Brief Notes

Chromosome 8 Analysis (Nature 19-January-2006): Genomics is providing some interesting insights into human evolution. Analysis of chromosome 8 shows two regions that appear to be undergoing very rapid evolution as revealed by linkage disequilibrium (linkage among chromosome regions increases over time so disequilibrium indicates recent origin) and synonymous/non-synonymous substitution ratio, that is, the ratio of neutral/protein-changing mutations (the ratio is lower if a gene is undergoing positive selection.) Two genes in these regions are MCPH1, mutations in which cause microencephaly, and so is thought to influence brain size, and CSMD1 which is widely expressed in brain tissue.

Small Interfering RNAs (siRNAs) Successfully Protect Mice Against Herpes Simplex Virus 2 (HSV-2) (Nature 5-January-2006): SiRNA technology has been around for a while but (as far as I know) has not been very successful as a therapy. In this study, siRNAs were mixed with lipids and appear to have been taken up by epithelial cells and silenced the expression of several HSV-2 genes without inducing an immune system response.

Rational Strategies in a World with Irrational Agents

Traditional economic theory assumes that economic agents (individuals or firms) always act in a purely rational manner, that is, agents always have perfect knowledge of potential outcomes and always choose optimal strategies for satisfying their preferences. A large body of evidence contradicts these assumptions. So in general the world consists of a mixture of some rational and some irrational agents.

How can aggregate behavior be understood in this context? One way to think about the problem is to use the twin concepts of complementary and substitute strategies.

Strategies are substitutes when agents profit by doing the opposite of others' strategies. In this case, rational agents counteract or limit irrational strategies. With substitutes, evidence indicates that a minority of rational agents may generate aggregate outcomes predicted by the fully rational model. This type of market provides an opportunity for better-informed traders to profit from poorly-informed traders. An example is the case of prediction markets in which an asset is traded up until a precise time when the asset price is determined. For instance, orange juice futures prices, which are very sensitive to cold weather, have been found to predict freezes in Florida better than U.S. Weather Service forecasts.

Strategies are complements when agents profit by matching the strategies of others. In this case rational agents' strategies amplifies irrational strategies. In the case of the stock market, for instance, because there is no fixed future time when a firm's value is determined, well-informed traders cannot guarantee a profit even if they have perfect knowledge of the fundamental value of a firm.

Because of the large amount of volatility in the stock markets, even a well-informed, well-capitalized investor takes a substantial risk by betting against the 'momentum' of the market and can be forced into following the crowd, that is, trying to predict the strategies of others and get there first. As Keynes said, "Markets can stay irrational longer than you can stay liquid." Thus we have examples of large mispricings in the stock market including mutual funds whose underlying aggregate value does not match the fund's share price.

A well-known example of the difference in these two situations can be seen when a firm is put into 'play', that is, when it appears that the firm will be acquired. Rational traders suddenly have an opportunity to use their knowledge to make a profit and the share price often increases dramatically. Clearly the reason is not a sudden increase in the intrinsic value of the firm.

Gender Differences in Feelings of Empathy and Revenge

Empathy is the ability to share feelings with others. Current models of empathy state that the observation or imagination of another person in an emotional state automatically activates a representation of that state in the observer. Imaging studies show, for instance, that similar activations in the brain occur when a subject experiences pain or observes another person in pain. So it is thought that the same neuronal systems underlie both our own experience of pain and our ability to empathize.

In the present study (performed at University College of London and California Institute of Technology) empathic response was inferred from the measurement of increased activation in the 'pain network' of the brain when subjects observed another person receiving a painful stimulation (an electric shock.) As expected, subjects displayed empathic responses when they observed others in pain. And the level of response was correlated with subjects' scores on standard empathy scales.

In order to investigate whether empathic responses vary depending on the perceived fairness of others, subjects were induced to perceive another person as fair or unfair based on their play in a simple game. The subject and another person (an actor) played a version of the Prisoner's Dilemma game in which the actor was instructed to make either a 'fair' or 'unfair' response in the game.

Then the subject observed the actor receiving painful stimulation. Responses showed a marked difference in the sexes. Men subjects showed no empathy when viewing an unfair player in pain but a significant response when viewing a fair player in pain. Women subjects, however, showed significant levels of empathy when viewing either fair or unfair players in pain, with only a slight decrease for the unfair player.

