Thursday, August 25, 2016

August 25, 2016 at 11:10PM

Today I Learned: 1) Phone numbers used to be associated with a word, the first two letters of which essentially made up the first set of digits for the phone number. 2) Remember the moon buggy? That iconic little bit of NASA engineering the Apollo astronauts used to get around on the moon? Today I learned that the moon buggy is properly called the LRV (Lunar Reconnaissance Vehicle), and that they were only used on the last three Apollo missions (15, 16, 17). 3) Speaking of LRVs, there's another kind of LRV -- the Lenticular Re-entry Vehicle. This was a flying saucer invented but never deployed by the US sometime during the cold war. I don't think a lot is publically known about the LRV, even though it was declassified in 1999, but I think it was meant to be a nuclear-powered, manned saucer that would sit in low Earth orbit until needed for missile defense... or possibly missile deployment.

August 25, 2016 at 03:13AM

Today I Learned: 1) You can send someone a location (including your location) through Gchat on a phone. 2) The vast, vast majority of magnesium in a bacterial cell is bound to other molecules. Only about 2-3% of the magnesium in a bacterial cell is floating freely in the cytoplasm at any given moment. 3) Pluto was discovered less than 100 years ago! (This fact brought to you by Chigozie Nri)

Tuesday, August 23, 2016

August 24, 2016 at 12:36AM

Today I Learned: 1) Here's a simple little game, designed to viscerally demonstrate how bad humans are at generating random numbers: http://ift.tt/2bAHZYi The game is simple -- you come up with a series of random bits (0 or 1), and a computer algorithm guesses what your next bit will be as it goes. The best I was able to get was about 40% (that is, the algorithm was correct 60% of the time), but mostly my scores ranged in the 30-35% range. It's not even a great predictive algorithm -- random bits from random.org scored 65% against it. Speaking of which, how would you go about writing an algorithm to predict the next bit in a human-generated bit series? 2) Twitter has a way for you to download all of the data on your Twitter account in a browser-displayable format. 3) As of 2014-2016, the US and China have the largest and second-largest GDPs of any countries in the world, respectively. The combined countries of the EU are first or second, depending on who's counting, if you count them as a single country. Otherwise, third is Japan, and it's not even close between China and Japan.

August 23, 2016 at 03:10AM

Today I Learned: 1) A great way to cook meatballs is to pan-fry them in a buttered skillet. If only IKEA meatballs were vegan.... 2) There are Uber-like services for grocery shopping. You just put in a grocery order online, pay a transportation fee, and a runner brings the food to your door. 3) Not a fact so much as a new angle on an old problem.... Let me ask you, what does it mean to learn something? What happens when you learn something? What changes? We all kind of intuitively have an idea of what it means, but I would argue that the details are not so obvious. This is especially apparent when you consider how often someone will *think* they've learned something without actually having acquired the ability to use or reproduce that something*. * Incidentally, while I'm on the topic, I would argue that the ability to avoid this trap is one of the most important skills for rational thinking. If you can't recognize when you're still confused about something, you're going to miss out on a *lot* of chances to learn.

Monday, August 22, 2016

August 22, 2016 at 06:05AM

Bonus TIL: You know that phrase "what doesn't kill you makes you stronger"? Well, today I learned that that isn't the whole phrase. In full, it's "what doesn't kill me makes me stronger; what kills me makes me incredibly strong". The author of that quote, Ernst Jünger, is one of the most interesting writers I've encountered, though I know very little about him. He was a soldier in World War I, and he was one of the few who... actually kind of liked it. I recommend googling "Ernst Jünger quotes" and read a few of his other quotes, and see if you can try to make sense of that man.

August 22, 2016 at 04:36AM

Today I Learned: 1) In evolutionary biology, a commonly-calculated number is N_e, or the effective size of a population. N_e comes from the fact that most of the math in evolutionary biology is based on models of "ideal populations" of organisms, with properties like random and independent assortment, constant population size, and others. Real populations, however, are rarely ideal. For example, many species have males and females in unequal number, or aren't monogamous, which means that some individuals may not have a chance to reproduce. That means that the number of breeding individuals is less than the total population size, so all the math has to be adjusted. In this example, and many others, you can simply calculate an "effective population size", or N_e, and plug it into all the existing math for ideal populations (in this case, N_e is the number of breeding individuals). 2) Speaking of effective population size, today I learned that when talking about *bacterial* evolution, the effective population size is quite, quite different than the actual population size. This basically has to do with linked mutations... say a bacteria happens to acquire a mutation that's slightly beneficial, by random mutation. Unfortunately, there's a good chance that it also happened to pick up another random mutation somewhere else in its genome, and *that* mutation is likely to be bad for it (because many, many mutations are). Now this bacteria, and its descendants, have *two* mutations, and the net effect of those on fitness is probably dominated by the deleterious mutation. Unfortunately, that means that this bacteria's genome will be selected against, *even though it has a novel beneficial mutation*. This is the problem of linkage, and in eukaryotes, linkage is ameliorated by recombination -- sex is really good at shuffling around alleles, so at a population level, any particular mutation quickly gets tested against a relatively diverse genetic background, which lets beneficial mutations accumulate more easily (specifically, with a lower required benefit threshold). Bacteria, however, largely lack recombination, so only mutations with particularly large benefit (about 10^-7 higher probability of survival, it turns out -- still small, but much larger than a naive analysis of bacterial genetics would predict). This can be corrected for by adjusting the effective population size (N_e) of a population of bacteria. 3) Whale sharks reproduce continuously, not discretely. Whale shark reproduction is pretty mysterious, but from what we know, it appears that a whale shark female mates once, then uses the sperm from that mating to slowly, continuously fertilize its eggs over the rest of its lifetime. The young develop inside the mother's body, hatching free when they can survive on their own.

