Starlight Temple

Project management

2010-03-07T10:15:00.004-06:00

Kevin posted this quote at The Smallest Minority:

There Comes a Time
in the
History of Every Project
When It Becomes Necessary
to
Shoot the Engineers
And Begin Production

Top engineers already know this, saying "Just shoot me already" near the end of a big project.

Reinvention

2009-10-03T11:21:00.004-05:00

DNA searching is basically a cross-correlation process, implemented with what amounts to a convolution algorithm if you use numbers to symbolize DNA nucleotides. The same is true for searching amino acid sequences. In fact, amino acids can be coded by chemical similarity, similar chemical properties being assigned nearby numbers.

The thing is, straight-up convolution is sloooow. If the sequence to be searched is N units long, and the sequence searched for is M units long, then it takes O(N*M) work to do a full convolution. If N=10e+9 and M=1e+3, typical values for genome searching, that's 1e+12 computations per query. Ouch.

It occurred to me that there is a much better way of doing this. The Fourier transform of a convolution turns out to be the point-wise product of the Fourier transform of the things being convolved:

F[ convolution(f, g) ] = F[f] * F[g]

For our digital data, the Fourier transform can be done with the Fast Fourier Transform, a clever algorithm with a computing workload of O(N * log N), loads better than O(N²) for naive convolution. The inverse FFT, F^-1, is equally fast.

With a little rearrangement, our convolution becomes simply a pair of FFTs, a pointwise product, and an inverse FFT:

convolution(f, g) = F^-1[ F[f] * F[g] ]

The Fourier transform of the sequence library you are searching can be precomputed and stored, saving computation. The Fourier transform of the sequence you are searching for can probably be computed with a simplified algorithm, since it contains so little data compared to the library sequence.

So you can do full point-by-point DNA alignment with reasonable computer workload. You just have to be willing to take the Fourier transform of a chemical structure, which is a bit unconventional. Although not really unconventional compared to the things quantum physicists take the Fourier transform of.

But it turns out it was already invented [ref 2] when I was 8 years old.

Dang. Why are all the good ideas already taken?

References:

1. Sequence Alignment by Cross-Correlation.

2. An efficient method for matching nucleic acid sequences.

3. MAFFT: a novel method for rapid multiple sequence alignment based on fast Fourier transform

Moldy software build systems

2009-09-28T03:09:00.006-05:00

James Hague points out that many software build systems are baroque, and used infrequently enough that only the truly hardcore ever become competent:

I'm pretty sure there's a standard old build system to do this kind of thing, but in a clunky way where you have to be careful whether you use spaces or tabs, remember arcane bits of syntax, remember what rules and macros are built-in, remember tricks involved in building nested projects, remember the differences between the versions that have gone down their own evolutionary paths. I use it rarely enough that I forget all of these details. There are modern variants, too, that trade all of that 1970s-era fiddling for different lists of things to remember. ...

Not to mention properly quoting pathnames that have spaces in them. Especially if there are wildcards involved.

But there's no need. ... It's easier and faster to put together custom, micro-build systems in the high-level language of your choice.

Hear, hear!

Lately I have been using ANTLR—a parser generator—to make a compiler for a new programming language. (Everybody needs their own programming language!) It appears to be a wonderful package ... but the build system uses Apache Maven.

Oh. Dear.

Somebody noticed that obtaining the prerequisites was a lot of work when building open source projects. Apparently that somebody decided to tackle the challenge by integrating the dependency tracker, package manager, and download tool into the build manager.

However, if you are operating under a restricted environment or behind a firewall, you might need to prepare to run Maven, as it requires write access to the home directory (~/.m2 on Unix/Mac OS X and C:\Documents and Settings\username\.m2 on Windows) and network access to download binary dependencies.

That's certainly reassuring. The build control file is written in XML:

<project xmlns="http://maven.apache.org/POM/4.0.0" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://maven.apache.org/POM/4.0.0 http://maven.apache.org/xsd/maven-4.0.0.xsd"> <modelVersion>4.0.0</modelVersion> <groupId>org.codehaus.mojo</groupId> <artifactId>my-project</artifactId> <version>1.0</version> </project>

As a wise man once said, "As God is my witness, I thought turkeys could fly."

Update: fixed XML. And title. And fixed the XML again. This time for sure. No, this time for sure.

A brief, incomplete, and mostly wrong history of programming languages

2009-05-10T16:01:00.004-05:00

This hilarious history of computer programming has been making the rounds. But the comments are as full of win as the post itself.

mx1 said...
HAI
CAN HAS STDIO?
VISIBLE "What about LOLCODE?!?!!"
KTHXBYE
May 8, 2009 12:25 PM

Sarah Newman said...
1999 - Dissatisfied with the lack of portability and abstraction in hardware design, a consortium of Electronic Design Automation companies create SystemC, allowing software engineers to design hardware and EDA companies to make lots of money selling separate compilers for CMOS and TTL based designs. Manufacturers later complain of reduced yields because of debug symbols not being stripped, increasing die sizes.
May 8, 2009 10:26 PM

1963 - Ken Iverson invents APL and bases its syntax on some gold tablets given to him by the angel Moroni.
May 8, 2009 5:34 PM

Happy and Sad

2009-04-25T23:11:00.004-05:00

Edit: Dammit, Blogger, when I say I want a large image, give me the full-size version.

Software transactional memory

2009-03-29T06:09:00.002-05:00

Software transactional memory (STM) applies the concept of database transactions to program variables. In a simple implementation, a thread simply executes a transaction without regard to concurrent threads, recording what it reads and what it changes as it proceeds. At the end of the transaction, it checks if any of the variables it accessed were concurrently altered. If they were, it rolls back all of its changes and retries the transaction from the start. If they were not, the transaction succeeds and any changes become permanent.

I don't like this naive approach because it gives up consistency. Because a transaction's input may be randomly altered by other transactions in progress, it may receive corrupt input, triggering foolish actions. The Wikipedia article gives an example of an inconsistency that sends one thread into an infinite loop, for which there are no good or general ways to recover.

Consistency could be provided by the standard means used by relational databases—snapshot copies, global version counters, etc.—but the cost of locking on large numbers of processors would be prohibitive.

STM strikes me as vulnerable to hijinks, since the first transaction to finish wins. A network attacker simply has to identify a fast, innocuous transaction that writes to the same data used by an important transaction that takes a long time to complete. The attacker can prevent the slow transaction from ever completing by simply sending requests slightly more often than the long transaction takes. One could say "Well, that is the system engineer's fault for putting an atomic { ... } clause around such a long process", but that dodges that (1) mistakes happen when complicated systems are being extended, and (2) any slowness larger than network jitter opens the vulnerability.

The more I think about concurrency on computers with many cores, the more sensible message passing seems. A datum lives on a single core, or in a small group of cores, and all manipulation of it is by requests that travel to the datum's personal hardware. Global synchronization across the many-core computer is just too expensive.

Unicide

2009-02-26T19:27:00.002-06:00

Originally it was a typo, but then I realized just how irritating Unicode and encoding conversions can be.

Politicians donating stolen money to charity

2009-02-20T17:30:00.002-06:00

Sen. Dodd is doing it.

Sen. McCain is doing it.

Pres. Obama is doing it.

What. The. Fuck.

Shouldn't the money be sent back to, you know, the people it was stolen from? With this sort of "morality" running the "stimulus", the market bottom is a long way off.

American Digest on the unread Stimulus Bill

2009-02-15T09:59:00.001-06:00

Sweet dreams, perishing Republic.

Our feudal future

2009-02-15T07:25:00.006-06:00

Friedrich von Blowhard points out that Wall Street is just about to turn America into a Third World financial oligarchy.

Well, the DEA is trying to start a massive new program of regulations that would ban most doctors from prescribing extended-release controlled substances.^**

If this program is approved, I reckon it will give a substantial revenue boost to the DEA's pet Mexican drug oligarchs, by reducing market competition for their expensive black market products.

We care because the drug oligarchs' insurgency, indirectly funded by the DEA apparat, is giving northern Mexico the rough equivalent of a 9-11 attack every three months. The insurgency already operates openly in many American cities, carefully ignored by politicians who are in the pay of the "undocumented immigrant" caucus. For instance, the LA suburb of Compton and its neighbors are experiencing black flight^## as the insurgency's violence exceeds what even black gangbangers are willing to tolerate. Phoenix, AZ has achieved the distinction of being runner up in the competition for kidnapping capital of the world (the winner is Mexico City), where the insurgency ransoms and decapitates almost with impunity.

In the long run, this situation is untenable and will stop. In the short term, it is likely to turn into open warfare, with bombings and widespread banditry.

It is not unlikely that within five years, the American Southwest could become occupied territory, with martial law, curfews, checkpoints for internal passports, and so forth.

And that is one of the better scenarios. If the 10th Amendment/secession movement takes hold before the insurgency ripens and bombings start making the evening news, it is likely the Army will intervene against those evil racist secessionists, giving us a double insurgency and civil war. (A real civil war, fought to annihilate the opposition, not a mere war between the states.)

^**Contrary to what they say, extended-release formulations are generally safer than their immediate release counterparts, because during an overdose they give the human body time to desensitize and compensate. You can live through quite a bit of poisoning as long as the full dose doesn't hit your bloodstream within a few minutes. Yes, some people are killed by misusing these formulations, but that's because thrill seekers and junkies are substituting the extended release drugs for much more expensive black market product. The historical evidence shows that such people kill themselves at an appalling rate no matter the context; by and large, the only thing society can affect is how much they spend on their way out.

^##Black flight! You know the shit has gotten crazy when the negroes haul ass. In fact, looking around the world, that is a pretty good litmus test for the question "Does civil government exist at these grid coordinates?"

Memoirs of Extraordinary Popular Delusions and the Madness of Crowds

2009-02-07T09:42:00.001-06:00

"In reading the history of nations, we find that, like individuals, they have their whims and their peculiarities; their seasons of excitement and recklessness, when they care not what they do. We find that whole communities suddenly fix their minds upon one object, and go mad in its pursuit; that millions of people become simultaneously impressed with one delusion, and run after it, till their attention is caught by some new folly more captivating than the first. We see one nation suddenly seized, from its highest to its lowest members, with a fierce desire of military glory; another as suddenly becoming crazed upon a religious scruple; and neither of them recovering its senses until it has shed rivers of blood and sowed a harvest of groans and tears, to be reaped by its posterity."

