07 November, 2010
The net sum of these is that I am currently in the process of starting my own company. That, coupled with the guilt I feel each time I come here for not making my own website for a blog, mean that this is probably the last post I will make here that isn't a re-direct to the new sites once I have them up.
06 September, 2010
How I missed seeing the car remains beyond me. Sure, it was gray and bleary outside with limpid bits of snow drifting down onto ice-crusted road mush and finely aged snow. And sure, it was my everyday route where I'd practiced crossing the busy street to get to the bus stop for the past several months. I had thought I'd gotten pretty good at it. I was wrong. I missed seeing the low-slung black sedan coasting along behind the large white van, so I stepped out into the road to cross. Suddenly there was a large black mass in my peripheral vision, and I turned to acquaint myself with the contours of its hood 3m away and rapidly closing. I tried to sprint out of its way, but it was too close. The bumper caught me in mid-air and I distinctly remember the dull thwang of my skull upon its hood. I bounced off of it and over the right side of the car.
I do not remember actually falling.
The next thing I registered was how cold the asphalt was as I drew a breath face down against it. Then I made the mistake of exhaling and every neuron called in in pain. My face was oddly warm. With the next inhalation of cold, wet air, panic bloomed as I realized that I was in the middle of a lane of traffic where motorists routinely zipped past the bus around a blind curve. I was quite certain that I did not want to be hit again.
Vision unfocused, I queried the location of my hands and feet, found them, and somehow managed to maneuver myself upright. I shuffled, bent and suddenly re-learning out how my limbs functioned, the 5 feet back towards the center line, somehow objectively impressed that I'd been thrown 5 feet laterally. It took about 3 minutes for my hearing to return enough to note that the driver was frantically screaming 10 feet away, asking if I was OK. She was shaking, tears in her eyes, and I immediately felt horribly guilty. As I fumbled out words trying to assure her that I was OK, I registered the warmth trickling down my face. My right hand felt weird. I remember her eyes widening as we made eye contact, and her gasping "Oh honey, your face!". I had no clue what she was talking about. But when I took the tissues from her and applied them to the trickling on my face I was surprised to find copious amounts of blood staring back at me. My hands were shaking, my knees were unfirm, and suddenly the bus driver was there, shepherding me and the driver to the side of the road and promising to wait until the police arrived.
A cruiser pulled up within 2 minutes and the officer within persuaded me to sit down on the curb while he got the driver's information. I tried as vehemently as I was able to at the time to convince the officer that no, I was fine, I'd just walk back home and patch myself up. The officer called bullshit and informed me that an ambulance was already en route. Meanwhile, I began to get very, very, very cold. I couldn't stop shivering, couldn't stop shivering, couldn't stop shivering. I managed to fumble off my right glove to see what was up with that hand and found that the stitching on my glove had de-gloved a decent-sized patch of my right thumb.
An ambulance arrived in 10 minutes, and the EMTs insisted that I lay down in the snow so that they could check my vitals. Then they insisted to put me in a neck brace and onto a backboard. In retrospect, this wasn't nearly as much fun as one would think. After that I got trundled into the back of the ambulance like a plank of wet potatoes. They began placing diagnostics and noted that my body temperature was apparently quite low, so they packed my coat with heat packs and tried to place an IV line. Normally, I have beautifully apparent veins that make nurses cry with joy at the ease to find and draw from them. But here, I had gotten so cold that all those squiggly green lines had retreated far beneath my skin and they were unable to place an IV.
Anyhow, at the hospital there was quick admission and 2 nurses deftly managed to take my clothes off without taking me out of the neck brace. This is an impressive feat because I had on a long trenchcoat buttoned and belted up with 2 thick sweaters and a dress shirt beneath it. My pants were easy, but the armored flight boots with lots of lacing were not so easy. They managed to do all of it without having to cut anything.
After that, I got checked out by neurologists to make sure everything was still functioning, and because I was still awake, coherent, and somehow coordinated they decided that I was OK and didn't need any X-rays or CAT scans. This is when they let me out of the neck brace and sit up. It was a relief to see what was going on. Not too long thereafter, they sent over a resident with forceps and saline to dig what gravel she could out of my face. Then she patched up my hand and I was free to go. Somewhere in this, a nurse passed by and noticed that my feet were bare, so she returned with a pair of pre-warmed socks and put them on me. That was pure joy right there, and was definitely the high point of that day.
This is where a logical person would go home and seek comfort. No. I went to lab. I opened up my computer and tried my damnedest to plan an experiment, but no dice through the haze of a now-throbbing headache. So I wound up going home early and sleeping for most of the rest of that day. I couldn't shave for the next week while the fine grit healed out of my chin, and my knees are still scarred from being scraped up, but overall I made it out quite luckily.
However, I can now empirically recommend that getting hit by a car is not wise. This should be common sense, and it is, but it is nice to have data anyway.
31 May, 2010
Those are the beginning of my goggles. Looking back at them, I could probably have planned them out a bit better, but for what I had to work with I'm rather happy with how they're progressing. I even got out all the metal burrs out so that they don't poke little splinters into my face anymore! That being said, though, the steel is a bit uncomfortable to wear right up against my eye sockets, so I'm thinking some kind of padding is in order. I've been thinking maybe I ought to add some rolled flannel fabric around the rims, but then I'm not exactly certain how I'm going to get it to stick to the steel. Hot glue feels like cheating, but it may be my only option. The heat gun that I used to braze the steel ribbon to the steel pipe would set the fabric on fire, so unfortunately that's out.
There will be no nonfunctional gears on my goggles. Instead, I intend to add some iris mechanisms to both eyes (once I can bribe my way onto someone's CNC machine, anyone have some good cookie recipes they're willing to share?), green lenses, and at least 1 laser mounted on the side. I probably ought to also make a headband at some point.
How to make Really Heavy Glasses Frames:
1) Procure 1 3" steel pipe nipple, diameter to your specifications (I used 1.75"), with both ends threaded.
