Reflected differential interference contrast (DIC) imaging can provide eye-popping images:

These are images of a polished metal surface, and *not* colorized in any way. DIC is explained in many places on the interweb, so I’m not going to add to the noise. However, the explanations *rarely* convey the beauty of the images.

Today about 1/3 of the cells (30 filters or so) got moved into differentiation conditions (37C, hold the insulin, EGF, and interferon). Hopefully in a week the ENaC (transepithelial sodium current) channels will activate and I can start taking data.

Scholarship can be a tedious activity. Specifically, searching the existing literature to determine the context for my own research activities.

There’s a few ways to simplify the process. First (and foremost), is that literature more than a few years old is less relevant than current literature. That is, a research paper from 1925 is likely to be less useful than one written in 2009 on the same topic. Also, there are periodic review papers that survey the literature, so locating a few review papers will allow me to sort through several hundred papers to find the (say) dozen or so that are directly relevant. There are others, as well.

However, research has always been a rich person’s game. Journals charge for papers, for example. Without access to an academic (or equivalent) library, there would be no practical way to stay abreast of the literature: if I had to personally pay for every article I read, I would probably spend more than $5000 per year. The business of scientific publishing is beyond the scope of this post.

It used to be a *lot* harder to stay current- before electronic access to 99% of the papers worth reading became commonplace, whole areas of publishing were seldom available to a larger audience. An obvious example is the Russian scientific literature prior to perestroika. Although much was translated by an American Publisher (the Consultants Bureau Enterprises) and the Foreign Technology Division of the U.S. Air Force, by and large Russian results were unknown to the West.

Another example is the Defense Technical Information Center (DTIC) library. Generally catering to the U.S. military and government research programs, the technical documents contain important and useful results that were generally unobtainable, even by academics. I spent many hours in the basement of NASA’s library, going through mountains of microfiche to locate interesting work not in the ‘open scientific literature’.

Who cares? Honestly, not many people do- that’s why the microfiche is relegated to the basement, in the back. But sometimes it’s the thrill of the chase- to locate some primary source, lost to time. It’s easier now, since most materials have been made available online. The experience of being in the bowels of a library, just you, the microfiche reader and huge banks of motorized storage cabinets is memorable, and unfortunately becoming less common.

I am not referring to “landmark” papers- those are trivially easy to obtain copies of, even ones that go back to 1805 or earlier, through JSTOR. I am referring to articles, while just as influential, are far more obscure.

The chase starts when I read an assertion in a current paper, the assertion does not make sense to me, and the paper is just quoting some *other* paper rather than justifying the assertion. I retrieve the referenced paper and usually, that clears up my confusion.

Sometimes, the referenced paper is *also* just quoting an earlier reference. Again, I get the ‘grandfather’ paper and see what *that* one says. Sometimes, I’ve traced back 4 or 5 times before getting to the original justifcation.

If I have to go back 5 generations or so (which can represent a paper published in the 1950’s or early 1960’s), the paper trail tends to go off the scientific journal path. Sometimes it ends in a conference proceedings, sometimes a PhD dissertation, but usually it goes to the DTIC archive.

Here’s a few examples:

1) Sandford, Brian P., “Infrared Reflectances of Aircraft Paints”. AFGL-IR-84-0307, Accession # AD-B092 172 (November 21, 1984).

I dug this one up when I was at Nichols Research. The code we were developing was a ‘synthetic scene generator’. The goal was to generate images that would be identical to that obtained by a weapons sensor (say an infrared camera or a LADAR guidance system). In a way, it was a lot like video games, and in fact we hired people with video game experience to do some of the work. Video games use a lot of the techniques the military pioneered- fast and accurate rendering of photorealistic surfaces.

In order to generate realistic scenes, we need the object geometry, the lighting conditions (for example, by specifying the latitude, longitude, date, and time to generate the position of the sun and a program like MODTRAN or LOWTRAN to generate atmospheric conditions), and the detector characteristics (waveband, signal-to-noise ratio, etc.). We also needed information about the materials the object was made of- how they reflect or emit light.

Some basic data can be found easily enough- the emissivity for building materials in the infrared, for example. But that’s not good enough- we needed the BRDF of materials to generate realistic scenes, and those measurements are hard to come by. There are some databases of materials (for example here), but there wasn’t anything we could use. Until I started digging around and came up with the report listed above: BRDF measurements from 0.3 to 25 microns of military paint samples. This sort of measured data is precious.

2) Ufimtsev, P. Ya., “Method of edge waves in the physical theory of diffraction”, Accession # AD733203 (1962).

This unclassified translated Russian work (you can get any of the references I am posting here- just give your librarian the reference and turn them loose) is the basis for stealth aircraft. Once the work was translated, Lockheed and Boeing used the results to develop aircraft with very small reflectances- that’s correct; stealth aircraft were under development since the mid 1960’s.