The demographics of research achievement

2009-01-20T02:28:00.003-06:00

This review of The Global Bell Curve: Race, IQ, and Inequality Worldwide explains something that had long perplexed me: why the University of Sao Paulo has an uncannily high quality and quantity of research output compared to typical Central and South American universities.

Lynn's new book provides fascinating historical vignettes to describe all the migrations and mixing of peoples. It also provides clear tables of data, which allow the reader to check the facts for themselves. For example, in Brazil, it is the Japanese who are the highest achieving population. They were brought in as indentured labourers to work the plantations after slavery was abolished in 1888. Yet, today, the Japanese outscore Whites on IQ tests, earn more, and are over-represented in university places. Although they are less than 1% of the total population they comprise 17% of the students at the elite University of Sao Paulo.

Fedthink

2008-12-22T08:57:00.002-06:00

"Stability" — price stability, financial stability — are to my mind like "liquidity": qualities widely considered virtues that are often actually vices. Nevertheless, the Fed pursues these goals, ...
— Interfluidity

Did the trade deficit cause the economic collapse?

2008-11-21T23:20:00.002-06:00

Was it a policy matter beyond the Fed's control? I don't buy it. If the Fed had simply stood pat with the money supply, the newly-opened markets would have drained dollars, causing a stable deflation resembling the situation of the late 1800s. Dropping American prices would have increased exports, while resource competition would have inflated commodities and choked off excessively fast growth in imbalance. The arrangement is reasonably self-stabilizing.

The losers would have been those who had borrowed lots of money for enterprises with thin profit margins. But on a long-enough time scale they are doomed anyway—an inevitable market fluctuation will eventually wipe them out—deflation just blows them up a little sooner. They can only survive with eternal credit expansion. Naturally, this is what the Fed did. The mistake was not treating Chinese goods as a windfall, but propping up marginal enterprises and mistaking the results for efficiency. The more they inflated the money supply, the more illusory "efficiency" sprang out of the woodwork.

Take a look at these charts of the monetary base, the denominator of our fractional reserve monetary system.

Look at the bottom chart. In 1985, the monetary base was growing on a dead steady exponential curve: fractional reserve banking was causing inflation, but the system was net profitable, and the profits were being reinvested in the basis of the system.

Now look at 1995. The monetary base jumped off the tracks as the effective reserve fraction was dialed up. Money was being created fast, but not producing profits fast enough to maintain the new rate of creation. The dot-com bubble promptly inflated and burst from the pressure of all that money creation.

That should have been a wake up call to dial up the effective reserve fraction, but Greenspan decided to try it again, only harder this time.

Now look at early 2008, the last data on the graph. The monetary base actually shrank ever so slightly! Malinvestment was finally destroying money faster than it was being created. That marks the point where our economic system went off the edge of the abyss. The Fed has since manipulated the system so that the graph went vertical, but it is far too late to avoid tremendous destruction of productivity.

Congressional immunity: blessing or plague?

2008-11-20T14:42:00.002-06:00

Firehand thinks that Congressional immunity from extra-Congressional prosecution is a bad idea.

Utter bastard though he might be, Murtha is exactly right about immunity: if lawmakers can be prosecuted at will, then the faction with the sleaziest lawyers can make them write whatever laws they want, and we will be ruled from the shadows. The FBI and DEA are nearly as good at blackmail as the Stasi was, and if they start routinely using those techniques on senators, then the final death of the Republic will be at hand. It is by far the lesser evil to let a few of The Elect get away with retail crime for a few years, and vote them out in due course. The Founders designed a large Congress with immunity and frequent elections for exactly this reason.

Damn the country club Republicans for setting this wolf loose with their perpetual legal campaign against the Clinton administration. The professional ass-clowns would never have figured out how to do it on their own if Gingrich's misguided children had not written a how-to manual and rubbed their noses in it for eight long years.

Toss 'em back, God will know his own.

2008-11-13T12:01:00.004-06:00

ShrinkWrapped talks about a journalist who had the misfortune to mention the Trig Palin abortion sentiments in public.

Barone's comment was not "much too close to the truth", it was the truth. I was flabbergasted to see numerous people writing about how giving birth to Trig was unfair and immoral, to the gleeful approval of other lefties. And it wasn't couched in elliptical or insinuating terms, people were coming right out and saying he should have been aborted to prevent his suffering, or so that society would not be burdened with a useless eater. For a moment the mask slipped and we saw their true ethos of tolerance and acceptance: certain people are disposable. It was no lesson from a dusty history book or a wry Vonnegut story—the door of the eugenics oven stood open and we could feel the heat.

It opened my eyes about something that had been a mystery to me: Why does the Left Reich have such a violent, reactive hatred of IQ tests? Because, according to their ethos, if there existed a group of people with an average IQ of 70, there would be nothing to do but plow them under as fertilizer. And that must not be said out loud.

Why do matter and anti-matter annihilate?

2008-11-10T22:05:00.003-06:00

Trivially, it is because the particles have a "matter charge" that is conserved. Add a particle to its anti-particle and they cancel out the matterness, leaving the more ephemeral aspects to come squirting out, often in the form of simple, energetic force carriers.

Why matterness should be conserved is an open question in physics. Things like momentum are conserved because of symmetries. If all positions in space are equivalent, then the rate of change of position has to be constant in the absence of "action". Thus momentum is conserved.

What the symmetrical thing might be for matterness/antimatterness is not obvious, nor is "action" in this context. The Schrödinger wave equation does not explain any sort of substructure we can sink our hooks into. Surely particles must get their properties for reasons, but clues as to how they do it are few.

Particle models based on topology and shape are attractive because they allow complicated relationships to flower from simple foundations. For example, we can pick two knots that fall apart into a simple loop when cut and spliced to each other. Or a pair of complementary Möbius strips that untwist when spliced together. Alas, deducing fields and forces from tangles seems to be a hard problem.

Books are weapons in the war of ideas

2008-11-08T09:49:00.000-06:00

Blast from the past

2008-09-26T15:40:00.003-05:00

An Amazon customer review of DOW 36,000:

Strong evidence for a market with P/E's of 100+
September 28, 1999
By A Customer
Glassman & Hassett pose a strong argument that the market is undervalued. In a nutshell, his reasoning is that, long term, stocks are no more risky than fixed return investments like bonds. Yet, because earnings tend to grow, they have higher rates of return. This suggests that stocks will rise in price until that gap is closed, which conservatively indicates a 36,000 Dow. Impressive data to back up a strong thesis!

I CAN HAZ BAKSTOP

2008-07-08T15:10:00.002-05:00

I got this email today from Chase:

Today's low rates make it a great time to use the equity in your home to do the things you need!

As a Chase customer, simply apply online or call before August 11, 2008. In just minutes you'll be on your way to doing what you want.

A Chase Home Equity Line lets you have the cash to do what you want...make home improvements, pay off high-interest rate bills, or make other purchases. And the interest you pay may be fully tax deductible. (Consult your tax advisor.)

Do More:
Consolidate debt and pay off bills

Make home improvements

Make major purchases—autos, appliances, furniture—whatever you need!

Gay marriage

2008-06-18T02:27:00.004-05:00

This started out as a comment on NCO Brief.

It is not unreasonable for the State to encourage the raising of children in families, by giving tax breaks, simplifying paperwork, and the like. To the extent that marriage means anything, it is about the making and raising of children, something that every self-sustaining government must take an interest in. It is not practical (or desirable) for the government to review every child to determine how much their parents should be rewarded, but it is possible to give useful general support with marriage subsidies. (IMHO divorce rates don't refute this. Marriage subsidies do help keep an extra parent around for the first few years of the kid's life, a time when extra social contact is uniquely valuable.)

To put a simple lifestyle choice on the same footing, with the same subsidies and benefits, is corrosive to those interests. It must either take money away from other needs, or the taxpayer must be held up at gunpoint for more money, while at the same time trivializing the real purpose of the laws. Proponents of government-subsidized homosexuality cannot plausibly pretend surprise that taxpayers might object to money being frittered away for their private gratification.

In any event, the ostensible reasons in support of gay marriage are probably a smokescreen. I do not mind if San Francisco and its provinces legalize gay marriage. However their experiment works out, we will all learn valuable lessons in due course, and any people harmed can simply drive over to Sacramento and harass the legislature into making some changes. The real reason gay marriage is being popularized is to set the stage for it being litigated in the Supreme Court, so that one more aspect of American life can be regimented in a single winner-takes-all contest. The statists want to bring to family law what they brought to drug law and race relations. The prospect of child custody cases being decided by a National Family Law Administration is chilling.

ATF versus radiator hose - steel cage death match

2008-06-01T17:49:00.002-05:00

The automatic transmission fluid wins.

I spilled fluid on the hose changing the transmission fluid. I thought "How bad could it possibly be? I'll just wash it off later." After just the test drive to make sure the tranny wasn't leaking, the hose was already sticky and well on its way to leave-fingerprints-in-the-rubber.

Go to bed hungry

2008-05-17T14:50:00.002-05:00

Linear Technology has, er, interesting Application Notes.

Voltage detector

2008-04-06T11:13:00.005-05:00

How did I manage to miss the LMV431 precision voltage detector until now? Internally it's like an ordinary precision shunt regulator, but the shunt transistor and error amplifier input have been brought out to separate pins. That makes it good for all sorts of voltage detector and regulation uses.

Here is an example voltage range detector from the datasheet:

Simple, useful, and cheap.

Update: Fixed typo and added "electronics" label.

The Great Deflation

2008-02-20T02:00:00.005-06:00

Yves Smith at naked capitalism points us to an article on the coming Great Deflation:

People borrowed money because they had to. Income growth simply did not keep pace with prices in housing, health care, transportation, energy and food.

Good grief. People did not run up $20k on credit cards because the price of rice and beans had skyrocketed. People did not take out 40 year loans on land yachts because Saudi transportation moguls bid 10-year-old cars through the roof.

They did it because of their psychological state. Material goods became cheap, plentiful, and fabulously diverse. Money became as easily borrowed as a library book, a chit among gentlemen rather than a serious duty. These trends were not merely obvious, they perceptibly accelerated while you watched. Many people observed these facts and concluded that they were now living in a post-scarcity economy. With no everyday evidence to the contrary, they gradually developed a contempt for scarcity.

And if the goods had come from a self-maintaining robot factory in Montana, they'd have been right. The only constraints would have been their imaginations and the universe's limited supply of ergs and atoms. That sort of technological mastery would upturn society and open bewildering vistas of possibility, a utopia of science. United Federation of Planets, here we come!

