Being right doesn’t mean that those people aren’t idiots. Unless you’re in Mexico or treating infected people, you’re still very unlikely to be exposed to the new virus. And if you’re in a developed country it’s probably better to get infected now than later, when the virus could have mutated and become more harmful, medical supplies have been exhausted and hospitals are overwhelmed. Get swine flu right now and you’ll see a Nobel Prize reunion happening at your bedside plus immunity for the rest of your life.

The Culprit

17 crime scenes, including two murders (including a 22 year old police officer) but also car jackings, unprofessional break-ins and on a bullet fired in a marital dispute. The crimes where spread around a large area including south-west Germany, France and Switzerland.

It now turns out that the several-hundred-men task force might have really been chasing a phantom. Alarmed by the apparent randomness of the crimes, involving both highly professional work and seemingly amateur break-ins, they started checking for contaminations in the labwork. The likeliest suspect now are the cotton swabs used to collect evidence at the crime scene. All the swabs used in the forensics works were sourced from the same supplier, a company in northern Germany that employs several eastern-European women that would fit the profile. Even more inciminating, the state of Bavaria lies right in the center of the crimes’ locations, without ever finding matching DNA in crimes on its territory. Guess what: they get their cotton swabs from a different supplier.

While the suspicion had already been growing in the last few months, the smoking gun apparently was a case where they tried to match a burned (male) corpse to DNA collected from fingerprint samples an asylum-seeker had given a few months earlier. The first test showed a match between those fingerprints and the Phantom’s DNA while a second test did not.

By the way: contaminated cotton swabs aren”t as trivial to avoid as one might think. It’s relatively easy to sterilize cotton to prevent infections. Forensics however require a complete destruction or removal of any DNA contamination, which is apparently a lot harder.

Firstly, I wasn’t really passing judgement. There’s nothing wrong with commercial software, I’ve written enough of that myself. Nor is there anything wrong with soliciting contributions to open source software projects, especially when they’re as good as pyMOL. However, looking at the pyMOL website and download page, it seems that DeLano Sc. is trying to create the impression that a subscription is necessary. There’s a list of commercially available builds and bunch of ways to get inferior or education-only versions. The source download is right there at the bottom, but I somehow missed that when I first went to the site and I know of at least two other people who where also confused. All the options are obvious now, but it is a bit misleading for a first-time user.

I guess it’s the old problem of how to get people to contribute to open source project, and the approach is much like MySQL’s. I’m not sure how useful it is, though. A student using pyMOL once or twice for assignments is not going to pay for it anyway. Any researcher or institution, OTOH, will learn quickly that there’s a OSS version available. They’re used to open source, so there shouldn’t be much corporate red tape that can be avoided with buying commercially, nor will they afraid of compiling it themselves or require much support. The actual value of a subscription is therefore quite low, and many will just choose to pay to support the project.

There is, then, not much use in misleading people into thinking the OSS version is inferior, or hiding it below a long list of commercial options. There’s nothing wrong with asking people for a little goodwill, and many will happily do so especially when it’s not their own budget. I just wished DeLano where a bit more open about it.

Update: the response by pyMOL below is worth reading.

1. Select Wizard -> Measurement from the main menu
2. (This is the non-obviousness) The headline “Distance” in the toolbox in the lower right-hand corner is actually a dropdown. Click on it and select “angle” or “dihedral”.
3. Click on any three (four for dihedrals) atoms that define the bond you want to measure.

Additional tip: the people behind PyMOL are heavily trying to commercialize it, but free versions are available here. They call those versions “outdated”, but there’s nothing wrong with them.

I’ve modeled different scoring function for each daily objective (running, eating fish etc). I’m trying to get the scores to agree with the measured effects on neurogenesis in the animal model. So if the experimental data indicates that i. e. the beneficial aspect of walnuts is logarithmic (i. e. eating 1kg/day has double the effect of eating 100g/day), the scoring function should reflect that. I’m collecting the raw data and will update the scoring functions and results whenever I find new evidence.

