Songs without Words

A significant portion of my studying (which of course isn’t saying very much, since I can’t focus on studying very well with all these problems) is devoted to figuring out what words mean. Once you get a word, it often saves you the trouble of having to memorize a separate definition.

Today’s focus: “chole,” courtesy of respective Wikipedia articles and Dictionary.com etymologies.

“Chole” is the root meaning “bile.” Therefore, cholic acid is a component of bile. Cholesterol (the alcoholic solid in bile) is so-named because it can precipitate to form a particular type of gallstone (”cholelith”), found amidst the bile stored within the gallbladder.

The gallbladder is a bile-containing pouch and therefore has the prefix “cholecyst-” (where a cyst is an enclosed sac, corresponding to “bladder” in the instances of the bladder, “cyst-” and gallbladder, “cholecyst-”). A cholecystectomy (cutting of the bile-containing sac) is the surgical removal of the gallbladder. The hormone CCK, short for cholecystokinin (movement of the bile-containing sac), is a hormone produced by duodenal and jejunal I cells which is involved in bile let-down from the gallbladder as well as pancreatic enzyme secretion.

However, “cholic” (pertaining to bile) has nothing to do with “colic” (pertaining to the colon). When a person has “colicky” pain, it relates to pain of the colon, not to bile acid.

As an aside, the punctuation mark called the colon (:) is derived from Greek kwlon (omega first) while the organ called the colon is derived from Greek kolon (omicron first). So, they do not have a common etymological root.

The most familiar solution to the oxygen-transport problem in larger organisms is hemoglobin, a collection of four-subunit (usually two pairs of polypeptides) proteins which utilize porphyrin heme rings containing a single iron atom.  However, the use of hemoglobin, carried within cell carriers (erythrocytes), is limited to vertebrates.  Invertebrates have independently developed different oxygen-transporting proteins.

Hemocyanin

Mollusks (e.g. octopus, horseshoe crabs, etc.) use copper rather than iron to carry oxygen, incorporated into a protein of the hemocyanin family.  Hemocyanin, which uses two copper atoms to bind each O2 molecule, is dissolved in the hemolymph (blood analogue).  Hemocyanin is translucent gray when deoxygenated and sky blue when oxygenated.  Although hemocyanin is generally less efficient than hemoglobin, it is advantageous in certain environments unique to the underwater milieu.  Hemocyanin, unlike hemoglobin, is designed to aggregate.  When hemoglobin subunits aggregate, for instance in the thalassemias, it is disastrous because the erythrocytes containing the aggregates are destroyed.  However, hemocyanin (MW ~400kDa) can form aggregates in the millions of daltons (see the Keyhole Limpet Hemocyanin (KLH) article on Wikipedia).

Erythrocruorin

Annelids such as earthworms present another solution, which is erythrocruorin, which like hemoglobin contains heme and a single iron atom carrier.  Although erythrocruorin is also not bound in cells, it is notable for forming exquisite protein structures composed of 180 subunits, with a macrostructure consisting of two stacked hexagonal rings (see http://www.uta.edu/biology/arnott/classnotes/5365/Erythrocruorin%20micrograph.jpg).  The total molecular weight of each dodecameric complex is 3.5 megadaltons, which includes 144 “hemoglobin” subunits and 36 linker subunits.  The PNAS paper publishing the structure posits that the giant size is a way of maintaining high oxygen tension and harnessing cooperativity while incurring minimal osmotic cost.  What is amazing in this case is the fidelity of protein assembly on such a grand scale.

Hemerythrin

Hemerythrin uses iron to carry oxygen, like hemoglobin, but uses two irons per oxygen and does not contain a heme ring.  Used by various marine invertebrates, hemerythrin is colorless when deoxygenated and violet-pink when oxygenated.  Each hemerythrin subunit is composed of four alpha helices, and the subunits join in trimers.  While hemerythrin does not exhibit cooperativity, it does exhibit a greater affinity for oxygen than for carbon monoxide.

Beyond nature

A recent Nature article from earlier this year detailed a UPenn group’s bioengineering feat of devising a new oxygen-carrying protein based on design principles.  Apart from heme groups, the rest of the protein was invented through rational design.  The resulting molecule, which is advantageous for being able to deliver oxygen faithfully in the presence of CO (unlike human hemoglobin), shows that the “hemoglobin fold” is far from mandatory.

This paragraph just flung out of my mind, and although it sits oddly in the paper, I think I like it.

