[Editor's Note: The October issue contains an article entitled "Experimental Drugs on Trial" (not free) that discusses the pros and cons of approving experimental drugs for individual use in certain cases. The following is some additional thoughts from Dr. Richard Miller, CEO of Pharmacyclics, a developer of cancer drugs who has had his own struggles with the issue.]

When I read Beryl Lieff Benderly's article entitled "Experimental Drugs on Trial" (not free) about the Abigail Alliance lawsuit, a topic I've been following for some time, I was glad to see it included a broad discussion of clinical trial methods and policies.

Much of the current debate on access to experimental drugs has been dominated by two points of view:

Individual dying patients have a constitutional right to early access

VERSUS

Drugs should be made available only after they have been proven to be safe and effective in definitive controlled clinical trials

Unfortunately, each of these extremes fails to address the most important issue in this debate: the need to rethink and reengineer clinical research methods and FDA policy for drug approvals.

Read more

Hot on the heels of the 2006 Nobel for physiology or medicine for the technology behind RNAi--a procedure for at least partially blocking the translation of a gene into a functional protein--the Nobel Foundation handed out its 2007 prize for the discovery of a procedure for knocking out a specific gene altogether.

The University of Utah's Mario Capecchi, Sir Martin Evans of Cardiff University in Wales and Oliver Smithies over at the University of North Carolina in Chapel Hill split the Nobel for their contributions to the designer mouse model-world we now live in.

As a journalist (one who writes a lot about genetics, to boot), studies involving knockout mice are ubiquitous, the way box scores are in the sports pages. So the awarding of this prize strikes me as a no-brainer.

Oddly enough, it didn't to a a Wired blogger (who, full disclosure, is a friend and former classmate of mine) who stepped into a small world of hurt when he adopted a "What have knockout mice done for me lately?"-sort of attitude. (He's since softened his position.)

A press statement from the Nobel Assembly at the Karolinska Institute supports my initial impression:

To date, more than ten thousand mouse genes (approximately half of the genes in the mammalian genome) have been knocked out. Ongoing international efforts will make "knockout mice" for all genes available within the near future.

Thus far, genes have been quieted to study models for everything from cancer to mental retardation.

Anyway, I'll try to describe what makes these men deserving of their medals: In the late-70s/early-80s, Capecchi and Smithies concurrently sought a technique to target and replace a specific gene in a cell's genome. They determined that if they inserted a similar (but inactivated) sequence of DNA into a cell, they could trick the cell into incorporating it during homologous recombination. (Homologous recombination occurs naturally when two complimentary strands of DNA cross and swap genetic material to form sex cells, like sperm and eggs.)

However, Capecchi and Smithies' insights into gene targeting needed to be paired with a delivery system, which was developed primarily by Evans, who discovered embryonic stem cells. The pluripotent cells were repurposed as the ideal vehicle for these mutated genes: The inactive genes are placed in stem cells, and injected into a blastocyst (clump of cells that become the embryo), which then develops into a mouse with some cells that have the inactive gene and others that do not. When a "mosaic mouse" mates with a normal mouse, some of the offspring will not have the gene at all, while others will. Those lacking, are the "knockout mice."

Then you watch the little knockout guys develop and see what's gone awry. The Reuters story on our site (available for limited time) regarding the Nobel announcement has a cherry quote from Capecchi: "If for example, you see a little finger disappear [in the knockout mice], then you know that gene is important for making little fingers."

Brilliant. Nobel-worthy. Trust me.

More Resources:
SciAm senior writer Gary Stix wrote an excellent profile of Capecchi in 1999. It has been freed from behind a paywall for you to download. And Capecchi contributed a piece to the magazine in 1994 about targeted gene replacement. (This one, folks, will require you to shell out some pesos.)

Gerhard Ertl turned 71 today.

Unfortunately, 71 doesn't typically carry the same cache as some other ages, like 16 (driving a car, at least in the U.S.), 18 (can vote here, can drink pretty much everywhere else), 25 (no more rental car penalties), 50 (AARP card!) and all the other multiples of ten, which ring in new decades.

But, I have a hunch Ertl's going to remember good ol', unremarkable 71 for a while.

After all, it's the day he won the Nobel Prize for chemistry. And not just that, he won it alone. Which means the 1.54 million is all his (no sharing required).

Ertl is the new, worldwide face for modern-day surface chemistry. Prior, his fame was confined to the scientific community alone; but now, when Paris Hilton, Mahmoud Ahmadinejad, or even a no-name peon like myself fire up a car, we'll think or Ertl.

Catalytic surfaces stoke reactions that underpin many of the innovations we rely on today, from artificial fertilizers to catalytic converters to fuel cells. This type of reaction can also be thorn in our side: creating the rust appearing on our bikes and the thinning of the ozone layer, which actually takes places when freon molecules mingle with ice crystals in the stratosphere.

Via a series of papers, Ertl, a physical chemistry professor at the Fritz Haber Institute (part of the Max Planck Society), won acclaim for investigating the surface reaction that shares a moniker with his institute's namesake: the Haber-Bosch process. In this reaction, nitrogen gas molecules are converted to ammonia for artificial fertilizers to increase crop yields. Using photoelectron microscopy, Ertl thoroughly elucidated the choreography and the energies involved in the atomic interactions between nitrogen, hydrogen and an iron surface. These insights allowed industrial operations to make the process more efficient.

