets anywhere near the levels seen in untreated controls, and within days it starts to decrease. Around 80% of day 5 and 100% of day 7 mice survive.

Okay, sure, you can stop another lyssavirus, but technically you did start treatment before symptoms appeared. What about symptomatic rabies?

The rodent-adapted rabies strain CVS-11 starts causing symptoms as early as day 3 after infection, and untreated mice die between days 8 and 11. The same single dose of antibody saved 67% of mice treated on day 5 and 50% of mice treated on day 7. Without making the luminescent version of the virus there's no real-time imaging of the infection, but you can still track symptoms.

Figure 2 from reference 3, accessed February 2024. CVS-11 is the name of the rodent rabies strain and F11 is the name of the antibody.

Disease score is a combination of several metrics including things like whether the mice are behaving normally and whether they show signs of paralysis. In untreated mice it goes up and up, and then they die. If one of those lines starts coming back down and continues past day 10 or so, that's a mouse that recovered. The success rate isn't as good as against ABLV, but again, this is a rabies strain specifically adapted to rodents and treatment wasn't started until it was well-established in the CNS.

So how on earth is this happening? The antibody neutralizes both ABLV and rabies really well in a test tube, but we've already established that there's no way a huge lumbering antibody is making it past the blood-brain barrier without serious help. Something about the immune response is clearly making it in there though. And it turns out that if you start trying this cure in mice missing various parts of their immune systems, mice without CD4+ T cells don't survive even with the treatment. By contrast mice without CD8+ T cells take longer to work through the infection, but they eventually manage it and are immune to reinfection afterwards.

To grossly oversimplify the immune system here, CD4+ are mature helper T cells, which work mostly by activating other immune cells like macrophages (white blood cells) and CD8+ T cells (killer T cells) against a threat.

Normally, T cells are also kept out by the blood-brain barrier, but we know that in certain specific cases including viral infection they can pass it to migrate into the brain. In the brains of the infected mice for which antibody treatment either wasn't given or didn't work, you can find a roughly even mix of CD8+ and CD4+ T cells along with a whole lot of viral RNA. But in the brains of those successfully fighting off the infection, there's less viral RNA and the cells are almost exclusively CD4+. So the antibody doesn't work by neutralizing the virus directly - something about it is activating the animal's own immune system in a way that gives it a fighting chance.

Again, neither of these proof of concept treatments is really workable yet as a real world cure. The first one is almost hilariously overkill and still has a pretty good chance of failure. The second is less invasive but careful sequencing still shows both low-level viral replication and signs of immune response in the brains of the survivors even at day 139, so it may not be truly clearing the virus so much as trading a death sentence for life with a low-level chronic infection. But now we know that 1. curing rabies after symptoms begin is at least theoretically possible, and 2. we have some clues as to mechanisms to investigate further.

Not today. Not tomorrow. But maybe not never, either.

References:

Zeiler, F. A., & Jackson, A. C. (2016). Critical appraisal of the Milwaukee protocol for rabies: this failed approach should be abandoned. Canadian Journal of Neurological Sciences, 43(1), 44-51.

de Melo, G. D., Sonthonnax, F., Lepousez, G., Jouvion, G., Minola, A., Zatta, F., ... & Bourhy, H. (2020). A combination of two human monoclonal antibodies cures symptomatic rabies. EMBO molecular medicine, 12(11), e12628.

Mastraccio, K. E., Huaman, C., Coggins, S. A. A., Clouse, C., Rader, M., Yan, L., ... & Schaefer, B. C. (2023). mAb therapy controls CNS‐resident lyssavirus infection via a CD4 T cell‐dependent mechanism. EMBO Molecular Medicine, 15(10), e16394.

[rotzaprachim]

Taking your mission partners name in a Comradely Manner etc

A more niche opinion I guess I have is that jyn might easily take Cassian’s surname (maybe even before they’re romantically involved) due to the realities of how tightly the Erso name has now been tied to, y’know, the Death Star, and what a liability it might be to walk around as an erso in the rebellion. And she’d rather be Andor than carry a false placeholder name again when she’s spent so long as a wanderer erasing herself from the world

[adarafaelbarba]

Rafael Barba for the only one bed square?

Bed Share and Conferences

✨ Covering the «One Bed» square of @storiesofsvu ’s holiday bingo ✨

warning: alluding to smut going to happen, but nothing explicit.

When the announcement for the annual seminar was made. Especially considering it would be held in Florida, and you’d been chosen to go again to give a talk.

