#jacquemont

[thedovahcat]

I got into playing around with the Arctium local server for Wildstar and just revisiting some old places has really put a zip back in my step.

Naturally there are bugs abound and you can’t play, but that’s to be expected. At least now we can still see all this work Carbine did :’) and it won’t ever go to waste. I do miss Roger and everyone a whole ton.

Funny enough though he never has green eyes when I make him. They always turn brown. Sooo...!

[thedovahcat]

the BOTS

[doctorveera]

A genetic exploration of ASD resiliency

As I mentioned in my earlier post, among the many papers that I bookmarked for “reading later”, this preprint was in the top of my list, and I managed to read it today. There are two reasons why I had a special interest in this preprint.

First, it addresses a question that I—and probably many others—were thinking about more and more recently: why some individuals carrying a large effect mutation(s) for a particular disease do not develop the disease; what factors make them resilient to the disease?

Second, I learnt about this preprint through Dr. Sébastien Jacquemont (a co-author in this paper,) a scientist whose work I’ve started admiring a lot recently. For e.g. I found two of his papers on the associations between copy number variants and intelligence highly insightful, which I have also summarized as twitter threads (thread1, thread2.)

In this paper, the authors have analyzed the exomes of around 10,000 ASD cases and 100,000 non-ASD individuals (who were mainly from the UK Biobank) with one particular aim: what makes non-ASD individuals who carry loss of function (LOF) mutations in known ASD genes resilient to ASD?

The authors have looked into a list of 156 genes what seem to be “robustly associated with ASD.” For each gene, the authors calculated the ASD penetrance (in terms of relative risk, which is “the risk of being diagnosed with ASD when carrying such variants,”) and compared the penetrance estimates with the LOF intolerance measures, and found them to be highly concordant. This reinforces the notion that genes linked to ASD are simply genes linked to brain in general. The most robust metric of a gene’s specificity to brain is its mutation constraint. And we see it for the ASD genes as well, also intellectual disability (ID) genes. Note that there is no clear distinction across ASD specific genes, ID specific genes and brain specific genes. And this has been the basis of a paper titled ‘Insufficient Evidence for “Autism-Specific” Genes,’ that came out last year, and stirred some tension among the ASD researchers.

Despite the high concordance between ASD penetrance and mutation constraints, there seem to be some interesting exceptions, e.g. PTEN, SHANK2, which are highly penetrant for ASD, yet less intolerant to LOF mutations. That is, despite mutations in these genes often leading  to ASD or ID, they seem to evade natural selection. How? Such outlier genes, perhaps, hold the key to opening the ASD mystery? The authors also report a list of 25 genes that are fully penetrant for ASD. That is, among the 100k non-ASD individuals, the authors found not even one person who carried a LOF mutation in any of these 25 genes and did not develop ASD. I find this list extremely intriguing, and I plan to dive deep into this list later.

The authors found that the cognitive functions of non-ASD LOF carriers in the UK biobank are significantly lower compared to non-ASD non-carriers.  More penetrant the genes are for ASD, higher the differences in cognitive functions between carriers and non-carriers. My immediate thought on reading this finding is if the authors repeated the same analysis in some brain-specific highly constrained genes (irrespective of their association with ASD), they would have seen the same. In fact, that’s what exactly was shown in Dr. Jacquemont’s previous paper. My point is all these analyses are reflecting brain specificity, rather than ASD specificity.

Importantly, the authors found that the liability threshold model holds true for ASD; non-ASD LOF carriers had lower burden of common ASD risk variants than ASD LOF carriers, which seems to indicate that the decreased common variant burden might have contributed to the resiliency of the non-ASD LOF carriers.

Finally, the authors searched for clues that might support the “female protective effect” hypothesis. The authors expected (or may be they didn’t) that female sex might be one of the contributing factors for ASD resiliency in non-ASD LOF carriers. Unfortunately, that wasn’t the case. The non-ASD LOF carriers were equally distributed among males and females.

Overall, this is a fascinating and thought-provoking paper, and I enjoyed reading it, tweeting about it, and also, summarizing it here.

[rogerbriden]

Veggie Soup

“One more game Roger then we'll stop! Pretty please?” Mara bobbed back and forth in her seat and clapped her hands together.

