in singulo: Single Molecule Biophysics

The Fat Man Cometh

2009-11-13T13:09:00.000-08:00

The Fat Alberts Man, that is. Just came back from hearing Bruce Alberts speak. He talked in general terms about his early career, his work on Molecular Biology of the Cell, his time as president of the National Academy of Sciences, and most recently about his work as editor of Science magazine. He had some interesting things to say, although nothing really ground-breaking. He generated a lot of good will by talking about his early graduate work and about how it was a complete failure, and how he literally failed his thesis defense and was required to go back and do another six months of research. One of the things I found most interesting, though, was his repeated insistence that young scientists need to come up with new, novel ways of doing things, and not just repeating the type of work that others have done before them, and about how he personally wanted to use the journal Science to encourage that sort of thinking. But this seemed to me to be highly ironic. Journals like Science and Nature, have a system of pre-peer-review editorial review, where they reject a large fraction of papers for not being interesting enough, or sexy enough, or relevant enough, irrespective of the quality of the science. This is actually the complete antithesis of what he seems to be striving for, and I think it's well accepted (at least among people that I know) that major journals play a pretty active role in discouraging experimentation on innovative systems with innovative techniques, because the journal editors just won't understand why it's interesting or important if it strays too far from the known corpus.

Compare this with the talk I heard at the Science Commons salon recently, by Peter Binfield, the managing editor of PLoS ONE. PLoS ONE operates in exactly the opposite fashion: they will publish anything, as long as the science is sound. They then rely on the community to rate the work based on relevance, importance, or whatever else they deem interesting, sort of like Digg or Reddit. The question, of course, is whether the Intarwebs-at-large is a better judge of what's interesting, useful, and innovative than the editors of Science. I'm not really sure. I'm not even sure that "interesting" is a useful metric. But, "interesting" is what interests people, so it will always have some relevance.

Pair Sciencing?

2009-10-16T22:51:00.000-07:00

I attended the Science Commons Salon last night and spent some time talking to intargoogles celebrity Joi Ito. He was very interested by my comments about the lack of a "Journal of Failed Experiments" and the question about why such a journal doesn't exist (even though most people agree it would be useful) and what cultural, institutional, and scientific barriers prevent it. The topic also touched on some questions about what Science(tm) could learn from Silicon Valley. Joi seemed to believe, as an article of faith, that making science more responsive to outside interests (money, medicine, engineering, et cetera) would be a good thing, and I was not entirely convinced of that, being a bit of a purist. I often like to point out that J.J. Thomson did not have cell phones and computers in mind when he discovered the electron. But I actually didn't broach this topic with Joi, preferring to try to glean from him what I could, rather than argue about Science(tm) versus "science".

One interesting idea I came away with was the thought that, if you look at most of the fast growing high tech firms, they gave up long ago on having extended 9AM meetings in which people put up PowerPoint slides and discuss their latest progress. This management model would be considered downright ossified in places that practice methods like "agile programming", and "extreme programming". (In the latter, for instance, 15 minute "stand up" meetings (nobody is allowed to sit) are the norm, to keep the meetings on track and short, and to keep people on the important stuff.) But, strangely, our project management style is exactly this, interminable 9AM meetings filled with PowerPoint slides and people falling asleep (literally, in some cases.) I started to think about some alternative ways to structure research, at a very basic level, and was thinking about an extension of the "pair programming" methodology, of which Joi seemed to be a big fan.

Imagine, if you will, the following: a research group is divided into two groups, 1 and 2. Alice, Barbara, and Cathy are in group 1, and Arthur, Bob, and Carl are in group 2. Each person is the lead on one project, so Alice has her own project, Bob has his own, et cetera. During the first week, one person from team 1 and one person from team 2 get together to work on the team 1 projects. So, for instance, Alice and Arthur work on Alice's project, Barbara and Bob work on Barbara's, et cetera. During week two, they switch, and work on the team 2 project with the same partner. In week three, now, they rotate partners, but go back to the team one project. So, now Alice works with Bob, Barbara works with Carl, and Cathy works with Arthur. Week three is for team 1 projects, and week 4 for team 2 projects. And so on, and so forth.