According to a Bloomberg News report, "The method now produces about 100 million tons of fertilizer a year. One percent of the world's annual energy supply is consumed in the Haber-Bosch process. Last year, Germany's BASF AG paid $5 billion to acquire Engelhard Corp. to expand its offering of catalysts."

Ertl performed similar detailed assessments of the conversion of carbon monoxide and other emission products from combustion to carbon dioxide, nitrogen gas and water via a platinum catalyst. These reactions take place in a car's catalytic converter.

"Research in surface chemistry already has underpinned innovations ranging from air pollution control technology to modern electronics products," said the American Chemical Society's President Katie Hunt in a statement to the media. "In the future, this research will help us tap new sources of renewable fuels, for instance, and produce smaller, more powerful electronics products."

(Here's a video that explains why the Swedish Royal Society found Ertl deserving.)

So, it ain't sexy--like an iPod hard drive--but it's essential. If not for Ertl's indelible mark, we'd be battling both climate change and passing monsoons of acid rain.

And for that (not to mention, the better crop yields), he deserves at least a million and a half. (Hell, Alex Rodriguez hits a ball with a bat and is worth more than 250 times that, at least to his agent.)

Happy Birthday, Gerhard, you Nobelist, you.

Getting the average person hooked on physics can pose something of a challenge. Black holes and multiple universes are an easy enough sell, but try the room temperature spin Hall effect on for size and you'll see what I mean.

Mercifully, the Royal Swedish Academy of Sciences has seen fit to award this year's Nobel Prize for physics to a couple of guys who did something we can all appreciate: making it technologically feasible to cram a wall full of CDs onto a slick white gadget the size of a deck of cards and thereby revolutionizing the art of gazing blankly into somebody's armpit during the morning subway crush (at least in New York City).

Albert Fert of Universite Paris-Sud in Orsay, France, and Peter Gruenberg of Germany's Forschungszentrum Juelich will split the $1.5 million prize for their independent discovery 20 years ago of an effect called giant magnetoresistance, in which the current flowing across a sandwich of thin magnetic and conducting layers varies dramatically depending on the direction of a magnetic domain placed next to it. If that sounds like a familiar concept, it's because hard drives in everything from the laptop to the Wii console Xbox 360 Hard Drive store data in precisely that form. Toggling a bit from 0 to 1 in a computer's memory is the same thing as switching the orientation of that bit's magnetic field.

By finding a vastly more sensitive way to distinguish those fields, which grow weaker as bits get smaller, Fert and Gruenberg paved the way for the high-density hard drives that brought us the iPod, digital video recording and the continuing gains in laptop and desktop memory. Our Reuters story (available for a few weeks) has a good quote:

"A computer hard disk reader that uses a GMR sensor is equivalent to a jet flying at a speed of 30,000 kilometers (19,500 miles) per hour ... at a height of just one meter above the ground, and yet being able to see and catalogue every single blade of grass it passes over," [Ben Murdin, a physics professor at the University of Surrey in southeast England] said.

And sort of like a B-movie franchise, researchers keep uncovering new, more powerful forms of magnetoresistance: colossal magnetoresistance, ballistic magnetoresistance and (my personal favorite) extraordinary magnetoresistance, to name three.

Mere giant magnetoresistance, which debuted in commercial hard drives back in 1998, represented the first example of so-called spintronics, or electronics based not on charge but spin, the property of an electron that makes it act like a tiny bar magnet. Physicists have started thinking that more exotic magnetic effects (like that spin Hall effect mentioned above) might allow them to build quantum computers that run on spin.

This year's physics Nobel should remind us that the notion of uninterruptible technological progress embodied in Moore's law doesn't just happen by magic. It takes researchers like Fert and Gruenberg working today to keep those trends moving as each new decade rolls around.

Related links:

SciAm explained vertical hard drives in the August, 2006, installment of Working Knowledge (available for a fee) and looked at other efforts to push hard disk density in this 2005 profile, "Kryder's Law."

Read more about the growing field of spintronics in last month's feature story, "The Diamond Age of Spintronics," and the 2002 feature, "Spintronics." In May I wrote about a way to control spin in silicon. And let's not forget the room temperature spin Hall effect.

Not to put too fine a point on it, but so is everything else. Nothing we experience falls outside the mind, and the wonderful wetware behind it we call the brain. So looking into it to find out what's going on when we experience some of the most profound--and ancient--of human experiences is a no brainer.

But researchers must tread with caution. Science understands little of the mind, let alone the brain that generates it (and even that would be debated by some). So it is nearly impossible then to probe a mindful experience like being touched by the divine, especially with the crude tools of fMRI, EEG and other neuroscans. If we cannot know the mind of man, how then can we know the mind of a presumed god?

Still, it's interesting to take a peek, no matter whether you are Richard Dawkins (who, interestingly, failed to experience anything in the putative "God helmet," a finding its progenitor Persinger put down to a brain abnormality), the Dalai Lama, or even Pope Benedict. What do you think we might find?

Welcome to

Mind Matters

where top researchers in neuroscience, psychology, and psychiatry explain and discuss the findings and theories driving their fields. Readers can join them. We hope you will.

