I got to wondering whether anyone had been bold enough to adopt .GOD for some proprietary file format. Turns out, according to the folks over at filext.com, there was once an Australian outfit called "Games on Demand" that used .godd to denote something called an "Arena Partial Downloaded Game" file, which is not so very exciting. Note that they opt for the four-letter extension with the extra terminal "D" to avoid potential blasphemy. Games on Demand is apparently no more, so maybe they paid the price anyway. The last few lines of Revelation tend to suggest that the Almighty is pretty touchy about his IP.
Which got me thinking about other provocative three-letter homonyms that might make amusing file extensions. SEX, for instance, has more than one usage: Alpha Software uses it to denote something called an "Alpha five set index," and there's at least one report that some Urban Chaos game files use the carnal extension.
.EAT, interestingly, appears to be unexploited. So, too, .DUG, .LOW, and .YAK. It's kind of an amusing game to brainstorm applications that might use such extensions...
2006-09-26
2006-05-10
A Scientist Watches the Evening News
I do not really believe in a cabal of conspirators sitting around a table beneath an eye-and-pyramid in a basement in Geneva any more than Descartes really believed that an Evil Genius had his brain trapped in a jar, but I think Descartes had the right idea in positing this paranoia as the only basis for a truly rational epistemology. We do not assume the worst is true, but we exercise maximum skepticism by imagining the worst and asking, "How do we know it isn't true?" The idea, for instance, that 9/11 was really the work of powerful behind-the-scenes forces who wanted to effect certain changes in the American political system and/or the world economy, and not demonic terrorists, deserves to be examined rationally. Although my personal belief is that things happened more-or-less as the mainstream media has presented them to us, I see that belief as irrelevant to the question of knowledge. I don't know what really happened on 9/11 any more than you do, and it is almost certain that neither of us ever will. We are wise, then, to withhold judgement idefinitely, and especially to avoid making important decisions based on judgements we might otherwise be tempted to make. Politicians are not citizens in a court of law and should be presumed guilty until proven innocent, for the same reasons that a man who stands to lose his life or his freedom as punishment for a crime should benefit from the opposite presumption, and that is, that it is better to err on the side of caution. For me, for now (and probably forever), 9/11 was a tragedy on par with an earthquake, a hurricane, or a tsunami: Certainly we would prefer that it never happened, but there is no one to blame for it but God.
2006-05-04
The Moussaoui Verdict
So I'm completely in a tither about the outcome of the Moussaoui trial. I am on the one hand pleased that they decided not to execute him, and on the other fairly vexed that the whole country--even the judge who sentenced him--seems to regard this as some kind of failure. I'm apalled by the fact that people across the nation seem to be comforting themselves with the thought that he's going to spend the rest of his life in supermax custody, which is by many accounts a fate worse than death. There were jeers in one editorial to the effect of "he'll rot in a cell before he burns in Hell." Shame on all of us.
To cap it off, there have been noises about how he's going to be denied even the 5 monthly non-contact visits afforded to other prisoners in this most extreme manifestation of solitary confinement, although I really don't see how they're going to get that one by the ACLU. The sentencing judge wagged her finger at him and said he would never get to speak publicly again, but that seems incredibly naive to me as I really doubt they're going to be able to hold him completely incommunicado, in which case lines from his letters and/or interviews will (probably sooner rather than later) find their way into various "true crime" and other exploitative books, copies of which will probably end up in the Library of Congress for indefinite historical preservation on the federal dollar. I would also point out to the scolding judge that, although most people in the English-speaking world today know Moussaoui's name, very few of those same people could produce hers if they were offered money to do so.
I really wish the media had paid more attention to exactly what crimes he was convicted of, rather than focusing almost exclusively on the outrageous things he said and did in the courtroom. The impression I get is that he was mostly convicted of vocally supporting Osama bin Laden, the 9/11 attacks, and Islamic jihad in general which, as distasteful as it may be to most of us, is not a crime. Considering that he was actually in federal custody as the 9/11 attacks took place, it would seem that the worst they could possibly get him on would be conspiracy, and although there's a long legal tradition of taking conspiracy very seriously I have had a problem with it since law school. Conspiracy is a charge that's relatively difficult to prove beyond a reasonable doubt (especially when, as in this case, the defendent wants you to believe he was involved) and relatively easy to trump up with courtroom theatrics and propaganda (again, much easier when the accused does his best to help you out). Although the federal prosecutors have produced long lists of Moussaoui's alleged crimes and he was obviously found guilty on some particular charge, we all know, deep down, that his was mostly a show trial. 9/11 happened, the people most directly responsible for it died in the act, Osama bin Laden slipped through our fingers, and the Iraq war proved to be about something else altogether: SOMEBODY STILL OWES US AN EYE! So it's politically expedient to barbecue this guy who's obliquely connected and who, guess what, wants to be a martyr anyway, so why don't we give him his chance?
