Today I Learned:
It's Punic Wars day! Not really, but I learned some interesting things about the Punic wars, so here are your three Punic Wars facts for the day (specifically, from the second Punic Wars)
1) The famous elephants that Hannibal brought across the Alps into Rome? It seems they were pretty effective until they died from the cold at the foot of the Alps.
2) The Romans lost a lot of political leadership during the Punic Wars. Today I learned that Roman politicians of the time of the second Punic Wars were a) without exception military veterans and b) led the military, directly.
In particular, Rome of the day had a position called the Consul, which was a bit like a president except that a) they served one-year terms, b) they were truly military commanders as well as politicians, and c) there were always two of them at a time. A lot of these led armies against Hannibal, and were killed in battle. Politics may have been pretty similar then and now, but being a politician was not.
3) Speaking of Roman military leadership, one of the most famous Roman generals *possibly* of all time was Fabius Maximus, of the eponymous Fabian strategy, which I'll get to in a second. Today I learned that Fabius was elected dictator of Rome early in the Second Punic War in response to a string of early humiliating defeats by Hannibal. His strategy, the Fabian strategy, was to beat Hannibal by not fighting him. After all, Hannibal had just smashed several competent Roman armies, so Fabius figured he probably wasn't going to out-fight Hannibal. Instead, he would shadow Hannibal's army across the countryside, never engaging it directly but ensuring that it couldn't really rest and recuperate, either. Hannibal was far from home and essentially not getting any reinforcements, while Rome was marshalling new armies as quickly as she could.
Friday, October 9, 2015
Cas9 Specificity, Armadillo Polyembryony, and Relaxation Oscillators
Today I Learned:
1) ... a bit more about the specificity of Cas9. Turns out that cas9 can cut targets that differ from the guide by one or two nucleotides, though at reduced efficiency. More than that makes it completely non-functional. This is really important for genome editing, because you really don't want it cutting in places you don't expect. Cas9 used for regulation may be another story entirely. According to some iGEM data I found, cas9 may still be able to *bind* (but not necessarily cut) at an appreciable rate (5% of the maximum-efficiency rate) with a dozen nucleotide differences. These particular numbers seem a bit absurd to me, but I also recall seeing one paper in which the authors made tunable cas9 repressors by mutating the guide RNA a little bit off of the target. Unfortunately, I can't find that paper right now, so I'm not going to link it. This needs corroboration.
2) Armadillos use a rare form of reproduction called “polyembryony”, in which a mother has a single fertilized egg during pregnancy, but that egg splits into multiple embryos which develop into multiple genetically identical siblings. This is how you get identical twins in humans and other animals, but a few species of armadillos are the only vertebrate species known to exclusively reproduce through polyembryony.
Polyembryony is a particularly weird form of reproduction because it seems to combine the biggest disadvantages of both sexual and asexual reproduction. Unlike asexually-reproducing species, armadillos have to find mates to reproduce, and only pass half of their genes to their offspring. But unlike sexually-reproducing species, an armadillo’s offspring are not particularly diverse, and so are vulnerable to parasites, diseases, and environmental conditions that disproportionately affect certain genotypes.
Why polyembryony, then? The best proposed reason I’ve found is that it’s an adaptation to a sort of pre-existing evolutionary condition in the armadillo — the structure of the armadillo’s uterus is such that only one egg can be fertilized at a time. Why? We don’t know. Presumably it happened for some other reason, or perhaps entirely by accident, but whatever the reason, *if* you take it as a given that only one egg can be fertilized, yet the mother can provide for more than one offspring in a litter (armadillo mothers don’t care for the young particularly much or long), then polyembryony makes some sense.
Thanks to Heather Leigh for pointing me to this fascinating armadillo information!
3) A relaxation oscillator is a system that behaves periodically but not sinusoidally. Simple examples include square wave oscillators and sawtooth oscillators. A more complicated example would be a ring tone.
A typical way to think about relaxation oscillators is that there’s some timer that counts down, and when that timer hits zero, the system produces some distinct output, like a square wave or a spike or a measure from some musical piece. Then the timer resets and starts counting again. Relaxation oscillators are a common motif in electrical circuits, where the “timer” is often a capacitor. The capacitor’s charge spikes out, triggering the output signal, then slowly decays (relaxes) back to its charge value. Hence “relaxation oscillator”.