Sunday, August 21, 2016

August 21, 2016 at 06:06AM

Today I Learned: 1) According to one paper comparing truly wild-type E. coli to a domesticated version (http://ift.tt/2bLJyBI), wild-type E. coli have slower and more error-prone translation than their domesticated counterparts. The authors hypothesized that this was because wild-type E. coli typically live in nutrient-limited conditions in which growth is limited, so there isn't as much selection pressure for accurate, fast translation as there is in a lab environment. 2) ...how to write a Python app to interface with a Facebook and/or Twitter account, at least in the broad outlines. It's amazingly simple, except where it gets hard. The simple part is the broad outline bit -- both Facebook and Twitter have public APIs and Python libraries that can access them, so it's just a matter of installing the library and writing a little simple code to make calls. ...Except where it gets hard. Right now I'm stuck on Facebook authentication. It's easy to manually generate an authentication token through Facebook, which is good for a couple of hours, but that's not a good solution for something I want to run a lot. For that, I probably need to emulate a Facebook login request, which means building a whole HTML form in my Python script. That should actually be doable, but it's more annoying than I want to handle right now. Anyone know a better way to log a bot in to Facebook? 3) Sci-fi author Gregory Benford is also a professional astrophysicist, faculty at UC Irvine, and a frequent consultant for NASA.

Saturday, August 20, 2016

August 20, 2016 at 03:50AM

Today I Learned: 1) ...that setting up a routing policy with multiple domains isn't trivial, even(?) for a University IT guy. 2) One of the big elephants in the room when it comes to synthetic biology is mutational escape from circuits. Most things humans try to program bacteria to do aren't actually good for those bacteria, so they tend to evolve out of whatever those things are. It turns out to be *incredibly difficult* to build circuits to be robust to mutation -- pretty much any circuit you can think of is one well-chosen mutation away from failure, and a population of billions of bacteria can choose mutations really well.... I've been thinking about how to get around the problem of mutational escape. One way is to reduce the mutation rate (for instance, by removing error-prone polymerases). A crazy idea I've been toying with is to grow a bacteria with multiple genomes, so that the cell can check its genomes against each other and correct errors (or die when a mutation is detected). How effective could that be? It's not perfectly effective, because even if a cell detects a mismatch between the two sets of genes, it would have no way to know which one is correct, so it would have some probability of flipping the backup copy to the mutation instead of flipping the mutated copy back to the correct sequence. Today I crunched those numbers, and figured that having a second set of chromosomal DNA to act as a correcting mechanism would reduce point mutation rate by about 50%. That's not a huge gain for the complexity that mechanism would require. 3) CRISPR was discovered in the '80s and '90s, not the '00s like I thought. That means that bacterial genome sequencing was happening well before I thought -- I assumed the bacterial sequencing craze happened in the wake of the human genome sequencing project, not before it.

Thursday, August 18, 2016

August 19, 2016 at 01:48AM

Today I Learned: 1) When buying a transilluminator, it can really pay to get the more expensive, brighter one.... A too-dim transilluminator isn't much of a transilluminator at all. 2) ...that space has a minimum temperature of 2.7 Kelvin. 3) The US is phasing out private prisons! I can't believe something so sensible is actually coming out of our government! Seriously, what's going on here?

