Take cisplatin in the morning and call me

Although we are most familiar with the circadian rhythm from its effects on our physiological state, the roots of the phenomenon lie in the molecular biology of individual cells. The circadian rhythm is the result of a transcriptional control system that regulates the levels of many different proteins in the cell with the passing of time. Not all of the proteins subject to this control have yet been catalogued, and as a result some surprising effects are still being discovered. A recent article in Proceedings of the National Academy of Sciences from the Sancar lab at UNC suggests that circadian control of a DNA repair factor may be a way to enhance the effectiveness of a chemotherapeutic agent. The article is open access, so I encourage you to open it up and read along.

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Larry the bilker

Matt Taibbi has an article about the destruction of Jefferson County up at Rolling Stone. I strongly recommend you read it, but take your blood pressure medicine first. I would like to be able to say that this story, in which crooked banks and corrupt politicians conspire to inflate the price of a public works project more than 1000 percent, saddling a county with billions of dollars of debt it will take a generation to pay off, is an elaborate April Fool's joke. Unfortunately, as the residents of Birmingham know, it's all too real. Like countless city councilmen, county commissioners, and mayors before him, Larry Langford played the city like a long con, adding the ruinous sewer project to his other notable failures, such as VisionLand. One wonders how much of his talent for failing upward was due to the assistance of men who knew he could be bought.

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Evony gives up

The lawyers for Evony have dropped their Australian libel-tourism suit against Bruce Everiss. In accordance with Australian law, they will have to pay his legal fees. In light of Evony's advertising strategy, it seems only natural to celebrate this news with a picture of some boobies:

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Obligatory PAX post

Like several thousand gamers, I spent the past weekend at PAX East. It was great to finally meet a bunch of the people I regularly communicate with on Twitter, Wave, and other places. There really are too many to be named, so I won't even try, but if I introduced myself to you at any point during the weekend it was because I felt it was a genuine pleasure to meet you, and I hope to see you again soon. Unfortunately, with the press of people and the absurdly long lines for some panels, I wasn't able to hook up with everyone I knew who was there. Hopefully the next iteration of the Expo will handle the lines a bit better.

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How native-like is a cold-denatured structure?

A protein has several different levels of structure. The primary structure is the arrangements of atoms and bonds, and it is formed in the ribosome by the assembly of amino acids as directed by an RNA template. The secondary structure is the local topology, the helices and strands, and this forms mostly because of the release of energy through the formation of hydrogen bonds. The tertiary structure is the actual fold of the protein, the way helices, strands, and loops are arranged in space. The fold forms primarily because of the favorable entropy of burying the protein's hydrophobic groups where water cannot access them, analogous to the formation of an oil droplet in water. This suggests that, in addition to the well-known phenomenon of proteins denaturing, or losing their higher-order structure, under conditions of high heat, proteins might also denature when they get too cold.

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Dynamics conservation in the Ras superfamily

The proposition that general fold architecture is preserved within a family of evolutionarily-related proteins is not controversial. The amino acid sequence of a protein determines its structure, and countless studies have substantiated the idea that proteins with similar sequences will adopt similar folded conformations. Because structure and dynamics are intrinsically linked, one could reasonably assume that many features of a protein's dynamics get conserved along with the fold. A growing number of experiments show that this is indeed the case, including a recent paper in Structure (1).

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Even more lab courtesy haiku

Alert your labmates
if your prep will require all
the lab's baffled flasks.

Refill or reorder
reagents before you empty
the goddamn bottle.

Touching toxins, gloves
go on. Touching telephones,
take those nasty things off.


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Capsule: Star Fox Adventures

Final Status: Complete.

Put this on your box: It's Star Fox without anything that you liked about Star Fox!

Most intriguing idea: Translating a sci-fi dogfighting character to a magical adventure setting. (It says intriguing there, folks, not good.)

Best design decision: The surprisingly smooth inventory/command system.

Worst design decision: The first-person targeting reticle's aggressive recentering behavior.

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Camp

The ultimate Camp statement: it's good because it's awful. ...Of course, one can't always say that.

—Susan Sontag, "Notes on 'Camp'"

This game is so bad, it's not just become good. It's pretty close to perfect.

—Jim Sterling, review of Deadly Premonition

Jim Sterling gave Deadly Premonition a score of 10 points out of a possible 10, easily the highest score the game received among major gaming review sites. In his review, he makes it plain that this game does not deserve that score in any "objective" sense. The graphics are dated, the gameplay is limited, and its systems pay too much attention to irrelevant details. This is to say nothing of its absurd plot and characters. In comparison to almost any other game, Deadly Premonition is awful, but within the bounds of a certain kind of sensibility, that does not preclude it from also being good. Sontag identifies that sensibility as Camp, and it's an idea worth thinking about in connection to games.

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One-button war

In comparison to systems like Pong or Pac-Man, modern games tend to be extremely complicated. An XBox 360 controller has 16 unique inputs, and many of the games for the system shift the meaning of those inputs contextually to multiply the possible ways a player can communicate intention to the game. But the complexity of controllers is a response to increasingly byzantine game systems, of which there are few better examples than the typical real-time strategy game, with its array of resources, buildings, and units. So it's refreshing to play a game that provides some RTS flavor without the need for a poster-sized command summary. Pax Britannica, from my friend Matthew Gallant and the other guys at No Fun Games, offers four-player deathmatch RTS using just one button.

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Prion diseases: protein is enough

Spongiform encephalopathies are transmissible diseases that can have a major economic impact on agricultural exports, and pose a significant challenge for surveillance of the food supply. Scientists generally believe that these diseases are transmitted via a self-propagating, aberrant conformation of the prion protein (PrP). This prion hypothesis suggests that PrP alone should be sufficient to cause symptoms or death. If this hypothesis is true, then it should be possible to reproduce the disease using recombinant proteins expressed in yeast or bacteria. In tomorrow's Science, researchers from Columbus and Shanghai report that they have managed to do this, establishing that PrP alone can account for prion disease transmission.

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The sea of broken dreams

During the initial hype cycle for BioShock 2, the game had the subtitle "Sea of Dreams". The player can find a recording in Siren Alley that ties this name into Dr. Sofia Lamb's view of Rapture itself. The world's brightest and most creative minds were drawn to Ryan's underwater would-be utopia, each trying to remodel its world to fit their own desires. BioShock drew much of its power from depicting the ways those dreams could grow out of control and become malignant obsessions. The sequel, in contrast, builds its world from the dreams that died. In many ways, the subject of BioShock 2 is failure.

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