Those two were very obscure works, but give a good ‘flavor’ for the sheer volume of results *not* contained in peer-reviewed literature. The next two have much more interesting stories:

3) G. G. Slyusarev, “On the possible and impossible in optics”, FTD-TT-62-175/1+2, Accession # AD-281847. (July 16, 1962).

More people should have copies of this. The first 10 pages of this report clearly demolishes a major ‘urban legend’: Archimedes’ death ray. Additional portions of the text decisively refute solar concentrators that violate the second law of thermodynamics and imaging systems that violate basic principles of optics. Just for busting Myth #1 (Archimedes’ death ray), this should be required reading in any optics class.

I’ll end with the following:
Parke, Nathan Grier., “Matrix Optics” (Ph.D. dissertation, MIT, 1948)
Parke, N. G., “Matric Algebra of Electromagnetic Waves” (MIT Research Laboratory of Electronics, Technical Report #70, June 30, 1948)
Parke, N. G., “Statistical Optics: I. Radiation”, (MIT Research Laboratory of Electronics, Technical Report #95, January 31, 1949)
Parke, N. G., “Statistical Optics: II. Mueller Phenomenological Algebra”, (MIT Research Laboratory of Electronics, Technical Report #119, June 15, 1949)

Here’s the primary sources for the ‘Mueller calculus’ representation of polarized light. The Mueller calculus (Mueller matrices and Stokes vectors) is completely different than the Jones calculus- it’s based on entirely different concepts- but is infinitely more useful. The Mueller calculus allows us to describe light that is not completely polarized (which is 99% of the light in the universe), in contrast to the Jones calculus which treats light as 100% polarized. The Mueller formalism is rarely taught and few are familiar with it. Even so, the Mueller calculus has allowed the development of very sophisticated techniques in telecommunications (both fiber and wireless) as well as LCD displays.

Parke’s dissertation references a technical report by Mueller (Mueller, H. “Theory of Polarimetric Investigations of Light Scattering”, Parts I, II. Contract W-18-035-CWS-1304. D.I.C. 2-6467. MIT (1946-1947)), but I have been so far unable to locate a printed copy of this report- most likely, the attribution has a typographical error. If you happen to come across this, I would appreciate a copy!

Hans Mueller never actually wrote a paper discussing his own invention- there is only a single paragraph, the abstract of a presentation, in the ‘official’ literature (H. Mueller, “The Foundations of Optics”, J. Opt. Soc. Am. 38, 661 (1948)). Apparently, Hans Mueller did not write *any* papers at all- at least, I haven’t found any. Let’s pause for a moment to contemplate the case of a faculty member at MIT making tenure and full Professor without having written a single peer-reviewed paper, and how that contrasts with academia today.

Today, the epithelial cells have been passaged onto their final resting place- after 4 expansions, we had enough cells to plate 120 small filters. The cells will grow to confluence, differentiate, and finally be killed; all the while subjecting them to fluid flow (or not) and measuring the transepithelial Sodium current. Once they are killed, the cells will be stained for a few different proteins of interest (polycystin-2, acetylated alpha-tubulin, STAT-6, etc), and the cells imaged and analyzed for cilium length and protein distribution.

In the end, we hope to answer some questions regarding the cellular response to fluid flow- for example, can cells become ‘acclimated’ to a certain velocity of flow?

A while ago, a friend gave me a comptometer from his factory. It mostly works, but I’m not skilled enough to take it apart and clean it. Here are some images I took- they have a distinct ‘steampunk‘ look, and at high magnification, you can see the fibers from the factory floor that drifted into the mechanism over the decades.

I just found out my National Science Foundation (NSF) CAREER application was rejected- it was assigned ‘Low Priority’.

Everyone has to deal with rejection- not making a sports team, college applications, a date for prom, job applications, etc. So it is with scientific research- and most people are unaware of the amount of rejection a successful researcher must deal with.

There are two basic elements to having a scientific career: publishing papers in peer-reviewed journals and obtaining funding to pay for the time/materials needed to obtain the results which are then published in peer-reviewed journals. Both of these components involve a lot of rejection- rejection by your peers. ‘Peers’ in the sense that they are researchers- they are anonymous, and I have no idea who reviews my papers or grant applications.

Dealing constructively with rejection is an essential part of being a scientist, and yet is rarely discussed. After all, every journal article you read is a successful endpoint- you never see rejected papers. And people don’t really like to discuss their own failures. I’ve seen what happens when a scientist can’t deal with rejection, and it’s not pretty. Some people start complaining about how the process is rotten with political back-room dealings, some people start to complain that nobody understands their work, some people just give up. I’m not going to deny that there is some social element to getting papers accepted and applications funded, but in my experience, reviewers are honest and try to be constructive, rather than adversarial. At least, the good reviewers are.