1) ... a bit more about the specificity of Cas9. Turns out that cas9 can cut targets that differ from the guide by one or two nucleotides, though at reduced efficiency. More than that makes it completely non-functional. This is really important for genome editing, because you really don't want it cutting in places you don't expect. Cas9 used for regulation may be another story entirely. According to some iGEM data I found, cas9 may still be able to *bind* (but not necessarily cut) at an appreciable rate (5% of the maximum-efficiency rate) with a dozen nucleotide differences. These particular numbers seem a bit absurd to me, but I also recall seeing one paper in which the authors made tunable cas9 repressors by mutating the guide RNA a little bit off of the target. Unfortunately, I can't find that paper right now, so I'm not going to link it. This needs corroboration.
2) Armadillos use a rare form of reproduction called “polyembryony”, in which a mother has a single fertilized egg during pregnancy, but that egg splits into multiple embryos which develop into multiple genetically identical siblings. This is how you get identical twins in humans and other animals, but a few species of armadillos are the only vertebrate species known to exclusively reproduce through polyembryony.
Polyembryony is a particularly weird form of reproduction because it seems to combine the biggest disadvantages of both sexual and asexual reproduction. Unlike asexually-reproducing species, armadillos have to find mates to reproduce, and only pass half of their genes to their offspring. But unlike sexually-reproducing species, an armadillo’s offspring are not particularly diverse, and so are vulnerable to parasites, diseases, and environmental conditions that disproportionately affect certain genotypes.
Why polyembryony, then? The best proposed reason I’ve found is that it’s an adaptation to a sort of pre-existing evolutionary condition in the armadillo — the structure of the armadillo’s uterus is such that only one egg can be fertilized at a time. Why? We don’t know. Presumably it happened for some other reason, or perhaps entirely by accident, but whatever the reason, *if* you take it as a given that only one egg can be fertilized, yet the mother can provide for more than one offspring in a litter (armadillo mothers don’t care for the young particularly much or long), then polyembryony makes some sense.
Thanks to Heather Leigh for pointing me to this fascinating armadillo information!
3) A relaxation oscillator is a system that behaves periodically but not sinusoidally. Simple examples include square wave oscillators and sawtooth oscillators. A more complicated example would be a ring tone.
A typical way to think about relaxation oscillators is that there’s some timer that counts down, and when that timer hits zero, the system produces some distinct output, like a square wave or a spike or a measure from some musical piece. Then the timer resets and starts counting again. Relaxation oscillators are a common motif in electrical circuits, where the “timer” is often a capacitor. The capacitor’s charge spikes out, triggering the output signal, then slowly decays (relaxes) back to its charge value. Hence “relaxation oscillator”.
Thursday, October 8, 2015
Light-Activated Cas9 Activation, Lobsters, and Cas9: A History
Today I Learned:
1) In March, a pair of researchers at Duke published a nifty system for activating target gene expression in the presence of light using a Cas9-based system. It’s pretty simple — they fused a light-activated transcriptional activator from Arabidopsis (the standard plant model organism) to inactivated cas9 (dCas9). Light-activated activator + targeting protein = targeted light-activation.
I guess we already had light-activation in the form of “traditional” optogenetics using channelrhodopsins, but those always struck me as pretty heavy-handed… for channelrhodopsin to work, it has to wildly change the cell’s salt balance, which seems like Not A Good Thing. This seems much more elegant.
2) Facts about lobsters!
2a) Lobster molting is pretty cool! The lobster actually sheds some of its digestive system during molting. As part of that process, the lobster dissolves a tooth-like thing at the back of its middle gut (lobsters have three guts) that normally helps break down food. The redissolved minerals are employed in the quick regrowing of the lobster’s shell.
2b) Background reading: http://www.smbc-comics.com/?id=3169
Now, serious question: where else might evolution put excretory organs? Set a five minute timer and list out all the better places to urinate from than where we do. I highly recommend taking the time to do this before proceeding — it’s a fun little exercise.
Ok? Done?
Did you write down “at the base of the antennae”? Because that’s where lobsters pee from.
2c) Lobsters can growl… but we have no idea why. They don’t seem to growl during social interactions, and as far as I know nobody’s come up with a better hypothesis.
