Commission Impossible

Oct. 30th, 2025 10:00 pm
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Posted by Not Always Right

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One day, the owner of the company caught wind of the fact that my paycheck was higher than his. This was because I'd just brokered a glorious five-digit print deal with a celebrity conference. I'd also figured out how to sell deadstock to a charitable non-profit, which resulted in tax benefits beyond declaring the deadstock a loss.
The owner, however, didn't care about what I did or the benefit it provided. He saw a bigger number on my check than on his own and decided it must stop at once.

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Two Different GM Styles

Oct. 30th, 2025 02:12 pm
lydamorehouse: use for RPG (elf)
[personal profile] lydamorehouse
 ...and now back to the subjects no one cares about (but me.)

I've spent the last couple of days preparing for my D&D group. One of our players has to have gallbadder surgery the day before our planned game and since his character is critical to that plot (we're rescuing his sister, who he also plays,) I'm running a micro-campaign, something to be one and done in three hours. The basic set-up is that in some time between adventures (we skipped a level between our first campaign and our second, so it's probably going to take place in those years? months?) Because many of my players read this blog, I won't tell you anything about it other than to say that I'd (long ago) bought a module with this adventure in it, so whole plot has been laid out for me, along with treasures and stats and such. This has not stopped me from spending an inordinate amount of time creating my own twists and flavors to things as well as inventing a reason for my players to have all gathered in this town--and a whole-ass town (not to mention designing a whole new part of my world, complete with mythology.) 

Meanwhile, I have stopped prepping for my Tuesday night Thirsty Sword Lesbians game.

Other than keeping track of the story so far (and having all of the locales and NPCs in my large, sprawling document--much of which I randomly work on when I'm feeling in a cyberpunk mood,) I just show up and start playing pretend with my players. I think in the last session, we maybe rolled the dice four times, tops. That group is just generally great fun. I off-handedly had them run into a pair of stoner boys in a stairwell the session before last and these two dudes invited the lesbians to "Bob's Party." An event I literally pulled out of my brain. Sure enough, my players remembered Bob's party and now we have a whole subplot involving Bob and the things we learned at that party.

And it's all just rolling out of my head in real-time.

Tons of fun.

But so is the game I prepare DAYS in ADVANCE. I think the reason RPGs are so popular is because they're almost always a surprise. Players and GMs can try to plan ahead, but dice rolls and improv are what ultimately shape the game. I just find it kind of funny that I'm both kinds of GMs. I over prepare and I'm also 100% winging it. I mean, that's probably true for a lot of GMs?

When Table Turnovers Turn On You

Oct. 30th, 2025 05:55 pm
[syndicated profile] notalwaysworking_feed

Posted by Not Always Right

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We're getting near the end of the night, and I've noticed that the other server has been progressively slowing down to basically a stop. I know EXACTLY what she's doing, she's trying to prevent new customers from being sat in her section (she's the type to always try to cut out early, and barely help with closing duties, etc).

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mindstalk: (science)
[personal profile] mindstalk

So in the first post I said "I remember that back in Albany, my peak traffic counts were on Marin or San Pablo, about 10.3 cars per lane-minute."

But I remembered something key last night: left-turn lanes. Both streets had them. Traffic on Marin could keep flowing smoothly through an intersection because cars going left could get out of the way. But that takes space. Assuming that each direction can carry 10.3 cars a minute, that's nearly 21 cars a minute, but spread over three lanes -- two travel, one shared turn. And we're back down to 7 cars per lane minute.Read more... )

Layman's conclusion: wide roads with little 'turbulence' can get up to 10 cars per lane-minute. More complicated streets are unlikely to get above 8, after accounting for turn lanes. This will have consequences for stuff like "is it physically possible for everyone to drive to work from here?"

A Rare Silicon Switch

Oct. 30th, 2025 12:10 pm
[syndicated profile] in_the_pipeline_feed

Here’s another example of an idea that has been kicking around for years in medicinal chemistry without ever really breaking through: substituting a silicon atom for a carbon. To be fair, most of the time this doesn’t seem to do all that much, while introducing various uncertainties around ADME and toxicity (since we don’t have all that much experience with organosilanes as drugs). So you can see why we’re not overrun with “silyl switch” compounds. But at the same time, there really do seem to be instances where it can help.

For instance, there was (is?) a camptothecin derivative, known variously as karenitecin, cositecan, or BNP1350, that had an alkylsilyl side chain that was claimed to help it be less prone to being removed by efflux pumps. As far as I can tell, this one has kicked around in a number of Phase I and II trials without ever advancing. And a silane analog of haloperidol did indeed show a different (and quite possibly beneficial) metabolic profile, but I don’t think that one even made it to the clinic. As I mentioned in that blog post linked in the first paragraph, I sent in a trimethylsilyl-for-t-butyl switch compound one time in an analoging program, and I have to say that the response from the project team was not a favorable one. But as often happens, there seemed to be no particular advantage to the TMS analog, so it didn’t become an issue, other than in the “Please don’t do that again” way.

