The Junction Potential

Guest blogging over a Scientopia

2011-06-06T11:53:00.002-04:00

I'll be spending the next two weeks blogging at the Guest Blogge at Scientopia. Here.

I love it, just love it!

2011-04-22T15:55:00.000-04:00

Doesn't matter how long I've been doing it, I love being a rig jockey.

LET'S GO YANKEES!!!!!

2011-04-08T08:48:00.002-04:00

Here we go Yankees, here we go!

Beat those goddamn mouthbreathers! WOOHOO!

Some things shouldn't go together

2011-03-03T14:08:00.002-05:00

Like ball-peen hammers, screwdrivers, and microscopes.

The first two would be much better served striking the head of whatever ingrate spilled solution all over the scope and then DIDN'T WIPE IT UP.

How do I measure the liquid junction potential?

2010-10-27T15:30:00.001-04:00

And so it emerges from the depths.....

For years innocent readers thought they had escaped...

A horror so horrible it inspires screams...of horror

It is...the...long awaited post on how to measure a junction potential!!

It's clear from the search terms that bring people here, plenty of folks are curious about this topic. The "What is a Liquid Junction Potentia l" post is one of the most read. So allow me to finally follow up with how to actually measure it. Although there are the standard descriptions about junction potentials in various texts and bibles of the field, a step by step 'how-to' is lacking. Seeing as I bridge these two in real life lab,why not here?

Ok, you have some internal solutions, and you want to report the correct voltages in your paper.

You've got to account for the junction potential between the internal solution and the bath solution present when you first stick in the pipette. Now, you can calculate it if you want; there's a program built into Clampex. But, are you sure that the constants are correct for what's in your solution, especially if it has something weird in it? TEA-methanesulfonate for example. Or NMDG-aspartate - a killer internal for recording sodium current by the way. Are you even sure you made the solution correctly?

It's easy, so measure it!

When I measure junction potentials, I follow the advice of my old granpappy, as discussed in E. Neher, Methods Enzymol. 1992;207:123-31.

Here's what you want to do:
1) Get your stuff together: battery powered chlorider (don't tell me you're using bleach - GAH!!), silver wire, 3 M KCl, 5+ mL of each of the internal solutions, plus a few mL of the typical bath solution, a few patch pipettes.

2) Make a 'flowing KCl' bridge, by taking a patch pipette, breaking off most of the tip, and filling it with 3 M KCl. Chloride a silver wire and use this as the bath ground. The high concentration of KCl, and the similar mobility of K+ and Cl- will help keep the junction potential at this electrode constant, even as the bath solutions changes. I fashioned a little jig to hold the bath pipette (on left below, a piece of plexiglass on a piece of white teflon).

3) Rechloride your silver wire on the headstage, fill a normal resistance patch pipette with one of the solutions. If you're measuring only a single internal/bath pair, then you can put the internal in the pipette. But since setting this up is somewhat annoying, I often measure multiple internals relative to the same bath solution. In that case, I put the bath solution in the pipette.
4) Whatever solution you put in the pipette, add it to the bath.

5) Put your amplifier in current clamp mode (slow versus fast doesn't matter), set the 'meter' to 'Vm', make sure that there's no external command signal coming into the amplifier.

6) lower pipette into solution.

7) Use the "pipette offset" potentiometer until the meter reads zero mV. Wait a minute or so; if the voltage drifts by more than a few tenths of a mV, then you might need to rechloride the wires.

8) Completely exchange the bath solution with the solution to be measured.

9) Read the meter, which shows the junction potential.

10) Replace the bath with the same solution as in the pipette, check that Vm is back close to zero. After that you can measure any other solutions.

11) Now, to get the total transmembrane voltage in your experiments, you have to add your command voltage (or recorded in the case of a current clamp expt) to the measured junction potential. NOTE: If you switched the bath and pipette locations, then you MUST reverse the polarity. So, in the 8.2 mV above, that's actually a junction potential of -8.2, and is added to the command (e.g., a step from -80 to 0 in Clampex becomes -88 to -8 mV). If you're an anal retentive scientist *whistles innocently*, then you already account for the junction potential in your voltage protocols, resulting in nice round numbers.

There you go, and hope that helps. Questions? Let em rip in the comments.

Damn I love being a scientist!

2010-10-01T11:40:00.001-04:00

Even though most times it's difficult, experiments don't cooperate (cells, I'm looking at you), the future isn't certain, there's NOTHING ELSE IN THE WORLD I would do rather than be a scientist. I love it.

I also love the actual doing of the experiments. There are many postdocs out there who are counting the days until they can stop doing experiments (well, no one forced you to be a Western jockey), and let other people do it. Not me. I get an inordinate amount of satisfaction from craft of experiments.

So, off to patch clamping. The soundtrack to Conan The Barbarian is blasting. We'll see if the Wheel of Pain has me or the cells as its subject.

Sometimes being a science dad...

2010-09-22T14:55:00.003-04:00

means leaving your experiments early because your son has been having lots of pee pee accidents, so they're worried about UTIs, and your daughter is coughing up a lung, so might have a pneumonia.

*sigh*

At least the cells weren't great, cause it's easier to leave them. Anyways, the kids need their daddy!

Falling to Autumn

2010-09-21T11:00:00.000-04:00

Not too much blogging going on obviously. Things aren't bad, just kinda meh. Why? Let us count the ways:

1) Return of illin'. No, I don't mean harkening back to early hip hop, I'm talking viruses. Day care center strength viruses. Day cares where the vast majority of parents are health care workers, shipping their gunk into school, letting it percolate among the young'uns, whereupon it descends upon fresh victims. I've already had one GI bug (seriously, WTF is that? They never tell you that before you have kids), and we're all getting over a head cold. Luckily though, the little girl fought it off well, didn't progress to an ear infection. *knocks on wood*

*knocks on formica*

*knocks on cinderblocks*

2) Watching young scientists get chewed up and spit out by their so called mentors. I've been in this business long enough to see some ugly stuff, and I realize that's the way of the world. But why does it seem to happen to women more than men? Maybe I shouldn't let it drag on me. What's the phrase? "Not a fucking Care Bears tea party?" There, now I feel better.

3) I have to sit through 8 one hour ethics training sessions, to fulfill some new NIH requirement. This is a total waste. No one in their right mind believes this will really change behavior, do they? It's just window dressing. I have a feeling I'm gonna be a pain in the rear in this class.

4) The filament in the pipette puller just broke, so now I get to make a new program. *sigh*

Friday Morning Quick Hits

2010-08-27T10:20:00.004-04:00

(Ed. - Sorry about the accidental posting clogging up your RSS tubes)

I am about to start patching some cells this morning. The cells have been a tad obstreperous and ornery these days. I want to warn them though, this crap's gotta stop. So here's your heads up you little buggers:
Figure 1: YOU TELL I'M COMING!!! AND PIPETTES WITH VARIOUS AND SUNDRY INTERNAL CONSTITUENTS ARE COMING WITH ME!!! PVSINCses ARE COMIN WITH ME!!!

In other news, DrugMonkey is highlighting an online comment on a recent Nature paper that point to possible GlamourMagz shenanigans: did a Nature editor string along one group working to refute a recent paper, only to publish a second group's similar work (thus scooping the first group)? And was this Nature editor friends with the 2nd group? Check it out.

Lastly, your Science Soundtrack for the week:

Yes, I just compared science to S&M. Dog upon a leash indeed.

Friday Morning Science Soundtrack

2010-08-20T09:30:00.001-04:00

To coincide with Genomic Repairman's daily music postings, and the awesome grad school blog carnival Samia is hosting over at 49 Percent, I present my own top pick on my personal Science Soundtrack. Though it doesn't actually convey my grad school experience (which was on the whole quite good), it sure nails the post-doc.

Here it is, arguably the greatest metal song ever:

MASTER OF PUPPETS - METALLICA

A perfect meditation on the at times abusive relationship I have with Science.

Master of puppets I'm pulling your strings

Twisting your mind and smashing your dreams

Blinded by me, you can't see a thing

Just call my name, 'cause I'll hear you scream

Master

Master

Just call my name, 'cause I'll hear you scream

Master

Master

Master, master, where's the dreams that I've been after?

Master, master, you promised only lies

Laughter, laughter, all I hear or see is laughter

Laughter, laughter, laughing at my cries

Hell is worth all that, natural habitat

Just a rhyme without a reason

Neverending maze, drift on numbered days

Now your life is out of season

My fellow masochists are invited to contribute their own picks for the Science Soundtrack.

Science Dads Reporting for Duty!

2010-08-06T14:15:00.002-04:00

ScientistMother's recent post about a new article in Science Careers (Scientist Dads Step Up by Vijaysree Venkatraman), was welcome, extending the Work-life balance theme that the bloggers at LabSpaces have been exploring recently.

Let me first make a big fat disclaimer: I don't know anything about work-life balance, because mine has been broken ever since the second baby came into our lives (hey, who knew a 4 1/2 lb preemie could bust that up?). I ain't no role model, as I'm far from doing either the work thing well, or the parent thing well. In fact, if I had to say which I was better at, right now it'd be the parent thing.

Figure 1: The Blair spawn frolick. I'm not in the picture cause Mom had to work on both weekend days. We all survived, the house survived, and I think I even got some laundry done. Can't remember if it was folded though.

Normally I don't think of blogging about my role as a parent. As most parents will tell you, parenting is by and large boring and repetitive tasks, punctuated by both incredibly heart warming and incredibly terrifying moments. So who cares when I have to stay home with a sick kid? Or that I made dinner last night - as I have just about every night for the past 11 years of our marriage? Or when night terrors in a 4 1/2 year old return us to the sleepwalking zombies of the infant stage? Or that I left the lab early to go to a parent-teacher conference at daycare? I already lived it, what's the point to discussing it further? Plus, god forbid it be seen as cookie-begging.

Well, maybe it isn't obvious that a lot of science dads are doing the hard grunt work of parenting. Maybe because there just aren't actually do do it. Or maybe those who do feel they need to hide or diminish it, for fear of not being taken seriously. In that case, having science dads talk about their involvement would help make it more normal.

And reading between the lines of the Science Careers article suggest we need to go even farther, as these quote suggest:

"...his lawyer wife, who works part time..."

"Currently, his wife stays home to care for their two young children -- "

"But women avail themselves of those [parental-leave] policies more often than men do because men fear they may not be regarded as serious, competitive scientists if they take parental leave..."

[now, each couple makes the decisions that are best for them. I get that. But the best we got from the men for staying away from work was Chad Nusbaum and his two months. Which is definitely great. Still, can't we do more? Shouldn't we?].

And some other quotes:

"Maybe pick two hours each day on Saturday and Sunday” to balance the needs of science and home life." (F*** you dude).

"Maybe you should have married a more supportive wife" (one male postdoc to another regarding long hours spent in the lab)

---

So, should I do more of daddy blogging? Like I said, I'm not a role model for someone doing well at parenthood and work. I wouldn't call myself a successful scientist; I'm just kinda getting by as well as I can (though things are improving). So in that case, maybe it's worse to do more daddy blogging?

Final note: we're on vacation next week, having family time on the beach. So whoever out there is reading (not that any of you lurkers would step up and respond to this - naughty naughty), no posts.

Team Fox or Team Hedgehog?

2010-08-05T14:00:00.001-04:00

Team Hedgehog, all the way!

In case you haven't been following, Notorious Ph.D. posted about the differences in academic approaches between “foxes” and “hedgehogs”:

"The fox knows many tricks; the hedgehog knows only one, but he does it well."

I’ll admit it, I am and have always been, a science hedgehog. There’s nothing like a nice 10+ figure paper, replete with detailed, technically excellent experiments, explicit consideration of other explanations (negative results, and their controls go here) to get me all hot and bothered. It’s what attracts me, what I find compelling science, and after enough time, I’ve realized that it’s not something I can easily change about myself (part of Notorious’s post concerns exactly that: changing from a hedgehog into a fox, and also how other scholars respond).

And yet, I realize the limitations of such a hedgehogian approach. Sometimes, a mix of approaches is required to get an answer; hedgehogs might miss this. Sometimes, you get so deep into something that you lose perspective, seeing only the trees, and not the forest. I get that. Still, there are ways as a hedgehog to evolve without completely changing species. You can be a serial hedgehog, going deep into different topics over time (I’d put my thesis advisor in this category). Or, you could be a topic hedgehog: sticking to one topic, going very deep into it, but bringing in other techniques as needed. I’d put the guy I started grad school with in that group.

But in all the discussion on this, which has largely been pro-fox, there hasn’t been much focus on what the limitations of the fox approach is. Sure, the best foxes are out there seeding fields with new approaches, new techniques, and both answering old questions while raising new ones.
There’s another species of fox too:

We all know them. Shitty experimentalists who flit from project to project, or people with a new fancy trick that they get the same answers people in the field had already gotten (BUT LOOK, IT’S PRETTIER!). Or they ignore the previous results that their "great new technique" doesn't replicate (probably because they don't really understand the earlier results, as they never engaged them seriously).

True, there’s fewer of these kind of foxes around for long, being selected against over time. In this vein, the idea/suggestion that younger scholars must start out as hedgehogs has a lot of merit. But I've seen young foxes; it often ain't pretty.

In the end, instead of pigeonholing hedgehogs as boring old, narrow minded, one trick ponies, and foxes and shallow, incompetent, jacks of all trades, I’d rather people agree that, when well done, BOTH approaches have their merit, and that it’s important to maintain a healthy equilibrium between the two.

I am the Norge Repairman of the primary literature

2010-08-02T15:45:00.000-04:00

In one of those strange coincidences of the blogosphere, Chad (at Uncertain Principles) and Janet (at Adventures in Science - now in her new digs are Scientopia) are discussing the role of the primary literature in the sciences, at exactly the same time as I was plumbing the depths of the primary literature.

See, for the past few weeks I myself have been conducting an extensive expedition through the literature on the M current. M current stands for muscarinic current, which is a potassium current in various neurons that is closed by muscarinic agonists (among others). This reduction leads to enhanced neuronal excitability and more action potentials. The current has been most widely studied in sympathetic neurons, which do something to pumps or plumbing or something. Go ask her.

This sort of detailed review is something I’ve been meaning to do for some time, but never forced myself to start. But the life-work balance has been recalibrated recently (hence the increased posting here - more on that later?), so I’ve finally begun. I’ve been tracing back through the literature and cited references, checking reviews, and also reading what I can find about the scientists who contributed to the field. I find this a great way to engage in the literature, because tracing the development of the ideas helps .e put them in a context that I find much easier to remember. I’d hazard a guess that this would be a lot more useful to undergraduates engaged in research, than simply throwing the “primary source” of a bunch of ganglia at them while telling them to “do research.”

I find the M current story compelling for a couple reasons. The first relates to why studying the primary literature can be an important part of doing science. The excitation resulting from muscarinic stimulation was obvserved as far back as the early 1950s, yet it wasn’t until the mid 2000s that a pretty complete picture of the entire process, including receptor proteins, ion channels, signalling molecules, was developed. And in that time, as you might imagine, there were a lot of missteps, and numerous errors. That lesson, that wrong things get published all the time, is a crucial lesson. Another lesson is that science doesn’t develop as a neat and tidy, linear march to more and more understanding. Both of these are rarely discussed in science textbooks. he only counterexamples I can come up with are Newtonian versus quantum mechanics, and Lamarck’s theory of evolution). Most of the rest of science in textbooks is so boring. Message to undergrads: Science can be a whole lot more fun than that.

The second reason is that the 55 odd year trip from initial observation to final signalling molecules gives me hope on my own research topic. In my day job I’m studying how G protein coupled receptors activate a particular transient receptor potential (TRP) channel, TRPC5. But it’s been a bear, because we’ve exhausted the usual suspects, and haven’t yet nailed down the culprit. (Also, the channel is just a pain in the f***ing ass, clearly being a devotee of Marquis de Sade.) In fact, it’s entirely possible that we’re on the wrong path entirely (I said “possible”. Not “likely”). Still, seeing as this channel was only cloned in 1996, and “real” recordings of its activity date from 1999-2000, I figure we still have some time to go before making a run at the title of “Longest duration from ion channel to signalling pathway elucidation.”

I plan to do some blogging on the seminal papers of the field, as well as the its overall development.

Good olden tyme science (now with Squid Axon videos!)

2010-07-29T14:30:00.001-04:00

Isis posted an awesome video of physiologist John Severinghaus discussing his work on altitude and...um...physiology, while working on White Mountain Research Station. Very interesting, and from this neurogeek's perspective, a part of physiology that I know little about.