2d) Lobsters can live a really long time — more than 50 years! — yet show none of the skeletal dysfunctions of aging that mammals show. Of course, it’s hard to directly compare the aging of species as dissimilar as humans and lobsters, but to anybody who argues that aging is “an inevitable breakdown of physiological processes”… “lobsters”, I reply. Also “tortoises”, but that’s a TIL for a different day.
Thanks to Lady Jade Beacham for pointing me to http://www.lobsters.org/tlcbio/biology.html, from which I got the content of this TIL.
3) So, speaking of Cas9 from #1, today I learned that a bunch of people figured out how it works independently. The one most biologists know about is Jennifer Doudna, who definitely figured out Cas9. Working off of CRISPR research from as early as 2007, Doudna and her lab worked out how Cas9 does its thing, then immediately realized that it was going to be huge and took it to Science, who fast-tracked it and published within the month.
The other relatively famous discoverer of cas9 is Feng Zhang, an MIT scientist who claims to have independently discovered Cas9’s function. He published definitively after Doudna, but he *patented* the enzyme first. That patent has been under dispute ever since.
Then there’s University of Lithuania researcher Virginijus Siksnys. He *also* jumped off of 2007 research and in 2012, figured out how Cas9 works. Unlike Doudna, he submitted his findings to PNAS, and unlike Science, PNAS did not fast-track the paper. As a result, Doudna’s paper came out first. Between Doudna’s precedency and her prior fame as an RNA biologist, Doudna got all the press and Siksnys remains largely unknown. (to be fair, Doudna did more in her paper — she not only elucidated the mechanism of cas9 and suggested its use as a tool for molecular biologists, but her lab also developed a modified version with a fused tracrRNA/guide RNA, which makes the thing much more convenient to work with).
1) In March, a pair of researchers at Duke published a nifty system for activating target gene expression in the presence of light using a Cas9-based system. It’s pretty simple — they fused a light-activated transcriptional activator from Arabidopsis (the standard plant model organism) to inactivated cas9 (dCas9). Light-activated activator + targeting protein = targeted light-activation.
I guess we already had light-activation in the form of “traditional” optogenetics using channelrhodopsins, but those always struck me as pretty heavy-handed… for channelrhodopsin to work, it has to wildly change the cell’s salt balance, which seems like Not A Good Thing. This seems much more elegant.
2) Facts about lobsters!
2a) Lobster molting is pretty cool! The lobster actually sheds some of its digestive system during molting. As part of that process, the lobster dissolves a tooth-like thing at the back of its middle gut (lobsters have three guts) that normally helps break down food. The redissolved minerals are employed in the quick regrowing of the lobster’s shell.
2b) Background reading: http://www.smbc-comics.com/?id=3169
Now, serious question: where else might evolution put excretory organs? Set a five minute timer and list out all the better places to urinate from than where we do. I highly recommend taking the time to do this before proceeding — it’s a fun little exercise.
Ok? Done?
Did you write down “at the base of the antennae”? Because that’s where lobsters pee from.
2c) Lobsters can growl… but we have no idea why. They don’t seem to growl during social interactions, and as far as I know nobody’s come up with a better hypothesis.
2d) Lobsters can live a really long time — more than 50 years! — yet show none of the skeletal dysfunctions of aging that mammals show. Of course, it’s hard to directly compare the aging of species as dissimilar as humans and lobsters, but to anybody who argues that aging is “an inevitable breakdown of physiological processes”… “lobsters”, I reply. Also “tortoises”, but that’s a TIL for a different day.
Thanks to Lady Jade Beacham for pointing me to http://www.lobsters.org/tlcbio/biology.html, from which I got the content of this TIL.
3) So, speaking of Cas9 from #1, today I learned that a bunch of people figured out how it works independently. The one most biologists know about is Jennifer Doudna, who definitely figured out Cas9. Working off of CRISPR research from as early as 2007, Doudna and her lab worked out how Cas9 does its thing, then immediately realized that it was going to be huge and took it to Science, who fast-tracked it and published within the month.
The other relatively famous discoverer of cas9 is Feng Zhang, an MIT scientist who claims to have independently discovered Cas9’s function. He published definitively after Doudna, but he *patented* the enzyme first. That patent has been under dispute ever since.