However, that quickly soured when everyone got there and the hotel manager announced that the hotel had been overbooked, and people coming from the District Attorney’s office in New York, that being your place of work, would have to couple up and share rooms. Throwing a quick glance over at some of the girls you were closest with proved futile as they seemed to be coupled up quickly, either with each other or with their office crushes. Which in the end left you with the very grumpy, Rafael Barba, your boss.

Room given, the staff offered to get everyone’s luggage upstairs as compensation, and you all made your way to the first meeting of the day, a talk given by someone from a law firm in D.C.. And for the most part, throughout the evening, you kind of forgot about the whole mishap. It wasn’t until later, when you and Rafael made your way upstairs to your given room that the horrors awaiting you revealed itself.

«Where’s the other bed?! Or at least a decently comfortable couch?!» You exclaimed, having entered the room first. All the air left your body, feeling deflated, and like you’d been robbed by the exciting time you were going to have here.

Rafael swore behind you. «I’ll see if there’s a way we can get another room—»

«It doesn’t help, sir, all the other rooms have been taken, and it’s too late to find another hotel.» You’d hate to admit it, even to yourself, but having to share a bed with your very attractive, albeit grumpy boss, for the next few days would for sure fuel some late night fantasies for when you got back home to New York. Trying to be civil about it though, you turned to look at him. «We’re both adults, this doesn’t have to be awkward, sir.» You said, trying your best to smooth him over.

«You’re right—doesn’t have to be awkward at all, y/n.» He still seemed on the fence though, however, seeing as you both had to get up early in the morning for the next full day of talks, you both got ready to turn in. Rafael was kind enough to let you use the bathroom first.

— 

The first night seemed to go off without a hitch, so did the next one. By the last night in the hotel, you’d both gotten to a workable routine. That was until you both stumbled back to the room, laughing over some jokes said over one too many drinks at the hotel bar.

You dropped your heels which you’d carried from downstairs, next to you and started pulling the dress zip down. «Could you help me get the zip?» You asked, turning your head to look behind you where Rafael stood, pulling his tie loose. As soon as you locked eyes with him however, you could see the hunger in his eyes. «Sir?»

He cleared the space between you in just a few quick strides, pulling you in for a messy kiss, his hands going up and down your body. As you made out, you could feel him dragging the zipper down behind you, then his warm had was on the soft skin of your back, pulling you even closer to his chest. 

«So soft for me, cariño.» He murmured against your lips, «I’m going to have some fun with you.»

Tagging:

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[thechekhov]

Hi! I'm working as a teacher for the first time this fall, and I'd like to ask you: in your experience, how do you go about working as a teacher and also finding time for your wips like the SU comic? And do you have any tips for someone who has zero experience working with kids (13-15 y/o)? Thanks in advance, and have a nice day!!

I think everyone's experience with this will be different - based on where you're teaching, what subject you're teaching, whether you'll actually be the main-teacher immediately or if you're simply observing class at first/assisting and how much guidance you'll get from actual experience teachers, etc..... but my biggest advice may be a bit counterintuitive:

Don't try to find time. Just wait for time to find you.

I think people often assume they have more time than they actually do. Teaching is pretty time-consuming, but it's also INCREDIBLY energy-consuming. It's difficult not only because of the hours, but also because it physically and mentally drains you more than, say, an office job would. You have to be On all the time as a teacher - you have to be watching the students, paying attention to what they're saying, paying attention to what YOU'RE saying, paying attention to the schedule, paying attention to the lesson, etc. It's a lot of brainwork!

Regardless of your level of experience, you're going to be coming home WAY too tired to do anything but lay down. That's going to be the bulk of your evenings.

Contrary to what it seems like, when I first started teaching, I also did that for the first 4-7 months. I didn't draw - I didn't have the energy or time to. I came home, I collapsed, I got up to make dinner, and then I spaced out. Sometimes I got dragged out by friends for social activities. I drew only on the weekends, IF I felt like it.

Eventually, though, I trampled down my schedule into something workable. I started drawing regularly because my body and brain got used to the daily strain and became stronger. (That's something that's less known about brains, I think... you have to train yourself to be able to handle that sort of mental stress over time. It's like endurance training.)

Also. And I need to make this clear:

At the time when I was drawing THE MOST and posting REALLY OFTEN (daily for @ask-whitepearl-and-steven) I was already living with my partner. About 3 years in, we were in the same apartment together and he helped out a TON with laundry and cooking. That made a huge difference. I had support on basic tasks which would have eaten into my time even more.

