Thing that make the world implode

Decaf americano?

I've heard this ordered at Starbucks(es) before... decaf americano. For those who do not know, americano is coffee language for espresso and water... aka "watered down espresso" for those who are too pansy to drink the real thing... or people like me who want the satisfaction of a whole mug without sacrificing the caffiene. But a decaf americano? What is the point of that... "Yes, hello, I would like watered-down fake coffee." FAIL.

The "luxury utility vehicle" (LUV)?

This includes all "SUVs" that are not made for "S"-- Acura MDX, Porsche Cayenne, etc. What is the point? Who buys a car for utility when it is not going to be utilized for anything more than driving around shopping. Shopping is not a sport. And SUVs should not have seat warmers. I think these cars exist to show that the consumer has the money to guzzle gas without hesitation. Either do something sporty... or don't. It's like the car version of "is cheerleading a sport?"

The Hannah Montana Guitar?

Is it Miley Cyrus? Or is is Hannah Montana? Is it a guitar... or isn't it? World ----> explode.

Snuggie?

Because it's cool to wear your blanket out of the house. If you are too lazy to take your arms from out from under the blanket to get the remote, but can still venture to walmart to stock up on all the latest consumer goods... while wearing your snuggie? Uhm. Yeah. And now they have those fashion snuggies? Making wearing blankets in public-- stylish?

The Elliptical Trainer?

So the idea is that you put your feet into these holsters that move your legs for you in a circular motion and somehow you burn more calories than running? How does that work? All I am going to say is... I have seen many fit athletes who run. I have not seen anyone who is a champion of ellipticalling. "Oh, look at me, I'm the BEST ELLIPTICALER IN THE WORLD. I can burn 100000 calories in an hour!" No.

Fur lined boots and shorts/skirts?

Why.... (EXPLODE)

Warranties on Running Shoes?

For ten dollars, you could protect your shoes against wear and tear. But running is not included in the list of actions protected against. I don't know about you, but the next time I go ice climbing in my DS Trainers I am taking that action back to sportsauthority. Unusual wear and tear? Think you got it backwards there, SA.

Jolly Ranchers and Bacon.

There is at least one thing in the world that does NOT go with bacon.

Mathematics

"Mathematics, rightly viewed, possesses not only truth, but supreme beauty -- a beauty cold and austere, like that of sculpture, without appeal to any part of our weaker nature, without the gorgeous trappings of painting or music, yet sublimely pure, and capable of a stern perfection such as only the greatest art can show."
- Bertrand Russell

"The mathematician does not study pure mathematics because it is useful; he studies it because he delights in it and he delights in it because it is beautiful."
- Henri Poincare

"Similarly, mathematics can achieve a proof that has no interaction with the physical world. It may even be the closest to divine truth that human beings can achieve."
- Andrew Sullivan

Solitude

"He who delights in solitude is either a wild beast or a god."
- Francis Bacon

"I lived in solitude in the country and noticed how the monotony of a quiet life stimulates the creative mind."
- Albert Einstein

"Language... has created the word "loneliness" to express the pain of being alone. And it has created the word "solitude" to express the glory of being alone."
- Paul Tillich

Politics

"The word 'bipartisan' usually means that some larger-than-usual deception is being carried out."
- George Carlin

Meditation

"The birds have vanished in the sky, and now the last cloud drains away. We sit together, the mountain and I, until only the mountain remains."
- Li Po

Effort

"It is not the critic who counts: not the man who points out how the strong man stumbles or where the doer of deeds could have done better. The credit belongs to the man who is actually in the arena, whose face is marred by dust and sweat and blood, who errs and comes up short again and again, because there is no effort without error or shortcoming, but who knows the great enthusiasms, the great devotions, who spends himself for a worthy cause; who, at the best, knows, in the end, the triumph of high achievement, and who, at the worst, if he fails, at least he fails while daring greatly, so that his place shall never be with those cold and timid souls who know neither victory nor defeat."
- Theodore Roosevelt

Freedom

"Live free or die. Death is not the worst of evils."
- John Stark

Commencement

"This, I submit, is the freedom of a real education, of learning how to be well-adjusted. You get to consciously decide what has meaning and what doesn't. You get to decide what to worship.