2) Sit down with calipers and devise needlessly complex formulas to make perfectly even angled cuts to get scalloped eye pieces.
3) Clamp the pipe to a firm surface.
4) Attempt to cut it with your Dremel, realize it will take about 7h to cut through it that way.
5) Get someone to teach you how to use the much more powerful angle grinder.
6) Attempt to use the angle grinder.
7) Observe that angle grinder has obliterated all planning of step 2.
8) Observe that angle grinder has kicked up a fine steel dust all over your face. Remove safety goggles and ponder your likeness to a raccoon for a couple minutes until you observe the twang that all the flying sparks left on the wall.
9) Continue angle grinding, creating several large burrs.
10) Finish cut.
11) Clamp down 1 of the eyepieces, burr side out. Change angle grinder head from cutting to grinding and apply to burrs. This may induce shrapnel. Eye protection is very important.
12) Get rid of all large burrs with angle grinder, then use Dremel to remove finer burrs.
13) Discover Dremel's polishing capabilities. This will set you back about an hour, but it won't get you much shinier.
14) Discover the 17 small burrs you missed. Go back over with a Dremel.
15) Cut slots for the 1/4" 14G steel ribbon. Thread precut lengths of steel ribbon through holes, manipulate with pliers into desired shape.
16) Rig up a vice on something fireproof.
17) Apply heatgun until goggles begin to glow, clamp down ribbon with long-handled pliers and apply some sort of binding flux*. You may have to do this sequentially, in which case it should be noted that the heatgun does not cool down rapidly.
18) Continue until all pieces are in place.
19) Be satisfied with progress for now.
20) Write self-deprecating blog post later about project.
*Yes, strangely enough this part where I was quite competent, but not with the angle grinder.
27 May, 2010
When Toaster was a young whelp in The Ozarks, it eventually came to that time in his life where he, like every young person in America, is contractually obliged to find something to annoy the hell out of their parents and stubbornly persist at it until they move out. Rather than drink illicit alcohol** and crash cars into trees, I chose to join a death metal band playing bass. As a direct result of this, I began listening to a lot more heavy metal music and going to concerts. I was never much for headbanging*** because being a wallflower is more fun, but I saw a lot of other people pursue it aggressively like a cocaine-addicted lab rat and I noted that over time these people gradually became a bit dimmer than they'd been when I met them. They were also almost always much less coordinated after they'd been to a concert.
This paper developed a mathematical model to explain why my peers were left so hammered after headbanging so much as they did. They analyzed the way people move when they headbang and developed an equation for a sinusoidal wave to describe peoples' head movements during headbanging and subsequently estimated the level of force experienced as described by the Head Injury Criterion (HIC) from the angular velocity of headbanging heads. Although the HIC projects serious injury is only likely to occur at rates of head movement/collision over 15m^2/s. However, since headbanging is a repetitive motion, they chose, with evidence, to evaluate any rate over 8m^2/s as potentially injurious. This means that the faster you headbang and the wider angle of motion your head travels through as you do so, the more likely you are to hurt your brain.
Now the methods get a bit strange. Not only did the researchers attend a couple metal concerts to observe headbangers in their natural element, but they also analyzed the way that the "legendary" headbanging duos Beavis and Butthead and Wayne and Garth headbanged. They concluded that Butthead was the one most likely to be injuring himself.
However, I drew some issue with the music they were calling metal. From the period of my youth described above, I considered such bands as In Flames, Dark Tranquility, Strapping Young Lad, and their doomy ilk to be metal. I'd never considered AC/DC or the Ramones to be music to headbang to because it was just hard rock and punk, respectively. It should be noted that metal comes in more flavors than anyone knows how to classify, but the primary ones are the American model (Static-X, Rammstein), the Scandinavian model (Hammerfall, Nightwish), and the experimental sort (Finntroll, Sleepytime Gorilla Museum).
In conclusion, they recommended that public health agencies issue headbanging warnings on headbanging-worthy CDs, issue neck braces to limit the range of neck motion, and advise that metal bands have tutorials before their concerts. This leads readers of the paper to conclude that the authors themselves have absolutely no metal cred, because everyone knows that the only way they'll ever get concert-goers to wear neck-braces is if they become a metal fashion statement.
*Swing is a musical concept that relates to the delay between upbeats and downbeats. Upbeats and downbeats refer, respectively, to beats 2+4 and 1+3 in 4/4 metered music. Much of rock has the space between all upbeats and downbeats even, but in jazz and some hiphop the space between them is staggered to create a "swing feel".
***OK, it was because I am and always have been a nerd and didn't want 1) to damage my brain or 2) lose my glasses. I knew what brain damage felt like, I was a clumsy kid and had been through a couple concussions--and headbanging felt far too similar to ever be enjoyable. Can't help but to feel a tinge of smug right now with science validating me choosing to almost entirely abstain from it.
Patton, D., & McIntosh, A. (2008). Head and neck injury risks in heavy metal: head bangers stuck between rock and a hard bass BMJ, 337 (dec17 2) DOI: 10.1136/bmj.a2825
24 May, 2010
Anyway, I've been thinking a lot about the applications of network information theory to TCRs lately. But that's not what I'm going to talk about today, because in thinking about TCRs like that I've recently come to appreciate just how absolutely unrefined, perhaps even crass, my initial understanding of TCRs was.
Back when I first took an immunology course through my university's medical school extension thing, this was the impression I got of TCRs. G-protein coupled receptors (GPCRs) had been beaten into our skulls with the Alberts' Molecular Biology of the Cell text and as such I figured it worked a lot like a GPCR. This turned out to be rather incorrect. In fact, I was also under the impression that almost everything in the world was some sort of GPCR***. Fortunately, this too turned out to be incorrect.