Metastasis is a daunting subject, probably because of its immense scope which requires the expertise of so many different branches of biology – and because despite valiant efforts, it is hard to conceive of a reasonable method of treating metastatic disease.  As horrific as classic warfare was, it was at least “winnable;” the latter half of the last century saw the rise of guerilla warfare and terrorism, blurring the lines between civilian and military and making millenia of military tactics and technological extravagance decidedly irrelevant.  The parallel between this new battlefield which knows neither boundaries nor conventional rules and the campaigns to halt and cure metastatic cancer is considerable.  In both cases, our capacity to destroy far outstrips our capacity to renew; given that curing metastasis through the death of the patient is highly unacceptable, it is clear that any solution must diplomatically engage both destruction and renewal, thus requiring the full knowledge of life as we do and do not understand it, from embryogenesis to apoptosis and necrosis.

The entire body of human knowledge has long since surpassed the point where any one person could ever hope to understand any significant proportion of it. This is apparent from the greater and greater levels of specialization in people’s everyday lives, despite surface appearances that the general populace is becoming more well-rounded in its knowledge. The truth is, people individually do not know much more (in quantity) than people really have; the knowledge that is gained of new technologies and such replaces knowledge that is perhaps less useful. What passes as broad knowledge is actually the accessibility to that knowledge, not the possession of it: humans are learning more methods of archiving and subsequently finding information, rather than better methods of retaining it within the mind.

The externalization of knowledge is hardly a new innovation. As I have often mentioned in conversations, I believe that evolution works in self-similar stages – think of the zooming-out sequence in Men in Black or, if you’ve seen it, the narrated preview for the upcoming game “Spore.” Basically, single cells, each of which used to know everything about day-to-day cell life, came together in a cooperative society, and the repository of knowledge turned into the ganglion or brain of the larger animal. The ganglion cells themselves – the brain cells – have no intrinsic knowledge of the knowledge that they store; the other cells access and use this information through signals, but they do not hold the knowledge within themselves.

Likewise, multi-organismal society is now at a point where it can no longer be like a brainless jellyfish. What is arising naturally are large repositories of knowledge, such as libraries, succeeded now by the larger internet. Knowledge is not only a sitting body but a dynamic conversation that exists on a time-scale and size-scale so large that people may view it as being a fixed entity.

The current methods of information exchange are very nice, but there is one fatal flaw: no meta-analysis outside of our own selves, the fundamental “cells” of the organism of humankind. The genius of human existence is the ability to take the “wikipedia” of inputs from all the five senses, compounded over many years, and distill out higher-level conclusions and theories.

Current knowledge databases such as, say, PubMed or ISI, which compile more research than any person could ever hope to even click on, not to mention read or understand, are rapidly becoming unwieldy. In the rush to create knowledge, there is not enough sustained effort to remold it. I am confident that many secrets and patterns of humanity and human disease already have enough research put in, if only that research were combined effectively and the correct connections made. And if the published literature is insufficient, then it is the combined knowledge and observations of the researchers themselves that would hold the answers. The “scientific hero” model dating from just a century ago, and epitomized by the Nobel Prize, is completely out-of-date, and the gradual lifting of the proprietary attitude towards science through the greater availability of full text publications, wikis, copyleft / free software, and wide-ranging collaboration confirms that the new era of knowledge will be built not by forefathers upon marble pedestals but by the average Joe.

Who, then, will be charged with the requisite meta-analysis that I alluded to earlier? In my belief, the entity to serve such a function is none other than a computer. Robotics has its triumphs in automated arms and belts that power current manufacturing by rapidly and accurately processing raw materials towards the production of just about every product – this is the only way production has been able to keep up with design and demand. The corresponding state-of-the-art for data which exists virtually rather than physically (virtual information being both encoded in computers and in human minds) is basically only indexing and searching. Wikipedia does not, to my knowledge, try to sift through its cross-references to discover the meaning of human existence or better ways for physics to inform biology or evaluate the best system of government. But the data is already there! For a human being, it takes so many years to write a single dissertation which looks upon a sliver of the pie of knowledge, and in turn is read by only a sliver of the people who ought to be reading it.