August 18, 2016 at 03:47AM

Today I Learned: 1) Industrial science is serious. Today I learned about GMP, or general manufacturing practices. In scientific and medical industry labs, there's a more specific version called GLP -- general lab practices. The gist of GMP (and GLP) is that everything is SUPER STANDARDIZED and SUPER GOOD. I don't really know most of the details of GMP (or GLP), but it includes things like online, company-accessible, government auditable notebooks. For everyone. Specifically for medical labs, it also includes the use of *closed systems* wherever possible, where here, "closed systems" are systems physically isolated from people as much as possible -- everything's piped straight from one reactor to the next, until the last possible second. I presume this is to cut down on contamination and to improve reproducibility of manufacture. You know, I never fully appreciated how complex it is to produce a drug, much less a biologic like a stem cell or an antibody. Pretty much every step of the synthesis has to be done in-house, in a totally controlled and perfectly reproducible way, in a manner that scales with demand, with *no* contamination allowed. It's not just manufacture, either -- a drug company also has to market, sell, and distribute the drug. Autologous* stem cell therapies are possibly the most difficult case on the market right now. Here are some of the processes that an autologous stem cell therapy company has to provide: -- Sales to point-of-care locations (including payment processing) -- Registration of patient cells -- Transportation of patient cells (not trivial! Especially at scale!) -- Tracking and receipt of cell transportation to facility -- Internal sorting and processing of patient cells -- WHATEVER THE ACTUAL SCIENCE IS TO MAKE MODIFIED CELLS -- Internal sorting and processing of modified patient cells -- Shipping of modified cells -- Tracking and receipt of modified cells to point-of-care locations Note how many places there are where a line of cells could potentially be mixed up with another vial of identical-looking cells from another patient. That can't happen. Ever. And that "WHATEVER THE ACTUAL SCIENCE IS TO MAKE MODIFIED CELLS" bit? Yeah, that's done under GLP -- it has to be closed-loop, reliably timed, and certified free of mycoplasma and other common contaminants. Oh, but wait, it gets worse -- this entire process has to be designed and finalized during phase III trials (or phase II for accellerated trials -- one of the many reasons accellerated trials might not actually be good for a company). If you discover that there's an inefficiency in your manufacturing strategy during the trial, or you discover that you can't meet demand (or that you're manufacturing way more than is demanded), tough luck unless you want to convince your investors to start the phase III over again (not happening). It also means you can't start off making everything small-scale and then plan on figuring out scaling late in the process -- you have to consider this stuff pretty early in development to have a chance of making it all work. Investors (and the FDA) know this, so one of the things they look for froma company in the early stages of testing is some cognition of the difficulties of moving to GLP and scale manufacturing. * Derived from the patient's own cells. Contrast with "allosteric", which means the stem cells are standardized cells from a central stock. 2) Basically everyone I know who's worked with stem cells has told me that it's really up in the air whether those cells are actually what scientists claim them to be. Stem cells, you see, have a nasty habit of differentiating, since that's *what they do* in the body. Worse, some of these differentiation steps seem to be phenotypically silent -- you can't tell that they've changed by looking at them, they just won't differentiate the way you expect. This problem is particularly important for induced pluripotent stem cells (iPSCs, or iPSs), which are stem cells derived from differentiated adult tissue (commonly skin cells). The early claim was that iPSCs were identical to embryonic stem cells (ESCs), and therefore could be used in place of them without the need for expensive, difficult-to-work with embryos (or the ethical controversies that come with them). But are they really the same? Today I learned that yeah, they are. Mostly. Almost. A professor (and former industrial scientist!) named Jeanne Loring* got really obsessed with the question of iPSC identity**, and her lab has subjected iPSCs and eSCs to genomic, transcriptomic, and epigenetic characterization at multiple stages of culture and production. Here are some results: -- iPSCs are genetically identical to normal cells... -- ...but they don't stay that way. When induced, the cells are fine; when expanded in culture, they start to accumulate cancer-like mutations, especially gene duplications and *especially* deletions in p53 (a critical cell cycle checkpoint and one of the first things to go wrong in most cancers). Therefore, expansion is the most critical stage of production for iPSCs, and will require the most stringent controls. -- iPSC gene expression clusters very nicely with eSC gene expression. The Loring lab put together a phone app for predicting stem-cell-ness from RNA-seq data. I'm not sure how you're supposed to pipe RNA-seq data through a phone, but that's another story.... -- The epigentics of iPSCs are *almost* normal, as validated by a screen of about 50,000 known epigenetic markers. The major differences are that, consistently, 1) Barr bodies are unravelled, so both X chromosomes are active in female cells, and 2) genetic imprinting (permanent silencing of either the maternal or paternal allele of a gene) is completely wiped. These changes do make some sense -- they're exactly what you would expect from a cell that just underwent reversion to an embryonic state. Interestingly, Loring is one of the few scientists I've encountered in medical areas who advocates for *more* stringent regulations by the FDA in her field. As of right now, the only QC the FDA requires in terms of validating the identity of stem cells is that they're karyotyped (their chromosomes are counted). Which is nice, I guess... but yeah, it seems like some additional validation would be nice. * very friendly woman, btw, if cheerfully blunt. ** The reason *why* she was interested in this question is really worthy of its own TIL entry. Loring was involved in some early (1990s-2000s) stem cell therapy trials for treating Parkinson's Disease. They harvested dopaminergic neurons from a tiny sliver of an aborted fetus's brain, and implanted those neurons in PD patients. The trial had wildly mixed results -- on the one hand, some of the patients were pretty much completely cured, and lived out the rest of their lives drug-free, continuously improving in behavioral measures for at least 14 years after the surgery. On the other hand, a bunch of them developed additional dyskinesia (involuntary tremors), which made their quality of life significantly worse. Overall promising, but a dud. Loring is now quite convinced that the original failures were due to non-dopaminergic neuron contamination from when the neurons were extracted from the fetus. The issue of quality control turned into a quite-publishable 10-year project. 3) Many kinds of common cancers commonly metastasize to the brain (~30$ of breast cancer metastases, for example). I'm not sure if that's because brain is a particularly fertile ground for cancers (less immune system access?) or if cancers commonly metastasize *everywhere*.

