Monday, March 31, 2014

Musings about Chipotle

Just went to Chipotle, one of my children's favorite places to eat. Decent burritos, etc. Here are a few things I've noticed about Chipotle:

  1. You can always ask for vegetables on anything. Very delicious grilled onions and peppers. A must add.
  2. I've been getting double beans (pinto, natch), hold the rice on my burritos, and I LOVE it. I don't like the rice so much, so this is great. But there's a problem: the beans are juicy and there's no rice to soak it up, so be prepared for, umm, breaches in hull integrity. Double beans has a number of other side effects as well.
  3. Kids meals are seriously the best deal ever. Tacos/quesadillas with a side of rice, beans, salsa, chips and milk.  All for something like $4-5. I can't tell you the exact price because I don't know it. Literally every time I go through the line, I pay a different amount, depending on whether the count some stuff as sides or extras. Whatever–it's a good deal no matter what.
  4. Paul in lab has told me that there's something called the quesarrito, which is a burrito that is wrapped in cheese sandwiched between two tortillas. Sounds divine! But I've never ordered one. I think I keep forgetting, and Paul also said they only like to do it when there's not a lot of people around because it's a bit slow. I gotta try it, sometime, though.

Sunday, March 30, 2014

MATLAB figure defaults

Working on a grant, and I have to do SO MUCH fussing in Illustrator just to get stupid MATLAB figures to look even remotely presentable. Why are MATLAB figures so terrible looking?  R makes everything look so much better. And it does it by default–MATLAB can make at least somewhat better looking stuff than what it spits out automatically, but it requires endless tweaking of parameters.

In the remote event that any Mathworks people out there are looking at this, here's a list of problems:
  1. Default axes are way overticked. I don't need to have 0, 50, 100, etc. all the way up to 1000.
  2. Font sizes are ridiculously small. For publication, figures need to be small. Text gets shrunk to the point of being completely illegible.
  3. Line widths are all way too thin by default. Except for axes, which are too thick.
  4. Default markers sizes are all way too small.
Please, MATLAB graphics people, help! Make me want to love you, rather than need to have you.

Saturday, March 29, 2014

GATTACA and modern biology

I was just watching the movie GATTACA, an old (and fairly mediocre) sci-fi movie from 1997 with Ethan Hawke and Uma Thurman. The movie is about a future in which the vast majority of humans are genetically engineered and constant genetic testing determines your entire future. Ethan Hawke is naturally conceived (a "God child" from a "faith birth") who ends up having all sorts of genetic flaws but somehow conquers the odds to succeed despite his genes.

Throughout the movie, they're always plugging samples into little devices that read out your sequence to determine what you're all about. I guess we're not all that far away from that now. I just got back from a Cold Spring Harbor Lab meeting about systems biology, and certainly in biology, that era's already here–people just sequence everything in sight. What's funny is that maybe the message of the movie applies just as much to modern biology as to society: maybe just sequencing everything won't reveal everything about how a cell works. It just happens to be what we're able to do.

There's an interesting line in the movie when Ethan Hawke takes over the identity of a "valid" (a person with good genes played by Jude Law) and in the process, he notes that "We don't look anything alike", to which the identity swapper agent guy says "When was the last time anyone looked at a photograph?" I was thinking, again, so true in biology, nobody even looks at cells anymore. Ah, but we do, I thought! But before I got too pleased with myself, I remembered that even our images are based on nucleic acid sequences!

Thursday, March 27, 2014

Another scene from the lab

Scene: Olivia getting DNA from a PCR purification kit, but the output smells a bit of ethanol.

Olivia: Ah, okay, let’s get this DNA!
[sniffs tube]
Olivia [talking to tube]: Have you been drinking again?
Tube: …
Olivia: You have, haven’t you?
Tube: …

Scene from the lab

Arjun: Hey Sydney, I was just thinking about something and wanted to bother you a bit and interrupt your work by talking about it.

