#tle3

[chdarling]

ok so, I can't, like, set a precedent for every time there is a catastrophic event in my country I post a TLE spoiler because let's be real, that's gonna be every day for the next four years at least and I only have so many non-major-spoilery TLE bits to share. But I'm making my way through an emergency bottle of prosecco and texting my friends about how in the face of the endless onslaught of late stage capitalism, fanfic -- a community built purely around love and joy and not a single drop of money being exchanged -- is in a small way something radical and precious and dare I say holy (did I mention I was drunk) and that should be honored on today of all fucking days, and ALSO we should all spend less time staring at gifs of that evil-ass motherfucker doing nazi salutes and more time crafting joy and creating community with each other so

here is a lil snippet from TLE3

as with all my spoiler snippets, I reserve the right to completely rewrite this before the final draft because honestly this was mostly an exercise in me learning how to craft sentences again mid-burnout, but!!!! here, have a lil moment of joy, maybe. i love you.

Excerpt from The Last Enemy: Marauders’ End

“So, what do you think?”

Sirius turned expectantly to his best mate, who stood beside him as the boys peered through the doorway of Sirius’s second bedroom. The room had been unoccupied at the time of Sirius moving into this flat a few weeks ago. Now…it decidedly was not.

“Er…” said James, who did not quite seem to know how to answer the question.

“Her name is Lola,” Sirius added in a reverent tone.

“She has a name, does she?”

“Of course she has a name, you pig.”

“Right,” said James. “Well, then frankly, I’m a bit hurt you moved out and left me for Lola.”

Sirius knocked his shoulder against James’s. “Come on. I didn’t leave you. We’ve been over this. I’m of age, I was going to have to get my own place eventually.”

“Yeah, okay, sure, but you barely made it a month before you shacked up with your new flatmate, Lola.”

Sirius grinned. “She’s sexy, isn’t she?”

“She’s…very shiny.”

“She’s the goddamn love of my life.”

“Okay, ‘she’ is a motorbike, mate. You’ve gone completely batty.”

Sirius laughed and strode further into the room where indeed the Muggle motorbike had been set up, dominating the space. It was a thing of beauty, all sleek lines and silver glint. The floor around the motorbike was haloed with the detritus of Sirius’s last few delicious days: all sorts of mechanical bits and bobs, empty beer bottles, an ashtray, a crumpled up bag of crisps, a few oily rags, and a confusion of Muggle tools, the names of which Sirius kept mixing up — a socket wrench, he thought that one was called. The spare bed that had once been the primary feature of this room — a springy mattress James had transfigured for the nights he was too pissed to apparate home (“Mum won’t mind, she put the security spells on your flat herself.”) — had been shoved into the corner to make room for this new sacred altar.

James did not seem as impressed with Sirius’s new acquisition as he felt his friend ought to be. “You’re just jealous,” Sirius told him, “that you’ve never known a love so true.”

“Ha. Touché.”

Sirius pulled a rag from his back pocket and began to lovingly polish a spot on the seat of the motorbike.

“You know,” said James, still observing from his post at the doorway, “I’m not sure it’s healthy, you spending so much time by yourself.”

“What time by myself?” laughed Sirius. “You’re here almost every day.”

This was true. Hardly a day had passed so far this summer that James hadn’t found a reason to come by. Not that Sirius minded. Though he’d never admit it, he liked living on his own rather less than he’d expected.

“Yeah, well…” James strode closer to inspect the motorbike. “Someone has to make sure you don’t go completely bonkers, all on your own here. Lola, I ask you. You know, if you start talking to the bike, mate, I’m hauling you off to St. Mungo’s too.”

Sirius leaned down and whispered to the handlebars: “Don’t listen to the mean man, Lola. I’d never leave you.”

James sat down on the spare bed with a mournful creak. “Besides,” he said, “Potter House is too quiet now, with you gone and dad all…entombed. Some days I think if I don’t get out, I’m the one who will go bonkers.”

Sirius turned back to his friend, suddenly somber. “Hey, you know I’m just joking, right? You’re always welcome over here. I love having you here.”

