A Failure To Communicate, Vol 67.

Sep. 25th, 2017 01:00 pm
[syndicated profile] cakewrecks_feed

Posted by Jen

I think this is what our grandparents call "a senior moment."

The best part?


[sad face here]


"Sprinkles All Over Momther" is the name of my Cake cover band.


Ahhh, NOW you're speaking my language.

(The language... OF WRECKS. [eyebrow waggle])


In a word?


Thanks to Lani T., Donna C., Patrick L., Anony M., & Rebecca P. for keeping those lines of communication nice and squiggly-like.


Thank you for using our Amazon links to shop! USA, UK, Canada.

Building Our Own Molecular Machines

Sep. 25th, 2017 12:58 pm
[syndicated profile] in_the_pipeline_feed

Posted by Derek Lowe

Let’s talk about enzyme envy. That’s what we organic chemists experience when we stop to think about how every complex natural product in the world is synthesized so much more quickly and efficiently than we can do it. All those crazy multiple rings systems, those bizarre heterocycles, huge macrolides, and dense arrays of stereochemistry are cranked out at ambient temperature, under aqueous conditions, on a time scale of minutes to hours. Oh, and they’re made offhand, in the background, as time permits, while the cells and organisms themselves are otherwise occupied with the even more startling business of being living chemical systems. Envy? It’s more like enzyme terror, when you really think about what’s going on.

Now let’s talk about nanotechnology. Not the press-release stuff, I mean hard-core nanotech. The dream of assembling molecules and materials to order, atom by atom, has been around for some years now, and it largely remains just that: a dream. Eric Drexler and others have taken a lot of grief for maintaining that such things are possible, and to be sure, I have trouble myself with the real atomic scale this-carbon-goes-right-here level of the idea. But what about “this acetyl group goes right here?” That is, small-molecular scale versus atomic scale? That is exactly what every living cell on the planet is doing right now – that’s enzymatic chemistry, and I see no reason why we can’t get smart and capable enough to do the same sorts of things ourselves, and more.

That leads up to this new paper, which is a big (but small) example of just that sort of thing. A group from the University of Manchester reports the system shown above, which is basically a molecular-sized stereoselective synthesis machine. You put that unsaturated ester together on the left-hand side, and the first step is an olefin cross-coupling with it and acrolein dimethyl acetal. Now comes that “rotary switch” in the middle. If you treat the molecule with trifluoroacetic acid, it deprotects the acetal, and the acrolein now is set up to do a tandem nucleophile/electrophile addition under the influence of the chiral prolinol group. That reaction is done in solution, as stereoselective synthesis fans will know, but you only really get the syn isomers.

This system will give you both, and both enantiomers, depending on the reaction conditions. Depending on the conditions (time spent treating with trifluoroacetic acid, or with triethylamine afterwards), that hydrazone in the middle can go from E to Z putting the acrolein aldehyde in range of either the (S) or the (R) prolinol, at your choice. That forms a chiral iminium, whereupon you add a thiol nucleophile. The iminium is now released, and you have your choice again of whether you want the hydrazone in the middle to be E or Z. Whichever one you choose, you now form an enamine intermediate and bring in the electrophile (a highly activated Michael acceptor, 1,1 phenylsulfonylethylene). That does the second bond formation, and reduction with LAH releases the ester linkage and frees the product as a primary alcohol. You end up with two chiral centers, and you can choose which of the four diastereomers you want by moving the hydrazone switch around during the reaction sequence.

OK, we’re not all going to be making compounds like this next week – fine. This system is set up with every bias possible to make it succeed (such as a terrific thiol nucleophile and a terrific sulfonyl electrophile), and it doesn’t produce pure stereoisomers out the other end, even with that. Rather, you get ratios from about 80:20 to about 60:40 (although, to be sure, the solution methods to do this reaction don’t always do much better, and they can’t give you all four isomers under any conditions). The point is not that this is a wonderful new stereoselective reaction that we can use to make chiral products; the point is not the chiral products themselves at all. The point, of course, is that this thing has been designed to give you such chiral products, in a programmable fashion, and that it can indeed switch states on command to give them to you. It’s a machine – a very small machine, with limited inputs, but the first computer circuits were also very small machines with limited inputs, too.

The scientific and engineering challenges are similar – how to make these things work more reliably and how to scale them up to greater levels of complexity and utility. It’s going to be harder for chemistry than it was for computation, since our computers, fundamentally, are all about moving 1s and 0s around (throwing on/off switches over and over in increasingly complicated ways). That made the development of processing circuits more straightforward, as difficult as it was in reality to get all that to work. Organic synthesis has a lot more letters in its alphabet than just A and B, and its processes are a lot more irreducibly complex than binary logic is. But that just means that it’s a trickier problem, not that it’s an insoluble one.