Roger grunted and looked down at the table. He was sick of playing card games. Mara seemed to like those however, and she was always really nice and brought snacks and those juice boxes...so he let it go without throwing a fit.

“Can we color pictures instead?” He asked, turning away and scratching his nose. “Jacquemont???” He called out, looking around for the scanbot.

Mara's tail swished back and forth slowly out the back of the plastic chair. “Yeah, we can draw if you want to. That's always fun! You did really good today too!” She reached forward, collected all the cards and wrapped a rubber band around them, tossing them into her pack shortly afterwards. “Got any paper?

Roger got up, went into the other room and came back with a folder of the stuff and a box of markers (the really big ones no less.) Jacquemont followed him, humming loudly and making little loops in the air. “Here!”

The Aurin smiled and pulled a sheet of paper over to herself, grabbing a marker at the same time. “These are nice! Did Walker get them for you?” She asked.

The human nodded. “Mhm! He did. I like them a lot,” He answered, uncapping a few and clumsily drawing out crude shapes with them.

As Roger moved his hands Mara made sure to keep note. “Having problems with your hands lately? Are they hard to move sometimes?”

The man looked up. “My hands?” He paused and stared at them, flexing his fingers carefully. “No? They're ok.”

“That's good. Make sure you stretch 'em out and such every now and then ok?” Mara explained as she drew a big circle. “What're you going to draw?”

“I dunno,”

“I'm gonna draw Acorn!”

Roger glanced over at her paper. “Acorn?” Jacquemont also bleeped questioningly, turning his entire body to show it.

The Aurin nodded, “Yeah! Acorn is my scanbot! He's not here today though, he's back at the lab keeping watch for me...on some uh...important experiments!” In truth, Acorn was watching out for Dr. McPhearson. If he of all people caught on that Mara had been coming here weekly, it wouldn't end very well. He and Walker HATED each other to the bone, maybe even further than that.

“Oh! Yeah...you're a scientist!” Roger added, grinning. “Just like Walker!”

“Yes!” Mara nodded, “I am! I'm so happy you remembered!” Her ears twitched and her tail puffed up. So far so good, Roger was improving. He even told her what he had for breakfast this morning, something he usually forgot. “Walker'll be pleased to hear that, you know?”

Roger's eyes lit up. “Really...? You really think so??” Just the thought of hearing Walker being remotely HAPPY about something in turn made HIM very happy. Excited even.

“Yeah! He just wants you to remember things is all. Since you have a hard time with it sometimes...Not that that's bad! You're getting better quicker than I thought you would, so that's really good!”

The human leaned back in his chair and looked up at Jacquemont, who was making what sounded like happy beeps and boops. Even the end of his antenna was lighting up brightly and sticking straight up in the air.

While Roger didn't recall being so forgetful, ironically, he did know something was wrong with him. It just didn't feel right. Walker was always so unhappy about whatever it was too, he could see it on his face. Walker would always talk about it in passing, wondering aloud why Roger wouldn't ever pay attention or sit still, much less remember what was going on, scolding him for it at times even though he knew it would do no good.

Roger remembered some of these things yes...Every day it'd be just a little more. Either way, it all made him feel ashamed of himself from time to time.

After a moment of thinking, he sighed, slouching in his chair. “...I don't want Walker to be so mad at me...” He muttered.

Mara stopped and looked up from her picture. “Mad? Walker's not mad at you Roger. What's wrong?”

“Yes he is,” Walker was always grouchy about everything and he wasn't helping the situation. “...He's never really happy.”

Mara tilted her head. “It's not because of you Roger, honest. He's just got a lot of work to do and when he finishes, he has even more work to do...it's like....pretend you just finished planting seeds outside...Well, imagine someone told you that you had to do ANOTHER garden-full of seeds, plant them that is. And then another when you were finished, and then another and another and suddenly you have so much to do.”

Roger thought about it carefully. Mara had a point. Who wouldn't get angry at that? Was that what Walker was dealing with? He never was outside planting as much as he used to... “...It's not me though?” He asked sheepishly.

“No, he really likes you Roger. He gets frustrated is all, with everything, and he's tired. That's probably why he got sick recently remember?”

