As usual, way behind in the note-keeping business, but a few random tidbits instead:

• Gotta love a city where catching an afternoon performance of Mahler’s Third by the Staatskapelle Berlin conducted by Daniel Barenboim (brilliantly filling in for James Levine), is as simple as: picking Nino fresh off her plane at Alexanderplatz, walking over to Staatsoper and buying three (very cheap) last minute-tickets.
• Used the excuse of miscellaneous out-of-town visitors to check a few of the more touristy items off my Berlin list.
• For an artist squat long past its underground heydays and part of even the most casual touristic tours of Berlin, Tacheles was still surprisingly fresh and unassuming: with some cool art, a relaxed atmosphere and a funky bar to grab a drink at in the middle of the night. You can also buy “Kultur kann man nicht kaufen” postcards for 1.30€ there.
• I apparently look very fetching in a tiara. A comforting thought, in case I finally quit research to pursue my lifelong dream of becoming a pretty princess.
• Only major piece left missing to our Berlin nightclub collection, Berghain was actually sort of a letdown: not bad, but definitely nowhere near what the legend gave it as. Perhaps just that particular night. Had fun anyway.
• Also caught Jazzanova (or a two people subset thereof) at Icon. Rather unimpressive DJing skills (at least before the 5th Vodka mit Red Bull), but some damn awesome blend of everything Latin, Jazzy and Danceable (from Calypso to Cumbia, with your fair share of random house beats in the middle). Funnily enough, threw the same Led Zep nod as Theo Parrish at Yellow, a couple years back: except they played Whole Lotta Love, not Kashmir…

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More Random Comments and Appreciation: a Berlin Wrap-Up

Too soon?

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Back from the Clubs…

1. You get shocked, touching your own desk.
2. You get shocked, touching the metal doorknob to your office.
3. You get shocked, washing your hands (not touching the faucet, mind you).
4. All of the above.
5. All of the above, over a 20 minute timespan.

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Electrostatic Research

… at 4 terabytes…

… per user.

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You know you are in a Bioinformatics lab when…

• Despite my impression of the past few years that Japanese cinema was losing ground to more daring, less formulaic Korean filmmakers such as Park Chan-wook, Japanese movies were particularly well represented at the Berlinale and fared pretty well.
• Of the three screening we attended, Korean movie Ki-chin was definitely the weakest: beautiful photography, unfortunately undermined by a contrived plot and the least engaging depictions of food I have ever seen in a food-oriented movie (not to mention terminally inept subtitling work, which made it difficult to follow even basic dialogues).
• Yoji Yamada’s films were of a much higher grade. Friday’s première screening of Kyoto Uzumasa Monogatari was a nice prelude to the more involved Ototo, on Sunday. Both had a rather typical Japanese vibe of quiet everyday life events mixed with deeper topics that never take themselves too seriously. Still not convinced about the Japanese conception of slapstick physical humour as the height of comic relief, but overall good movies.
• Thanks to Berlin’s opulence in Opera venues, we obtained last minute tickets for a representation of my all-time favourite (my undying love of Verdi’s works, over any Bellini, Wagner or even Mozart, is a clear reflection of my mundane operatic tastes, sure, but I stand by it).
• Musical happiness.
• Small aside: people who can’t help loudly coughing, right in the middle of Violetta’s dying aria, deserve to be put to a slow and painful death. I don’t care how much your throat itches: put a lid on it or stay home. And while we are at it: do not clap at the end of every single fucking scene. Keep it limited to the overture, the end of each act and at most a few noteworthy arias and find something else to keep your hands and cerebral-motor cortex busy.

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Random Comments and Appreciation

Sometimes I do work too.

Now you know why updates are scarce around here…

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This month’s ticket purchases…

Liebes Diary,

It has now been 15 days that the great yellow star has vanished from the sky. Ancient ones have prophecised that it shall return one day if we make the proper sacrifices to the gods. Then again, ancient ones will say anything for a chance at skinning a dozen virgins, while getting high on mystical plants. According to German news, such a dark spell had not occured since 1964. I liked it much better back when meteorological records involved “longest dry spell ever recorded on a rainy season” or “warmest autumn since the invention of thermometers”. Now that we have successfully debunked the liberal global warming hoax, can we go back to abnormally mild winters, exquisitely hot summers and dangerously rising sea levels? That Siberian datcha I bought last year is not gonna become a waterfront on its own.

As predicted last month to easily amazed Japanese friends, our German flat comes with such marvels of 19th century technology as central heating and double-windows. Unfortunately it also features 10ft high ceilings, which sorta defeats the purpose. Something is not quite right when the longest dimension of your bedroom is height. I assume, however, than my no doubt imminent transformation into a blood-sucking creature of the night will solve this issue by making “upside down, hanging from the ceiling”, a perfectly natural sleeping position.

Although technically “in” Berlin, my laboratorium sits in the middle of the German tundra. Access requires usage of the entire bahn alphabet, followed by a vivifying walk through neighbouring parks and forests. I spotted a couple wolves in the distance, on my way home yesterday night. They fortunately seemed too busy fighting over the remains of some unlucky coworker to notice me. I did notify the lab secretary this morning that I did not think Hans was staying home with the flu, as was initially assumed.