"Because here's something else that's weird but true: in the day-to-day trenches of adult life, there is actually no such thing as atheism. There is no such thing as not worshipping. Everybody worships. The only choice we get is what to worship. And the compelling reason for maybe choosing some sort of god or spiritual-type thing to worship--be it JC or Allah, be it YHWH or the Wiccan Mother Goddess, or the Four Noble Truths, or some inviolable set of ethical principles--is that pretty much anything else you worship will eat you alive. If you worship money and things, if they are where you tap real meaning in life, then you will never have enough, never feel you have enough. It's the truth. Worship your body and beauty and sexual allure and you will always feel ugly. And when time and age start showing, you will die a million deaths before they finally grieve you. On one level, we all know this stuff already. It's been codified as myths, proverbs, clichés, epigrams, parables; the skeleton of every great story. The whole trick is keeping the truth up front in daily consciousness.

"Worship power, you will end up feeling weak and afraid, and you will need ever more power over others to numb you to your own fear. Worship your intellect, being seen as smart, you will end up feeling stupid, a fraud, always on the verge of being found out. But the insidious thing about these forms of worship is not that they're evil or sinful, it's that they're unconscious. They are default settings.

"They're the kind of worship you just gradually slip into, day after day, getting more and more selective about what you see and how you measure value without ever being fully aware that that's what you're doing.

"And the so-called real world will not discourage you from operating on your default settings, because the so-called real world of men and money and power hums merrily along in a pool of fear and anger and frustration and craving and worship of self. Our own present culture has harnessed these forces in ways that have yielded extraordinary wealth and comfort and personal freedom. The freedom all to be lords of our tiny skull-sized kingdoms, alone at the centre of all creation. This kind of freedom has much to recommend it. But of course there are all different kinds of freedom, and the kind that is most precious you will not hear much talk about much in the great outside world of wanting and achieving.... The really important kind of freedom involves attention and awareness and discipline, and being able truly to care about other people and to sacrifice for them over and over in myriad petty, unsexy ways every day.

"That is real freedom. That is being educated, and understanding how to think. The alternative is unconsciousness, the default setting, the rat race, the constant gnawing sense of having had, and lost, some infinite thing."

- David Foster Wallace

The long way home

It was hot today! I'd forgotten how much I miss the heat. Even at 8:30 this morning it was too warm for gloves on my motorcycle, and it got up into the 80s as the day went on. It felt wonderful.

I got off work at about 8, and it was still warm and breezy. Instead of going up onto the highway, on an impulse, I drove west through the city, looking for a slow route home. I meandered through the colorful, off-beat Mission District until I happened on a hole-in-the-wall sushi place called Yo's Sushi Club. It felt authentic, with a clean, very Japanese aesthetic. The chef, Yo, stood behind the counter, a white towel wrapped tight around his bald head. There was no bento or teriyaki on the menu, just sushi, and I watched as Yo made all the sushi himself. The chirashi was delicious. I ate slowly, then rode the rest of the way down Mission until I found myself on the hilltop at Daly City. It was starting to cool off by the time I made my way to the road across the mountain, and saw the lights of San Francisco spread out north of me as I wound through the pass.

I've got to take the long way home more often. I hope the weather stays nice! If it's clear, tomorrow night I'm going with some friends out past Livermore in the east bay, and we're going to watch the meteor shower.

If I had a million dollars...

I worked a half day today. I didn't have a particular reason for going in, but there were a few things I wanted to catch up on, so I fired up the bike and rode up to campus. I spent most of the day sitting at my desk, reading a mathematical physics textbook, and tinkering with a simulation I'd written earlier in the week.