Tuesday, August 16, 2016

August 17, 2016 at 12:33AM

Today I Learned: 1) Today is day 1 of the Rejuvination Biotechnology 2016 conference, so I have a bunch of aging-research-related facts for your perusal. I'll start with senescent cells. Senescence is a state that many different kinds of cells can flip to permanently, and it's associated with three coupled phenotypes -- senescent cells are highly resistant to apoptosis and in general rather resistant to death; senescent cells don't replicate; and senescent cells secrete a complex (but consistent) mix of proteins, hormones, and other factors. Senescence seems to do a few things, some of which are good and some of which are bad. Good thing #1: It's a dead-end for an otherwise pre-cancerous cell. Senescence is thought to be one of the mechanisms by which a cell can prevent itself from going cancerous, presumably if the normal apoptotic pathways break somehow. Good thing #2: Senescent cells increase inflammation locally, and seem to be important for promoting normal, effective wound healing. When you lacerate a mouse, a bunch of cells in the region of the wound turn senescent, which appears to recruit a bunch of machinery to repair the wound. Once the wound is healed, most of the senescent cells get eaten up by the innate immune system. Bad thing: Senescent cells increase inflammation locally, and seem to be highly stressful and possibly carcinogenic when they stick around chronically (for decades). When a wound is healed, *some* of the senescent cells in the area tend to survive, and they basically never, ever go away. They also never stop secreting all those inflammatory factors, which is pretty hard on your body if you accumulate too many senescent cells. Today I learned that one possible reason some senescent cells survive is that they secrete a lot of proteases (enzymes that break down proteins). There's variation in how much protease each senescent cell produces, and it turns out that the ones that survive cleanup by the innate immune system tend to be the ones that secrete a ton of protease. It sounds to me like all that secreted protease is digesting one of the factors the immune system uses to recognize senescent cells. This protease secretion may also be what makes senescent cells carcinogenic, or at least makes cancers worse -- all that protease eats at surrounding extracellular matrix, which makes cancerous cells more likely to slough off and metastasize. 2) There have been a ton of studies on C. elegans (an almost-microscopic soil worm) showing that some compound or another dramatically increases their lifespan. Usually, these make big news, and are quickly followed up by a bunch of studies which fail to replicate the findings. Why? A joint team from the Buck Institute for Research on Aging, Southampton University, and UC Davis ran a cross-lab comparison study to try to figure out what was going on. Along the way, they found some compounds that look like they really do reliably increase C. elegans lifespan, but the part I found really interesting was the control experiment. One of the key points of the study was to figure out just how much variation there is in C. elegans lifespan experiments, and where the variability comes from. To do this, the teams came up with a joint, carefully planned-out protocol, trying to nail down every possible variable down to the lot numbers of their equipment and reagents. The three labs then ran simple longevity experiments on a bunch of different strains of three different worm species -- they grew the worms on a plate full of bacteria, and watched to see how long the worms lasted. Unsurprisingly, there was a lot of variation in worm lifespan. Surprisingly, there was *almost no* variation across labs -- roughly 0% of the variation could be explained by intra-lab differences. There were certainly differences between strains of worm, and even bigger differences between species, but the single biggest source of variance (by about a factor of 2) was *experimental replicates*. Sometimes, you would culture a plate of worms and the whole plate would live a really long time. Other times, you would put in a seemingly-identical plate of worms in the incubator and they would all die relatively quickly. This was consistent across the three different labs, and it actually seemed to follow a *bimodal* pattern -- lifespans weren't just random, they would tend to either all be high or all be low, depending on the plate, but not in a predictable way. Exactly where that variance was coming from isn't clear, but it *does* sound like a likely explanation for the fiascos over stuff like sirtuins -- the initial experiments showing effects of the drug happened to grow a bunch of short-lived plates for their controls, and a bunch of long-lived plates for their drug-treated condition. You can read more here (open access!): http://ift.tt/2aY5vcc 3) The Wake Forest Institute for Regenerative Medicine can reproduce decent facsimiles of mammalian follicles in vitro (that's the kind of follicle that produces eggs, not the kind that produces hair). They extract cells from an ovary, then culture those cells on a plate with tons of tiny little inverted-pyramid-shaped wells, which causes the cells to form clumps. Those clumps look an awful lot like follicles, and they behave a bit like them, too -- they can secrete estrogen and progesterone more-or-less stably (with more-or-less the right dynamics), and they can produce egg cells that can be fertilized (though it's still up in the air whether those fertilized eggs can be implanted successfully). 4) Speaking of culturing mini-organs, did you know you can produce milk in a culture dish? Apparently it's not *that* difficult to grow mammary cells in a slightly structured way that lets them produce milk in vitro. Also, if you add senescent cells to the culture, it disrupts their structure and kill milk production.... 5) There was an interesting idea from the MIT Economics department about how to fund expensive medical treatments. One of the huge problems with bringing preventative anti-aging treatments to market is that they're not necessarily good money, and there might not be a good way to pay for them if they're too expensive, even if they would end up saving money in the long run. One idea for how to better finance expensive medical treatments is to provide a medical loan to the patient -- whoever makes the treatment pays for the treatment, and then as long as the patient remains healthy, they pay back the producer in regular, small installments. It still costs money, but it means the patient doesn't get hit with an impossible-to-pay bill (or get outright refused), and it provides good incentive to the producer to make sure the treatment works. 6) Speaking of MIT, but otherwise completely unrelated to regenerative medicine, Duoskin tattoos! MIT media lab and Microsoft have teamed up to bring wearable electronic tattoos to the world. The tattoos are made of printed gold and silver leaf, and can be worn on any skin surface. So far they've demonstrated a touch pad/scrollpad, a small LED-like color-changing display (a few pixels by a few pixels), and a wireless communication circuit a la RFID tags. More at http://ift.tt/2bguLyI Thanks for cluing me in on this, Sarah Seid!