I think this work points to one way around the difficulties: try, whenever you can, to reduce the key steps to binary ones. The heart of this molecular machine is that hydrazone, which can point in this direction or in that one, which makes all the difference. If we develop these and other spatiotemporal switches to be faster, more responsive, more reliable, and more orthogonal to other functional groups, we can adapt them (as this paper does) to do some fairly complicated chemistry by positioning our other reagents in the appropriate places. Some of these things are already out there in the literature (azo groups or other double bonds that isomerize photochemically, pH-responsive hydrogen bonding groups, and others). We can take our cues from the biochemical world, which uses both of those just-named processes, and how, and we can design new ones that no living cell has ever gotten around to. Cells, when you get down to it, build incredible synthesis machinery, but it’s bespoke stuff: it does what it does with fantastic speed and precision, but if you don’t want exactly what it does, you’re out of luck. What we’re after is are tougher, more general solutions: machines that will make whole ranges of molecules, the way we tell them do, with (ideally) the ability to be switched around to different functions as needed.

T. Ross Kelly and Marc Snapper have a good commentary on this paper in the same issue of Nature.

It is commonplace to dismiss seemingly impossible ideas, such as Drexler’s molecular assemblers, out of hand, and the use of such devices in chemical synthesis might indeed never find favour. One could further argue that Kassem and colleagues’ “programmable molecular machine” is more contrived than ingenious. But given that the most recent chemistry Nobel prize was awarded for the design and synthesis of molecular machines, those who dismiss the concept of molecular assemblers should heed the lesson of Lord Kelvin’s infamous 1895 pronouncement that “heavier-than-air flying machines are impossible”.

As opposed to some other similar statements that get quotes, Kelvin apparently really did say that, as well as saying (in 1900) that he didn’t think there was anything new to be discovered in physics. Anyone who watched a bird knew that heavier-than-air flight was possible; the question was whether we could figure it out ourselves. The attempt to make molecular assemblers – which is, after all, the attempt to make our own enzymes, when we know that enzymes exist – is the same sort of problem. The molecular-machine folks (last year’s Nobel!), who care about rendering fundamental ideas and processes into molecular form, and the more traditional synthetic organic chemists, who care about what products any new reaction or machine can produce for them, can find common ground in building such things. Bring on the molecular machines!



Note: All opinions, choices of topic, etc. are strictly my own – I don’t in any way speak for my employer

No, really?

Sep. 25th, 2017 01:56 pm
oursin: The stylised map of the London Underground, overwritten with Tired of London? Tired of Life! (Tired of London? Tired of Life!)
[personal profile] oursin

Dept of, did you do any research?

That Uber vs TfL thing, with TfL refusing to renew their license - okay, I do not use Uber (I am probably not their target market) and everything I hear about it makes me deeply suspicious - but when I read various articles claiming that London black cab drivers are the trad white working class, I wonder how often, if ever, any of these people have ridden in a black cab. Because in my limited and anecdotal experience, finding a Trad London Cabbie who will give you his Salty Cockney Opinions whether you want him to or not, is not the default at all.

This article about Some Artist's exhibition on what he calls 'pseudo-Georgian architecture' in the UK and dates to the 1970s.

Marvel at a London Waitrose – “the pearl of Holloway Road”, according to Bronstein’s caption – with a cupola-crowned tower floating above its entrance. That oddly proportioned line of columns, running above the shopfront windows, suggest the architect once glimpsed a photograph of Vicenza, but not for long enough.
I know that Waitrose and shop there regularly and I am old enough to remember when it was Jones Brothers, by that time part of the John Lewis Partnership, but dating from an era when suburban department stores were built as retail palaces - as far as I can see, dates back to the 1890s.