Well, they had to try somebody for it, right?
Right?
To cap it off, there have been noises about how he's going to be denied even the 5 monthly non-contact visits afforded to other prisoners in this most extreme manifestation of solitary confinement, although I really don't see how they're going to get that one by the ACLU. The sentencing judge wagged her finger at him and said he would never get to speak publicly again, but that seems incredibly naive to me as I really doubt they're going to be able to hold him completely incommunicado, in which case lines from his letters and/or interviews will (probably sooner rather than later) find their way into various "true crime" and other exploitative books, copies of which will probably end up in the Library of Congress for indefinite historical preservation on the federal dollar. I would also point out to the scolding judge that, although most people in the English-speaking world today know Moussaoui's name, very few of those same people could produce hers if they were offered money to do so.
I really wish the media had paid more attention to exactly what crimes he was convicted of, rather than focusing almost exclusively on the outrageous things he said and did in the courtroom. The impression I get is that he was mostly convicted of vocally supporting Osama bin Laden, the 9/11 attacks, and Islamic jihad in general which, as distasteful as it may be to most of us, is not a crime. Considering that he was actually in federal custody as the 9/11 attacks took place, it would seem that the worst they could possibly get him on would be conspiracy, and although there's a long legal tradition of taking conspiracy very seriously I have had a problem with it since law school. Conspiracy is a charge that's relatively difficult to prove beyond a reasonable doubt (especially when, as in this case, the defendent wants you to believe he was involved) and relatively easy to trump up with courtroom theatrics and propaganda (again, much easier when the accused does his best to help you out). Although the federal prosecutors have produced long lists of Moussaoui's alleged crimes and he was obviously found guilty on some particular charge, we all know, deep down, that his was mostly a show trial. 9/11 happened, the people most directly responsible for it died in the act, Osama bin Laden slipped through our fingers, and the Iraq war proved to be about something else altogether: SOMEBODY STILL OWES US AN EYE! So it's politically expedient to barbecue this guy who's obliquely connected and who, guess what, wants to be a martyr anyway, so why don't we give him his chance?
Well, they had to try somebody for it, right?
Right?
2006-04-26
Resident Evil 4
In 1983, when I was but a tot of eight, a new videogame appeared at the arcade ("Tilt," it was called) in the local shopping mall. This was in the days of the Atari 2600, when the arcade experience was still emphatically superior to that of home-console players. The new game, "Dragon's Lair," offered a radically different approach than other games on the market at the time, which were almost entirely sprite-based. The stand-up cabinet housed an early laserdisc player, and the game featured full-motion animated video, giving it a look which was light years ahead of its competitors like "Centipede" and "Defender." In today's terminology, "Dragons Lair" was all "cut scenes." Gameplay was miserably poor, however: It amounted to moving the joystick in a particular direction at a particular time in the video, thus affecting the "action" of the game and determining which video clip would play next. As in a choose-your-own adventure book, making the wrong choice would lead to death. UNLIKE a choose-your-own-adventure book, there were no instructions; you had to guess, based on what was happening onscreen, which direction to move the joystick and exactly when. The superior graphics (which even now is often the standard by which all videogames are judged, rather than playability) justified its 50-cents-a-game pricetag when ALL the other games were just a quarter. In fact, now that I think about it "Dragon's Lair," may well be the first 50-cent arcade game I ever saw. I played it once or twice but quickly recognized it as a rip-off. Choose-your-own adventure videos, thankfully, did *not* take off in the market, and "Dragon's Lair" was relegated to the domain of historical curiosity.
Until today! The dunderheads at Capcom have included the concept in the latest installment of their highly-successful Resident Evil franchise. On the whole, RE 4 is a pretty good game. The atmosphere is appropriately 'orrifying throughout. Also, the game looks spectacular - better than any other console game I've seen - and the playability of the shoot-em-up stuff is not bad at all. The environment has some good "actions" built into it, which can induce some impressively cinematic spontaneous gameplay. Now, instead of just blasting everything in sight when the "zombies" attack, you can run into an empty building, push a dresser in front of the door, run upstairs, and knock down the ladder that the zombies are using to climb up and get you *while they're climbing.* Then you can toss a grenade down on them and watch the parts splatter. The PlayStation 2 version of the game even supports progressive-scan video, so if you have the right connectors and a good display you can enjoy all this action in high resolution. The various weapons available to the male lead, Leon, are satisfyingly powerful and effective, and there's plenty of the oh-my-god-I-can't-believe-this-new-gun excitement. Plus, once you've played the game all the way through you can go back and play parts of it again as a different (female) character with different weapons and moves, which is a hallmark of the RE series and a clever way to recycle all those environments the designers put so much thought into.