The CD4/8 molecule pictured above is a rather handy cell-surface marker that is expressed, respectively, on CD4+ and CD8+ T-cells, which in turn respectively recognize antigen in MHC-II and MHC-I proteins. If that didn't make any sense, don't worry about it, what's important here is that CD4 or CD8 help the T-cells see the antigen that elicits a signal. CD4 and CD8 are co-stimulatory molecules without which antigen-presenting cells cannot effectively transmit information.
Anywho, as evolution would have it, there are more proteins involved in TCR signal transduction.
At the time I learned of the existence of CD3 and CD28, I had absolutely no clue what they did, so I merrily accepted that they were part of the TCR complex and moved on. Why I didn't look further into them is currently beyond me, but the most likely answer is that I was distracted at the time by free cookies. As such, I thought that signal transduction just carried on with CD3 and CD28 as handsome bookends.
Little did I know of the strange superpowers these two molecules have. Eventually, because science enjoys knocking over the obelisks of my ignorance despite how hard we've labored to keep them intact****, I gained that knowledge.
I couldn't believe it. It was like when I found out that I couldn't eat clouds. Signal transduction WITHOUT antigen stimulation? What sort of stochastic heresy was this? This shattered the beautifully deterministic world-view that my undergraduate education had instilled, that every receptor has a ligand that can be defined and that the cell is a place of beautiful complacency and order. I had known that ligands::signals weren't always 1::1, and I had accepted that, but this, this was somehow darker and more malevolent, and the knowledge that TCRs could be so deftly manipulated and easily fooled was tantalizing. This assumption, also, turned out to be wrong. TCRs are stubborn little bastards.
Nonetheless, I set aside my beloved copy of Janeway's Immunobiology and leaped into the scientific literature face first. I read cell biology papers, I read biochemistry papers, I read biophysics papers, I read autoimmune pathogenesis papers, I read genetics papers, I may have read some enzymology papers, and I know I read a bunch of computational biology papers. I emerged with a mouthful of bistable switches and nonlinear dynamics, and I believe that my understanding of molecular biology as a whole was greatly enhanced by it. Cells weren't orderly little machines, they were complex and messy tiny mechanisms that had error and chaos built in as part of their very functions. And that chaos and nonlinear responses can be harnessed by evolution to increase the sensitivity, response range, and efficiency of cells was absolutely beautiful in its inhumanity. Humans build orderly structures, boxes and flat surfaces and well-engineered machines, but cells don't given a damn! Cells get by, thrive, and capture the very entropy we try so hard to scrub out of our lives, and that, that right there was something that I didn't appreciate until I wound up climbing up atop the tallest stuff at hand one night (Halloween, exactly) and laid sprawled out on top of it watching the sky. Seeing the moon reel about the sky and the stars wheel away above it while the earth beneath me tangibly spun made me feel so very small and tiny and insignificant in the face of such a vast expanse as the universe. But then, at the same time I knew that I was composed of billions of microscopic cells to the point where we are complex molecular galaxies unto ourselves and that, too, made me feel small and insignificant. And lastly, knowing that the stars in the sky and the cells in my body will get by without giving a damn about whether I know they exist or appreciate them was a sort of beautiful thought that has remained with me, probably as the closest thing to faith that I've found.
Epic literature reading aside, the mechanisms of TCR activation as I now envision them are rather complex to draw, so I am going to use art instead.
This isn't meant to be tongue-in-cheek about it being epic*****, but more that it is incredibly crowded and busy and spatial location matters a LOT. You see, resting T-cells have TCRs scattered across their cell surfaces more or less at random, and each of those TCRs is identical. But once 1 of those is conjugated with the triggering antigen at just the right specificity, they all suddenly (within a matter of mere minutes) condense over to the site of that triggering and form an immunological synapse.
The synapse polarizes the TCRs all to 1 side of the cell and clusters them together. Actin also gets rearranged. This provides a cell surface anchor point for intracellular proteins to begin forming a complex cascade. The TCR proteins themselves change shape and CD3's intracellular domains are released from the cellular membrane where they were held. CD3 can then serve as a scaffold for effector kinases such Lck and Fyn. Some JAK/STAT scaffolding proteins eventually transmit the signal from Lck/Fyn/Zap70 to ERK and JNK, which in turn then affect transcription of NF-kB and other response genes such as IL-1b. At the same time, there is a massive calcium flux across the cellular membrane.
However, the synapse is presently more interesting than its effector functions. The immunological synapse is actually composed of 2 parts, the central supramolecular activation complex (cSMAC) and the peripheral supramolecular activation complex (pSMAC). As you might have already imagined, the cSMAC is surrounded by the pSMAC. Within the synapse, many T-cell surface proteins are able to interact with their ligands on the surface of the antigen-presenting cell and vice versa. The SMAC structures are stable (relatively for T-cells) and allow the antigen-presenting cells to properly stimulate the T-cell with both its cognate antigen and some pro-proliferation cytokines such as IL-2.
Now here's where I really have no idea how to visually illustrate it. Within the cSMAC, TCRs are systematically obliterated as the activated, presumably phosphorylated?, TCRs get pulled into the cell and chewed through proteasomes to allow fresher TCRs to get at the antigen-presenting action. This degradation of activated TCRs from the cSMAC is essential for proper T-cell activation (if you block it the T-cells keel over and die, as they are wont to do). And this is what is really frackin' cool: bistable switch behavior in the activation kinetics of TCRs is mediated first by formation of the immunological synapse, and then sustained by endocytosis and degradation of activated TCRs.
Toaster, what the blugoon is a bistable switch?
A bistable switch exhibits the property of hysteresis, which is rather awesome. Hysteresis essentially means that a signal going 1 way across some response action (sensor) doesn't necessarily get the opposite response when the signal goes the other way.