Then there’s University of Lithuania researcher Virginijus Siksnys. He *also* jumped off of 2007 research and in 2012, figured out how Cas9 works. Unlike Doudna, he submitted his findings to PNAS, and unlike Science, PNAS did not fast-track the paper. As a result, Doudna’s paper came out first. Between Doudna’s precedency and her prior fame as an RNA biologist, Doudna got all the press and Siksnys remains largely unknown. (to be fair, Doudna did more in her paper — she not only elucidated the mechanism of cas9 and suggested its use as a tool for molecular biologists, but her lab also developed a modified version with a fused tracrRNA/guide RNA, which makes the thing much more convenient to work with).
Monday, October 5, 2015
Drugged Leaders, Rat Melatonin, and Zebrafish Sleep
Today I Learned:
1) JFK was physically very challenged, and spent much of his presidency on medication. Some of that was pretty damned strong medication. In fact, it's very possible that he guided the nation through the Cuban missile crisis while on opiates. Relatedly, Hitler apparently was pretty heavily medicated during his reign as well? Also Napoleon?! Rumor has it he was in terrible pain the night before Waterloo and couldn't sleep, so he took some opiates to ease the pain -- perfectly by-the-book medicine for the time, but maybe not the best thing to do the night before one of the most important battles of his career. These need confirmation.
2) Even though mice and rats are noctornal, they have virtually identical patterns of blood melatonin to humans, a diurnal species. So either they have the opposite response to melatonin from humans, or they don't use melatonin to regulate sleep.
3) Zebrafish sleep, though not particularly soundly -- they'll still dart around once or twice a minute, but they're considerably less active, and harder to stimulate, at night (or in the dark (controlled for temperature))
1) JFK was physically very challenged, and spent much of his presidency on medication. Some of that was pretty damned strong medication. In fact, it's very possible that he guided the nation through the Cuban missile crisis while on opiates. Relatedly, Hitler apparently was pretty heavily medicated during his reign as well? Also Napoleon?! Rumor has it he was in terrible pain the night before Waterloo and couldn't sleep, so he took some opiates to ease the pain -- perfectly by-the-book medicine for the time, but maybe not the best thing to do the night before one of the most important battles of his career. These need confirmation.
2) Even though mice and rats are noctornal, they have virtually identical patterns of blood melatonin to humans, a diurnal species. So either they have the opposite response to melatonin from humans, or they don't use melatonin to regulate sleep.
3) Zebrafish sleep, though not particularly soundly -- they'll still dart around once or twice a minute, but they're considerably less active, and harder to stimulate, at night (or in the dark (controlled for temperature))
Sunday, October 4, 2015
Mine-Clearing Rats, Cumulative Distribution Plots, and Gun Safety
Today I Learned:
1) There are rats who are trained to smell out land mines! They’re light enough that they don’t set off the mines, so they’re not put in any danger. They sniff out TNT, scratch at the surface, and alert their handlers to the mine. The mines can then be safely dismantled and the rat gets a treat.
2) Cumulative distribution plots are pretty much always better than cumulative histograms. They give you all the same distributional information, but without any binning choices! (pro tip: all binning choices are bad binning choices. Some are just less bad than others)
3) The CDC is specifically disallowed from researching gun safety. Thanks to Bear Bear Bear for alerting me to this one.
1) There are rats who are trained to smell out land mines! They’re light enough that they don’t set off the mines, so they’re not put in any danger. They sniff out TNT, scratch at the surface, and alert their handlers to the mine. The mines can then be safely dismantled and the rat gets a treat.
2) Cumulative distribution plots are pretty much always better than cumulative histograms. They give you all the same distributional information, but without any binning choices! (pro tip: all binning choices are bad binning choices. Some are just less bad than others)
3) The CDC is specifically disallowed from researching gun safety. Thanks to Bear Bear Bear for alerting me to this one.
Saturday, October 3, 2015
Molecular Biology Laboratory Practice Trivia Day!
Today I Learned:
1) Warning: detailed molecular biology laboratory practice trivia inbound.
One thing that comes up a lot while cloning is checking PCRed parts. Today I learned a way to speed up gel loading when there are a lot of parts, using a multichannel pipette. You make a stock of loading dye in an 8-tube PCR strip, then use the multichannel pipette to load a small amount of loading dye into your samples super quickly (about 5 uL will work in any reasonably-sized PCR). You’ll still have to manually load the individual samples, but it’s still well worth it to avoid having to individually mix all the dyes. Make sure to do this step before running your samples through PCR cleanup — that way the dye will come out in the cleanup step.