Among biology's more riveting inquiries is the investigation of gene-environment interactions -- the demonstration that a person's genes constantly react to experience in a way that changes behavior, which in turn shapes environment, which in turn alters gene expression and so on. As David Olds described a few weeks ago, this new subdiscipline is yielding startling insights about how nature and nurture mix to help determine one's health and character.

This week reviewer Charles Glatt reviews a study that takes this investigation a level deeper, examining how two different gene variants show their power -- or not -- depending on whether a child is abused, nurtured, or both. As Glatt describes, this study, despite its grim subject, suggests promising things about the power of nurture to magnify nature's gifts or lift its burdens.

For centuries, philosophers, theologians and biologists have debated the relative roles of inborn traits versus environmentally defined experiences in determining what and who we are. This nature-nurture debate carries fundamental implications for our understanding of self-determination, or free will. Indeed, as research has begun to identify genetic risk factors for certain behavioral traits, these risk factors have already been used in court (see here and here)to argue that punishment should be lessened for convicted felons -- the presumption being that their genes made them inherently more likely to misbehave.

The importance and challenge of the nature-nurture debate in behavior has recently spawned a new area of research that looks at the interaction between genetic risk factors and experience in the development of psychopathology. A study led by Joan Kaufman and Joel Gelernter, both of Yale, and published in Biological Psychiatry, has demonstrated what many of us have intuitively concluded, which is that both nature and nurture contribute to who we are. In this particular study, genetic and environmental factors interact to determine risk for depression.

In their study, "Brain-Derived Neurotrophic Factor-5-HTTLPR Gene Interactions and Environmental Modifiers of Depression in Children," Kaufman, Gelernter and colleagues found distinct gene-environment interactions in the risk for depressive symptoms. Other studies have found similar interactions, but looked mainly at interactions between single genetic and single environmental risk factors. This study ups the ante by examining various interactions among two genetic and two environmental factors, including a four-way interaction with two genetic and two environmental variables.

Where the Money Is

Kaufman and colleagues took the approach of bank robber Willie Sutton who, when asked why he robbed banks, is said to have replied, "Because that's where the money is." Kaufman and colleagues focused on the most well known and accepted genetic and environmental risk factors for depression to see how they interacted with one another to alter risk.

On the nature side, they focused on polymorphisms -- genetic differences between individuals -- that have been implicated in depression through a variety of methods. The first polymorphism is in the regulatory region of the gene for the serotonin transporter. This polymorphism is the 5-HTTLPR, which stands for the serotonin (5-hydroxytryptamine, 5-HT) transporter linked polymorphism. The 5-HTTLPR has received much research attention because it appears to alter the expression of the serotonin transporter molecule, which is the target of the commonly prescribed serotonin-selective reuptake inhibitor (SSRI) class of antidepressants and is itself implicated in depression. Caspi and Moffit and other research groups have repeatedly found this polymorphism to be associated with depression in the presence of stressful life events.

The second polymorphism Kaufman studied is the gene for brain-derived neurotrophic factor, or BDNF. BDNF is a molecule that seems to encourage the growth of new neurons; it appears to be central to brain growth and learning. This polymorphism in the BNDF gene alters the efficiency of secretion of this molecule. Recent studies in animals and humans have shown that BDNF levels are decreased during stress and depression and that SSRIs act at least in part by normalizing the levels of BDNF. (BNDF levels have been shown to rise in response to successful SSRI treatment, as well as in response to successful psychotherapy and, for that matter, exercise. An earlier Mind Matters by Francis Lee and Larry Tecott reviewed a rare paper finding a downside to BNDF. ) Thus it is not hard to imagine that polymorphisms (that is, certain variants) of the BDNF gene might interact with other factors to contribute to depression risk.

BNDF and 5-HTTLPR, then, were the "nature" factors Kaufman and colleagues examined. From the "nurture," or environment/experience, side they added two epidemiologically established modifiers of risk for depression -- childhood abuse/maltreatment on one hand and, on the other, positive social support.

Please Interact Amongst Yourselves

The researchers studied 109 children who had been removed from their parents' care due to reports of abuse or neglect and 87 control children with no reports of abuse or maltreatment. They scored all the children for depressive symptoms such as irritability, crying and reluctance to see friends. High scores on this scale indicate greater depression. They then compared the distribution of these scores in children with different combinations of the 5-HTTLPR and BDNF polymorphisms described above.

They found that children with the "bad" form of 5-HTTLPR had higher depressive symptom scores -- but only if they had a history of maltreatment. Bad 5-HTTLPR made it more likely (but not certain) that an abused child would develop depression. But it created no effect on depression scores in children without a history of maltreatment. It was like a seed that had to be watered by abuse. This replicates similar findings in studies by Caspi and Moffit and other groups.

Kaufman and colleagues then looked at how the different forms of BDNF might affect this picture. They found that a certain version (or allele) of the BDNF gene amplified the effects of the 5-HTTLPR gene, making it even more likely that a given child would develop depression -- but again, only if the child had suffered abuse.

Finally, Kaufman and colleagues looked at the effects of social support. They asked the children about people in their lives whom they could talk to about personal things, count on to buy them things they needed and other, similar signs of supportive relationships, and from the answers derived a social support score. Children were then characterized as having high or low support. The researchers found that high levels of such nurturing counteracted the effects of the genetic risk factors almost completely.