But there is no robot factory. The cheap goods came from foreigners working damn hard for little return, held in peonage^* to conventional factories. A lot of domestic production (housing, agriculture) was even done by foreigners, legal and otherwise. The easy money was the purchase price of those goods shipped right back to the First World as the foreign central planners held inflation in check.

What seemed to be a new permanently-high plateau was actually a situation balanced on the edge of a knife. Trade imbalances cannot continue forever; the exporter either implodes in a revolution, or completely industrializes. Either way, the imbalance stops. Borrowing cannot continue forever in any economy; it stops when debt exceeds future income, whatever artifice delays the day of reckoning. Financial derivatives cannot be infinitely re-derivatized; eventually their behavior becomes so opaque that dynamic stability cannot be maintained and the whole web unwinds, maybe in white knuckle trading, maybe in a crash. The boom in non-exportable labor (housing, services) was nothing more than the pent up labor from the off-shored jobs finding an outlet. Like the rest of the universe, economies are governed by unavoidable natural laws.

Like natural laws, ingenuity can harness the laws of economies, make them work for our long-term benefit. Alas, in this matter many of the public and the leaders have chosen by default to be kites instead of making themselves into airplanes, tossed by the wind instead of setting their own course. Yeah, the ride starts out more exciting, but what of the storms?

Many will say to me in that day, Lord, Lord, have we not prophesied in thy name? and in thy name have cast out devils? and in thy name done many miracles?

And then will I profess unto them, I never knew you: depart from me, ye that work iniquity.

Therefore whosoever heareth these sayings of mine, and doeth them, I will liken him unto a wise man, which built his house upon a rock: And the rain descended, and the floods came, and the winds blew, and beat upon that house; and it fell not: for it was founded upon a rock.

And every one that heareth these sayings of mine, and doeth them not, shall be likened unto a foolish man, which built his house upon the sand: And the rain descended, and the floods came, and the winds blew, and beat upon that house; and it fell: and great was the fall of it.
— Warren Buffet

^*In peonage for now. It's a long, hard road that leads to industrial prosperity, but the road does get there. The ephemeral nature of mercantilism is a trap for the idle importers, not for the laborers.

"Reserves"? You keep using that word.

2008-02-03T15:50:00.000-06:00

I do not think it means what you think it means.

This comment on The Financial Ninja points out that the Fed has redefined how the NFORBRES data (net free or borrowed reserves) are calculated:

"Notes: Prior to 2003-01-01, the data are calculated as excess reserves minus total borrowings plus extended borrowings. From 2003-01-01 till 2007-11-01, the observations reflect excess reserves minus total borrowings plus secondary borrowings. From 2007-12-01, the definition changes to excess reserves minus discount window borrowings plus secondary borrowings."

This would appear to mean that the proceeds of loans from the Fed's Term Auction Facility (TAF) are being accounted for as income to the banking system. Before this change, the reserves graph had gone negative to the tune of over $10G.

Tick. Tick. Tick.

Deflation of the ready cash supply

2008-01-26T18:13:00.001-06:00

The graphs below show the growth of the U.S. monetary base over time. (The monetary base is physical currency plus reserve accounts held at the Federal Reserve.) The blue trace is an exponential curve fit to 1975–1994, while the green trace is the raw data. The first graph is plotted in log-linear form: a constant inflation rate (exponential growth) would be a straight line. The second graph shows the same data in linear-linear form.

Note how the monetary base falls behind inflation in the mid-1990s. Money is being created but not being added to rainy day cash.

I have no idea what this actually means for social stability. While there is less cash to help ride through glitches in the system, modern telecommunications makes it vastly easier to send money where it is needed.

Sources:

What caused the financial meltdown?

2007-12-30T01:42:00.001-06:00

One theory is that a feckless Alan Greenspan cranked interest rates down too close to zero and left them there too long. The result was excessive creation of money, which inflated asset bubbles. A given asset category was inflated to the extent that it had machinery for rapidly turning over money; real estate suffered so badly because the mortgage industry had a pre-deployed infrastructure that hooked right up to the printing presses.

But the longer I think about it, the less I believe the interest rate theory. The main direct effect of the government loaning out money cheaply is to cause inflation. In standard hyperinflation, risk pricing is refined to a high art. For example, restaurants call the farmers every few hours to lock in a price for replacements for the vegetables used since the last call (to spend the money from their customers before it wastes away). growing up in that environment get the time value of money with mother's milk. Hyperinflation also causes a flight from monetary instruments to hard assets of all kinds.

What we saw preceding the present meltdown was the polar opposite: careful, systematic ignoring of the time value of money. The waitresses buying mansions, the bond insurers, and everybody in between, were all smoking crack on an epic scale. Monetary instruments were prized, the more complex the better.

As Market Ticker lucidly describes in this article, what we have is not an asset bubble, but a credit bubble. The Fed did not print a mountain of money. Rather, money already in the system was loaned out, changed hands in a purchase, was redeposited back into a financial institution, was loaned out again, and so on and so forth. For each new loan, the creditor could treat the balance due almost like real money—it could be bought, sold, traded, repackaged, even borrowed against—and that is the real source of the price inflation and supply glut that developed over the past 5 years. For a while, that sort of spiral looks virtuous. The easier it is to create debt, the richer everybody gets.

One could argue that the U.S. Federal Reserve and other central banks had primed the pump, but it's too big a leap from borrowing money merely at low rates to loaning it back out with total indifference to repayment. One could also argue that the central bankers were remiss in the securities they would accept in temporary open market operations, and perhaps that made some contribution, but it would have been little trouble for a bank to pawn only its sound collateral. In any event, temporary operations are just that—temporary—and have to be repaid with interest in a few weeks or months.

Nor does simple rapacious cheating explain the problems. A professional cheat slyly shifts the risk, so that the counterparty eats the whole loss. In many cases in this meltdown, the biggest cheaters kept the loans on their own books, and even many conservative organizations have taken painful losses.

No, the failure here was regulatory. The government regulators should have required that promised payments only be reported as an asset to the extent that they are likely to be paid. And then they should have randomly audited payment obligation contracts, from individual credit card purchases to giant corporate insurance deals, to verify that the probability of repayment was at least vaguely as promised.

This regulation would not have needed to be invasive or risky. One does not need to split legal hairs or make three-significant-figure measurements to determine that a $10/hour laborer cannot afford a $650k house. The thresholds can be set to ignore transactions that are unprofitable or even moderately risk, and still catch the stuntman transactions. The cost of appropriate regulation would have been a small fraction of a percent of each transaction, the interference with productive endeavors would have been minimal, and they would have uncovered systematic risk mispricing years before it became a civilization-threatening problem.

U.S. Treasury slashes annual savings bond purchase limit by 83%

2007-12-15T04:54:00.000-06:00

A person could previously purchase up to $60k/year of Series I savings bonds, which are an inflation-protected, tax-deferred investment bond. Starting 01 JAN 2008, the limit will be reduced to $10k/year.

In case you were wondering whether the feds were terrified of inflation, now you know.

More hating on Greenspan

2007-09-18T02:28:00.000-05:00

There's a definite lack of love towards Greenspan:

"Watching Chairman Greenspan comment on his handiwork in speeches and in his memoirs, and rake in the six-digit speaking fees all the while, we can't help but ponder the victims of the subprime debacles, especially outside Wall Street. Like the individual US home owner who was unlucky enough to get a subprime loan (which ended up inside some hideous CDO) and now faces foreclosure. Or the shareholders of UK mortgage bank Northern Rock, which was rescued by the Bank of England over the weekend and is likely to be sold. Or the investors in dozens of other mortgage companies which have failed in the past six months."

Not that the blame goes to him alone. He just loaded the gun—the mortgage holders aimed it at their own foot and pulled the trigger. Repeatedly, in many cases.

Greenspan on the housing bubble runup

2007-09-18T00:48:00.000-05:00

"While I was aware a lot of these practices were going on, I had no notion of how significant they had become until very late." "I really didn’t get it until very late in 2005 and 2006."

WTF, Greenspan? You were handing out bales of cash to anything that had a pulse. That money had to go somewhere. Inflation of the consumer price index showed that it wasn't being widely and evenly distributed to everyone. Ergo, the money was either being put on a shelf somewhere, or a few specific markets had to be massively inflating.

Dark matter 3

2007-08-19T16:54:00.000-05:00

This pre-print tells the story of Abell 520, a galaxy cluster formed by the collision of several smaller clusters.

In many respects it is an ordinary cosmic train wreck. The original clusters are still grouped together. The big, fluffy gas clouds collided and ground to a halt, being left behind by the stars. The gas was heated in the process and can now be seen glowing x-ray hot in the gulfs between the clusters. Gravitational lensing of distant background galaxies shows that Abell 520 has the usual ratio of dark mass to stars, about 4:1.

But the dark matter has a surprising location: like the gas, it too is separated from the galaxies in the vast gulfs between them. Dark matter had been thought to not interact with itself much, as shown by the Bullet cluster of galaxies, and also thought to start out as a spherical halo around ordinary galaxies. It is mysterious and surprising for the dark matter to be so thoroughly separated from the stars.

I see two possibilities. One is that dark matter can interact with itself, and Abell 520's dark matter has an unusual density or composition that facilitates this. The other is that the Big Bang managed to synthesize the dark matter and ordinary matter at different locations. For whatever reasons, they are usually created together, but in, say, an unusual primordial swirl, they need not be.

I lean towards the second explanation. We have already discovered a galaxy, VIRGOHI21, that is 99.9% dark matter. It is only a leap of scale to imagine that happening to a whole cluster.

I am very curious to see rotation curves for some of the galaxies in question, to verify that they are dark matter depleted.

Ha ha

2007-07-24T00:29:00.000-05:00

From an unfortunately-misspelled EE Times newsletter:

Advanced Micro Devices Inc. said it is intensifying efforts to rebalance its cost-structure and improve profitability by adopting what chairman and CEO Hector de J. Ruiz described as an asset-lie strategy. In pursuit of that strategy, the company expects to sell some plants and equipment as well as buildings and land to raise about $1 billion.

Norkgeld

2007-06-23T03:21:00.000-05:00

According to the Beeb and other fine news outlets, we are paying North Korea $25M and a million tonnes of fuel oil to not make any more nuclear bombs. They get to keep the reactor and all the fixins.