My German is slowly crawling back to the satisfyingly mediocre level of my high school years. I still tend to answer all questions with “sou desu ne“.

The Fall of the Berlin Wall, German reunification and ensuing economic and sociological challenges of the early 90s, are expectedly way less popular a conversation topic than may have been implied by 7 years of high school language classes relentlessly covering the subject. Had Frau Wagner spent just a little less time obsessing about Wiedervereinigung, Ossis, Wessis and balloons coming in easily roundable numbers, I might actually know how to say useful everyday things. As it is, I am now known in my social group as the guy with a surprisingly rich German vocabulary pertaining to the plight of disenfranchised and politically disillusioned East German workers confronted to consumerist and individualist values inherent to the capitalistic system of the West. Also known as: that guy with the tedious conversation who can barely order for himself at the restaurant. Fuck you Frau Wagner.

Linguistic limitations aside, and despite the equally unsurprising lack of opportunities for congratulating one’s interlocutor about the cuteness of their monkey in casual bar conversations (“Was fur ein süße Affe!” — year 1, lesson 1), people are friendly and fun to hang out with. Sadly, my considerable repertoire of Hitler jokes remains largely unappreciated, strangely enough.

I have an increasingly hard time repressing the urge to punch newly met acquaintances who mention how great and enjoyable Summer in Berlin is. Which they never fail to do. Preferably shortly after it has been announced that the negative double-digit temperature is likely to last until at least the end of February (“When did you say you were leaving again? Oh… I see… sorry”).

I must now step out to go replenish our survival chocolate supply at the store across the street. It looks like there’s yet another small snow storm outside. Where did I put the damn polar bear gun.

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Deutsch Chroniken, Teil 1

It took a while, but I think I finally know how it feels to be the ancient one, sitting helplessly while the younger ones try to operate antiquated machinery from another era… say, a turntable.

Picture if you will: a standard Berlin bar, two cheerful yet terminally hopeless barmaids, a pair of standard-issue decks, a [presumably rather cheesy German] record to be played…

It went a little bit like this:

1. Barmaid places record on deck, tries to play it for 2 minutes before realising said deck has no needle (stylus or cartridge, for that matter).
2. Barmaid repeatedly tries to spot the beginning of some track she is presumably looking for, using a lighter for sole light source. Gets ever so slightly pissy when yours truly points [as gently as possible] toward the button to enable the dedicated target light that comes standard on all SL-1200.
3. Barmaid #2 [unsuccessfully] tries to fit a raw stylus into the standard needle connector, apparently oblivious to the obvious size/shape difference.
4. Barmaids have stroke of genius and finally decide to switch the entire deck with the other deck (changing cables and all), yet again failing to notice that simply switching the cartridge, would have been a considerably easier endeavour.
5. After finally plugging the new deck in, barmaids enter long struggle to figure the on/off dial on the new deck. Get increasingly pissy at any attempt to point them in the right direction… Finally give up in frustration and put a CD instead.

Seriously: now I know exactly how old-timers feel, when they see condescending-yet-clueless youngsters trying to operate a 1930s radio… and miserably failing at it, as if it was some alien technology.

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The Youth of Today…

The only question is: does either go up to 11?

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Stronger or Strongest?

In Paris for New Year’s Eve (and a few more days after that), before going back to Berlin until the end of Winter.

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Snowy Winter Break

If your talk lasts 25 minutes and goes into the minutiae of protein-protein interactions with regard to oncogenic pathways, maybe spending half of it convincing an audience of biologists and bioinformaticians that cancer is a bad thing that needs curing is not the best use of presentation time.

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Bioinformatics Conference Pro Tip

Although it could probably go lighter on the whole Mission: Impossible antics (unfortunately, it seems you just can’t sell a documentary nowadays if it doesn’t feature endless gratuitous action montages), the scenes it captures are captivating and hard to ignore. Beyond the expected money shot of an expanse of ocean literally red with dolphin blood, the investigative work offers some fascinating insights into the cynical political maneuvering that goes on to ensure the fishing doesn’t stop.

The vast farce that is the International Whaling Commission and a long tradition of Japan’s bribing third world island countries for votes, gets the bashing it deserves: I don’t care what your opinions on the whaling issue are, if you seriously believe in the “scientific whaling” argument, you are very misinformed or a moron.

Casual observers of Japanese modern history do not need to be told of its infamous propensity to always side with industries against public welfare, when environmental or public health scandals strike. Others will probably think that the recount of Minamata disease’s infamous cover-up is exaggerated… After all, while Western countries routinely poison locals in remote third-world countries and get away with it, it is quite a rare thing for a country to let companies do it on its own soil and unfalteringly support them when things go awry (and long after that). Long-time residents will also enjoy the nod to Japan’s sub-par criminal justice system, delight in spotting the usual cast of Japanese administration characters (the blatantly corrupt – yet utterly polite – cop on local business’ payroll, the roboticized bureaucratic talking-head, the government “scientist” spouting pseudo-science etc. etc.), without, unfortunately, escaping the usual trite clichés (is there a single japanese story that cannot be illustrated with a nail and a hammer?).