Hystersis can be found in TCRs at several levels. First, it is part of the kinetic proofreading that occurs at TCRs prior to cSMAC formation. TCRs have to be extraordinarily sensitive to their cognate antigen and must be vigilant in screening out false positives. Therefore it takes a stronger signal to activate TCRs than it does to deactivate them. Second, use of hysteresis in this is an efficient way of screening out false positives; the formation of the cSMAC and subsequent degradation of activated TCRs both help to sustain hysteresis behavior. Condensation of TCRs into a cSMAC requires a stronger activating signal than deactivating signal, which means it will remain active at a signal weaker than that which activated it. Thirdly, degradation of activated TCRs helps sustain hysteresis by ensuring that the signal is propagated into the cell at a proper rate. Too fast and the T-cell's built-in anti-autoimmunity mechanisms will kill the whole cell, and too slowly risks death by anergy, while still the net signal from an antigen presenting cell must be higher to activate the T-cell than to deactivate it.
There are many finer details of TCRs that I did not cover here, and still more that I probably don't yet know about. T-cells are an essential part of the immune system, able to differentiate into several different useful phenotypes. CD8+ cytotoxic T-cells can circulate around the body and survey for viral infection or cancerous abnormalities. CD4+ Th1 cells secrete massive amounts of IFNg and help direct innate immune effector cells to combat bacterial infections. CD4+ Th2 cells secrete lots of IL-4 and are involved in battling away parasites or, more relevantly in the Western world, causing allergies and asthma. CD4+ CD25+ regulatory T-cells shut down the immune response by secreting IL-10 after the pathogens have been cleared away to prevent Th1 T-cells from tearing up the place (see: cytokine storm). Memory T-cells lurk around and provide lasting immunity to previously encountered pathogens. And Th17 T-cells do something, they seem to be involved in protection against autoimmunity but we're not quite sure yet. Each of these T-cell phenotypes relies upon the TCR to detect their cognate antigen and help defend the body against the invading microbes that find its squishy, nutrient-rich nooks so very appealing. At the population level, I sometimes think of T-cells as a library of exquisitely-finely-tuned peptide detection machinery that we all carry around with us, and I find that chaos they usefully harness in hysteresis to be beautiful and captivating. There may be other, as of yet, undiscovered T-cell phenotypes and functions despite an already broad and deep literature, and that is an exciting prospect. T-cells and the exact mechanisms of their TCRs remain a relatively open biological frontier, and the best we can do is to dive in face-first.
*Not quite, but explaining it goes beyond the scope here. Look here for more information.
**If it doesn't get killed off first, as the grand majority of developing lymphocytes do, due to anergy or too strong a reaction against self.
***I really liked imagining that there were little Ggamma subunits shuttling around everywhere, all the time, in absolutely everything making a "BlootablootalootaLOO!" burbling sound as they went, with tiny ADP bubbles behind them.
****This is an obligatory joke notification footnote.
*****Also to help break up large blocks of text.
04 May, 2010
The Atari Punk Circuit was designed as a beginners' project by the venerable Forrest Mims, III. I built it as a prototype of a much grander project still to come, once I get around to making those flex resistor circuits for it. The Atari Punk circuit uses 2 555 integrated circuits (or 1 556), which is a timer circuit, and slaps resistors downstream of the inputs to vary the rate at which it pulses and capacitors on the outputs to modulate that pulse into a continuous and audible waveform. In this iteration I used 2 10K Ohm linear potentiometers as resistors. The 1st one modulates the frequency of the output wave, thus changing pitch; while the 2nd one is bridged across 2 input pins to provide destructive interference and noise upon the 1st wave, thus making buzzy distortion.
Shortly after running it in the video above, I connected this circuit to a power supply without checking what it was set to first, and promptly burnt one of the 555s out. Smoke and everything. Luckily, I have a replacement and will be putting it back together once I've wired up some flex bars in the place of the current linear potentiometers, even though linear potentiometers are dead sexy.
I have no idea how this relates to molecular biology. Yet.
28 April, 2010
1) Construct vacuum chamber with heavy-duty anode and cathode within.
2) Bridge electrodes with carbon rod, evacuate atmosphere from chamber.
3) Arc 220V electricity through the carbon rod.
4) Carbon nanotubes will grow upon the anode.
5) Modulate chemical properties of carbon nanotubes by changing the atmosphere of the vacuum chamber. Apparently it's not so much important that there be no atmosphere as it is that there be no oxygen, which is fine by me as it is easier to build. Hydrogen makes sweeter nanotubes, while a nitrogen mix makes for more bitter ones.
It should probably be noted that I don't exactly yet know what it is I'm going to do with carbon nanotubes once I've grown them--in fact, that's an understatement, I have no clue--but that's not likely to stop me here. Now all I have to figure out is how to build a "vacuum" chamber. Maybe I can bribe a hacker with muffins to suck all the air out through a scuba mask regulator...
19 April, 2010
23 March, 2010
The more I've pondered the luster of a purely academic career, the duller its enticing sheen has become. I'm not certain that I want to spend the rest of my life trapped in an office thinking thinking writing writing chasing funds and collaborators and students. There's nothing wrong with that career, it's the endgame for many scientists and most are very effective at commanding some incredible science from their desks, but I'm just no longer sure that I want it. As the sheen of academia has faded, entrepreneurship has become more enticing. I know it would involve a lot of the same office-bound paper chasing that I mention above, but that somehow doesn't make it less appealing. I think the primary appeal of it may be that the organization I build would be a product of my own devotion and charm more than bound by the strictures of bureaucracy and tenure requirements. I am terrified of complacent mediocrity (terrified I may someday see it in myself), and I'd much rather fail spectacularly than piddle along because there's a lot more to learn in failing than in middling.
However, right now I'm just a Bachelor of Science, not even a Master thereof, so I know that founding a start-up now would be substantially more complex than doing so later after I've attained more letters behind my name and the experience (wisdom?) that goes with them*. So grad school remains as a goal, I'm just content at the moment to polish my street cred and scientific credentials to help me get in next year rather than be disappointed by this year's rejection.
*This may not stop me anyhow right now.