A recurring theme of me-at-work, pretty much ever since I started working when I was 15, is the thought, Sigh...if only I had a few million dollars, so I could do X instead of this... Today, it struck me that, if I was independently wealthy and could do whatever I wanted, I probably would spend my time doing what I did today. I'd find somewhere quiet to sit, and learn some new physics.

On top of that, I found out a couple of weeks ago that I won a competition for a federal research fellowship, so I'll get an extra $4000 or so per year to do exactly what I'd be doing anyway, with no strings attached. (I worked out the total value of the fellowship, and was surprised at how large it is: it pays for everything for three years, which comes out to be around $150,000!) As an additional bonus, it's considered very prestigious, looks good on a CV, etc. (not that I'll be applying for jobs anytime soon...).

I hesitate to say so, but I feel honestly satisfied with the way things are going. It's the first time I've felt this way in a long time, so it's a bit alien to me, but...I'm happy. (On a related note, I also feel completely vindicated in my decision to switch research groups.)

Everyone loves grad school!

I dug up a funny transcript of a conversation I had with my brother a few months back...pretty much captures how much I hated my previous lab:

2:49:47 PM Gheed: man grad school blows though
2:49:50 PM Me: lol
2:50:00 PM Me: WUT DO U MEAN IT'S AWESOME
2:50:01 PM Me: :\
2:50:51 PM Gheed: >:o
2:51:08 PM Me: >:o indeed
2:51:22 PM Gheed: u have any idea how useful a "masters of science" degree is?
2:51:29 PM Me: i wake up every morning and think to myself: >:o
2:51:47 PM Me: i do not
2:51:51 PM Me: inform me immediately
2:52:23 PM Me: btw i do a lot of >:o while i'm at work too
2:52:31 PM Me: then when i get home i'm all like >:o
2:52:45 PM Gheed: lol yeah that face sums me up pretty well too
2:52:47 PM Gheed: >:o
2:53:04 PM Me: there's a few :\ and :( thrown in there for good measure, too
2:53:12 PM Me: but for the most part it's all about the >:o
2:53:28 PM Gheed: >:o
2:53:32 PM Me: >:o

Counting things

I've got a cup that has a little glass wall dividing it in half. It's half full of salt water, and half full of fresh water. If the glass wall is suddenly removed, then the salt water mixes with the fresh water, until the salt ions are evenly distributed in the cup. This is diffusion: the tendency of particles to move from regions of high concentration to regions of low concentration.

A simple way of thinking about diffusion is to imagine the cup is composed of a large set of very small blocks, big enough to hold a salt ion. Each block may be filled or empty. (This is called a lattice model.) If there is no bias built in to the particles, the probability of each system arrangement should be equal. An even distribution of particles is the most probable system configuration because it contains the highest number of total possible arrangements.

To see this, imagine there are four salt particles in a very small cup, and we partition the cup into four little boxes in the left half, and four more in the right. How many ways are there to have all four particles on the left side, and none on the right? Assuming the particles are indistinguishable (that is, we don't care what order they're in), since there are only four boxes, there is only 1 system configuration that has all four particles on the left side. On the other hand, there are 6 different ways to arrange the particles to have 2 on the left side and 2 on the right. If each individual arrangement is equally likely, the most probable state in which to find the system is with 2 particles on the left, and 2 on the right. To be precise, this would be six times more likely than having all the salt on one side! (Mathematically, these are just binomial coefficients, so if you're lazy like me and don't like doing a bunch of counting, you can get the number of arrangements by reading across the fifth row of Pascal's triangle, 1 4 6 4 1.)

The idea of maximizing the number of states is central to statistical mechanics. The number of states (or, more specifically, its natural logarithm) is a measure of the amount of disorder, or entropy, in a system. One of most important conclusions of thermodynamics is that in a system with a conserved amount of total energy (and number of particles, taking the classical view that these are distinct items), its entropy will always increase. (This has a number of interesting, and disquieting, implications for, for example, the future of our universe, if it is an isolated system.) This counting approach is a microscopic model for systems at equilibrium, but in a real system -- e.g., a real-life cup of water -- of course we don't sit there and count the number of salt ions in the cup. In one gram of table salt, there's around 3.6x10²⁵ pairs of sodium and chloride ions. This is a ridiculously huge number: it's 36 followed by 24 zeros, or 36 trillion trillion ions in a single gram. If you consider the number of arrangements of 36 trillion trillion ions where all the ions are on one side of the cup (total: 1), versus the number of arrangements where they are approximately equally distributed (total: a stupidly big number), it's clear that in this simple lattice model, generally all the salt is not going to be on one side of the cup!