“Yeah,” said James, though the faintest tint of melancholy compromised his credulity. Sirius watched as James plucked an oil-stained rag from the bed, sniffed it, then tossed it aside with a wrinkled nose.

“How are things…?” Sirius ventured. “With your dad?” Fleamont Potter’s health had been in steady decline for years, but last Christmas things had taken a turn for the worse. The diagnosis seemed to be simply that he was old…though Sirius had a hard time wrapping his head around that. “Have things gotten any better?”

“No,” said James shortly. “And they’re not going to. It is what it is.” He glared at the wall for a brief moment, then sighed — a deep, intentional sigh, as though exhaling all his miseries in order to transform himself back to Sirius’s good-natured friend. “So…does she work?”

“The fuck d’you mean, ‘does she work?’”

“Well,” said James, “it hasn’t escaped my notice that the bike is in your spare bedroom, rather than, say, on the street. So either you and Lola have a far kinkier relationship than I care to know about…or she doesn’t work.”

A pause.

“She’s a work in progress, okay?”

“Knew it,” grinned James.

“Hey, have some respect,” said Sirius. “I’m fixing her up myself. It’s far cooler than just buying some shiny toy from a shop. This is my bike. Mine. I’ll make her fly, just you wait.” He stroked the bike handle. “Isn’t that right, Lola?”

“Yep,” sighed James. “Completely bonkers.”

[memebijin-love]

#I want to read (in #TLE) the moment when James and Lily found out Remus is in love with Sirius... Wahhh.. ❤️ #Maybe in the volume 3...❤️

Lily: so what’s a green flag for you?

Remus: when he’s smart

Lily: obviously-

Remus: and when he has black hair, grey eyes, has lots of money, sits on me, lets me read him my nerdy books, kisses all my scars, and tells me I’m pretty even though I’ve thought of myself as a monster my whole life

Lily: those are a lot of green flags

[yallthemwitches]

Hey!

First off, I just gotta say I’m a huge fan of your Lily and James stories, especially the smutty ones, haha. I love them! Seriously, I adore my smutty jilys and can’t wait to see what else you have in store for them. I’ve been reading your fics for a while now, and I’m totally hooked – your writing is amazing!

Speaking of which, what do you think of CH darling and their story The Last Enemy? I’m absolutely hooked, even though I know they’re taking their time with the next book (TLE 3 confirmed). I’m dying for it to be published, but I get it – every writer needs their space. Still, the wait is killing me, haha. I’ve been reading their stuff for years, and after all this time, I finally worked up the courage to message them, and they were so sweet in their reply.

And of course, I really want to thank you so much for always responding to my writing requests and ideas. You’re awesome! You always deliver and make my day with your stories.

I just wanted to say that, right now, you and CH darling are my two absolute favorite writers, and I’m always looking forward to what’s next from both of you. I seriously love everything you write!

Sending you a big hug, hope you’re having an awesome day!

Love ❤️

So, I had to step away from this message and hold my heart for a minute because, wow. Uhm. THANK YOU.

I'm sure you're aware but The Last Enemy is my biblical jily and marauders. period. end of story. I've been reading jily fics since I was a stinky 13 year old and I've never found a fic that felt so close to canon that honestly jkr should just give copyright to chdarling and call it a day.

To even have someone say that @chdarling and I are their favorite writers is insane. More than insane. Like you don't understand, I'd cut off my own hand to have half the talent she has for cobbling a plot together, weaving in character povs, political commentary, obscure canon references AND keeping it succinct for THAT long. My god. So thank you, I actually might tear up. I am not worthy.

So you can imagine I am not doing well waiting for TLE3 but I respect her needing the space and time and I totally understand where she's coming from when she says it's hard to find motivation to write while the world is literally on fire. Do I very selfishly wish she would say 'fuck it' and release what she already has? Absolutely- would ritually sacrifice a small child for it-but again, life comes first and I'm already so thankful for everything she's given us. I also mad respect her for using her platform during this hiatus to keep people politically aware and involved. Absolute queen.