August 16, 2016 at 03:59AM

I'm postponing tonight's TILs. But worry not, there ought to be six good ones in less than 24 hours' time.

Monday, August 15, 2016

August 15, 2016 at 03:26AM

Today I Learned: 1) Here's an interesting bit of experimental new tech: http://ift.tt/2bwW219 (or, for a non-paywalled digest, http://ift.tt/2aX8PX0). In short, a joint team out of Bangor and Fudan University have figured out a way to lay own lenses made out of bazillions of titanium dioxide nanoparticles, which each act as a tiny little microlens. The net effect is a lens which can provide images with resolution down to 45 nanometers -- about a tenth the size of the wavelength of light, or about 1/25th the diameter of a bacteria. 2) Crickets can really chew through stuff if they need to! I have a box full of crickets right now for feeding my mantis, covered by a plastic mesh and an attached paper towel. Today I discovered that some enterprising cricket had chewed a hole through both the paper towel and the plastic mesh! This explains why I've been finding crickets around the house.... 3) I just had a rather unusual experience with a moth, from which I may have learned an adaptive behavior. I had just put a moth in my mantis's cage, and poured in a bit of water to soak some paper towels in the cage and keep it moist. The moth got hit with some water, and panicked for a bit, fluttering around. When it came to rest, I... you know how it is when you show a dog or a cat something really outside its previous experience? Like a roomba, or a mirror for the first time? And it just... can't seem to get it in its head what it's seeing? I think that's what I experienced. The moth landed, and stopped moving, but its wings were... blurred. It looked like nothing so much as a video of a moth just starting to take off, stuck in mid-frame. Or perhaps a glitch in the matrix. Eventually it did actually take off and flittered around several times. Each time it landed, it kept doing the same thing with its wings. What was it doing? Maybe its wings were damaged somehow, but it didn't seem to have any trouble flying when it did fly. I'm betting it got its wings wet, and was humming them to dry them. What do you think?

Sunday, August 14, 2016

August 14, 2016 at 04:18AM

Today I Learned: 1) Mantises keep their wings protected inside two thin secondary wing sheaths, one on the outside and one on the inside. I'm not sure how much the sheaths are there for flight purposes, how much they're there for physical protection, and how much they're there for camouflage. 2) When sea turtle mothers lay their eggs on the beach, they will sometimes dig false nests with no eggs, which confuses any predators that may be watching and keeps them off of the real thing. 3) SENS, an organization that is trying to end aging through biotechnological interventions, has recently announced a program called Project|21, which aims to start clinical trials for anti-aging preventative treatments by 2021. They're looking ot raise something like $50 million between now and then to make this happen. That's a *huge* jump in funding -- they've been making single-digit millions for the last five years or so, so they're going to have to push pretty hard to make this happen. I'll be keeping an eye on it, though. See here for details: http://ift.tt/29NGhR8

Saturday, August 13, 2016

August 13, 2016 at 06:13AM

Today I Learned: 1) ...the difference between aquaponics, hydroponics, and aquaculture. Aquaculture is any kind of rearing of aquatic critters, usually plants or fish. Hydroponics is any kind of growing of plants in water, usually mineral-rich, without soil. Aquaponics is a hybridization of the two. Typically in aquaponics hydroponically-grown plants provide bits of food for fish in the form of detritus, and the fish provide fertilizer for the plants in the form of body wastes. 2) ...the difference between viruses, worms, and trojans (in the context of computer malware). The divisions between different kinds of malware can be fuzzy, but in general they follow these patterns: a virus is a program which inserts itself or other malicious code into another, usually legitimate, program, and can replicate itself when the host code is run; a worm is a standalone program that runs on its own, spreading itself without any particular intervention required; a trojan is a standalone program that tries to mimic a legitimate program in order to get a user to run it. Also, an anti-worm is a standalone program that forcibly spreads itself, patching known security vulnerabilities as it goes. They are, as one might imagine, extremely uncommon, and not recommended best practice by... anyone. 3) Although a number of animals *can* rhythmically entrain (a.k.a., move their bodies to rhythms), the ones that are *best* at it are humans, parrots, and sea lions. Just why sea lions are so good at dancing isn't really know.

Friday, August 12, 2016

August 12, 2016 at 03:12AM

Today I Learned: 1) So, I got to peek pretty deeply inside our lab's big floor shaking incubator, and it turns out it has a few nice features to protect itself from spills. The interior is one big basin, with only a couple of holes in the middle for the rotor and a couple of stabilization hard points, so mostly anything spilled down there just sloshes around. Water (or media full of bacteria...) can get through the rotor-hole and the stabilization hard points, though, which would be bad. To protect against this somewhat, those three holes have their edges curled up, as a little barrier. There's another hole that leads to a drain line, which is sunk in slightly. The interior has a large enough floor area that the half-centimeter or so of difference in height is enough to keep media out of the guts of the incubator unless you spill a LOT of media. The only problem I have with the design is that the drain line is literally just a piece of tubing, maybe two and a half feet long, with a valve at the end. It doesn't hold much liquid at all -- it would be much better to have it drain into a detachable reservoir. I guess the point is that if you spill a ton of stuff, you drain out the bottom instead of mopping up everything from inside the way I did. 2) Greenland sharks are now probably the oldest-known vertebrates, with the oldest-known greenland shark clocking in at about 400 years old -- in other words, about as old as calculus. Shamelessly reposted from Caroline Golino's post today: http://ift.tt/2aGujKe 3) From the same article as above -- did you know you can radio-carbon date biological tissues from specimens less than 50 years old? It turns out that there was enough carbon-14 dumped in the ecosystem by nuclear weapons tests in the 60s that you can carbon date extremely young things with it.