This documentary is not without its faults and I honestly have my doubt about the efficiency of the “Us vs. Them” brand of activism, when confronted to Japanese culture. But regardless of which side of the Blubber Hamburger / Cute Smiling Cetacean debate you stand on, there are a couple items worth pondering in there.

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The Cove: Japan’s Delicious Dolphin Burger Industry

Guess them all and win a bunch of iTunes coupons for free installs of KanjiBox for iPhone (along with my undying respect for your extensive musical culture).

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Think you know Japanese music?

Am I a bad person for even wondering how many years I could live off that, were I to accidentally end up on some remote beach island instead of Berlin’s Max Planck Institute for Molekular Genetics?

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So many zeros…

I wasn’t exactly handed a winning ticket at the Genetic Lottery. As a kid, it would have taken less time to list the parts that did work as they should have. But things got under control and I am generally fine these days (beside that violent twitching on the left side of my face and the regular furball coughing, that is).

However, God personally hates me and wants to make sure I know it. Which is why I belong to the statistically improbable demographic of young people with recurring kidney stone problems despite relatively healthy dietary habits (people in their twenties who barely drink a can of coke a month aren’t supposed to get kidney stones, let alone chronic ones). On a nearly regular basis, about once every two years, I get to enjoy the pain of childbirth, minus naming process and postpartum hormones rush.

On the plus side, with the years, the routine has started to take the edge off (or I am developing a much higher tolerance to pain): when a stone episode strikes, nowadays, I just casually recoil in a fetal position for a couple hours at a time while waiting for it to pass; years ago: I would longingly stare at a kitchen knife while considering my options for self-surgery on the spot.

The other good thing is that I have learned to recognise early symptoms (as well as the time they are likely to occur: mine always happen in Winter, for no reason any specialist has ever been able to explain satisfyingly), which helps preventing me from making bad decisions… such as embarking on a 15 hour trip home to San Francisco from Paris via London (aka: the Story of my First Stone). Testament to the good old pre-911 days: when some security guy at Heathrow noticed the sweaty, grimacing guy waiting for his plane, went and asked “Sir, I must ask you: have you been consuming any drugs?” and got a near-hysterical answer of “No, but if you have any, I’ll take them!” through gritted teeth… he just walked away as he came.

These days, once the chest pain shows up, I would know better than trying to lob it with 2 aspirins and a cup of boiling hot tea purchased on the Eurostar for sole comfort.

Three days into the current episode, I finally went for a consultation at my nearby hospital: a CT scan confirmed the obvious and I was sent on my way with the usual advices and a couple prescription drugs.

Incidentally: I payed ¥5,000 (less than $50) for a full consultation and a CT scan, both of which took a grand total of 40 minutes, from the moment I stepped into my neighbourhood clinic. The actual cost, pre-universal-coverage, was ¥19,000, or about $200 (for that money, a US CT technician won’t even spit on you): dear US readers, aren’t you glad you live in a country gloriously free of such pesky Universal Healthcare and reasonable health costs.

Anyway, all that to say that I am slightly incapacitated at the moment, and lagging on communication (although oddly productive on whatever I manage to put my mind to, in between two bouts of holding my abdomen, wondering if downing a bottle of Draino might help). It will get better and I’ll catch up on email and everything, soon (i.e. anywhere from next week to next year).

That’s it for the immediate personal health update. Everybody with a normally working pair of kidneys and zero interest in the practice of hobbyist medicine at home can (and should) stop reading right now. Trust me, there’s nothing interesting under the fold.

Kidney Stones remedies

Like anybody confronted to their 4th or 5th stone in a decade, I have collected a good deal of empirical knowledge on the issue. It also helped that the first two episodes happened outside of the realm of modern medical medicine: the magic of timing, transatlantic flights and insurrance-less lulls between [proper] jobs in the land of proudly unaffordable healthcare (needless to say: in between years of fully covered, perfect health… try to tell me God doesn’t have it in for me, after that).

Googling and webbing of all stone-related issues tends to yield a mix of obvious, factual and completely moronic/batshit insane advices. With a recurring theme being the product-pushing agenda of the websites giving said advice. In light of this, I figured I would compile a few of my anecdotal findings on the matter, for the sake of the odd Google seeker who may end up here.

Note that:

1. I am not a doctor (unless you count that honorary degree in Love Potion and Curse Healing from Kinshasa’s University of Black Magic). I shouldn’t even have to tell you to consult with a professional, before anything else (frankly, if you hadn’t figured that for yourself, you shouldn’t have the IQ required to operate a computer). Once you have seen a physician, received a diagnostic, commiserating pat on the head, painkiller prescription (and little useful else): feel free to come back here.

2. These aren’t tips to prevent reoccurrence of stones. I’ll let you google/consult for these. Although, they may not always do the trick (take it from somebody who’s been drinking liters of water a day and depriving himself of chocolate for the past few years, and yet is currently contemplating removing the coating from his painkillers to try and snort them for faster absorption).

3. The focus here is on things that will help you deal with pain (and, possibly, but with absolutely no guarantee, help pass the stone faster… on the assumption that not wriggling in pain and spams, helps smooth the descent).

4. Any [already questionable] advice contained here applies only to calcium oxalate crystals (you know, the cool spiky-looking ones that seem designed to tear your insides while clawing their way out). Some might work for other types of stones, but no guarantee here.