Sydney [loudly, with headphones on]: Sorry, I can't hear you. I've got this song on from the Backstreet Boys. It's so good. It has a really good story.

Arjun: ...

Tuesday, March 25, 2014

Statistics is not science

[Disclaimer: I am NOT suggesting that statistics is not a science, rather that statistics is not science. Important distinction. Read on. I love stats! Not that I'm particularly good at them...]

I was writing back and forth with Gautham a bit, and he observed that statistics truly is a grim science: the whole point of it is to curb your enthusiasm, be the wet blanket, rain on the parade. I think it’s also true that statistics as applied to science today is perhaps not used the way statisticians really intended it to be used. From what I’ve read (correct me if I’m wrong, dear readers), things like the p-value were designed as quick tests just to make sure that whatever you were observing might not just be a fluke. It is not a substitute for scientific thought. But in our desire to systematize our analyses, we’ve created a system in which the p-value is an end in and of itself. We’ve all heard of people digging through statistical tests to check whether such and such effect is statistically significant, and that is of course bad, and we'd of course never do anything like that ourselves :). But at least there is an effect that someone has reasoned may have scientific significance, so the problem can in principle be rectified with more data. The other situation, where you just look for statistical significance as the scientific finding itself, seems more troubling to me from the perspective of gaining scientific insight (I have been guilty of this myself). We have a tricky situation in biology now, where our measurement tools are getting so good that we can pick up tons of effects with statistical significance. The real question is scientific significance. As an aside, at Nature, I think you can’t even utter the word significant unless it comes with a p-value. To me, this is placing the wrong emphasis on the use of the word significant.

One of my favorite Gautham quotes is “Would Newton have come up with the theory of gravitation by machine learning?” A corollary quote could be “What is the p-value on the theory of gravitation?” Lately, my thinking is that a theory cannot have a p-value: it is the product of scientific thinking and trying to understand our world, and that is what is significant. A theory can lead to a model of a system, which you can use to make predictions which can have p-values (like the five-sigma standard for the discovery of the Higgs) to evaluate whether the theory is right or wrong.  But the theory itself stands or does not stand on the collective judgement of us as scientists and humans as to whether it is telling us the truth about reality. I feel like that is the truest test of significance.

Sunday, March 23, 2014

Screen blight

Was watching a talk the other morning from the back of the room, and this was the scene. How many people do you think were actually watching the talk? At least everyone clapped! [Note: I am totally guilty of this myself.]

Thursday, March 20, 2014

What causes the variance in protein abundance levels?

Just saw a great talk by Mark Biggin at CSHL about some work he has done in quantifying the degree to which protein abundance differences depend on translation rate vs. mRNA abundance. It relates to data from Schwanhausser et al., in which the authors claim that most of the variance comes from differences in protein translation. They arrive at this claim by showing that there is a lot of variance about the fit line between protein abundance and mRNA abundance. Mark made the excellent point that any sources of error would also lead to such variance, thus leading to an overestimation of the role of translation rate in protein abundance. Once you take this into account, the role of translation is much diminished, with transcription making up most of the difference. Very cool! And important, I think...

Knowledge, wisdom, insight

It occurs to me that knowledge, insight and wisdom are related but not the same thing. Ideally one would be simultaneously knowledgeable, insightful and wise, but that seems very rare. I wonder if the best collaborations are ones where people complement each other in this regard. Of course, to me, the most important consideration is whether someone is cool and not a jerk. Also rare!

Monday, March 17, 2014

Social networks and self-censorship in science

I love posting on the lab blog. It’s been a great way to post thoughts about science (and other stuff) quickly and easily, and I’m really happy that there are some people that even read the thing! In comparison to the standard, hopelessly out of date lab website, it’s just so much more alive and interesting. I long for the day when journals and “peer review” are a distant memory, and we all just post on our blogs.