Balance of Power

As with any behavioral genetic study, one must be careful not to overinterpret these findings, because virtually no study in behavioral genetics is consistently or completely replicated. Nonetheless, some additional points about this paper can help inform us on the nature-nurture debate. First, depression scores and categorical diagnoses of depression were significantly higher in children with a history of maltreatment versus controls even before any genetic analysis was factored in. In a similar vein, the highest average depression score of any genotype category in the unabused control children was lower than the average depression score for any genotype category in the maltreated children; genes alone weren't likely to make the child depressed, but maltreatment alone could.

These findings suggest that, at least regarding these specific polymorphisms, nurture beats nature. This conclusion will come as a relief to believers in human free will. It also argues strongly for the identification of children at risk for maltreatment and strong actions to reverse the negative effects of this experience.

Charles Glatt is an assistant professor of psychiatry at Weill Cornell Medical College and an assistant attending psychiatrist at New York-Presbyterian Hospital.

Save for the media swarm in the wake of the hand raises by Republican candidates Sam Brownback, Mike Huckabee and Tom Tancredo, it appears Hillary Clinton is the first to put science in the spotlight in the race for the White House.

Speaking on the 50th anniversary of the Sputnik launch Thursday at the Carnegie Institution for Science, Clinton took the opportunity to talk about Bush's less publicized war--the one on science. (This, no doubt, had author and columnist Chris Mooney doing backflips.) She also released, via her website, an "Agenda to Reclaim Scientific Innovation."

Here's an outline of the other "war," thus far:

...instead of fostering a climate of discovery and innovation, the Bush administration has declared war on science. The record is breathtaking: banning the most promising kinds of stem cell research, allowing political appointees to censor studies on climate change, muzzling global warming experts like Dr. James Hansen, overruling doctors and the FDA on emergency contraception, suppressing and manipulating data on mercury pollution, even delaying one report which found that 8 percent of women between 16 and 49 years of age have mercury levels in their blood that could harm future children, denying the risks of toxins like asbestos in the air after the 9/11 attacks, overruling scientists who sought to protect animals under the Endangered Species Act, eliminating scientific committees at the Department of Health and Human Services that did not parrot the politically accepted ideology -- or packing those committees with industry insiders, altering scientific tests on the lead content of children's lunch boxes -- and appointing a lead industry consultant to a key panel formed by the Centers for Disease Control, barring a USDA researcher from publishing or even discussing his work on antibiotic resistant bacteria, censoring government websites on breast cancer research, contraception, climate change, and so much else.

She covered all the highlights of science and policy: stem cells, the mess at the FDA, budget woes (at agencies from NIH to DARPA), space exploration (both manned and unmanned), climate change, and renewable energy. While, these issues are likely not new to readers of this publication and other science-savvy individuals, it's heartening to see them introduced on the political stump.

Of course (and here's my cynical streak erupting from my bile-filled belly) this speech was at the Carnegie Institution for Science. What was she going to talk about? Tax cuts for the rich?

Within the context of the entire Clinton campaign, this is something Mooney, author of The Republican War on Science, and his colleague Matt Nisbet would call "framing." Hillary's platform is no doubt broad and has primarily focused on Bush's more well-known war, healthcare, education reform and whether or not she wants to pow wow with some of the more controversial world leaders in power today. But, on this day, she chose to focus on science.

Rather than framing, I call this "playing to the crowd." (I will consider calling it framing as soon as Mooney and Nisbet admit they are writing a book about framing in the Gladwellian mold, which, lucky for them, a recent Wired article can help them title and turn into a cash cow. For those interested, myself included, Mooney will be further breaking down the elements--or frames--of the speech all week on his blog.)

But, leaving the semantic discussion on framing, I am more concerned with whether the substance of this speech will just fade away to the bottom of Clinton's bullet-point list of stances, or whether such a strident call-to-arms will necessitate others (both Democrat and Republican) to refine their ideas about the role science plays in the next election.

I would like to see some alternative options to Clinton's proposals from other candidates because, frankly, this is a topic that's important to me. There is plenty to tweak, massage or offer alternative ideas here: The issue of manned vs. unmanned space exploration, new ideas for improving science education, how to increase the number of women pursuing science degrees, etc. The hope is that the Obamas and Edwards (and to a less likely extent the Giulianis and Romneys of the world) won't just say, "Hey, that sounds good, just fold all that business Hillary was talking about into my campaign, as well."

But will anyone step up and take what Hillary has proposed and run with it? Will Hillary even mention the subject in similar breadth and depth when it's not a significant scientific anniversary and she's not standing in front of a group of researchers?

With all the aforementioned highlights, it seems as though, if science and technology are going to have their day in the political arena, now would be the time. Hell, just days before Clinton's speech, Michael Griffin, NASA chief, admitted that China will likely beat the United States back to the moon. Do we have to wait another 10 years for another Communist country to beat us to a space goal before we re-prioritize science in our culture? (That last time really served to chap our collective hide.)

If no one else in either party puts their chips down, remember New York mayor (and rumored independent presidential candidate) Michael Bloomberg has been there, done that.

Hey, Hillary, can you say "running mate"?

That's the main thing I took away from the inaugural episode of the new show WIRED Science. But don't take my word for it -- intrepid gumshoe Adam Rogers visited the Chemical Heritage Foundation in Philadelphia, home of the world's largest chemistry set collection in order to get the straight dope. Let the kits speak for themselves:

God forbid the girls should ascend to the rank of actual chemist.