The researchers then investigated activation in the 'reward' system of the brain looking for evidence of a desire for revenge. Again a marked difference in the sexes was observed. Men, but not women, showed a greater response in activation when perceiving the unfair player receiving pain compared to the fair player. And, for men, this response correlated with the expressed desire for revenge.

The authors conclude that a neurobiological foundation exists for our preferences to reward fairness and punish unfairness and the social dynamics that derive from these feelings. They also speculate that the observed gender differences may indicate a biological mechanism underpinning the predominant role of men in enforcing justice and punishment in society.

Ref: Science 26-Jan-2006 Pg 466

What I Like About the Internet

It's a great outlet for creative people. Here are three of my favorite videos from YouTube:

Tasha and Friends

Dancing Around the World

Supermarket Disco


If you live in or near Cleveland Heights: I think we need a Cafe Scientifique! Hey, there is a storefront for rent on Lee Road near Lopez that would be perfect!

The Threat of Real ID

If you live or work in the United States, you'll need a federally approved ID card to travel on an airplane, open a bank account, or take advantage of nearly any government service.

The Real ID Act hands the Department of Homeland Security (DHS), the department that was responsible for the Hurricane Katrina response, the power to set these federal standards and determine whether state drivers' licenses and other ID cards pass muster. Only ID cards approved by DHS can be accepted "for any official purpose" by the feds.

The card will contain name, birth date, sex, ID number, a digital photograph, address, and a machine-readable technology to read that data. DHS is permitted to add additional requirements--such as a fingerprint or retinal scan--on top of those. We won't know for a while what these additional requirements will be but DHS has indicated that it may require radio-frequency identification (RFID) chips which would allow your ID card to be read remotely without your knowledge. (The State Department is already going to be embedding RFID devices in passports.)

Real ID demands that all driver's licenses or ID cards have pictures that can be read by facial-recognition technology.

The Real ID Act also requires states to interconnect their databases to a national database.

The machine-readable technology embedded in your ID card will make it possible for banks, retailers, airlines, etc. to demand your ID card and to easily collect all your personal data into their systems. This will clearly make identity theft much easier. And the data collected could be sold to commercial companies such as CheckPoint which have had large amounts of data stolen by identity thieves.

Cleveland Clinic Part I

Last December the Wall Street Journal ran a series reporting on the relationship among the Cleveland Clinic, the Clinic's CEO Dr. Toby Cosgrove, and medical device companies. The Cleveland Plain Dealer also commented on the controversy. The articles looked at how these relationships create a conflict of interest between financial and patient care concerns at the Clinic.

While at the Clinic, Dr Cosgrove sat on the board of the medical device maker AtriCure, was an investor in the company, and continues to receive royalty payments from the company. The Clinic itself invested $25 million in the company which makes equipment used in an operation to correct atrial fibrillation or heart flutter. Doctors at the Clinic performed the procedure on over 1,200 patients without informing them about the financial ties among the Clinic, AtriCure, and Dr Cosgrove.

Our society has longed recognized the corrupting influence of financial inducements that may conflict with the primary responsibilities of politicians and other government officials as well as many others who are entrusted with providing vital services to the public. The Governor of the state was convicted and fined for accepting a round of golf without disclosing it. Financial services firms pay huge fines for conflict of interest violations that may mislead investors.

Medical professionals, especially, carry a huge responsibility to avoid flirting with the possible corrupting influence of financial ties that may influence patient care. As the Hippocratic Oath says, "I will remember that I remain a member of society, with special obligations to all my fellow human beings."

Personally, I am stunned that Dr Cosgrove and the Clinic allowed themselves to be put into this position, if for no other reason than that it damages the reputation of the Clinic and the trust that patients place in their Clinic physicians. I suppose that, with a board of trustees consisting of about 90 members, many of whom are retired CEOs, no individual member feels much responsibility for the hard job of enforcing ethical behavior.

But if I were one of the 1,2000 patients who have undergone the AtriCure procedure, I would be feeling quite betrayed.

