We can both read our email. At the same time!
Anyone know what this is? It's been springing up on the edges of the woods:
The ducks really don't like pigeons. If they see them in the front garden, they run at them, beaks open and ready to grab on!
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#ok but the thing i love about this#is that there is literally no line steve is not willing to cross#the only reason he’s been the capital letters Good Person all this time#is other people keep taking the brunt of the darkness#there are always natashas and buckys and fury and peggy to do the shady things#to accept the world for its shades of grey where steve has the liberty to see black and white#but what everybody always forgets#is that steve didn’t start as a magically above-it-all demigod#he was a skinny kid who made all sorts of personal allowances for the world being less than it should#never backing down was one of those things#a line he drew in the sand when he wasn’t in charge of anything at all#a line to say this is what i am and this is what i mean#but there’s no line he won’t cross#not for a greater gain#the wonderful thing about steve is you don’t actually need to shield steve#his kind of optimism comes from within not from ignorance or innocence#so yeah he can give up#this once#because it was only a line in sand#he can make a new one tomorrow (tags via ifeelbetterer)
A federal appeals court panel in the District struck down a major part of the 2010 health-care law Tuesday, ruling that the tax subsidies that are central to the program may not be provided in at least half of the states.
The ruling, if upheld, could potentially be more damaging to the law than last month’s Supreme Court decision on contraceptives. The three-judge panel of the D.C. Circuit Court of Appeals sided with plaintiffs who argued that the language of the law barred the government from giving subsidies to people in states that chose not to set up their own insurance marketplaces. Twenty-seven states, most with Republican leaders who oppose the law, decided against setting up marketplaces, and another nine states partially opted out.
[I]f subsidies for half the states are barred, it represents a potentially crippling blow to the health-care law, which relies on the subsidies to make insurance affordable for millions of low- and middle-income Americans.
The subsidies are in many cases sizeable, sharply reducing the cost of coverage.
About 5.4 million people signed up for health insurance on the federal marketplace through the spring, the government says. Of them, about 87 percent received subsidies.
The plaintiffs in the lawsuit — three private employers and four individual taxpayers — argued that Congress intended for the subsidies to go to people in states that set up their own insurance exchanges. They cited language in the law that said the subsidies would be available to those “enrolled through an Exchange established by the State.”
Lower courts, however, have sided with the government, which has argued that Congress’s intent was for subsidies to be available in all states — a meaning it said is obvious from the law’s context.
Via a comment in yesterday's post by hunningham:
How to Read More: The Simple System I’m Using to Read 30+ Books Per Year
It is to point and mock at Little Mr Gradgrind, C21st incarnation:
Now, there are plenty of excellent articles on the web, but generally speaking, the quality of good books is better. Books typically have better writing (more tightly edited) and higher quality information (better fact-checking and more extensive research). From a learning perspective, it’s probably a better use of my time to read books than to read online content.
I usually wake up, drink a glass of water, write down 3 things I’m grateful for, and read 20 pages of a book.... As of today, I’m 100 pages into my 7th book. At that pace (7 books per 10 weeks) I’ll read about 36 books in the next year. Not bad.
Here’s why I think this pattern works: 20 pages is small enough that it’s not intimidating. Most people can finish reading 20 pages within 30 minutes. And if you do it first thing in the morning, then the urgencies of the day don’t get in the way.
Finally, 20 pages seems small but adds up fast. It’s a great average speed.
If time allows, I’ll read at other times as well.... But regardless of what happens during the rest of the day, I still get my 20 pages in each morning.
What if you woke up an hour before you needed to each day and worked on yourself? How much better would you be at work, in your relationships, and as a person?
We do not think that the concept that reading can be a pleasure and something one does not grind through at a 20-page a day rate (honestly, that sounds like the reading-reducing maintenance diet for the reading addict, no?) but pursues avidly in any spare moment has really crossed his horizon: '[I]nvest in yourself. Before your life turns into a whirlwind of activity, read a book that will make you better.'
I sure hope this young man does not come across one of the pieces abou the value of playfulness - such as this one encountered recently - because he'll then have to schedule in some time to be freely and spontaneously playful. Or his head might explode...
Give the guy a P G Wodehouse and see what happens.
Though, ghastly though the above may be, I am also vaguely creeped out by this: Outlaw Catalog of Cagey Optimism. No, really, I am not entirely on board with the concepts such as:
* AGGRESSIVE SENSITIVITY. Animated by a strong determination to be receptive and empathetic.
* ALIGNMENT WITH THE INFINITY OF THE MOMENT. Reveling in the liberating realization that we are all exactly where we need to be at all times, even if some of us are temporarily in the midst of trial or tribulation, and that human evolution is proceeding exactly as it should, even if we can't see the big picture of the puzzle that would clarify how all the pieces fit together perfectly.