What I'm saying is - having time for hobbies is great. But you need to make sure you're not cutting off pieces of yourself, or your sanity, in order to make that happen. Try to be kind and give yourself time to adjust.

As for the advice about kids/teens:

They're people with complicated lives outside of you/the school. If they don't immediately respond to you, don't take it personally.

They're people who haven't yet learned total emotional regulation - try to be kind about how grumpy/angry/moody/anxious they often are. Try to react like you would to an adult.

They're only people. Be kind to them.

They're full on people. Don't let them get away with being cruel to you or others. They CAN understand at that age that they hurt others. If they make a rude joke, don't laugh awkwardly - a good stare can go a long way.

Good luck!

[sabersandsnipers]

Halsin Building a Crib

@inmyloveworld continues to feed our shared Halsin obsession

The thought wakes you from a deep sleep. You sit straight up in bed, a small panic gripping you. Halsin stirs beside you at the sudden motion.

"Halsin," you gasp, grabbing his massive bicep. He sleeps on his stomach, face buried in his pillow.

"Hm?" he mumbles.

"Where is the baby gonna sleep? We don't have a crib or anything!" Your voice is both a whisper and a scream.

His eyes crack open a bit at the concern in your voice. His large hand slides over your swollen belly, rubbing slow circles along your taut skin. "Don't worry about that right now, love. We'll figure it out."

His words do little to satisfy your worries. But you listen to your husband and lay back down. He keeps his hand on your belly. The act is almost protective.

Little to your knowledge, Halsin immediately begins plans in his head to build a crib. His woodworking skills give him the expertise to build a safe space for your baby to sleep.

He gets to work first thing in the morning, after making you your favorite breakfast. He leaves your shared cabin and sets out to the thick forest surrounding your home.

His first task, and perhaps the most important one, is to find the perfect tree. He takes his time in choosing, taking in the height, width, and ensuring he'll have enough material to work with. Once he finds what's he's looking for, he sets to work.

He grabs his axe and begins swinging. He’s quick to work up a sweat, so he peels his shirt off and tosses it into the wheelbarrow next to him. The strain in his muscles is a welcome one. Even as more years wear on his bones, he always finds solace in a hard day’s work.

In the midst of the continuous swinging motion of his axe, his mind wanders. And, of course, it always wanders to you. He thinks back to the moment you shared with him your belief you were pregnant, and the joy that rang through him at your words. He thinks of the first time he felt the baby kick, and how he felt the overwhelming need to protect you two.

Throughout his long life he's always known he wanted to be a father. But the world is cruel, and after all the events he had been through, he never thought he would get the chance to share this kind of life with someone. Until he met you. Singlehandedly being the most exceptional creature he ever laid eyes on, he was eager to start a family with you. And you were happy to give him that gift.

Once the tree has been felled and cut into workable pieces, his hands are quick to work. He shapes the pieces into their desired sizes. He carves patterns into the wood.

The sun is nearly setting by the time he’s finished. His back aches but he can’t stop the smile on his face as he admires his work. He knows you’ll be expecting him about now. He told you he was going out to hunt for the day.

You’re curled up in front of the fireplace when Halsin returns, a warm mug of tea in your hands. You hear his heavy footsteps outside the door and excitement sings within you. Your heart already aches to see him even after spending the morning together.

He swings the door open, shirtless and sweaty and covered in wood shavings. Butterflies race through you at the sight.

“What on earth have you been doing?” You ask him, a little breathless due to the sight before you.

He grins. “I’ve got a surprise for you.”

Your heart flutters at his words. He disappears outside for another second, before carrying in a beautiful crib. Your jaw drops as you stand and make your way over to the gorgeous work set in front of you.

You slide your fingers along the smooth finish, appreciating its sturdy structure. Images of ducks and bears are carved into its siding, and the sight of it nearly brings tears to your eyes.

“I don’t know what to say, Halsin,” you tell him. You meet his gaze, and there’s a slight tinge of red to his cheeks. A shy Halsin is a rare sight, and you’re overwhelmed with the need to hold him.

You step forward and place a long kiss to his cheek. His hands instinctively find their way to your belly. Once you’re able to see pull yourself from the warmth of his skin, you pluck a wood shaving from his dark hair. A small laugh leaves his lips.

“Thank you,” you say, gratitude surging through you.

He grasps one of your hands and brings it to his lips. “You and the baby are my world now. I would do anything for you.”

A sweet feeling stirs within you. After the horrors of your past, you never thought you could find a life of peace. Yet here you are, living a life with Halsin, and growing the promise of a future inside you.