What is needed for this project is not artificial intelligence that mimics human thought, per se – the brain does not think in the manner of cells. What is needed is a new paradigm of thought, which is simpler yet more powerful than human thought. Whereas cells are concerned about the minutiae about particles and neighboring cells and fluid flows, the brain ignores most of that and considers the hunger level of the entire body, the status of sheep in the meadow which none of the cells know about, and the relative attractiveness of members of the opposite gender, which certainly cells would not understand at all. Not just the scale, but the nature of the thoughts transcend the capabilities of any contributing member of the knowledge.

The idea of a “brain” for an entire species has been entertained many times before, but usually in the context of some dominating hive-queen. There is nowhere in the description above that suggests that such a central unit would ever have to be dominant in function; nor that it even has to be “alive” in the way we understand it. It is just that, now with humanity trying to deal with problems of the entire body of its billions of people and with the Earth as a whole, there must be a better way of thinking globally than using our feeble minds which have yielded brazenly useless solutions such as the recent agreement to cut emissions by 50% by 2050 (what human can conceive of 42 years of future events? And why is only one small part of the problem being addressed)? Without a guiding mind that can at least put together the crises in fish, bees, the atmosphere, forests, rivers, trash, toxic chemicals, radiation, soil quality, and so forth, in a meaningful way, how will the environmental issue ever be tackled effectively?  All of these issues are interconnected, but people only become interested in them one at a time, or in all of them with no particular plan or comprehensive understanding.  Synthesizing the next layer of knowledge is probably the only way the human race can make peace with the world and with itself.

Yes, the original creator of some work or technology should be protected from other people trying to profit from non-collaborative, unapproved use of that creator’s work. But that being said, I think that the extremes of so-called “intellectual property” in the modern Western society are bizarre and inappropriate.

Unlike my frying pan, which I rightfully own through the trade of money and which represents a tool and not some link to society or the greater human consciousness, my ideas – my songs, drawings, whatever – are not simply purchased through my earnings in work or service. I would not be much of a composer had I not studied Bach and Brahms and Schoenberg. I would not be much of a cartoonist without being exposed to the work of Kiyohiku Azuma or Rumiko Takahashi.

It is arrogant to think that ideas, which stem from the amalgamation and then fusion and recombination of thought and inspiration from past and present, are so easily demarcated and tangible that they may be analogous to a frying pan. This is as absurd as the idea that a human can “own” a cat. Ideas and living things – and they are largely the same thing – owe their existence to a phenomenal amount of sources. In an ideal situation, they belong to everybody.

It is because there are thieves in this world who seek to counterfeit, people who did not contribute to the idea at all, that we have to have laws about copyright and patents. That is all well and good – I certainly would not want someone selling my music under his or her name for his or her profit. But nothing should be so absolute so as to hamper the progression of knowledge and its applications to human benefit, especially with regards to technology that were not all that innovative in the first place.

As an example of this grotesque culture of greed, in which people who have no intellect to think that there might exist a metaphysical significance to objects attempt to levy ownership over what was never theirs in the first place, I’ll give the example of the Bristol-Myers Squibb taxol fiasco. BMS opposed strongly the entrance of generics into the taxol market. Broadly speaking, taxol was discovered by the US government and belongs to the US people. BMS attempt to patent taxol as delivered with castor oil as an injection. Then, it sued a Canadian generic company (after the 5 year exclusivity period) with a patent it never had and never will have.

All of this for a compound that was never created from human intellect. It is absurd to think of paying the yew trees for it, but if that’s so, then it’s even more absurd to pay humans for the idea (paying for the object is of course reasonable, as it costs money to extract and/or to produce). If anyone owns a patent on taxol, it’s God or Gaia or Mother Earth.

Claiming that taxol is your “intellectual property” is tantamount to the Europeans landing in America and claiming that all the land belonged to them.

Art is the same way, and I intended a long time ago to write about derivative works (fanart, doujinshi, etc.) but I never got around to finishing that entry. An art is generally speaking passed down, directly or indirectly, from some master to some apprentice. There is no artist that I know of who can create works without (a) having things around to look at, (b) training through class or self-teaching, or usually both. Both of these are acts of absorbing outside influence.

Human creation comes from two stages: first, the acquisition of source data, then second, inspiration and transformation of those sources into a final product. No creation and no genius exists without precedent. Here are two cases to underline my point:

1. Takashi Murakami of “superflat” fame created the petal-y design for Louis Vuitton (which I happen to like a lot), but he is hardly the first to use four-petal motifs in art design. Louis Vuitton is foolish to sue artist Nadia Plesner over her not-for-profit fundraising t-shirt logo, which neither promotes counterfeiting (no moreso than Evangelion’s famous “Eila” in place of “Fila”) nor is any more alike to the LV design than Takashi Murakami’s own art draws on Doraemon and Ghibli.