18 March, 2010
Audio quality is bad due to the room being boomy and the microphones on my camera being tiny. There ought to be Official Footage showing up soon that will likely sound much better.
I recommend listening to this on big speaker system with the EQ spiked for mids for maximum comprehensibility.
04 March, 2010
After the presentation, a bunch of people whose names I no longer remember shook my hand and told me that I'd given a great talk that was very interesting and many people shared their stories with me of how molecular biology has randomly affected their own lives. There were also a lot of people who knew about the Central Dogma, but had always viewed it as something to be memorized and had never considered biochemical pathways to be a form of useful, active information. Nonetheless, what people very specifically pointed out about my talk were my slides. I painted about half my slides by hand with soluble ink and watercolor. Here are many of them:
Sonic hedgehog. It helps you tell your head from your ass.
Sonic Hedgehog talking to his buddies Smoothened and Patched.
Concentration gradient of Sonic Hedgehog helps Embryonic Pony determine anterior-posterior patterning.
Transcription. I chose to leave out semi-conservative replication to keep my talk focused.
Proteins have distinct functional motifs, like this one's tongue.
02 March, 2010
Right now I'm thinking it'd be lovely to move to Norway, somewhere up in Trollheim, and become a goatherder. Goats are nice, they'll eat pretty much anything you throw at them, and they even make milk and cheese (I believe you have to shake them to obtain the latter, though). The primary advantage of doing this in Norway instead of the Ozarks would be that I'd have no neighbors, and those that might be over the next mountain would be far too busy eating fish and enjoying socialized health care and education to care about me genetically engineering the goats.
I'd need 2 phenotypes, 1 with hooky fur and the other with loopy fur, but if I was successful, I'd have VELCRO GOATS!!! Not only could I harvest their wool for useful uses, but they've be velcro uses.
Now, what sort of uses would a velcro goat possibly have, you ask?
Well, for structural elements, of course. Specifically a bridge. A bridge over a fjord. Made out of velco goats. Sure, it'd be a loud bridge with all of the bleating and whatnot, and goats' eyes are damn creepy, but still, it would be a bridge made of goats over a fjord! Not only would it be biodegradable and able to consume the next Trollheimstadt's municipal recycling, but it would output bridge cheese!!!
28 February, 2010
And, because I'm
This is going down this coming Thursday, March 4th, at 7p. It'll be live-streamed, so I'll post a link as soon as I have one.
15 February, 2010
In beginning the activation of the adaptive immune system, dendritic cells process and present sampled antigen in distinct molecules (MHC) that T-cells can recognize (via the TCR and CD4/8). Due to chunk recombination of V, D, and J regions of the TCR binding motifs and subsequent pre-programmed random mutagenesis* there is extremely high heterogeneity in the recognition cognates of the TCRs. So as dendritic cells (DCs) crawl through the thymus, lymph node, spleen, or other, they have many distinct antigens loaded into their surface display molecules, and every once in a while a TCR that has some binding affinity for that antigen will bind. What follows is the immunological synapse.
The immunological synapse starts out with the binding of the TCR and CD4/8 to the MHC, which nucleate the formation of the central supramolecular activation complex (cSMAC), when all of the TCR/MHC complexes from microclusters and merge into 1 more stable site. A lot of other things happen downstream of that, most of which are very interesting**, but what I find intriguing about this is: what sort of topology do the kinetics of microcluster condensation add up to?
All optimized networks have some sort of topology. This means the hierarchy of one node over another, because to have all nodes processing the same exact bandwidth is rather energetically inefficient. As such, there can be strictly hierarchical topologies like those found inside human corporations with management, there can be scale-free topologies in which hierarchy arises due to through-put optimization and is not strict (a good example of this is the server structure of the Internet), or others I don't know anything about yet.
Is microcluster condensation hierarchical or scale-free?
Unfortunately, it is extremely difficult to answer that question empirically because it happens so fast and because the cells involved are rather camera-shy unless given very exacting and munificent conditions. Therefore, this is more or less a thought experiment.
I posit that microcluster condensation is both hierarchical and scale-free, in turn; first, hierarchical and then, later, scale-free. Cook your noodle on that for a bit, and I'll explain my reasoning for why within the next few days.
*Not a contradiction of terms. The immune system allows for random mutagenesis of a restricted set of amino acids residues on T-cell receptors and B-cell receptors to greatly increase the range of possible binding motifs without great additional informational storage costs (DNA).
**E.g., I find the activation of such factors as NFAT, mTOR, et al to be interesting, but generally find the dynamics of histone deacetlyation to be rather dull.
13 February, 2010
3kg ground beef
1 medium yellow onion, coarsely chopped
2 smallish yams, cut into ~5x10x7mm chunks
2 handfuls carrots, peeled and chopped like the yams above
1 large can tomatoes
1 can kidney beans
1 can black beans
4 cloves garlic, crushed
pinch lapsang souchong
1) Combine onion, garlic, yams, and carrots in large, deep saucepot.
2) Add generous dash of oil, salt, and black pepper.
3) Heat on high until onions are sweaty and garlic is nutty, then add whiskey and 10ml honey.
4) Stir in, continue stirring on high heat until most of alcohol smell is gone (we're after the colloidal flavors of the whiskey to caramelize them in suspension, not the ethanol itself).
5) Stir in ground beef until it is barely done.
6) Add in undrained can of diced tomatoes and tomato paste, stir.
7) Add drained cans of beans, stir.
8) Stir in remaining honey and lapsang souchong*.
9) Add generous cayenne pepper, ancho chili powder and Tabasco, moderate amount more of salt, black pepper, and file powder, and small amount of cloves and cardamom.
10) Reduce heat and let simmer, uncovered, until the protein leaking out of the beans begins to thicken the sauce to your desired consistency.