It got me thinking about the great old experiments in my own subfield of ion channels and electrical excitability. I'm a big fan of going back and actually, you know, reading the foundational literature in the field. That's just me, I don't expect everyone to love it, but I always wonder at how clearly those greats viewed things, and how much their work shapes the later development of the field (especially with regards to what questions are considered important).

For electrophysiology, this leads to One Prep, One Prep to Rule Them All:

THE SQUID GIANT AXON!!!!!!!!1!!ELEVENTY!

As most biologists likely learned at some point in school, the squid giant axon provided the system that Alan Hodgkin and Andrew Huxley used to analyze the basis of the action potential. Nowadays though, I'd gather there aren't many electrophysiologists who have actually seen the axon or it's beautiful action potential in real life. I know I haven't.

Luckily, we have our own kick ass old science videos. Back in the 1970s, J.B. Gilpin-Brown at the Marine Biological Laboratory in Plymouth, England, filmed a movie called "The Squid and its Giant Nerve Fiber". Now, the entire work has sadly been lost, but there are some parts which have been saved. These videos are available at the Bio 300 course site taught at Smith College, and they include J.Z. Young dissecting out the giant nerve (which he was the first to describe). If you're interested in this kind of stuff, I highly recommend you go check them out (Quicktime needed).

My favorite video is the one aboutvoltage clamping the squid axon. Here are some stills I captured from it:

Figure 1:The squid axon action potential. A thing of beauty, no doubt. Complete with hot oscilloscope action (yeah, that ain't digital!). Note the afterhyperpolarization.

Figure 2: Here, Alan Hodgkin, Nobel Laureate, prepares to ACTUALLY DO AN EXPERIMENT ZOMG!!! He's picking up the axon and getting ready to insert the electrode. I know, sorry, it's an old white d00de, wearing a vest and tie ferchrissakes. But I'll admit that I love his papers.

Figure 3: A family of voltage step currents, showing the early inward sodium current followed by the delayed outward potassium currents (responsible for the membrane depolarization and repolarization, respectively). IT'S EXACTLY LIKE THE DAMNED TEXTBOOKS! Hell, I think it might be the textbook figure. Note the slight deviation in the voltage clamp (pesky series resistance; now that's a post for another day), and the potassium tail currents.

Phew, ok, sorry to get all hot and bothered. Beautiful currents will do that to me. Now I need to get to my own electrophysiology. But these are awesome. Anybody got any more old science videos to share? I love this stuff.

Belatedly, and memely, yours

2010-07-29T10:15:00.001-04:00

Earlier this month the "Who are you, what are you doing and why do you keep looking at me!!??!" meme came back with a vengeance worse than the West Nile virus fears in Eastern Massachusetts. I saw it on Drugmonkey, wherein I cringed at my old age.

Two years ago, Ed Yong at his Not Exactly Rocket Science blog (currently living here) posted this question to his readers, asking them why they come to the blog. From there it spread to various other science blogs.

Since my own return to blogging, I thought I'd ask my readers out there why they follow these ramblings, and what brings them here. What posts do you find most interesting. I'm especially interested in hearing from any lurkers out there. Besides, DM tagged people, and who am I to ignore that?

It starts early

2010-07-28T16:10:00.001-04:00

The Patriarchy that is.

The other day my 4 1/2 year old son told his mother the following:

boy: "But you can't be a doctor, you're a girl, and girls aren't doctors. They're nurses. Only boys can be doctors."

Which is of course odd, because not only is his mother very much a doctor, but so are the vast majority of mothers of the kids we hang out with (as well as a large majority of the mothers at his daycare). And he had no problem saying that Daddy is a scientist, and "does science."

It's also a big odd, because when my wife was admitted to the hospital before our second kid arrived, he referred to all the nurses and doctors as "doctors" - male or female. Even though he knew what a nurse was, as his aunt is one.

So what was it that turned the tide, and sent him to the DarkPatriarchy side?

A buncha stupid flashcards at school that show a doctor as a man, and a nurse as a woman. WTF?!?

Of course his parents reacted in the way all good generally socially progressive types would: His mother gave the daycare folks a stern talking to, while his father beat him.

Case closed!

Seriously though, how much of this can we counteract in his little brain? We're just going to have to teach him to see it as well.

(Disclaimer - if you need a disclaimer to inform you which part of this post not to take literally, you really oughta move along elsewhere.)

juniorprof's #painresearchmatters campaign

2010-07-27T13:30:00.001-04:00

In case any of you readers out there missed juniorprof's roaring back into the science blogosphere, I thought I'd take a moment to highlight his campaign to improve the awareness of pain and pain research, in all its facets, from the toll it takes on those who suffer from it, to current and new therapies, to new basic science. If you have a story to add to the discussion, from whatever perspective, head over to his blog to contribute. Or check out his Twitter feed if you're into that sorta thing.

From a neuroscience standpoint, I can attest to the fact that although pain is an incredibly interesting topic, it isn't up there front and center with the Big Questions of Neuroscience. Off the top of your head, how many Nobel prizes have been awarded for pain related research? I got nothing (OTOH, there's a number of ion channel and synapse related prizes I can name). During out intro to neuroscience course in grad school, I think we had one, count 'em ONE, guest lecture about pain. Try and guess how many we had about synapses, or the visual cortex? Nothing against those systems; I love them too, and some of my best friends are synaptic physiologists. It just serves to illuminate the priorities of the field.

Come to think of it, this is reflected in my own bias as well. See, during grad school I did research on nociceptors, those ornery little neurons that convey signals about injury to the central nervous system. And yet, I never did call myself a "pain researcher," nor do I know think back on that as "pain research." Why is that?

I'll admit that some of that it to prevent being labeled as "too applied" or "too disease oriented" in my research question. I liked to believe my research had broader applicability to questions of excitability and action potential electrogenesis, so I shied away from it. Now that I think about it, that personal bias is counterproductive when it extends throughout the community. I'd hazard a guess that you probably know the feeling, that applied research is somehow lesser, or done by "those clinical people (and we all know how good they are, knowwhatImeannudgenudge, aren't we great, high fives) leads to a situation like juniorprof tweeted yesterday:

"Pain #1 reason people seek medical attention but pain rsrch less than 1% of NIH budget"
(reference for that here)

That's just crazy. Crazy crazy crazy. It makes me regret how I characterized both my research and myself as a scientist.

So I'll say it loud, and say it proud, I was, and still am (for about ~35% of my time depending on which project I'm currently focusing on and don't even get me started about that last grad school paper but don't forget I had two kids so cut me some slack) a PAIN RESEARCHER!

I think in the near future I'll write up a few posts on nociceptor excitability and ion channels. Thanks for the inspiration juniorprof!

You know what else sucks?

2010-07-23T12:29:00.002-04:00

Blogger.

But I'm guessing all you on Wordpress already know that.

Somehow the block quotes in the previous post are screwing up the text color. Any ideas?

Citation Classics -

2010-07-23T12:15:00.006-04:00

Bill Hooker over at the LifeScientists feed at FriendFeed posted a link to a collection of “Citation Classic” articles, which were short reflections written by authors years after publishing a paper that were highly cited. Many of these are available for downloads as pdfs, and I find them endlessly fascinating. Sure, many of the highly cited papers are reviews, and reflections on “What I did this summer - Sat in my office and wrote a review that my secretary typed up” aren’t terribly interesting. But by and large, those about experimental papers are cool.

Sometimes these reflections really bring home how much the practice of science has changed over time. Bernhard Frankenhauser describes his paper with Alan Hodgkin on the effect of calcium on squid axon excitability (i.e., surface charge screening effects):

“The exciting [Ed. Wait, Bernie, you forgot to tell us whether that was an unintended pun or not!] and exhausting three-month period of experimental work was followed by two years of struggle with the analysis of the measurements and with the manuscript.” [EMPHASIS ADDED]

Not too much worrying about getting scooped I see. Seriously though, how the hell did this work? I always find that halfway through the analysis and initial drafts, I need to go back and do a few more experiments, either because the initial ones weren’t quite good enough (“crap, we really needed to wait 3 minutes after agonist removal to have full recovery, not the 2.5 we used”), or to follow up and extend the observations.

But they also show that somethings haven’t changed: And that means griping about Nature editors. As John Foreman puts it (writing about his paper with Mongar and Gomperts on calcium and secretion):

“Our experiments were written up and sent to Nature. The referees’ reports were both favourable and enthusiastic, but the editorial staff of Nature was not quite so keen. It took quite a lot of pushing, as I recall, to convince them to publish the paper. In the end, of course, the relented and now, with the hindsight of the Science Citation Index, I guess they are content that we fought for what we considered to be the right place to publish this manuscript.”

HAHAHAHA, take that you bastards! Are you happy with the 550 citations you got in the 14 years since we published what you thought was boring crap? How do you like your impact factor now, eh? (Foreman wrote the above in 1987; Web of Science presently reports 615 cites).

So go check em out, and lemme hear what your favorites are.
For the electrophysiology/excitability geeks out there, here’s a few worth your time::

-Hodgkin and Huxley on their 1952 paper presenting the model of action potential. I’ve cited this, have you?
-Eccles on “how my book that was cited on 9 pages of some recent other book was published right in time for me to get my Nobel”
-Toshio Narahashi on “how I brought a vial of TTX into the US and boy I’m glad there wasn’t a TSA back then”
-Denis Noble and Dick Tsien’s on cardiac pacemaker currents. (this one’s interesting because they themselves called the current a K+ current, though they were upfront in saying the reversal potential was actually off for a strongly K+ selective pore. As we now know, HCN channels are permeable to both K+ and Na+. See, sometimes it’s ok to report observations that you’re not quite sure what to do with. Somebody else will come up with an answer.

Calcium imaging sucks...

2010-07-22T15:30:00.001-04:00

...unless you’re interested in calcium. If you’re using it as a proxy for channel activation then it sucks.

There’s a tendency among those of us who study calcium permeable channels to use fluorescence imaging of Ca sensitive dyes as a way to assess channel activity. And sure, the degree of channel activation will determine the resulting fluorescence signal, and generally speaking more activation will lead to more signal. Plus it’s just easy to do: in a day you can try a huge range of manipulations, you’ll get hundreds of cells as a result (making those statistics sure seem impressively significant). Compare that with a good day of patch clamp where 10s of cells is a GREAT day. I get it. I’ve been tempted by that dark side as well.

Still, frankly, it sucks. There are so many uncontrolled and/or untested variables present in your typical Ca imaging run that if you’re making dose-response curves, or inhibition curves, or whatever, then really, you’re deluding yourself if you think you’re only looking at the channel. And don’t even get me started on those people who treat a given delta ratio as equivalent over the whole range of ratios. GRRR.

In that case, it’s time to suck it up and do the electrophysiology. Yeah, it’s hard, it’s slow, blah blah waa waa whatever. If you want to characterize a channel, do electrophysiology. If you want to see how that channel affects intracellular [Ca2+], do imaging. But then really, WTF are you doing overexpressing that channel in some poor cell line, sitting in the incubator, just minding it’s own business?

Did I really just do that?

2010-07-21T14:45:00.000-04:00

I put a happy face emoticon in the comment line after stopping an acquisition run.

WTF?

Of course, this was a cell that I left in the middle to go to CVS and pick up some stuff. It was still happy when I got back, holding current not more than 1 pA different. By that point though, I start to get the willies using any results. Too long whole-cell and weird stuff happens.

Come to think of it though, I bet if you trawled through my lab notebook, you'd find some "WTF" in there as well. Probably some much worse language to.

So, how many of you out there do the same?

Shallow thoughts

2010-02-05T09:15:00.000-05:00

Following the latest ScienceBlogs-NatureNetwork steel cage match (start here and follow the links), in my head the Nature Network theme song is Sarah Smile, whereas ScienceBlogs's is Rock and Roll High School.

Strike that....substitute silence.

2009-11-19T13:15:00.000-05:00

Dear all,

I have made a mistake, and perhaps led you all astray.

It is true that in the Axopatch, the signal ground is not connected to the power ground.

But, it turns out that it's very difficult to isolate power ground from signal ground, without essentially breaking every BNC connection between the amplifier and the digitizer. And when I did that, I got a good amount of hum pickup from those now unshielded wires. At times you could find a position where the pickup was minimal, but it wasn't easy. And figure that you've got at least 3 connections at a minimum (signal output, analog input, and gain), that all equals one big pain in the butt.

This advice originated when the digitizers were the old Digidata 1200. That digitizer is specifically designed to isolate the signal ground from the power ground (most important to isolate it from the computer, whose fast switching power supply is a huge noisemaker). That all changed in the 1300 line of Digidatas.

However, it does seem that the simple act of using the grounded to non grounded plug adapter on the amplifier, does dramatically reduce the RMS noise level. Why it exactly does this, when there's still a connection between signal ground and power ground, I am not clear on.

Nevertheless, I am available to come and lay my hands on your setups, to reduce the noise. Cause it seems I'm back to that level of rationality for this whole process.

Gotta bring this up with the big guy soon.

Geek alert

2009-11-18T12:15:00.000-05:00

I might just be in productivity nerd heaven:

Liquid Planner added task timers!

Now I can reach new levels of accuracy in tracking blogly time wasting.

A Tale of Two Grounds

2009-11-17T17:00:00.001-05:00

It was the best of rigs, it was the worst of rigs,
It was the age of 0.07 pA RMS, it was the age of 0.5 pA RMS, ±5 pA p-p at 60 Hz,
It was the epoch of separating signal ground from power ground, it was the epoch of connecting all power grounds to the signal ground,
It was one really annoying run on sentence written by some old white dude, it was a kick ass blog post written by a middle aged white d00d.

There's one thing I've learned here as postdoc that I've actually never seen discussed in other places. When I first heard it, I did a "Watch you talkin' about" head turn, thinking it was crazy.

That thing is, to get really good noise on your patch clamp rig (good meaning low here), you can make 2 grounds. One ground connects everything that is physically close to the headstage. This gets connected to the signal ground plug. The second ground connects everything else. That gets connected to power ground.

Figure 1: Nat's newly refurbished set up (which is tight if I do say so myself). Axopatch 200B and Sutter MP-285. Green As indicate things attached to signal ground. Magenta Bs are connected to power ground.

So what goes on the signal ground?

Microscope
chamber
condenser
bent piece of metal that can be put right in front of headstage/chamber to further shield (not shown)

That all gets connected to the gold pin at the back of the headstage (or equivalently at the signal ground input on the back of the amplifier). Note that you'll need to break the power ground connection (with a 3 to 2 adaptor). Doing this will get you most of the way there.

What goes on power ground?

Faraday cage
air table surface
manipulator

This is connected to power ground (either attach it to an exposed copper pipe or to power ground through the case of the manipulator). Doing this will get you to the super low RMS values specified in teh Axon manual.

Now I no longer fear denoiseing the setup.

The only tricky things I've run into are that most of the BNC inputs on the Digidata are connected to power ground. So usually I have to break the ground connection to connect the gain value output from the amplifier to the digitizer input (I've never had the amplifier signal output to digitizer analog in cause this).

I just turned on my amplifier, and with a pipette holder on, the PATCH mode RMS noise is 0.099, and WHOLE-CELL mode is 0.48. SHU-WEET!

What have I, what have I, what have I done to deserve this?

2009-10-29T12:45:00.000-04:00

When your electrophysiology rig has only a single BNC cable connecting the patch clamp output to the digitizer, you know things aren't good.

Especially when there's still a little 60 Hz ripple visible.

And when you still haven't solved the periodic pipette vibration that makes getting seals hard.

[Then after you write some schlock like this, you worry about what PLS thinks about it.]

In other news, I have discovered a couple things:

When there is 0.5 pA RMS noise on a well shielded headstage, cleaning where the holder attaches can do wonders. Isopropanol + canned air = 0.05 pA RMS.

When ultrasonic cleaners are used correctly, they kick total ass. If you have one, try the glass slide test. HOLYMOLYCOWTHATISCOOLANDSADLYMIGHTBETHEWEEK'SHIGHLIGHT!

InaDWriMo2009 - do it, do it now!

2009-10-28T17:15:00.001-04:00

As if it weren't patently obvious, I'm still swamped under the combination of multiple projects, multiple collaborations, and multiple offspring. I just haven't hit upon a way to incorporate much blogging.

One of the other things languishing is a couple of projects in different stages of writing. One is a manuscript revision that has been in periodic hibernation since I left my thesis lab. (Ok, it is embarrassing to write that. The reasons for such a state might be both understandable and inexcusable, but at this point, who cares? It's time to get it done). This requires a substantial rewrite of the Discussion section, as well as the Introduction. This also requires some time with the literature, which I have been only peripherally following once this project came off the front burner.