That was right. Roger recalled seeing Walker sniffling a lot more and coughing, moaning and groaning and looking even worse than usual. He tried to get Walker to do stuff with him but the Mordesh was never really in the mood for it, and understandably so now.

“Really likes,” He repeated slowly. “...He does?” Just the thought made him feel funny again. Warm and tickly even.

“Mhm,” Mara nodded, watching him. “If he didn't you'd know, ahah. He's really...clear about that much I'd say.” If Walker hated you he'd be polite about it at first, at least until you were out of the room.

“Ooh...OH! Oh, that's good, I'm glad,” Roger smiled, returning to his own drawing. It was the garden, and a whole lot of flowers, and Jacquemont flying around like a little bee. “I really like him too.”

“Yeah?” Mara giggled a little bit. “Well it's a good thing you work for him then. He probably couldn't take care of the garden outside if he were all by himself you know. So I'm sure he appreciates it.” While she did wonder just how far Roger DID like Walker and vice versa, it was a pointless venture at this time. Not to mention none of her business. Just so long as nothing bad was happening.

“Say,” She started, “You seem to really like scanbots don't you?”

Roger nodded, and put his hand on Jacque, who was sitting on the table watching him draw by now. “Mhm! They're nice, just like Jacque, but they're not yellow like him so he's special.”

The little yellow bot turned away shyly and hid his face with his wing flaps briefly.

Mara always did enjoy watching them interact. Too gosh darn cute. “Yellow's a good color for him I'll give ya that! You ever think about being a scientist too? Everyone gets their own scanbot you know.”

Roger's eyes widened. “OH no! No, no I don't wanna be a scientist,” He shook his head. “I don't want another scanbot. I wanna go explore, just like Dorian Walker... His name's Walker too, it's funny.” That was probably the only reason he even remembered the man, other than the fact that he practically worshipped him and the other explorers running around Nexus. Especially the Roan Ranger, fictional as he was. “Walker- uh...this one- he's taken me to his museum before!” And while he didn't remember what was there, he did remember going up to the highest plateau in the city and seeing all of Thayd. He wanted to climb even higher but Walker told him not to (or rather, physically kept him from doing so.)

“Has he? It's really nice! You know, I've seen you climbing around on the ship outside sometimes, you're really good at it! You could be a good explorer I bet.” A thousand times Walker asked Mara not to plant ideas into the boy's head but...with that puppy-dog look? She just couldn't help it. Maybe once he got better he could do what he always dreamed of. Have adventures on Nexus just like so many other people were.

“You think so?? I want to.” Roger nodded, looking very excited again. He glanced down at his drawing and held it up, satisfied with it. “I'm finished!”

“Oh let me see!” Mara hopped off her chair and moved around the table to get a better look. “Aw! That's Jacque! And Bell too!”

“I should show Walker-”

“Ah- maybe later, I think he's sleeping downstairs.” Which was beyond good for him at this point. “Want to watch a movie? I brought something you might like.”

Roger set his picture down gently and wipes his marker-stained hands on his pants. “Movie?”

“Mhm! C'mon!”

“Can we have popcorn?”

“How about some fruit instead? I brought all kinds of snacks.”

As the television played some corny movie about hoogles upstairs, Walker opened one eye, face still glued on his work-space. Stars above he was so tired. But at least Roger was taken care of upstairs.

“...Explorers,” He snorted. Jacquemont came hovering down the stairs and plopped down next to him on the table with a soft kerplunk. “...What's she telling him?” He mumbled, sniffing loudly and wiping at his nose some more. If only this damned cold would go away.

Jacque rolled around happily before flapping his little wings in response, antenna blinking.

“Hmph...” Slowly the Mordesh sat up and rubbed at his eyes. He'd only dozed off for about an hour and a half, but still, it was a lot better than not sleeping at all.

Upon looking to the side, he spotted a note sitting on his desk. So he picked it up. It was Mara's handwriting alright. She certainly was becoming a medical doctor like she wanted to be; the words were barely legible and looked more like long scribbles. Something about soup and vegetables and the fridge. It sounded like she'd brought more food for them and was telling Walker to make himself something to eat if he could, though, if that wasn't what it said, then it was anyone's guess.