2) Also molecular biology trivia — today I learned how to use a repeater pipette. Also super-useful (if quite expensive). I hear they’re not as accurate as normal pipettes… but they’re plenty good enough to set up PCR. They do tend to be a bit wasteful, though, as they have a habit of picking up excess liquids.
3) And to round out a day of molecular biology — Phusion 2x master mix (for PCR) is stable on the bench for hours. Possibly days. Not months, though. (also, most antibiotics will apparently break down in incubator conditions over 2-3 days? Can anyone confirm or deny?)
1) Warning: detailed molecular biology laboratory practice trivia inbound.
One thing that comes up a lot while cloning is checking PCRed parts. Today I learned a way to speed up gel loading when there are a lot of parts, using a multichannel pipette. You make a stock of loading dye in an 8-tube PCR strip, then use the multichannel pipette to load a small amount of loading dye into your samples super quickly (about 5 uL will work in any reasonably-sized PCR). You’ll still have to manually load the individual samples, but it’s still well worth it to avoid having to individually mix all the dyes. Make sure to do this step before running your samples through PCR cleanup — that way the dye will come out in the cleanup step.
2) Also molecular biology trivia — today I learned how to use a repeater pipette. Also super-useful (if quite expensive). I hear they’re not as accurate as normal pipettes… but they’re plenty good enough to set up PCR. They do tend to be a bit wasteful, though, as they have a habit of picking up excess liquids.
3) And to round out a day of molecular biology — Phusion 2x master mix (for PCR) is stable on the bench for hours. Possibly days. Not months, though. (also, most antibiotics will apparently break down in incubator conditions over 2-3 days? Can anyone confirm or deny?)
Friday, October 2, 2015
Lightsabers, Assyrians, and Robust Cloning
Today I Learned:
1) ...some history of the lightsaber. The precursor of the lightsaber was a weapon called the force saber, developed by the Rakata (more on them later). It ran off of pure force energy channeled from the user, and was effectively a "frozen blaster". The technology behind the force saber was lost along with most other Rakatan technology when their Infinite Empire fell.
The first lightsabers were developed by the Jedi (or possibly the Sith) probably in immitation of the Rakatan force saber. They required immense amounts of energy, which could only be supplied by a small belt-mounted nuclear reactor, and even that could only power the devices for seconds or minutes at a time. As such, they were mostly ceremonial, and were really only used as handheld seige weapons in combat.
As an aside, during this time and for a long time afterwards, the role of the modern (if such a word can be used in a fictional universe that takes place a long time ago....) lightsaber was filled by swords, sometimes enhanced by the force to be extremely good at cutting things. Swords were considered a more elegant weapon, and, like lightsabers later, the skilled use of a sword signified a certain mastery of the force.
It was the Sith that refined the lightsaber into something closely resembling the modern version. The Sith developed a technique for reflecting a blaster-like beam back to the hilt, a technology somewhat distinct from designs based on earlier Rakata weapons. These lightsabers had vastly reduced power requriements and could run without a tethered power supply. The Sith developed a kind of synthetic crystal to focus the device (I believe they lacked access to the natural crystal caves of Ilum, Adega, and Dantooine), which gave their lightsabers their traditional red color. The use of synthetic crystals actually fell out of favor for a time, and during this time the Sith used lightsabers of the same color as the Jedi. Red lightsabers were reinstated in the Sith Empire around the time of Darth Revan. The Imperial Knights circa ~50-137 ABY would later use a different form of synthetic crystal, which produced a silver color.
It took a long time for lightsabers to become standard weapons of force users. Probably out of tradition, swords dominated for quite a while after the modern lightsaber's introduction. This was especially true among the Sith, who were quite good at alchemically modifying their swords to resist lightsabers, or at simply building their swords out of cortosis or other lightsaber-resistant ores.
A friend of mine claimed today that the lightsaber was really developed as a weapon that couldn't be disrupted by the force, in order to break the kinds of stalemates that tended to happen in battles between adept force users. I have not been able to corroborate this claim.