This was absolutely delicious, and it made enough to feed me for 2-3d. It was at once spicy and savory, but not sweet as one might expect from the ingredients because the low-weight sugars from the honey, cardamom and whiskey caramelized and added depth to the smoke of the lapsang souchong, ancho chili powder and cayenne. There was a faint hint of a mellow, orange sweet echo on the top of the palette, but this was largely obscured by the very well-complexed clay and blue flavors below it.
I set out in inventing this spice combination to get the mild tones of traditional chili while using sweet potatoes as the base. I succeeded on both accounts, I believe, and I really do recommend giving this one a try. I know I will be making it again sometime soon.
*Lapsang souchong is a Chinese tea that's much better at cooking than being drunk. It's a black tea that is dry-roasted over a fire of dry pine needles, and a hot cup of it tastes like literally drinking smoke. So I just added a very small amount this time to get the smokiness without resorting to liquid smoke. The tea leaves steep in the tomato juice, and they're completely edible.
08 February, 2010
Toaster Sunshine - "Arc"
1. Oxidative Periphery
2. A Retrospective Abnegation of the Postmodernist Solipism
3. Swiftly Daftly Boom Boom Doom
4. Density Earache
5. Dishware Flossery
6. Additivity (Damitol)
7. Suburban Dirge
9. Thermal Counterpart
10. Thunder Melted Your Words
11. Läpikuultava Syndan**
13. The Nineteen Shades of Concrete Unbeknownst to Sunlight
14. Saccharine Nocturne
15. Somewhere the Magic Happy
This is just a working title, and all the songs are in rough draft form. I think "Retrospective Abnegation of the Postmodernist" needs some more slices mixed in to make it more interesting (it was composed entirely out of about a dozen samples from Shostakovich and Bartoks' string quartets), "Suburban Dirge"'s violins need EQ tweaking, and I have noticed that there is a high pitched percussive artifact in "Thermal Counterpart" that needs to be found and dealt with. Also, something weird happened with "Saccharine Nocturne" upon conversion to an .mp3 that I'll have to track down.
Anyway, if you'd like to listen to the raw tracks in all their muddy glory, you can download a zipped version of the above album at: http://drop.io/ji4trez#. If you do so, please, by all means, criticize it as bluntly as you'd like.
*Notwithstanding the background music I tend to produce whenever there's a guitar handy, despite whatever else is going on around me.
**This translates to 'translucent heart'.
03 February, 2010
Part of this is due to my dream of one day delivering a data talk in the form of a power ballad, but it's also due to confusion as to when I may break down the barrier of formality and ask a douchey question within the cloak of excited admiration? I recently saw a speaker present some really awesome new biotechnology she had developed in the course of her project and its applications. The tangibility of the data (real-time fluorescent tracking of cells in a living matrice by 2-photon microscopy; which basically meant actually seeing immunotyped immune cells crawling around and interacting with each other) was surreal and exhilarating, but when she talked about her methodologies I was left wanting. I don't want to out the speaker, so I cannot say exactly what my beef was, but it had to do with the algorithms by which she chose to quantify her data. I refrained from asking this question in the Q&A session because of the very civility I mention above, it just seemed like too rude a question to ask in such a polite intellectual subculture as an academic presentation. Of course, on the other hand, there was also the possibility that my question would have revealed my ignorant n00bity, and to be honest that also played a part in me not asking.
Nonetheless, when can we whup it up and get excited about the science all around us? Can I ever high-five or fist-bump a speaker when they've shown me something awesome or would doing so break down this fifth wall academic politeness has surrounded us with?
28 January, 2010
Nov. 20. 1905
J. H. Todd
1212 Webster St.
San Francisco, Cal.
Your letter is an insoluble puzzle to me. The handwriting is good and exhibits considerable character, and there are even traces of intelligence in what you say, yet the letter and the accompanying advertisements profess to be the work of the same hand. The person who wrote the advertisements is without doubt the most ignorant person now alive on the planet; also without doubt he is an idiot, an idiot of the 33rd degree, and scion of an ancestral procession of idiots stretching back to the Missing Link. It puzzles me to make out how the same hand could have constructed your letter and your advertisements. Puzzles fret me, puzzles annoy me, puzzles exasperate me; and always, for a moment, they arouse in me an unkind state of mind toward the person who has puzzled me. A few moments from now my resentment will have faded and passed and I shall probably even be praying for you; but while there is yet time I hasten to wish that you may take a dose of your own poison by mistake, and enter swiftly into the damnation which you and all other patent medicine assassins have so remorselessly earned and do so richly deserve.
Adieu, adieu, adieu!
This was a response to an advertisement from a patent medicine salesman, apparently seeking endorsement. I hope to remember in the future to slam the proponents of alt-med woo with such grace and wit, for at the very least it is more elegantly entertaining. In the meantime, my respect for Mark Twain* has only increased.
*Sooooooo much better than Kierkegaard.
18 January, 2010
I grew up in an area of the country where racism is everyday and accepted. African-Americans lived on Grand Blvd., Benton Park, Boonslick, Blanchette and in East St. Louis. Koreans lived down Manchester Blvd., Serbians lived through the worse ends of Kingshighway, Italians lived on The Hill, Irish lived in Dogtown, French lived in Soulard, Jewish people lived in Tower Grove and University City while Hispanics were practically invisible. Generic white people lived anywhere they damn well pleased, but were especially adamant in Florissant, Chesterfield, Hazelwood, Maryland Heights, Forest Park, and the Central West End. Saint Louis is a city of several million people that has been standing for more than 200y, and these divisions remain, perpetuated by infrastructure and class. The neighborhoods around the dying industrial zones just west of downtown are crumbling and so are the schools within them, and this just sets the stage for a cyclic repetition of the same social injustice. Meanwhile the office towers of Clayton feed the vibrant school discticts of Forest Park and the Central West End as well as luxury shopping villas like the Galleria.