I hope you know she has little snippets here and there on her tumblr which I always go back to reread when I just need a little pick me up in the day. Her jily just is so flawless...(ok, I'll stop gushing.)

Anyways, again THANK YOU SO SO MUCH. I know thanks can sometimes sound hollow but I honestly don't know how people even continue to read what I write. Every message in my inbox or comment or kudos or like or whatever feels like a little firefly fluttering in my heart in the greatest of ways.

[lyrics365]

Paranoia

[Refrain] 7it 7yati ma tel3atch ki bghit bentlii fake A7lam w future zwine kifa9t l3in tle3 kolchi fake Mamsayn ta khir yjini mn ta chi fake hit f3aylhom fake Ghar9 f chak mserfe9 b blaka mktob 3liha koulchi fake [Couplet 2] Stora kay2rkho li fat Li 3chto khlanai paranoia khayf Ta mn nfsi wlat katbanliya khant Mab9it nfr9 bin kdoub ou li fact Sknli fe dmaghi ghi lkhouf Mab9itch nti9 fe dli balia…

[chdarling-tle]

I LOVED the new chapter. Always love James, but this was such a satisfying read - James being confronted so forcefully with an unjust world that he desperately wants to fix, but realizes he can’t. But he CAN do small things. And those small things can make all the difference. Also James interpreting Lily’s inability to look at him bc he’s the sun as anger, just perfect. Just a hunch, and feel free not to answer if this is too spoiler-y, but in your TLE3 first kiss snippet, is the [redacted for TLE2 spoilers] part about training Valmai in quidditch? Feels like something that Lily will learn about and feel so touched by. Continually astounded by you, masterpiece, incredible characterization etc etc etc.

I’m not going to answer about the TLE3 snippet yet, but that is a very popular theory indeed 😌🥰❤️

Thank you so much for this kind message. I’m so pleased you enjoyed the chapter!! I’ve been looking forward to getting to this point in James’s development, so it was a joy to get to share it with you. He’s been progressing through the various stages of ignorance ➡️ denial ➡️ excuses ➡️ despair and now we are at ACTION JAMES! Yay! 😂

Much love to you ❤️❤️❤️

[chdarling]

Oh my goodness. TLE Lily is extremely dear to my heart, so this means so much to me. Thank you, thank you, thank you.

Lily: Yeah, yeah, yeah. But is there an award for meanest writer? Most Likely to Needlessly Torture Her Undeserving Heroine For No Good Reason? Because I'd like to vote.

Me: Listen, I know you're going through a rough time right now...

Lily: And whose fault is that?!

Me: It's not all bad! Have you read the TLE3 snippet? That's nice!

Lily: James, if you want to hex her, I won't tell.

James: Actually, I rather liked the TLE3 snippet myself.

Lily: 😤

Favorite Lily Characterization Winner is:

The Last Enemy: Dark Marks by @chdarling-tle

The entrance to Hell is hidden at the base of a large willow tree, a human-sized hollow tangled in its roots, ready to swallow you whole…

It’s 1976 and the events of the past term at Hogwarts have left their mark on all involved. But it’s a new school year now, with new teachers, new rules, and new regrets. Yet as the war clamoring outside the castle walls grows ever louder, the students inside will learn that some marks are impossible to wash away.

[smartphone-science]

This is part 3 of the bacteria-killing-with-arrows series. The first two parts were bacteria killing each other and bacteria firing powerful spikes. You might want to read these two before delving into this current article.

This current article is based on a study that has just been published and which caused me and my former lab buddy long evenings discussing it and coming up with a great (and fun!) concept.

So I guess you remember the arrow bacteria use to fire into other bacteria. Different lethal toxins are attached to this arrow. When bacteria fire this arrow together with the toxins nearby prey bacteria, this usually leads to death of the prey bacterium.