Our Visit to the Zoo



Hi, guys! Came to see me right? Well I'll tell you all about what's going on ...


Hey, wait a minute! Come back, I'm not done yet ... Aww, gosh ...


Hey, human, make yourself useful, give me a back rub ...


Oh, yeah, that feels good ... a little lower please ...


Well, I gotta go hang out with my boys ...


Check it out, can you do this? ...


Yeah ... boring ... Anyway, I gotta fix this door ... now, let's see here
... looks like I'm gonna have to go to Home Depot for this one ...


Oy, there he goes again, always trying to fix stuff ... if his brain were
any smaller ...


Hey, sucker, who you talkin bout with a small brain? Don't dis me ... Bring
it on, fool ...


OK, here I come, Ostrich ...


I didn't mean it ... I didn't mean it ...


Are you two goin at it again ... Gorilla, if you wanna date me, you gotta
have some manners ...


But baby, feast your eyes, you know I'm fine ...


Hmmm, there he goes again, struttin like he's all that ... now if I could
just get Polar Bear to pay me some attention ...


I've been trying to tell you ... I'm already in a committed relationship ...


Oh, no, here we go again, the great Polar Bear romance ... gag me with a
spoon ...


But isn't love wonderful? Look how cute we are ...


Hey, are they arguing about who's the cutest again ...


Yeah, I think so ...


I prefer to be judged by my intellect rather than my appearance ...


Yes, Turtle, I fully agree ...


That reminds me ... I have some physics homework to do ...


Oh, Turtle, you are so smart, can we hang out sometime ...


I'm afraid not, I'm going for a swim ...


Oh, Turtle, why don't you care for me? ... boo hoo ...


If only someone would notice me ...


On my way, baby ... the gansta of love is comin ...


Are you guys leaving so soon, but wait I wanted to tell you about my day ...
Aww, gosh ...

Publicly Funded Research Not Available to U.S. Businesses

I am currently working on pattern recognition ideas and tried to download a face database for testing. The author did not respond to my emails so I sent this letter:



Victor L. Lechtenberg
Vice Provost for Engagement
Purdue University

John A. Schneider
Assistant Vice Provost for Industry Research
Purdue University

Dear Mr Lechtenberg and Mr Schneider,

I am writing to ask about the policy of Purdue University regarding resources generated by researchers at the University.

Specifically, the AR Face Database (see http://rvl1.ecn.purdue.edu/~aleix/aleix_face_DB.html) is a set of photographs of faces that was built at Purdue to test computer face-recognition algorithms. According to the web page above, it is totally free to "academics wishing to test their software" and has been downloaded by researchers in France Germany and Japan. However, according to the web page, it is apparently not available to any form of commercial entity engaged in similar research here in the United States. In fact, the faculty member who generated the database did not respond to two emails asking for access to the database.

It seems odd to me that resources generated, at least partially, with state and federal funds is freely available to academic researchers world-wide but not to businesses here in the U.S. working on similar research. I would be interested to know if Purdue University condones this practice of discrimination against business researchers and if any Purdue policies cover this situation.

Sincerely,

Where I have lived ...

This graphic shows all of the places that I have lived since 1975 starting at the red circle and going to my current home represented by the orange circle. So in thirty years, I have moved a total of about 10 miles. I wonder what that says about me? Anyway, your challenge is to identify the city in which I live.

Why Do Animals and Plants Reproduce Sexually?

Sexual reproduction is costly. Half of the individuals in a sexually reproducing species do not produce offspring and time and energy expenditures involved in searching for and selecting a mate are significant. Also, sexual reproduction may disrupt favorable gene combinations.

A hypothesis originally proposed more than 100 years ago asserts that sex allows natural selection to operate more effectively because it increases genetic variation. This hypothesis was recently put to the test by researchers at Imperial College London.

When supplied with sufficient nutrients and a benign environment, yeast cells reproduce asexually but when subjected to a harsh environment, cells produce haploid spores (spores containing only one copy of each chromosome) which can, when conditions improve, germinate and mate with spores of the opposite mating type.