What would be the practical consequences of this arrangement? Well, for one thing, everybody is invested in everybody else's project, and everybody gets their name on every paper. One of the impediments to collaboration in the lab is the question of lead authorship: if I give over too much control to somebody else, I might lose my slot as lead author! But this system preserves lead authorship, which, although artificial, is extremely important for job searching and funding. The principle on each project is still the lead author. It gives everybody in the lab a broad range of experience working on a lot of projects, and it allows people with fresh eyes to contribute to projects, by bringing new perspectives, which is often what's needed. And, by maintaining the rotation, people stay up to speed on their peers' projects, and don't need to be retrained too often (hopefully.) I'm curious if this would be a workable lab environment. I can see pitfalls (what if Alice and Bob hate each other?). And, also, this organization isn't idea, because Alice never gets to work with Barbara. But, there's probably some simple permutation that could get us around that problem. In any case, I think it would be a bold experiment. If I ever have my own lab, it would be something I genuinely think I'd like to try.

You have mistaken me for someone who cares

2009-10-01T13:31:00.000-07:00

From: "Lynda T. Carlson, Director, Division of Science Resources Statistics"

Dear Matthew Paul Gordon,

Help! The survey is closing soon, and your perspective is important to us.

The National Science Foundation (NSF), Division of Science Resources Statistics (SRS) really needs your input on the survey of early career researchers with doctorates or equivalent degrees, including postdoctoral researchers (postdocs).

Dear NSF:
I asked you for some money a bunch of years ago, and you said "Go shove it, kid." So, allow me to return the favor. You can take your survey and stick it where the sun don't shine.
Sincerely,
Dr. Matthew P. Gordon, Ph.D.

Bad Bob! No biscuit!

2009-09-25T17:18:00.000-07:00

I like Bob Park's "What's New" newsletter, but he can be pretty shrill at times. And the times that I've written him to point out errors, I've gotten a cursory reply. If he's going to play the "I'm a physicist so I'm smarter than you" card, he should at least be, you know, correct. To wit, in regard to cell phones not causing cancer, we are told today, "[A]ll known cancer agent act by breaking chemical bonds, producing mutant strands of DNA." Uh, Bob, have you ever heard of HPV?

Arbitrary Friday: Happy New Year

2009-09-18T13:37:00.000-07:00

I'm spending today cleaning up and RNAse purifying a PCR, so it's a lot of waiting and not a lot else to do until I get back on the optical trap. In the meantime, thoughts turn to Rosh Hashana, the beginning of the Jewish new year on the lunar calendar, which starts this evening. The high holidays tend to make me lonely, and a bit homesick. I don't know a lot of Jews in the bay area, my immediate family all lives in Chicago, and my extended family lives on the east coast, so I usually spend my high holiday time in a contemplative mode (read: alone.) I go to the campus Hillel, I follow along with the prayers, and I think about my relationship to the ineffable, and how that relationship can help me be a better person.

I say "the ineffable" because my relationship to God qua God, which is to say, God as a disembodied entity, has changed radically over the last twenty years or so. In my youth (said the sage, as he shook his gray locks) I was a devout adherent to the Reform Jewish movement. I went to Jewish summer camp, I had my Bar Mitzvah, and I had a strong and personal relationship with God. When I prayed, it was fervently, and with intention.

But, as much as it sounds like a cliche, 10 years in the relentless, ruthless pursuit of empiricism at all costs has had its toll on me. I now think of myself as somewhere between deism and agnosticism. The more I learn about the natural world, and the more time I spend with my brain in a mode of empirical observation, the less room there seems to be for a God in the universe. At the same time, it's obvious that "God", as an idea, serves a purpose to people, giving them hope and meaning, so there's an incentive to believe in such a thing, an incentive that has nothing to do with what can be deduced about the world. Occam's razor thus cuts God to pieces*.

So, then why not atheism? Why settle for agnosticism? A few reasons. First: Gödel's Incompleteness Theorem puts limits on what we can deduce from purely mechanistic logic. No matter how ruthless our logic is, there are still statements that can be notionally outside of our ability to prove them. It's obvious that the Occam's-razor-appoach to God (i.e., why believe in God if we don't need one?) is not a proof, and one can readily construct ideas about God (such as deism) that are beyond our capacity to prove or disprove, at least within a logical framework. Does this mean that I believe in God? No. But it means that I accept that I cannot prove that there is none. And given the very idea of God as an interloper and creator of human affairs, it is not unreasonable to suppose that such a being might hide himself behind layers of obscurity.