The terrifying thing is that I cannot tell whether this is because Team America has lost its freakin' mind, or because subtle behind-the-scenes machinations are now bearing fruit. With the present administration, it is no longer possible to distinguish insanity from cleverness.

Missing the point on evolution

2007-06-05T22:20:00.000-05:00

GNXP pointed out a nice rant on Good Math, Bad Math about a silly new book that preaches against the theory of evolution.

Mark Chu-Carroll thoroughly tears into the book, knocking down its math and logic in detail. However, he passes up the best argument: even if all the other B.S. were correct, a species' parasites and prey bulldoze its fitness peaks into fitness craters with overlapping rings. The more strongly mutations are rewarded and punished, the smoother the landscape becomes and the more frequently the rings meet on the same level.

We actually observe this from start to finish with RNA viruses, which sometimes evolve extreme virulence and exterminate broad swathes of their host species. Moreover, they are so simple, reproduce in such vast numbers, and mutate so rapidly that the evolution of virulence is consistent with microevolution^* alone. Yet despite RNA viruses repeatedly taking a shotgun to the host species' fitness landscape, the host survives and indeed thrives because it has not converged to a single "perfect" fitness peak.

^*Logic and strong evidence have forced many anti-evolutionists to accept microevolution, the idea that individual single-nucleotide mutations affect fitness, and will cause some sort of genetic drift even if intelligent intervention is needed for major biological innovation.

If we posit gigantic Calvinist selection pressure—selection Heaven for beneficial mutations, selection Hell for deleterious mutations—the landscape would be perfectly smooth, with the aggregate Terran genome slowly oozing along a gentle slope in whatever direction up currently happens to be. And that is a far more interesting subject than macroevolution, from a theological point of view. Does the global landscape have local maxima at which Earth-descended life can become trapped? Should Man accept those lesser peaks as a natural limit? Should he strike out across the valleys for an unknowable Genetic Promised Land? It's a pity that certain theologians have become stuck at their own local maximum of interesting things to talk about.

I wonder, were there any medieval scholars who argued vehemently about how many angels could dance on the head of a pin without understanding it was an allegory?

Civilization and the prisoner's dilemma

2007-05-23T01:54:00.000-05:00

Last weekend I was reading Douglas Hofstadter's Metamagical Themas on the subject of the prisoner's dilemma. The prisoner's dilemma is a toy model of the central question of civilization: on what logical basis do I refrain from screwing the other guy? Or rather, since social structures are putty in our hands, what structures do we build so that friendly cooperation helps us both? Obviously we want to avoid exploiting every possible advantage, since we both lose if we pound each other flat. Likewise we want to avoid unthinking deference, since the first Viking to come a-viking with pound both of us flat.

In the book, Hofstadter talks about using computer simulations to find a good social structure. The researchers came up with a variety of rules for social interaction. Some of the rules were dead simple ("always be nice"), while others were complicated predictive algorithms. To start with, each rule had the same popularity factor. Each rule was pitted against all the others, and its success was judged by how well it did on average multiplied by its popularity factor. If a rule was successful, its popularity quotient was increased, and vice versa.

What happened was both boring and remarkable. The simple rules like "always turn the other cheek" promptly disappeared, as common sense would predict. Then the others fought it out for a long time, gradually converging on rules that were nice but willing to be vengeful. The remarkable bit is that one simple rule always did well, often being the best: Tit for Tat. If the other guy hurt you, hurt him back this time and then be nice next time. Swift vengeance followed by swift forgiveness.

That crystallized my thoughts about civilization and stability. There are people who want everybody to be nice all the time. All sunshine and butterflies, never a storm or wasp. They say that an-eye-for-an-eye leads to everybody being blind. They rarely articulate their logic clearly, a careless and dangerous habit, but it goes something like this: Nearly everybody is nice nearly all the time. It wouldn't take much for everybody to be perfectly nice all the time. Therefore we should make Nice our highest law. All the cow people should be roped into the corral of sweetness and light.

BULL. Their vague handwavy logic ignores a critical matter. The current situation in the First World—most people nice most of the time—is not a static equilibrium. We did not wake up one morning in the Valley of Milk and Honey, surrounded by mountains so steep we couldn't climb out if we wanted, trapped in eternal prosperity and happiness.

But this I will say to you: your quest stands upon the edge of a knife. Stray but a little and it will fail, to the ruin of all.
— Galadriel, The Lord of the Rings

The free world is a dynamic equilibrium. It is a broom carried upon the tip of its handle, or a rocket balanced on a pillar of fire. We climb a ridge into the heights, and if our legs buckle, our grandchildren might not live to see above the clouds. Look at the path behind us. It's ten parts daring leap, and nine parts slide and fall. So many cultures have reached material and spiritual prosperity, only to crumble and fall into darkness, sometimes for a generation, sometimes for a thousand years, and some terrible times forever.

We had all the momentum; we were riding the crest of a high and beautiful wave. So now, less than five years later, you can go up on a steep hill in Las Vegas and look West, and with the right kind of eyes you can almost see the high-water mark—the place where the wave finally broke and rolled back.
— Hunter S. Thompson

So I thought to myself "Self, I ought to write a Bill Whittle-style essay about how the prisoner's dilemma applies to industrial society. It would rock."

Well, crap.

Bill Whittle went and wrote his own two-part essay (1, 2) about the prisoner's dilemma. He just posted it Monday. Synchronicity &c.

Oh, and as for an-eye-for-an-eye, what it leads to is a couple of idiots with no eyes, and the rest of the people helping each other get sand and stray eyelashses out of each others eyes.

Dark matter 2

2007-05-18T01:04:00.000-05:00

A continuation of Dark matter: what do we know.

So dark matter is mysterious. How do we learn more?

Good question. The trouble is it doesn't appear to interact much with laboratory equipment. If it came in small, dense chunks, laboratory evidence would have turned up by now. We've done quite a few experiments with enough sensitivity to detect tonne-scale chunks—ultracold calorimeters and acoustic resonators, pendulums, optical interferometers, and so forth. The excellent stability of atomic clocks rules out higher-order quantum effects caused by dark matter.

We likewise see very little evidence of it in solar space. The planets and assorted rubble appear to move to ancient Newton's laws, with an ocassional tiny correction for that upstart Einstein. Deep space radars don't show spacecraft bobbing around in the wake of tonne+ masses. (Although maybe nobody has looked closely enough—I'll ask my personal space radar expert.) The Pioneer 10 and Pioneer 11 probes have subtle anomalies in their deceleration curves, but I expect that is just a chemical or mechanical effect.

Even within our galaxy, dark matter's effects have not been clearly observed. We are getting lots of good data from distant galaxies. However I doubt this will illuminate the quantum physics of dark matter, assuming it has any. We just don't have the resolving power to see fine enough details, and are not likely to get it soon.

So where do we look? I favor looking for dynamical friction near our galaxy's gigantic central black hole (Sagittarius A*). It has both immense gravity and close-orbiting stars. The stars orbit so fast that we could just about afford a telescope to watch them move from week to week. If dark matter comes in chunks less than a light-year wide, that's where we will see it.

Nearby globular clusters are also a good place to look for dynamical effects. If anything smaller than a galaxy is big enough to have a dark matter density gradient, they will. (Globular clusters can reach hundreds of light years in size.) Depending on how dark matter works, they might even have captured some of it. At the same time they are close and bright enough that we can distinguish individual stars, which lets us do detailed measurements of the cluster's gravitational structure.

I can't come up with any plausible laboratory experiments for dark matter. High-energy particles do not seem to have any interaction, or the effect would show up in particle accelerators. It would probably also eliminate the high-energy cosmic rays that we observe, which helps rule that out. If big stars capture dark matter, then it might affect the neutrino brightness curve of a nearby supernova. We could measure that with a terrestrial instrument, but nearby supernovae are once-in-a-lifetime events.

Dark matter: what we know

2007-02-14T19:57:00.000-06:00

I've been thinking a lot recently about the cosmic dark matter problem. It really is vexing.

First, what do the data say:

It was discovered that we can measure how galaxies rotate, by looking at the Doppler shift of atomic emission lines. It's the same basic principle as pointing a Doppler radar at a tornado or hurricane, although what we see is the y-z plane instead of the x-y plane. Great precision is possible because an atomic emission line covers a very narrow frequency range, and we know how to precisely separate different frequencies of light. So we made all these cute hook-echo-like pictures of galaxies, showing how fast the various parts of the galaxy are orbiting its center. (For each pixel we actually get a distribution of velocities, because we see through the whole thickness of the galaxy. The peak/valley of the distribution is from the stuff we see moving head-on and is the rotation speed for that distance from the center.)

And since the stars in a galaxy orbit according to gravity, and gravity depends on the mass enclosed by the orbit, this tells us how a galaxy's mass is distributed.

We can also tell how mass is distributed by the amount of light that shines out. We have to make guesses about how bright the average star is, how far away the galaxy is, and how much dust there is blocking the light, but the predictions turn out to be constrained to a pretty narrow range as cosmological things go. And even if we get it wrong for a particular galaxy, many of the errors will average out to zero when we measure a large number of galaxies.

Both types of measurement were made. They turned out shockingly different. It varies for different galaxies, but on average the rotations show about four times the mass that the brightnesses show. Nor can it be an evenly-distributed error, because although many galaxies have been observed with faster rotation than predicted by brightness, not a single one has ever been observed with slower rotation.

Because the missing gravity source does not glow, it was dubbed dark matter. (However it need not be ordinary everyday matter, so don't take the word "matter" too literally.)

The Doppler rotations were confirmed by radio emission lines from hydrogen gas clouds, so it isn't some sort of problem with UV/vis spectrometry.

In fact, an entire galaxy has been discovered [1] [2] that has only the radio "glow" of a handful of hydrogen gas, no apparent visible stars at all, and the usual amount of dark matter expected for a typical galaxy. The dark matter to normal matter ratio is at least 100:1. If this discovery pans out, the deficit of ordinary matter will be impossible to explain away as a measurement error. Even if the entire galaxy were hidden by dust, the dust would be visible by dint of covering up distant background galaxies.

Other evidence for dark matter comes from the hydrogen clouds in large galaxy clusters. We can measure their temperature from their x-ray emissions, and temperature tells how fast the atoms are moving. Because the clouds have not evaporated, there must be enough gravity to confine them given the atoms' thermal motion. And once again, the visible matter in the clusters does not have enough gravity to explain the confinement.