2. Bach was astounding, but he had Palestrina before him, and polyphony dates back centuries farther, back in the days when all harmony was chant in parallel fifths. That Mendelssohn could freely quote Handel and that “a theme by Paganini” became a virtuoso piece for piano, of all ironies – that is a testament to the importance of what amounts to “fanfiction” in the musical world. These days, it is the absurd vogue that you can quote dead people’s music but not live ones’. Quoting anyone straight up is just unintelligent, no matter how you look at it. But the worst is when people claim sole copyright on works that include quotes. The notes belong to no one, and a computer given sufficient time could permute notes to produce the melodies of all songs every written with the twelve Western tones and certainly not own all exclusive rights to their use. Heck, I could do that, too, and technically copyright all non-previously-used melodies. And lawsuits based on copying chord progressions – well, I’m not even going to go there.
All in all, I think that the whole concept of IP and copyright as it stands is outdated and needs to be re-examined. They belong to an era of obsessive possession that runs contrary to the modern themes of inclusivity, cultural awareness, and the trading of ideas. Sites such as Wikipedia have taken an important step by championing the person who contributes work without needing to bask in the glory of one-man/-woman heroism.

The 21st century is about global civilization and the power of multidisciplinary collaboration. It is about time to change our conception of the very nature of ideas to catch up to the post-Imperialist, post-world dominance, post-megacorporation society.

… is to find the equivalent resistance starting from any vertex to the node directly across from it.

…

Just kidding ^___^.

My girlfriend made this beautiful polyhedron for me and I’m going to hang it up soon. Isn’t it really beautiful? The graceful mathematical form, pulled down into a cloak of pragmatic engineering … . It is a world unto itself that tumbles and tumbles on its five dozen little resistor knobs …….

The human mind, like any database or encyclopedia, rapidly becomes outdated with the times — and yet one must treat the most current information as being true. So what happens to knowledge that we acquire at a young age, then never update for decades? Well, naturally, it becomes irrelevant and dusty, and yet we continue to spout it as if it were the current truth. It was once said that human beings are the collection of prejudices learned by the age of 18. While of course people can change after that age, it is true that we do a lot of our “general learning” before reaching maturity, and afterwards, we only bother to update certain portions of our knowledge. My understanding of biology and contemporary music, for example, are pretty modern and continue to be shaped and refreshed every day.

But today I was faced with a complete jolt to one of my older sectors of memory: dinosaurs. Deinonychus, when I was growing up, was the epitome of the evil dinosaur. It had that Sauron-like piercing yellow eye, dragon-like front limbs and of course its eponymous sickle-shaped toe claw that was used to tear viciously into unsuspecting herbivores. It was sleek, clean, brownish-gray, and altogether the definition of “terrible lizard.” See: http://www.ansp.org/museum/dinohall/deinonychus.php for an illustration.

And then today, I saw this: http://en.wikipedia.org/wiki/Image:Deinonychus-antirrhopus_jconway.jpg. Yes, a cute fluffy feathery friend. With the evil toe claw.

What happened in just ten years? Did the extinct creature evolve through a couple hundred years of being featured in anime?  No – it just wasn’t that big, and it had feathers, and the humongous sickle claws were probably unique to certain “well-endowed” individuals.  It was probably warm and fuzzy.  Even when in predatory mode, it looks more like a pissed-off turkey: http://en.wikipedia.org/wiki/Image:Deinonychus_BW.jpg.

And of course I cried to the gods: how could you do this?  Why would evolution select these fluffballs over my vision of giant evil bloodthirsty predators?

Brachiosaurus now has a monstrously thick neck.  It looks positively ridiculous, like a giraffe on steroids.  What happened to the slender, snakey necks?

The truth is that we all wanted dinosaurs to look like dragons.  Of course, you could take a chicken skeleton and pretend it was all scaly and thin and looked like a dragon, too – it’s not as if the feathers have bones.  But that’s just it – dragons are heavy, prone to having their necks cut off, and altogether the product of the human aesthetic, nothing more.

Dinosaurs were the product of evolution, and if you look around today, you can see that it was on the right track.  No more dragons.  Plenty of birds.

I challenge you to catch a pigeon with your bare hands.  It’s pretty tough, isn’t it?  You could probably drag down a dragon using some rope booby-trap, but you’re not going to be trapping any street-smart pigeons.