In this study we look at the very tip of the arrow, because on top of the spike of the arrow sits another protein. We call this protein PAAR and it is a super sharp protein. This sharp needle-like protein helps to punch a hole into the prey bacterium. So this super sharp PAAR protein seems to be quite important for the firing and punching process.

Our beloved bacterium Pseudomonas aeruginosa contains seven different PAAR and ten different spike proteins. However, we still don’t know which PAAR sits on top of which spike and which of the PAARs plays a double role and occupies two spikes.

Here we focused on an arrow that is composed of three G2b spike proteins (purple in the below figure). We already knew that G2b is a special spike protein because it contains an extension which at the same time is a toxin (purple pacman). Then we could also show that the toxin Tle3 (red pacman) binds to the G2b spike and is delivered together with this spike.

This already makes this arrow pretty special, because it carries more toxins than the other arrows that I talked about before. In the previous article I discussed the G4b spike that carries the A toxin, and the G5 spike that carries the B toxin. So in many cases it is one spike – one toxin, while the G2b is one spike – two toxins.

Then we wanted to know which of the many PAARs might binds on top of the G2b spike. We indeed found that when PAAR3 was not present in the bacterium (we also tested a bunch of others!), no G2b and no Tle3 were fired out of the cell. Also, neither Tle3 nor the toxin domain of G2b was delivered into other bacteria. This likely means that PAAR3 (orange) sits on top of the G2b spike.

By accident, we then found that when the PAAR3 is not present in the cell, the A toxin (from the G4b spike) was delivered more efficiently. This was surprising, as this means two things: the A-G4b spike has another PAAR on top than PAAR3. Second, PAAR3 seems to inhibit the delivery of the A-G4b spike.

But that is something new. The G2b-Tle3 spike seems to be preferably delivered than the G4b-A spike. But was that also the case with other spikes? Could PAAR3 together with the G2b spike and its many toxins even be the favoured spike of all arrows?

We tested that by looking at another toxin. We found that the G2a spike with the Tle4 toxin was also delivered a lot more efficient when PAAR3 was missing in the cell.

So this means that there is some kind of hierarchy when it comes to the spikes and arrows to be fired. And it looks as if PAAR3 together with the G2b spike and all those toxins is the master arrow to be fired.

Let’s take a step back and look at the whole picture here.

We know that the PAAR protein is actually the protein that is first binding to the crossbow before the rest of the arrow is loaded. We also know that to each PAAR protein a specific spike (G2b, G4b or G5…) is binding. Thus, it seems as if the PAAR protein is something like the “sorting hat” when it comes to making the decision which of the many spikes and thus which of the partner toxins are delivered. This is actually pretty cool and is shown in the picture below.

So, as I said at the beginning, those pointy PAAR proteins are really important in the whole arrow firing process. Looks as if they are even more important than we thought.

This was the third articles of the bacteria-firing- spikes series and if you want to read more, have a look at those publications or send me an email with questions or drop me a comment. I’m always happy about any type of feedback.

via Science Blogs

[cancersfakianakis1]

Appendix-derived Pseudomyxoma Peritonei (PMP): Molecular Profiling Toward Treatment of a Rare Malignancy