Another writing project is a draft of a short manuscript, on some old results that started fast and then got stuck in neutral. While this project isn't completed, I think I know enough of the general story to at least start a draft. Writing that will make it much more obvious what needs to be done in order to publish it.

To help motivate me, I've decided to join up with the InaDWriMo2009 that Dr. Brazen Hussy is hosting. It's derived from a dissertation specific "fork" of the NaNoWriMo, that has been extended to all sorts of academic writing projects.

I figure that combined, the both of these will require something on the order of 5000 words. My goal is to complete them during the month of November. Watch the side bar for progress.

And, who else is in? The motivation is contagious. Sorta like H1N1, but with mental pain rather than physical.

Shallow thoughts

2009-08-31T09:15:00.000-04:00

Sometimes I feel like experiments are performance art with no audience.

Oh my god, I'm so sorry I forgot...

2009-08-06T12:00:00.000-04:00

...our blogoversary.

However, there's no doubt that this is much better than forgetting my wedding anniversary. I suppose, back in mid-June, that I should have connected the sighs of freshly minted M.D.s and Ph.D.s with the start of my blogging. Instead all I could think was, "Why the hell are these people milling around when I'm rushing to pick up my kids at daycare!"

So more than a year has passed, and though I haven't had much time to write a coherent blog post, I do have time for:

Nat's Bullet Points Highlighting the Last Year!

Accomplishments:

Successfully (more or less) integrated a new family member into the finely tuned machine that was Family Blair (HA!). There are posts aplenty conceived to cover this, from the innate differences between kids, to balancing the demands of two kids with work/science. Sadly, balancing the demands of two kids with work/science means writing these posts doesn't happen. Still though, the productivity hit after the second kid was MUCH more minor than after the first.
Finally published a good chunk of my work covering the modulation of a particular TRP channel. This project has been tortuous at times, yet through many difficulties, I stuck with it. The result is somewhat limited in its scope, but the treatment is thorough. Hopefully it will prove useful to those interested.
Started collaborating with another group on a cool new project. Things seem to be progressing nicely, and it has been a lot of fun.
Actually made some progress in finishing up my final paper from...gulp...my thesis work. Or as I like to refer to it, My Own Personal Albatross.
Have the prospect of starting another collaboration, that would help me complete some older preliminary work.
I have totally regained my calcium imaging mojo, after neglecting those long lost 1997-1999 era skills.
Lastly, I finally came to the realization that it's no use to fight against the core of my own personal scientific style. Sure, some parts can (and should) be bent in response to outside considerations. But to fight against the core will lead only to madness.

Failures:

I haven't made sufficient progress on the other side of the story to the TRPC channel regulation. The conceptual framework is basically there, and I've got tons of planned expts, but little time to carry them, or the requisite troubleshooting, out.
I didn't complete the manuscript of My Own Personal Albatross. Really though, I blame the daughter. I thought I had 6 more weeks!
I haven't done enough to move from heterologous to endogenous systems for studying TRP channels (TRPCs in particular). There are a number of reasons this is tricky, but honestly, that potential trickiness has prevented me from really trying. That's got to change.
I definitely haven't been able to get any sort of blogging routine down.

Overall, that's not too bad. Sure, I could always have done a lot more, like learn Esperanto or program my own electrophysiology software in COBOL, but it was a pretty good year.

So what did you accomplish this past year?

Meme-licious

2009-06-01T09:45:00.000-04:00

The always alliterative Ambivalent Academic haz tagged me with the Cover Meme. Though I feel like I might be at the center of the maelstrom, that doesn't mean I have no time for a meme, right?

So, I present to you, the best cover. Ok, not the best, Jimi Hendrix's version of Dylan's "All Along the Watchtower" was taken, as was Johnny Cash's "Hurt." But this certainly is pretty cool. Let's set the scence for when you'd look to fire this up:

You're a parent, you've got a crabby/colicky/ornery child who just won't go to sleep despite drooping eyelids above black circles. Aha, a lullaby, that'll work. Now what to pick?

Need you ask? The answer is obvious: The lullaby renditions of Tool. Because there's nothing else I want my infant going to sleep to besides such sweet compositions as "Opiate" and "Schism." Here's hoping Volume II has Stinkfist. (Actually, I dig Tool, but c'mon.)

As for the worst cover, I have to go with Sixpence None the Richer's version of The La's "There She Goes". Why? Because other than the switch to a female lead vocal, this cover is essentially exactly the same as the original. That's a big fail in my book. Great covers reimagine the original in ways that the composer never saw, adding and extending it. Everytime I hear Sixpence's version I just think, "sheesh, I liked the version in 'So I Married an Axe Murderer' a helluva lot more."

Here it is if you must:

Wordly advices

2009-05-26T16:45:00.000-04:00

If you ever find yourself writing a scientific abstract containing the terms "unitary conceptualization" or "cannot be considered equipotential in either its BLAH BLAH BLAH" please just stop.

Happy Mother's Day!

2009-05-10T09:10:00.000-04:00

HAPPY MOTHER'S DAY to all you moms out there!!!!!1!!1Eleventy!!1!

Here's hoping you get a little extra time for yourselves to relax and enjoy the day. Here in the Blair house we're celebrating with a spinach and pepper frittata, bacon, home fries, and mimosas made with fresh squeezed orange juice. Break out the champagne flutes!!!

Then later we'll feast on the chocolate mousse cake. YUM!

HAPPY ANNIVERSARY WIFE!

2009-05-02T11:15:00.001-04:00

Ten years ago today, my wife and I stood in the same church where her parents were married, where she was baptized and received first communion and was confirmed. We pledged ourselves to one another, and we've survived through residency and fellowship, graduate school, the travails of children. It hasn't always been easy, but there's definitely no other person I'd want to experience these things with.

Here's to the next decade together!

CAN YOU SMELL....WHAT THE ROCK U. PRESS IS COOKING?

2009-04-29T11:30:00.001-04:00

There's a couple of interesting editorials out in from the Rockefeller University Press, which publishes the fine journals Journal of Cell Biology, Journal of Experimental Medicine, and one of my personal favs, Journal of General Physiology.

In the first, the Press's Executive Editor, Mike Rossner, discusses the practice of bundling large numbers of journals by the mega scientific publishers, and the effects on university libraries. Unsurprisingly, the current economic climate is affecting not just newspapers (do you hear that Boston Globe? That...is the sound of inevitability), but will have big impacts on science publishing. And that doesn't even take into account moves towards Open Access. Check it out here.

Here's one very interesting tidbit from the editorial:

"The Rockefeller University library subscribes to bundles ofonline journals from several megapublishers. For one of thebundles, the top 10% of journals garner over 85% of the hitsto the bundle from users at the University. Over 40% of thejournals in the bundle had no hits at all from the Universityin 2008!"

In the second editorial, from the May issue of JGP, Editor Edward Pugh takes on one of my personal hobby horses: Supplementary Data. Now in principle there's nothing wrong with Supplementary data; it's just currently there seem to be few standards about how they should be dealt with, both in review and archiving. Pugh clearly sets out at least JGP's position on them:

"Several pressures now call for a review of policy on SupplementalMaterial. One pressure comes from the growing use of such materialby other journals as an omnibus substitute for publishing scientificmaterial. Increasingly, methods, theory, and even primary resultsare offloaded to supplements. As a community, we need to questionsuch practices, asking whether they are dictated by the goalsof science or by financial expediency, and inquire as to theshort- and long-term consequences of such practices for science."

So go check that out too. Oh, and while you're there, check out a modest little paper by Blair, Kaczmarek and Clapham. All 14 figures of it that is!

Poll crashing vanguard for the science!

2009-04-24T08:23:00.002-04:00

Ok, we all know internet polls are far from scientific, but if nothing else, they give an inkling of the organization behind the alternative positions.

In this case, there's a poll at the LA Times blogs (here), stemming from a recent pro-research rally helpd at UC in support of animal research. The results have tilted towards the anti research poll option, so for any of those folks out there who support the responsible use of animals in research, and realize that there can be little biomedical science without it, go and vote. And tell your labmates, friends, parents and grandparents to do the same.

And if you're interested in the things that impede meaningful debate about animal research, go check out Dr. Free-Ride's recent series on the topic!

Phew, so glad that is over!

2009-04-14T10:15:00.000-04:00

I know there are many of you out there, sitting around, cooling your heels, and waiting with bated breath to learn how to actually measure a junction potential. And that post is coming. It's just not this post.

This post is the final end of a big sigh that wraps up last week's Week of Not Very Much Fun.

-First, I spent the weekend before last worrying about whether I had left my bag (complete with laptop) inside our daycare center or outside in the parking garage. The first being probably ok, the second not so much. It's amazing the complete and utter lack of recollection 5 months without >4 hours of continuous sleep will do to a brain. Luckily, the bag was saved by one of the day care folks. So I didn't loose my 4 year old laptop with its broken hinge, on which I'm writing this very post to you good readers.

-Second, I was all ready to spend last week working on a data presentation for the lab on Thursday (which is fairly involved, given the size of the lab and long stretches of time between turns), as well as a 25 minute talk for the Neurobiology Dept. on Friday. But, fate intervened, as we got our paper finally accepted (good!!), but the editors asked us to turn the final changes around in 2 days (ok, doable, but starting to cut things close).

-The final straw was the girl coming down with an ear infection. She needed a couple days off daycare, which my wife and I split. She improved so quickly after the ped visit, and thank FSM for antibiotics. That basically killed the possibility of the lab data club, but I was able to get the final manuscript changes done and the talk prepared. Of course, with even less sleep than usual. I think this led to one assessment of my talk, which was "Clear, but needed more enthusiasm." Fair enough, but we're almost at the breaking point here people.

Mythbusters!

2009-04-14T10:00:00.003-04:00

No, not those guys on TV, though they do kick ass.

What I'm referring to are some myths we live by in the lab. One of cherished one among some people is that competition inside the lab improves productivity. That's complete bullcrap. Sure, there are lots of PIs whose management styles use it, but it's simply wrong. Apparently Candid Engineer's PI feels this way. Which sucks, even if it is all too common.

Unfortunately, what these jerky PIs ignore is the actual data that suggests that competition within groups hurts overall productivity. Teresa Amabile is a Harvard business school prof who has tracked the daily work of people in high tech, chemical, and consumer products industries, and the results run completely counter to many of the preconceived notions we have about creativity. An article in Fast Company discusses the 6 Myths of Creativity. All of them are good, but here's the money quote for this discussion:

5. Competition Beats Collaboration

There's a widespread belief, particularly in the finance and high-tech industries, that internal competition fosters innovation. In our surveys, we found that creativity takes a hit when people in a work group compete instead of collaborate. The most creative teams are those that have the confidence to share and debate ideas. But when people compete for recognition, they stop sharing information. And that's destructive because nobody in an organization has all of the information required to put all the pieces of the puzzle together.

I wonder how well this observation scales beyond individual lab groups to science as Science. How much competition is good, and when does it start to be detrimental? Certainly the last sentence here can be applied to Science.

Next, Bob Sutton is a Stanford B-school professor, who wrote a book called "The No Asshole Rule" (how great is that? Plus he has a kickass blog, which has been on the Googly Reader for some time). His recent post highlights another group's paper

...using quantitative analysis to uncover patterns across large numbers of studies -- in this case, 72 studies of nearly 5000 groups. The overall findings aren't a surprise, that groups that engage in more information sharing enjoy better performance, cohesion, knowledge integration, and satisfaction with decisions made

Now sure, these aren't academic lab groups, but as all the crankass PIs out there seems to insist on saying, academic science is the real world. So for any of you PI types who buy into this line of fallacious thinking, just stop. You're a scientist, go with the data.

And if not, then do us all a favor and wear a goddamn button that says, "I'm the Michael Vick of pitting my trainees against one another." Then we'll all be fairly forewarned.

What is a junction potential?

2009-04-01T13:30:00.001-04:00

It's clear to me that a number of visitors to this humble blog arrive each day via a Googly search for the term "junction potential." I can only imagine that some must be fellow electrophysiologists, perhaps in their formative larval stages, searching for more information about this important topic. So, as a service to these folks, I thought a post or two about junction potentials, would be in order. First, what is a liquid junction potential? Then, How do you measure and correct for them?

So, what is a liquid junction potential? Sure, maybe you could look in some of the Electrophysiology Bibles. Or maybe you could even hit up an electrochemistry textbook. But it's 2009, and you've got two things on your side: Google, and me. So forget that, and allow me to regale you with the story of the liquid junction potential:

Long ago, in a galaxy far far away, there was a Gedanken experiment...

Figure 1: Set up of the Gedanken. No, it ain't to scale, though aspartate is bigger than potassium. Not shown is the impermeable wall separating the two solutions. Hey, it's my Gedanken thank you very much.

And in this Gedanken experiment there was a pipette filled with your typical pseudo-intracellular solution: You know the drill, high potassium (light blue), low calcium, and an anion species that's usually not chloride. This anion could be something like methanesulfonate, gluconate, or my own personal favorite, aspartate. The main thing to note is that all of these are bigger than chloride, and bigger than potassium. Thus, they have a lower mobility, meaning they don't diffuse as quickly as the accompanying cation.

Now, what happens when we stick this pipette into a bath solution that has your typical extracellular saline, made to mimic extracellular fluid (i.e., mostly sodium chloride)? Well, the chemical gradients favor the pipette constituents diffusing into the bath, and the bath constituents diffusing into the pipette. But remember, the aspartate is big, so it doesn't diffuse as quickly as any of the other ionic species. That slower diffusion of the anion leaves a net negative charge in the pipette. This charge separation across the junction between two solutions is THE LIQUID JUNCTION POTENTIAL!!!11!!!1!

Figure 2*: The Gedaken imposed barrier is removed, and ions are diffusing down their electrochemical gradients. The bigger, slower aspartate can't keep up relative to the smaller, faster potassium, sodium and chlorides. They get left behind in the pipette, generating an excess of negative charge.

Note that a liquid junction potential would also occur if the bath solution has cations and anions with significantly different mobilities. It just turns out that sodium and chloride have pretty similar mobilities, so that their contribution to the liquid junction potential is much smaller. But if you have N-methyl-d-glucamine (NMDG) as the main cation in your pipette solution, you'll have an excess of positive charge in the pipette solution, and a corresponding slightly positive junction potential.

Next up, how to measure the liquid junction potential.

---

*-Note that these figures were created using Inkscape, a very cool and usable opensource vector
graphics drawing program (a la Illustrator). Check it out, download it, play around with it!

Science sometimes makes me feel like...

2009-03-31T09:30:00.002-04:00

Let's just hope I don't die some rock and roll death. You know, the "Nat didn't show up in the lab for the big experiment, we found him having choked on vomit, but we don't know whose vomit it was, cause you can't dust for vomit." It's either that or a bizarre gardening accident, and it is spring time.

(Seriously though, I love science, right beneath the family, but sometimes it's a heartbreaker. Goddamned unrequited love.)

Sometimes, the little things are what keep you going

2009-03-27T10:45:00.002-04:00

When you're having a crazy busy morning, and experiments are going kinda crappy (I'm at the "let's remake the solutions" stage), it can be nice to get a Friday morning email alert to 3 fresh citations to your papers! Sure, it's a little thing, but at this stage I'll take what I can get.

People are out there reading, so there must be people out there who care. Keep 'em coming folks, keep 'em coming!

By the way, what's with variability between the citation search engines? I know this has been covered before somewhere, but really.

Searching on my first paper from grad school, we get:

90 cites in ISI from the J Neurosci site.
93 from ISI itself
98 from Scopus (I got a free preview for reviewing a paper. It's pretty cool, but I haven't used it enough to say much substantive. I do like the display of citations by year, Journal, author).
102 from Google Scholar

Now, so of these I'd cut slack for (e.g., J Neurosci probably only pulls cite numbers from ISI infrequently, and who know how reliable Google Scholar is, but what's the difference between ISI and Scopus? Anyone look deeper into this?

If citations, h-indices and impact factors have traction as important metrics, shouldn't they be, oh I dunno, accurate?

Electrophysiology isn't a technique you add to your CV; it's a state of being!

2009-03-26T11:00:00.001-04:00

Neuropharma's comment on my last post contained something that stuck in the craw of this old electrophysiologist. Some grad student she knew thought he could waltz over and learn some electrophysiology right quick, and include it in his thesis.

Then reality struck this student, rapidly disabusing them of this conceit:
"He was shocked to discover that it would take him such a long time to learn the technique (he's starting from level 0) and said that it seemed so easy when reading it from some published paper!"

