Those punks felt lucky

I can't imagine how anyone can vote for Rand Paul. I'm not even talking about his moronic take on the Civil Rights Act. I mean, that's pitiably foolish, and his whole "I"m not a racist, but..." act doesn't excuse his adopting the position that government must never interfere with private business even in the face of egregious social injustice. But at least if the people of Kentucky are fools enough to elect the man, the CRA is in no danger of being undone by Paul's idiocy. We might not be so lucky when it comes to his potential choices for dealing with the disaster in the Gulf of Mexico, which he recently had the goddamn gall to characterize as an "accident". Paul even criticized the anger towards BP as un-American. To which I say: Fuck you, sir, and the political philosophy you rode in on.

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What's wrong with Leanne

In my last post I mentioned the difficulty I sometimes have in connecting with characters that express values opposed to my own. Because a game is an interactive entertainment that requires the player to exert considerable effort in order to progress, it's important to make sure that the player identifies or sympathizes with the characters he's controlling. This is especially true of 40+ hour games like RPGs. You're spending a lot of time with these people, so they'd better be worthwhile company. Unfortunately, Resonance of Fate had a small cast I didn't enjoy spending time with at all. I found the personalities of the male characters, Vashyron and Zephyr, to be completely repulsive and tiresome. But the female character, Leanne, was problematic in a different way. It wasn't just her personality, although she's not the sort of person I'd generally care to hang around with. Leanne just made me sad, because she was so obviously a patriarchal caricature.

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Who wants to be Lloyd Irving?

Having explained what I thought was wrong with Infinite Space, I feel obliged to talk about what it did right. In this context I'm going to discuss something lots of other games get wrong, from my point of view. Let me start with the proposition that games express values. That may seem trivial to anyone who has played through twenty or so JRPGs with the same neo-luddite earth-friendly themes, but I'm actually not talking about that kind of expression. Games also have intrinsic values that are communicated by the kinds of characters that are chosen as protagonists, the way that the plot evolves around them, and the systems with which the player affects that plot. In marked contrast to many notable JRPGs of the last decade, Infinite Space values intelligence and pragmatism. Because I share those values, I appreciated the game more, perhaps, than its gameplay and plot strictly deserved.

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Lost in Infinite Space

The last three games I've played have something in common, in that they are noble efforts with imperfect outcomes. Infinite Space, Metro 2033, and Fragile Dreams: Farewell Ruins of the Moon all have significant positives offset by serious negatives. In particular, I thought Infinite Space and Metro 2033 were pretty compelling despite their problems. The easiest of these to talk about is what's wrong with Infinite Space, so I'll start there.

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Do metamorphic proteins mediate evolutionary structural transitions?

On several previous occasions on this blog I've discussed proteins that undergo significant changes in structure without drastic changes in their primary sequence or solution conditions. In some cases, a few mutations can take a protein to a novel fold, as with Philip Bryan's protein G work. In others, closely related sequences within a whole family populate different kinds of folds, as Matt Cordes illustrated for the case of Cro proteins. In addition, there are some cases such as lymphotactin, where interconversion between two very different structures takes place at equilibrium, as illustrated by Brian Volkman's research. Each time stories like this come up I have mentioned that this kind of behavior (termed "metamorphism" in a 2008 commentary by Alexey Murzin) suggests a means by which proteins could evolve from one structure to another without losing foldedness or function. Recently, a group from the Weizmann Institute published results in PNAS that speak to this possibility.

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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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