Dept of, is that really the solution? PETA co-founder says we should stop wearing wool. I cannot help feeling that if there is no longer any economic reason for rearing, even if 'sheep are so gentle, they’re so dear!' they are likely to vanish from the face of the earth except in zoos (to which I imagine PETA are also opposed). Might not doing something about introducing legislation for more humane shearing practices be a better use of their time and energies?

laughing_tree: (Seaworth)
[personal profile] laughing_tree posting in [community profile] scans_daily

The narrative behind these things changes all the time. And what fascinates me especially is how people who espouse different versions of the legends can appear on the same bill together at UFO conventions and not argue. These are sometimes mutually exclusive theories! As a body of fiction, this is fascinating. The fact that that fiction actually contains some people's real experience is doubly fascinating. This is all the stuff we'll be exploring. -- Paul Cornell

Read more... )

little moments of alienness and not

Sep. 25th, 2017 09:10 am
brainwane: My smiling face, including a small gold bindi (Default)
[personal profile] brainwane
Years ago, when Leonard was writing Constellation Games, he named the various alien species after different human words for "alien" or "foreigner". So there are Aliens, Foreigners, Farang, Gaijin, Extraterrestrials, the Others, and so on. One species of them is the Auslanders; later a German-speaking friend told us the spelling of the plural ought to be Auslender.

Today I was rereading a little chunk of Lake Wobegon Days and came across Keillor referring to Ausländers, and was reminded of that moment years ago. And then just after that was the passage about Flag Day, and I was catapulted far further back, to fourth grade and the first time I read (or was read?) any of this book. I was in a Gifted and Talented class in an elementary school in the suburbs of St. Louis, Missouri, with that teacher who had a chunk of the Berlin Wall in her classroom. Did she read that to us or did I read it by myself?

Saturday I was on the 7 train back home from Maker Faire and I was sitting near some girls who -- as they happened to say aloud, in their conversation with each other -- were 12 or 13 years old. I am about three times their age. Yet I wanted them to look at me not as an alien grownup but as someone they might be like. They all have smartphones and evidently deal with boys sending them dick pics. And they act blasé about it; I don't know how they actually feel. The next day I talked about this with the people staffing the table next to mine. One of them suggested that boys have always done sort of body-part-display to girls less as a sexual come-on and more as a thrill-of-the-forbidden act, with dick pics as analogous to mooning. We joked about the dedication of an imaginary man from a previous century who worked in rotogravure or lithograph or woodcut. Or at least, like, Matthew Brady or someone using silver nitrate film.

cue "Ashokan Farewell"

My dearest Elizabeth. Tonight the Union Army rests. We know not what battle the general will order us to tomorrow. But know that my love for you is the wind that calls your name through the trees. Here's a dick pic. I had to sit for five hours for the army portrait painter boy to make this.

Sergeant Cowling was killed at the Battle of Bull Run.

I was laughing pretty hard by the end of this.

Maybe one reason I like laughing with others, and making others laugh, is because it is a kind of proof that we are not entirely aliens to each other.

Free Excerpt from The Glass Town Game

Sep. 25th, 2017 09:03 am
catvalente: (pic#941394)
[personal profile] catvalente

If you’re in or around Seattle tomorrow, Cat would love to say hello! She’s doing a reading of The Glass Town Game on 9/26 at Secret Garden Books: the event begins at 7 PM, and the store closes at 8 PM. Bring your books, bring your kids, and bring your smiles!

Haven’t gotten The Glass Town Game yet? You’re missing out on the Brontës and their secret world! To tempt you, here’s an exclusive excerpt from the book over at YA Interrogbang. Enjoy!

Mirrored from cmv.com. Also appearing on @LJ and @DW. Read anywhere, comment anywhere.

Find and Replace

Sep. 25th, 2017 08:49 am
goss: (Yip yips)
[personal profile] goss
...is truly a blessing. Thank you, Microsoft Word.

- Any version of Mycroft other than "Mycroft" makes me want to die inside. (My, Myc, Myke, Croft. WTF. I'm just waiting to come across "Ycro". LOL.)

- Also, who is Noah? Sheriff Stilinski's name is John, dammit. :b

So what are *your* favourite "Find and Replace" words in fic?

(no subject)

Sep. 25th, 2017 01:01 pm
nunila: (Default)
[personal profile] nunila
QOTD: What is so important to your life that you would resort to violence to protect it?

Me: My family, the ability to read the books I want, the entire constitution.
puppetmaker: (Default)
[personal profile] puppetmaker
NFL viewing is down by about 15% this year according to ESPN and some other sports pundits.

The why has turning into a lovely round of finger pointing at various groups and the call for boycotting for various reasons including a number that seem to revolve around Colin Kaepernick’s silent protest last year that has now blown up into a national issue. Some are boycotting because Kaepernick seems to be being punished by not be hired by a team even though he is so much better than the QB they have on the field. Others are boycotting because they oppose the players who have been exercising their first amendment right both on and off the field. So according to those screaming the loudest, that’s why number are down.