To measure the benefits of sex, researchers engineered a yeast strain lacking certain genes necessary for meiosis so that the mutant yeast could not reproduce sexually but instead produced diploid spores (spores containing both copies of each chromosome) which were genetically identical to the parent and developed directly into new cells. They then subjected both the normal and mutant strains to repeated cycles of the benign environment (during which asexual reproduction occurred in both strains) followed by the harsh environment (to induce sporulation) simulating evolution over about 300 generations. The growth rates of the yeast cells were then assayed by comparing the growth rate of the new cells to that of the original ancestral strain. In the benign environment, no difference in growth rate was found between the sexual and asexual strains. In the harsh environment, both strains showed an increased growth rate, the asexual population showing an increase of 80% and the sexual strain 94%. The researchers conclude that the sexually reproducing strain's more efficient adaptation to the harsh environment was due to the beneficial effects of genetic recombination.

Ref: Nature 31-Mar-2005 Pg 638

Why Do Mice Have ADAMTS5?

Human osteoarthritis is a progressive disease of the joints characterized by degradation of the cartilage, a major component of which is aggrecan. Several groups of researchers have recently identified ADAMST5 as the primary enzyme responsible for the degradation of aggrecan and the resulting loss of cartilage in mice.

Adult mice lacking the active portion of the ADAMST5 gene (knockout mice) were found to have no gross abnormalities and 17 tissue types as well as blood and serum were examined and found to be normal. Knockout mice underwent surgery to simulate joint injury. A significant reduction in cartilage destruction was observed in these mice compared to wild-type mice.

Again (see the previous article), ADAMST5 appears to confer no benefit and actually exacerbate injury and yet has been conserved in the mouse genome.

Ref: Nature 31-Mar-2005 Pg 644

Why Do Mice Cells Have Cyclophilin D?

Several groups of researchers investigating the mechanisms of cell death have reported a puzzling result. Mice lacking the gene for Cyclophilin D appear to develop normally and additionally to be more resistant to cell necrosis.

Cells die in two ways. Apotosis is a controlled process in which the cell's contents are broken down before the cell membrane ruptures thereby avoiding inflammatory damage to nearby tissue. Necrosis is an uncontrolled process which occurs in response to injury such as lack of oxygen and causes further injury to nearby tissue.

When blood supply to a tissue is disrupted (ischaemia), cells begin to die by necrosis. If a long time elapses before blood flow is restored (reperfusion), additional cells undergo necrosis causing even further damage to the tissue. The recent research establishes that Cyclophilin D mediates the process of necrosis after reperfusion.

The puzzling finding is that mice lacking Cyclophilin D develop normally but also appear to be protected from reperfusion injury following ischaemia. Why would a gene that appears to confer no benefit and actually exacerbate injury be conserved in the mouse genome?

Ref: Nature 31-Mar-2005 Pg 658

Can Plants "Evolve Backwards"?

Researchers at Purdue may have discovered a revolutionary new ability of organisms to correct their DNA. Using a mutant variety of the plant Arabidopsis, they found plant offspring that had apparently corrected various mutations in their DNA.

The rate at which the corrected mutations occurred ruled out chance as the explanation. The possibility that the correction came from another similar DNA segment acting as a template was also considered and ruled out. The researchers scanned the entire genome for similar sequences without result. Also, the fact that the correction was to a single nucleotide and no flanking DNA was different from the wild-type gene makes it unlikely that a similar but not identical sequence was used as the basis for the correction.

The authors speculate that the correction mechanism is based on a cache of ancestral sequences in RNA carried in the gamete. If true this would be a powerful new evolutionary mechanism that could help to explain how organisms can evolve at observed rates. The authors further speculate that the phenomenon may be related to some type of stress-recognition system.

Assuming that gametes carry a cache of ancestral RNA templates, when an organism detects that is undergoing stress, the new mechanism may use the cached templates to "evolve backwards" by correcting recently mutated genes thereby passing to offspring the ancestral DNA sequence.

Because it is generally thought that the vast majority of DNA mutations are detrimental, such a mechanism would allow a mutation to be "tested" in one generation and corrected in the next generation if it were determined to cause stress to the organism. So the evolving organism could avoid some detrimental mutations becoming fixed in the genome. And thus the overall rate of beneficial mutation in a population would increase.

Ref: Nature 24-Mar-2005 Pg 505