Along those lines, one of the hopes I had initially for the blog was that we could use it as a forum to post negative results or other little tidbits that just aren’t worth the effort (or, more accurately, misery) of publishing in a journal. That has not happened, sadly, and let me tell you, it’s most definitely not because we never got any negative results. The main thing is that I’m scared. If we make negative comments about a particular paper (or, indeed, an entire field), even our comments are substantiated by fact, it doesn’t matter: you will make enemies of the people who review your papers and grants, and you will find it that much harder to get your own point across. Note that it’s not just the big name power players who you have to be wary of. Peer review (grants, papers) crosses many layers of the food chain, and there are a vast number of stakeholders in any given field.

Of course, I am a junior faculty member, and so these misgivings might be construed as the trepidations of a person on thin ice. Maybe. But I can say that I certainly wouldn’t change this behavior just because I had tenure. Papers and grants are important no matter what your career stage. Without them, you would just end up being that “crusty old guy” who isn’t “with it”. So even if you’re right, nobody listens.

I’m thinking that the only way around this is to build your own community that can sustain itself on some level. The only problem with this approach is that it’s hard to rally a field around a negative result (perhaps with good reason). So maybe you just have to wait for a field to wither away and die on its own. Or finally build up the courage to just post this stuff on the blog!

Tuesday, March 11, 2014

Ask a weird question, get a weird answer

Was talking with my 4 year old son the other night at dinner, and we had a little Q&A session:

Q: What do you like better, tacos or quesadillas?
A: I like both the same.

Q: What do you like better, green on blue?
A: Green.

Q: What do you like better, tall or short?
A: Bambi.

Sunday, March 9, 2014

You're probably hot if you have a fast metabolism - rudimentary thoughts on "fast" and "slow" metabolism.

- Gautham

(An update of something I posted on facebook many years ago on applying some simple thoughts related to machine efficiency to the topic of human weight loss and gain and "slow/fast" metabolism).

I sometimes run into people (usually young males) who want to gain weight but claim they can't because they feel they have a fast metabolism. The first question I ask is what did they have for breakfast. The answer was nothing or not much, which is typical. Literally >80% of people that I've run into that say they can't gain because of metabolism don't eat a substantial breakfast. It is extremely hard to make it over the bar with two meals a day rather than with three or four. I have grown very suspicious of this talk of "metabolism" differences. They may be there but my guess is that they are overstated.

What would it mean for someone to have a fast metabolism?

If your body composition and weight is at steady state, the following must be true, because a fuel that is not stored must be either burned, used for work (which also produces some heat), or thrown out (can you think of another option?):
Food in = Food out (excreted) + Work done + Heat produced.
In this scheme, the only way you can eat more than someone of identical mass but remain at steady weight is if: 
  1. You excrete more.
  2. You do more work. Maybe you run more than someone, or you run the same but inefficiently. Maybe you are a fidgeter as opposed to a laid-back relaxed type. This could include having a more muscular composition, which is said to require greater work to maintain.
  3. You expel more heat. This could be some combination of the following factors:
  • You have a harder time keeping your body temperature because of higher surface area, less clothing, or colder ambient temperature.
  • You have a substantially higher body temperature. 

Considering that heat loss is proportional to the temperature difference between you and your surroundings, a 10% faster metabolism that doesn't involve more excretion, more work or higher surface area means that your temperature difference with the environment is at least 10% larger. For a normal human being at room temperature (25C), this would mean your body temperature is at least a full degree celsius warmer: from 37C to 38C. And that is just for a 10% faster metabolism.
So if you want to claim that you have a fast metabolism, an implication is that you are likely running hot. The other option is a high heat transfer coefficient.

More likely, a close examination of total food intake and activity will show that systemic differences are smaller than they seem.

Metabolism slowing down when you get older 

Looking at things this way, it reduces the plausibility that anybody's metabolism 'slows' down when they grow older. That used to make sense - oh it slows down, like cars or other devices with age. 