Soup sounded pretty good right now anyway, even if he couldn't taste very much of it.

As for all that talk about exploring and Roger? He sat there for a while, thinking on it, before finally setting the note down and putting his head down again as well.

Roger would just forget. No big deal. He always said he wanted to be an explorer but he wouldn't go out and actually DO it if only BECAUSE he'd forget to. He wouldn't go anywhere and he'd be safe here on the house lot, away from all the dangerous things like Ravenous and...more Ravenous.

In the back of the botanist's mind though, it did bug him, at least a little. What if Roger did suddenly remember everything? What if he wanted to leave after that? What if he wanted to go get himself into trouble? That much he wasn't doubting at this point. That boy could wander off damn near anywhere and not be afraid if he were distracted enough.

And to make matters worse, well, Mara was making it worse actually. She didn't have bad intentions, he knew that. But still.

No...he'd have to be cautious and put a stop to it fast. No more dreams about exploring. No more nonsense about going out into dangerous places only to either be eaten by wild animals, mad Ravenous or blown up by the Dominion. Roger was NOT going ANYWHERE.

“...Gonna hafta...tell her,” He muttered again, closing his eyes and inhaling slowly. His nose was all stuffed up again. “...Later.”

Jacque watched as the Mordesh slowly and uneasily fell back asleep.

He had no idea what Walker was so worried about. Didn't he ever watch the Roan Ranger? The best explorer on television? Nothing bad ever happened to him, so it wouldn't happen to Roger either.

Eventually the little bot floated back upstairs and plopped down onto the couch in between Roger and Mara to watch more of the movie, while running searches for veggie soup recipes in the background.

[thedovahcat]

I have every reason to believe there is in fact a show called The Roan Ranger on Protostar networks for television.

And that Roger is absolutely obsessed with it.

[thedovahcat]

Walker's weird, weird, weird little family spanning over ...well probably a good century and a half or so

preciousbbs alla them

[thedovahcat]

A doodle that got out of hand. It was for this initially, then it just got away from me.

MARKET SHOOPPPPINN. WITH TOUCHABLE HOLOGRAM CARTS.

[rogerbriden]

Hoogles

“Ugh- where's my tablet-” Walker pat around himself, turned around several times before slapping a palm onto his face and running it down. “Roger go look in that aisle right there, I probably put my datacron down for a moment when I heard you screaming. Jacque go check, hurry up.”

Jacque buzzed loudly and floated over towards the designated aisle, leading a grumpy Roger over to it.

The man scowled and stood on his toes, leaning to one side to look down said aisle. A datacron was sitting on a shelf not so far away; he ran over to it, picked it up and looked at it.

As he was about to return, however, he paused. Glancing over at the book-area. Quickly he looked back to Walker. The Mordesh had his back turned to him and was fighting with the scanning machine.

Good...

Quickly he pulled off his coat and snuck back towards the books. Jacquemont watched him go, confused.

“ROGER? GET OVER HERE!”

“OK! COMING! Coming...”

_______________________________

Walker was far too occupied with getting the 'groceries' back home in one piece to notice Roger lingering behind him. “Where are you? For gods' sakes, get over here before you get left behind again.” He grumbled, pressing a series of buttons on the teleporter's keypad in order to send them back to their home lot.

Roger caught up with him and almost crashed into him, his coat bundled in a big wad in his arms.

Walker eyed him suspiciously. “What's that? Why're you holding your coat like that?”

“N-nothing!” Roger chirped, hugging it closer to himself. Before the botanist could question it any further, there was a flash of bright blue light. They were home now.

Immediately the human darted out into the yard and turned back to make sure Walker was still there. He was.

Jacque made a strange noise before turning to Walker, startled to see he was being stared at. The Grismaran narrowed his eyes. “What did he do.”

The yellow bot hovered up and down, 'wing-flaps' moving up and down, antenna perking up and blinking rapidly. He looked nervous somehow (as much as a piece of A.I. could be.) And that wasn't a good sign.

What on Nexus did Roger do now??

After frowning extra hard, the Mordesh grumbled to himself some more, bringing the bags of cereal and cup noodles over and into the house. There they would sit in the cabinets until they were consumed. What a cruel fate.