2) The Assyrians were some seriously important people. They were a major power in the Middle East (which was a HUGE chunk of the Western world at the time) from the 23th century BC to the 6th century BC. Hold on a second. Stop. 23rd century to 6th century -- SEVENTEEN HUNDRED YEARS. And they survived as a somewhat-independent region until the 7th century AD, so that's 2.3 THOUSAND years of civilization. I mean, I knew the Assyrians were important enough to merit a mention in any history book covering the period, but I had no idea they went that far back. Oh, and they also ruled over just about all of the peoples of the Middle East for three hundred of those years.
I also learned a little bit about Assyrian culture. Most of it was militaristic, for the Assyrians were a pretty militaristic culture. They pretty much invented the pre-modern system of military division, with cavalry, missile infantry, and modern-ish infantry. Their economy, it seems, was run largely off of invading neighboring empires and looting them, then annexing them and demanding regular tithes. This worked shockingly well for a long time -- there was one king in particular, whose name I forget, who took his army to the field almost every year of his 30 year reign.
These were a bloody people, by their own accounts. They used an Imperial form of terrorism to discourage rebellions -- they had a habit of wiping out entire cities, killing the population down to the animals and reserving particularly brutal and torturous executions for the leaders of those cities, often with the Assyrian king watching. This didn't keep rebellions from popping up all the time, which goes to show how much the Assyrians' vassal states disliked them. Internal politics were no less blody, with the deaths of Assyrian kings typically followed by bloody civil wars between the kings' relatives.
When the Assyrian empire was finally toppled more or less for good (by a confluence of a particularly nasty war of succession, a very expensive war in Egypt, and a coalition rebelling Babylonian/invading Medes/invading Persians), their capital city of Assur was sacked in more or less the same fashion employed by the Assyrians. The ruins left behind was described in awe a couple hundred years later by a Greek army moving through the area -- its fortifications, devestated though they were, still far outstripped anything the Greeks had seen. When the Greeks asked the peoples of the area who had built those walls, nobody knew.
I can't help but be reminded of the Rakata of the Star Wars universe. The Rakata were a brutal Empire-building species who ruled over most of the galaxy for over 10,000 years. They developed the first hyperdrive technology, and left behind some truly devestating structures and weapons, most notably the Star Forge. And, much like the Assyrians, they were very nearly completely erased from history by their conquerers, many of whom had numbered among their slave species. (Unlike the Assyrians, the Rakata were felled by a combination of a deadly plague and a mysterious loss of their connection to the force, possibly brought on by their dark-side corruption, which itself was fueled by centuries of powering their most potent technologies from dark-side-sources.) Admittedly, the theme of a massive, highly-advanced, now-extinct civilization is a pretty common theme in fiction in general and in sci-fi in particular, but I can't help but wonder if any of the Star Wars writers responsible for the Rakata were inspired by the story of the Assyrians.
3) Ok, let's make this short. Apparently at least some kinds of molecular cloning are ridiculously robust to DNA molarities. A couple days ago, I and another student accidentally ran a bunch of golden braid cloning reactions with essentially random amounts of DNA. The result... they basically all worked. The ones with 10-fold too much of one part might have failed... or we might have just not amplified them up properly afterwards. We'll know tomorrow.
1) ...some history of the lightsaber. The precursor of the lightsaber was a weapon called the force saber, developed by the Rakata (more on them later). It ran off of pure force energy channeled from the user, and was effectively a "frozen blaster". The technology behind the force saber was lost along with most other Rakatan technology when their Infinite Empire fell.
The first lightsabers were developed by the Jedi (or possibly the Sith) probably in immitation of the Rakatan force saber. They required immense amounts of energy, which could only be supplied by a small belt-mounted nuclear reactor, and even that could only power the devices for seconds or minutes at a time. As such, they were mostly ceremonial, and were really only used as handheld seige weapons in combat.
As an aside, during this time and for a long time afterwards, the role of the modern (if such a word can be used in a fictional universe that takes place a long time ago....) lightsaber was filled by swords, sometimes enhanced by the force to be extremely good at cutting things. Swords were considered a more elegant weapon, and, like lightsabers later, the skilled use of a sword signified a certain mastery of the force.