Every newb thinks that a technique they haven't mastered is easy, until they actually try it. And in fact, the bare bones mechanics of patching are pretty straightforward. I've taught a lot of novices how to patch, and by and large they can get to the point of gigaohm seals in a week or two (ok, we're talking transfected HEK cells here). Hell, I'm thinking any primate above lemurs could learn to get seals. (Not a bad idea actually; screw those automated patch systems, gimme an army of squirrel monkeys and an old warehouse, and I'll screen your chemical library right quick! It'd be like the nut shelling squirrels in Willy Wonka. And they'd literally be DrugMonkeys! LOLZ.)

But there's a huge distinction between the currents you're recording at that point, and 'good' currents. These first currents are crap, e.g. the leak is terrible, the series resistance is awful, the throughput stinks, the solution applications kill cells or generate huge noise, you've got visible 60 Hz pickup. At best they're barely interpretable. But Electophysiologicus will dole out a decent cell here, a nice recording there. That'll be just enough to keep you coming back for more, and to keep the image of good recordings in your mind's eye.

The transition between the crappy recordings of the apprentice and the regular good recordings of the master takes a long, long time, on the order of a year I'd say.
These are the dark times, where the progress is non-existent, perhaps to a greater extent than an analogous part of the curve for other technical subspecialties. Most electrophysiologists I've talked with had this time in their training, typically falling into the 2nd year of graduate school.

And yet, there's very little useful advice the masters can give their apprentices during this time, other than "keep at it". Sure, there are suggestions to try this, or don't do that. In the end though, everyone just has to put in their time, slowly perfecting each requisite skill, and evolving their own personal technique. It sucks, for sure, but it does end.

It's just not gonna end before your rotation or your last few months before you finish your thesis.

A pictorial presentation of pipette pulling

2009-03-25T16:30:00.000-04:00

In the interests of both responding to Dr. A's request for pipette pulling related pics, and appeasing the apparently still irked electrophysiology gods, I present to you a brief montage of the glorious task of patch pipette fabrication!

First, what the heck are we even doing? Well, we're gonna pull a glass needle, fill it with salt solution, stick it on a plastic holder with a wire inside, maneuver it to a cell, apply a little suction, and let the magic of "seal formation" occur. Next, assuming we're doing whole cell voltage clamp, we break the seal membrane with more suction, gaining control of the voltage across the cells' remaining membrane, while recording the current (also filling the cell with our pipette solution). Sheesh, when you distill it down to two sentences, it pretty much trivializes what I spent years learning and do everyday.

The opening of the pipette tip will be ~1 µm, while the cell is on the order of ~10 µm. Obviously, if the pipette tip is too big, then we'll just suck up the entire cell. Not good. But, as the pipette tip gets smaller, the resistance between the pipette interior and the cell interior gets larger. Also not good. In fact, that causes a whole host of problems that are left as an exercise for the reader to derive (ok, just kidding. There's a series of posts reserved for this, with current working title: "Dr. RseriesLove, or, How I learned to stop worrying and love the fact that my currents are all wrong)

I start by cutting the capillary glass, by scoring it with a diamond pencil and breaking it off to the correct length (so it'll fit in my particular set up, given the headstage position, etc.).

Then I smooth the ends of the capillary glass with a bunsen burner flame, because jagged end (even how it comes from the factory) will scrape off the silver chloride on the wire that transmits the current from the ions in solution to the electrons in the amplifier circuitry (as well as tearing up the O-ring in the headstage holder).

Then we move onto the puller itself. There are many different kinds of pullers, but having been in a number of electrophysiology labs, I would say most people use pullers made by Sutter Instruments. The basic puller operation is to melt the glass capillary while pulling on either end, drawing the ends apart. Now to get a nice wide tip patch pipette, we use computer controlled application of the heat, allowing you to stop the heating a certain time after the capillary begins to pull apart. Over repeated heating/cooling cycles, you can make the perfect pipette.
Here's the puller, a P-97, and if you unscrewed the 5 screws on the font panel, you could peer in and see the brushless super quiet 92 mm fan we installed (way in the back of course, a real pain in arse to reach). The smoked plexiglass cover opens to reveal:

The business end of the puller. The circle thumbscrews clamp down on the ends of the capillary and maintain tension. The capillary feeds through the box filament, which gets hot when the puller is activated (sorry for the flash glare here). When the glass separates, we're left with a pair of pipettes, which we fire polish by bringing them close to a red hot wire (observing under the microscope). Finally, we're ready to patch!

The pipette is filled with intracellular solution, stuck in the polycarbonate holder (which has the silver wire in it), and stuck into the headstage of the amplifier. The suction tube allows you to provide postive pressure while you're approaching the cell, or negative pressure to form the seal and to breakthrough. The cells are sitting in an extracellular-like solution in the chamber, and the pipette approaches under micromanipulator control (here, a piezoelectric based Sutter MP-285), all the while watching through the microscope. In fact this pipette in this picture is making a GOhm seal on a little HEK cell. Of course, when I applied suction to break through, this cell was terribly leaky (again, Electrophysiologicus, patron of patchers, I'm like so over that hubris- could we maybe move on now?).

If you look closely, the tip of the pipette is wrapped with a thin strip of Parafilm. This helps reduce the capacitance of the pipette, but isn't nearly as time consuming or messy as using Sylgard. A requirement for setting the series resistance compensation. All of which are good topics for future posts!

Hope this was at least mildly useful to some people out there, and marginally enjoyable to others. If anything's not clear, just fire up the comments and lemme know.

We got monkeys running all over the house!

2009-03-23T11:00:00.000-04:00

Ok, well not so much running, though those little legs are always moving! There's plenty of room to grow into it, as the young'un is still pretty mini. But she's a happy one, especially while modeling DrugMonkey schwag! So what are you waiting for? Got get yours here. Do it, do it now!

In other news, I turned 35 yesterday. It was a great day (thanks to the wife and family!), but frankly it's a crappy age. First time I actually feel old on my birthday. *sigh*

2 grand? How about 20 bucks?

2009-03-19T12:30:00.000-04:00

Ha!

I've been having a recent bit of difficulty with our pipette pullers in the lab. Well, pulling program parameter searching is no news to any of the l33t electrophysiologists who frequent this blog. We've all been there, and we'll all surely revisit that terrible state of being.

But not too long ago one of the pullers started making a horrible noise when switched on, as the cooling fan must have lost a ball bearing. The company service folks were in the area for the recent Biophysical meeting (how was it Dr. Samways?), and made a swing through the lab. They offered to refurbish the whole thing and replace the fan for $2000. Not a pressing issue, but apparently as the heat builds up inside the puller, it would slowly dim the display, making it hard to edit programs.

Economic times being what they are, we demurred. Which is a good thing, because when we pulled the front panel off that sucker, the fan was just a 92 mm fan like you'd have in your computer. So we got one of those, pulled out the old dead one, and slipped in the new. Voila! And while we were at it, we got rid of the decade plus layer of dust in that thing.

Still though, I miss the old P-84 I used in my thesis lab.

Hubris - and that ain't a circumscision in Whoville

2009-03-10T14:12:00.002-04:00

Alas, I fear I have angered the Gods of Electophysiology with my last post.

For now in their puckish ways, they have sentenced me to several hours fidding with the puller, in a vain sisyphusian search for something resembling a stable program. Or really anything that might give a useable pipette.

I've been burned bad. So what does one do when burned like Icarus in the tale of old?

WHY, IT'S TIME FOR MAIDEN!

(I'm digging the bass in this one!)

And it's back to the puller...

It's a beautiful....pair of sodium currents!

2009-03-10T10:35:00.000-04:00

I was recently looking back over one of my papers from my thesis work, and came across a recording that I frankly find just beautiful. I had it in my mind to post it, and then Dr. J's post about their recent beautiful gel spurred me on to finally do it (another of the benefits of non-pseudonymity):

Figure 1: Sodium currents during action potential waveforms in nociceptive sensory neurons.

Look at that goddamn subtraction! And that outward transient current in TTX-R? Gating. Current. Sure it might be from a 6 year old paper, but it still thrills me a little. Some of this nostalgia might be related to the comparative lack of beautiful TRP channel currents I encounter these days. Oh, for a TTX of TRP channels. Oh, for closing your channels with negative potentials. *sigh*

As I commented over at Dr. J's place, beautiful data don't necessarily equal meaningful data (same with the converse), but I do think there's likely some correlation between the two.

Me, cool? Not hardly!

2009-02-17T13:30:00.000-05:00

Cool is no adjective to apply to me. But thanks for making me feel better.

The thrill of victory...

2009-02-12T10:30:00.000-05:00

On the off chance that any of my miniscule readership does not already follow Ambivalent Academic's blog, you have to go over and check out yesterday's post over there. In it AA discusses the positive aspects of being a basic academic scientist, and I'd hazard a guess that many of us can strongly relate to those feelings. It serves as a welcome counterpoint to all the crappy and ugly aspects of the practice of science, and all the bitching and complaining that goes on in the blogosphere (and in lunchrooms, coffeebreaks, and post seminar chats between scientists in real life). Now, don't get me wrong, discussing all those negative parts are very useful and necessary. But it's also nice to sit back and reflect on the things we love about science. I find it helps stoke my passion for science, which too often nears extinguishment. And I really do love being a scientist.

Physioprof added a great comment as well, about his excitement at an old breakthrough achieved in grad school. You can feel his enthusiasm, even for an event that must be years old by now. And as he says, we're all chasing that feeling. I remember one of my own as well, which I will share. For my first project in grad school I was recording sodium and calcium currents during action potentials in nociceptors. As there's no good blocker for TTX-resistant sodium currents, I settled on using ionic substitution, replacing external sodium with NMDG. That worked well for the subtraction, but I did notice that the resulting sodium current kept increasing even as the voltage approached ENa, which obviously shouldn't happen. I kept that stuck in the craw of my brain, which chewed over it as I proceeded to look at calcium currents in other cells. (Which is how I normally let it happen; given time the craw digests whatever problem is given to it).

I can still remember sitting at my desk, looking over some other experiments, when it hit me. It was obvious that intracellular Na+ and K+ were making outward currents through unblocked TTX-R channels, and these became sizeable at depolarized potentials near the peak of the AP. In retrospect it isn't so surprising. But it wasn't so obvious to me that the outward currents would really be large enough to make a big difference, relative to the large inward currents when external sodium was high. Turns out they were. Very soon after that I figured out a way to correct my previous results, which became a figure on its own in the final paper. All in all a great feeling.

I think we all just hope that our science doles out sufficient number of these moments to keep us from totally giving up in the face of so many difficulties.

Perversity isn't always fun.

2009-02-06T17:30:00.001-05:00

Judging scientist performance by impact factors is like judging CEO performance by short term share prices.

And both produce perverse incentives.

Let me add as a final note, if you scan people's CVs for Cell, Nature, Science papers, then you're judging by impact factor.

First Axiom

2009-02-05T12:30:00.001-05:00

I've been doing lots of thinking about teh Scienz lately, from the little details to the big pictures. (Yeah, ok, so maybe I'm having a scientific midlife crisis. What's it to ya?)

Sure, most of these thoughts are neither particularly well considered nor highly developed. Indeed, they're probably not very insightful either. But the best way of improving upon them is to just start writing about them, and hopefully get feedback from other people (especially fellow working scientists). One benefit of this approach is that I'm not so wedded to my thoughts that there's a huge congitive barrier to overcome if they need altering.

With this entire morass in my head, regardless of the current state of each, I've begun by thinking explicitly about the "why?" question*. Why do we do what we're doing? What's the ultimate purpose of it? In my mind, before we can judge whether a particular way of doing things is good or bad, we need to figure out the answer to the "why" question.

So let's ask the question about Science, broadly speaking. What is the purpose of our endeavor? The answer to that question forms the ultimate basis by which its attendant ethics, practices, and structures must be judged.

My answer is that Science's aim is to produce true statements about the world.

I consider this to be the first axiom. I don't even claim this phraseology as my own, as I'm sure I must have read something to this effect over at Dr. Free-Ride's (which is the place I go when thinking about All Things Philisophical). But I can't think of a better way to put it. And I would guess that essentially all scientists would agree with it. If not, I'm all ears about what is the ultimate goal of Science.

Now onto whittling down that morass!**

* - I understand that this isn't terribly insightful. Either River Tam or Arlenna brought it up some time ago (i.e. - the hazy time that existed prior to the daughter's arrival) in a discussion about authorship order issues. Furthermore, just about every project planning book out there contains something similar. Hell, it's in David Allen's Getting Things Done book, so that means about 1.18 billion people on the Earth know it.

But knowing it and doing it are two very different things. If you don't believe me, consider just about any committee meeting you've had the pleasure of attending. How many actually started with "Why?" And how much talk was really about "How"? Besides, having done exactly this in project planning of various sorts, I'm often surprised by how useful it is in producing different ways of approaching and solving problems.

** - Something about this sentence really makes me happy.

Ruminations of the temperature sort

2009-01-29T11:15:00.001-05:00

Last night, while "shoveling" the slushy concoction from our driveway, I came to an unexpected realization: My cold weather tolerance has returned.

We've already had some bona fide cold weather this winter, with multiple sub 20 degree F days, and some nights in the single digits. And I really haven't felt terribly cold. This stands in contrast to much of the time spent here in Massachusetts, where I was always freezing. A breath of Canadian artic air would send me running for the long underwear.

And yet, I wasn't always like this. I grew up in Connecticut, which though not particularly cold is far from tropical. Then I went to college in Chicago- Ah, I remember the day, trudging to a morning class, where the air temp was -25 deg F (-50 with wind chill). Overall, I remember the cold as being present, but no big deal.

Then, I started grad school at Stanford. Palm trees! Orange and lemon trees! Chelsea Clinton! I wore shorts EVERY day that first winter. It was the El Nino year, and it rained every fricking day, but I still wore shorts. I distinctly remember the odd looks I received from those Palo Altans. They'd be wearing their hats and gloves, and I'd be traipsing across campus, bare legs and all.

But then a funny thing happened the next winter in California. I froze my ass off. I had to wear pants all winter, and even turned up the electric baseboard heat in my on-campus apartment. WHAT? Apparently, a year of living West Coasterly obliterated any and all cold tolerance I had built up. A reversal that took about 10 years to reverse.

Which brings me to what prompted me to even post this bit of boring biographical information: Is this a real phenomenon, and if so, what's the neurobiological basis for it? Do people in different geograpical locales actually perceive temperature differently? Is the difference peripheral (i.e. sensory neurons) or later in the processing? For example, what would you see if you compared the sensory neuron activity of lifelong resident of Alaska and Florida, recording their sensory neuron activity? And how does that change?...trp channels?? trp channels?? trp channels??...And is there a sex difference in this aspect (how many of us can recount the differences between our sense of temperature versus our partners?). And how does aging impact this?

The final question is:when will Spring arrive? Cause though I don't mind the cold so much, I'm already sick of the snow.

2008-12-30T13:30:00.001-05:00

Life seems to be approaching a new steady-state of normalcy. I suppose adding a new member to the family, especially under difficult circumstances, will do that to you. But as with many stressful, tiring, and anxiety provoking events (grad school, post-doc, residency, arrival of the first child), these are times that show we have more inner wherewithal than we expected. Of course, that's not to say that there aren't a lot of ups and downs!

Let me just note that this experience of the second child is so different than that of the first. We're different as parents obviously, having so much more confidence. I'm not examining the baby every few seconds thinking, "OMG, is she breathing????" Also, this baby might be a little more chillun than the first, though of late she has certainly found her "voice". Then there's the consideration that we have another short person who needs attention, and is determined to retain his 6:30-7 AM wake up time. *rubs bleary eyes*

Still, although the amount of work is greater, it's kinda more of the same. In that way, it's so different than the complete sea change that occurred when we brought the first one home. Cause sheesh, we made some goofy rookie mistakes. So, if you're expecting, let me give you some advice. Set up your changing table early. Because no baby wants to be experience the touch of a cold leather sofa minutes after arriving home! And bring extra clothes to the first pediatrician appointment..and, aw, there's plenty more *blushes*

Other than all the work at home, and the work at lab, I'm trying to carve out a little time to blog. There are a whole host of things as post material that are on my mind.

Movie mania memes!

2008-12-22T10:45:00.000-05:00

This is just too fun of a meme to pass up. I don't consider myself a huge movie fan, but let's see how this shakes out.