On the other hand, logic itself is a system of belief, and it also has its dogmas, such as induction. We base most of our "logical" conclusions on induction, but induction is really only a rule of thumb, and one that we can't even prove: try proving the validity of inductive reasoning without using induction. (Go ahead, I'll wait here.) So, our instinct that logic is the only reasonable mode of interpretation of the universe is itself suspect. It tends to produce useful results, so I'm willing to stick with it for most things. But, once again, I'm not willing to rule out the possibility that there are other modes of understanding our experience and our universe that might not also be valid. As an example, we have an entire emotional life that is not governed by logic. We believe things that we have no reason to believe, we frequently know with great certainty things that are provably false, and we make errors in judgment all the time because of our feelings. We can, at a fundamental level, understand this by logic, by understanding the evolutionary processes that got us to this point, and by understanding the neurological processes that underlie these feelings. But that doesn't make the feelings any less real or urgent: you can explain lust as a biochemical reaction, but it doesn't make me want what I want any less. And I'm here, inside this meatbag, trying to make sense of a world distorted by these chemical reactions, and logic sometimes doesn't help with that. A different paradigm is sometimes needed.

So, all that said, what do I do on the high holidays? What do I do when I'm sitting there, being urged to repent my sins, and trying not to fall asleep? Why subject myself? The answer is kind of the same as the above: I'm still inside this meatbag, and I still crave meaning. I still need direction. And whether that direction comes from a book purportedly written by an entity, or from a feeling that I owe certain things to my fellow man because of some comsic duty, or because Dogar and Kazon command it of me, I have to find it somewhere. To do otherwise is to give in to nihilism, which may be logical, but isn't very satisfying. And, deep down inside, when the cantor intones the age old melodies of Kol Nidre, asking God to forgive me for the vows that I cannot keep, I can feel the stirrings of that truth, that urgent feeling I had at age 13, that there's something outside of myself that talks to me from without, but also from within, and that asks me to think of my life as part of a giant Rube Goldberg contraption with a singular end, to improve the world. And I am invited to examine those pieces, and see which of them are helping, and which are hurting. And to make a choice. And for who do I make that choice? אהיה אשר אהיה‎...I am that I am...

*Perhaps this is what was meant by Hattori Hanzo in Kill Bill Part 1, when he says, "If on your journey you encounter God, God will be cut" by the superb craftmanship of the sword he produced. The relentless pursuit of perfection in engineering leaves no room for chance, or God, if every factor can be accounted for and controlled. The perfect sword will indeed cut God.

The Elements

2009-09-15T11:34:00.000-07:00

I know I posted another video from this new They Might Be Giants science album, but this one is just too awesome to not post (via BoingBoing):

Not to be confused, of course, with:

Science is Real, Yo

2009-09-09T07:57:00.000-07:00

Finally, a use for carbon monoxide!

2009-08-28T11:11:00.000-07:00

Via my friend Don Weber*, via Slashdot, via Science (the journal, and, I suppose, thence via science, the epistemological pursuit), comes a report from IBM Zurich on imaging single surface adsorbed molecul es at the atomic level** using an AFM tip functionalized with carbon monoxide atoms. Imaging single adsorbed molecules, not in a lattice context, is very difficult. In this case, they were directly imaging Pauli repulsion, which is pretty neat. It's interesting to think, sometimes, that the fact that your coffee cup doesn't pass through the table is basically just the Pauli exclusion force at work. And here it is, again, writ very small. I don't know what the implications for biology are, since interesting biological molecules are generally not planar. But interesting work nonetheless. c.f. this work on im aging single spins using an AFM.

*Before I went to grad school, Don and I worked at a now defunct software company together in Chicago called Geodesic Systems, and shared an office with two other people. I once gave a lunchtime talk on biophysics, back when I had never given any talks and didn't really know how to give a decent talk, and Don fell asleep in the middle of the talk. His comment upon mailing this to me was, "I didn't even fall asleep while reading it!"