However, this way of thinking implies that the design goal of human physiology is to be able to eat more without increasing in weight. Our long-ago ancestors would strongly disagree that this was the main problem they were facing.
A 'slowdown' in metabolism in the sense people usually seem to mean (I am doing everything the same as when I was younger but I am gaining weight) actually would imply an increase in work efficiency of the body. You work more efficiently or you expel less heat. In this sense, a person's metabolism slowing down with age is like a car's gas mileage increasing the longer you have it.

More likely, as a friend pointed out, an older person with a "slower" metabolism is simply doing less physical work (perhaps due to learning how to do things more efficiently), not exercising, not fidgeting, living in comfortable climate-controlled surroundings, etc. 

So in both cases: decline with age and apparent variation between people, perhaps best to first carefully look at what one eats and what one does before concluding that the difference is in one's own system.

Friday, March 7, 2014

Let others organize your e-mail

One of the biggest management issues people have with e-mail is that so much different stuff comes through your e-mail box that it’s hard to keep track of. For instance, research e-mail, teaching e-mail and committee e-mail all come into the same inbox, waiting for me to sort it all out. I could sort it all into mailboxes/labels, but honestly, it’s too much work, so I rely on search. But search is only so good–it’s not perfect, and sometimes there are times when I need to find *all* responses to a particular e-mail from a variety of people, and it’s not okay to miss one of them. It’s tricky because sometimes the respondents will change the subject line or not include the original message in their reply, which means stuff can slip through the search engine. What to do?

Recently, it occurred to me: why not let people who e-mail me do the sorting? There are a couple ways of doing this, and I’ve implemented one and am considering implementing the other:
  1. Just make a new e-mail address. This term, I made myself a specific e-mail address just for teaching. I instructed my students to just use this e-mail address for contacting me. This serves two purposes: first, it makes it much easier to sort for these messages so that I can find *all* teaching associated e-mails without having to do any filing or searching. Second, it makes me much less likely to miss some teaching-related e-mail tangled in their with the rest of my e-mail, making me more responsive. So far, so good–I think it’s a clear win here. But I don’t think this strategy can work except for cases where you have a very clear delineation of communication. Some people have a “important” e-mail vs. a “everyone else” e-mail. But any time there’s a blurry line, there will be bleed through, and over time it just devolves into a mess. For teaching, though, this works well.
  2. Use the trick. I just learned recently about a cool Gmail feature, which is that if your Gmail address is, then if “string" is any string, will also come to your Gmail inbox, but the “To” field will be Basically, this allows senders to add tags to the e-mails they are sending you! The problem, of course, is that they have to know about your tags ahead of time, and actually be conscientious enough to stick to it (which of course I wouldn’t do). But there is a way to encourage this: use the “Reply To” field. Let’s say I’m asking for faculty feedback on some departmental matter. Then I can send out the e-mail with in Reply To and hopefully all the responses will be all nicely tagged. I haven’t tried this yet, but let me tell you, I really wish I had thought of this about 2 months ago…
Anybody else have other tricks for how to manage e-mail?

Wednesday, March 5, 2014

Being the best

I was just playing the game "Threes" (very addictive, highly recommended) with my son, and I was thinking, "Huh, this is a fun game, I wonder what's the highest number you can get?" Then I thought, oh jeez, there's got to be some kid in Estonia who has gotten some simply astronomical score–better not to even check. It's a unique time in history, I think, when we can so easily see the best in the world at just about everything. Is this good or bad? I can see it pushing people to get better, to be the best. I can see it making people give up entirely, thinking about how hopeless it would ever be to get so good at something (I find myself in this camp with most video games these days). Maybe some people even respond in the way we always imagine we would, namely ignoring the world at large and focusing rather on how to make ourselves better, which is the truest form of the journey we are on.

At the same time, our society has also evolved to make everyone feel like a "winner" all the time. Sometimes there are so many awards for stuff for kids that you would feel bad if your kid didn't win anything. Then we end up with these kids in college who can't believe that they got a B+ for getting the class average.  It's a strange dichotomy, I feel...