But it's a long way from perfect. The storyline and dialogue are *feeble* to say the least, and although the angry villagers and other beasties that attack you throughout the game aren't technically zombies (they're hosts of mind-controlling parasites), you tend to end up thinking of them as such anyway. It's easy to identify the game's various cultural influences: the parasites look exactly like facehuggers from the "Alien" movies, and the beseiged-in-a-farmhouse-by-zombies motif of the early chapters is clearly evocative of "Night of the Living Dead." The girl, Ashley, whom you're supposedly rescuing and who follows you around all the time, falls in and out of the clutches of the bad guys so many times you rapidly stop caring. The random scruffy vagabond "merchants" that inexplicably inhabit the enemy compound to sell you state-of-the-art weaponry (but no ammunition) during slow spots in the game stretch the credibility of the storyline well past the breaking point (to say nothing of the random "shooting ranges" that you can practice at from time to time). None of the puzzles are in the least bit difficult. The bosses, while requiring a good balance of arcade and puzzle-solving skills, are entirely predictable. If I have to watch one more "nightmarish transformation" of a humanoid badguy into some kind of polytentacled arachnid whose only weak spot is its eyes, I'm going to laugh myself silly.
But the absolute worst part of the game are the random choose-your-own-adventure cut scenes. Those habituated to "resting" during video game cut scenes are in for a rude shock: RE 4 demands that you *closely* watch the action of the cut scenes, because every so often you're faced with a "Press B quick or die!" scenario. No matter how carefully you play during the shoot-'em-up portions of the game, these *BOO!* scenes are almost certain to take you by surprise, the first time, and flush all your hard work down the drain. They're easy to clear when you know when and where they're coming, of course, so including them just seems like a mean way to randomly kill the player his or her first time through the game. It's almost as if somebody at Capcom got annoyed with the thought of people not watching their (insipid) cut scenes, and therefore designed them with built-in pop quizzes. The final jet-ski chase out of the exploding cavern is a particularly annoying instance of this. It's easier to kill the final boss than it is to successfully navigate the caverns on the jet-ski without being killed, which of course breaks the tempo of the game's final moments in a very frustrating way.
Still, I enjoyed RE4 enough to play it all the way through, at least the first time. Faced with the prospect of starting over as the female character, I find myself less than enthusiastic, although I'll probably play the new chapters through anyway so I can see all of her available weapons, which promise to be much cooler than Leon's, at which point my opinion of the game may have to be revised somewhat. I'll let you know. But until then, RE4 gets an emphatic "eh."
Until today! The dunderheads at Capcom have included the concept in the latest installment of their highly-successful Resident Evil franchise. On the whole, RE 4 is a pretty good game. The atmosphere is appropriately 'orrifying throughout. Also, the game looks spectacular - better than any other console game I've seen - and the playability of the shoot-em-up stuff is not bad at all. The environment has some good "actions" built into it, which can induce some impressively cinematic spontaneous gameplay. Now, instead of just blasting everything in sight when the "zombies" attack, you can run into an empty building, push a dresser in front of the door, run upstairs, and knock down the ladder that the zombies are using to climb up and get you *while they're climbing.* Then you can toss a grenade down on them and watch the parts splatter. The PlayStation 2 version of the game even supports progressive-scan video, so if you have the right connectors and a good display you can enjoy all this action in high resolution. The various weapons available to the male lead, Leon, are satisfyingly powerful and effective, and there's plenty of the oh-my-god-I-can't-believe-this-new-gun excitement. Plus, once you've played the game all the way through you can go back and play parts of it again as a different (female) character with different weapons and moves, which is a hallmark of the RE series and a clever way to recycle all those environments the designers put so much thought into.
But it's a long way from perfect. The storyline and dialogue are *feeble* to say the least, and although the angry villagers and other beasties that attack you throughout the game aren't technically zombies (they're hosts of mind-controlling parasites), you tend to end up thinking of them as such anyway. It's easy to identify the game's various cultural influences: the parasites look exactly like facehuggers from the "Alien" movies, and the beseiged-in-a-farmhouse-by-zombies motif of the early chapters is clearly evocative of "Night of the Living Dead." The girl, Ashley, whom you're supposedly rescuing and who follows you around all the time, falls in and out of the clutches of the bad guys so many times you rapidly stop caring. The random scruffy vagabond "merchants" that inexplicably inhabit the enemy compound to sell you state-of-the-art weaponry (but no ammunition) during slow spots in the game stretch the credibility of the storyline well past the breaking point (to say nothing of the random "shooting ranges" that you can practice at from time to time). None of the puzzles are in the least bit difficult. The bosses, while requiring a good balance of arcade and puzzle-solving skills, are entirely predictable. If I have to watch one more "nightmarish transformation" of a humanoid badguy into some kind of polytentacled arachnid whose only weak spot is its eyes, I'm going to laugh myself silly.