Roger on the other hand was nowhere to be seen. But he did hear the man's footsteps running back and forth upstairs.

“...Roger? What are you doing up there??”

The noises stopped. “...UHM...”

That wasn't helping his case. Walker waited for a response, but none came. Did he forget again? Maybe so. “...Roger...”

“NOTHING!”

Like hell was it nothing.

Scowling, the botanist moved up the stairs, glancing around the kitchen. No, Roger was probably in the other room. “Roger, I'm not going to ask you again, WHAT did you do, WHY are you acting so strangely?”

As he turned the corner into the living-slash-bedroom, he saw why.

Roger stood with his back turned to him, looking over his shoulder with his coat still bunched up in his arms. Amongst it though was something green and soft-looking with blue button eyes.

It was that hoogle doll.

Roger must have stolen it from the store when he brought back Walker's datacron.

The botanist didn't know what to feel about it. It wasn't often that Roger did something like this (if at all,) but at the same time, not surprising either.

“...Roger did you steal that from the store earlier?”

The man's eyes darted to and fro, unable to settle on Walker's face. In fact, Walker was amazed he remembered about it this long in the first place. Roger must've been really focused on this.

“Answer me.”

Ashamed, Roger held his hands behind his back and looked down at the floor, or at his feet in particular. He didn't answer right away. “...I ...I just-” He sounded upset.

Walker tapped his foot impatiently, waiting for an answer.

“...I just wanted it I-” Sheepishly he looked back at the stuffed green lump sitting on his bed, 'nestled' in his coat. All the other animals were around is as if they were 'greeting' the thing. “I'm sorry- I'm sorry-” He whimpered afterwards, rubbing at his eyes.

Great, just the thing Walker didn't want. “...Roger- no- no stop- don't cry. Look, you can't go taking things from stores without PAYING for them. That's called STEALING. And I'm not housing any THIEVES either. Do you understand?” It was hard to be angry with him, even if he just committed a crime (petty as it was.)

Roger nodded several times too many before returning to the doll and squeezing it tightly. “Don't take it back- Don't take it back-” He shook his head after that. “Please-”

Walker stared at him for a while, mentally debating on what he should do. If he took the thing back, they were likely going to give him more trouble than the object was even worth. And if he didn't...Well, it wasn't like he wanted to reinforce the idea of stealing.

“Gimme it. I'm putting it away for now. You can work to get it back and pay for it like you should have done.” He held out a hand in his typical 'give me' fashion.

Roger swallowed and looked from the Mordesh's face to his open hand. He really didn't want to fork it over, but it was probably the best thing to do. “...You promise?” He asked, or squeaked.

The botanist nodded once. “Yes.”

Reluctantly, the human gave him the hoogle, very unhappy about it all. It just looked and felt so soft; he didn't want to leave it at the store. Big globby tears came shortly after that.

Walker sighed loudly. “...Don't cry anymore...You'll get it back soon.” If Roger didn't forget about it, and if he could save his money. Usually he never could hang onto it, so this was going to be particularly difficult for him.

Still, he could be determined when he wanted to be. He did remember the movie marathon on television after all.

“Look, go pull some of the weeds outside ok? Before it gets dark...take your mind off it.”

Roger sniffed loudly, wiping at his eyes and dragging his feet all the way downstairs and out the door.

Walker groaned loudly and looked up at the ceiling. Jacquemont floated next to him, bleeping questioningly and looking at the hoogle. The bot opened up, revealing what had happened at the store. Jacque had seen the whole thing (which Walker had expected anyway.)

“Right then... I'm going to have to keep a closer eye on him in that case.”

“You used to steal, too. But, not because you were bad.” The narration-app's voice said suddenly and clearly.

Walker froze and looked right at the scanbot, before shivering and swallowing the lump that was rapidly forming in his throat. “...Deactivate that program. Now.”

Jacquemont did so quickly and closed up again, taking on his usual spherical shape. Walker hated that voice and he didn't know why. Didn't he miss it?

The Mordesh closed his eyes, inhaled slowly and shook his head before returning downstairs to his workspace. The yellow scanbot hovered there, tilting his entire body to the side (a gesture of confusion if anything.)

In the end, he returned to his charger to settle down for a while.