The latest, and most interesting, evidence of dark matter is from the Bullet cluster of galaxies, a pair of galaxy clusters that have collided. The stars are teeny tiny compared to the empty space between them, and so they mostly just pass by each other. Conversely, the gas/dust clouds are fluffy and diffuse, and so they collide strongly as the galaxies pass through, practically plowing to a stop and forming a new combined cloud (which glows x-ray hot from all the kinetic energy that has been thermalized).

The cool thing about the Bullet cluster is that the non-cloud parts can be directly weighed by optical means. They form a gravitational lens that bends light, distorting the images of the distant background galaxies. The lensing measurements show the usual amount of dark matter, located right there with the visible stars. As usual, the lens mass is much greater than the visible mass of the stars. Rather than plowing to a halt alongside the gas clouds, one set of dark matter passed right through the other set.

However, other measurements have looked for gravitational lensing inside our own galaxy. If there are dense, star-sized clumps of matter in our galaxy, they will occasionally pass between us and a distant star, causing lensing for a few hours or days. Individually such alignments are rare, but with billions of objects zipping around, the odds are actually good we will see dozens a year. These measurements have been made and do not show nearly enough "microlensing" to account for the missing mass. So dark matter is not organized as clumps.

What else do we know about dark matter:

It doesn't participate in the electromagnetic force. Otherwise light would bounce off and space would be pretty foggy.
It doesn't intereact via the weak force much, if at all. Otherwise radioactive decays would be much faster or much slower.
It doesn't interact via the strong nuclear force much, if at all. Otherwise it would do obvious things to ordinary baryonic (made of protons and neutrons) matter, and spectacular things to neutron stars.
The relationship between its inertial and gravitational masses are not clearly shown by the data.

Valproate + parthenolide risky?

2006-09-12T23:39:00.000-05:00

The abstract for this paper says that valproate and parthenolide interact to cause cells to die. (Albeit thoracic cancer cells grown in culture, so the wider applicability is not guaranteed.) The relevant quote from the abstract:

Kinase inhibitor-mediated suppression of NF-kappaB transcriptional activity played an important role in sensitising cancer cells to valproate as direct inhibition of NF-kappaB by Parthenolide drastically synergised with valproate to induce apoptosis (valproate+Parthenolide: 60-90% compared to <20% following single-drug treatments). [They refer to valproic acid, which I have changed to the more general term valproate.]

Background: Valproate is an FDA-licensed drug. Originally used for epilepsy, it has also found use for migraine and other disorders. Parthenolide is a chemical that naturally occurs in many medicinal plants. It is found in feverfew, among others, and preparations containing that herb are sold for migraine prevention. Both substances appear to penetrate the brain well.

What is disturbing is that both valproate and parthenolide are commonly used for migraine prevention. Their combined use is a real possibility, particularly with self-medicating patients adding on "a harmless natural herb". Their synergism is therefore not necessarily a recipe for good results. Undoubtedly people are out there right now running their own private uncontrolled experiments.

Reference: Br J Cancer. 2006 May 22;94(10):1436-45, Potentiation of the anticancer effect of valproic acid, an antiepileptic agent with histone deacetylase inhibitory activity, by the kinase inhibitor Staurosporine or its clinically relevant analogue UCN-01.

Forteanum

2006-08-22T23:26:00.000-05:00

The Leaking Tree of Texas

Magnetoresistive RAM

2006-07-11T21:46:00.000-05:00

Freescale has a neat new computer memory technology, MRAM, that uses magnetism to store the data. It's a little like old-fashioned magnetic core memory, but with the pieces laid down photographically instead of weaving wires through magnetic rings.

MRAM's claims to fame are that (1) the data is preserved even when the power goes off, and (2) it does not wear out when written. Flash memory does #1, but fails miserably at #2, inevitably corrupting the data when it is written too many times.

MR2A16A parameters
Parameter	Value
Capacity	4 Mib (512 kiB)
Organization	256 ki × 16 bits
Max. ambient magnetic field	1.5 mT = 15 gauss
Operating temperature	0 – 70 °C
Power @ 3.3 V Peak Standby	155 mA 12 mA
Cycle time	35 ns (28 MHz)

The tolerance to ambient magnetic fields is respectable, equivalent to the field in the middle of a 1 cm² circular loop carrying 23 A of current. In most systems it ought to be pretty easy to keep currents that big suitably far away from the MRAM chip.

The operating temperature range, however, is a real limit. Not going below 0 °C makes it suitable only for appliances that sit indoors in a heated office. (I supposed you could design a heater into your circuit board, but what a pain.) Presumably this will be improved in a future iteration. There are all sorts of neat industrial applications for a nonvolatile RAM that doesn't wear out.

Verdict: nifty and cool, but not quite ready for every application under the sun.

Fast comparators

2006-06-22T01:15:00.000-05:00

Last week I went looking for ultrafast voltage comparators^* for a new project. I've never used these things before, and it's a bit intimidating to be turning radio waves directly into binary digital signals. To my surprise, you can get >3 GHz devices pretty easily, and for not a lot of money. That's fast enough that you could run a wire into your microwave oven and the comparator would watch the individual radio cycles going by. For instance, the Analog Devices ADCMP572 has 35 picosecond rise and fall times, and only costs $7.

These parts even look pretty easy to use—just be real thorough with the usual high-speed design techniques. The annoying part turns out to be processing the signal upstream of the comparator. Nobody makes stable, predictable operational amplifiers that run at 5 GHz, and even if they did it would be sheer madness to try making it work. No, I'm afraid it is going to be microwave radio amplifiers all the way, perhaps with a separate wideband transistor to help reshape the pulses. At this rate I'm going to turn into a radio designer.

^{*^{A comparator measures whether one voltage is greater than another. Electrical engineers commonly use that function in their designs. For instance, a comparator can tell you when the battery is completely charged.}}

Trace amine receptors

2006-04-07T02:10:00.000-05:00

This interesting paper is about cellular receptors for trace amines. (Amines are simply chemicals that contain one or more atoms of nitrogen—the human body uses a variety of them for transmitting signals. ) Some, like histamine, are used all over the place in large quantities, and so it was easy to figure out what they did.

Others are consistently present at very low levels. The low levels of the amines and their receptors have made it hard to figure out what is going on. Research has shown that trace amines appear to function as transmitters, and that they are often disturbed in certain disease states, such as migraine and schizophrenia. Unfortunately for many years the understanding stalled at that point: intriguing but mysterious.

As the linked review paper shows, the answers are finally starting to arrive. A family of receptors has been discovered that are highly-specific to trace amines, in particular tyramine, β-phenylethylamine, octopamine, and dopamine. They are present in many species of mammals, and are localized to intriguing brain regions like the amygdala (which influences emotional responses). It will be interesting to see if any answers to the migraine puzzle turn up in this new molecular territory.

Finally, an environmentally responsible nuclear bomb

2006-03-28T00:56:00.000-06:00

"US researchers say they have developed 'green' chemicals that could replace the lead-based primary explosives that are used to detonate everything from blasting caps to ballistic missiles."

What will they think of next?

Biological electric fields

2006-03-18T01:53:00.000-06:00

Many living cells keep their interior at a different voltage than their exterior. The upper limit for human cells seems to be about 50 millivolts. Normally we think of that as a puny voltage—a flashlight battery is 30 times higher.

But I got to thinking. Sure, the voltage is smallish, but cell membranes are super thin, in the range of 5 nanometers. If we divide the voltage by the distance it acts over, we get the electric field strength:

50 mV / 5 nm = 10 000 000 V/m

Good grief, that is big! (The dielectric breakdown strength of air is a couple of MV/m.) So cell polarization is not a subtle force that gently touches trans-membrane proteins. It is definitely more of a fold-spindle-mutilate interaction. I am impressed that ion transporters can pump against a potential gradient that large.

Microwaved marshmallow Peeps

2006-03-08T23:28:00.000-06:00

Food. Of the. Gods.

(Granted, unhealthy, brightly-dyed Gods, but holy nonetheless.)

The strategy of victimhood

2006-01-23T02:36:00.000-06:00

The Amazon.com product page for Ghost in the Shell - Stand Along Complex warns that it contains "violence against women".

Yeah, and also violence against:

Men
Children
Cyborgs
Robots
Buildings
Shrubbery
Computer defense software
Cars
And just about everything else that can be shot up, blown up, or burned down

But only that against women deserves a special note. Apparently there is some hidden ranking and women come at the top.

Curious non-vasoconstrictor effects of a triptan

2006-01-13T18:50:00.000-06:00

The triptan drugs used to treat migraine are widely regarded as vasoconstrictors: they shrink bloated blood vessels, relieving the irritation that contributes to migraine. To quote Walgreens on Imitrex, "This medicine is a cerebral vasoconstrictor used to relieve migraine headache attacks as they occur."

As luck would have it, they are not terribly specific. They also shrink blood vessels elsewhere, including the heart. So people with heart disease cannot use them. Ditto for peripheral artery disease and similar vascular problems. This bad side effect is shared by other migraine drugs like the ergot derivatives.

Enter donitriptan, a newer migraine drug under development. It seems to have little effect on blood vessels. Researchers are finding, though, that it still has major effects on the brain. In that paper about a study of rats, researchers found no regional blood flow changes anywhere in the body. Yet they found that the brain's oxygen use dramatically increased. (As measured in the jugular vein by decreased oxygen and increased carbon dioxide. Sumatriptan (Imitrex) has a similar metabolism increasing effect.) This bodes well for a new family of safer migraine drugs. They also found that the metabolism increase was cancelled by giving the rats a 5-HT_1B/1D receptor antagonist. That localizes things to receptor subtypes that were already known to be important in migraine.

I want to know where the metabolism was happening. The neurons themselves are not really built to burn much energy, and doing so tends to kill them. If it was the neurons, we would expect triptan overdose and overuse to cause brain damage, along the lines of glutamate toxicity.

I'm guessing (pure speculation by a non-expert) that triptans affect the big support cells called astrocytes. They are the logistics system of the brain, delivering chemical supplies to delicate neurons, hauling away their waste, and constantly sweeping the environment so nothing unpleasant builds up. They are richly endowed with chemical transporters that take energy to run, and we know from studying spreading depression that they can survive huge gains and losses of certain chemicals. Perhaps 5-HT_1B/1D stimulants force their transporters to run overtime, changing the equilibrium of one or more internal chemicals. This change would spill over into the neurons, to which they are directly connected, making them harder to trigger and quenching the abnormal sensitivity that causes migraine suffering.