Another thing I learned from Wired Science is that Chris Hardwick is no Alan Alda.

Chris, better known as the former host of MTV's Singled Out, had the kind of flat, glassy-eyed delivery that suggested to me that all he really wanted to do was end every sentence with "dorkus!"

(As in, that's what he was accusing the audience of being. Nevermind.)

I just didn't buy that he was actually interested in anything other than avoiding making VH1's The Surreal Life the next stop on his television career.

The rest of the show was remarkably true to the print version of WIRED, right down to the fireside chat with, not a scientist, but a venture capitalist who invests in scientists.

If you're a techno-utopian libertarian, or you just enjoy seeing TV personalities panic after being covered in life-threatening quantities of Uranium dust, this one's for you.

Scott Aaronson, the blogger who moonlights as an MIT quantum computation researcher, just discovered that an Australian commercial (on YouTube) has cribbed most of its script from one of his lectures on quantum mechanics posted online.

Link

Model 1: But if quantum mechanics isn't physics in the usual sense--if it's not about matter, or energy, or waves--then what is it about?

Model 2: Well, from my perspective, it's about information, probabilities, and observables, and how they relate to each other.

Model 1: That's interesting!

The commercial then flashes the tagline "A more intelligent model," followed by a picture of a Ricoh printer.

Scott finds himself in a quantum superposition of |speechless>, |flattered> and |thinking about cashing in>. (If only it was a quantum printer.)

The spot is apparently the work of one "Love Communications":

The Intelligent Model campaign was developed at Love by creative director Scot Waterhouse, art director Andrew Leftley, copywriter Guy Lemberg and agency producer Paul Johnston. Filming was shot by director Mark Furmie via Filmgraphics with producer Simon Ritch.

Note to CBS: Hire the Love guys to punch up the dialogue of The Big Bang Theory. No uber-nerd would be telling another uber-nerd about the double slit experiment as if he had just read about it on CNN.com.

Welcome to

Mind Matters

where top researchers in neuroscience, psychology, and psychiatry explain and discuss the findings and theories driving their fields. Readers can join them. We hope you will.

Bad memories can seem to have their own power, as if they are independent agents infecting our thoughts and moods. Yet memories are creations of mind and brain, and the organ that makes them can also temper their power. A new study, reviewed here by Daniel Weissman and Clare Porter of the University of Michigan, sheds light on how we accomplish this vital and welcome feat.

Memories provide us a personal history and a sense of identity. There are times, however, when we'd like to forget a social blunder or other embarrassing incident -- or in some cases, a memory so traumatic that it is painful to recall. Soldiers who have experienced horrific events may suffer from post-traumatic stress disorder (PTSD), emotional distress stemming from an inability to stop recalling traumatic events. Our comfort, and sometimes our mental health, can depend on suppressing such memories. How do our brains manage this task?

The Past in Many Parts

An emotional memory has many components. For example, the memory of a car accident might be associated with the sound of tires squealing, the sight of two cars colliding, the smell of gasoline, and feelings of fear and panic that build as the accident unfolds. One might imagine that suppressing such a memory would require suppressing each of the individual components.

Brendan Depue, Tim Curran and Marie Banich, all of the University of Colorado, explored this hypothesis in their study entitled "Prefrontal Regions Orchestrate Suppression of Emotional Memories via a Two-Phase Process." Human participants were trained to associate each of several female faces with a distinct photograph of an emotionally distressing event (such as a car crash). Later, they were shown each of the faces in turn and asked either to think or to not think about the associated photograph. While participants were performing this task, the authors used functional magnetic resonance imaging (fMRI) to measure their brain activity. (Functional MRI reveals where blood flows in the brain when a stimulus is presented, thereby indirectly indicating which regions become active). After the fMRI scan was completed, participants were given a memory test in which they were shown each face and asked to describe the photograph it had been paired with.

Block That Memory

The results suggested that participants did indeed suppress the face-photograph pairings that they were told not to think about during the fMRI scan. Specifically, when they were tested later, the participants remembered these pairings least accurately. They remembered with intermediate accuracy pairings they had been trained to associate but that were not shown during the fMRI scan. And they remembered most accurately pairings they had been asked to think about in the scanner. Consciously trying not to think about the association between a face and a photograph, then, seemed to weaken the association.

With those behavioral indications of memory suppression in hand, the researchers examined the fMRI data to determine which parts of the brain were involved in squelching the associations.

The fMRI data showed that a number of brain regions participate in suppressing emotional memories. First, there was increased activity in multiple regions of the frontal lobes. The frontal lobes are thought to underlie higher cognitive abilities --like attention, memory and inhibition -- that require coordination with other brain regions to be carried out. One of the activated frontal regions, the right dorsolateral prefrontal cortex, is thought to control the retrieval of information from memory. A second, the right inferior frontal gyrus, seems to play an important role in inhibition. A third, the frontopolar cortex, is relatively unexplored but may help to coordinate the activity of other brain regions. These findings appear to extend the established role of frontal lobe structures in higher cognitive abilities to suppressing emotional memories.