Instead of counting trillions of ions, instead what we measure are macroscopic quantities -- for example, the average concentration of ions on each side of the cup. If we take this measurement, and discover that there's actually a higher concentration on the right side than the left on average, then that tells us something about our system: it gives us a constraint that we can use to weight the entropy calculation we did before. As mentioned before, if our system contains 36 trillion trillion particles, we're probably only going to be interested in average quantities, since the stupidly big number-of-states will make shifts away from the average very improbable: the probability distribution, in this case, will be approximately Gaussian (a bell curve), with a tiny standard deviation. But, what about our oversimplified tiny cup with only four particles of salt in it? In that case, there's a 1 in 6 chance of finding all the salt on one side of the cup! Given this non-negligibly small probability, for very small systems, the microscopic fluctuations can be important. That is to say, we're interested in how the system evolves with time -- we care about its dynamics.

Let's go back to our tiny cup, and start with 2 particles on the left side, and 2 on the right. Assume there's no bias built in to the system, and that every particle is independent of the others, so that each particle has some fixed probability of jumping to the other side. The sequence of jumps and stays that a particle follows over a period of time is called its trajectory. If there are no constraints on the system, we'd predict that every trajectory is equally likely, and if we tabulate the number of trajectories that result in 0, 1, or 2 particles jumping, 6 out of 16 trajectories result in 2 particles on the left, and 2 on the right (the same result as before). However, the table also says that there is a 1 in 16 chance for 2 particles to jump from left to right, and 0 to jump from right to left, putting all the salt on one side of the cup! For a given starting distribution of particles, this quantifies how the system's fluctuations are likely to alter the overall state of the system with time, and also how the fluctuations themselves are likely to change over time. A system's trajectory multiplicity is called its caliber.

We think that the idea of maximum caliber will be a useful way to analyze systems far from equilibrium, very small systems, as well as highly correlated systems. All three are true of many biological systems, and one system I'm particularly interested in applying maximum caliber to is long term potentiation, the way we form memories. My short-term project is a little farther afield: I'd like to apply caliber to correlated stock prices, and see if the predicted fluctuations in the stock market correspond to what's actually been observed. Because stock prices can be highly correlated, the independent-particle assumption does not work, which is why random-walk statistics do not accurately describe the probability of large fluctuations in the market. Instead, markets approximately follow an inverse quartic power law, but as far as I'm aware, no one's provided a quantitative, microscopic explanation for this. It will be interesting to see if a power law distribution follows naturally from thinking about the caliber of the market.

An anecdote

"I'd like to spend a week or two doing some reading," I said to my new research advisor, vaguely apprehensive. "I want to get a better feel for what's been done and how master equations work, and to review some math and physics I don't remember as well as I'd like."

He grinned at me. "That's fine. Work at your own pace."

I returned the grin. Suddenly, the future looks very bright.

It's winter, and I'm discontented

Science for its own sake can be really cool, if you're studying the right things. Aging interests me. Cancer interests me, although to a lesser extent. I love physics for its own sake, and of course I am interested in anything space-related. I am also interested in the medical applications of science. The medical applications are really the only applications of science that interest me.

I joined my current lab with the expectation of working on medically relevant problems, or, failing that, at least to be able to do interesting theoretical, physics-based work. My current research does not fall into this category. I write scripts to assist with genetic circuit design. There's little to no actual physics involved. It's not basic science. It's applied science (engineering, really), with essentially no medical relevance. It's not even novel work, really; I'm applying some neat work that's already been completed and integrating it for larger-scale design work. It bores me to tears.