That being said, and before going into things that work, let’s start with:

Things that don’t work

Cranberry juice and all other bullshit herbal grandma remedies. Not because they are bullshit herbal grandma remedies with usually zero evidence-based medical results, but because they all apply to a completely unrelated issue. Kidney stones (calcium oxalate ones, that is) aren’t UTI, nor even caused by UTI and rarely have anything to do with UTI. Whatever anecdotal health benefit cranberry juice (and dozens other Flower Power remedies) may have, are entirely geared at UTIs. Drinking cranberry juice while passing a stone has been proved to help, only insofar as drinking any fluid helps. So feel free to replace cranberry juice by gallons of gin&tonic and call it a family remedy: your chances are the same.

Things that work

Water goes without saying. Gallons and gallons of it. All the time, all day long. That stone isn’t gonna carry itself down (that being said, if/when your kidney shows sign of excessive straining on echo or CT scans, lots of water might no longer be a good idea: that’s what your doctor’s advices are for).

Painkillers obviously work. Although if you have tried, you already know that even the strongest painkillers have a very limited effect, in time and in strength. Dosage increases will barely help. And unless you fancy a life of addiction to opiates, they are rarely a good idea. NSAID are the standard fare (also: they are easier to keep on the stomach than opiates, which helps if you aren’t hooked to an IV feed). I have found antispasmodics to be more helpful in the long term (less direct pain relief, but less cramping, which is precisely the point).
Anyway, no real point discussing pharmaceuticals here: you will need a prescription (or a very good dealer), that, again, is what your family doctor is for.

Cannabis. Yep, herbal remedies aren’t completely useless after all. Surprisingly enough, medical cannabis isn’t just a hoax pulled by aging Californian hippies trying to ensure good-quality supplies at cheap price: there’s a reason cancer patients are told to smoke some reefer.
In addition to being a powerful analgesic, cannabinoids have antispasmodic and muscle-relaxant properties, which is precisely what your strained tubes need (less spasm/constriction = less friction = less pain). Trust me (err, I mean: trust my good friend who tried once, officer), it works well. And if it doesn’t, you can always just put on some Bob Marley records and bob your head to it until you forget all your troubles (just kidding).

Of course, were you to choose the weedy path of natural remedies, you should probably avoid living in a country where possession of any drugs (that are not tobacco or alcohol) is a crime on par with killing kittens or having sex with underage schoolgirls (just kidding, of course: the latter is perfectly OK and barely frowned upon by Japanese society, provided you are a well-off middle-aged businessman who doesn’t mind buying them Hello Kitty toys in return).

Which leaves you with:

Heating pads. No joke.
Heating pads (preferably the strong, chemical kind, universally available in Japan, where they are known as ‘kairo’) are a real life-saver. Staying warm is key: keeping one or two strong heating pads over your lower abdomen at all time, greatly helps with the background pain and seems to lower the recurrence of acute pain episodes. During last year’s episode, I was able to be nearly functional for three weeks, including a (very sober) New Year’s Eve party, patiently waiting for my two stones to go down their merry way (or, more exactly: until a very nasty surgical device was inserted to bring them out once it was realised they wouldn’t come out on their own, but that’s beside the point).
If you live in Japan (or another country where these awesome little pads are easily available), go to your nearest pharmacy and buy a few hundreds. If you don’t:

Hot baths are an obvious piece of advice. But just in case you had not noticed yet: dipping into near-boiling water at regular intervals will do miracles to subdue the pain. Just make sure not to get cold chills when you get out.

Things that Might Work

For pain management, the doctor at my local Japanese clinic only prescribed antispasmodics and told me to come back if I needed stronger (which didn’t bother me much, considering how little effect stronger meds usually have anyway).

Along with the antispasmodics, was a prescription for a slightly stranger medication called Urocalun, which turned out to be a rather Japan-specific drug, based on some plant extract (yes: another herbal remedy, but this one comes with somewhat scientific studies attached, rather than your crazy grandmother’s aunt recommendation). Most salient research papers I could find on the topic are in Japanese and only appeared in domestic publications (as is unfortunately typical of a vast amount of Japanese research) where methodologies are, ahem, not always of the highest scientific grade, or sometimes feature downright bizarre ideas (rope jumping as a way to pass stones, anybody?). More importantly, it is not always clear whether Urocalun is only effective as a preventive treatment or can also help during acute episodes.

But at least, there seems to be some scientific basis going for it (which is more than lots of pseudoscientific remedies like homeopathy ever had) and is the first I ever hear of a widely distributed drug treatment for kidney stones (other than palliative, that is). I have the tablets and will be taking them religiously for the next few weeks, we’ll see if it helps.

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Kidney Stones: A Beginner’s Guide…

Japanese girl at local bar: Do your prefer Japanese girls or foreign girls?

Dave: Err… huh… dunno… Country doesn’t have much to do with it…

Japanese girl: Aaah, of course… It does not matter…

Dave: Indeed.

[...]

Japanese girl: Ok, so… Which type of girl do you prefer: long straight black hair or blonde with blue eyes?