Hmmm... It would be interesting to know what a 5-HT_1B/1D antagonist drug does to migraineurs. If this theory is correct, small doses would reduce the migraine threshold, and largers doses would trigger an outright attack. Good luck finding volunteers for that study.

(This is based on my reading of the abstract, not the full paper.)

Judicial activism, part one

2005-12-23T01:39:00.000-06:00

Part One: What they do

Let's do a thought experiment. Imagine the First Amendment to the U.S. Constitution was just a little different:

Congress shall not paint stars on its bellies.

Now to you and me, the meaning is pretty plain. There are no fuzzy points, no areas of contention.

What if somebody gets tricky and asks about taxi drivers? Our imaginary amendment says nothing about them. Maybe another law somewhere says taxi drivers shall not wear stars on Thursdays. Maybe not. The point is: it is not about taxi drivers or Thursdays. It controls Congress.

Now if you were a U.S. federal judge, it is just as plain. The Constitution exists to Protect People From Tyranny and Oppression. No matter which rock Evil tries to hide under, it will be found and smashed.

So in this case, our fearless judges would discover that Americans have a natural right not to see star-bellied Congressmen. The Founding Fathers would not have mentioned it at all if there wasn't a universal right that needed protecting. All the circuit judges reading this nod their heads at this point.

And at this point, a justice of the Supreme Court would whip out his great, shining Chainsaw of Generalization. For the right cannot be limited to only Congressmen. What's the point, if the town council and postmen can go about with nasty stars? To really have teeth, the right has to eliminate all government starifying. Only then can people gaze freely on the starless public spaces, in this great free land between the two seas.

For the star would be a symbol of oppression and control, a tool of fundamentalist oppressors. If the mayor put a big star on the town square, he might as well have sent a starry Senator Kennedy to belly dance in your living room—it's just that horrible.

So the people have to be protected by any means necessary. A noble defense lawyer can find something star-shaped, help someone learn how offended they are by it, pay their court filing fees for them, and presto! a federal court will protect their rights. Rights they may not have even known they had, until an officer of the court helped the victim discover them.

Of course, the First Amendment really says

Congress shall make no law respecting an establishment of religion.

Now once again, the meaning is pretty clear to you and me. Unfortunately, once again it is also clear to our glorious federal defenders: all governments everywhere must be completely cleansed of every trace of religious contamination. Slapping a cross on the city seal causes such injury to someone (exactly what injury is never mentioned) that it must be remediated.

Good news for chronic migraine

2005-12-21T23:48:00.000-06:00

This study looked at family history of vascular risks in migraineurs. Vascular risk factors tend to run in families, but are not easily measurable in younger migraineurs. Looking at older family members makes the risks easier to measure, and gives more accurate results (larger experimental sample). I find the following result particluarly interesting:

[Chronic migraine] patients were more likely to have a negative [family history] of stroke compared to other headache types, suggesting that [chronic migraine] is likely a neuronal disease rather than a vascular one.

This result is not unexpected. If continuous chronic migraine were caused by symptomatic vascular problems, we would expect a spectacular increase in vascular adverse events. (Like how a person with daily heart pain is living on borrowed time.)

Unfortunately, this study only compared different types of migraine to each other, so it does not tell us the absolute vascular risk caused by migraine. Researchers: always use a normal control arm! For only a little higher cost, you can give your study meaningful results.

Public benefits of GMOs

2005-12-17T15:19:00.000-06:00

A comment on this post provoked me to think about what benefits we are getting from genetically modified organisms (GMOs). A common claim is that while they might theoretically be good, all they really do so far is line the pockets of the agri-giants. My reply was that GMOs already give a lot of public benefits:

Consumer: Fewer chemical treatments have been applied to the foods they eat. Protein levels are higher because of reduced competition for nitrogen by weeds.

Economy: Higher crop yields drive farmers and farm product suppliers out of business, freeing their labor for other work and industries. (Well, this is good if you subscribe to the creative destruction theory of economics.)

Land: Less land needs to be under cultivation at any given point. This reduces topsoil loss and airborne dust, and permits land to be left fallow for longer. I suspect that it also allows less aggressive, and therefore environmentally friendlier, tilling to be used.

Pollution: More concentrated cultivation means less fertilizer is wasted, less fuel is used to power farm equipment, less pollution is produced by farm equipment with poor pollution controls, and so forth. Not only good for the environment, this also lowers prices of other products that compete for the same feedstocks, and reduces strategic dependence on unstable supplies (such as Arabia).

Public: Many of these purportedly-greedy agribusinesses are actually wholly-owned by the public. (And don't whine that most stock is owned by giant institutional investors, not the general public. Those institutions are the public's insurance and retirement piggy banks.)

Future developments: Research budgets come out of the margin, the gap between income and expenditures. When a profitable company increases their income by X%, they can afford to increase research funding by substantially more than X%. Monsanto, for instance, ploughs about 10% of revenue back into research, which is astonishing for a company that exists solely to put commodities on the shelves of Wal-Mart. (The benefits are not just theoretical. Agri profits paid for the development of soybeans whose oil can be used to replace trans fatty acids, which will have tremendous cardiovascular benefits for Americans.)

Security: More efficient crops mean less possibility of shortage during drought or pestilence.

Gravity Probe B data finishes collecting data

2005-12-17T01:40:00.000-06:00

This actually happened back at the end of September, but it was not covered much in the news (or I missed it).

Einstein's theory of general relativity predicts that a spinning object produces slightly different gravity than a non-spinning one. (It is called frame dragging, in case you care.) Gravity Probe B is a satellite designed to measure this effect for the rotation of Earth. If the results are reliable, they will either confirm relativity or blow it out of the water.

In principle, you can measure it by just putting a test mass in orbit around Earth and watching its orbit. Unfortunately for scientists, the rotation-and-gravity effect is absurdly, ridiculously tiny. The test mass must be highly isolated from anything that might affect it, like a single grain of dust, or even just sunlight. (Seriously: sunlight exerts way too much pressure.)

The measurements must be made far more meticulously than even the normal standards for scientific instruments. The test masses are the best spheres ever made by man, polished to within a few dozen molecule-widths of perfection. The masses are spun at thousands of RPMs to magnify the rotation-and-gravity effect. They are kept in a very high vacuum so aerodynamic drag will not affect them. Their container is made of superconductor to keep out magnetic and electric fields. The surroundings are chilled to within a few degrees of absolute zero to keep thermal radiation pressure from doing much. The test masses travel in their own orbits without being touched by anything, meaning the satellite has to constantly adjust to keep them from bumping into the walls of the container.

In short, it is one of the most audacious and precise projects every carried out. And so far the engineering seems to have been a success.

Blocking the destruction of endocannabinoids

2005-12-16T02:37:00.000-06:00

Ars Technica has a short article about URB597, a drug that prevents the enzyme fatty-acid amide hydrolase (FAAH) from working.

Well FAAH is the enzyme that degrades endocannabinoids (marijuana works by stimulating endocannabinoid receptors). Blocking FAAH effectively amplifies the levels of naturally occurring endocannabinoids. The increase caused by the drug should be proportional to what the body is already putting out. This should give more gentle and targeted control than drugs like marijuana, which indiscriminantly stimulate all cannabinoid receptors.

A paper to be published in PNAS shows that URB597 is a potent antidepressant in several animal models, and that this is "prevented by the CB1 antagonist rimonabant" and "accompanied by increased brain anandamide levels" In plain English, it improves mood like marijuana, and is blocked by the same drugs that block other cannabinoids. (It's usually impossible to tell which receptors a drug affects, so researchers administer known blockers and stimulators to find out by way of comparison.)

The abstract also says that the effects "are maintained upon repeated URB597 administration". Good. The drug doesn't "wear out" over time. Lots of good drugs crater because the body rapidly develops tolerance to them.

These results are of considerable interest to chronic pain patients. Cannabinoids are known to affect pain, as shown by considerable anectdotal evidence and some controlled trials. They are also famous for their ability to reduce nausea and increase appetite. This is relevant to migraine because the disease process often has the opposite effect: spectacular nausea and food aversion (to the point that some sufferers need hospital treatment for dehydration).

The abstract for the paper also says "Unlike direct CB1 agonists, URB597 does not exert rewarding effects in the conditioned place preference test or produce generalization to the discriminative effects of Δ⁹-tetrahydrocannabinol in rats." In plain English, it does not cause obvious addiction-related behavior in animals. This is good because it means the prohibition industry might leave it alone.

The abstract mentions the drug rimonabant in passing. That's an interesting new drug that blocks CB1 receptors. It seems to have some of the opposite effects as marijuana, in particular producing "anti-munchies". It therefore is promising for the treatment of obesity and diabetes. I do worry that CB1 antagonism may have depressant side effects, which would be just terrible for folks who need to lose massive amounts of weight.

Irony...

2005-12-16T02:27:00.000-06:00

...is going to Walgreens and hearing the Rolling Stones' "Mother's Little Helper" playing on the radio.

Hmmm... that reminds me of the time I heard a Wal-Mart play Queen's "Fat Bottomed Girls". I am thinking that some employee was not allowed to choose the music after that.

Activist "scientific" journal joins Merck pile-on

2005-12-11T14:58:00.001-06:00

The New England Journal of Medicine has published a direly-worded Expression of Concern about a Merck paper on Vioxx's heart risks. They claim Merck withheld data from the paper, and insinuate that secret evidence shows Merck deleted it at the last moment before publication. They finish by saying "Taken together, these inaccuracies and deletions call into question the integrity of the data on cardiovascular events in this article. We have asked the authors to submit a correction to the Journal."

Sounds bad for evil ol' Merck, eh? Well have a look at the NEJM's own data:

Rofecoxib (Vioxx) to naproxen relative risk
Study Group	Relative risk, 95% confidence range
Study Group	Original data	NEJM Allegations
Entire group	1.39 – 17.37	1.68 – 20.13
Aspirin indicated subgroup	1.65 – infinity	1.66 – infinity
Aspirin not indicated subgroup	0.63 – 10.02	0.91 – 12.78

There are some major problems here.

Problem 1: Confidence ranges as wide as the Grand Canyon. This is not surprising, since the study produced less than two dozen measurable events. The results are just too small to draw precise conclusions. About all you can say with any confidence is that Vioxx looks fairly scary.

Problem 2: Alleged missing data makes no clinical difference. No doctor said "Oh no! If I had known the relative risk as 20 instead of 17, I never would have prescribed the drug!" It makes no practical difference. The data show a clearly risky drug, with a few percent chance of being spectacularly dangerous.