**More memories: We did an AFM lab when I was an undergrad, with a "teaching" AFM, trying to image a HOPG lattice. The AFM was suspended from the ceiling using bungee cords as a method of noise dampening. Unfortunately, in the other half of the lab, people were trying to do Compton scattering, which involved moving lead bricks around. We would sit, holding our breath, as line after line of the image would form, and then somebody on the other end of the lab would drop a lead brick on the ground: BANG! And the image would do the optical equivalent of a phonograph needle squealing on a record. Fun times, fun times.

Weekly roundup

2009-08-20T13:47:00.001-07:00

Steve Quake sequences his own genome, one molecule at a time (Nature Biotechnology)
SMB writes up the Aspen conference on SMB as a guest editor at Current Pharmaceutical Biotechnology, hosting a special issue on single molecule biophysics. Steve's essay is free, but the rest of the articles you have to pay for, I guess, or. At least, Stanford doesn't give me online access. (Your guess is as good as mine as to what any of this has to do with pharmaceuticals.)

Meanwhile, in other parts of the scientific world...

Arbitrary Friday: Argh

2009-08-14T17:39:00.001-07:00

My experiment may be made of fail, but at least there's funny stuff on the intargoogles to cheer me up, with the knowledge that there are some really dumb people out there. Some of my recent favorites:

There I Fixed It

Passive Aggressive Notes

DNA synthesis with ATTO dyes?

2009-08-04T15:30:00.001-07:00

Does anybody know if there's a DNA synthesis company that will make oligos modified with ATTO dyes? I've looked at IDT, Midland, and Sigma-Aldrich. I want to do a quick-and-dirty experiment which will be easier if I can just buy a pre-modified oligo, and if it works, I can then maybe buy amine-modified oligos and label my own.

Arbitrary Friday: The Easiest Nobel Prize?

2009-07-31T14:02:00.000-07:00

Let's say you're 18, you're just entering college, and you have decided that your life's goal is to win a Nobel Prize. You don't care which, you just want to taste that sweet Swedish gold. So, what's your best bet? Which is the easiest prize to get?

I'm going to rule out physics, chemistry, and medicine right off the bat. That may be my biophysics science bias showing, but seriously. I don't think you can count on any of those as a good bet. The odds are really astronomical, even if you're fucking brilliant to begin with.

I'm also going to rule out economics, because it's a fake Nobel prize. We're talking the real thing here.

That leaves us with Literature and Peace. I've done my share of writing (including several chapters of a never finished book, and two ten minute plays, one of which was a musical about the life of the Danish astronomer Tycho Brahe, titled Uraniborg), and it's really hard. And I've gotta say, when I read really good writers, I'm usually just left drained, unable to comprehend how they quite do it. Like Michael Chabon, or David Foster Wallace. You can't emulate that, you can't fake it. Writing is hard, certainly hard in a different way than physics, but I think it's even harder to get good at than physics is. I think you pretty much have to be born a writer, there's no two ways about it. You can't just work really hard and get really good at it.

So, that leaves us with Peace. I would say, based on the history of the Nobel peace prize, Peace is definitely the way to go. If Yassir Arafat and Henry Kissinger can win the Nobel peace prize, I think it strongly suggests that there is a serious dearth of people out there trying hard enough, and there must be a few openings. In fact, if you consider the aggregate contribution to overall peace, I think you would probably rank higher than Yassir Arafat if you simply consistently opened doors for old ladies. And let's not forget Mother Teresa, that sainted old lady who won the Nobel peace prize for denying the poor the one thing that would have really actually helped them, which is to say birth control. So, given some of the less than stellar contributions made by these people, I think you've gotta put your money on the peace prize. There seem to be a few different ways to go about it, but I think that if you're genuinely interested in trying to bring peace to the world (or at least genuinely interested in trying to win a Nobel prize), and aren't too worried about material wealth, the field is pretty much wide open. You just pick a cause and run with it until you're out of breath, and hope that people notice.

Sick Day

2009-07-29T12:15:00.000-07:00

[Editors note: This got stuck in my draft queue and didn't get uploaded. I'm feeling better today, but am still having some stomach issues. Hopefully I'll be okay by the weekend.]

Been at home clutching my stomach for most of the morning, but I'm now sitting upright and eating cereal, and think I might be able to go into the lab in the afternoon. Meanwhile, I share with you: Acoustically driven programmable liquid motion using resonance cavities, in PNAS.