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The Art of Subtle Rephrasing

KanjiStory.com is a website geared towards people studying Japanese kanji (and, I guess, to a lesser extent, Chinese… but it probably needs some tuning for that). It provides a simple yet powerful interface for people to write kanji mnemonics in the form of a simple story.

The best way to see what I mean is to go register (10 seconds, one click), read a few stories and finally: take a stab at writing your own. Allowing users to contribute stories is at least 90% of the point of this website at this stage, so please do not just go, check out the dozen sample stories and call it a day without trying the editor.

The current version of the website, although quite spiffy code-wise, needs a huge amount of work to be called a proper beta. And then, there are two million cool features just waiting to be added. However, given my very limited time resources, I figured I would first check to see how much interest (and active participation) in the project I can raise, before committing any more time working on it.

Do not hesitate to post your comments and suggestions below, but keep in mind that this is all very early-stage development and that many new features will come, once (if) this ever takes off the ground as a community project.

As an aside, if you are a reasonably experienced PHP dev with an interest in contributing to this project: get in touch (use the address: “zedrdave” at Google’s mail).

If you want to be kept informed of future KanjiStory-related news, easiest way for now is to sign-up as a fan on the facebook page (until I set up a proper forum and RSS feed on the website).

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Kanji Stories…

Note to Self of Yesterday Night: Maybe not so heavy on the distilled sweet potato juice, next time. Should consider picking a recreational heroin habit instead.

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Weekend Patterns

It was… MURDER!

The things you learn, chatting with your elderly neighbours, stark-naked and soaking in boiling hot water…

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Sentō Gossiping

Translators working on closely related language pairs such as French and English (as opposed to more distant ones, like Japanese and English) have a tendency to be writers first, translators second. Their actual mastery of the source language is sometimes surprisingly low, but (for good or bad reasons) editors seem to think that the quality of their written production in the destination language can make up for their weakness. This is an especially common occurrence in English to French translations, where French speakers barely English-fluent have been known to translate major English literary works (not a new practice either: Baudelaire’s famous translation of Edgar Allan Poe’s, while delightfully written, is so incredibly riddled with errors that it could be a new work in its own right).

The smug pleasure of pointing out errors in the work of so-called professional translators can only be beat by one thing: the even smugger pleasure of pointing out errors in said corrections…

In a recent Guardian article, Germaine Greer plays on a rather trite cultural tropism: “Why do people gush over Proust? I’d rather visit a demented relative“.

Yes, we get it: Proust’s writing is long, convoluted and not exactly packed with action. I am far from his greatest fan and would not even put him in my personal top ten of French authors, but criticising his style on length and paragraph count is about as subtle as calling Picasso’s paintings a bunch of kid scribbles by a guy who couldn’t draw a normal face.

The translation comment, however, is what grabbed my attention. Ms Greer chose to illustrate the poor quality of Proust’s English translations with a sentence drawn from the fifth volume (La Prisonnière, aka The Captive):

Tirant d’un flûtiau, d’une cornemuse, des airs de son pays méridional, dont la lumière s’accordait bien avec les beaux jours, un homme en blouse, tenant à la main un nerf de boeuf, et coiffé d’un béret basque, s’arrêtait devant les maisons.

Then goes to quote the two main translations in turn:

This Scott Moncrieff hilariously renders as: “Drawing from a penny whistle, from a bagpipe, airs of his own southern country whose sunlight harmonised well with these fine days, a man in a blouse, wielding a bull’s pizzle in his hand and wearing a Basque beret on his head, stopped before each house in turn.”

In Carol Clark’s version for Penguin we read: “Drawing from a penny-whistle or bagpipes melodies from his southern homeland, whose light the fine morning recalled, a man in a smock with a bludgeon in his hand, and wearing a beret, stopped in front of the houses.”

Upon reading these, I was confused as to what either translator may have done to deserve Ms. Greer’s hilarity: both translations seem to convey, in a reasonably faithful tone and language, the admittedly obscure meaning of the original.

Her ire stems from one “mistranslated” word in particular:

The translators’ manifest difficulties stem at first from Proust’s own imprecision, and are then compounded by their ignorance. The Pyrenean goatherd carried neither a dried bull’s penis nor a bludgeon – what would he be doing with either? He is going to milk his goats and he needs something with which to restrain them: a hobble made of dried bull sinew.

There are just two small problems with this interesting — and indeed creative — approach to the original meaning:

1. A “nerf-de-boeuf” (literally “bull sinew”) is not actually made of dried bull sinew. It is merely one of these delightful euphemistic idiom people have come to use, in order to avoid having to say “bull penis” in proper company. As such, translating “nerf-de-boeuf” by “bull’s pizzle” is not only correct, but perfectly renders the euphemistic idiom (the old English word “pizzle” is used both for “non-human penis” and a whip made from such).

2. I have very limited first-hand experience as a mountain goat-herder, but I can very easily imagine how a sort of whip or flogging instrument (say… a pizzle) could come handy to herd a pack of goats. While “bludgeon” might stray a bit far from the original (and fail to reflect the actual material used), it still sounds considerably less far-fetched than a hobble. There too, I cannot claim much experience, but a cursory web search showed absolutely no trace of a “nerf-de-boeuf” ever being used as a hobble (which would seem to be made of much softer, more flexible materials).