Most scientists have been “top 10%-ers” their whole life- in order to get into a competitive college, you need to be in the top 10% of applications. In order to get into a competitive graduate school, you need to be in the top 10% of applications. In order to get a research-type job or appointment, you need to be in the top 10% of applications. This is very stressful- especially since you are competing against a smaller and smaller population of peers, each of whom have also been in the top 10% their whole lives- and the stakes get higher and higher, since with each step along the career path there are fewer alternative options. People start to behave badly.

So, after 30 years of getting rejected from girls, colleges, grad schools, jobs, and more jobs, I arrive here- a tenure-track academic appointment. I am fully aware of the rarified company I am in, and am grateful for the opportunity. In a lot of ways, it’s not much different from getting drafted onto a professional sports team, signing a major record deal, getting a book deal, or any other objective mark of professional success. Believe me, I am acutely aware of all my classmates and colleagues that didn’t make it this far.

So now comes “securing research funding”. In order to be successful in academic research, I must obtain research funding from one of the major agencies: NSF, National Institutes of Health, NASA, Department of Energy, etc. There’s a lot of smaller agencies, foundations, state-level agencies, etc that provide research funding as well, mostly for new faculty- and I am grateful for their past support- but I can’t make a career off of those agencies. The success rate for the major grants is, as you can guess, about 10%. Rumor is, next year NIH is going to be at 5%.

Think about it- after 30+ years of striving and competing to beat out 90% of my peers, again and again, here I am again, tossed into the pool. Only now *everyone in the pool* has been in the top 10% of their peers for 30+ years. This is like making it to the Pro Bowl in professional football, or the All-Star game in baseball. Except, if I don’t get a grant within the next 5 years, I most likely won’t get tenure, which means I lose my job (most people don’t realize that getting rejected for tenure is the same as getting fired). Again, this is a lot of stress- unless I make it to the Pro Bowl, get a top-10 record, or something similar during the next 5 years, I’m out. This continued level of stress makes some people behave badly.

Now, this is not the first rejected application I’ve had. I’ve applied to NIH twice before, the first time the application was ‘triaged’, and the second time it got scored. This NSF application was ranked ‘Low Priority’, which is equivalent to getting a score- it was not give a ‘Not Competitive’ rank. It’s important to *read* the reviewer comments.

My first NIH proposal (two years ago), was ‘triaged’- it was judged to be in the bottom 50% of proposals and not scored or discussed during the review session. But, the reviewer comments had a *lot* of helpful information- what made sense, what was weak, etc. So, I gave myself permission to drink the pain away for a day or so, then sat down and carefully read the reviewer comments. I re-wrote my application addressing (I thought) all of the comments, resulting in a stronger proposal. And the next round, it indeed was a stronger proposal- I got a score. But the reviewer comments were *terrible*- there was nothing I could do to address them. The comments were essentially “We don’t think you can do the work you say you can do. Even if you are able do the work you say you can do, we don’t think you will get any results worth publishing. Even if you get results and publish them, nobody will care about the papers.” *That* hurt.

So, my NSF proposal was not “Non Competitive”, and the reviewer comments are helpful- nobody said my idea is worthless, but that my proposal was ‘immature’, and there are gaps in the logic. That’s something I can work with. I’ll resubmit next year, and I have a total of three chances to get this particular award (NSF CAREER)

One final comment, since this post is starting to ramble- I am *extremely lucky*. Many of my peers- new/new-ish faculty- are at institutions that require ‘salary recovery’. That is, in order to get paid, they have to get grants. I am lucky in that even though I have been (yet again) rejected, I can still put food on the table.

We had to thaw a new batch of cells; the cultures we were using had lost their ENaC activity. Why this happens is unclear; qualitiatively, ‘bad cells’ grow faster than good ones and eventually overrun the culture. Our previous group at CWRU has spent (and is still spending) time manipulating the culture media to reproducibly abolish and regain ENaC function. So far, nothing we have done can restore ENaC from cells that have lost the activity. It is not clear what the origin of the problem is, and since trying to figure it out is a very time-consuming distraction, it’s a lot easier to simply thaw a new batch of cells. In any case, we have a new batch thawed and growing, and simply from the morphology we are hopeful that we will have a strong ENaC signal. At least we checked before using all those filters….

A long time ago, when the Earth was young, people would record sounds by scratching a sharp object across a soft piece of plastic (a ‘record’). The groove in the plastic was then tracked by another sharp object (a ‘needle’), and the movement of the needle was converted back into sound. By this mechanism, people could record music, spoken words, or just the environment around them.

Nowadays, we record sound digitally on highly polished discs. Those are boring to look at. Here’s a record:

A vertebrae from a fish, found one day on the beach. Again, good texture- almost architectural.

Some sort of rock; possibly a leftover from a local steelmill or a volcanic stone. Either way, lots of good texture.