I don’t think that it is at all. I blame the NFL red zone. When you can get all the exciting plays in one place and have your electronic leash tell you when they exist so you can go and watch them, why take 3 hours out of your Sunday to watch a game in hopes of seeing an exciting play? The red zone has ruined it for teams whose markets are not the biggest. In our immediate gratification society, the NFL Red Zone is tailor made for that sort of behavior. Plus you don’t have to listen to the refs ruining the game for your team by some lame ass penalty that was not applied fairly to your team.

I do think that concussion is playing a role in this too. The awareness of the viewing public about what those hits do to those players is very much on the rise. We also come to understand that the absurd contracts that we hear about is for the minority of players and the majority have to try to make as much money playing as they can before they go out on injury or they don’t remember their name. So the violence, that use to be a selling point, now seems to become a detriment.

Also it hasn’t been that good over all. They are still trying to sort out the new rules. The celebration in the end zone has not added to the game for me in fact it is just eating up time that is going to make my show later in the evening because the game is going to go over. The refs use to call the game and, some how, they have made themselves part of the game with their antics. So it can be a long haul with a lot of commercials to see a team that you like play. Thus the immediacy of the Red zone plays.

I really don’t know if they are taking all the other ways to watch games into account.

I do know that college football’s attendance has been better than the NFL but if you consider the absurd price of even a crappy ticket, it is understandable. They have priced their fan base out of their stadiums. The cash cow has moved on and the stands are looking rather empty in some markets. It has become a game for the rich and the working class who might like to attend a game cannot afford a seat much less a hot dog.

So NFL you did it to yourselves. What are you going to do about it.

I am grateful that I can still watch football on a network that is not a cable network but that’s probably going soon as well.

Busy Weekend

Sep. 25th, 2017 07:47 am
marthawells: (Stargate)
[personal profile] marthawells
This weekend we ended up going to my husband's 40th high school reunion. It was a lot of driving and sitting in traffic to get there and get back (perpetual high way construction taking four lane highways down to one lane, trying to exit onto another highway just as a large sports event was ending, etc) but we had a good time. (Also we went to a party out in the country where our GPS tried to direct us into an open field.) But everybody ended up having fun. At one point we went into Denton with friends and went to Recycled Books which is a bookstore so huge I think it hurt my brain. We also got to see my family including my two year old grand-nephew, and that was a lot of fun.

I posted a story to the Raksura Patreon: https://www.patreon.com/user?u=2458567 and that was about all the work I did this weekend besides answering email.

Discovering Discovery

Sep. 25th, 2017 07:17 am
garyomaha: (Default)
[personal profile] garyomaha
M was unfortunately busy with homework, so needs to watch later.

(No spoilers, I don't think -- not that I figured out enough to share any.)

I was intrigued by the new Star Trek: Discovery series.  But I was not (yet) compelled to subscribe to CBS All Access to watch future episodes.  That's what I expected going in, and that's definitely where I stand now.

I always have trouble grasping (should "grokking" be used here?) fast-moving concepts, and have always needed a second pass for new information and fast-moving items.  With the small screen, my attention can be pulled by everything from dogs to food, thunder to a sneeze.  That's why I nearly always watch via the DVR, but I did not last night because it was an event

I wavered between "I am so confused" and "Ooh, pretty" while watching.  For this long-time Trek viewer (as in, back to the very beginning) the show was way too much about special effects.  I understand how that's needed to hold today's (read: younger) viewers, it just didn't blow me away.

The biggest question for me was, the show is called Discovery, yet that ship was nowhere to be seen.  I haven't read much about this, so I have no clue why this was. 

I guess, perhaps, I needed a synopsis or primer of some sort going in.  After watching, I still do.  I may watch the recording again (perhaps with M) to see if it's clearer and/or captures my fancy more.  Yeah!  Talk myself into spending the money!'

(no subject)

Sep. 25th, 2017 07:24 am
copperbadge: (radiofreemondaaay)
[personal profile] copperbadge
Good morning everyone, and welcome to Radio Free Monday!

Ways To Give:

Anon linked to a fundraiser for [tumblr.com profile] onomatopathetically, a disabled woman trapped in an abusive and dangerous home situation. She's raising funds to relocate to somewhere safe where she can get a job; you can read more and support the fundraiser here.

[personal profile] pinesandmaples linked to a March of Dimes fundraiser being run by their friend Karen, who recently lost her infant son to a terminal birth defect. She is raising funds to help support research into infant birth defects in memory of her son. You can read more and support their walk here.

[tumblr.com profile] rilee16 is struggling to cover medical expenses after two head injuries last year, and has a fundraiser running to cover living expenses, previous medical bills, and a recent rent increase. You can read more and help out here.