But the absolute worst part of the game are the random choose-your-own-adventure cut scenes. Those habituated to "resting" during video game cut scenes are in for a rude shock: RE 4 demands that you *closely* watch the action of the cut scenes, because every so often you're faced with a "Press B quick or die!" scenario. No matter how carefully you play during the shoot-'em-up portions of the game, these *BOO!* scenes are almost certain to take you by surprise, the first time, and flush all your hard work down the drain. They're easy to clear when you know when and where they're coming, of course, so including them just seems like a mean way to randomly kill the player his or her first time through the game. It's almost as if somebody at Capcom got annoyed with the thought of people not watching their (insipid) cut scenes, and therefore designed them with built-in pop quizzes. The final jet-ski chase out of the exploding cavern is a particularly annoying instance of this. It's easier to kill the final boss than it is to successfully navigate the caverns on the jet-ski without being killed, which of course breaks the tempo of the game's final moments in a very frustrating way.
Still, I enjoyed RE4 enough to play it all the way through, at least the first time. Faced with the prospect of starting over as the female character, I find myself less than enthusiastic, although I'll probably play the new chapters through anyway so I can see all of her available weapons, which promise to be much cooler than Leon's, at which point my opinion of the game may have to be revised somewhat. I'll let you know. But until then, RE4 gets an emphatic "eh."
2006-03-06
Do-It-Yourself Supercritical Fluid Extraction (DIY SFE)
So I've been fascinated with supercritical fluid extraction ever since the idea was first mentioned by Dr . VandenBout in my general chemistry class some four years ago. For the uninitiated, a supercritical fluid is a substance heated and compressed above its so-called "critical point," which is a coordinate on the pressure-temperature plane above and to the right of which the distinction between liquid and gas becomes meaningless. Theoretically, any substance can be made into a supercritical fluid, but of course some substances have more accessible supercritical domains than others. Carbon dioxide, for example, is the most commonly-used and -studied supercritical fluid because its critical pressure and temperature are accessible with relatively inexpensive apparatus.
The neat thing about supercritical fluids is that their capacity to solvate particular organic molecules can be tuned very selectively by precise adjustments of temperature and pressure. So they make useful solvents for industrial processes. In the case of CO2, an added "green" benefit is that the supercritical solvent is entirely benign, environmentally. Ever since I first learned about supercritical fluid extraction, I've been interested in the possibility of constructing a "garage-scale" supercritical fluid reactor. After doing some light reading on the subject in my old instrumental analysis book, I realized that, if a suitable pressure vessel could be found, performing supercritical fluid extraction of, say, natural products or pharmaceuticals could be readily conducted by the average shmoe in his garage using widely available materials. It is not even necessary to purchase or rent a high-pressure CO2 cylinder, as grocery-store dry ice can serve as the CO2 source, and can be conveniently measured out in the solid phase by weight or even volume. Simple calculations using the ideal gas equation give particular volumes and weights of dry ice to achieve particular pressures at particular temperatures. The dry ice is simply loaded into the pressure vessel, along with the material to be extracted, before sealing. The spreadsheet below gives all necessary physical constants and the results for an 8-quart pressure vessel:
DIY SCF Calculations
PV = nRT
SCP(CO2): 100 bar / 98.69233 atm / 1450.377 psi
SCT(CO2): 40 C / 313.15 K
Ves.Vol.: 8 qt / 7.570824 L
R 8.21E-02 L atm mol-1 K-1
MW(CO2): 44.01 g/mol
d(CO2[s]): 1.6 g cm-3
n=PV/RT
n = 29.08 mol => 1279.7 g => 799.8 mL
The big problem turns out to be the pressure vessel. My first thought was that a high-end kitchen pressure cooker might do the trick. NOT SO. A "high pressure" in the world of pressure cooking is 15 psi overpressure, which is about 2 atm. To access the supercritical fluid domain for CO2 requires nearly 50 times that pressure. A pressure cooker would explode (messily) long before the necessary pressure could be achieved. What's more, that pressure needs to be dynamically maintained. To recover solutes by supercritical fluid extraction, the SCF itself is slowly bled from the reactor and bubbled through an appropriate solvent, e.g. methanol. The CO2 blows off into the atmosphere and the goodies remain behind in solution. The reactor, however, needs to be designed to maintain constant pressure during this slow bleeding of the SCF. On a garage scale, this might be achieved by steadily elevating the vessel's temperature to compensate for bubbled-off SCF, but what effects the temperature ramp may have on substrate solubility are unknown to me. In "professional" SCF reactors, constant pressure is maintained by employing a syringe-type pressure mechanism in which reactor volume is continuously decreased during the extraction. Even if the "temperature ramp" method proposed above proved workable, the development of a useful garage-scale technique would still await the discovery or invention of a suitably accessible pressure vessel.