This year tens of thousands of Central American children, fleeing violence and poverty, have been arriving in the U.S. seeking refuge. It’s a stunning story that has been covered widely in the media and Americans’ opinions about immigration have taken a hit.
The Pew Research Center collected data regarding American leniency toward undocumented immigrants in February and July, before and after media coverage of this crisis began. The results show that members of all political parties, on average, are less inclined to allow “immigrants living in U.S. who meet certain requirements” to stay legally (see far right column).
The strongest opponents are Republicans and members of the Tea Party. These groups were more opposed to enabling undocumented immigrants to stay legally to begin with and they showed the greatest change in response to this new crisis.
Republicans and Independents are also more likely than Democrats to think that we should speed up the deportation process, even if it means deporting children who are eligible for asylum.Lisa Wade is a professor of sociology at Occidental College and the co-author of Gender: Ideas, Interactions, Institutions. You can follow her on Twitter and Facebook.
Being chronically ill is like having a part-time job you hate but can’t quit. It’s a constant suck on your resources that healthy folks don’t understand – overseeing the never-ending battle between your insurance and the pharmacy and the doctor who forgot to call in your fucking scrip again, finding a physician who actually listens when you tell her there’s something wrong, a rocky employment record because on any given day you might collapse.
Dating while being chronically ill? Even harder.
It takes a special kind of partner who’s going to be okay when you’re too sick to go to that fun party, to drive you to the doctor’s office six times a month because the medications make it dangerous for you to take the wheel, to deal with the fact that sometimes you’d like want to do the kinky-kinky but dammit your legs just aren’t up to that today.
So a lot of sick and/or handicapped people are also terribly lonely. You have to find a partner who fits the craggy edge of this life you didn’t choose, and hunting down someone that generous is difficult at best.
If you’re dating someone who is sick like that, and are sticking by their side when the “in sickness” part consistently outweighs the “health,” let me offer you a personal word of thanks: you’re on the side of the angels, here. Your empathy is an inspiration.
Make sure to take care of yourself, too.
See, the reason I say this is because sick people can be jerks, too. It’s not like the doctor comes along and says, “You’ve contracted a case of lupus and also, sainthood.”
Sick people are, well, people. And some folks who get sick were abusers before they got ill.
And in the very rare circumstances when a chronically ill person is an abuser, they can do a lot of damage. The guilt-hammers they can drop are devastating, because yes, they’re dependent, and yes, they’re often needing other people to help them along…
…but most chronically ill people don’t use that as a way to shape your life to their convenience.
I say this because I’ve watched some friends who stayed with someone ill, a person who was actively corroding their self-esteem and taking advantage of them – and yet didn’t feel right about leaving this clearly toxic environment because “S/he needs me.”
So they stayed while their partner cheated on them, and spent their money, and dispensed their affection in carefully-calculated slot-machine doses of “neglect today, insult tomorrow, but maybe a sweet word this weekend.”
But they couldn’t leave, because that would make them a bad person.
So let’s be clear here: There’s no reason to endure constant abuse. Ever. You’re not a bad person for leaving someone who treats you badly. Even very sick people don’t get a “get out of responsibility free” card which enables them to treat you like shit all the time.
…which is not to say that the chronically ill won’t snap at you, from time to time. I think of my Uncle Tommy, a hemophiliac with such terrible arthritis that if you listened to his shoulder you could hear the bones rubbing against each other like stale crackers – and while I loved him dearly, he was not always a ball of fun. He had really angry days. He had surly days. He had withdrawn days.
The difference was, he didn’t justify his angry and surly and withdrawn days by telling me they were my fault. He had them, but never blamed me for them or used them as an excuse to take out his frustrations on a nearby target. He apologized, when he was in a better place – and sometimes when he wasn’t. And even towards the end of his life when he was in constant pain, he still devoted what limited resources he could towards worrying about my well-being, making sure I took care of myself, squeezing my hand to let me know that he loved me.
My Uncle Tommy, in the middle of all that pain, wanted me to be happy.
Sometimes, someone’s just depressed or chronically ill or handicapped, and yes, they need your support. They don’t mean to be a pain in the butt – and they’re doing their best to be functional human beings despite some soft spots.
So you should not be too eager to pull that switch. Sick people need love, too, often much more of it.
Yet some sick people chew up love and spit it out, always expecting more and not caring how they get it. (Or, more accurately, some people do this, and some of those people happen to be sick.) Some segment of the depressed and the chronically ill and the handicapped will callously treat you as though you were a medicine-and-money-and-support-dispensin
And when you hit your limit, they’ll jam hard on the “But what will happen to me if you go?” guilt button.