Objectives: Pseudomyxoma peritonei (PMP) is a rare malignancy originating from the appendix, characterized by disseminated mucinous tumor implants on peritoneal surfaces. We examined the role of multiplatform molecular profiling to study biomarker-guided treatment strategies for this rare malignancy. Methods: A total of 54 patients with appendix-derived PMP were included in the study. Tests included one or more of the following: gene sequencing (Sanger or next generation sequencing), protein expression (immunohistochemistry), and gene amplification (C/fluorescent in situ hybridization). Results: Targeted sequencing of 47 genes detected variants in KRAS (81%), GNAS (74%), SMAD4 (16%), and ATM (16%). Mutations were found at low frequencies (n=1 to 2) in APC, BRAF, PIK3CA, MLH1, and TP53. GNAS and KRAS co-occurrence was found in 87%. Protein overexpression was found in epidermal growth factor receptor (83%), cyclooxygenase-2 (73%), cMET (63%), cKIT (58%), and platelet-derived growth factor receptor alpha (58%). Immune checkpoint expression was found in 36% (programmed cell death protein 1) and 18% (programmed death-ligand 1). Surrogate markers of cell proliferation were found at low rates (TLE3 23%, TOP2A 22%), consistent with the slow-growing biology of PMP. Phosophatase and tensin homolog was intact (wild type [100%]) and positive (immunohistochemistry [80%]). Patients exhibited stable microsatellite status and mismatch repair proficiency (93%). Importantly, multidrug resistance protein expression was elevated (100% BCRP, 94% MRP1, 88% PGP). Markers for gemcitabine (RRM1), fluorouracil (TS), oxaliplatin (ERCC1), and irinotecan (TOPO1) chemosensitivities were detected at favorable rates: 93%, 87%, 77% and 65%, respectively. Conclusions: Molecular profiling by multiple platforms identified potential therapies for the nontargetable KRAS-mutated population. The role of cMET-targeted therapeutics and immune checkpoint inhibitors merits further investigation. Biomarker-guided selection of cytotoxic chemotherapies may facilitate efficacy to systemic treatment. https://ift.tt/2A9Dz6K

[chdarling]

I continue to not have any real updates, HOWEVER for old times sake I do feel the need to inform you all that I was sitting here casually daydreaming and just thought of a TLE3 scene that made me legit do this:

So, the work continues, etc.

Hope y’all are well. ❤️

[chdarling-tle]

I am looking forward to the Snape POV chapters once Jily starts happening because I enjoy watching him suffer. Haha, I'm kidding! (Not really)

I have already written a few of these scenes, so clearly I agree...😉😘

[chdarling]

As we’re getting closer to a truly awful day for America, I just wanted to check in on you. Things are bleak and about to get so so much worse, I want you to know I’m here and many others are here too when you’re ready

This is very kind of you, thank you. Honestly, I have not been doing great. Watching my neighbors elect a racist, fascist, Nazi-loving rapist triggered a pretty bad depressive episode on top of what was already the worst period of professional and creative burnout of my life, so….I’m struggling. Still trying to claw my way out of the dark. I’m deeply appreciative of the kindness of this community and am sorry that I haven’t (and probably won’t for a little longer) been able to engage the way I once did. I will again one day, and I am so thankful to know all you wonderful people online. <3

On a note that is completely unrelated to this gentle ask, I’ve been getting a ton of messages lately asking for a date when TLE3 is coming out and I don’t feel up to answering them (sorry) so I’m just going to tack this on here since I buried my last post on the subject under a mountain of despair reblogs: TLE3 is going to take a while.

I’m still planning to continue with my writing projects (be they TLE or other things), but right now I’m focusing on securing my own oxygen mask, etc. When I finished posting TLE2, I said that I would be taking a break and also that I would not be posting TLE3 until I had written all of it (like I had for TLE1). Even if I had been writing diligently every single day since I posted the last chapter, I still wouldn’t be done, so please understand that it’s going to take a while. It certainly will not be coming in the next 6 months, very possibly not in 2025. I know some people won’t be happy to hear that, but just a fun statistic: OOTP has 257,045 words and took three years to write/publish after GOF. TLE2 has (and this makes me cringe a little) 407,079 words and took roughly 3 years to write as an unpaid side hobby on top of full time work, education, etc. I don’t say this to toot my own horn (frankly, it just makes me desperately want to retroactively edit the crap out of TLE2 lol), but rather to reiterate that writing a book-length work takes a lot of time, energy, and love. I don’t want it to take 3 years (and I don’t think it will, TLE3 will be a more reasonable length), but it’s certainly not going to be finished in a few months. That would be insanity and I am not that talented lmao.

I do know that the requests for updates come from a place of love and enthusiasm and excitement and I really, truly appreciate that. I also appreciate all of the kind words of the asks I haven’t been answering. Please know that I’ve read them, I love you, and I will be back eventually. I just have to focus on my health right now, and unfortunately these days being online is pretty bad for that, so I'm going to try to be logged off for a while.