I'm frustrated. I joined this lab with a fairly specific project in mind, and was encouraged by my future boss that I would be allowed to design and work on this project. After joining, I was curtly denied this opportunity. I don't doubt that his reasons for this denial are good but I suspect he knew of these reasons prior to my agreeing to work with him. I have requested more than once to switch off of my current project, which I find to be both conceptually uninteresting and dull in its implementation, and I have been denied not only the chance to switch projects, but indeed to have any real creative input even into the implementation of this current project. My boss pays lip service to the idea that I should have my own interests and area of expertise, but in practice, what he wants is not independent thought, but a diligent servant to carry out exactly what he wants done.

Also, my boss is an asshole. There's no polite way to put this, really. He's charming enough when he cares to be, and he's a sharp guy, no question, but when it comes down to it, he's a fucking jerk. He also has invested essentially nothing in me, so far. I'm funded by my program until the end of May (I think it's May), so he's really got no basis for complaint if I left.

I am seriously considering leaving the lab. I'm meeting up with my boss this week, and am going to lay this out in so many words, as politely and firmly as I can. I have a few ideas for projects that I'd be willing to work on, that are somewhat related to work currently taking place in his lab, but I have the sinking feeling that he is just going to point-blank refuse again. And then...well, it's not an idle threat. I'll threaten to leave if he won't work to accomodate me, and I'll follow through on the spot if he doesn't.

It's all about science!

The phrase 'global warming' brings a slight froth to both far-leftists (who I will affectionately call by their not-at-all preferred name, moonbats) and far-rightists (who will likewise be referred to by that timeless endearment, wingnuts). Moonbats, who recently received instructions from their hive mind to start using the phrase 'climate change' instead and will take great exception to any attempt to use the older term, get a bit religiously frothy about it -- there is no god but Al Gore, and I am his Prophet! Raise the specter of doubt to these rabid fans of (certain kinds of politically correct) science and like as not you'll be faced with a self-appointed Clarence Darrow thundering righteously against a frightening amalgamation of George W. Bush, Adolf Hitler, Ned Ludd, and William Jennings Bryan (also known as 'you'). Wingnuts, on the other hand, will egg you on into their pre-prepared verbal mine-field, citing misleading popular sources and asking probing but utterly loaded questions. The worst of these folks are ace debaters who wouldn't know science from scientology if Tom Cruise picked them up and strangled them with it.

But who cares, right? Someone recently enthusiastically recommended I read an anti-global warming tract written by some guy. I forget his name, but I looked it up at the time. He wasn't a climatologist, or even a scientist. He was a lawyer with a conservative advocacy group. I pointed out to my mine laying interlocutor that it seemed a bit odd to try and refute the significant library of peer-reviewed scientific literature on global warming with a non-technical, non-scientific policy tract written by a conservative lawyer. He responded, and I quote:

"This is not about science." (emphasis his)

It is, though. You've absolutely got to design policy from a knowledgeable standpoint of the underlying issue. What should our policies be with regard to climate change? Yes, it's a cost/benefit analysis -- but those costs and benefits can only be determined if you understand the process under consideration.

So, what does the science say? Here's my take:

There's three distinct issues here: first, do we observe warming, second, can we draw a reasonable conclusion that warming is anthropogenic, and third, how much can we trust the general circulation models? So, let me state that I don't trust the GCMs. A lot of my own research involves dynamical simulations, so I'm wary of trying to make forward predictions for such a complex system. With a GCM, you can't build-a-little-test-a-little with controlled experiments, so you're stuck saying, Well, this matched previous data pretty well. But that can just be curve fitting: you bounced around parameter space until you found a set that fit pretty well, but that doesn't guarantee your parameters are physically meaningful. If they're not, will that model work for making forward predictions? Probably not. In particular, I think there's so many external factors that are not taken into consideration in the GCMs, as well as parametrizations for factors that are included but that we know we're not able to model accurately (the effects of cloud cover, surface albedo, etc.), that quantitative in silico predictions about climate change shouldn't be taken too seriously. It's important to differentiate between doubts about GCM accuracy, which can be well-founded, and saying The observed global temperature data is wrong!, which isn't.