This new paper (first link in the post) is a silyl-containing KIF18A kinesin inhibitor, which is class of compounds with several representatives, some of which are in the clinic already for susceptible cancers. Like the example mentioned above, this switch (a silapiperidine for plain piperidine) seems to have improved efflux stability. I’m not completely sure how this occurs, though - the silicon analogs are a big less hydrophilic, but what efflux transport proteins like and dislike is still a mystery to me (and no, not just to me!) 

I find it hard to believe that “silicon slows down efflux pumping” will turn out to be a general rule, but I think it’s an idea that’s worth testing if your particular project is having that sort of trouble. Just be ready for some pushback! We’ll see if this compound (ATX020) advances. The company behind it (Accent Therapeutics) is calling it a “tool compound”, but we’ll see if they have the nerve (or the need!) to take a similar organosilane into human trials. . .

[syndicated profile] naomikritzer_feed

Posted by naomikritzer

If you would like to learn more about any of the races, or any of the groups involved, or politics in Minneapolis more broadly, or if you’d like to support the people whose work I turn to when I’m writing my election guide, there are in fact a LOT of people whose original reporting and data-gathering I rely on heavily, and I’d like to list some of them along with Patreons and fundraisers and so on.

John Edwards of WedgeLive, who provides social media coverage of a whole lot of events on Bluesky, writes a blog about local politics, and does amazing interviews on his podcast, which you can find via a podcast app (it’s called the WedgeLive podcast) or on YouTube. Something distinctive about his interviews is that he likes to interview people while biking or engaged in some other physical activity, which means you often get a much more genuine and authentic look at the candidate or politician than you would normally, because they’re just a little bit distracted. I listened to many, many of his interviews with local candidates, followed his coverage of conventions, and deeply appreciate his work. Support his Patreon here.

Taylor Dahlin has done a ton of research on the PACs that have been throwing money around the Minneapolis city races. You can find her on Bluesky here and her blog (full of useful coverage of those PACs) is here. I don’t think she has a Patreon but she does have an open GoFundMe to support her ongoing fight against breast cancer.

Josh Martin documents meetings and also has this absolutely AMAZING set of spreadsheets (link is to his Google Doc that rounds up all the stuff he does) that give you summaries of (and links to more) campaign finance stuff, endorsements, his “campaign viability matrix” where he tries to calculate the people who might actually win, just a TON of stuff. I could not find a Patreon.

The League of Women Voters Minneapolis hosted a TON of forums this year, all staffed by volunteer moderators and livestreamed. You can donate to the LWV Minneapolis here. LWV St. Paul also hosted a forum. You can donate to LWV St. Paul here. They’re also both always looking for volunteers; volunteers run all those forums but also register voters, answer questions about voting, and educate people about voting. Volunteer with LWV Minneapolis / Volunteer with LWV St. Paul.

Racket is an online arts and politics weekly that is staffed by people who once worked for the City Pages. It’s terrific and you can subscribe to it here.

Sahan Journal does immigrant-focused news coverage and is my go-to source for anything related to the Feeding Our Future scandal (other stuff as well, to be clear). It has no paywall, and you can support it here. MPR News and MinnPost also provide paywall-free coverage of local politics at least some of the time.

I also pretty regularly use coverage from the Star Trib (you can find that on your own) and the Pioneer Press (ditto). The Minnesota Reformer has moved away from local political coverage in an unfortunate way (the decision they made resulted in extremely fine-grained coverage on everything Fateh has ever done wrong, and no coverage of anyone else) although they’ve been a key source for me in the past.

(I’m probably forgetting someone, so I may come back and add stuff.) Anyway, if you value news, please support journalism!

The Littlest Baby Boomer

Oct. 30th, 2025 02:30 pm
[syndicated profile] notalwaysrelated_feed

Posted by Not Always Right

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Adorable Children

We were out of town, and my husband took my three-year-old with him to the grocery store, leaving me at the hotel with the baby. So, my three-year-old decided that she had an imaginary baby sister with her.

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When The Comeback Is A Homerun

Oct. 30th, 2025 01:30 pm
[syndicated profile] notalwaysfriendly_feed

Posted by Not Always Right

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When I was a kid, I was lucky enough to be at a baseball game where I was close enough to the players that I could hear what they were shouting at each other.
A batter was arguing a call from the umpire, and it was getting heated.