One of the problems with microfluidics is that, no matter how micro you make the fluidics, you still need big computer controlled pumps to run everything. The above paper has attempted to solve this problem in a very elegant fashion, using resonant cavities to apply pressure, with the pressure controlled by externally generated sound waves, allow you to control your microfluid device with a veritable symphony:

Of course, if you had six or eight of these things in your lab, it might quickly turn into a cacophony, a la the acoustic memory scene in Cryptonomicon.

Recent Literature

2009-07-28T15:01:00.000-07:00

Some recent entries of interest in the single molecule literature:

A former colleague of mine, Anne Gershenson, now a professor at Brandeis, has written a review of single molecule enzymology for Current Opinion in Chemical Biology. It holds up as an example the work on HIV-RT done by Elio Abbondanzieri, formerly of the Block lab, now at the Zhuang lab. But it's a good examination of the state-of-the-state-of-the-art.
The Bustamante lab has published new work on optical trapping of frameshifting psuedoknots in PNAS. People have been working for some time to understand what exactly is the origin of psuedoknot frameshifting efficiency, with mixed results, but figure five is where the money is here, strongly suggesting a relationship between unfolding force and frameshifting efficiency. I haven't read the whole thing, though, so I will reserve further comment.
Helicos has a paper in Nature Methods reporting on a "virtual terminator nucleotide" for sequencing. These appear to be nucleotides that can reversibly terminate elongation, like a di-deoxy nucleotide that can be un-di-deoxied, if you will. This ensures that the next base added in a single-molecule addition assay is really only a single base, but that further bases can still be added afterwards, elegantly fixing accumulated off-by-one errors.
Also, Hagar Zohar from the Muller lab at Berkeley writes in with news of their new web page of links to resources for single molecule biophysics, put together by a grad student organization called the CharISMA Idea Lab. I added a link on the right as well.

Arbitrary Friday: Danger Edition

2009-07-10T11:35:00.000-07:00

People often think of scientists as men in lab coats and wire rim glasses living lives of quiet desperation. While the quiet desperation is true in most cases, the idea of scientists as nerdy milquetoasts has remained pretty well embedded in our cultural consciousness (see, for instance, the execrable TV show "Big Bang Theory" for countless examples), in spite of a plethora of counterexamples. Richard Feynman was of course famous for his womanizing, lock picking, adventure seeking, and numerous practical jokes. The late great David Schramm was a 240 pound red haired demon who climbed mountains and tragically died at the fairly young age of 52 while flying his own single engine airplane. But, even apart from the famous and infamous, scientists that I know are generally a sensitive, artistic, and adventurous lot. They play piano, banjo, and rugby, they dance the salsa, they climb mountains, and that's just counting the people in my lab.

On the other hand, scientists are, by and large, a careful lot. They calculate, they consider, they assess risk, and they eschew it in most cases. I grew up in a Jewish household in the suburbs, where danger seemed to be all around, where taking the bus to the mall seemed fraught with opportunities for death and dismemberment, and where even a jungle gym presented terrifying, murderous possibilities.

But, lately, I've definitely taken a turn for the more dangerous. For starters, as bland as it seems, moving to California was an adventure for me in a lot of ways. I was moving far from my family, far from any of my friends, to a place I had never lived, with a lot of distinct cultural differences, and with very little context to guide me. And, in a lot of ways, my Grand California Adventure has been a fantastic success. I've taken all sorts of risks and experienced all sorts of new things (some of which are not really appropriate for discussion here.) But, I have also definitely started to incorporate danger into my life in more tangible ways.

About six months after moving here, for instance, I finally went and bought my first motorcycle, a 1997 Harley 883 Sportster (which you will find pictured to the right.) Hardly the most dangerous motorcycle in the world (it has trouble getting above 80 miles an hour), but a significant departure for me. Of course, I didn't just go out and buy it: I started even before I moved by taking a course from the Motorcycle Safety Foundation, and simultaneously studying up on motorcycles, riding, and what kind of bike I should get as a beginner bike. (Motorcycles for Dummies suggested the Sportster as a good intro bike, and I've been happy with it in that respect, although I'm starting to feel like it may be time to get something with a bit more oomph, that handles a bit more solidly.) Which is to say, I didn't plunge into it with abandon: I carefully selected and pursued my choice of danger, and mitigated the unecessary risk.