In the end, it is pretty obvious that, of all three translations, Ms. Greer’s is the least accurate, bordering on a mistranslation, while the professional translators had, for once, done an adequate job.

I could probably go on the importance of double-checking before going about correcting others, but then I am not sure what this would imply on the present entry… So let’s just agree to say that Proust’s work, while certainly daunting from the outlook, is worth a read; and the people taking on the thankless task of translating his humongous body of work should at least get credit and benefit of the doubt for trying.

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Mistranslations and Miscorrections…

Aside from breeding deadly mutant monkeys to serve in my army of evil minions when I kickstart the world-domination part of my plot, that is.

Before I go any further, let me remind the casual reader that: 1) it is most likely nice and sunny out there where you live and you would be considerably better off looking at squirrels running through the trees 2) if you have even the slightest inkling of formal mathematical/computer science training, you will be better served foregoing this edulcorated version in favour of one of the 10 million tutorials and entries on bioinformatics available throughout the internets (Wikipedia being a good place to start). The entry written henceforth is geared at some hypothetical grandparents who would care to know what the fuss with modern Science is all about (for instance mine, were they not already perfectly content in the sole knowledge that the good Lord has put all these tiny amino-acids together in the best possible way of all worlds and that modern genetics are the work of the Devil¹).

In last month’s episode, we laboriously learnt that Biology abounds with really, really, tough problems. Two major points were:

1. For all practical matters, NP-Complete problems are all in the same bag: finding a way to solve one efficiently would mean you can solve any other in roughly the same order of time.

2. Once you have proved that a problem is NP-Complete, trying to find an exact solution for a real-life set of data, is about as meaningful as trying to take down the Everest with a toothpick. There are however plenty of ways to find an approximate solution. Proving NP-Completeness is your cue to start looking for approximation algorithms; and thus the fun begins.

Today, instead of going straight onto the myriad fun ways in which mathematicians solve biology problems, and which one of those I am actually connected to, another digression and an illustration everyone has heard of: genome sequencing.

Full genome sequencing (mapping the entire DNA of a given organism) is one of the earliest application of modern bioinformatics techniques, a seminal example: it starts off as a rather straightforward bio-chemistry problem, soon runs into pesky matters of size, complexity and intractability, goes through a difficult phase of alcohol and substance abuse, but is ultimately saved by the power of Love and Mathematics.

Before I go into the gory details, allow me to dissipate a common misconception about DNA sequencing: it is nowhere as easy as you might have been led to believe by your TV (most people’s preferred source of Science™ facts). Hearing of “DNA tests”, “DNA crime database” and other everyday life DNA-related techniques might make it sound like sequencing is as easy as sending your saliva swab to the lab and waiting a couple days for the results. In reality, despite serious advances, actual full genome sequencing is still a multi-year, multi-million-dollar affair. When people talk about DNA in a forensics or medical context, they are usually looking at a single base nucleotide, located at a precise location on one gene, out of the entire genome. Even cases that require a larger sample of such observations (e.g. DNA matching, when it actually uses sequencing altogether) are still somewhere in the lower hundreds (if that). That’s a mere 100 bases to look at, against 100+ million for the first organism fully sequenced, 10 years ago (make that 3 billions for humans). Quite a difference in scale. And, of course, this is one of those problems where solving twice the size requires much more than twice the time (hopefully by now, this does not surprise you, otherwise you might want to go back and read episode 1 again).

OK, let’s start:

The Easy Part

Long before full-genome sequencing arose, there have been many efficient methods to map small fragments of DNA. How small depends a lot on how efficient, how fast and how reliable you want the result, but 100 bases is a good figure to go with (could be 100 or 1000: it would not matter much when compared to aforementioned billions bases of the human genome). The methods used to do small-scale sequencing are quite nifty, but since they merely rely on boring² bio-chemistry stuff, I will let you google around (Wikipedia’s entry on the topic is not the greatest introduction, for once). For our sake, let’s just say we have biological tools that can accurately map segments of DNA of 100 bases (or smaller) in a fairly short time with near-perfect accuracy.

Other magical tools that we have at our disposal in our bio-chemistry toolbox allow us to somewhat painlessly:

1. replicate a sequence (of any length) an arbitrary number of times.

2. cut sequences in smaller bits at arbitrary positions: usually upon encountering a specific pattern in the sequence and with a certain frequency rate (e.g.: upon encountering the pattern ‘CCCGGG’ anywhere in the sequence, the cut will occur 1 out of 6 times).

3. work on a subsequence at a specific position (as if it was cut from the rest): provided you have an exact pattern where you want to do it (and the pattern is long enough to be unique in the sequence), you can isolate a subsequence from the rest with absolute precision and accuracy. However, engineering such an artificial cut is infinitely more complex, long and costly as using some of the “ready-made” cutters of 2.

The same with more science and less words, you ask? Sure, here you go: DNA primers, DNA polymerase, PCR, restriction enzymes, kangaroos³.

For the sake of keeping things simple (ha!) we will blatantly ignore the fact that DNA is not a single strand, but two complementary sequences tied together that need to be periodically pried apart or rebuilt during these operations. In the end, it does not matter much to the problem at hand.