The neat thing about supercritical fluids is that their capacity to solvate particular organic molecules can be tuned very selectively by precise adjustments of temperature and pressure. So they make useful solvents for industrial processes. In the case of CO2, an added "green" benefit is that the supercritical solvent is entirely benign, environmentally. Ever since I first learned about supercritical fluid extraction, I've been interested in the possibility of constructing a "garage-scale" supercritical fluid reactor. After doing some light reading on the subject in my old instrumental analysis book, I realized that, if a suitable pressure vessel could be found, performing supercritical fluid extraction of, say, natural products or pharmaceuticals could be readily conducted by the average shmoe in his garage using widely available materials. It is not even necessary to purchase or rent a high-pressure CO2 cylinder, as grocery-store dry ice can serve as the CO2 source, and can be conveniently measured out in the solid phase by weight or even volume. Simple calculations using the ideal gas equation give particular volumes and weights of dry ice to achieve particular pressures at particular temperatures. The dry ice is simply loaded into the pressure vessel, along with the material to be extracted, before sealing. The spreadsheet below gives all necessary physical constants and the results for an 8-quart pressure vessel:
DIY SCF Calculations
PV = nRT
SCP(CO2): 100 bar / 98.69233 atm / 1450.377 psi
SCT(CO2): 40 C / 313.15 K
Ves.Vol.: 8 qt / 7.570824 L
R 8.21E-02 L atm mol-1 K-1
MW(CO2): 44.01 g/mol
d(CO2[s]): 1.6 g cm-3
n=PV/RT
n = 29.08 mol => 1279.7 g => 799.8 mL
The big problem turns out to be the pressure vessel. My first thought was that a high-end kitchen pressure cooker might do the trick. NOT SO. A "high pressure" in the world of pressure cooking is 15 psi overpressure, which is about 2 atm. To access the supercritical fluid domain for CO2 requires nearly 50 times that pressure. A pressure cooker would explode (messily) long before the necessary pressure could be achieved. What's more, that pressure needs to be dynamically maintained. To recover solutes by supercritical fluid extraction, the SCF itself is slowly bled from the reactor and bubbled through an appropriate solvent, e.g. methanol. The CO2 blows off into the atmosphere and the goodies remain behind in solution. The reactor, however, needs to be designed to maintain constant pressure during this slow bleeding of the SCF. On a garage scale, this might be achieved by steadily elevating the vessel's temperature to compensate for bubbled-off SCF, but what effects the temperature ramp may have on substrate solubility are unknown to me. In "professional" SCF reactors, constant pressure is maintained by employing a syringe-type pressure mechanism in which reactor volume is continuously decreased during the extraction. Even if the "temperature ramp" method proposed above proved workable, the development of a useful garage-scale technique would still await the discovery or invention of a suitably accessible pressure vessel.
2006-01-15
Despair
Perhaps 15 minutes ago I awoke from another dream featuring characters and scenes from my adolescence. I was wandering around in the upstairs rooms I enjoyed as a teenager in our house in Richardson, TX, and my longtime-schoolmate Joel Efrussy was there. I was explaining to him in an expert tone my theory of the causal link between certain types of coat-hangers and various disease-states--some types of coathangers could cause anemia, for instance. My tone was sardonical, and Joel understood it to be sardonical, but both of us winked at the joke and played along, he nodding and grunting appreciatively, and I gesturing and expounding dramatically. During the discourse I wandered back and forth between my sitting room and my bathroom, changing clothes, and I definitely remember that at one point I was talking to him with my pants around my ankles, wearing only boxers besides. I was at ease in this condition, but he was not. Before he left he regarded me with concern and asked if I were abusing cocaine, and I assured him that I had not taken cocaine in a very long time. After he left it seemed like a lie, and I had to reassure myself again that, no, I was not abusing cocaine.
