Using the DNA origami method, in which complex three-dimensional shapes and objects are constructed by folding strands of DNA, Douglas and Bachelet created a nanosized robot in the form of an open barrel whose two halves are connected by a hinge. The DNA barrel, which acts as a container, is held shut by special DNA latches that can recognize and seek out combinations of cell-surface proteins, including disease markers. When the latches find their targets, they reconfigure, causing the two halves of the barrel to swing open and expose its contents, or payload. The container can hold various types of payloads, including specific molecules with encoded instructions that can interact with specific cell surface signaling receptors.
Douglas and Bachelet used this system to deliver instructions, which were encoded in antibody fragments, to two different types of cancer cells -- leukemia and lymphoma. In each case, the message to the cell was to activate its "suicide switch" -- a standard feature that allows aging or abnormal cells to be eliminated. And since leukemia and lymphoma cells speak different languages, the messages were written in different antibody combinations.
"We can finally integrate sensing and logical computing functions via complex, yet predictable, nanostructures -- some of the first hybrids of structural DNA, antibodies, aptamers and metal atomic clusters -- aimed at useful, very specific targeting of human cancers and T-cells," said George Church, Ph.D., a Wyss core faculty member and Professor of Genetics at Harvard Medical School, who is Principal Investigator on the project.
Man, I love this stuff. Some choice excerpts:
The SI second is defined based on specific transitions of a cesium atom. If this is measured on the rotating Earth, relativistic effects that depend in part on the earth's rotation will influence a cesium clock's rate relative to a clock in an inertial frame. Thus, even the measurement of the SI second that is used to define Terrestrial Time will be at least slightly dependent on the unpredictable rate of Earth's rotation, although the effect of variations in the Earth's rotation is not currently within the sensitivity of our measurements.And:
Uncorrected Solar Time is computed from Pendulum Time by adding a seasonally varying correction for the equation of time. This varies about half an hour or so over the course of a year. The analemma is a two-dimensional graph of the equation of time. The equation of time also varies from year to year, century to century. This variation is predictable within the uncertainty of the Earth's rotation rate, so it is pre-computed over the clock's 10,000-year operating interval and stored in the equation-of-time cam based on values is derived from an extended form of the JPL DE422 solar system solution. The function encoded in the cam assumes the predicted slowing of the earth's rotational period at the rate of 1.8 milliseconds per day per century. The cam function also encodes the uncertainty of slowing of the Earth's rotational period, by a mechanism that will be described later.And:
All displays on the clock are designed to maintain accuracy to within a five-minute tick over the entire 10,000-year lifetime of the clock, as long as the clock detects solar synchronization at least once a year. It is possible that an unusual event such as a volcanic eruption could prevent the clock from detecting noon for more than a year. In this case, the clock may temporarily drift away from the correct time, but it will eventually resynchronize when clear skies reemerge as long as it has not drifted more than 12 hours.And:
As previously discussed, the Earth's rotation is currently slowing at a rate of about 1.8 milliseconds per day per century. Of course, the trend may not continue, especially if the climate changes. The variation is caused by a variety of effects including tidal drags, shifts in the Earth's crust, changes in ocean levels, and even weather. For example an ice age would put more mass near the poles, making the day shorter. Melting icecaps would make it longer. This creates an uncertainty in the average length of day of about 10 parts per million, an uncertainty of plus or minus 37 solar days over the design lifetime of the clock.
The only problem is that identifying pregnant customers is harder than it sounds. Target has a baby-shower registry, and Pole started there, observing how shopping habits changed as a woman approached her due date, which women on the registry had willingly disclosed. He ran test after test, analyzing the data, and before long some useful patterns emerged. Lotions, for example. Lots of people buy lotion, but one of Pole's colleagues noticed that women on the baby registry were buying larger quantities of unscented lotion around the beginning of their second trimester. Another analyst noted that sometime in the first 20 weeks, pregnant women loaded up on supplements like calcium, magnesium and zinc. Many shoppers purchase soap and cotton balls, but when someone suddenly starts buying lots of scent-free soap and extra-big bags of cotton balls, in addition to hand sanitizers and washcloths, it signals they could be getting close to their delivery date.
As Pole's computers crawled through the data, he was able to identify about 25 products that, when analyzed together, allowed him to assign each shopper a "pregnancy prediction" score. More important, he could also estimate her due date to within a small window, so Target could send coupons timed to very specific stages of her pregnancy.
One Target employee I spoke to provided a hypothetical example. Take a fictional Target shopper named Jenny Ward, who is 23, lives in Atlanta and in March bought cocoa-butter lotion, a purse large enough to double as a diaper bag, zinc and magnesium supplements and a bright blue rug. There's, say, an 87 percent chance that she's pregnant and that her delivery date is sometime in late August. What's more, because of the data attached to her Guest ID number, Target knows how to trigger Jenny's habits. They know that if she receives a coupon via e-mail, it will most likely cue her to buy online. They know that if she receives an ad in the mail on Friday, she frequently uses it on a weekend trip to the store. And they know that if they reward her with a printed receipt that entitles her to a free cup of Starbucks coffee, she'll use it when she comes back again.
"We have the capacity to send every customer an ad booklet, specifically designed for them, that says, `Here's everything you bought last week and a coupon for it,' " one Target executive told me. "We do that for grocery products all the time." But for pregnant women, Target's goal was selling them baby items they didn't even know they needed yet.
"With the pregnancy products, though, we learned that some women react badly," the executive said. "Then we started mixing in all these ads for things we knew pregnant women would never buy, so the baby ads looked random. We'd put an ad for a lawn mower next to diapers. We'd put a coupon for wineglasses next to infant clothes. That way, it looked like all the products were chosen by chance.
"And we found out that as long as a pregnant woman thinks she hasn't been spied on, she'll use the coupons. She just assumes that everyone else on her block got the same mailer for diapers and cribs. As long as we don't spook her, it works."
And of course they're terrified that anyone find out about this:
When I sent Target a complete summary of my reporting, the reply was more terse: "Almost all of your statements contain inaccurate information and publishing them would be misleading to the public. We do not intend to address each statement point by point." The company declined to identify what was inaccurate. They did add, however, that Target "is in compliance with all federal and state laws, including those related to protected health information."
When I offered to fly to Target's headquarters to discuss its concerns, a spokeswoman e-mailed that no one would meet me. When I flew out anyway, I was told I was on a list of prohibited visitors. "I've been instructed not to give you access and to ask you to leave," said a very nice security guard named Alex.
Earlier today, the Wall Street Journal published evidence that Google has been circumventing the privacy settings of Safari and iPhone users, tracking them on non-Google sites despite Apple's default settings, which were intended to prevent such tracking. [...]
Unfortunately, that had the side effect of completely undoing all of Safari's protections against doubleclick.net. It caused Safari to allow other DoubleClick cookies, and especially the main "id" tracking cookie that Safari normally blocked. Like a balloon popped with a pinprick, all of Safari's protections against DoubleClick were gone.