The researchers also found that suppressing emotional memories reduces activity in brain regions that process sensory information (the thalamus and the visual cortex) and emotional/memory information (the amygdala and the hippocampus). This reduction in activity was measured relative to activity when subjects fixated on a dot in the middle of a blank screen -- an important baseline not included in previous studies. These results agree nicely with the conceptual picture of active suppression: when we are told to inhibit a memory, our brains shut down emotional and sensory processing that relates to the memory.

A Timing Thing

Given that frontal regions frequently coordinate other brain regions to accomplish a goal, frontal regions activated during memory suppression might be inhibiting activity in emotional and sensory regions in order to suppress these distinct components of emotional memories. How might one measure such an inhibitory effect?

When brain regions communicate, their activity becomes correlated. Thus if one region is working to curb another, then whenever the first region's activity increases, the second's should decrease. Consistent with such inhibition, the authors found that greater activity in the right inferior frontal gyrus was associated with reduced activity in the visual cortex and the thalamus, which process sensory information. Furthermore, greater activity in the right middle frontal gyrus was associated with reduced activity in the hippocampus and the amygdala, which underlie memory and emotion. Finally, these restricting effects occurred earlier in the sensory regions than in the emotional/memory regions, suggesting that emotional memories are suppressed via a two-phase process -- first the relevant sensory information, then the emotional reaction to it.

How is the timing of these two phases controlled? The authors found evidence to suggest that the frontopolar cortex boosted activity in the right inferior frontal gyrus just before the right inferior frontal gyrus suppressed activity in sensory regions. Slightly later, the frontopolar cortex boosted activity in the right middle frontal gyrus just before the right middle frontal gyrus suppressed activity in emotional/memory regions. Thus, the frontopolar cortex appears to control the order in which different components of emotional memories are suppressed.

This study by Depue and colleagues raises several fascinating questions. First, might the sequence in which different components of emotional memories are suppressed change in various clinical disorders? For example, might patients with post-traumatic stress syndrome (PTSD) suppress the emotional aspects of traumatic memories earlier than healthy participants because their memories are so disturbing? Would treatment for PTSD be more effective before or after the emotional aspects of traumatic memories are suppressed?

And how much specialization is there? Given that distinct subregions of the sensory cortex process different types of sensory information, can we suppress some sensory components of an emotional memory more easily than others -- visions or sound, for instance, more easily than odor? Finally, since different brain regions process emotional as opposed to nonemotional information, are different brain mechanisms involved in suppressing emotional versus nonemotional memories? The questions framed by this study open the way to a much more nuanced picture of how we contain and temper the power of the past.

Clare Porter is an undergraduate and Daniel Weissman an assistant professor in the psychology department at the University of Michigan, where Weissman heads the Attention and Cognitive Control Lab.

A few days ago a Reuters report described how Africans (and others) have devised ingenious methods to communicate with cell phones without incurring charges. This is accomplished by beeping: placing a call and allowing the screen on the receiving party's phone to flash for long enough to identify the caller. The person placing the call then quickly hangs up, hoping that the call recipient will phone back.

Of course, there is a winner and loser in this game because someone has to complete the call and pay the minutes. Jonathan Donner, who works for Microsoft Research India, investigates the economics and social dynamics of cell phones and is going to publish a paper in the Journal of Computer Mediated Communication (Vol. 13, No. 1) in mid-October called "The rules of beeping: Exchanging messages via intentional 'missed calls' on mobile phones." The article is based on a series of interviews with cell phone users in Kigali, Rwanda who are identified in the article only by their first names.

Here is a first peek at the "rules" detailed in the article that govern the elaborate etiquette behind beeping:

Rule 1: Send callback beeps to people with more money

Returning to the most common kind of beep--the request for a callback--there are clear conventions as to who should beep, and who should not. The negotiation, of course, centers on whom should pay for the voice call. Upon returning to Ghana, [Rodney] Nkrumah-Boateng [a Web columnist] learned this rule from his cousin:

Noticing my confusion, she laughed and patiently explained it all to me. She would allow her mobile phone to ring only once when she called me on mine, and then deliberately cut it, thereby indicating that she wanted me to call her back. Obviously, because I had just come home from abroad, the automatic assumption was that I could afford to call her back.

Such calculations are not restricted to interactions between friends and family. Telecommunications expert Andrew Dymond calls this the "richer guy pays" rule, and suggests that it is part of "the accepted way of doing business in Africa".

Employers and employees represent a special case of "richer guy pays". Generally, employees can beep employers to request a call back, as long as the resulting call is about business matters. Indeed, Innocent actually purchased used mobile handsets for each employee of his garbage-hauling business [everyone mentioned is from Kigali, except where noted], providing only enough access and airtime to allow for beeping, and transforming the handsets into one-way call receivers. He encourages his employees to beep him to stay in touch on the job, but says he ignores the beeps on days when his employees are not working.

Though most Rwandan mobile users pay for calls via prepay cards, which run out frequently, a few elites have post-paid monthly contracts. Not surprisingly, owners of post-paid numbers get many beeps from people a) knowing they have minutes to cover the call and b) assuming--correctly--that they have financial wherewithal to do so. To make matters worse, phone prefixes in Rwanda include a special designation for contract accounts, meaning that one's status as a person who "always has units" is broadcast to the handsets of all one's communication partners. Originally, this special designated number was a desirable status symbol. However, some are suffering from beep fatigue, and according to Filicien [a marketing student], are hiding their numbers and contract status by disabling caller ID. Says Nicole, the [computer science] student, "My dad [owner of a contract account] did not know that people beep for saving money. He used to call back all the time but now that he knows it is about saving money, he has stopped."