Which is the last thing I remember before awaking, again myself at 30. In the foggy transition state that is more waking than sleeping but not very clearly either, I was assailed by a sense of nostalgia for friends and associates from high school--Joel, Lindsey Grayson, Melissa Henry. I could not, at the time, remember Melissa's name, but I did remember catching mononucleosis by kissing her, which led eventually to my two-years-long bout with tonsilitis and associated health problems, and which I mark as the beginning of the depression which characterized most of my 20s and the origin of my taste for prescription painkillers. I began then to think of my mother, and of the fact that, at thirty, I am still the focus of her irrational anxiety, when it materializes, and of the responsibility that devolves upon me in that position. I had again the thought, which assails me in times of despair, that I was living only to protect my mother from the pain of my death, and that--somewhat shamefully I write it--once she were gone I would at last be free to die. Then the mounting pressure of despair was upon me, and I felt panic swell as I lay there in the darkness in the bed with my beloved, and in that moment even she I questioned, and some effort was required not to begin crying.
And I was reminded of a scene from Roman Polanski's film "The Tenant," in which the protagonist, played by Polanski himself, witnesses a similar emotional breakdown in a woman in a cafe who is, to him, essentially a total stranger. She is so far gone that she does not care whether she weeps publicly or not. After looking uncomfortable for a moment, he rises to the occassion, grips her by the arm, and says with appropriate concern, "You must not give in to despair." The sense of the scene (the mise-en-scene, maybe?), however, is that it's a hopeless effort and he is rather naive to try to help her. Still, I was comforted by the memory of the line--"You must not give in to despair"--and I think that is because it both offers practical advice to the desparate and, in its succinctness, in its familiarity, in its ethos, it suggests a commonality of experience which is the best balm for profound suffering: The sense that one is not alone in one's unhappiness. We all know the experience of despair. It is utterly common to the human condition, and the sin is not in feeling it, but in giving up in the face of it. There *is*, of course, a certain reward that comes to those who do give in to despair, but it is a bitter peace, and it is characterized by the kind of eagerness for death that culminates in suicide. Acceptance of death, of course, is a fundamental spiritual milestone, but I do not believe at present that total abnegation of hope is the correct route thereunto.
Which leads me to consider the sensation of despair: What is it? The adjective that first comes to mind, when I free-associate the word "despair," is "overwhelming," and I think if we were to examine the average English sentence containing the word "despair," very often the word "overwhelming" would appear nearby. Despair overwhelms us, in the sense that we feel powerless or hopeless before it. That, indeed, is the essence of despair--the obliteration of hope beneath a crushing wave of guilt, sadness, and anxiety. These emotions are the triple threat of depression: The afflicted person is guilty about the past, sad about the present, and anxious about the future. All three temporal faculties--memory, perception, and imagination--are colored by darkness. This taxonomy is interesting to me, in that, like all taxonomies, it suggests a systematic approach to the problem: To manage despair, we need healthy ways of responding to the past we remember, to the present we perceive, and to the future we imagine.Now, as I write, both the act of writing and the physiochemical transition from sleeping to waking have relieved me--the despair I felt on awakening has evaporated almost completely and I can see the potential of the day. This is a transformation I have to undergo almost every day of my life. Usually on waking (in the morning, at least), I am more or less miserable, and the temptation to retreat back into sleep, rather than face the uphill climb into consciousness, is strong, which is why I frequently sleep so late. If I am somehow obliged to be awake, I will eventually overcome my inertia and find my happy place again, but very often it takes an hour or two to get there. I have a hard time with afternoons, as well. My best times are the dusk-hours from 6 to midnight; this is the time that the earth seems most beautiful to me. This type of daily mood-cycle, again, is characteristic of the clinically depressed, although, like most of the qualities of that disease, almost everyone experiences it to a lesser extent. Thus we have "morning people" and "night people." This observation itself suggests a strategy: I should try to schedule my activities so that I can sleep during the times of day which are most unpleasant to me.
And that's what all this is about, ultimately: strategies. I was terribly afraid when I began this journal that it would be nothing more than an exercise in adolescent "whine-tasting"--a chance for me to come out and pray openly on the streetcorner like the Pharisees. BUt that's not what it is: It's about examining my emotions so I can find intelligent ways of coping with them. Did I make any progress today? I think so. Recognizing that I'm a night person and planning my days accordingly--that is, chiefly to avoid obligations in the afternoon--is a good one. Another useful trick is recognizing the difficulty of mornings for me and trying to plan to ease them: going to bed early, taking measures to ensure comfortable sleep, and doing something I enjoy first thing are all useful strategies in this regard. Also, the breakdown of phenomena into memory/perception/imagination is also a useful starting point--I should begin collecting positive mediations for each mode. I already have one: the guided mindfulness regime promulgated by Jon Kabat-Zinn is exactly a meditative exercise for improving the present. That may be the best place to begin.