Not long after that, I was driving up to San Francisco, and passed by Fort Funston. All of a suddent, I realized that hang gliding was not just something that people did in movies: I was in California! There were mountains! If you had the desire (and the money!), you could fly. And so I got myself a block of lessons, and, well, the rest is history:

So, the question I ask myself is: why? Why live dangerously? My parents certainly ask me that. Is it just to impress the babes? (I hope not.) Is it because I'm some sort of thrill junkie? Honestly, I don't feel like the risks I'm taking are that unreasonable in a visceral sense, even if they are statistically more likely to result in me dying in a horrible accident than if I were to not pursue them. Therein, though, lies the answer, I think. William Gurstelle, and author and recent guest poster on BoingBoing, was discussing his new book, Absinthe & Flamethrowers: Projects and Ruminations on the Art of Living Dangerously. He hypothesizes that "the golden third", living in ways that are more dangerous than average, but still short of making pipe bombs out of match heads, is correlated with overall happiness and contentment. Fair enough, it seems like I'm toeing that line. But, still: why? Why does it make me happy? Why do it?

I don't really know the answer, but I suspect that there is an element of control involved, or, more precisely, lack of control. Most of us spend a lot of time exercising control over our lives, and, as discussed above, scientists want to control everything. (Even our experiments are sometimes called "controls"!) But sometimes, it pays to let go of that. It pays to intentionally step out over the ledge and look over. Because, not everything in life can be controlled. And if you spend all of your time in your bubble of control, in your circumscribed safe space, then what the hell are you going to do when the shit hits the fan? How are you going to cope? How are you going to deal when you're not in control? I've gotten into near accidents on my motorcycle; I've had the wind shove my glider around and nearly lost control; and it's pretty damn scary. But, your blood gets pumping, and your heart takes over, and you learn a little lesson about yourself, and how you react, and you internalize that. Flying is fun! But sometimes you crash, and in life, the decisions with the most importance almost never happen when you're in control, they happen when things are flying off the handle, and you don't have the time for sober reflection.

Total internal pedantry

2009-07-07T14:58:00.000-07:00

Glancing over some new articles on single molecule stuff, I came across the following curious title:
"Ultrastable combined atomic force and total internal fluorescence microscope." Surely, this had to be a mistake, but no, the article actually uses the term "total internal fluorescence". Now, certainly, I have been accused of being a pedantic word nerd at times, but this construction really irks me. For those of you still scratching your head, the correct term is "total internal reflection fluorescence microscopy", or even just "total internal reflection microscopy." But, the the term "total internal" refers to the reflected excitation light, not the fluorescence emission. "Total internal reflection" (TIR) is actually a quite common phenomenon in physics and has applications far beyond fluorescence microscopy (for instance, fiber optics are based on TIR.) "Total internal fluorescence" on the other hand seems like it would be useless: the fluorescence is totally internal, and never gets out, so what's the signal?

Just to make sure I wasn't smoking crack, though, I checked around the intergoogles a bit. On Pubmed, for instance:
"total internal reflection fluorescence": 629 hits
"total internal fluorescence": 11 hits

But, this hit in particular startled me. It lists in the references:

E. Sund and D. Axelrod, “Actin dynamics at the living cell submembrane imaged by total internal fluorescence photobleaching,” Biophys. J. 79, 1655–1669 (2000).

If no less a luminary that Dan Axelrod, the GODFATHER of TIRFM, could use the term "total internal fluorescence", then clearly I was way off base. Fortunately for me, clicking through the link reveals that in fact the authors had misquoted the title of the paper! The actual title, as you might imagine, is "Actin dynamics at the living cell submembrane imaged by total internal reflection fluorescence photobleaching."

In other news, I have heard tell around the water cooler that certain Block lab associated people have been selected for various Biophysical Society awards at the 2010 meeting, but since the BPS website doesn't have any info on it, I'll keep a lid on it until a formal announcement is made.

OMG ROTFLMAO LOL NIH NCBI HIV TAR

2009-07-02T13:11:00.000-07:00

Via boingboing: from the land up north, we get NCBIROFL.COM, a collection of published bioscience papers that are probably only slightly more absurd than your own research. Although I must point out that they're a bit behind the curve: the June 30th entry has already been widely hailed, having won the 2003 IgNobel prize in physics.