Yet again: It’s not wrong to leave someone who abuses your kindness. Even caretakers get to set proper boundaries. And if someone keeps violating your trust in ways that hurt you, then they’ve sent you a clear message: I don’t care about you.
In which case – sadly, tragically, and hopefully avoidably – you are not required to care for them. It’s kind if you do, of course. (And slightly different if you’re dealing in terms of end-of-life care, of course, which is brutal but at least has an end date baked into it somewhere.)
Yet if you’re consuming your own mental health in order to take care of someone who doesn’t give a crap about how you feel, then remember that your kindness is a gift. You deserve to give that kindness to someone who genuinely appreciates it on whatever limited level they can.
There’s one person you must be kind to above all others, in the long run – and that’s you.
Cross-posted from Ferrett's Real Blog.
The Broad Institute seems to have gone through a bit of rough funding patch some months ago, but things are looking up: they've received a gift of $650 million to do basic research in psychiatric disorders. Believe it, that'll keep everyone busy, for sure.
I enjoyed Eric Lander's characterization of much of the 1990s work on the genetic basis of mental illness as "pretty much completely useless", and I don't disagree one bit. His challenge, as he and the rest of the folks at the Broad well know, is to keep someone from being able to say that about them in the year 2034. CNS work is the ultimate black box, which makes a person nervous, but on the other hand, anything solid that gets discovered will be a real advance. Good luck to them.
You might also be interested to know where the Stanley Foundation, the benefactors here, came up with over half a billion dollars to donate to basic medical research (and more to come, apparently). You'd never guess: selling collectibles. Sports figurines. Small replicas of classic cars, trucks, and tractors. Miniature porcelain versions of popular dolls. Leather-bound sets of great (public domain) novels. Order now for the complete set of Presidential Coins - that sort of thing. It looks to be a lot more lucrative than discovering drugs (!)
So, when you put some diverse small molecules into cellular assays, how many proteins are they really hitting? You may know a primary target or two that they're likely to interact with, or (if you're doing phenotypic screening), you may not have any idea at all. But how many proteins (or other targets) are there that bind small molecules at all?
This is a question that many people are interested in, but hard data to answer it are not easily obtained. There have been theoretical estimates via several techniques, but (understandably) not too much experimental evidence. Now comes this paper from Ben Cravatt's group, and it's one of the best attempts yet.
What they've done is to produce a library of compounds, via Ugi chemistry, containing both a photoaffinity handle and an alkyne (for later "click" tagging). They'd done something similar before, but the photoaffinity group in that case was a benzophenone, which is rather hefty. This time they used a diazirine, which is both small and the precursor to a very reactive carbene once it's irradiated. (My impression is that the diazirine is the first thing to try if you're doing photoaffinity work, for just those reasons). They made a small set of fairly diverse compounds (about 60), with no particular structural biases in mind, and set out to see what these things would label.
They treated PC-3 cells (human prostate-cancer derived) with each member of the library at 10 µM, then hit them with UV to do the photoaffinity reaction, labeled with a fluorescent tag via the alkyne, and fished for proteins. What they found was a pretty wide variety, all right, but not in the nonselective shotgun style. Most compounds showed distinct patterns of protein labeling, and most proteins picked out distinct SAR from the compound set. They picked out six members of the library for close study, and found that these labeled about 24 proteins (one compound only picked up one target, while the most promiscuous compound labeled nine). What's really interesting is that only about half of these were known to have any small-molecule ligands at all. There were proteins from a number of different classes, and some (9 out of 24) weren't even enzymes, but rather scaffolding and signaling proteins (which wouldn't be expected to have many small-molecule binding possibilities).
A closer look at non-labeled versions of the probe compounds versus more highly purified proteins confirmed that the compounds really are binding as expected (in some cases, a bit better than the non-photoaffinity versions, in some cases worse). So even as small a probe as a diazirine is not silent, which is just what medicinal chemists would have anticipated. (Heck, even a single methyl or fluoro isn't always silent, and a good thing, too). But overall, what this study suggests is that most small molecules are going to hit a number of proteins (1 up to a dozen?) in any given cell with pretty good affinity. It also (encouragingly) suggests that there are more small-molecule binding sites than you'd think, with proteins that have not evolved for ligand responses still showing the ability to pick things up.
There was another interesting thing that turned up: while none of the Ugi compounds was a nonselective grab-everything compound, some of the proteins were. A subset of proteins tended to pick up a wide variety of the non-clickable probe compounds, and appear to be strong, promiscuous binders. Medicinal chemists already know a few of these things - CYP metabolizing enzymes, serum albumin, and so on. This post has some other suggestions. But there are plenty more of them out there, unguessable ones that we don't know about yet (in this case, PTGR and VDAC subtypes, along with NAMPT). There's a lot to find out.