(x) Rocky Horror Picture Show
(x) Grease
(x) Pirates of the Caribbean
(x) Pirates of the Caribbean 2: Dead Man's Chest
( ) Boondock Saints
(x) Fight Club
( ) Starsky and Hutch
(x) Neverending Story
(x) Blazing Saddles
(x) Universal Soldier
( ) Lemony Snicket: A Series Of Unfortunate Events
( ) Along Came Polly
( ) Joe Dirt
(x) KING KONG [The 1976 Jeff Bridges, Jessica Lange version, not the original or Peter Jackson one]
Total so far: 9

( ) A Cinderella Story
(x) The Terminal [I hate Tom Hanks. Well, let me qualify that. I hate post "Big" Tom Hanks.]
( ) The Lizzie McGuire Movie
( ) Passport to Paris
(x) Dumb & Dumber
( ) Dumber & Dumberer
( ) Final Destination
( ) Final Destination 2
( ) Final Destination 3
(x) Halloween
( ) The Ring
( ) The Ring 2
( ) Surviving -MAS
( ) Flubber (orignal only)
Total so far: 12

( ) Harold & Kumar Go To White Castle
( ) Practical Magic
( ) Chicago
( ) Ghost Ship
( ) From Hell
( ) Hellboy
( ) Secret Window
( ) I Am Sam
( ) The Whole Nine Yards
( ) The Whole Ten Yards
Total so far: 12

( ) The Day After Tomorrow
(x) Child's Play
( ) Seed of Chucky
( ) Bride of Chucky
(x) Ten Things I Hate About You
( ) Just Married
( ) Gothika
(x) Nightmare on Elm Street
(x) Sixteen Candles [One of the best in the John Hughes, suburban teenage white kid flicks]
(x) Remember the Titans
( ) Coach Carter
( ) The Grudge
( ) The Grudge 2
(x) The Mask
( ) Son Of The Mask
Total so far: 18

(x) Bad Boys
( ) Bad Boys 2
( ) Joy Ride
( ) Lucky Number Sleven
(x) Ocean's Eleven
(x) Ocean's Twelve
(x) Bourne Identity
(x) Bourne Supremacy
( ) Lone Star
( ) Bedazzled (original only)
(x) Predator I
(x) Predator II
( ) The Fog
( ) Ice Age
( ) Ice Age 2: The Meltdown
( ) Curious George
Total so far: 25

(x) Independence Day
(x) Cujo
( ) A Bronx Tale
( ) Darkness Falls
(x) Christine
(x) ET
( ) Children of the Corn
( ) My Bosses Daughter
(x) Maid in Manhattan
( ) War of the Worlds
( ) Rush Hour
( ) Rush Hour 2
Total so far: 30

( ) Best Bet
(x) How to Lose a Guy in 10 Days
( ) She's All That
( ) Calendar Girls
(x) Sideways
( ) Mars Attacks
( ) Event Horizon
( ) Ever After
(x) Wizard of Oz
(x) Forrest Gump
( ) Big Trouble in Little China
(x) The Terminator
(x) The Terminator 2
( ) The Terminator 3
Total so far: 36

( ) X-Men
( ) X2
( ) X-3
(x) Spider-Man
(x) Spider-Man 2
( ) Sky High
( ) Jeepers Creepers
( ) Jeepers Creepers 2
(x) Catch Me If You Can
(x) The Little Mermaid (With a happy ending? Are you kidding me?)
( ) Freaky Friday (original only)
( ) Reign of Fire
( ) The Skulls
( ) Cruel Intentions
( ) Cruel Intentions 2
( ) The Hot Chick
(x) Shrek
(x) Shrek 2
Total so far: 42

( ) Swimfan
( ) Miracle on 34th street
(x) Old School
( ) The Notebook
( ) K-Pax [Did anyone see this garbage?]
( ) Kippendorf's Tribe
( ) A Walk to Remember
( ) Ice Castles
( ) Boogeyman
(x) The 40-year-old-virgin
Total so far: 44

(x) Lord of the Rings Fellowship of the Ring
(x) Lord of the Rings The Two Towers
(x) Lord of the Rings Return Of the King
(x) Indiana Jones and the Raiders of the Lost Ark
(x) Indiana Jones and the Temple of Doom
(x) Indiana Jones and the Last Crusade
Total so far: 50

( ) Baseketball
( ) Hostel
( ) Waiting for Guffman
( ) House of 1000 Corpses
( ) Devils Rejects
(x) Elf
(x) Highlander
( ) Mothman Prophecies
( ) American History
( ) Three
Total so Far: 52

( ) The Jacket
( ) Kung Fu Hustle
( ) Shaolin Soccer
( ) Night Watch
(x) Monsters Inc.
(x) Titanic
(x) Monty Python and the Holy Grail
( ) Shaun Of the Dead
( ) Willard
Total so far: 55

( ) High Tension
( ) Club Dread
( ) Hulk
( ) Dawn of the Dead
( ) Hook
( ) Chronicle Of Narnia The Lion the Witch and the Wardrobe
( ) 28 days later
( ) Orgazmo
( ) Phantasm
( ) Waterworld
Total so far: 55

( ) Kill Bill vol 1 [It's on my list of things I'd like to see, but really, with two kids watching movies is kinda low on the priority list]
( ) Kill Bill vol 2
( ) Mortal Kombat
( ) Wolf Creek
( ) Kingdom of Heaven
( ) the Hills Have Eyes
( ) I Spit on Your Grave aka the Day of the Woman
( ) The Last House on the Left
(x) Re-Animator
(x) Army of Darkness
Total so far: 57

(x) Star Wars Ep. I The Phantom Menace [F.U. JarJar]
( ) Star Wars Ep. II Attack of the Clones
( ) Star Wars Ep. III Revenge of the Sith
(x) Star Wars Ep. IV A New Hope
(x) Star Wars Ep. V The Empire Strikes Back [I agree with Dante, this is the best]
(x) Star Wars Ep. VI Return of the Jedi
( ) Ewoks Caravan Of Courage
( ) Ewoks The Battle For Endor
Total so far: 61

(x) The Matrix
(x) The Matrix Reloaded
(x) The Matrix Revolutions
( ) Animatrix
( ) Evil Dead
(x) Evil Dead 2
( ) Team America: World Police
( ) Red Dragon
(x) Silence of the Lambs
( ) Hannibal
Total so far: 66

( ) Battle Royale
( ) Battle Royale 2
( ) Brazil
( ) Contact
( ) Cube
(x) Dr. Strangelove [Peter Sellers's greatness and James Earl Jones's first role.]
( ) Enlightenment Guaranteed
( ) Four Rooms
(x) Memento
( ) Pi
( ) Requiem for a Dream
(x) Pulp Fiction
(x) Reservoir Dogs
( ) Run Lola Run
( ) Russian Ark
( ) Serenity
( ) Sin City
( ) Snatch
( ) Spider
(x) The Sixth Sense
( ) The Village
( ) Waking Life
( ) Zatoichi
( ) Ikiru
( ) The Seven Samurai
( ) Brick
( ) Akira
Total so far: 71

Phew, that was actually pretty easy to do. It's also useful for fleshing out the NetFlix queue.

As for tagging folks, I tag anyone who's actually reading and actually wants to do this!

No jokes this time: HAPPY BIRTHDAY LITTLE GIRL!

2008-11-29T18:15:00.000-05:00

Our baby was born today at 9:07 AM.

She's awesome. Doing great right now, breathing on her own, and just amazing her parents by how beautiful and wonderful she is.

Older brother has opted to reserve judgment, but the presents his little sister "brought" him are an excellent start. A right whale, an orca, and a crocodile for our budding naturalist.

Happy Thanksgivings and Birthdays

2008-11-27T08:00:00.000-05:00

Happy Thanksgiving to everyone out there. Hopefully you're getting to spend it with your loved ones.

As for me, I'll be meeting my new daughter today. After some prematurely broken membranes, it's time to bring this little girl into the world. She's early, at only 34 weeks, but in the grand scheme of things, that mean she'll very likely do great.

And the benefit is now we have an easy name choice. Cornucopia Blair anyone?

Discussion of blog policies

2008-11-11T10:31:00.000-05:00

If anyone has comments, thoughts, discussion on the newly posted blog policies, please feel free to do so here.

Blog privacy policy

2008-11-11T10:30:00.000-05:00

Commenting:

In the spirit of keeping the debate as open and honest as possible, I will give my commenters with significant leeway when making comments. Anonymous comments are ok, as is some level of profanity (let's keep it R-rated at most).

Spam is not ok. Offending comments will be deleted without warning.

There are some guidelines: If a person's attacks on another become unduly personal or threatening, then you will be warned. After sufficient warning if the behavior does not change, you will be banned.

Private emails:

Anything you send me via email I will keep private, unless you specifically agree otherwise.

Real life interactions:

If you know me in real life, I will not discuss any real life interactions here without your explicit prior consent. Of course, at times real life occurrences will suggest topics I want to explore more fully on this blog. In that case, my approach will be to broaden the scope of the discussion to remove any possibility of attributing specific things to specific people.

Personal data:

I will never intentionally divulge personal information to any other party. Period.

So, if you use a pseudonym, I will not seek out your real life identity. If I do come to learn your real life identity, I will never propagate it to others.

There is only one exception to this rule:

If I suspect a person of participating in illegal activities, then I will turn over any and all information to the proper legal authorities.

I have installed a site counter on this blog, but only for the purposes of seeing how many people come to visit, and to see what sites are linking here. I will not release any IP information.

Changes to this policy:

Seeing as no policy can foresee all eventualities, changes to this policy are possible. When such a case arises, I will discuss it openly to make people aware of the change. Note that the new policy will not be considered to apply retroactively.

Paper sections, hunh, what are they good for?

2008-11-10T09:15:00.003-05:00

Phew, it took a helluva lotta time, but the twin attention grabbers of finishing/submitting our manuscript and then the U.S. election have finally subsided. And that's good, because I was going crazy, first obsessing over the details of the paper, and then the daily election polls.

Working on the paper made me realize that I am simply crazy about some things. Like, I'll argue six ways from Sunday against abbreviations, which any sane person would just let go of. And that there are some aspects of a paper that I will work for hours upon end to reach some personal Platonic ideal, whereas there are others that I couldn't care less about. That made me think more about the goals and importance each section in a paper (e.g. Abstract, Intro, etc.). Coincidentally, today Female Science Professor posted about Introductions.

It made me wonder how other people rank the importance of paper sections. For me, I would put it as follows:

Figures. It's the data stupid! Figures have to look good, and embody the points you want to make. I love it when a good figure whallops me with its significance. I'll admit that this is damn hard, and I can't be sure my own figures always meet this criterion. And, it's not simply the visual design of the figure; it's also a combination of experimental design, clarity of the data themselves, and the placement within the flow of the argument. This is perhaps obviously the part I spend the most time and effort on.
Abstract. I put this here, even though typically the amount of time and effort spent writing the abstract isn't terribly large. But it's so important IMO for two reasons: first, it's indexed in PubMed, so beyond the keywords, this is a place to put terms you think your target audience will be searching. Second, it's a place to put the one or two take home messages that you want the reader to come away with. Something short and sweet that will stay identified with your paper, perhaps a nice number indicating the size of your effect.
Results. Speaking as a reader, I may not always fully read this section, but if and when I do turn to it to evaluate one of your experimental findings, it'd better be super clear. Usually I want to know why. Why did you actually do this experiment? Sure, it might be obvious to the authors, but it's not always to the reader. So tell me. Throw me a frickin bone once in awhile. Then tell me what you think the results mean. Don't leave the interpretation to the methods.
Materials and Methods. Again, these are required to really evaluate the experimental findings. And by the gods, if you use a method but mention it solely by referencing one of your old papers, then you're likely to lose me. It's ok to reference yourself there, but at least give me a brief sentence to describe what you're doing.
Discussion. Try and tell me where your stuff fits in with the previous literature, and extend what you think it might mean. Suggest new experiments.
Introduction. Turns out I differ from FSP here. I like a nice short and sweet introduction, with just the barest essentials. But I wonder if this is a disciplinary dependent effect: there are so many reviews published in biosciences now, that it's easy to reference those as a stand in for any more detailed consideration in a single given paper. Is that the case in physics?

Actually, this list make perfect sense to me. I have always considered myself very datacentric person, in that data has the highest priority over theories, models, frameworks, whatnot. And, this list matches the order of sections when I read papers, and the importance I give to each. For example, if I'm pressed for time, I might not read the Intro or Discussion at all, or maybe just read the first sentence of each paragraph.

Still though, maybe other people have different lists, and if so, perhaps my papers are failing them? So let's hear it readers!

Excuse me , but what plasticware did you use for these experiments?

2008-11-07T10:30:00.000-05:00

Checking my daily feeds in Reader this morning, I came across this little nugget in Science:

"Bioactive contaminants leach from disposable laboratory plasticware" by G. Reid McDonald and colleagues. From the abstract we get the money quote:

Wedemonstrate that these manufacturing agents leach from laboratoryplasticware into a standard aqueous buffer, dimethyl sulfoxide,and methanol and can have profound effects on proteins and thuson results from bioassays of protein function.

Now, I honestly haven't gone and read the entire short paper, but it immediately brought to mind an example of something similar known for some time in the ion channel field:

"A light stabilizer (Tinuvin 770) that elutes from polypropylene plastic tubes is a potent L-type Ca(2+)-channel blocker" by Glossmann and colleagues. With wonderfull Teutonic thoroughness these folks found a component in polypropylene tubes that can leach out and block calcium channels. Having done my thesis with a guy who knows a little about calcium channels, this was a finding that was well known in the lab. Inevitably a new postdoc or student would order a case of polypropylene tubes that would end up donated to some molecular biologists posthaste. Polypropylene: good for centrifuging, autoclaving, and holding phenol solutions. Not so good for making your recording solutions. Instead we used polystyrene.

But I get the sense it isn't something appreciated that widely in the field. So, this is my attempt to serve you all, increasing awareness of the pernicious effects of these components on your recordings. A modest contribution, to be sure.

And if you're having trouble making people remember it in your labs, here's something to chant while marching through the hallways. It's already trite and overused, so why not?

"What do we want?"

"Polystyrene!"

"When do we want it?"

"NOW!"

Meme-licious

2008-10-30T10:05:00.000-04:00

I can haz been tagged? Yes, apparently. And since there are those among you who believe I never respond to memes, here goes the 6 random things that you never really cared to know about Nat. Gripping reading, truly. Hopefully you all don't have grants or papers to finish, because you might just be spending all day today reading and pondering these 6 little pieces. First, the rules:

1. Link to the person who tagged you. River Tam! but I think someone else did too! Not sure who though.

2. Post the rules on your blog.

3. Write six random things about yourself.

4. Tag six people at the end of your post and link to them.

5. Let each person know they’ve been tagged and leave a comment on their blog.

6. Let the tagger know when your entry is up.

So here goes!

1) I'm an obligate left sided person. Writing, eating, kicking a ball, hell even my left eye (R.I.P.) has higher acuity. The right side is only good for sleeping on, and mousing, or using a manipulator for electrophysiology. In fact, I find it hard to do the last two with my left hand. Years of training apparently can overcome the natural preference I suppose.

2) I have a family nickname, that nobody else calls me: Bugs. In fact, when my family refers to me by my name, it feels weird.

3) I started grad school at Stanford. During the whole interviewing process, I never thought that I'd end up there, but I was interested to see the department I applied to and also to see California. Yet when I visited, I could really get the sense that it was a special department, and came away convinced that it was the right place for me. And it was great. But the whole residency match process didn't want to cooperate, so when my soon to be wife matched to do her residency in Boston, I immediately started the process of trying to find a place in Boston to which I could come. We had already lived apart for nearly 2 years, and there was no way I wanted to let that continue. Actually in the end, it all worked out for the best. The only thing I miss about California is the weather.

4) When I was a little kid, whenever someone would ask me what I wanted to be when I grew up, I answered zoologist. And though I'm not really a zoologist, I am a biologist. So that's pretty close.

5) When I entered college, had no intention of majoring in biology. I thought I'd do something like economics or study languages or something. In fact, as a second year I took a series of non-major biology courses to fulfill the Core requirements. But it turned out I enjoyed them so much that I completely switched over, and never once looked back.

6) I had to retake a driver's test in 2005 after 11 years of not having a driver's license. I had (stupidly it turned out) let mine lapse after I went to college and my parents moved to England. During that time I was living in Chicago so it wasn't much of an issue as public transportation was fine. Of course it stunk in California, which it turns out it not made for pedestrians. But after a few years driving around Boston, I'm back to being the mediocre driver I always was!

Okay, I won't tag anyone, but if you're reading, feel free to join in and blame me!