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Flower Power, Part 4

Oct. 30th, 2025 12:30 pm
[syndicated profile] notalwayslearning_feed

Posted by Not Always Right

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When I went to pick up my nine-year-old daughter from school today, I passed a group of students also walking home. One had a gorgeous red dahlia. She handed it to me.
Student: "Here, would you like this?"

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The Fairy of Ku-She by M. Lucie Chin

Oct. 30th, 2025 08:49 am
james_davis_nicoll: (Default)
[personal profile] james_davis_nicoll


A fairy's efforts to recover stolen arcane tools via illicit means produce spectacular calamity.

The Fairy of Ku-She by M. Lucie Chin
[syndicated profile] seaofstarsrpg_feed

Posted by seaofstarsrpg

Once a heroI was reading along my feed and encountered an article on cursed monsters for Halloween (article here if you are interested), nothing very exciting or innovative, but it did mention medusa and, specifically, their ability to turn people to stone and how, once they are stone, you can do whatever you want with them.

What a great setup for the start of a campaign: the character “awake” fresh from the middle of combat with a medusa and find themselves . . . in a quiet garden? On pedestals? How much time has passed? What is the world like that they are awakening to?

The set-up is nice as the characters already have ties between them and need to work together to find out what has happened and what the world has become in their absence. Are they remembered as heroes? As unlucky venturers? Or not at all? (What a blow to the ego.) Depending on how much time has passed, they may still have surviving friends and allies (or enemies) waiting out there to be rediscovered.

However, the characters out of time is a trope that can be used in most settings.

For fantasy, travel to other planes where time runs at different speeds. A classic effect of visit faerie, you think you are gone hours but come back days, months or even decades later. Or a magical time trap or gate could knock the characters into the future. What better way to get the heroes out of the way than to send them to the future? There are also not small number of stories of great heroes put to sleep, awaiting the right moment to awake to save people from a great evil.

Through timeIn science fiction, there is cryosleep, and other forms of suspended animation, time dilation from near light-speed travel, stasis effects, or even time travel. All of those can place the characters in a world that is obviously their world but one that has changed, possibly beyond recognition.

If you are playing superheroic games, you can use all of the above and more! I had a character from the 1960s who was tossed into the modern era because their power interacted badly with a hero’s time magic!

Of course, there are also less disruptive ways to achieve a similar effect; memory wiping (technological or magical) can place the characters in the same position without wrenching the timeline into new shapes. As both magic and technology have ways to mess with memories if you want to go the quasi-amnesia route for characters who feel out of place. Memory manipulation also gives the player the opportunity to entirely reinvent the character’s personality and beliefs, a classic character evolution arc, if they so wish.

I have had an idea for a Shadowrun campaign arc that starts with the characters coming back to consciousness sitting around a coffee table piled with their tools of the trade. Each person recognizes the others as allies, but cannot remember anything else. Not their name, not the other characters’ names, where they are or why. Each character has a set of physical characteristics, some of which the player chooses, others of which are clues to finding out who they are. While I like the idea, I mfeel it would be difficult in execution and I have never had a group that I thought would want to dive into such a situation, so it sits on my mental shelf, neglected. Until now! So, use it if you think it would be fun.

For the Game Master, if you are using established characters and moving them through time, you will wish to consider the players’ ties to the setting as it is. This is probably not a good choice for a campaign shift if the players are heavy invested in the world as it is. But it might be a good way to return to an abandoned campaign with characters the players want to revisit. Or as a way for a player to bring an old character back into play with a new group.

Readers: Have you ever played characters who were displaced from their original time? Or one who had lost their memory? What about in  a game you have played, have such characters shown up? Game Masters, have you used these or similar ideas in your campaign?

Notes: Just playing around with interesting ideas for characters and campaigns. One must write as inspiration strikes.

There are some games built around this kind of framework such as the Morrow Project and Year of the Phoenix (both science fiction). Do you know of any others?

Image upper image from Pikist and the lower image is from ChROnoScOpE WOrLd and both are in the Public Domain.

Fire Alarm

Oct. 30th, 2025 03:09 am
[personal profile] ndrosen
There was a fire alarm in my apartment building at around 11:30 PM on Tuesday. I put on my shoes and evacuated the building, before I could return, take care of a few things, and go to bed.