Buy Stuff, Help Out:

Recently I made a post about a new word I'd come up with to describe the gallows humor of Millennials, "Millennihilist", and [tumblr.com profile] dr-kara asked if she could make it into a shirt; the result is on sale now, with all proceeds going to the Hispanic Federation to help with the crisis in Puerto Rico. You can read more, reblog, and find links to purchase here.


[personal profile] in_the_bottle is still looking for a roommate; they're looking to let a bedroom just off Fulham Palace Road in Fulham for a short-term from October to 19th November for £850 per month including utilities, negotiable (length of stay also negotiable). You can read more and get in touch here.

And this has been Radio Free Monday! Thank you for your time. You can post items for my attention at the Radio Free Monday submissions form. If you're not sure how to proceed, here is a little more about what I do and how you can help (or ask for help!). If you're new to fundraising, you may want to check out my guide to fundraising here.
[syndicated profile] io9_feed

Posted by Shep McAllister on Deals, shared by Shep McAllister to io9

The advent of sound bars has made it easier than ever to get premium audio out of your home theater, and this Yamaha deal means it’s awfully affordable too.


Palazzo Publico

Sep. 25th, 2017 12:37 pm
cmcmck: (Default)
[personal profile] cmcmck
We paid our customary visit to the Palazzo Publico which fronts onto Siena's main square (the one where the Palio horse race is run).

The buildings are simply full of wonders!

View across the square from the palace:

We went first to the wall paintings of good and bad government. These are world famous and I see something new every time I look at them. The pig in this image (it's 15th century) is a Cinta Senese- a recognised breed which is still very much around as you'll see in a later post:

There's pics! )
icon_uk: (Default)
[personal profile] icon_uk posting in [community profile] scans_daily
To start Monday morning off with some sort-of comic news, they've finally announced who will be voicing the Ray in the forthcoming "Crisis on Earth X" crossover event for the various DC TV series.

This is a little bigger than some news, since the Ray will be the first gay male hero that the DCTVU (There must be an easier name for it than that) has featured;

The Ray will debut in the crossover (which will also include Arrow, Supergirl, Flash and the Legends of Tomorrow team), before getting a four episode animated series "Freedom Fighters: The Ray", and will be played by openly gay British actor Russell Tovey, best known perhaps, aside from an appearance in Doctor Who as Midshipman Alonzo Fraim in "Voyage of the Damned" (And later making a brief cameo as a potential new boyfriend for Captain Jack in "The End of Time") as George, a werewolf in the supernatural comedy-drama "Being Human" (The UK version that is).

Some promotional art was put together by Phil Jimenez, in the style of the old multiple Earth crossover covers to publicise the event, which also hints that it will take place around the wedding (or not) of Barry Allen and Iris West.

(Click to embiggen)

Now, understandably, there has been some eyebrows raised at the decision, in the current political climate in the US, to make the Arrowverse/Supergirl crossover be based around Earth-X; the DC Earth where the Nazi's won World War II, and where we will see several Nazi versions of established heroes, so we'll have to see how THAT is handled (Secret Empire is a low bar to clear, but here's hoping)

As a geeky aside; Earth-X debuted in 1973, when WW was less than 30 years finished, as a separate home for a number of Quality Comics characters DC had acquired, like Uncle Sam, the Human Bomb, Doll Man, the Ray and Phantom Lady. They were folded into the WWII heroes following Crisis on Infinite Earths, though more modern takes on them have surfaced a time or two in the last couple of decades.

sarken: leaves of mint against a worn wall (Default)
[personal profile] sarken
I'm on this scene in the high school AU and it's not going how I planned. I like how it's going, mostly, because it's forcing me to think about something I hadn't considered.

See, it's the scene where Sharon asks Brenda if she'd like to have sex. And now that this is a very real thing, Brenda is... I guess nervous is the word. It'll be her first time. So, by the laws of high school fiction, she should talk to her more experienced female best friend.

But her more experienced female best friend is the person she's going to be having sex with.

And I love that. And I know exactly how I want to write it: I want it to be not weird at all. I want them to just go ahead and have the conversation.

But I'm worried. That it's unrealistic, sure, but mostly that I'm passing up an opportunity to explore a complicated situation. I was going to say I'd love to read something like that, and I'd be disappointed if the author took the easy way out, but I'm not sure it's true. I just feel a strange sort of obligation to make it more complicated than I want.


Sep. 25th, 2017 06:53 am
supergee: (bug)
[personal profile] supergee
Alex Acks on how to win an online argument (fsvo win)

Thanx to File 770


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