Thursday, August 11, 2016

August 11, 2016 at 03:23AM

Today I Learned: 1) If you're going to put something unattached in a shaking incubator by running it with the shaking off, for goodness sakes, STICK AROUND TO MAKE SURE IT'S ACTUALLY OFF. 2) For some reason, I had it in my brain that sea mammals (whales, dolphins, porpuses, etc.), and their other close relatives like elephants and hippos, were fairly closely related to rodents/primates. Turns out they're not particularly closely related to us, as mammals go. 3) A short, incomplete list of animals known to spontaneously dance or otherwise move to rythmic sounds: Humans, parrots, elephants, sea lions, dolphins. Also, rumor has it that gorillas hum while they're eating?

Monday, August 8, 2016

August 09, 2016 at 12:06AM

August 08, 2016 at 03:29AM

Today I Learned: 1) The bacteria Bacillus Subtilis (B. sub) can differentiate into at least 8 cell types. The "default" cell type (the one it defaults to if no other genetic differentiation programs are activated) a highly motile, flagellar type, good for moving around and finding fresh sites to colonize. Once a B. sub colony takes hold and starts to grow, the colony will differentiate into a few different cell types. "Miner" cells specialize in excreting hydrolytic enzymes into the environment, which is good for digesting random proteins into amino acids that the colony can eat. Others specialize in excreting the extracellular matrix proteins that make up the bulk of the colony's mass and protect it from small-scale intrusion and viral infiltration... but those cells won't actually excrete matrix protein without signals from B. sub specialized for surfactin production. Surfactin also acts as a broad-spectrum antibiotic, further protecting the colony. When exposed to stress, B. sub can and does differentiate into all of the above, plus a few emergency-response phenotypes. Some go motile again, fleeing for more fertile ground. Others enter a cannibalistic state, in which they specialize in eating up dead B. sub, therefore taking maximal advantage of all the dead material around. A few enter a state called competency, which means they open up their membranes a bit and start sucking down any DNA floating around in the hopes that something will carry a gene that will let them survive.* Most competent cells will fail and die, so it's not worth having much of the population attempt competency, but occasionally it works. The last-resort phenotype, and the one that all B. sub will flip to if stressed hard enough, is sporulation. A sporulating B. sub gives up any hope of surviving in the present environment and forms a kind of extremely tough lifeboat for its DNA and just enough machinery to boot up a new cell. Committing to sporulation is not a decision to make lightly -- the spore is built *inside* the mother cell**, and is dehydrated and released forcibly, killing the mother cell. It's a measure of last resort, but it *does* let cells survive ridiculously hostile conditions, like being boiled or actively attacked with lytic toxins. This is just a reminder that bacteria, though technically single-celled, can really be thought of as a kind of colonial organism. For more details on B. sub population differentiation, see http://ift.tt/2aTBCfO (not sure if it's open access, sadly). It one of the cuter and more helpful first figures I've seen in a paper, so at least check it out for that. * That competency works at all should tell you something about how different the microbial world is from our macro-scale world -- bacteria live in an environment where eating and incorporating random genes is a matter of choice, and is occasionally useful. That's a bit like a poisoned person eating every random plant in sight in the hopes of finding an antidote, or a computer under attack grabbing random download links for binary files and trying to execute them in case it helps. I'd say the other emergency-response phenotypes are totally familiar to anyone who's read any apocalyptic space opera, but competency is a stress response more or less alien to human experience. ** The spores are impressively complex. Check out the "Structure" subsection on the Wiki page for "Endospore". In case you don't, here's a summary: the cell's DNA is packaged tightly inside UV-protective, chromatin-like proteins. The DNA/protein mix is further packed with calcium dipicolinate, a small acid that essentially acts as packing foam by protecting and stabilizing the core contents, along with a bunch of ribosomes and critical enzymes. The core is packaged inside a peptidoglycan membrane called the "cortex" that I asssume forms the outer cell wall of a hatched spore. The cortex is further wrapped in a molecular seive that protects the spore against most toxins, especially lytic enzymes. This package is released 2) One of the weird quirks of studying bacteria is that the bacteria we study in the lab aren't really what's in the wild. After all, lab conditions are only vaguely similar to real environmental conditions, and bacteria start evolving to adapt to lab environments *very quickly*. After a couple of days-to-weeks of growth in a lab, bacterial populations become "domesticated" -- they lose a lot of their wild adaptations and become heavily optimized for lab conditions, which are extremely nutrient-rich and well-mixed (not spatially-structured). In some ways, this makes them more convenient for lab work, since domesticated bacteria grow more quickly and more robustly (in a lab) than their wild counterparts. If you just want to use bacteria to grow plasmids, it's great, but if you want to *actually study* bacteria, domestication can be a real annoyance. Today I learned that one of the hallmarks of domestication is that bacteria lose a lot of their phenotypes related to colonial life. The colonies formed by domesticated bacteria are weirdly smooth and unstructured, and in many cases are smaller than wild-type colonies. This makes sense -- bacteria in a lab are usually grown in shaken liquid media, where they have no opportunity to form colonies. In those conditions, evolution favors bacteria that can eat and divide quickly, not bacteria that can form stable, thriving colonies. See http://ift.tt/2aZXjw3 for details, especially figure 2 (probably paywalled, sorry!). Incidentally (or maybe not incidentally), similar changes happens in mammalian cell culture all the time, too. That's doubly true for cancer lines, since cancers tend to mutate early and often. That's *extra* annoying because cancer cells are used disproportionately for cell culture studies due to their unlimited replicative potential. 3) Cleaned a keyboard for the first time today. Not really a fact to put here, but I now have a very good idea what's under the keys in a ten-year-old keyboard. (...actually, there *is* a bit of a fact to this one -- today I learned that keyboards are a really efficient sink for, of all things, cat hair. This keyboard hasn't cohabitated with a cat for somewhere between 4 and 6 years, yet it had a nice thick layer of redish cat hair under the keys)