And finally, on another completely unrelated but perhaps mildly tangential note: if anyone has any books recommendations or resources on processing climate grief, I, uh, could use them. 🫠

[chdarling]

Ok, so I’m going to be THAT person: I was rereading the snippets you have here from TLE3 and with a bit of sleuthing I have gathered that the KISS happens at Sirius’ flat (rooftop? Idk you mention seeing a skyline so I assume London) which makes me imagine that the KISS will spawn jily spending the rest of the summer snogging/shagging all over Sirius’ very few possessions (like Lola ;) )

Needless to say, I am very ravenous and hopeful that TLE3 will finally give us the much needed jily snogging/shagging they deserve. And please, if you are ever worried that they might be doing it too much—i promise you, there’s never too much.

-Tay

Hahahaha no comment but I promise they will make up for plenty of the time they lost in TLE2 being f’ing idiots. 😌

[chdarling]

Hii, I recently finished reading tle 2 and I was wondering what years do tle 3 and 4 cover? I would assume tle 3 covers the seventh year at hogwarts but then again I'm not sure.

TLE3 is the marauders’ 7th year (1977-1978) and TLE4 is the war years (1978-1981). At one point I was going to split TLE4 into two books because it covers so much time, but I think thematically I want it to be one. Or maybe it’s because the idea of “TLE5” provokes in me a deep sense of dread hahahhaa. TLE5? What’s next, TLE792?!?

[chdarling]

Would you make another trailer video for TLE 3 when that comes out? I am STILL obsessed with the TLE 2 Trailer (particularly your song choice that was beyond brilliant). I could write a whole dissertation on how excellent you paired Fort Nowhere’s The Times They are a Changing with the themes of your fic and it’s seriously brilliant and you are seriously brilliant.

Anyway that’s the end of my gushing much love to you dear I hope you are doing well 💕

Oh this makes me happy. 🥰 thank you!! I have a soft spot for my obsessively plotted trailers hahah. I have trailers planned for both TLE3 and TLE4. Whether I’m able to make them depends both on my time and energy as well as whether I can afford premier pro at that time in my life. 😅 But I want to, so for now I’ll say yes, I will. 🥰

[chdarling]

When will you release TLE3?? Just waitingg

I realize I need to get my act together and make an FAQ to pin because things get buried by reblogs, but I’ve said a few times that it’s not coming in 2025, and that hasn’t changed. I appreciate the enthusiasm but it takes a long time to write these stories and there’s a lot going on in life right now, so it’s going to be some time yet. Thanks for understanding!

[chdarling]

Hello CH Darling, I saw you respond to someone that you’re thinking of slowly releasing each chapter of TLE3 instead of posting the whole thing. I really do apologise because I’m sure this is an annoying question but would you ever consider posting the whole book or however much is completed? Please queen, I’ve never yearned for a book as much as I’m yearning for TLE3 and 4. I’m literally writhing in anxiety because I’m about to finish TLE2. I started reading The Last Enemy 2 weeks ago and waiting for each chapter of TLE3 and 4 sounds like torture. Torture that is absolutely worth it but agonisingly painful.

I promise I’ll comment 10 times on each chapter if you release all of TLE3 🙏🏽🙏🏽🙏🏽

Hahaha I’m so glad you’re excited for it! But tragically I can’t release it because I haven’t written it yet. I promise I’m not just sitting on a fully written novel out of spite or something 😂❤️

I definitely won’t be posting it before it’s completed though, sorry. I did that with TLE2 and I swore I’d never do it again. I do admire people who thrive in writing as they go, but it just doesn’t work well for me, and particularly with TLE3 and TLE4, they are very intricately plotted and trying to do all of that chronologically is just a nightmare.

But, there’s pros and cons because while there will be a longer wait in between the books, I should hopefully be able to maintain a consistent posting schedule. I think back very fondly to the early pandemic days when I was posting consistently twice a week. My dream scenario is to do that again. We’ll see!

Thanks so much for your message and your enthusiasm ❤️