When I got home late Wednesday, I just collapsed and fell asleep, before getting up to eat a very late dinner. One bright spot in my day Wednesday was that I met a friendly beagle mix and his human, near the Patent Office. And now to shower and go to bed.
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Richard Wagner - Der Fliegende Hollander (The Flying Dutchman): Overture


Slovak Philharmonic Orchestra


Michael Halasz, conductor


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Stuck in Paradise for the Foreseeable

Oct. 29th, 2025 05:16 pm
fairestcat: Dreadful the cat (Default)
[personal profile] fairestcat
So, as I mentioned in my Festivids letter, I am currently in Hawaii. Hilo to be specific. I have been here since October 10th and I genuinely have no idea when I'll get to go home.

My mother was diagnosed with congestive heart failure five years ago, but this fall she got significantly worse and also developed pneumonia. She was in the hospital for two and a half weeks and is now in a short-term rehab working on getting back her ability to do exciting things like walking across a room without getting shaky-legged and out of breath and using the bathroom unaided.

I'm in an itty bitty postage stamp sized airbnb room in Hilo, since my mom's place is a nearly two-hour drive away. I can't go home until we figure out what happens next for my mom. I don't think she can go back to the place she's been sharing with my sister. My sister is also disabled and not really able to help my mom with stuff, their tiny house is cramped and crowded, has built-in steps and is a constant tripping hazard, and honestly my mom and sister are driving each other completely mad.

Hawaii is beautiful and all, there are certainly worse places I could be stuck indefinitely, but I really want my own bed and my own spouses and my own pets and my own time zone.

Blasting Through Cells

Oct. 29th, 2025 12:04 pm
[syndicated profile] in_the_pipeline_feed

I think that I can guarantee that you haven’t heard this phrase before: “ballistic microscopy”, the subject of this recent preprint. What the authors describe a combination of near-medieval technology on the one hand and cutting-edge analytical work on the other. They are bombarding cells with focused streams of gold nanoparticles (which range from 50 to 1000 nm diameter). These things are traveling at speeds up to 1 km/sec (over 2000 miles per hour (edit: fixed!)) and blast straight through their cellular targets. That’s a thickness of 2 to 4 microns for something like a HEK cell, and those velocities mean that the transit takes only a few picoseconds.

They come out the other side of the cell and splat into a hydrogel matrix on the other side. They’ve already slowed down a bit from their passage through the cell, and the hydrogel brings them to a halt. But when you examine them there, you find that they have carried along small amounts of the cellular material with them. It’s only a few attoliters, but by gosh that’s enough for current proteomic, nucleic acid, and cryo-EM techniques to get a handle on what’s in there. So what you get is an instantaneous snapshot of the cellular contents from a very small, very well defined needle-stick through a living cell. (People have actually done that, sampling cells with micro-needles and micro-straws, but this seems to be a step further). 

You can tell that the authors are enjoying themselves: the technique itself is abbreviated BaM, and the hydrogel sample obtained is referred to as a “SPLAT-MAP”. (If that’s an acronym it seems to be undefined in the manuscript!) You get a lot of information from doing fluorescent imaging while the bombardment is underway - location of the particle stream hitting the cell (complete with streaks through the cytoplasm in high-speed side views), xy spatial distribution on the hydrogel itself, and depth (z) which is dependent on the size of the particles involved. 

The group tested this in lysate from cells that had been expressing GFP-labled actin protein, and sure enough: the particles entrained fluorescent bits of cell material that corresponded to the labeled protein. And those particles penetrated less into the hydrogel braking material than control particles that were shot in directly, showing that they had experienced drag from schlorking through the cellular contents (my term, which all are welcome to if this technique catches on). Moving on to real cells, HEK293 cells were stained for nuclear membrane and cell membrane (to aid in IDing the now-fluorescent particles after capture), and they could be cultured right on top of the hydrogel surface. 

If the fluorescent label was applied instead to another protein, then everything around that protein could be checked out. This was done with the known condensate-former CLIP170, and the nanoparticles pulled condensate droplets right out of the cell. Proteomic analysis showed 641 proteins (with a large number of them annotated as RNA binders, which fits with previous condensate work). One was keratin-18, which hadn’t been seen in these before but which seems to form filaments inside the droplets. But about 17% of them are unannotated, which is just the sort of thing you’d like to dredge up with a method like this. 

Electron microscopy of the particles and their associated cellular samples showed that the cell contents that were brought along tended to be bunched up on the high-curvature edges of the gold particles (and not wetting the entire surface) and that they tended to be membrane-enclosed, sometimes with more than one membrane layer. There’s going to have to be more work done to interpret that, but it does seem significant (and might represent a type of sampling bias with this technique?)

There are a lot of things to be done in general! Zapping all sorts of cellular substructures, in both healthy and diseased or stressed cells, is an obvious set of experiments, and it’ll be interesting to see if some protein distribution maps can be produced from such runs. It’s certainly a new label-free assay technique, and I urge everyone interested in it to fire away and collect piles of data!

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