That said, back to the empirical question: have we observed statistically significant warming? Yes, and perhaps more importantly, the observed warming is nonlinear: recent years have seen it accelerate, and the per-continent surface temperature average increases are consistent with increased sulfate aerosols and greenhouse gases. Furthermore, although ocean temperature has been increasing at a slower rate (about half) of the land surface warming, it absolutely is increasing, and this observation isn't limited to the ocean surface -- temperature increases are observed down to depths of several thousand feet. The issue of the lack of a warming trend in Antarctica illustrates two important points -- that global and local temperature trends are often conflated, by people who should know better, and also that Antarctica (and parts of the tropics) has substantial gaps in its historical temperature data set. This data has been 'filled in' with data interpolation and averaging techniques, but in any consideration of Antarctic temperature trends, it's important to keep this caveat in mind.

Second, is this observed warming trend anthropogenic? This is tricky, because you need to de-couple it from natural climate forcings -- for example, obviously the Medieval Warm Period wasn't caused by man-made aerosols. So, you're trying to draw a statistical correlation between anthropogenic forcings (GHGs, aerosols) and temperature, and you've got GCMs to make this link -- and as I mentioned before, I'm leery of the predictive power of these models.

Using Statistical Mechanics to Link the Sequence and Dynamics of a Genetic Circuit

Bacteria can be reprogrammed with new genetic commands encoded in synthetic DNA. These programs require a signal processing circuit to analyze sensory input and control the cell's response. Genetic circuits have been developed that function as toggle switches, oscillators, pulse generators, and band-pass filters. This circuitry is needed to write the complex instructions necessary for applications such as nanoscale manufacturing, metabolic engineering, programmed therapeutics, and embedded intelligence in materials.

Genetic circuit assembly is challenging because genes are specific to their native systems. There is currently no method to predict the spatiotemporal dynamics of a genetic circuit directly from its DNA sequence, and coupling components from different systems requires the tedious trial-and-error adjustment of the components' kinetic characteristics. My objective is to apply biophysical models of gene regulation to predict the DNA sequence of genetic circuits in silico for a desired dynamical behavior.

Natural components of biological systems have widely varying gene expression levels. To effectively design large or complex genetic programs, we will need a detailed biophysical link between DNA sequence and gene expression dynamics. Gene expression is controlled by the transcription of DNA to produce mRNA, and the translation of mRNA to produce proteins. The rates of these processes are controlled by the DNA sequence around the expressed gene, so it is possible to tune the dynamical expression of the gene by adjusting these sequences. The promoter and ribosome binding site (RBS) sequences can be used to modify the transcription and translation rates, respectively.

Quantitative biophysical models of bacterial transcription and translation initiation have recently been developed, and their predictions are consistent with experimental data.^1,2 These models present a starting point to connect the dynamics of a genetic circuit directly to its DNA sequence. Genetic circuits can utilize a variety of sensory input signals, including chemicals, light, and temperature; here I will consider a single transcription factor input processed by a genetic inverter circuit in Escherichia coli³, shown schematically in Fig. 1. The inverter's dynamics are well-characterized for many promoter and RBS sequences, making it an ideal test circuit.

Aim 1: Predict the dynamics of a genetic inverter circuit from its DNA sequence.

Using the models referenced above, I will calculate transcription and translation rates from the DNA sequence. The equilibrium thermodynamic model of translation predicts the free energy change of ribosome binding to the mRNA, which is proportional to the translation initiation rate.