The somewhat bad news is that the official start of my little experiment will be January 1st. It’s partly because of a lapse in discipline (you try finding kiwis in that backwater place my parent inhabit) but mostly because it makes the data processing easier to start at the beginning of a year.

The rest of the holidays was spent reading Feynman’s Lectures and dreaming up things to do with openCL.

Neurons and Glia

Rat Neurons (Image: Dmitry Sarkisov@flickr)

A neuron is basically a cell that can conduct an electric signal, and therefore information. There are about 10¹¹ (100 billion) neurons in the average human brain¹, each of which can have thousands of connections to other neurons. While a single neuron’s activity is simple (it either fires its action potential or not), the connections are not. It might require activation by two or more different incoming neurons with a certain timing for a neuron to fire. Neurons can also depress each others activity, so if neuron A fires, neuron B will remain silent, even if it is excited. These connections are though to be the critical factor in allowing the complexity we see in human and even animal behavior to emerge from a rather simple basic building block, the neuron.

There is another type of cell in your brain that deserves mention, called glia. Outnumbering neurons 10 to 1², glia cells have traditionally been thought of as the brain’s maintenance brigade, providing structural support, nutrition and immune defenses. In recent years, there is growing support for assigning glia a more important role in the CNS, as interactions between glia and neurons have been found³

Now to neurogenesis. Obviously a large amount of neurons (a complete brain) are created even before birth. I might revisit pre-natal neurogenesis at a later point⁴, but for now, when I use the term neurogenesis, I’m talking about adult neurogenesis.

Adult Neurogenesis

Adult Neurogenesis in humans is, like continental drift and epigenetics, a relatively new concept. Consensus until 1998 was a fixed amount of neurons that could only be lost, never gained. Though it is a relatively new proposition, adult neurogenesis is now widely accepted and the evidence is strong. When my previous article hit Hacker News⁵ a user called a-priori was skeptical:

Let me be the first to say, “sources please”. Adult neurogenesis in humans is largely speculative, which leads me to think you’re confusing it with neuroplasticity.[..]⁶

It is important to continually challenge scientific theories, and it’s even more important not to take “but the majority believes it” as definite proof. So let’s take a look at the evidence. The standard method to detect and measure neurogenesis uses a substance called Bromodeoxyuridine

BrdU-Labeled Cells in the Human Brain (Image: Peter S. Eriksson)

or BrdU. It’s a molecule that closely resembles Thymidine, the T in the ACGT alphabet DNA is written in. When cells divide, they copy their DNA. If there’s BrdU around (i. e. if an evil scientist has injected it), it will be incorporated into the newly synthesized DNA. When the animal dies, new cells contain BrdU that can be colored so they show up clearly under a microscope. The image shows a slice of human brain tissue with three BrdU-labeled cells. These cells must have been created after the BrdU injections.

While the decades-old dogma that adult neurogenesis does not exist in humans was overturned should caution us not to blindly accept the new, reversed dogma, this evidence is much stronger than before (“I cannot find my wallet” does not proof that my wallet does not exist, while “I have my wallet in my hand” is pretty good evidence that the wallet does exist).

Adult neurogenesis was first shown in canaries by Goldman and Nottebohm⁷ It took until 1998 before it was shown in humans⁸ . So adult neurogenesis in humans exists. The next questions will be where in the brain it is located, what goes on in those regions and what effects neurogenesis actually has.

1. Wikipedia: Brain
2. Society for Neuroscience
3. Haydon P: Glia: listening and taking to the synapse, Nature Reviews Neuroscience 2001
4. at least some of the ideas I’ll be talking about should also be applicable in pre-natal neurogenesis, such as anything regarding substance abuse
5. http://news.ycombinator.com/item?id=397537
6. http://news.ycombinator.com/item?id=397628
7. Goldman et al. … Production, Migration, and Differentiation in a Vocal Control Nucleus of the Adult Female Canary …. Proceedings of the National Academy of Sciences (1983)
8. Eriksson et al. Neurogenesis in the adult human hippocampus. Nature Medicine (1998)

The first day was almost perfect. Somehow, I managed to get by without cigarettes, but could not avoid getting (and drinking) a coffee. I guess it felt like the lesser sin. Since neurogenesis takes at least three weeks to kick in, most of the effect I’m feeling (insomnia and soreness) are probably results of nicotine withdrawal and exercise.