Which is the last thing I remember before awaking, again myself at 30. In the foggy transition state that is more waking than sleeping but not very clearly either, I was assailed by a sense of nostalgia for friends and associates from high school--Joel, Lindsey Grayson, Melissa Henry. I could not, at the time, remember Melissa's name, but I did remember catching mononucleosis by kissing her, which led eventually to my two-years-long bout with tonsilitis and associated health problems, and which I mark as the beginning of the depression which characterized most of my 20s and the origin of my taste for prescription painkillers. I began then to think of my mother, and of the fact that, at thirty, I am still the focus of her irrational anxiety, when it materializes, and of the responsibility that devolves upon me in that position. I had again the thought, which assails me in times of despair, that I was living only to protect my mother from the pain of my death, and that--somewhat shamefully I write it--once she were gone I would at last be free to die. Then the mounting pressure of despair was upon me, and I felt panic swell as I lay there in the darkness in the bed with my beloved, and in that moment even she I questioned, and some effort was required not to begin crying.
And I was reminded of a scene from Roman Polanski's film "The Tenant," in which the protagonist, played by Polanski himself, witnesses a similar emotional breakdown in a woman in a cafe who is, to him, essentially a total stranger. She is so far gone that she does not care whether she weeps publicly or not. After looking uncomfortable for a moment, he rises to the occassion, grips her by the arm, and says with appropriate concern, "You must not give in to despair." The sense of the scene (the mise-en-scene, maybe?), however, is that it's a hopeless effort and he is rather naive to try to help her. Still, I was comforted by the memory of the line--"You must not give in to despair"--and I think that is because it both offers practical advice to the desparate and, in its succinctness, in its familiarity, in its ethos, it suggests a commonality of experience which is the best balm for profound suffering: The sense that one is not alone in one's unhappiness. We all know the experience of despair. It is utterly common to the human condition, and the sin is not in feeling it, but in giving up in the face of it. There *is*, of course, a certain reward that comes to those who do give in to despair, but it is a bitter peace, and it is characterized by the kind of eagerness for death that culminates in suicide. Acceptance of death, of course, is a fundamental spiritual milestone, but I do not believe at present that total abnegation of hope is the correct route thereunto.
Which leads me to consider the sensation of despair: What is it? The adjective that first comes to mind, when I free-associate the word "despair," is "overwhelming," and I think if we were to examine the average English sentence containing the word "despair," very often the word "overwhelming" would appear nearby. Despair overwhelms us, in the sense that we feel powerless or hopeless before it. That, indeed, is the essence of despair--the obliteration of hope beneath a crushing wave of guilt, sadness, and anxiety. These emotions are the triple threat of depression: The afflicted person is guilty about the past, sad about the present, and anxious about the future. All three temporal faculties--memory, perception, and imagination--are colored by darkness. This taxonomy is interesting to me, in that, like all taxonomies, it suggests a systematic approach to the problem: To manage despair, we need healthy ways of responding to the past we remember, to the present we perceive, and to the future we imagine.Now, as I write, both the act of writing and the physiochemical transition from sleeping to waking have relieved me--the despair I felt on awakening has evaporated almost completely and I can see the potential of the day. This is a transformation I have to undergo almost every day of my life. Usually on waking (in the morning, at least), I am more or less miserable, and the temptation to retreat back into sleep, rather than face the uphill climb into consciousness, is strong, which is why I frequently sleep so late. If I am somehow obliged to be awake, I will eventually overcome my inertia and find my happy place again, but very often it takes an hour or two to get there. I have a hard time with afternoons, as well. My best times are the dusk-hours from 6 to midnight; this is the time that the earth seems most beautiful to me. This type of daily mood-cycle, again, is characteristic of the clinically depressed, although, like most of the qualities of that disease, almost everyone experiences it to a lesser extent. Thus we have "morning people" and "night people." This observation itself suggests a strategy: I should try to schedule my activities so that I can sleep during the times of day which are most unpleasant to me.