5 Year Plans

2008-10-15T09:00:00.000-04:00

On Monday we got a flat tire on one of our cars, which luckily happened in a parking lot while the boy was sleeping. I put the spare on without waking him up, but the tire place didn't have the exact tire in stock. So while waiting for it to arrive from their warehouse, yesterday I went to Starbuck's to help force myself to edit the paper with the final changes. There I sat, getting high on caffeine.

I took a quick break from red pen action, and sat down to start something that Odyssey over at Pondering Blather suggested some time ago, which was to make a 5 year plan. This has been frankly somewhat daunting, but really I found it pretty helpful. It has made me prioritize what I want to do, by thinking explicitly about my broader goals.

Sure, this is blatantly obvious, and I have done broadly similar things before, but never quite kept up on it. Nor had I made it so explicit, but with greater experience, I feel more comfortable filling out the details. Previously I was also hesitant to formulate a plan like this because I hate the idea of forcing scientific projects into definite time frames, for fear of adding some unconcious bias to the thought process. First though, a lot of what goes on this isn't necessarily about experiments, but other related goals. And it's all fungible anyway, since no one can predict how things will turn out. One reason, you know, why we do experiments.

Besides, there are ways to keep yourself honest and keep yourself open to seeing unexpected things in your data, while still being able to evaluate how much progress has been made and what tasks remain. In the past I think I was able to get away with just sorta going with the flow, but now that I have more family responsibilities and helluva lot less time, this approach no longer works.

I definitely recommend taking Odessey's advice in this case, so go fill out your own 5 year plan. Ok, now I'll get back to plotting world domination *ahem*, I mean advancing human knowledge, while at the same time fighting my inner organization-productivity nerd lust to implement it all in Liquid Planner.

Well this one goes to eleven - NOW NEW AND IMPROVED!

2008-10-06T09:30:00.001-04:00

Seeing as I'm still deep in the paper production time, I've been thinking a lot about whether there is an optimal number of figures, and if so, what that number might be. Then Dr. Jekyll + Mrs. Hyde got the ball rolling in wondering why seven figures seems to be the norm. Also, we've probably all heard the anecdote that as the number of figures in a paper increases, the number of people who read it decrease.

I think that the number of figures per se is not terribly meaningful. Unless there are journal dependent requirements (think GlamourMagz), then a paper should have as many figures as are needed to tell the story. If that's 5 figures, good. If that's 15 figures, so be it.

But what's important to me is that each figure contains a coherent point*, conveys that point as succinctly as possible, while still reflecting the reality of the result.

What really gets all up in my grill is when people cram panels into a set number of figures, while blending the points together. That's one way to fit into an external figure limit, while increasing the amount of data presented. I think it fails because it dilutes the take home message from each figure. Also, it destroys any visuo-cognitive impact a figure has. When I look at a figure, I want to be able to see that message almost immediately, and preferably without referring to the legend. When I have to go through each of A-J panels, that ain't gonna happen.

So as a little test, I quickly went through 15 pdfs that were in my "PapersToSummarize" folder, and looked at the total number of figures, as well as the total number of panels in each figure. What struck me was that regardless of the total number of figures, the total number of panels was actually not that different. Now, this is a completely non-random sample, and reflects mostly electrophysiology related papers, with only a smattering of GlamourMagz, but let's look:

Table 1:

Ok, so the median number of figures was 7, perhaps reflecting DrJ+MrsH's impression that 7 is heaven. But also, it's pretty clear that regardless of total number of figures, right about 29-35 panels (overall avg was 32 panels). So those people who don't read a paper with too many figures (if they even exist) are deluding themselves in thinking that really means anything. See, here's a graph to prove it (and they say there's no science on science blogs. There's goddamn regression line in there. You call that no science?):

See, there ya go. Papers with more figures have more panels, but the slope is only ~2 panels/figure. Also, extrapolating to zero figures gives us the predicted absolute minimum panels for a zero figure paper, ~20. Anyway though, the correlation is crap here, with R-squared 0.21.

After doing this, I decided to check back on my papers from my thesis lab, since as those were two author papers, I did the lion's share in planning the figures and their layouts (I'll include the albatross around my neck, one manuscript that will, will see the light of day, even if I have to drown a couple hundred crewmen to publish it; it'll make for a kick ass song though):

11 figures, 27 panels, for 2.5 panel/fig.
11 figs, 27 panels, 2.5
10 figs, 29 panels, 2.9
And the number of panels ranged from 1-5. Pretty consistent.

So readers, tell me: What is your ideal number of figures?

*by point here i mean someting like a quantum of scientific result. Yeah, I just made it up, but maybe other people intuitively understand it.

Horse, get over here! Cause I'm getting back on ya.

2008-10-02T10:45:00.001-04:00

Ok, it's been way, way too long since I last posted, but now I'm back.

For those of you out there who've hardly been able to contain yourselves in my absence, here's a real quick update:

The SGP Calcium and Disease meeting was great. It was one of the first small meetings I had ever been to, and though I am definitely a fan of one of the biggest of the big scientific meetings, namely the SfN meeting, I can see the benefits of a small meeting. Especially as just randomly chatting and conversing with new people is not one of my strengths, the forced interactions in a small meeting really facilitate that (more discussion on optimal meeting size was had over at DM's tree). So I was able to meet and chat with people ranging from other postdocs, to new faculty, to some bigwigs. At this stage, that's important for me. I'll be making it a point to try to go to more of these small meetings.

Overall my talk went well, but it occurred to me that while it was a good post-doc talk, clearly it was not job talk level. Now that criterion can't be the sole guide for what I'm doing science wise, but it has to enter the equation at some point. That I've at times willfully ignored this fact in the past is clear, to my own detriment. But I'm working on altering my approach to a lot of things, while still working within my own set of values. I'm currently in the midst of a lot of self evaluation, which I'll likely post more about later.

The other reasons for light blogging include the work on our paper, which is nearly complete, as well as a combination of moving spaces within the lab (which everyone thought was crazy, to my utter amusement), and the wife's semi-annual hospital service time, which kept mommy at work longer than usual.

But all of those things are done or in the home stretch. So in the immortal words of Optimus Prime, "LET'S ROLL!"

At the SGP Calcium Signalling and Disease conference

2008-09-03T15:00:00.002-04:00

As I referred to in my earlier post, I'll be heading to the Society of General Physiologists' conference on Calcium Signaling and Disease down in Woods Hole, starting tonight and running through Saturday. I'll be giving a short talk about the work I've been doing on TRPC5, and the meeting overall looks to be quite interesting. If any of you folks out there are attending the meeting, swing by and introduce yourself, and we'll celebrate with the appropriate libation, and talk some science!

Dear Brain Thingy in My Head

2008-09-03T09:15:00.001-04:00

Dear neurons residing in my skull,

I realize I've been working you hard recently, to write up this paper and get ready for the SGP meeting. And you've responded in force, and we've been in the flow for what seems like forever, so much so that it's been nearly effortless. Finally it seems like we've got a solid toe-hold on this wonderful, amazing, and beautiful TRPC5 channel that has messed with us for so long (stupid, annoying, crap TRPC5 channel that it is - I know, it's a love-hate relationship). The secrets of the connections between intracellular and extracellular calcium and voltage won't remain hidden forever. But might I make one request?*

At 1:30 AM, I think it'd be best if we all were sleeping, and not thinking about shifting G-V curves. Cause you need your slow-wave sleep and we all end up feeling it when 5:30 rolls around. Just sayin.

*Still though, given the choice between this state and just about any alternative, I'll stick with dreaming of currents.

Let's make some stuff!

2008-08-28T16:45:00.001-04:00

One of the things I really like about being a physiologist is that you get to make stuff, maybe something for your rig. So, you head down to the machine shop, and do your best impersonation of these guys:
Figure 1: Devastatingly handsome hosts of PBS' Router Workshop. Yes, that's correct, an entire show on the beauty you too can create with just a router and some weird ass bits. (Thanks to Isis, whose inclusion of figures I have totally ripped off - what's that saying about flattery?)

So, after agonizing over figures for what feels like countless hours, I was more than happy to help someone in the lab make a little extender thingy*, as a place to attach "sewer pipes*" for changing external solutions while patching. I don my trusty safety glasses (I love science and all, but I ain't losing a friggin eye for it), fire up the heavy artillery, and get covered in plexiglass dust! Good times indeed. The best part is, the result actually is better than my previous designs for extender thingies, and when compared to what someone else in the lab tried to deliver, it looks downright purty.

Figure 2: Nat's extender stands triumphant above a hideously maimed chunk of aluminum. Not that we're keeping score or anything.

Now, let's be clear here, I may be an anal retentive freak when it comes to figures and my recordings, but I am an utter mess when it comes to machining. I subscribe to the measure 6 times, cut 4, and still have the thing look like crap when you're done. All I care is that I make something that works, lasts long enough that I'm not continuously rebuilding it, and do it in a short amount of time. Remember, we're here to do physiology, not learn to be an expert machinist. Likewise with writing code and the like. Sure, it's gotta work and be maintainable, but it's a tool. Use it.).

* - Yes, we like to get technical here at junctionpotential.

I love making figures! I hate making figures!

2008-08-27T16:00:00.000-04:00

I am deep in figure making and paper writing at the moment, which is why blogging, and the science book list, are languishing. But figure making is obviously is a good thing, and a much better place to be than, say, having no data to make figures. Still though, it's a difficult process for me, probably because I'm an anal retentive freak about figures, but also it's a challenging intellectual and creative act.

Figure 1: Nat's inspiration for figure making. (damn Phil Hartman was one funny dude)."This one's a little bigger than the rest, so we'll just discard that one. [pulls out another piece] And I don't think this little wrinkly one belongs in here. [pulls out another] And this ... well, I just don't like the look of that one at all. Alright, as a matter of fact, why don't we just start over and throw this out? [places bowl on counter]"

Good things about making figures:

As said above, it means you have data.

After 11 years of using Igor for data analysis and figure presentation, there are very few annoying questions like, "I want these symbols to stand off the x-axis, how do I do it?" Or, "why is there a limit in the number of columns I can have?" And since all my initial analysis there as well, there's no added importing data, etc.

It's rewarding to make something. Figure making is something where you can really bring out your creativity and where you can distinguish yourself. There's just something satisfying about seeing that figure, which distills the essence of your experiments, come together.

Bad things about making figures:

It hurts. Literally. Maybe my computer/desk set up isn't a paragon of ergonomic-osity, but it isn't so bad. Still, gimme a few days of dragging labels around to get them where I want them (as I said, anal retentive, see Fig. 1) brings out the repetitive stress injury like kegs of Busch bring out the new freshmen (who by the way, are descending upon Boston like locusts. What hell, I thought it wasn't much of a college town?).

It hurts. Like in the brain. The process of defining exactly what you want to convey in every figure panel, and then realizing that on paper is hard. For me it's a relentlessly iterative process, starting out with an idea in my mind's eye, which then undergoes radical alterations (Fig.1). Sure, this is what it's all about, but that doesn't make it easy. Ask an artist. You think their process is easy?

Sometimes it's hard to find all the appropriate expts for a given point you want to make. This is just partly my own organization problem, but sometimes I really wish you could easily add tags to your data files, and then use those for searching. But, prior to the arrival of offspring, this wasn't as much of an issue, since it fit pretty well up in my noggin, but a good couple of years of crap sleep has wrecked my memory. So now I need to keep much more explicit records for this. Which I'm getting much better at, but unfortunately doesn't apply retroactively.

Sometimes you realize you wish you had done certain experiments a little differently. Not so much that what you're thinking was wrong, but sometimes things like exact timing of solutions or voltage steps could be a little different, or some cells were recorded a little differently than others. This just makes talking about the figure painful. (Again, see Fig. 1).

The toner! The paper! I think I've printed 20 versions of this current figure I'm working on, and it's not even done. Well, what's a rich lab good for if not for profligate supply usage?

Ok, time to get back to the figures! I am interested to hear about others' figure making thoughts and feelings.

And we're back!

2008-08-25T00:15:00.000-04:00

It was a great and truly relaxing vacation, but it had to end. That's ok though, cause I was getting antsy, needing my experiment fix.

So what did we do? Get up late, go to the beach every day, eat fried seafood and ice cream, and read.

I reread a bunch of Hille's book, the first part of Hume's Enquiry concerning human understanding, some Comte. Man I'm a geek!

I had a couple other ideas for the book list (I wrote em down somewheres here), and will add them before getting ready to propagate it!

Vacation's all I ever wanted, vacation trying to get away

2008-08-16T07:08:00.003-04:00

We're off to the Cape for a week, where we go to the beach every day so the boy can get crazy in the sand and water! And hopefully I'll get a lot of those in mentis experiments experiments completed.

But when I get back we can finish up the science book list and send it out! I updated the original post so check out the additions.

2008-08-15T14:45:00.001-04:00

Our Igor, which art in RAM,
Hallowed be thy waves,
thy function compiled,
thy procedures be called,
In silico as it is in heaven.
Give us this day our daily our cell that so totally supports our hypothesis (and is figure quality to boot).
And forgive us our series resistance,
As we forgive them who couldn't tell a reversal potential from a junction potential,
And lead us not into Origin,
But deliver us from Excel.

The Rule Of Three

2008-08-12T09:23:00.003-04:00

Does anyone else think there is a place for The Rule of Three in science? As in, for any of the main points of your work, give the reader (or listener) three items that support it. If you do that, then most likely the reader will buy into your line of reasoning. It's especially good if these points cover the most obvious and common objections.

After the first one, the reader thinks, "Hmm, ok, that's plausible."

After the second one, the reader thinks, "Yeah, they're probably onto something here."

And if the writer throws in one more, the reader thinks, "Alright, alright! I hear you! Enough already."

Give more than three, and you're risking pissing off the reader. Give less than that, and you're risking leaving some convinceable people unconvinced. (At this stage there's no need worrying overly much about those close-minded folks who will never change their minds).

[It's somewhat interesting to think about why adding more points, any single of which alone are not convincing, ends up makes the overall argument more persuasive. But I'll leave that for the epistemologists to worry about. Suffice it to say, most scientists are comfortable with terms like, "preponderance of the evidence" and "reasonable doubt" as standards for deciding when a certain thing is "known."]

*sigh* This is all brought on by revisiting some TRP channel literature, which is making me curse up and down, doing my best to channel my inner PhysioProf (though really, who am I kidding). Seriously people, if you're gonna string a bunch of experiments together, could you maybe, I dunno, try to convince me of one before you move onto the next? This is especially true if you're using a bunch of drugs of undefined specificity, which we all know are dirtier than my kid's diaper after a losing bout with the latest day-care GI bug.

The Science Book Meme - let's start it! - UPDATED AGAIN!

2008-08-07T09:15:00.003-04:00

After completing the "100 Books" meme recently, a number of folks (this blogger included) seemed to be annoyed at the dearth of science related books on the list. Well, rather than whining about it, let's start our own frickin meme. Take that you literary, fiction types!

Let's make a list of the "N* Science Books", populated with the most important/interesting/well known/seminal books in science, tag a bunch of people, and watch it spread through the blogosphere faster than an action potential travels down the squid giant axon.

Fire up some suggestions in the comments, discuss what belongs where, and let's see where this takes us. My thought was to leave off textbooks, and technical manuals, but if there's a consensus otherwise, then the mob rules!

Here's my initial list: (Updated to reflect additions by the excellent commenters - at least some people are reading!)

Origin of Species, Charles Darwin
The Structure of Scientific Revolutions, Thomas Kuhn
The Double Helix, James Watson
Rosalind Franklin and DNA - Anne Sayres
Nerve, Muscle and Synapse, Bernard Katz
Lives of a Cell, Lewis Thomas
Art of the Soluble, Peter Medawar (something else here perhaps?)
What is Life, Erwin Schrodinger
Random Walks in Biology, Howard Berg
Elbow Room - Dan Dennett
Godel, Escher, Bach - Douglas Hofstadter
Apprentice to Genius - Robert Kanigel
In search of memory - Eric Kandel
Neurobiology of Nociceptors - edited by Carlos Belmonte and Fernando Cervero
The Sexual Brain - Simon Levay
Advice for Young Investigators - Santiago Ramon y Cajal
King Solomon's Ring - Lorenz and Huxley
The Man Who Mistook His Wife for a Hat - Oliver Sacks
The Elegant Universe - Brian Greene
The Mismeasure of Man - Stephen Jay Gould
The Blind Watchmaker - Richard Dawkins
Genius - James Gleick
Surely You're Joking, Mr Feynman! by Richard Feynman
Brief History of Time, Stephen Hawking
Woman - Natalie Angier
Karl Popper - The Logic of Scientific Discovery
T-rex and the Crater of Doom - Walter Alvarez
An essay on the principle of population - Thomas Malthus
Astonishing Hypothesis - F. Crick
Witchdoctors and Psychiatrists - E. Fuller Torrey
The Eighth Day of Creation - Horace Freeland Judson
Intuition- Allegra Goodman
The Billion-Dollar Molecule - Barry Werth
The Discoverers - Daniel J. Boorstin
Natural Obsessions- Natalie Angier and Lewis Thomas
The Genome War - James Shreeve
General Chemistry - Linus Pauling

Ok, that's what comes out of my brain without much prodding. What do other people have? Hopefully we'll get some coverage from non-neuro geeks.