But in all of this, it was the Page Avenue Extension project that most clearly illustrated the dystopic undercurrent of casual racism in the city. This project built another bridge west across the Missouri River, providing a direct line of transit from Page Avenue, which runs from downtown St. Louis all the way through to Maryland Heights, out to suburban St. Peters now. The largely white denizens of St. Peters nearly shat themselves in consternation, and the reason I kept overhearing was that now "black people could move in" and apparently would ruin everything. This highway project shaved about 30min of driving time off of getting from St. Peters to downtown, and I found it absolutely ridiculous to suppose that 30min by car would have effectively stopped African-Americans who wanted to move in from doing so. But that's what people were nonetheless afraid of.
And what disturbed me most about the whole thing was that the same people who had problems with the highway project were those who frequently also had tactical armories in the basements of their homes. That venal and irrational hatred, coupled with such easy access to powerful firearms, never sat well with me. This is the same city that sees the homes of interracial couples defaced with defamatory graffiti and witnessed the firebombing of the only Muslim mosque in the city with nary a murmur after 9/11. With Obama being elected, I would like to believe that racism has gone away, but I'm not so naive as that. Racism persists not because powerful people wish to keep oppressed minorities explicity repressed, but rather because those that have "made it" are desperately afraid of having to share their slice of pie with a strange group they perceive as not being of themselves.
Well, I cannot morally identify with those who cower in their suburban homes with semi-automatic assault rifles and hollow-tipped bullets in their basements for fear of simple progress. I reject their fear, I reject their hatred, and I condemn them for their prideful ignorance.
I left St. Louis in 2004. It had already left me much earlier.
*I can understand hunting guns and have no problems with them, but there is a massive difference between a single-shot hunting rifle and a semi-automatic tactical assault rifle loaded with bullets designed to inflict maximal harm.
15 January, 2010
I am also a genius.
How do I manage to operate simultaneously at both extremes of intelligence? It's not as simple as a statistical mean, but rather a wild and exhausting oscillation between them, careening from high level metacognition to struggling to tap out a single important word that I can see in my posterior inferior frontal gyrus, stubbornly not moving despite my need of it.
Simply put, I wouldn't have the slightest clue that I am intelligent if not for others around me reinforcing their perception of my intelligence upon me. This isn't to say that differences in processing speed, retention of information, or synthesis of broad principles would not have eventually become apparent to me, but they would have taken quite a while as I, and others, have found myself to be profoundly dense when it comes to the nuances of human emotional social behavior. Basically, this stems from the contrast between feeling my sentience buzz with tantalizing data and sometimes feeling remarkably stupid.
I am aware that feeling stupid or feeling smart is an entirely subjective internal experience. Furthermore, it is likely that feeling remarkably stupid is actually due to being able to perceive my mistakes and/or shortcomings in their full implications and on (perhaps too) many scales. I am not writing this to polish my own ego here, this is speculation. I have been very frequently puzzled by other peoples' behaviors, and this is not the pleasant, relaxing kind of puzzled where there is some verifiable formulation of the question to begin with*, but the kind of maddeningly unquantifiable mystery that follows no logic except self-interest.
I don't understand most people. I believe I understand a large aspect of them, but I don't understand why. I have met so many people who seem content to live in the shallow end of the pool, who have never regarded information as anything other than temporary and fleeting, and I cannot help but wonder why they are content with it. Sure, everyone becomes a philosopher on their deathbeds, but what of the rest of their time before it? I cannot relate my frame of experience to theirs. I make no claim that my mode of thought is superior. I cannot comprehend satisfaction without questioning the vast beauty and complexity of the world sparking all around me.
On the other hand, nerds and scientists are comprehensible people. They operate on the same strong currency of curiosity and wonder that I do, and as such I find them much much much more relatable than most "normal" folks. Sometimes I amuse myself by trying to view the nerd/hacker/scientist cultures of which I am a part like I am an outsider to it, and the way that we interact with one another is in many ways fundamentally different. We are scientists, nerds, or hackers because we love what we do and are deeply emotionally vested in the outcome of our clever work. We question the world around us and reinvent our relationship to our understanding thereof frequently, and that, more than anything, is what sets intelligent people aside from others.
*E.g., a jigsaw puzzle has a solution if the complete set of pieces are placed in the correct spatial sequence, or the structure of a protein may be hacked to test its function in measurable environments.
10 January, 2010
1 bag cinnamon chips
1 glop of breadcrumbs
1) Wash radishes thoroughly.
2) Boil radishes until slightly soft. Drain and let cool.
3) Cut off top sprout of each radish and use end of a potato peeler to excavate a narrow cavity.
4) Stuff as many cinnamon chips into that cavity as will stay.
5) Roll around in beaten eggs.
6) Roll around in breadcrumbs until well-coated.
7) Fry in 4cm hot oil, turning as needed, until evenly golden-brown.
8) Remove from oil with slotted spoon, shake off excess oil.
Not too complicated, but sort of laborious. These will be crunchy on the outside, and the tart starchiness of the radish will both offset and complement the sweet kick of the cinnamon melted inside. Best served with a dollop of Sour Pepper Sauce on top.
Sour Pepper Sauce*
2 fat limes
100ml soy sauce
100ml Thai pepper sauce
3g ancho chili powder
1.5g black pepper
1) Stir all wet ingredients and powder together. Bring to an vituperous boil.
2) Squeeze in all juice from limes.
3) Continue stirring intermittently at a high boil until the sugars in the ketchup begin to carmelize and turn the whole sauce a ruddy brown.
4) Cover and simmer for 30min.
5) Remove from heat and refrigerate overnight.
6) Serve cold.
This will be both hot and smooth with a nose tingle. It's is highly acidic, so exercise caution and titrate with base in such a case as indigestion develops. Pepto-Bismol may be used as a base.
*Also an effective way to clear one's sinuses.
08 January, 2010
HD isn't doing me any kindnesses, but I stand by my thesis: we need more dinosaurs! Or robots!!! Or robot dinosaurs. Just something more charismatic than "Scientists have discovered..." in media reports as though we're all faceless data drones. I mean, if sports teams can have mascots, why can't we have them too?