Sunday, August 7, 2016

August 07, 2016 at 04:33AM

Today I Learned: 1) There is at least one species of cockroach that lives around here that I had never seen until today! It's a smaller species than the usual ones I've seen (which are themselves quite similar to typical dorm cockroches I've seen on the East coast), and could *almost* be confused for a non-cockroach beetle... but on closer inspection, it's definitely a cockroach. 2) A while back, Lady Jade!!! and I did some back-of-the-envelope calculations to figure out how many people a typical teen working at McDonnalds could support with the standard of living of a peasant from the late dark ages/early middle ages in Europe. It's not a simple calculation, but we figured it was somewhere on the order of "a few" (2-5?). It's pretty incredible that we've managed to compress the full time, all-day every day labor of a full grown person down to something like 10-20 hours of relatively light* service work of a relatively unskilled post-adolescent. Today I learned a concrete fact that hammers home just how ridiculously wealthy we are now. In the middle ages, a set of clothing required labor which at present minimum wage would cost about as much as a new car. According to a quick estimate by Eve Fisher, a medieval shirt on its own would cost a *minimum* of $4,200 to produce, and would likely cost more (http://ift.tt/2aw1wn1). Clothes are really, really, really expensive to produce, and modern clothes are essentially free by historical comparison. *relative to a Medieval peasant!!!! 3) ...of a nasty little bit of Amazon's public relations history. In 2009, somebody noticed that Amazon had just put a new adult content filter in place, and that it had systematically removed just about any literature about sexuality, particularly anything written on the topics of homosexulity, bisexuality, or transgenderedness. Plenty of sex toys could still be found on Amazon, as could downright nasty books like Mein Kampf and The Protocols of the Elders of Zion -- just nothing literary about nominally deviant human sexulity. To a lot of people at the time, this looked like a systematic expunging of LGBT-friendly literature from the literary marketplce by Amazon, which rightfully got people angry, leading to a brief flurry of "#amazonfail" on Twitter. The story from Amazon, which frankly sounds pretty plausible to me, is that their adult content filtering system was designed to filter blatantly pornographic material from front-page search results. That system relied on user-generated tags to identify pornographic material, and someone or someones had gone around and tagged a bunch of LGBT literature with pornographic-like tags that were picked up by the automatic filtering system. Unfortunately, not a whole lot of people were using the tagging system, so a relatively few taggers were able to cut off huge swaths of literature. Not a pretty day for crowd-sourcing.

Saturday, August 6, 2016

August 06, 2016 at 05:52AM

Today I Learned: 1) You can buy air plants (plants without soil requirements) on Amazon, and they're surprisingly cheap (a couple of dollars per plant). Typical air plants can be hung on pretty much anything, and can live off of misting or moist air, if you live in a state with moist air. They supposedly need pretty specific light requirements -- strong light, but not direct, much like a plant might receive in the canopy of a tropical forest. 2) Bio lab fact: It's relatively easy to buy PCR tubes in strips, and it's relatively easy to buy PCR tubes with attached caps, but if you want to buy PCR strips in tubes *with attached caps*, the price jumps up two- to three-fold. 3) Another Bio lab fact: Be careful buying PCR plate lids! They are not all compatible with all PCR plates -- some have notches in the corners BUT NOT ON THE SAME CORNER AS YOUR PLATES. Rgh.