I’ll probably write a small script later this week to plot my compliance and test results, so future updates should be all pretty and colorful.

Neuron by Neurollero@flickr

The benefits of neurogenesis

There are a number of benefits ascribed to neurogenesis. One is improved mood. Indeed, the current hypothesis is that the mood-enhancing effects of antidepressants can be ascribed to a stimulation of neurogenesis.

Another, less certain, benefit is improved learning. There’s a lot of disagreement and conflicting results regarding the link between neurogenesis and learning, even in rats. But it seems the evidence is growing that neurogenesis improves at least certain types of learning, and I’m hopeful that these results also apply to humans.

At this point I should mention why I’m interested in these benefits. Firstly: who wouldn’t like to be in a better mood and learn faster? And secondly, I’m a student, plagued by the No. 1 student disease, procrastination. There seems to be a link between procrastination and mood (more on that in a later post), so improving the latter should help. I’m also at a point in my studies where I’d like to learn some highly mathematical stuff (like quantum mechanics) and a little boost of mental capabilities wouldn’t hurt. Lots of students and scientists take stimulants like Ritalin for this purpose. I should probably do so, too,  but I’m just not the type I guess.

The plan: Six ways to stimulate neurogenesis

The benefits are great but useless if there’s no way to influence the amount of neurogenesis. Fortunately, there seem to be quite a few².I’ve picked the most promising six and plan to implement them all at once, which will obviously require a certain amount of discipline. To measure compliance, I’m going to award points each day for correctly implementing these.

1. Exercise

The most effective way to stimulate neuron growth in rats has been physical exercise. Aerobic exercise is thought to be more effective, so my plan is 4km of running every morning. The distance should increase once I get better. Running will count as 1.5 points. I will complement this with another unit of sports each evening, alternating weigh lifting, (the physically stressing type of) yoga and meditation (not a sport, still effective) (1 point).

2. Change of environment

A “new, but benign” environment also seems to increase neurogenesis. I’ll get 1 point if I manage to learn/work for five hours in a place I haven’t visited for at least a week. This can be anything: one of the many libraries or the even larger amount of coffee shops. For the purpose of this experiment, all Starbucks shall count as one, as they really aren’t distinctive enough to call the second one “new”.

3. Omega-3 fatty acids

Unsaturated ω-3 fatty acids seem to be an important building block of new neurons. I’ve developed a somewhat drinkable milk shake that contains about 80g of linseed oil, which is very rich in Alpha-linolenic acid. Gets me 1 point for drinking it. Another 0.75 point are added for a ω-3-rich dinner such as fish.

4. Avoid junk foods

Junk food is bad for you. I haven’t found any paper directly linking Big Macs and stupidity, but it seems prudent to stay off the stuff for a while. 1 point for each day without Ben&Jerry’s and pizza.

5. No caffeine

This will be hard. There is, unfortunately, pretty good evidence that caffeine inhibits neurogenesis. The new stainless steel espresso maker will therefore be my girlfriend’s exclusive territory, unless I want to forfeit the 1 point.

6. No nicotine, either

With the coffee goes the cigarette. I’ve smoked a pack a day for the last three years, so this will require a lot of willpower. Points: 1-(#of Cigarettes/17).

Measuring success

There is, unfortunately, no easy way to measure my success. I will record and publish my compliance as measured by the point system above. I will add to that my effectiveness in work/study as measured by RescueTime and the results of a weekly memory test (remembering as many digits of a random number in one minute as possible).

Is this science?

Yes and no, but mostly no. For this to be a scientific experiment one would (a) test each measure by itself, (b) have a control group and (c) do each experiment on more than one person.

1. http://en.wikipedia.org/wiki/Neurogenesis
2. at least in rats