Problem 3: Secret evidence. The NEJM claims "We determined from a computer diskette that some of these [relevant adverse cardiovascular] data were deleted from the VIGOR manuscript two days before it was initially submitted to the Journal on May 18, 2000." What diskette? Of what origin and chain of custody? Determined how? By whom? In accordance with which published forensic data analysis standards? The NEJM is not saying.

This is not science. It isn't even journalism.

Problem 4: Uncontrolled data. At least from what the NEJM is showing here, the original trial had no placebo arm. It only compared one drug with another, not with no drug treatment at all. Merck told the FDA that naproxen must have been protecting people against heart attacks, and that the more frequent rofecoxib events were just the underlying heart disease of the study group. Without a placebo subgroup, who's to know? Skeptical scientists, that's who. Crap like this would get a bad grade in undergraduate biology. The FDA and the original NEJM reviewers should have sent Merck back for a do-over.

Lies. Damn lies. Statistics. Medical trials without a placebo subgroup.

Problem 5: Activism, not accuracy. Speaking to the New York Times, one of the NEJM article's authors says

"They did not disclose all they knew," Dr. Curfman said. "There were serious negative consequences for the public health as a result of that."

Say what?! The original data showed Vioxx to probably be dangerous, and the alleged data makes no material difference in that conclusion. Furthermore, Curfman provides no evidence that the data were hidden from the FDA, or witheld from the Prescribing Information sheet.

The NEJM appears to be outpacing The Lancet in the political activism olympics. I hear the winner gets a gold-plated Sphincter Medallion.

UPDATE: One of Derek Lowe's commentors, which I somehow missed earlier, makes many of the same points:

So are calculations made "incorrect"? Only in a way that an innumerate reader would care about. ... I doubt this "Editorial" would have made it through peer review without changes. I wonder what process NEJM used to assess it before going ahead and publishing? And will they be reconsidering that process going forward?

Goto for Python

2005-12-10T22:23:00.000-06:00

Wow, how could I miss this? Somebody added goto to the Python programming language! Not just plain gotos, either, but real computed gotos as well. Unfortunately it was just an April Fools joke. Yes, I said unfortunately. try/except works well for most uses, but sometimes a good ol' fashioned goto really hits the spot. They also seem to have added comefrom, perhaps the most nefarious idea to ever be visited upon computer science.

Migraine prophylaxis with naratriptan

2005-12-06T19:35:00.000-06:00

This study shows that naratriptan can be used daily for migraine prophylaxis to very good effect. Unfortunately, all the triptan vendors are chasing the lucrative acute treatment market, so prophylactic use would cost US$8 000/year.

Scanner

2005-11-20T20:22:00.000-06:00

I recently bought an Epson Perfection 4990 scanner. I am remarkably happy with it. It has high resolution, reasonable noise, scans quickly, and it can handle paper, photos, and film. The scanning software does a wonderful job at correcting the color of yellowed old color photos. So far it has only crashed about half a dozen times in around a thousand scans, unlike the crashy crapware provided with many scanners. It simply works, and produces good results. The automatic stuff generally does a good job, and is trivial to turn off when it gets confused. Preview scans, are fast, and you can interactively crop the desired images out of the preview window.

It does have several problems. One complaint is that while the scanning software can record and save 48-bit scans, none of the included software can do anything useful with them. This makes the scanner considerably less useful for enhancing old snapshots with deep shadows or burned-out highlights.

Another is that the scanning software makes extremely poor use of memory. While scanning and compressing images, it constantly accesses the hard drive, whilst hundreds of megabytes of RAM sit idle. Very short-sighted. Bad Epson, no biscuit.

Finally, an irritation is that the Epson scanning software allows you to save and recall commonly-used settings for resolution, color depth, and so forth, but not using your own names. No, they're only listed as "Setting 1", "Setting 2", and so forth. Once again, a superb piece of electromechanical engineering screwed up by some troglodyte programmer drooling into his keyboard.

Here's a sextant I scanned out of an old book.

(Image hosted by Flickr.)

Katamari food

2005-11-11T21:56:00.000-06:00

This is quite silly.

A new migraine prophylactic?

2005-11-08T22:00:00.000-06:00

Memantine (brand name Namenda), marketed for Alzheimer's disease, was found possibly useful for migraine prevention. The drug antagonizes the NMDA receptor, blocking the action of glutamate, the primary excitory neurotransmitter in the brain. It makes sense that that would calm down the overexcitable processes thought to cause migraine.

Unfortunately, the study was small, so it does not have much statistical predictive power. Worse, it was open label. The patients knew they were getting the drug, so there was almost certainly a big placebo effect.

Another problem is that NMDA antagonists are known to cause brain damage, at least in rats, in doses that are not all that much higher than the therapeutic dose. So far the drug has mostly been tested on the demented elderly, which does not really rule out brain damage. I would not want to try memantine until several years of testing has been done on non-demented younger patients.

Side effects: antidepressants for chronic pain

2005-11-08T21:03:00.000-06:00

The web page linked above has an excellent table of the pharmacalogical effects of various drugs used for chronic pain. I came across it many moons ago but foolishly did not save a link, and only now have found it again. I will save a copy here to make sure I don't lose it again.

Antidepressant Effects
Drug	Antimuscarinic Activity¹	Antihistaminic Activity²	α-1 blocker³	NE reuptake inhibition⁴	5-HT reuptake inhibition⁵	T_1/2 (hours)^*
Amitriptyline	3	3	3	2	4	32–40
Doxepin	2	4	3	1	2	8–25
Imipramine	2	1	1	2	4	6–20
Desipramine	1	0	1	4	3	12–54
Nortriptyline	1	1	2	2	3	15–90
Trazodone	0	0.5	2	0	3	3–9
Fluoxetine	0.5	0	0	1	4	168–210
Bupropion	0	0	0	0	0	0
Blocks the muscarinic-type acetylcholine receptors, an effect commonly called anticholinergic. Causes side effects like increased heart rate, dry mouth, digestive slowing, and so forth. Blocks H1 and H2 histamine receptors. Causes side effects like drowsiness, reduced stomach acid, and so forth. Probably helps allergies, not that you'd take these drugs for that. Blocks α-1 (alpha-1) receptors. Causes a variety of effects, most notably relaxation of smooth muscle. This causes small blood vessels to dilate, lowering blood pressure, possibly enough to cause dizziness or even fainting. Blocks the norepinephrine reuptake transporter, thus exposing brain cells to more of the neurotransmitter norepinephrine. May be responsible for antidepressant effects. Blocks the 5-HT reuptake transporter. (5-HT stand for 5-hydroxytryptamine, also known as serotonin.) This exposes brain cells to more of the neurotransmitter serotonin. ^*Half-life, the time it takes for half of a dose to leave the body.

So what does all that mean? For starters, that I ought to try switching from amitriptyline to nortriptyline. It ought to give much less of the obnoxious side effects, but retain much of the anti-migraine value.

Live organ transplants

2005-11-08T00:30:00.000-06:00

So, do you mind if we have your liver? Not just for Monty Python any more.

Paris, the city of lovers, is glowing...

2005-11-07T00:47:00.000-06:00

True, that's because it's on fire, but still... ^*

Fortunately the New York Times is on top of the story:

"The corrosive gap between America's whites and its racial minorities, especially African-Americans, is the product of centuries: slavery, followed by cycles of poverty and racial exclusion that denied generation after generation the best the United States could offer. France, on the other hand, is only beginning to struggle with a much newer variant of the same problem: the fury of Muslims of North African descent who have found themselves caught for three generations in a trap of ethnic and religious discrimination."

Note the semantics of victimhood. Trap. Exclusion. Denied. Caught. Discrimination. Underclass.

Not their fault, those nasty Frenchmen dragged their parents to Paris, kept them from seeking out education, forced them to sit around and be angry, made them worship in tatty secondhand mosques. We hates France! Nasty France! We hates it forever!

Meanwhile Aunty Beeb had a story, since quietly altered, tugging your heart strings about the two young boys heartlessly electrocuted. In reality they were nearly-grown men (15 and 17) fleeing police pursuit, who hadn't the sense not to play in the electricity. You know, lads, that's why that big fence with the warning signs and lightning bolt icon is there. That loud hum is the sound of nasty death. Of course, "young boys" can't be expected to know about these things.

To everything
spin spin spin
There is a slant
spin spin spin
And a lie for every purpose
Under heaven

^{*Title lyrics from Disney's The Hunchback of Notre Dame.}

Forteanum

2005-09-23T18:47:00.000-05:00

"The other day we had a bird strike. We sent the sample to the DNA lab and it came back as rabbit. How do you explain to the FAA that we had a rabbit strike at 1,800 feet?"

Zero-threshold MOSFETs

2005-07-06T00:11:00.000-05:00

Advanced Linear Devices makes a series of MOSFET transistors with zero threshold voltage. That means they can work at ridiculously low power supply voltages—ALD quotes 0.2 V. T

Zero-threshold MOSFETs are not a new concept. Previously, however, the threshold was determined by dopants (trace impurities) in the transistor channel, and there wasn't enough accuracy to guarantee a threshold close to zero. ALD appears to be getting around that by using floating gates to compensate for channel variability. Rather than perfectly dope the channel, the factory simply has to measure the imperfect channel and program the floating gate to compensate. A side benefit is that all the transistors are well-calibrated to the same settings; engineers normally have to design with sloppy (as in +/-50% on a good day) transistors in mind.

Downsides: The transistors can only handle low voltages. High voltages will cause electric charge to quantum-mechanically tunnel onto the floating gate, which would wreck the delicate calibration. (I bet they handle static electricity poorly.) Ionizing radiation is also a concern, as it can toss charge onto the floating gate, erasing the calibration. (What about airport and postal x-ray scanners?) Ambient radiation will certainly cause slow drift over time.

As their data sheet doesn't talk about the problems, I'd be leery of using these parts in an aircraft, military, or long-life industrial application, and certainly not in spacecraft. They talk about the low threshold being useful for medical apps, but say nothing about what would happen during a long session with a fluoroscope (the kind where the patient comes out with x-ray burns). Until I see some more numbers, I'll have to limit these parts to less-critical applications.

Medical use of deuterium

2005-07-06T00:03:00.000-05:00

This paper says that injecting heavy water (deterium oxide, D₂O) into the cerbrospinal fluid reduces the damage caused by a subarachnoid hemorrhage.