Rule 2: Send callback beeps to friends and family when you've run out of minutes

Among equals who trust each other, and call each other often, the "richer guy pays" approach may not apply. Instead, there is an understanding that if one person runs out of money on his prepay account, he or she can beep the other. Husbands and wives can do this, or, as Fred, a plumber notes, colleagues: "I beep people I work with so that they call me when I don't have money."

Rule3: If you're asking for a favor (or a favorable treatment), don't send a callback beep

In the course of daily life, there are certainly cases where it is important to start off with a good impression, or to keep a favorable impression. The subtle obligations and expectations which tie people together influence when it is acceptable to send a callback beep, even beyond the "rich guy pays" credo described in rule #1. Two examples--customers and courtships--came up in the interviews. Patrick, a supplier of live chickens to hotels and restaurants, explains: "With customers I have to take care, because it's me who wants their orders, and mostly they can't spend their airtime on me, so it's me who always calls. I can't beep them". Like supporting a toll-free number in the United States, some Rwandan customers expect their suppliers to foot the cost of communication.

Lillian's lunchtime customers at her restaurant beep her daily, demanding a callback. She explains, "Customers beep to check on whether there is food left. Some are customers who are going to bring me money. So, when I see a number that I know, I have to call back, so I use a unit or two. There are some whom I don't call back because they have nothing constructive [profitable] to tell me." Like Patrick, Lillian says she never beeps customers.

There are exceptions. James, a baker, has a single major client, the local university, which accounts for half his business. He sometimes beeps this client when he is low on airtime, but tries to keep it to a minimum so as not to abuse the trust they have built up. As described above, Immanuel's rural dairy suppliers beep him, because they think he has more money than they do. He explains: "The supplier only calls when he wants to be paid."

Romance and beeping have their own rules. Nkrumah-Boateng observes, "No self-respecting man would dream of merely flashing his wife or girlfriend...Never mind the fact that it was Sugar Daddy himself who bought the phone and regularly buys her units." Filicien the student makes similar point:

If you are chasing after a lady, you cannot beep. You have to call. Beeping is for friends. When a girl you do not know well beeps you, you have to call back if you are interested. You cannot even text. She has to see that the effort is being made. Borrow a friend's phone if you do not have airtime. Text is not two-way.

Also single, Fred puts it bluntly: "I don't beep girls because it's me who needs them. In Jamaica, Host and Miller found a similar attitude towards use of the "call-me" feature offered by Digicel; male suitors who sent a "call me" message to their prospective partners were considered "cheap".

Rule 4: Don't beep too much
Beeping twice may increase the likelihood that a call target will call the beeper back. If the beep is between two people who know each other, the second beep can remove any confusion as to whether the beep was intended to request a callback or just to say hello. If beeping from a number that the recipient will not recognize, the beeper must be prepared to beep multiple times, just to get a response. Immanuel [who works in dairy sales] explains: "When the number is not programmed in my mobile, I can't call back but if he/she insists, beeping me again and again, I finally call back." Filicien reiterates the unwillingness to return calls from unknown beepers: "Recently, someone has been beeping me, but I don't have his name. If it were really important, he'd call".

And yet, don't over-do it. This warning seems to apply to both callback and relational beeps. Innocent, the garbage collector, complains that his daughter beeps "too much". Filicien explains, "There is gossip if someone beeps too much. If my friend beeps once in the morning, I smile. If she does it two or three more times in the day, and is doing it to others also, it gets bad." Indeed, it may be a faux pas to force others into calling you back to talk about nothing in particular. In Uganda, The Weekly Oberver notes: "In 99.99% of the time, there is even no serious issue to beep you about. It is a beep and when you call back someone simply asks: "Where are you?"

The full article will be available later in October at this url:

http://jcmc.indiana.edu/vol13/issue1/donner.html

Who could stay away from a keynote promising to demonstrate the latest in home robot technology? Not me. It doesn't matter whether the robots have been elegantly crafted to delicately perform surgery on the human body or if they've been bolted together with the sole purpose of destroying anything in their path (remember the show Robot Wars?), I hear the word robot and I'm automatically interested. I suspect most technophiles feel the same way.

So why did iRobot co-founder and CEO Colin Angle devote the opening minutes of his keynote at Thursday's DigitalLife conference to dispelling what he perceived to be Jetsonian expectations of what robots are and aren't?

Most of us came to the hand-wringing realization some time ago that we wouldn't be living in glass bubbles perched on poles high above the city streets or driving jet-powered cars to work in our lifetime. Surely we could handle Angle's definition of robot as an automated vacuum, floor mopper or pool vacuum.

Angle wasn't taking any chances. "Say goodbye to Hollywood robots, and say hello to a little boring--but fantastically useful--robots," he said. Angle later added, "Skepticism is one of our main challenges." Fine, fine, but when do we get to see the robots?