*- I figure this will run its natural course like any good brainstorming session. Whatever number we get to, we get it. (Currently it's at 26; NO, 36! NO, 37!), but this list isn't set in stone; more can likely be added, and with sufficient agreement, removed if need be).

Genealogies, of the academic variety

2008-07-31T10:00:00.001-04:00

Neurotree is a really cool website that aims to create and store the training relationships between neuroscientists. From it, I learned that on one side of my family, the Bean side, I am 6 steps from Charles Sherrington (below, from Wikimedia), the English physiologist who coined the term "nociceptor" (yup, I actually read his book The Integrative Action of the Nervous System, where he used that term. How come that wasn't on the damn book list meme, eh?). Sherrington shared the 1932 Nobel with Lord Adrian for their work on neuronal physiology, and trained three Nobelists as well: Eccles, Granit and Florey.

The other half of my tree, the Clapham side (hmm, I am Bean-Clapham spawn! Something about that makes me chuckle. In an uncomfortable way), brings me to a distinct group of physiologists, with Erwin Neher (gulp, another Laureate), up to Haldan Keffer Hartline (another Laureate) , who himself trained with Werner Heisenberg!. Wow, I didn't know that! For those of you keeping score at home, that's another Laureate, this time in Physics.

Great; now I can fail to live up to my academic parents' expectations, as well as my real life ones! :) Ok, my real parents always said they'd be happy with whatever I chose to do. Hopefully my academic parents agree!

The other cool thing about Neurotree is the cluster analysis of neuroscientists, which reflects the relatedness of the various subdisciplines within neuroscience. Having some way of tracking the changes in this through time would be pretty cool. I wonder if you had the information about how those clusters changed through time, would you be able to pinpoint the early papers and workers who led this shift? They are real pioneers of new clusters. Could you also tie that into people's published works? I wonder how those papers that signal the birth of a new cluster would rate on the citation analysis metrics some people are so worried about?

Now anyone can browse the tree, so go check it out. If you're a neuroscientist and haven't been added, then go make an account and fill in some details.

The Book Meme

2008-07-30T08:45:00.002-04:00

Alrighty, let's not get all serious and stuff in here, with the science and whatnot. Let's do a meme! It's 2008, memes are the new worm, and juniorprof tagged me with the 100 book meme. Here's the list below, with completed reads in bold and partial reads in italics.

1 Pride and Prejudice - Jane Austen
2 The Lord of the Rings - JRR Tolkien
3 Jane Eyre - Charlotte Bronte
4 Harry Potter series - JK Rowling
5 To Kill a Mockingbird - Harper Lee
6 The Bible -
7 Wuthering Heights - Emily Bronte
8 Nineteen Eighty-Four - George Orwell
9 His Dark Materials - Philip Pullman
10 Great Expectations - Charles Dickens
11 Little Women - Louisa M Alcott
12 Tess of the D’Urbervilles - Thomas Hardy
13 Catch 22 - Joseph Heller
14 Complete Works of Shakespeare -
15 Rebecca - Daphne Du Maurier
16 The Hobbit - JRR Tolkien
17 Birdsong - Sebastian Faulks
18 Catcher in the Rye - JD Salinger
19 The Time Traveller’s Wife - Audrey Niffenegger
20 Middlemarch - George Eliot
21 Gone With The Wind - Margaret Mitchell
22 The Great Gatsby - F Scott Fitzgerald
23 Bleak House - Charles Dickens
24 War and Peace - Leo Tolstoy
25 The Hitch Hiker’s Guide to the Galaxy - Douglas Adams
26 Brideshead Revisited - Evelyn Waugh
27 Crime and Punishment - Fyodor Dostoyevsky
28 Grapes of Wrath - John Steinbeck
29 Alice in Wonderland - Lewis Carroll
30 The Wind in the Willows - Kenneth Grahame
31 Anna Karenina - Leo Tolstoy
32 David Copperfield - Charles Dickens
33 Chronicles of Narnia - CS Lewis
34 Emma - Jane Austen
35 Persuasion - Jane Austen
36 The Lion, The Witch and The Wardrobe - CS Lewis
37 The Kite Runner - Khaled Hosseini
38 Captain Corelli’s Mandolin - Louis De Bernieres - They made a book out of that crap Nick Cage movie? Who knew?
39 Memoirs of a Geisha - Arthur Golden
40 Winnie the Pooh - AA Milne
41 Animal Farm - George Orwell
42 The Da Vinci Code - Dan Brown
43 One Hundred Years of Solitude - Gabriel Garcia Marquez
44 A Prayer for Owen Meany - John Irving
45 The Woman in White - Wilkie Collins
46 Anne of Green Gables - LM Montgomery
47 Far From The Madding Crowd - Thomas Hardy
48 The Handmaid’s Tale - Margaret Atwood
49 Lord of the Flies - William Golding
50 Atonement - Ian McEwan
51 Life of Pi - Yann Martel. Well, the wife read it. Does that count?
52 Dune - Frank Herbert - Yeah, I read the trilogy. Multiple times. It's still sorta whack though.
53 Cold Comfort Farm - Stella Gibbons
54 Sense and Sensibility - Jane Austen - What is UP with the Jane Austen on this list?
55 A Suitable Boy - Vikram Seth
56 The Shadow of the Wind - Carlos Ruiz Zafon
57 A Tale Of Two Cities - Charles Dickens - And the Dickens. What the hell?
58 Brave New World - Aldous Huxley
59 The Curious Incident of the Dog in the Night-time - Mark Haddon
60 Love In The Time Of Cholera - Gabriel Garcia Marquez
61 Of Mice and Men - John Steinbeck
62 Lolita - Vladimir Nabokov
63 The Secret History - Donna Tartt
64 The Lovely Bones - Alice Sebold
65 Count of Monte Cristo - Alexandre Dumas
66 On The Road - Jack Kerouac
67 Jude the Obscure - Thomas Hardy
68 Bridget Jones’s Diary - Helen Fielding
69 Midnight’s Children - Salman Rushdie
70 Moby Dick - Herman Melville
71 Oliver Twist - Charles Dickens - Listen, whoever wrote this list, 19th century British novels are not my thing. You've proved it, ok. Are you happy now?
72 Dracula - Bram Stoker
73 The Secret Garden - Frances Hodgson Burnett
74 Notes From A Small Island - Bill Bryson
75 Ulysses - James Joyce - I'll take The Dubliners or Portrait…please.
76 The Bell Jar - Sylvia Plath
77 Swallows and Amazons - Arthur Ransome
78 Germinal - Emile Zola
79 Vanity Fair - William Makepeace Thackeray
80 Possession - AS Byatt
81 A Christmas Carol - Charles Dickens - I sat through Scrooged.
82 Cloud Atlas - David Mitchell
83 The Color Purple - Alice Walker
84 The Remains of the Day - Kazuo Ishiguro
85 Madame Bovary - Gustave Flaubert
86 A Fine Balance - Rohinton Mistry
87 Charlotte’s Web - EB White - I find "Elements of Style" to have a much better plotline
88 The Five People You Meet In Heaven - Mitch Albom
89 Adventures of Sherlock Holmes - Sir Arthur Conan Doyle
90 The Faraway Tree Collection
91 Heart of Darkness - Joseph Conrad
92 The Little Prince - Antoine De Saint-Exupery
93 The Wasp Factory - Iain Banks
94 Watership Down - Richard Adams - Somehow couldn't get into it. Watched the cartoon on TV with my dad though.
95 A Confederacy of Dunces - John Kennedy Toole
96 A Town Like Alice - Nevil Shute
97 The Three Musketeers - Alexandre Dumas
98 Hamlet - William Shakespeare
99 Charlie and the Chocolate Factory - Roald Dahl And James and the Giant Peach and The Twits and have read some of his non kid stuff.
100 Les Miserables - Victor Hugo

Wow, 13 completed reads, and 7 partial reads. 20 per cent! Still, this proves two things. Nat doesn't read fiction. Which I freely admit. I am much more of a non-fiction creature. Secondly, overwrought and needlessly wordy 19th century fiction sucks. What a waste of time!

There are actually very few books on this list I haven't read that I actually wish I had. I count only 1984 and One Hundred Years of Solitude on that list. If you got an argument as to why any of the others is a must read, with which I should edify myself, let me hear it.

I won't tag anyone, but if you're reading this, feel free to put your own up, in the comments here if you have nowhere else to put it.

David Linden starts as Editor in Chief of Journal of Neurophysiology

2008-07-15T13:57:00.001-04:00

Linden is professor of neuroscience at Johns Hopkins, and an electrophysiologist to boot! He replaces Eve Marder (Brandeis) another electrophysiologist (we izz in ur science, recording ur currentz!), as the Editor-in-Chief.

In his opening editorial, he says some things I like to hear. Here's a snippet:

I've always greatly admired the scientific ethos of the Journal of Neurophysiology. Reading the Journal reminds me of what I like best about science. I like that it publishes full-length reports, which are still being cited 20 or 30 years on. I like that each paper can stand on its own, without 10 supplemental online figures...I like that the Journal of Neurophysiology has been guided solely by publishing excellent and interesting science, regardless of perceived "sexiness" or "impact factor."

Hoo-ray! I like the sentiments, that's easy to see. Turns out Linden is actually a pretty funny guy, who has a blog, The Accidental Blog, where I found a link to a podcast of neuroscientists, Neuroscientists Talk Shop. Sounds interesting, and it's getting loaded onto the MP3 player as we speak. Yay, more geek talk!

Course, I haven't published in J. Neurophys. But it's always been on my watch list.

Dreaming of heaven...of the electrophysiologist's type

2008-07-11T11:29:00.002-04:00

I've often said that in electrophysiologist's heaven, there's no series resistance, and you have an infinite number of solutions in a special magic fridge/shelf, containing every possible permutation of divalents, weird anions, or whatever.

Cause dealing with the lack of those two things is a series pain in the ass.

*sigh*

What are the 'bibles' of your field?

2008-07-10T15:45:00.000-04:00

Dr. Jekyll & Mrs. Hyde had a quick post on about how she doesn't read too many science books anymore (she's a postdoc), leading to the question of what's the point of a book length treatment when the science is always progressing? That's a good question, so go over there and comment on what you think is the proper role for science books.

But it's obvious that there are some books which most scientists in a given field own, and have read, and have incorporated into their thought process.

You know, the bibles of the field.

They're the books that everyone has on their shelf, the ones you spent your book money on as a grad student, the ones you point younger scientists to when they have a question, the ones you just know in your gut will have the answer once you peruse the table of contents. Some are methodological bibles, some are conceptual bibles, and some blend the two.

For electrophysiology, I can immediately think of three main bibles. They are, in no particular order:

"Ion(ic) channels of Excitable Membranes", by Bertil Hille, currently in its third edition. If it's a question about some fundamental basic property relating to ion channel function, or you want a good overview of the squid action potential, then this is the place to start. Still a favorite, though I have to say I prefer the 1992 2nd edition, for the tactile sensation of its cover, it's wonderfully incorrect title, as well as its modest overall size. The third edition sadly fails each of these criteria.

"Single-Channel Recording", 2nd edition, edited by Erwin Neher and Bert Sakmann. Maybe you've heard of them, having won the Nobel in 1991 for their development and use of the patch clamp technique. The book is largely covers methodological questions, though it's title is a misnomer; it covers a lot more than just single channel recording.

"The Axon Guide" edited by Rivka Sherman-Gold. Published by Axon Instruments (now owned by Molecular Devices), it covers a lot of basic material as well as more detailed questions in an accessible, easy manner. It was out of print for some time, and then Axon made it freely available in pdf form. You can download it from the Overlord Master Molecular Devices here. Everybody I train in patch clamp gets this, and I quiz em about it. I especially like its treatment of filters and digitization, two topics which many young biologists haven't heard much about. And series resistance. Oh the series resistance. That my friends is a post in itself.

So, what are the bibles of your field?

Yeah yeah, Maniatis, ok whatever. What else ya got? Cause that's bor-ing!

Wednesday quick hits

2008-07-09T11:32:00.003-04:00

When blogging has been nonexistent for years, is it fair to say that recent blogging has been "light"? Still, things have been quite busy around here lately, mostly as we work to firm up the shape of a manuscript looking at the regulation of TRPC5 channels (Hmm...seems like a post describing TRP channels more generally is in order - put it in the hopper, which is already bursting at the seams). But in between bouts of analyzing current amplitudes and looking for series resistance errors (pine away you molecular and cell biologists, but remember, you made your choice, wrong as it was), I have been following some interesting science related blog posts and whatnot.

Yaroslav Nikolaev posted an interesting picture of scientific progress. Not sure I agree that the real bottleneck is always assessment stage but check it out. Hmm, it seems I should list 'epistemology' as a hobby in my social networking personae. Whoa, geek overload coming!

The Amazon Kindle looks pretty cool, anyone out there using it? Because I'm in the process of totally phasing out paper printouts of journals (which is going pretty well), so maybe I could expand the scope even further.

Sigh, research misconduct is such a downer. How prevalent is it really, and in what ways is the current architecture of science promote it?

What online reference managers are people out there using? I've been using Connotea, but have also checked out CiteULike a little bit. And I've tried Zotero as well, but it was SLOW. None of these have really grabbed me, so does anyone have a killer app they want to suggest? And no, please don't mention Papers. We're non Mac type in Junction Potential land.

AutoHotKey is an awesome little free app that let's you easily make shortcuts, etc. I don't think I could live without it now.

It's been a few weeks, but my brother and I hit the Iron Maiden show they played in Massachusetts at the Comcast center. Yeah, it was as awesome as it sounds. And yeah, I can hear the jealousy out there.

Conceptual and experimental innovators in science and Galenson's creative types

2008-07-02T11:42:00.004-04:00

I just read the Wired article "What Kind of Genius are You?" by Daniel H. Pink from 2006 about University of Chicago economist David Galenson's then recently published book "Old Masters and Young Geniuses: The Two Life Cycles of Artistic Creativity". It's a tad old, and I have lost the source of the link, but it's definitely worth reading, and I just had to write a blog post about it.

Reading the article, I felt intellectually buffeted by the force of Galenson's hypothesis and its apparent explanatory power, similar to the way I felt the first time I read Kuhn's "The Structure of Scientific Revolutions." Galenson's idea arises from studies of artists' lifetime production (well, he is a economist) and is this: there are two essential types of creative artists, the "conceptual" innovators" and the "experimental innovators". The conceptual innovators make dramatic leaps in their fields, often doing so at early ages after which their production declines. The second type, "experimental innovators" instead often take much longer to develop their most significant output, spending a long time developing and experimenting with techniques. Conceptual innovators seem to 'know' where they're going and where they want to take the field, whereas experimental innovators don't, and evolve bit by bit, letting the work develop and seeing where it takes them:

Picasso and Cézanne represent radically different approaches to creation. Picasso thought through his works carefully before he put brush to paper. Like most conceptualists, he figured out in advance what he was trying to create. The underlying idea was what mattered; the rest was mere execution. The hallmark of conceptualists is certainty. They know what they want. And they know when they’ve created it. Cézanne was different. He rarely preconceived a work. He figured out what he was painting by actually painting it. “Picasso signed virtually everything he ever did immediately,” Galenson says. “Cézanne signed less than 10 percent.”

Experimentalists never know when their work is finished. As one critic wrote of Cézanne, the realization of his goal “was an asymptote toward which he was forever approaching without ever quite reaching.” (p.2).

Now, I immediately starting thinking about how this might apply to different scientists. I am convinced that there are many parallels between how artists work and how scientists work. That's not suprising, as both are intensely creative human endeavors, and probably many scientists would agree. Could this be another region where there are significant parallels between artists and scientists?

I say yes, but exactly how meaningful these categories are remain to be examined (and is rife with all the difficulties of measuring the output of scientists). But I definitely think there are conceptual and experimental innovator types among scientists, at times manifested in their approach to questions. There are those who are good at coming up with new hypotheses and models when the hard data to make any of those connections is weak or even non-existant. This might lead to a lot of negative experiments, but if you can do it right and you hit on something new, then significant progress can be made. In fact this led me back to Kuhn, regarding those scientists who develop the new paradigm must buy into it before there is significant data to show it's better than the current (think Copernicus pushing the heliocentric model of the solar system before it performed better than the Ptolemaic model-it took ~80 years and Kepler to make the heliocentric model perform better).