The "science" of child abuse

2005-06-28T23:01:00.000-05:00

MetaFilter has an intersting article about Munchausen's by proxy. The syndrome's originator, Roy Meadow, is charged with scientific incompetence and/or misconduct for his work on child abuse. For example, he testified against parents in court claiming that the odds of two unexplained infant deaths in the same family were 73 million to one, which clearly ignores correlated causes such as genetics.

This Times article has some pointed things to say about Munchausen's by proxy:

Munchausen’s syndrome by proxy is a quintessential example of that most suspect of scientific theories — one that brooks no rational argument, a closed circle we all must accept at face value.
For example, the only cure must begin by the sufferer accepting that he or she is afflicted with the condition — which, of course, the alleged sufferer is loath to do. But if someone who is diagnosed as a sufferer vociferously denies it, this serves to reinforce the diagnosis. A denial of the condition is, perforce, a symptom of the condition.
...
So there we have it: an illness that has no cause or cure and that is diagnosed at least partly by the alleged victim’s denial that he or she is so afflicted. The more the victim denies it, the more obviously the victim is afflicted. And it is an illness that may somehow exist within a person without cause or cure or indeed any manifestation of its symptoms.

Certainly some parents become dangerously obsessed with their child's health, or use the child to gain attention. But I also know from personal experience that certain illnesses can be extremely tricky to diagnose, especially in mild cases or in the early stages. Putting the latter in the factitious pigeonhole is a Bad Thing, not to mention frustrating beyond the patience of saints.

All this reminds me of the diagnostic cult that sprang up around satanic ritual abuse, with lurid tales of babies sacrificed on dark altars, and children forced to do unlikely and preposterous things like eat a jar of scabs^*. "Therapists" described the activities as unspeakable, then proceeded to talk about them at length and with enthusiasm. The recovered memory cults were absurd in the same way.

Incidentally, childbirth is more traumatic than most people suspect. Rather than make assumptions, researchers in the UK actually scanned a bunch of non-abused newborns in an MRI machine. Their paper Frequency and natural history of subdural haemorrhages in babies and relation to obstetric factors found that 6% of the normal vaginal births studied (n=3) resulted in subdural hematoma (bleeding between the brain and its surrounding membrane) detectable by MRI. No doubt there are parents rotting in prison because a jury was told that a newborn with a subdural hematoma must have been abused.

^*Where the heck do you get a jar of scabs, anyway? The pain and scarring would require considerable devotion to the Dark Lord, that's for sure. And what about a jar of pus? Nevermind where it comes from: does it need refrigeration?

Chinese misuse ruins drug against avian flu

2005-06-21T19:17:00.000-05:00

People in China have apparently been using the anti-influenza drug amantadine indiscriminantly on poultry, so that the dangerous H5N1 strain of influenza is now resistant to that family of drugs. As there are only two families of anti-flu drugs, this will be a major blow to fighting the next virulent flu pandemic.

Just like their lethal approach to SARS containment, the Chinese deny that anything is going on and promise never to do it again. Now why do these jokers get Most Favored Nation status?

Interestingly, not only is amantadine an antiviral, it is also a CNS dopamine enhancer useful for treating Parkinsonism. It was also used to treat that girl who recently survived rabies. Drug discovery involves a great deal of serendipity.

No wonder they're fat

2005-06-06T23:56:00.000-05:00

"The issue of food selection in rural areas is a big challenge," Meit said. "They tend to have smaller grocery stores with less selection, and exercising outdoors can be difficult because of the terrain and there are no malls for walking."

"No malls." Oh, my.

Electrical madness

2005-06-04T16:14:00.000-05:00

When you realize that masking tape isn't a suitable insulator for 120 volt AC power, you cannot improve it by adding a layer of metal tape. (But if I tracked down the person who did this and slapped them silly, I'd be the criminal. It ain't fair.)

Migraine prophylaxis and drug design

2005-05-30T20:22:00.000-05:00

Those of us with frequent migraine attacks want drugs that will prevent attacks before they even start. The list of drugs that sometimes work is motley: beta blockers, calcium channel blockers, anticonvulsants, a particular antihistamine, certain toxins from the ergot fungus, and so forth. Unfortunately it's rather hit-and-miss. What works for one person doesn't always work for another.

It was noticed that many of these drugs interact with serotonin receptors in the brain, in particular the 5HT-1B and -1D subtypes. For someone taking a beta blocker for high blood pressure this is a tiny side effect, but for a migraineur it is the main event and the blood pressure effects are unwanted. The ergots hit serotonin receptors like gangbusters, which is good for migraine, but bad for gangrene, so they can't be used for prophylaxis.

The drug companies sensed a major opportunity. Looking at the patient population, they found two major groups. Lots of people have infrequent migraines and would gladly pay $20 a pill for relief. Twenty dollars is cheap insurance against not having a brain meltdown at a business meeting, date, big exam, etc. The other group is a few people who have frequent migraines and need daily prophylaxis for a few dollars a day. They cannot afford $20×365 = $7200 a year.

And that is a problem. A drug company could design something that works for the second group, but then folks in the first group would just use it too and get relief for a couple of dollars a pop. Whereas if you make something for the first group, they'll pay $20/pill, and the second group will also pony up for quite a few $20 pills. Do the math and the $20 version is worth many billions of dollars more.

Naturally the drug companies went for the $20 pill. They put emphasis on drugs that were fast acting, and could be dosed to the gills without excessive side effects (sumatriptan is available in 100 mg tablets). Many drugs were discovered and approved: sumatriptan, naratriptan, etc. All of them but one (frovatriptan) leave the body within hours, so that prophylaxis would require multiple daily doses even if it was affordable. (One wonders if frovatriptan was an accident, from a discovery effort whose shorter half-life candidates bombed.)

I am not entirely complaining. The triptans are incredibly helpful, and have paid for loads of much-needed migraine research. It's just a drag to ask yourself "Is it worth $20 this time?" on a near-daily basis.

I should mention that there is some question as to whether triptans are safe and effective for prophylaxis. They are vasoconstrictors, so there is some theoretical risk of infarction, including stroke. However large studies have not found a worrisome stroke rate for occassional use, one small study found prophylactic efficacy and no bad effects with daily dosing (although the statistical power was small), and lots of people seem to use them heavily without stroking out.

Triptan Half-Lives
Compound	Half-Life (hours)	Brand Name	U.S. Approval
Sumatriptan	2.5	Imitrex	Dec. 1992
Zolmitriptan	3	Zomig	Nov. 1997
Naratriptan	6	Amerge	Feb. 1998
Rizatriptan	2–3	Maxalt	Jun. 1998
Almotriptan	3–4	Axert	May 2001
Frovatriptan	26	Frova	Nov. 2001
Eletriptan	4	Relpax	Dec. 2002

Ouch

2005-05-30T19:08:00.000-05:00

Power tools. Soldering iron. 400 watt power supply. How do I manage to hurt myself? I somehow rip off skin with the edge of my workbench.

That's what I get for going in to work on a holiday.

Not all see change in Los Alamos administration as bad

2005-05-29T22:20:00.000-05:00

C. Paul Robinson, physicist and former Sandia National Laboratories director, lashed back Friday, saying his team was appalled at the lack of competent business practices and focused scientific direction at Los Alamos National Laboratory,...
"No wonder science is hurting. You've got scientists with no support for their work," Robinson said. "We think Sandia is a good proof test that good processes are not incompatible with good science. We know how to bring processes into being that can streamline and simplify things for scientists."

Amen—that's exactly what I have been saying for a long time. The management incompetence led by the University of California was appalling: large-scale embezzlement by employees, lax tracking of secret documents and data, and weak management vision.

The best defense UC has been able to scrape together is that private industry will scare away scientists by crimping their style. Yeah, just like at Bell Labs, IBM, Xerox PARC, Microsoft, Google, Sandia National Labs, and so forth. I don't know what's worse: that they would use such lame rhetoric, or that they would seriously expect people to believe it.

University of California officials recently have suggested that only academia has the scientific rigor and "moral strength" to watch over the aging nuclear explosives in the U.S. arsenal and objectively judge, for example, whether a return to nuclear testing is necessary.

So only Left Coast Academe has the "moral strength" to discover how to kill the entire human race faster and cheaper? Pardon me whilst I scrape my sense of humor off the walls.

Eneman

2005-05-25T19:12:00.000-05:00

Eneman! Faster than a ... uh. Able to leap ... better not say. Nevermind.

Which reminds me of the song Working Where The Sun Don't Shine (The Colorectal Surgeon's Song).

Army Recruiters Deceptive

2005-05-21T10:17:00.000-05:00

From the Headlines That Have Been Current Since the Roman Empire Dept.

I'm shocked, shocked I say.

Global brightening

2005-05-05T22:30:00.000-05:00

On the one hand, the global warmingists claim they understand how the atmosphere works and can predict the temperature a century from now to within a few degrees. On the other hand, they couldn't predict a major change in atmospheric transparency. Well, which is it?

Incredibly, green pundits are trumpeting that this makes the global warming hypothesis even more dire.

What kingdom barrier?

2005-05-01T19:57:00.000-05:00

Most viruses are content to afflict a few species. Not flock house virus: it can replicate in plants, insects, and yeasts. One wonders how many other viruses have a similar ability but just don't do it well enough to get noticed.

Picosecond flashes from mercury and glass

2005-04-30T21:18:00.000-05:00

This paper says that mercury and glass in vacuum exhibit triboelectricity (static electricity charging due to surface contact). The electric force causes a stick-slip interaction that produces picosecond flashes of light.

That's neat—there are not very many ways to make sub-nanosecond flashes of light. Most techniques, like mode-locked lasers, are expensive and balky. This might make a good (or at least cheap) bench-top picosecond source for the lab.

Hmmm...with further thought I'm having trouble seeing the physical mechanism behind the flashes. Bulk liquid doesn't accelerate on a picosecond time scale. When a slip occurs, the gap will grow gradually. (Microseconds? Certainly no shorter than nanoseconds.) Likewise for electric arcs, which tend to grow and diminish gradually. The only fast effect I can think of is that an empty wedge forms as the mercury separates from the glass. Because the wedge is not made of matter, its tip can move fast, potentially faster than light, so particles that follow the tip can reach ludicrous energies. When the tip suddenly stops moving (the "stick" part of stick-slip), the particles catch up and crash into solid matter, making the picosecond flash.