Watch Yer Mouth

2009-06-17T13:20:00.000-07:00

I read way too many political blogs, so although only tangentially relevant, here are some interesting tidbits I read today:

First, over at Crooked Timber (one of the few blogs where I bother to read the comments), Michael Bérubé offers a writeup of some developments in free speech in higher education. He points to the case Hong v. Grant, which basically states that a university can administratively punish a professor for job-related speech which is not related to teaching or research (committee work, for instance.) Hence, this chilling letter from UC Davis to the Faculty Senate:

According to recent court rulings, your speech and behavior in job-related duties as a public employee rather than a private citizen have no First Amendment protection. This means that disciplinary action may be taken against you (including dismissal) for statements you make in the course of your employment. According to recent court rulings, your speech and behavior in job-related duties as a public employee rather than a private citizen have no First Amendment protection. This means that disciplinary action may be taken against you (including dismissal) for statements you make in the course of your employment. Any activity performed on the job falls within this purview. According to the recent court rulings, speech and actions in shared governance activities are certainly not protected...In light of the present deep economic recession and dramatic cuts under discussion at UC Davis, faculty participating in shared governance are in a position in which they may voice strong views and concerns that could lead to lawful but punitive reaction by the administration, including denial of merits and even dismissal. Given the legal and policy realities at hand, we highly recommend that you use caution, restraint, and judgment in your speech and actions in all job-related duties.

So, as Eric Rauchway put it, "If I follow the logic correctly, Hong is obliged to participate in the administration of his department. But the definition of 'actively participate in the interworkings and administration of his department' appears here to be, 'say only those things which won’t lose you a merit increase.'"

I find this particularly interesting as a scientist because we tend to think that "academic freedom" debates mostly apply to people like Ward Churchill, and not to scientists. Not so! Now you can get canned for being a loudmouth at your departmental committee meetings. And there are no shortage of loudmouths in the sciences, that's for sure.

On a completely unrelated note (except for the fact that it's about politics): The Great Paul has pointed up some very interesting legislation:

On Monday, Sens. Jon Kyl (R-AZ), Mitch McConnell (R-KY), and Pat Roberts (R-KS) introduced the “Preserving Access to Targeted, Individualized, and Effective New Treatments and Services (PATIENTS) Act of 2009,” a new bill prohibiting Medicare or Medicaid from using “comparative effectiveness research to deny coverage.”

This really just leaves me speechless. The War on Science continues unabated. At least the Republican Party is consistent on that front.

More 3D tracking

2009-06-09T16:51:00.000-07:00

Another entry in my ever growing docket of 3D tracking techniques: A nice paper in Nano Letters from Yale Goldman's lab on a new method of 3D single molecule tracking using a system they call "Parallax". Their data is very nice, and they manage to achieve something that I was actually trying to do in grad school: visualize 3D helical motion of myosin VI around an actin filament. The technique is very nice, and is a somewhat simpler realization of a system proposed earlier here. It utilizes a splitting of an image into two halves with slightly different optical path lengths, which causes the images to move differentially in the X-Y plane based on their localization in the Z plane. Worth a read! Their use of mirrors instead of prisms is quite clever.

Focus on Microscopes

2009-06-04T13:00:00.001-07:00

Nature has five articles focusing (ha ha) on new types of microscopy, including Stefan Hell's STED (with brief mentions of PALM and STORM), and Sunney Xie's foray into Raman spectroscopy. They also have the gigantic (a 13 meter electron microscope) down to the tiny (the 3 cm microscope-on-a-chip). Written in conversational style, nothing too heavy. Some fun summer reading!

If I Only Had a Brain

2009-05-26T16:24:00.000-07:00

Via the always awesome Makezine blog*, this is an interesting article promoting "The Importance of Stupidity in Research." It's worth a read. The premise is that research, actual honest-to-goodness groundbreaking research, involves a lot of flailing about in the dark and feeling stupid, and people tend not to be accustomed to that feeling, because it's the opposite of how you're supposed to feel in your classes, where you're supposed to always know the answer.

This meshes well with a truism that I've been known to spout, which is, "If it was easy to do, somebody would have done it already." At least, for really novel and groundbreaking research, that's true. I suppose there's plenty of fill-in-the-gaps type of stuff that people have to do, the sort of stuff that requires labs full of technicians and grad students using time-honored techniques and a lot of elbow grease. But I think that's almost an entirely different category of research.