And that's what all this is about, ultimately: strategies. I was terribly afraid when I began this journal that it would be nothing more than an exercise in adolescent "whine-tasting"--a chance for me to come out and pray openly on the streetcorner like the Pharisees. BUt that's not what it is: It's about examining my emotions so I can find intelligent ways of coping with them. Did I make any progress today? I think so. Recognizing that I'm a night person and planning my days accordingly--that is, chiefly to avoid obligations in the afternoon--is a good one. Another useful trick is recognizing the difficulty of mornings for me and trying to plan to ease them: going to bed early, taking measures to ensure comfortable sleep, and doing something I enjoy first thing are all useful strategies in this regard. Also, the breakdown of phenomena into memory/perception/imagination is also a useful starting point--I should begin collecting positive mediations for each mode. I already have one: the guided mindfulness regime promulgated by Jon Kabat-Zinn is exactly a meditative exercise for improving the present. That may be the best place to begin.
2006-01-12
Salutaridine Synthase
Today I met with Dr. Marvin Hackert, a specialist in protein crystallization at the University of Texas at Austin, to discuss my plans to isolate and crystallize an enzyme critical in the biosynthesis of morphine, which I imagine as a step on the way to developing a synthetic or semi-synthetic catalytic preparation for use in the manufacture of morphine. The enzyme, salutaradine synthase, has not previously been crystallized and the purpose of doing so would be to determine its 3D structure, particularly at and around the active site.
My notes from the meeting suggest a two-sided approach to the problem, which might be called top-down and bottom-up. The top-down approach is theoretical; it begins with the enzyme's gene sequence, or that of an isoform, and would approximate the 3D structure by computerized "fitting" of the primary sequence derived from the genome to the known structure of an analogous protein, if one can be found. Although inexact, this approach has the virtue of being inexpensive. It could give useful insight into the structure of the active site and, hence, to the mechanism of catalysis, thus paving the way for the development of an entirely synthetic catalytic system. The program to perform the "morphing" operation in which the sequence is extrapolated to a structure by analogy to a known protein is called SWISS-PDB, and is freely available through the internet.
On the practical side, the approach would be to isolate and purify the enzyme from a homogenous biological sample, crystallize it, and attempt to regenerate its catalytic activity in vitro. It would appear that the 1995 Amann, et. al, paper includes an assay that depends on the catalytic activity of the enzyme to track it through the isolation and purification process. This is something of a revelation, as my previous understanding was that the enzyme was inert apart from its associated cell membrane and that it had not been regenerated in vitro. It's a good sign because it indicates that such regeneration is possible and, moreover, routine enough to be used as an assay. Even if I fail ultimately to determine empirically the protein's structure, development of a reusable catalyst derived from the biological matrix could provide publishable and patentable results. Although this secondary goal does not require elucidation of the enzyme's structure, the effort to crystallize the protein is wasted in the absence of sequence data, because ultimate structural determination depends on both an x-ray diffraction pattern and knowledge of the primary structure.
First questions:
1. What parts of the poppy genome have been sequenced?
2. Is there compelling evidence of the existence of salutaradine synthases in man?
3. Are the seminal investigators still working on this problem and are they willing to talk?
4. How much protein should I reasonably expect to need for the crystallization project?
My notes from the meeting suggest a two-sided approach to the problem, which might be called top-down and bottom-up. The top-down approach is theoretical; it begins with the enzyme's gene sequence, or that of an isoform, and would approximate the 3D structure by computerized "fitting" of the primary sequence derived from the genome to the known structure of an analogous protein, if one can be found. Although inexact, this approach has the virtue of being inexpensive. It could give useful insight into the structure of the active site and, hence, to the mechanism of catalysis, thus paving the way for the development of an entirely synthetic catalytic system. The program to perform the "morphing" operation in which the sequence is extrapolated to a structure by analogy to a known protein is called SWISS-PDB, and is freely available through the internet.
On the practical side, the approach would be to isolate and purify the enzyme from a homogenous biological sample, crystallize it, and attempt to regenerate its catalytic activity in vitro. It would appear that the 1995 Amann, et. al, paper includes an assay that depends on the catalytic activity of the enzyme to track it through the isolation and purification process. This is something of a revelation, as my previous understanding was that the enzyme was inert apart from its associated cell membrane and that it had not been regenerated in vitro. It's a good sign because it indicates that such regeneration is possible and, moreover, routine enough to be used as an assay. Even if I fail ultimately to determine empirically the protein's structure, development of a reusable catalyst derived from the biological matrix could provide publishable and patentable results. Although this secondary goal does not require elucidation of the enzyme's structure, the effort to crystallize the protein is wasted in the absence of sequence data, because ultimate structural determination depends on both an x-ray diffraction pattern and knowledge of the primary structure.
First questions:
1. What parts of the poppy genome have been sequenced?
2. Is there compelling evidence of the existence of salutaradine synthases in man?
3. Are the seminal investigators still working on this problem and are they willing to talk?
4. How much protein should I reasonably expect to need for the crystallization project?
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