Thursday, August 4, 2016

August 05, 2016 at 12:24AM

Today I Learned: 1) Back at the beginning of the year, a joint team of various New York state university scientists created a mouse whose feeding behavior could be controlled by radio waves... and not in the way you'd expect. The team genetically engineered a mouse with a fusion between a calcium channel (TRPV1) and a radio-sensitive, iron-binding protein called ferritin. The fusion protein was engineered to be expressed in glucose-sensitive neurons. When triggered by radio frequency photons, the proteins could either switch the channel on or switch it off, activating or inactivating the glucose-sensing neurons and altering feeding behavior in the mice. 2) Ever heard of a hornworm? Go do a quick google search. Those things are about the size of a human finger. You can buy them, one to a box, at Petsmart. 3) Monopoly is based on an earlier board game called The Landlord's Game, which was designed to demonstrate the benefits of single tax systems. It was meant to be played in two phases. The first phase was pretty familiar to anyone who's played Monopoly. In the second phase, the rules switched to show off the single tax system, and to make the game more egalitarian and less zero-sum. Turns out that the zero-sum version of the game was more fun, so someone else tweaked those rules and released their own version of the game, which they called Monopoly. Thanks to Andrew Montequin for teaching me about this!

August 04, 2016 at 05:07AM

Today I Learned: 1) Jeff Hasty's lab has engineered bacteria which can synchronously grow and die off together once they reach high density. This lets them maintain log-phase growth more or less indefinitely. The lab put some of these engineered bacteria into a mouse model for a human cancer, and the bacteria stayed more or less synchronous and pulsed together, maintaining a fairly steady population over a long period. 2) There is an algorithm, called the Bailey-Borwein-Plouffe (BBP) formula, for calculating any single binary digit of pi, directly, without calculating any of the intermediate digits. For some reason, it involves base 16 calculations. The BBP formula was a total surprise to mathematicians when it was introduced in 1995, and I imagine it still comes as a total surprise to math students today. More surprisingly, a bunch of other formulae for well-known irrational numbers have been discovered with the same form. There is no general technique for discovering those formulae. It's not clear whether or not all irrational numbers could be defined in terms of similar formulae. Here's the general idea of the algorithm. The BBP formula says that pi is an infinite sum over k from 0 to infinity of (1/16^k) * (p(k) / q(k)), where p and q are some (simple) polynomials in terms of k. Each term in the sum is a window of four binary digits (bits) of pi. If you want to know the 56th digit of pi, you figure out which window it's in by dividing the digit number by 4. That's k (in this case, 14). Now crunch out the values of p(k) and q(k) for your chosen k. Divide p(k) by q(k), and that gives you the k/4th digit of pi in base 16. Convert that digit to four binary digits, and you have your 56th binary digit. 3) Mantises can, to my surprise, rearrange their grip on their prey mid-meal. They're quite single-minded once they've caught prey, basically doing nothing but wolfing down the insect as quickly as possible, chitin and all (except for wings, often), backing away from overt threats lazily. So I was surprised to see a mantis *let go* briefly and rearrange its grip.

Wednesday, August 3, 2016

August 03, 2016 at 04:15AM

Today I Learned: 1) Sometimes, getting post from a USPS station requires a lot of patience and the willingness to escalate the problem to higher levels of management when lower-ranking servicepeople fail. 2) Firefly larvae are mean little creatures -- they're carnivorous. Some species eat dead meat. Other species hunt down snails and earthworms and similarly soft prey. Some of *those* species inject whatever food they find with a paralyzing venom so they can munch it up in peace. Don't mess with firefly larva. 3) I've spent a fair amount of time wondering why someone decided it would be a good idea to build a city in the LA area. Today I learned that LA was originally* settled largely by Spanish missionaries. Hence the name. And of *course* they thought it was a good place for a city -- the climate in LA isn't too dissimilar to what they were used to back at home in Spain. * in the European sense. I don't know if anyone lived here before the Spanish.

Tuesday, August 2, 2016

Oral Bias, Lichen Triplet, and Elon Musk's Personal Life

Today I Learned:

1) There was a big study in this month's Science on gender bias in technical tests in France. It was a huge, non-randomized study that analyzed data from a national series of standard professional tests in a number of fields. The tests are split into a written portion, which is name- and gender-blind, and an oral portion, which obviously isn't gender blind. The (rather surprising) finding of the study was that minority genders (women in math, physics, and philosophy; men in languages and literature) scored better on the oral portions than on the written portions, in comparison to the other gender. The effect was stronger for women than for men, and the effect was greatest in the fields with the most gender gap. The authors therefore suggested that oral exams might be helpful for closing the gender gap in male-dominated fields.

Not sure if this study can be taken to mean much solidly, in the big picture, but it's an interesting tidbit. Link here, paywalled, of course: http://ift.tt/2awXlIK

2) Lichens are a symbiotic superorganism made up of a fungus (which provides the structural support for the lichen) and a photosynthesizer, usually a basal plant or prokaryote (which provides the food). Until today! Again from this month's Science, researchers performing transcriptomics on a bunch of lichens found unexpected evidence of *yeast* in the mix. It turns out that several lichen species *also* have a yeast symbiote, though exactly what it's doing for the other two (if it's doing anything at all) is unknown.

That's really about all the article has to say, from what I got from a quick read, but here's the (paywalled) article for completeness: http://ift.tt/2aJ6ctV

3) Elon Musk has been married three times... twice to the same woman. If their public statements are to believed, they separated under good, even loving, terms. Sounds likely to me that they really do love each other and get along well... but Musk just doesn't have time for a wife. With, y'know, saving the world and all.