Equipped with such tools, how should we go about processing entire chromosomes (usually north of 10k bases for simple organisms, 50 million for humans)?

The Straightforward Method (aka The Doomed Approach)

“Primer walking” is a (comparatively) simple method that more or less consists of focussing on segments small-enough to fit our small-scale sequencing method: start at a given position (see tool 3. above), map a few hundred bases, use the chunk just mapped to find the next starting position, lather, rinse, repeat.

There are two major problems with this method: As mentioned, “starting at a specific position” on a sequence is a very ad hoc and therefore costly (in money, in time…) operation. That operation furthermore requires knowing where to start, which means having processed the previous segment (so we can use the end of this segment as the pattern to start at in the following step).

The entire process therefore requires sequentially executing a series of operations, each of which requires a certain time. Surprisingly no NP-Completeness or exponentials involved here: only a very, very long task with no way to parallelize, which is only theoretically better. In practice, this makes this method viable (albeit slow and costly) for sequences of up to 10,000 or so bases.

On longer sequences, and particularly on our friendly multi-billion genomes, that would be a Fail.

The Smart Way (aka The One That Gives Headaches)

From the above, it seems obvious the only way to stand a chance at decoding entire genomes in less than a lifetime is to tackle many small segments, possibly all of them, at the same time. And this is exactly what shotgun sequencing does: after making a good number of copies of the original sequence, we sic a bunch of ready-made sequence cutters on them. The resulting mixture is a horrible mess of small fragments, that are small enough to be each sequenced easily. Which is great, except you then have no idea how to put them back together so as to get the bigger picture.

Not clear? Need another silly analogy? Sure:

Imagine you have a (very very long) text printed on a piece of paper: make a dozen photocopies and leave them in a room with your 5-year-old nephew and a good pair of scissors (arranging the pages in such a way that each is cut separately, in its own unique way). Put all the resulting confetti in a bag, shake a few times.

Now put the original text back together. Go ahead, I’ll wait.

Funny enough, this is near-exactly what DNA sequencing entails: once the first phase of sequencing is done, you are given a large bag of short strings (long sequences of ‘A’, ‘G’, ‘T’ and ‘C’ instead of common words in our analogy, but the same for every other purpose). You are looking for the text that is made of these strings in a specific order (and repeated over, as many times as there were initial copies). An “easier” problem is to find any text on which you could fit each little fragments (with lots of overlap, since there are many copies, each cut a different way) without worrying too much about whether this text really is your original. In practice, to get the real solution, all you have to do is find the shortest such text⁴: the one where you have no “superfluous” bits of text (not covered by any fragment) and as much overlap as possible (ideally in such a way that each bit of text is covered exactly as many times as there were original copies).

This problem is known as the shortest common superstring. And guess what: remember that little list I mentioned last week? Yea, bummer.

Given a candidate, merely verifying whether you have found the true Shortest Common Superstring is an NP-Complete problem. Finding that string from scratch, belongs to an even harder class of problems known as “NP-Hard” (where, as the name lets on, real badass NP problem kids hang out). Given the size of your data (millions of tiny fragments), finding an exact solution is obviously not gonna happen in this lifetime. Neatly enough, solving this problem turns out to be exactly the same as solving a particular brand of Traveling Salesman Problem (remember?). But as I mentioned last week: where standard algorithm fail and exact solution cannot be found, it is usually still possible to find a decent approximation in a fraction of the time. Sometimes this solution even turns out to be the exact solution, or so close that it doesn’t matter. This is the case here.

And excited as I am sure you were all, to jump into the actual mathematics of solving this particular problem, a sense of human decency and the already astronomical word count on this entry conjointly force me to skip to the end and suggest that the morbidly obsessed bravest among you peruse their local Google to look for some fascinating readings on reducing Shortest Common Superstring to Asymmetric Traveling Salesman Problem and/or finding approximation algorithms for the Shortest Common Superstring problem.

One of the trick behind Shotgun Sequencing, beside the actual approximation algorithm used to rebuild the original sequence, is the clever use of statistical redundancy to reach a guaranteed level of accuracy. That’s how we are able to say with certainty that the accuracy for the current Human Genome project is “no more than 1 error every 100,000 bases on average” (which sounds an awful lot better than “fuck if we know, but we dang sure hope it’s enough to tell it apart from them monkey DNA”).

The thankfully brief conclusion

And there we are, I have exposed, in nearly less time than it takes to kill a grizzly with a feather⁵, how Mathematics and Algorithmic can save the day in Genetics and help ensure that we will all have a bright future made of beautiful blond, three-eyed babies.

Of course, given that Shotgun Sequencing in its earliest incarnation, dates back about 40 years, there is very little left to be done for young upcoming bioinformaticians in this particular direction. And none of my work has anything to do with common sequencing problems.

But next week month soon, I will maybe talk of more recent challenges in bioinformatics, perhaps even some of mine!⁶

1. I know: one is not supposed to capitalise the name of God’s evil nemesis, but I am going on the assumption that Satan is a vindictive bastard and one can never be too prudent in courting the good graces of major players of the afterworld.
2. just kidding, fellow biologist friends: keep looking after those test tubes and churning out my data. kthxbye.
3. Have fun with your friends: can you spot the famous Australian marsupial among these terms related to DNA engineering?
4. the only reason this is not 100% true is the pesky problem of highly repetitive sequences. Something unlikely to arise in a real book, but very common in some DNA.
5. Pro tip: go for that spot under their foot, grizzlies are extremely ticklish there.
6. … in part 205 to 300 of this entrancing 1400-part series!