The rate-limiting step in transcription initiation is open complex formation. Prediction of transcription rate from the promoter sequence is done by computing the rate of open complex formation. However, the initiation rate is adjusted by the equilibrium binding probability of RNA polymerase to the promoter DNA. This permits the use of a statistical thermodynamic approach to model how transcription factor concentrations affect the circuit: calculating the system's partition function provides a way of adjusting the predicted transcription rates according to the population of each discrete system configuration.⁴

These predicted rates will be incorporated into a dynamical mathematical framework: a system of differential equations describing the rates of change of the inverter’s internal concentrations. This system of equations will be solved numerically to update the concentrations of the inverter's components. The result of this model will be a transfer function (Fig. 2) showing the predicted dependence of the inverter’s output, a fluorescent protein, on the concentration of its input signal, a transcription factor. Comparison of the in silico transfer functions with previous experimental data will provide a convenient way to assess and modify the model described here.

Aim 2: Forward engineer the sequence of an inverter circuit for a specified dynamical behavior.

I will wrap this model with an optimization routine to search parameter space for optimal transcription and translation rates for a given transfer function. The unknown shape of the parameter space makes a Monte Carlo simulation well-suited for this problem. The dynamical mathematical model described in aim 1 quantitatively links these parameters to the promoter and RBS DNA sequences. This link provides a systematic way to search for optimal DNA sequences, given a known parameter list.

I will generate in silico transfer functions by mutating each nucleotide in the promoter and RBS sequences, followed by experimental construction of these sequences using site-directed mutagenesis. Analysis of the in silico transfer functions should provide guidelines for efficient mutagenesis, by identifying nucleotides predicted to significantly alter the transfer function.

Verification and stress testing will be done by generating in silico promoter and RBS sequences for diverse transfer functions, then comparing the requested transfer function shape to an empirical transfer function measured using flow cytometry. These tests will focus on quantitative adjustment of the transfer function's shape, in particular, the curve's steepness (how well it approximates a digital output signal) and its gain (the range between its on and off states).

Impact: This modeling strategy is useful because it can be generalized to more complex genetic systems. Applications of this method include automated tuning of existing genetic components as well as guiding the assembly of new, more complex genetic circuits: synthetic constructs to perform arithmetic and other logical operations, such as conditionals and control logic. Automated in silico control of the dynamical behavior of synthetic genetic circuits will help synthetic biology mature into a practical and useful engineering discipline.

References:
1. Salis H, Mirsky E, Voigt C. “Designing synthetic ribosome binding sites.” Submitted 11/2008.
2. Djordjevic M, Bundschuh R. 2008. Biophys J 94.
3. Yokobayashi Y, Weiss R, Arnold FH. 2002. Proc Natl Acad Sci USA 99.
4. Bintu L et al. 2005. Curr Opin Genes Dev 15.

Snake oil

Sirtris has developed a new wonder drug, it's an all-in-one caloric restriction mimetic and no-effort-required weight loss program! It's like resveratrol but 1000 times better!!!

...

Wait, is there any actual evidence of resveratrol extending lifespan in metazoans? Even the yeast and C. elegans evidence is unconvincing; to my knowledge, no one outside his lab has ever been able to duplicate Sinclair's results. Since the lifespan assay is so prone to experimenter-introduced bias, Linda Partridge went through and did a more thorough analysis of the putative lifespan extension, and didn't find anything. (Being a veteran kool-aid drinker, I actually ran an experiment myself using wild type C. elegans and some other worms treated with dsRNA to give them an unusual germ-cell 'cancerous' phenotype...didn't help with aging, or the cancer, for that matter.)

I'd be pretty leery about using large amounts of resveratrol (which is effectively what this new compound is) as a supplement. People have picked up all kinds of low-affinity (~micromolar) targets for it, with a variety of mechanisms, which isn't surprising, given its structure. In particular, it seems to hit the adrenergic receptors and affect Wnt signaling, which is ok in small amounts but you wouldn't want to deluge your system with this stuff.

Obamania!

I hovered over the Barr/Root checkbox for a long moment, but I ended up voting for Barack Obama. I have many reservations about him, but ultimately, for me at least, the combination of McCain's temperament, age, and astonishing bad judgment in choosing Sarah Palin as his running mate did it for me. And, let's face it, Bob Barr just plain sucks.