On the other hand, the converse of this sentiment was expressed once by Albert Young** when I was at Princeton, and he said, "90% of physics is just not being stupid."

*Speaking of which, if you're in the bay area, you should definitely attend the Maker Faire this weekend.

**Remembering Albert's name took a Herculean effort of googling. Basically, I had to remember that he was a classmate's thesis advisor (to whom he imparted the wisdom), and then I had to find a catalog of Princeton theses and look up that classmate's thesis. Albert is now apparently at NC State in the physics department, according to the intarwebs.

Dueling acronyms

2009-05-25T10:19:00.000-07:00

Courtesy of Greg Snyder:
SHRiMP: Accurate Mapping of Short Color-space Reads

Not to be confused, of course, with:
SHRImP: Single-molecule high-resolution imaging with photobleaching

It's all in the placement of the capitalization (apparently.)

I also note that the first author of the SHRiMP paper is one "Stephen Rumble," who I can only assume is a third cousin once removed of Stephen Quake.

Nanorobotique

2009-05-15T12:01:00.001-07:00

From Laboratoire De Nanorobotique (how freaking cool does that name sound?) at the École Polytechnique de Montréal:
Magnetic sensing bacteria are used as an external propulsion system to direct a solar-powered microsensing device. No published details yet as far as I can tell, but that is really awesome.

Non-Blinking Quantum Dots

2009-05-12T14:58:00.000-07:00

Quantum dots are cool. They're bright, small, and they don't photobleach. The problem: they blink, and the "off" state can last a long time. Certain preparations can reduce the blinking, but personally my luck with this has been pretty middling. Now, apparently, a group of researchers has produced non-blinking quantum dots. All I can say is: wow! And: when can I buy them?

Arbitrary Friday: Sandwiches

2009-05-01T16:48:00.001-07:00

Thinking lately about what it is I want to do with my life when I get out of here, and I have been thinking about things like professorship (hard to get in any place I want to live), biotech (I don't really want to spend the rest of my life at the bench), software (my first real job, and always a convenient fallback), VC (will six figures soothe a tortured soul?), and other possibilities. But, six or seventh down the list, I think I'd like to open a sandwich shop. Not really, of course. There's no better way to lose your shirt than to open a restaurant. But, I do love sandwiches. I mean, I lurrrrrve me a good sandwich. And I would love to spend my days perfecting the art of the sandwich, serving them to others, and making the world a better place by making it more sandwichy. Here are some of my favorite sandwiches:

Primanti Bros in Pittsburgh. They put the french fries in the sandwich!!!
Bat 17 in Evanston. Man do they make a good sandwich. Everything is toasted and smothered and cheesy and goddamn now I'm hungry.
The Bread Company in Urbana, IL. Their swiss bread is amazing, and they make a really mean tuna salad.
Jimmy John's. As fast food goes, these guys are the best. They use very high quality ingredients, and their selection is great. I would take a Jimmy John's over a Quiznos or a Subway anyday. Or over almost any other fast food, for that matter. And they're also headquartered in Champaign-Urbana.
Lutticken's at Stanford. Lutticken's isn't amazing, but it's certainly the best you can get locally. They don't do sandwiches well here on the west coast, in my opinion, but Lutticken's gets points for their excellent Dutch crunch bread, their very tasty meatball subs (both meatful and meatless), and for being locally owned.
Hoagie Haven in Princeton. Whenever I go back to Old Nass, I try to stop by The Haven for a peppersteak hoagie. They are legendary, for good reason. Fried on a greasy grill, and stuffed into your eager mitts at 1AM. Nothing satisfies like a Hoagie Haven hoagie.
Mr. Beef in Chicago. Italian Beef is to Chicago what Cheesesteak is to Philly, and nobody does it better than Mr. Beef. Portillo's can stuff it, they don't even come close. One glance at the wall covered in the media coverage and the unsolicited celebrity endorsements is enough to convince you that the place has a well deserved reputation. (I've read two different interviews with Chicago native Joe Mantegna in which he extolls the virtues of Mr. Beef, apropos of nothing, he just feels the need to tell the world.)

I think you get the idea. I have to go make a sandwich now.