But the other approach is to take a subject of interest, and just start doing experiments, and try and let the results 'talk' to you, leading you to the next experiment. At some point, if you're lucky and perceptive, you have a decent shot of seeing something that isn't expected, and is the first step in the path towards a significant advance forward.

I'll be the first to admit that I am firmly in the second camp, and am an avowed experimentalist (hard to call myself an innovator). For just about all the projects I've worked on, I've decided on a particular subject or subfield, and then started to do experiments.

In my view, both of the approaches are valid and useful, and in principle I don't think either has an inherent greater probability of leading to something "new." I sometimes wonder though whether the slow approach, might produce something in the end which is perceived as being less shocking simply by virtue of the fact that all of the preceding experiments made the final result likely, or even inevitable. With the conceptual innovator, it's more obvious when "before" and "after" occurred. In that case, is the conceptual approach more likely to garner the attention needed for publication in a high profile journal? This might be taking things too far, but I suspect there is something to it.

Of course, the dichotomy between the two types isn't anywhere near complete. Conceptualists aren't making up things willy-nilly, totally disregarding all that has come before. And experimentalists must have some sort of model, however implicit, or else how would they choose among the infinite number of possible experiments. Galenson himself has said there are certainly people who straddle the extremes. Yet there are strong tendencies, and I wonder how far the concept can be extended to scientists.

So, my small and somewhat reticent readers: Are you a conceptual or an experimental innovator?

I won't surrender my idealism

2008-06-26T09:18:00.003-04:00

There's a thought provoking discussion going on among some of the heavier weight science bloggers which has so many subthreads running through it that it's hard to summarize. So it's prolly best to go check out the posts over at DrugMonkey (here) and YoungFemaleScientist (here)

It's a back and forth that goes back a number of posts, with a lot of commenting. Essentially I think it boils down to this: YFS is a postdoc who thinks the system of science is in many ways fundamentally unfair, and as such needs changing. Physioprof and DrugMonkey are faculty members who aim to describe the system as it is, to help postdocs succeed in that system (which they readily grant it flawed, yet over which they feel they have limited ability to change).

Overall both make good points, but I take issue with some of the things that PhysioProf says in his latest post.

The money quote:

"In a winner-take-all system like this, there will always be people who do not succeed through no fault of their own. People who are smart, talented, dedicated, hard-working, articulate, persuasive, and who do all the right things sometimes still fail. This is the nature of a winner-take-all system: there is an intrinsic randomness that influences to some extent who succeeds and who fails. It is the same in professional sports, law, medicine, performing arts, entertainment, comedy, business, entrepreneurialism, journalism, engineering, and most other professional career enterprises.

Many of us may not like this situation, but this is how things currently work. Academic science is not a fucking Care Bears tea party, and wishing that it were is not going to make it so."

I have two big issues with this. First, there's no consideration for how well the current system of science might work to improve, or hinder, the quality of the end product: knowledge. Might it be that the system as is exists produces worse science than a different system? The fact that the essential randomness of the system might lead people to lose faith in the justice of the entire process. And when they do that, they start behaving badly. Dr. Free-Ride has it right, so check out her post.

If it is the case that the system is worse than it was (or might be), don't you have some obligation to change it? DrugMonkey does say in the comments that his blogging is one way of changing things, and that he also does his best to nudge things towards a better course in his real life working as a scientist. That's good, but it leaves me to wonder why the vitriol towards YFS, who is doing the SAME thing, in her way.

Secondly, I hate the way that PhysioProf impugns people who might want to change the system with the dismissive reference to a "CareBear tea party." I read it as saying to anyone who is an idealist about science qua science, or who feels that some current practices pervert what we see as a noble a pursuit worth dedicating one's life to, is hopeless naive. To that I say, fine, and can I get another helping of naivete?

Because I won't surrender my idealism for the project of Science. If that means I "fail" in the end, well, I will have my head held high when that time comes. I would rather live with the failure than to abandon my principles.

The Messy Phase of a Scientific Problem

2008-06-24T09:14:00.008-04:00

-juniorprof started an interesting discussion about whether to be a producer or consumer of the literature. I started to write a comment in response, but it sorta ballooned up, went off on a bit of a tangent, and so I moved it here. Be sure to check out his post there (and his blog in general, it's a good one).

Overall, I find the message behind the dictum of the famous neuroscientist that juniorprof relates, which is to "be a producer not a consumer [of the scientific literature]" to be kinda ambiguous; of course all scientists need to have some engagement with the body of work they're involved in, and of course it can be easy for some folks to be too wrapped up in the literature to the detriment of their own creativity and experimental production. As juniorprof added in the comments, with which I agree, it's best to start a new project by going through the literature, and then after that to let your experiments guide you.

As part of his post juniorprof also warned against getting too wrapped up into the minutiae of details that can at times overcome a particular subfield (the state of which can be diagnosed by the presence of negative results against this or that hypothesis). I like that too in principle, but I can think of a couple examples where it took the field several years and a lot of negative experiments to converge on a better understanding of a process, and in so doing helped to reveal a more broadly interesting and relevant results.

Cases in point are the signalling mechanism that causes M current inhibition by receptor activation, and whether long-term potentiation (LTP) occurs as a result of changes in pre- or postsynaptic properties. It took a long time before it became generally agreed that PIP2 depletion inhibits M channels, or that postsynaptic glutamate receptor insertion underlies many forms of LTP, and I can think of lots of experiments with negative results done to assess the multiple alternatives. Sure, in isolation any one of those results isn't terribly informative, unlike a good positive result would have been; yet in the aggregate they reflect the shared knowledge of the field which had to be accounted for in the final scheme. And I would argue that only the existence of these negative results enabled the final positive result. (Still though, if you do have a negative result, stick it somewhere where you also have some amount of positive results and appreciable march towards the final answer. And by the gods do NOT highlight the negative result in the title. GAH!).

Also, the final papers which cemented the current understandings of these processes were published by people who were actively researching these questions throughout the messy period when lots of negative results and back and forth papers were being produced. So, I find it unlikely that any single researcher could sit out the ugly phase, work on something else, and then "swoop back" in and make a strong positive situation). Instead, I think that only by those people actively involved and invested in the line of inquiry were likely to have the ability to make the final connections and apply them to their question.

Now, I'll grant first that spending time on expts in the "dirty" phase isn't glamorous, and might be a hard sell to funding and promotion folks. I'm more thinking about how this process plays out for science per se (naive and unwise, I understand). Secondly, you have to make sure your initial process has some level of importance before you decide to commit to it. In this way it helped that M current (as an example of ion channel modulation more generally) and changes in synaptic strength such as LTP were intrinsically important questions. These two also had the lucky effect that their answers became important in and of themselves, as examples of PIP2 modulation of ion channels and activity dependent insertion of ion channels, respectively. Maybe it's not lucky though, since you should probably assume that a question which takes that long to settle is likely to generate an answer that is pretty novel when all is said and done.

So where does that leave us? Hmm, my main dictum is, "Do good science".

Well, at least it wasn't a terribly offbase decision...

2008-06-19T10:21:00.004-04:00

You Should Get a PhD in Science (like chemistry, math, or engineering)

You're both smart and innovative when it comes to ideas.

Maybe you'll find a cure for cancer - or develop the latest underground drug.

What Advanced Degree Should You Get?

Ok then, so I chose correctly, and I certainly did enjoy getting the Ph.D. (as well as generally enjoying my time now). Though it might also explain why the whole current situation in science feels so...psychically disturbing at times.

Do citations in supplementary data not count in ISI?

2008-06-13T14:56:00.003-04:00

I came across something troubling today in the supplementary information that accompanied a paper I was going over. Now I have a lot of misgivings about the whole concept of supplementary data, yet I hadn't realized this one until now.

That is, in the Thomson ISI database, citations made in supplementary data are not counted in the "Times Cited" count. That's worrying to me, because one of the most prevalent ways for people who are not experts in a given field (or subfield, or subsubfield...) to assess the influence of a scientist or paper is to use the number of citations the paper garners. For example, these citation counts are used to create the impact factor to rank journals (and at times erroneously to rank individual papers), and the Hirsch, or h-, index used to evaluate scientist output.

Meaning, if these citations are not included in ISI, then for all intents and purposes they do not exist.

So now, not only can supplementary info be used as a dumping ground for your inconclusive or crappy data, but you can also stick references to your competitors in there and shaft them their citations.

But hey, at least you've got your plausible deniability!

Anyone else troubled by this? Anyone else have opinions on supplementary data?

Some open access goodness from the Clapham lab

2008-06-12T10:43:00.002-04:00

Recently, my colleagues in the lab have published open access papers describing their work on various TRP channels.

One, headed up by Sebastian Brauchi (a former postdoc in the lab, who now has his own lab in Chile) and Grigory Krapivinsky, describes the role of TRPM7 on cholinergic vesicle fusion. It was published as open access in PNAS. Download it here.

The second describes work by Stephanie Stotz and colleagues on the sensory transduction mechanisms elicted by the chemical citral (a component of lemongrass). They found multiple effects of citral on a number of TRP channels expressed in sensory neurons, and published their work in PLoSOne. Get it here.

Yay for open access! Actually though, my advisor David always self-archives all of his publications, and they're available at the lab website here.

Wait! You're a postdoc, blogging under your own name? Are you insane?

2008-06-12T09:32:00.004-04:00

Heh, I know, it does seem a little kooky at times.

Am I worried that my current advisor, or future colleagues (wherever they may be) will look askance at the idea of spending time blogging? I'd be lying if I said I was completely at ease with it, but I always come back to convincing myself of the personal utility of blogging. What do I mean by that?

Well, I plan on focusing primarily on blogging about science related topics, whether it be my own research, commenting on other research in my fields, and in thinking about issues related to science at large. This won't be a blog where I discuss my personal life, or complain about coworkers or things like that. There are definitely places for those kinds of blogs, but this isn't one of them. There won't be a hard firewall between the personal and professional, but there won't be LOLcat links (beyond that one, promise).

Instead, I see this as a way to more fully explore and think about issues that are already kicking around in my head. Stuff that my brain is chewing over, and will not let go. So while it may seem that this blog is going to take up a lot of time (and it may) but it might just let me offload some of that congitive processing time, refine its use, and free up resources for more obviously pertinent tasks. And this is one reason why I decided to do my blogging under my real name. That will force me to think a little more about my writing. Also, I didn't want to worry about my anonymous blog becoming 'outed' at some point, and risk hurting people I had written about. Better to prevent that temptation from doing that in the first place (but I certainly don't fault anyone for being anonymous. Sometimes a little spleen needs to be vented, and somethings in science are all messed up, and talking about that helps us all. A great example is YoungFemaleScientist).

And there will prolly be more indirect, and more distant in time, benefits of the blogging, related to becoming part of the broader science blogging community. That community is just a tip of the iceberg in the burgeoning Science2.0 movement (though I hesistate to call it a 'movement', that implies too much of a top down approach - it's more organic and distributed). I've got another post in the brain to discuss some aspects of Science2.0, but it seems obvious, and I'm convinced, that the increases in communication and interaction enabled by the spectrum of Web2.0 technologies can only help improve science and will improve the research and recognition of those involved. If I can get some 'early adopter' advantage, well, at this point I'll take whatever I can get! See, there is a selfish benefit to it all, which is a good way to motivate people to do things that also benefit the group at large.

The Very First Post

2008-06-05T15:00:00.001-04:00

Well, everything has a beginning, and so it is with this blog. Today, appropriately enough on Harvard's commencement day, I begin my foray into blogging. It's been some time coming, and I've wrestled with whether I should even get into this in the first place, and if I did take the plunge, what I hoped to accomplish.

Having no particularly clear answers to those questions, I just decided to take the plunge, and let the blog evolve towards whatever state the forces involved dictate. Consider it a beta version if you wish.

Of course I do have things I want to talk about, thoughts to share, and conversations I hope to start. Many of them will likely involve neuroscience, my academic field, which at least in terms of cellular neurophysiology seems poorly represented in blogspace (I couldn't use the term blogosphere here; to me that connotes some cloud of more politically interested blogs, carrying on discussions between themselves. I have no interest in becoming a part of that). I think it's clear that blogs will emerge as an important medium to enhance communication among scientists, and that's something of which I want to be a part. As a place for less formal communication about science, blogs appear ideally suited; I just wish there were more researchers doing it.

Beyond that, I've always taken a keen interest in "Science" and the big issues that surround it: the ethics of science, the practice of science, and how we can organize science to produce the best ultimate outcome, which in my view is the production of information that informs and improves humanity. I don't claim to be anything more than an interested layperson in these areas, but I can bring a "view from the trenches."

Lastly, why "The Junction Potential" for a blog title? There are a couple of reasons. First, it's an electrophysiology thing. As every young electrophysiologist learns, there is a junction potential between your pipette solution and the external solution, arising from the different ion mobilities. This affects the actual voltage you're applying to the cell membrane, and needs to be correctly measured or calculated, and then offset. In terms of electrophysiology, the junction potential isn't always paid a lot of attention, nor it is usually a big deal if you don't account for it initially (you can always correct it after the fact). That's a perfect analogy for this blog I'd wager.

The second reason is perhaps more profound. I have become convinced recently that many aspects of Web2.0, be they social networking/bookmarking tools, folksonomies, wikis, and blogs, will profoundly change the practice of science (this is by no means an original conclusion of course). They have the potential to drastically increase the junctions scientists make with their subjects and with their colleagues (yes, I know, groan). Besides, I needed to call it something.

The Junction Potential

Guest blogging over a Scientopia

I love it, just love it!

LET'S GO YANKEES!!!!!

Some things shouldn't go together

How do I measure the liquid junction potential?

Damn I love being a scientist!

Sometimes being a science dad...

Falling to Autumn

Friday Morning Quick Hits

Friday Morning Science Soundtrack

Science Dads Reporting for Duty!

Team Fox or Team Hedgehog?

I am the Norge Repairman of the primary literature

Good olden tyme science (now with Squid Axon videos!)

Belatedly, and memely, yours

It starts early

juniorprof's #painresearchmatters campaign

You know what else sucks?

Citation Classics -

Calcium imaging sucks...

Did I really just do that?

Shallow thoughts

Strike that....substitute silence.

Geek alert

A Tale of Two Grounds

What have I, what have I, what have I done to deserve this?

InaDWriMo2009 - do it, do it now!

Shallow thoughts

Blogrolling, Junction Potential Style!

Oh my god, I'm so sorry I forgot...

Meme-licious

Wordly advices

Happy Mother's Day!

HAPPY ANNIVERSARY WIFE!

CAN YOU SMELL....WHAT THE ROCK U. PRESS IS COOKING?

Poll crashing vanguard for the science!

Phew, so glad that is over!

Mythbusters!

5. Competition Beats Collaboration

What is a junction potential?

Science sometimes makes me feel like...

Sometimes, the little things are what keep you going

Electrophysiology isn't a technique you add to your CV; it's a state of being!

A pictorial presentation of pipette pulling

We got monkeys running all over the house!

2 grand? How about 20 bucks?

Hubris - and that ain't a circumscision in Whoville

It's a beautiful....pair of sodium currents!

Me, cool? Not hardly!

The thrill of victory...

Perversity isn't always fun.

First Axiom

Ruminations of the temperature sort

Movie mania memes!

No jokes this time: HAPPY BIRTHDAY LITTLE GIRL!

Happy Thanksgivings and Birthdays

Discussion of blog policies

Blog privacy policy

Paper sections, hunh, what are they good for?

Excuse me , but what plasticware did you use for these experiments?

Meme-licious

5 Year Plans

Well this one goes to eleven - NOW NEW AND IMPROVED!

Horse, get over here! Cause I'm getting back on ya.

At the SGP Calcium Signalling and Disease conference

Dear Brain Thingy in My Head

Let's make some stuff!

I love making figures! I hate making figures!

And we're back!

Vacation's all I ever wanted, vacation trying to get away

The Rule Of Three

The Science Book Meme - let's start it! - UPDATED AGAIN!

Genealogies, of the academic variety

The Book Meme

David Linden starts as Editor in Chief of Journal of Neurophysiology

Dreaming of heaven...of the electrophysiologist's type

What are the 'bibles' of your field?

Wednesday quick hits

Conceptual and experimental innovators in science and Galenson's creative types