To give a creature flight, and to give it a means of keeping warm enough to be always alert and not in need to recharging with sunlight – that is pure genius.  It is no wonder that the forces that be chose the cute fluffy thing over the hunkering assassin.  It just goes to show that humans have a long way to go before they truly understand the world around them, ridding themselves of the prejudices of centuries of folklore and facing the truth that is being revealed – and that has been revealed already.  Just the other day, I saw a pigeon with that same evil claw-toe.  Okay, so I didn’t really – but you could imagine it.

Even without the legendary meteor, I bet the same evolutionary path would have occurred.  The small feathery ones would have won out against the high-maintenance classic dinosaurs, and that would have opened up the land for mammals.  Just a theory, of course, but it’s always good to rethink everything you learn in a textbook.  And especially things you learn from Jurassic Park.

Outside the Green Building, Bartlett Tree Experts are removing several sycamores and pine trees, continuing work from last year. The sycamores they’re cutting down aren’t really dead, a fact that probably no one else will notice. There are lots of little sprouts coming out from various points in the trunk, and I have no doubt that there have been for years, except that people keep pruning these little outgrowths (which come out from apical meristem left over after lower limbs are removed to give the trees the characteristic head-on-a-stick look that is among the most unnatural shapes for any tree to assume when given full sunlight and ample space). The upper branches of the sycamores all over campus have been sickly ever since I came here – perhaps it’s acid rain or something. No matter what, I’ve honestly never seen such shriveled, ghastly looking things. That’s probably why they want to get rid of them – not because they’re a risk if they fall over, but because they’re ghastly. No one wants ghastly trees on campus.

They’ll probably attempt to replace the trees, but if the pine project is any indication, they’ll screw it right up. Besides the fact that a baby sycamore will take our lifetimes to grow into the ones they’re cutting down, they also seem to have little understanding of tree species in general.  Indeed, I would not be surprised if they planted a few red maples or perhaps some tulip trees by mistake.  Instead of replacing the dead red pines with more red pines (2-leaf bundles), they replaced them with Eastern white pines (5-leaf bundles).  The two trees look nothing alike, and the wispy, dense, straight-as-a-needle white pines will never look like the sparse, shaggy, almost Asian-looking red pines.  While this is more of a landscaping issue than anything else, I think it reveals a great deficiency in basic tree training.  Perhaps I shall write a more extensive entry about species of trees in New England.

I’m learning how to make red bean (hong dou, or azuki) soup today, and it’s a rather simple recipe that follows the main principles of bean-cooking.  What struck me first was advice from my girlfriend’s mom to soak the beans for 2-3 hours in water prior to cooking.  Then I read online to soak the beans overnight.  I talked to my dad this morning about it, and he said, “[We] never soak the beans, but we boil them and let them cook for a long, long time. [. . .] Do NOT add the sugar to the soup until the very end, or they will stop cooking.”  At this point, I suddenly remembered the lab I had just done on Friday, where we pushed cell solution at 1x PBS into a microfluidic PDMS trap and replaced the liquid with 0.1x PBS.  The cells bloated and bordered on exploding, with a 1.5-fold increase in diameter (coinciding with approximately a 3-fold increase in volume).  Yet another recipe I just came across warns you not to add any salt whatsoever to the soaking water – hard evidence that maintaining a strong concentration gradient is the key to cooking red beans.

Just as making crunchy Chinese pickles must be done by patting the cucumbers with loads of salt in order to coax the water out, to bloat and explode the beans so that they form that characteristic grainy red soup, one must only use pure, solute-free water.  Because the sugar (carbohydrate) concentration of in beans in extraordinarily high, adding sugar too early to the soup would be deadly – something that seeing the ingredients list off-hand would not convey.

Wouldn’t it be fun to compare the osmotically-driven expansion curve of the white blood cells in dilute saline solution (or even ddH2O) to the expansion curve of red beans in soup solution?

I am trying to logically plan the next experiment, to build a protocol and set of controls that will have the highest chance of yielding a success.

And yet, there is this overwhelming desperation and sense of helplessness and hopelessness that fogs the clear view of logic, and I feel that at any moment, I might succumb to tears, even as my spirit claims that it doesn’t want to give up, and it feebly tries to think of yet another protocol, yet another way to spend the rest of my hours, withering away …

Two years

without success

is too much for my soul to handle

I am already crying on the inside