Post originally published on: Dave's Blog (please leave your comments over there)

What is Dave doing in Bioinformatics? Pt. 2

And now it’s already the 6th of November in Japan.

Maybe it’s not too late to go buy some gunpowder and have a celebration on my balcony tonight.

Post originally published on: Dave's Blog (please leave your comments over there)

Talking about remembrance…

Much to my surprise, I not only still remember a sizable chunk of German despite over 10 years with zero practice, but my level has in fact improved since then. That is to say, I am nowhere near fluent, nor able to remember half the vocabulary I once knew. However: turns of phrases and idiomatic expressions that I know would have me staring painfully for minutes on end back in high school, now seem perfectly natural to me… Most phrases hit the comprehension part of my brain directly, without going through the lengthy “decoding word-by-word and digging up through memory for idiomatic equivalent” phase. In some way I have magically become more “fluent” than I was, when last I studied ten years ago.

At first, I just assumed my memories were being overly modest and that, maybe, I was not the teutonic classroom failure I remembered being. Then I thought back of the long evenings laboriously spent stringing together 20 lines of homework, endless hours of classroom procrastination, barely coasting by, year after year, and the extremely mediocre A-level — or French equivalent thereof — grade that ensued. There is ample objective evidence that I really sucked as a high school student of German and it appears that I suck ever so slightly less, now that I am resuming ten years later… Which goes squarely against the widely accepted notion that foreign language acquisition skills decrease with age.

In proper logic-obsessed OCD fashion, I tortured my brain for days, trying to come up with a rational explanation for this, which did not involve being abducted, probed and experimented on, by German-speaking aliens.

And I think I found it…

The better half of the years spent studying German, were when I lived in Paris. I therefore studied in French. Grammar explanations, bilingual vocabulary lists, chatting with classmates, thinking about the ongoing lesson, were all done in French.

Nowadays: I live in Kyoto and there is very little French language in my life. Lots of Japanese, of course, but I would venture that well over 90% of my thoughts and interactions occur in English. When I read up a text in German, that voice in the back of my head, trying to make sense of what I am reading, is speaking English, not French.

If you have spent any time looking at all three languages, you have noticed how close English and German are, especially compared to French: English is essentially a Germanic language (with lots of Romance language forms subsequently introduced by the Norman French conquests), whereas French is, well, as Romance a language as you can get. Linguistically speaking, there is practically no bridge between French and German (the closest common ancestor being Indo-European, which takes us way back), whereas English is German’s twin brotha’ from another motha’.

Closing the pedantic aside: what I find really cool, is that this does not have to do with knowing one language or the other, but with which language you are more-or-less consciously using while learning another one.

The pathetic part is that, over the course of my entire senior high school years, it never occurred to me to make that switch myself: I was taught in French and never suspected that it might be easier, thinking about it in English. That’s what you get for being a lazy teenager.

Post originally published on: Dave's Blog (please leave your comments over there)

Erinnerung

I must obviously be doing something right. (or very wrong, depending on which side of the ‘gratuitous boobage action’ moral debate you sit on).

Post originally published on: Dave's Blog (please leave your comments over there)

Why wear a t-shirt after all…

It is all about sex.

Sex and sexual desires, are solely to blame for every single one of those nights you spent attending overpriced, underwhelming, “art” performances. You know the kind: some friend-of-a-friend-of-an-acquaintance, half naked, banging on pots, ululating while playing the electric guitar with an egg beater and a 2000W amp or just exploring the relation between art, space and materialistic consumerism by slithering in a kiddy pool filled with mashed potatoes while their partner sprays them (and the first two rows of the public) with milk and coke.

To be fair, most art is about sex, great art included. When masterpieces do not straight up depict sex, they are most often about their author hoping to get laid, or consistently failing to.

On the other hand, mediocre art is all about keeping your existing sexual partner(s) happy. Sex is the glue that keeps together delusional twenty-something “experimental” artists, long after the last of their friends haゔぇ faced up to their talentlessness.

Behind every over-affected improv actress, is a bored but madly in love partner. Behind every shitty garage rock band, is a dedicated girlfriend ensuring none of her friends ever miss a gig. Behind every pointless expressive dancer’s performance, is a poor sap playing a detuned violin with a hammer, too busy checking her ass to wonder if it really was worth enduring 15 years of classical training for this. The fecund fields of experimental artistry are littered with people who would have long given up inflicting their fumbling on a sine-wave generator to the public at large, were it not for a support base, spinelessly ready to dish out all sort of undeserved praise and support, as long as it grants them VIP pants access.

And please do not come telling me this is a victimless crime: my eardrums and psyche, battered by hours of uninspired pseudo-stream-of-consciousness drivel recited to the sound of glass rim music, beg to differ.

Post originally published on: Dave's Blog (please leave your comments over there)

Mediocre Art: a Theory