07 January, 2010
Anyway, I have noticed a large number of people who complain about the greater-than-desired circumference of their waistlines very often. I cannot force these people to do sensible things such as eat better or exercise more regularly, and I am wholly unqualified to perform bariatric surgery. Therefore, I will help motivate them to exercise more intensely.
For just $20/session, Toaster will chase you full-speed with a pointy stick. You supply the pointy stick! Each time you slow down or stop fearing the stick, Toaster will give you a gentle jab with the stick to re-motivate you.
And for just $50/session, Toaster will come to your house in the morning and ambush you with not just one, but TWO pointy sticks as you walk to your car and chase you all the way to the nearest health food store, lurk ominously until you have purchased low-calorie, high-fiber foods, and then chase you back to your home screaming obscenities in a foreign language of your choosing!
Toaster is offering this service for a limited time only because he is well aware of the rate at which people lose their convictions to stick to their New Year's Resolutions. So don't delay, email Toaster now to schedule your first one-on-one personal weight-loss consulting session!!!
*Even if that means drawing a hotsauce face on a block of tofu and slashing at it.
06 January, 2010
This is real flow cytometry data I collected. The terraced blotches represent different populations of cells as differentiated by staining their surfaces with fluorescent antibodies, as such the axes represent 2 different fluorophores' distinct staining intensity. Non-floaty blobs like the sandworm blob are common because primary cell populations are always somewhat heterogeneous and as such will rarely stain in perfectly discrete pots. I couldn't look at this plot and not see a sandworm, so I made it better.
04 January, 2010
I like food. I like science and the engineering/hacking methodologies. But I know it's not a good idea to eat off of labware, so the natural solution is to hack food. To this end, I am hosting a food hacking potluck with many of the local hackers this coming weekend*, and I've been trying to figure out what to make.
Essentially, I want to make blueberry muffin ravioli. I will serve it in a mango avocado basil reduction. Now, making either raviolis from scratch or muffins from scratch is relatively straightforward, but combining them so that the ravioli is still pasta-ey and the muffin is still muffiny is an issue. Will pasta cook if I just bake it in the oven? Or do I have to boil it first? I know from literature research that lasagna noodles must be boiled before being baked. It is possible that I could blanch the muffin batter-filled raviolis in boiling water and then bake them, but I am concerned that this would lead to leathery pasta shells. I mean, honestly, I think my best bet is to cook the ravioli squares first without muffin batter, fill them, seal them, and then bake them moist.
What do more experienced cooks think?
If this falls flat, I have a backup plan: caramel-filled radishes breaded, fried and then served with a sour pepper sauce.
*I will be posting pictures and recipes of the things that turn out tasty.
03 January, 2010
Notwithstanding my circadian malfeasance, I can't just have a job. A job is something you go to for 8h a day and detach yourself from coming home, something that pays the bills and fits in a big chunk of your daily routine. Something that weekends are an escape from.
Science isn't just a job. Science isn't just a career. Doing science is a mode of being, a way of thinking and a pervasive outlook that permeates all aspects of life. To be sure, there are people doing science to whom science is nothing more than a job, but to the scientists, doing science is a passionate outpouring of their innate internal curiosity and excitement at the sheer wonder and awesomeness of the reality around them.
As I said, I can't just have a job, I need the storm and flow of science's complex funneling of my creativity, cleverness, and joie de vivre. Even as I define the parameters of my experiments, science, in many ways, defines me. My education in science has sharpened my inquisitive and skeptical predispositions to become useful tools and not just the occupation of idle daydreams. This utility of my innate urge to create new stuff, to explore and discover are why science isn't just a job for me, it's awesome.
There are times that I get frustrated with my benchwork. Recently I had a long series of experiments not work properly for a couple months, and tearing through my methodology to try to find where I'd gone wrong, trying to plot out possible sources of error and chafing at the bit as each of these experiments took several days to validate was draining and discouraging. There are times that the poor quality of my data, such as getting a higher event count from bleach than my sample on the flow cytometer, makes me question my scientific aptitude in the first place. How could I ever expect to succeed in this experimental endeavor when I wasn't smart enough to begin with?
But it is this that is also valuable. Science forces us to question ourselves. We wrap up our self-esteem in our experimental results and we take rebukes from reviewers personally. We chase windmills of perfect data and push the capabilities of our minds ever further seeking to integrate our data into a new story the world has never seen before. This is important. By being both scientists and science, by loving what we do and the delightful but exhausting challenges it confronts us with, we are pushed not only to improve the quality, scope and ambition of our experiments themselves, but also to become better, savvier scientists and humans as well.
As a science, biology is weird. It's messy, it's frequently stubborn, it's complex and chaotic and these are what attracted me to studying it. And then into more complexity I realized how awesome immunology is. But it's not so much the complexity itself that draws me back into the lab, it's that with molecular biology I am literally peeling back levels of reality with my mind through the careful design of experiments with cells and reagents that I cannot see, feel, or taste. It could not be cooler, unless I had more lasers, but I digress:
Science ain't a job so much as it is riding an angry horse through a buffet of cookies and ice cream.
02 January, 2010
And I like drawing caricatures.
So, dear readers, would you like a Toaster-drawn caricature of yourself? Email me* a picture you want drawn through my distorting parameterization and I will send you back a quick caricature, with no guarantees as to humility or reverence. It should be noted that I will also post them here, but will not append your name and/or pseudonym if that is your wish.
*Toaster DOT Sunshine AT gmail DOT com
01 January, 2010
In practice, however, securing the copper laminate has been more difficult than expected. Turns out there are a lot more different types of copper foils than I had ever expected and I'm not sure exactly which one would suit my purposes best. And while we're on practice vs. theory, it turns out that Ethernet cables are much easier to make into complex braids than 16G aluminum wire. While a 42 braid of Ethernet does look cool, it is not a torc.