Caveats issued and expectations adjusted, Angle proceeded with his presentation, which quickly turned more into an infomercial than a keynote. No problem with that, in fact, I wished it was more like an infomercial. He gave his company's flagship Roomba carpet cleaner only a modest pile of dirt to tackle before picking it up and moving on to the less exciting floor-washing Scooba. The Dirt Dog and Verro where given only modest screen time in videos that depicted them sucking up garage-floor sawdust and water-logged leaves, respectively. What I really wanted to see was these robots going to town on some awesomely daunting patch of pet hair or pile of broken glass.

No such luck, but I did get a chance to see (and later touch) iRobot's latest inventions: the gutter-busting Looj and the cycloptic ConnectR, a Roomba-like device with voice-over-IP connectivity and a digital camera mounted on top like a large eyeball.

The Looj is a flat (2.25-inch high), rectangular mobile robot designed to clean entire stretches of gutter without the need for its owner to move or reposition his or her ladder. In the video and subsequent onstage demonstration, the Looj pile-drove through fairly new looking gutters, shoving away leaves and other debris as it went. At $100, the Looj is a tempting piece of equipment, although I'm skeptical that it could make it all the way down the average house gutter without getting stuck (most gutters I'm familiar with are bent in some way or have broken gutter straps that would impede the Looj's progress).

The ConnectR is an altogether different animal. Angle presented several scenarios in which its "virtual visiting" robot could be useful. In one scenario, a businessman uses his laptop to log onto a ConnectR operating in his home. Once the connection is made, the businessman can speak to whomever happens to be at his house, controlling the robot's movement and camera at the same time. If his kids are in the next room, he simply drives the ConnectR over to say, "Hi." The ConnectR could be placed on a table next to a board game to allow the homesick traveler to join his family for a game of Monopoly. It could even be set in front of an open story book so that a mom or dad could read to their children before bed (as long as one of the kids turned the pages).

I laughed a little at the video, but at the same time my mind was running a list of scenarios better suited to my life. Is the dog lying on the couch again when I'm not home? (The speakerphone function could let me address that immediately.) Did I remember to close the living room window before leaving on a business trip? (I could call my landlord to give me a hand with that one.) Was my mousetrap successful? (This could have helped me out last year when I discovered some unwanted roommates.)

So maybe we won't see a T-800 (the original model that appeared in 1984's The Terminator) or even a Rosie (see The Jetsons above) anytime soon. With the Roombas' success (there are 2 million of them out there), I'm confident home robots will reach at least knee level before too long. And if they keep me from having to climb a ladder to unclog my gutters in a rain storm, who am I to look down on them?

via The Onion, natch

The Onion's decades-long critique of science journalism and the public's understanding of science is nothing short of remarkable.

Why they haven't won a AAAS science journalism award for classics like these is beyond me:

National Science Foundation: Science Hard
Fifth-Grade Science Paper Doesn't Stand Up To Peer Review
Rhino, Tickbird Stuck In Dead-End Symbiotic Relationship

They even have an entire channel devoted to the subject.

Kannuu, a Dallas company, has just come up with a technique that allows text entry with one thumb that it claims may be able to match the entry speed of a full keyboard, reports Electronic Engineering Times. The software anticipates what the user is typing by providing partial entries as feedback, not full words.

If a user wishes to build the word "technology" using the Kannuu system, he or she would enter "t" and then "h", "w", "e", and "o" would appear on the screen at the four compass points. After selecting "e" using the up, down or sideways keys," the letters "r", "mp", "chn", and "st" would pop up and so on. The word can be constructed in seven clicks on the four-way dial of a handheld device instead of the usual 13 keystrokes.

A one-thumb device that matches the speed of a full keyboard would be an answer to my dreams, the critical enabler for truly useful pocket computing.

I dunno, though. I just finished reading an article in Science that contained this sentence:

"The metallic state resolved by photoemission on the 111 surface (normal to the trigonal) has a Fermi surface whose radius is on the order of 0.5 to 3 nm-1 and the expected oscillations would have a frequency range of 100 to 1000 T."

If the Kannuu system "anticipates" and lets me thumb type that sentence at the rate of 60 wpm, the founders of the company deserve the riches of Page and Brin.

I think I'll still be lugging my laptop for a few more years to come.

Good old Bill Clinton has done it again. Perhaps inspired by David Mills' speculation on the capacity of solar thermal power plants to deliver emissions-free electricity in this country, his confab going on in NYC presently has united said visionary's solar thermal company Ausra with utility giants Florida Power and Light (FPL) and Pacfic Gas and Electric (PG&E).

According to a press release, FPL has committed to building 500 megawatts of solar thermal power while PG&E promised to purchase 1,000 megawatts of electricity generated at such solar thermal power plants. No word on exactly where such plants might be built, but California has plenty of strong solar resource (and already hosts one of the world's oldest solar thermal power plant) as do adjacent states. And Florida gets enough sunshine to make Ausra's technology viable, at least according to its proponents. "Anywhere you get 4.5 [kilowatts-per-hour of sunshine] per square meter on an average day around the year or better you are in the money with these plants," says John O'Donnell, Ausra's executive vice president.

A lot of promises get made at the Clinton Global Initiative but not all of them are fulfilled. Remember the billion dollar "Green Fund" to invest in renewable energy and headed up by former World Bank president James Wolfensohn from last year? That effort was organized by Vinod Khosla, who is also the money man behind Ausra. Apparently, that wilted. Living up to the promise, both for this commitment and the technology, will be the problem.