It was the Sith that refined the lightsaber into something closely resembling the modern version. The Sith developed a technique for reflecting a blaster-like beam back to the hilt, a technology somewhat distinct from designs based on earlier Rakata weapons. These lightsabers had vastly reduced power requriements and could run without a tethered power supply. The Sith developed a kind of synthetic crystal to focus the device (I believe they lacked access to the natural crystal caves of Ilum, Adega, and Dantooine), which gave their lightsabers their traditional red color. The use of synthetic crystals actually fell out of favor for a time, and during this time the Sith used lightsabers of the same color as the Jedi. Red lightsabers were reinstated in the Sith Empire around the time of Darth Revan. The Imperial Knights circa ~50-137 ABY would later use a different form of synthetic crystal, which produced a silver color.
It took a long time for lightsabers to become standard weapons of force users. Probably out of tradition, swords dominated for quite a while after the modern lightsaber's introduction. This was especially true among the Sith, who were quite good at alchemically modifying their swords to resist lightsabers, or at simply building their swords out of cortosis or other lightsaber-resistant ores.
A friend of mine claimed today that the lightsaber was really developed as a weapon that couldn't be disrupted by the force, in order to break the kinds of stalemates that tended to happen in battles between adept force users. I have not been able to corroborate this claim.
2) The Assyrians were some seriously important people. They were a major power in the Middle East (which was a HUGE chunk of the Western world at the time) from the 23th century BC to the 6th century BC. Hold on a second. Stop. 23rd century to 6th century -- SEVENTEEN HUNDRED YEARS. And they survived as a somewhat-independent region until the 7th century AD, so that's 2.3 THOUSAND years of civilization. I mean, I knew the Assyrians were important enough to merit a mention in any history book covering the period, but I had no idea they went that far back. Oh, and they also ruled over just about all of the peoples of the Middle East for three hundred of those years.
I also learned a little bit about Assyrian culture. Most of it was militaristic, for the Assyrians were a pretty militaristic culture. They pretty much invented the pre-modern system of military division, with cavalry, missile infantry, and modern-ish infantry. Their economy, it seems, was run largely off of invading neighboring empires and looting them, then annexing them and demanding regular tithes. This worked shockingly well for a long time -- there was one king in particular, whose name I forget, who took his army to the field almost every year of his 30 year reign.
These were a bloody people, by their own accounts. They used an Imperial form of terrorism to discourage rebellions -- they had a habit of wiping out entire cities, killing the population down to the animals and reserving particularly brutal and torturous executions for the leaders of those cities, often with the Assyrian king watching. This didn't keep rebellions from popping up all the time, which goes to show how much the Assyrians' vassal states disliked them. Internal politics were no less blody, with the deaths of Assyrian kings typically followed by bloody civil wars between the kings' relatives.
When the Assyrian empire was finally toppled more or less for good (by a confluence of a particularly nasty war of succession, a very expensive war in Egypt, and a coalition rebelling Babylonian/invading Medes/invading Persians), their capital city of Assur was sacked in more or less the same fashion employed by the Assyrians. The ruins left behind was described in awe a couple hundred years later by a Greek army moving through the area -- its fortifications, devestated though they were, still far outstripped anything the Greeks had seen. When the Greeks asked the peoples of the area who had built those walls, nobody knew.
I can't help but be reminded of the Rakata of the Star Wars universe. The Rakata were a brutal Empire-building species who ruled over most of the galaxy for over 10,000 years. They developed the first hyperdrive technology, and left behind some truly devestating structures and weapons, most notably the Star Forge. And, much like the Assyrians, they were very nearly completely erased from history by their conquerers, many of whom had numbered among their slave species. (Unlike the Assyrians, the Rakata were felled by a combination of a deadly plague and a mysterious loss of their connection to the force, possibly brought on by their dark-side corruption, which itself was fueled by centuries of powering their most potent technologies from dark-side-sources.) Admittedly, the theme of a massive, highly-advanced, now-extinct civilization is a pretty common theme in fiction in general and in sci-fi in particular, but I can't help but wonder if any of the Star Wars writers responsible for the Rakata were inspired by the story of the Assyrians.
3) Ok, let's make this short. Apparently at least some kinds of molecular cloning are ridiculously robust to DNA molarities. A couple days ago, I and another student accidentally ran a bunch of golden braid cloning reactions with essentially random amounts of DNA. The result... they basically all worked. The ones with 10-fold too much of one part might have failed... or we might have just not amplified them up properly afterwards. We'll know tomorrow.
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