Here's hoping he governs well...

I'd better just change the subject

I should qualify this by saying that my field is physics, not economics, but I think there's a strong argument you can make about the financial crisis that is not at all an indictment of the free market. My understanding of the financial crisis is that there's three primary culprits: 1) a systematic underestimation of credit risk, 2) excessive subprime lending, 3) mortgage derivatives linked to the excessive subprime lending (credit default swaps, CDOs that apparently no one knew how to quantify).

(1) seems to me the underlying factor. One interpretation of this is that bankers just used the wrong probability distribution to estimate risk (a normal instead of a Lorentz distribution, and a gaussian decays much faster than a Lorentz function, which follows a power law). Alright, but why? One answer, I guess, is that bankers (to paraphrase the unlamented Rumsfeld) didn't know what they didn't know. If you're modeling a chaotic system containing lots of recursive feedback loops, and things seem to be following a roughly bell-shaped curve, to start with, shouldn't you examine the function's asymptotic behavior carefully to make sure it's actually a bell curve, and not, for example, a Lorentz function, which has a completely different scaling form? Another, possibly more convincing answer, is that bankers just assumed that even though their mathematical model was incorrect, it wouldn't matter, because they could just use (in my opinion, absurdly complicated) derivatives to push the risk off onto the big investment banks, by way of Fannie Mae and Freddie Mac. Which are, of course, government-sponsored enterprises, which had, as I understand it, fairly explicit instructions from Congress to encourage subprime lending. At least some of the complex credit derivatives, and the special legal classifications built around them, were created by Fannie and Freddie, as well.

So, as a political football (and it's nothing if not that), there's plenty of blame to go around. From what I've read, there was plenty of bona fide stupidity involved. (Anecdotally, the guys I knew in college who went into banking didn't seem like the brightest folks around, but they were geniuses compared to the people who wanted to go into politics.) My understanding is that both John McCain and Barack Obama were complicit, although they're both dissembling ferociously and scrambling for the moral high ground. Not having Rick Davis blathering on his behalf has probably helped Obama in this regard. Congressional Democrats have firmly exonerated themselves, which makes no sense, but the Republicans see the whole economic mess as such electoral poison (economic issues tend to favor the Democrats, etc.) that they're not making an issue of it. This is reasonable short-term (read: electoral) but disastrous long-term politics, to say nothing of policy. The worst part is that the argument is so simple: the Republicans could really drive home the point that 1) the housing and financial markets were actually heavily regulated, 2) these regulations were a big part of the problem, so 3) in reality it wasn't anything like a free market, so this isn't an indictment of free market economics.

This doesn't mean the bailout is good or bad, and I really have no idea what ought to be done at this point. But I think the near-universal consensus that this was caused by an unregulated market run amok is wrong, and while I do think the bailout itself has to be very carefully regulated, I don't think a blind charge into more regulations on this or other markets is necessarily going to help. Obama's been quite vocal about McCain's history of deregulation, but unfortunately, McCain's response to this has been to recklessly invent schemes to out-regulate the Democrats. But hey, who needs principles when you can change the subject?

Sigh.

Further thoughts: I guess I should append to this that the actual unregulated markets were the secondary markets (credit default swaps and collateralized debt obligations), and it's the fact that each default had a huge number of derivatives attached to it that allowed the subprime crisis to amplify to the point where it could sink these huge investment banks. This is, of course, what everyone's focusing on, and why the Republicans are so leery about confronting the issue: the deregulation of the secondary markets was, I think, pushed through by Republicans. But the key point that often gets missed is that this only became an issue because of the heavily (but poorly) regulated mortgage market. To draw the analogy out a bit, everyone's up in arms trying to figure out how the signal got amplified (which is important), and completely ignoring the faulty wiring that produced the signal in the first place.

A cure for cancer

I thought of a way to cure cancer, using gold, light, and a genetic circuit. I'll update this later; I'm going to flesh this out for a fellowship proposal!