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DNA Gets a New — and Bigger — Genetic Alphabet

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In 1985, the chemist Steven A. Benner sat down with some colleagues and a notebook and sketched out a way to expand the alphabet of DNA. He has been trying to make those sketches real ever since.

On Thursday, Dr. Benner and a team of scientists reported success: in a paper, published in Science, they said they have in effect doubled the genetic alphabet.

Natural DNA is spelled out with four different letters known as bases — A, C, G and T. Dr. Benner and his colleagues have built DNA with eight bases — four natural, and four unnatural. They named their new system Hachimoji DNA (hachi is Japanese for eight, moji for letter).

Crafting the four new bases that don’t exist in nature was a chemical tour-de-force. They fit neatly into DNA’s double helix, and enzymes can read them as easily as natural bases, in order to make molecules.

“We can do everything here that is necessary for life,” said Dr. Benner, now a distinguished fellow at the Foundation for Applied Molecular Evolution in Florida.

Hachimoji DNA could have many applications, including a far more durable way to store digital data that could last for centuries. “This could be huge that way,” said Dr. Nicholas V. Hud, a biochemist at Georgia Institute of Technology who was not involved in research.

It also raises a profound question about the nature of life elsewhere in the universe, offering the possibility that the four-base DNA we are familiar with may not be the only chemistry that could support life.

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The four natural bases of DNA are all anchored to molecular backbones. A pair of backbones can join into a double helix because their bases are attracted to each other. The bases form a bond with their hydrogen atoms.

But bases don’t stick together at random. C can only bond to G, and A can only bond to T. These strict rules help ensure that DNA strands don’t clump together into a jumble. No matter what sequence of bases are contained in natural DNA, it still keeps its shape.

But those four bases are not the only compounds that can attach to DNA’s backbone and link to another base — at least on paper. Dr. Benner and his colleagues thought up a dozen alternatives.

Working at the Swiss university ETH Zurich at the time, Dr. Benner tried to make some of those imaginary bases real.

“Of course, the first thing you discover is your design theory is not terribly good,” said Dr. Benner.

Once Dr. Benner and his colleagues combined real atoms, according to his designs, the artificial bases didn’t work as he had hoped.

Nevertheless, Dr. Benner’s initial forays impressed other chemists. “His work was a real inspiration for me,” said Floyd E. Romesberg, now of the Scripps Research Institute in San Diego. Reading about Dr. Benner’s early experiments, Dr. Romesberg decided to try to create his own bases.

Dr. Romesberg chose not to make bases that linked together with hydrogen bonds; instead, he fashioned a pair of oily compounds that repelled water. That chemistry brought his unnatural pair of bases together. “Oil doesn’t like to mix with water, but it does like to mix with oil,” said Dr. Romesberg.

In the years that followed, Dr. Romesberg and his colleagues fashioned enzymes that could copy DNA made from both natural bases and unnatural, oily ones. In 2014, the scientists engineered bacteria that could make new copies of these hybrid genes.

In recent years, Dr. Romesberg’s team has begun making unnatural proteins from these unnatural genes. He founded a company, Synthorx, to develop some of these proteins as cancer drugs.

At the same time, Dr. Benner continued with his own experiments. He and his colleagues succeeded in creating one pair of new bases.

Like Dr. Romesberg, they found an application for their unnatural DNA. Their six-base DNA became the basis of a new, sensitive test for viruses in blood samples.

They then went on to create a second pair of new bases. Now with eight bases to play with, the researchers started building DNA molecules with a variety of different sequences. The researchers found that no matter which sequence they created, the molecules still formed the standard double helix.

Because Hachimoji DNA held onto this shape, it could act like regular DNA: it could store information, and that information could be read to make a molecule.

For a cell, the first step in making a molecule is to read a gene using special enzymes. They make a copy of the gene in a single-stranded version of DNA, called RNA.

Depending on the gene, the cell will then do one of two things with that RNA. In some cases, it will use the RNA as a guide to build a protein. But in other cases, the RNA molecule floats off to do a job of its own.

Dr. Benner and his colleagues created a Hachimoji gene for an RNA molecule. They predicted that the RNA molecule would be able to grab a molecule called a fluorophore. Cradled by the RNA molecule, the fluorophore would absorb light and release it as a green flash.

Andrew Ellington, an evolutionary engineer at the University of Texas, led the effort to find an enzyme that could read Hachimoji DNA. He and his colleagues found a promising one made by a virus, and they tinkered with it until the enzyme could easily read all eight bases.

They mixed the enzyme in test tubes with the Hachimoji gene. As they had hoped, their test tubes began glowing green.

“Here you have it from start to finish,” said Dr. Benner. “We can store information, we can transfer it to another molecule and that other molecule has a function — and here it is, glowing.”

In the future, Hachimoji DNA may store information of a radically different sort. It might someday encode a movie or a spreadsheet.

Today, movies, spreadsheets and other digital files are typically stored on silicon chips or magnetic tapes. But those kinds of storage have serious shortcomings. For one thing, they can deteriorate in just years.

DNA, by contrast, can remain intact for centuries. Last year, researchers at Microsoft and the University of Washington managed to encode 35 songs, videos, documents, and other files, totaling 200 megabytes, in a batch of DNA molecules.

With eight bases instead of four, Hachimoji DNA could potentially encode far more information. “DNA capable of twice as much storage? That’s pretty amazing in my view,” said Dr. Ellington.

Beyond our current need for storage, Hachimoji DNA also offers some clues about life itself. Scientists have long wondered if our DNA evolved only four bases because they’re the only ones that can work in genes. Could life have taken a different path?

“Steve’s work goes a long way to say that it could have — it just didn’t,” said Dr. Romesberg.

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Artificial intelligence pioneers win tech’s ‘Nobel Prize’

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Computers have become so smart during the past 20 years that people don’t think twice about chatting with digital assistants like Alexa and Siri or seeing their friends automatically tagged in Facebook pictures.

But making those quantum leaps from science fiction to reality required hard work from computer scientists like Yoshua Bengio, Geoffrey Hinton and Yann LeCun. The trio tapped into their own brainpower to make it possible for machines to learn like humans, a breakthrough now commonly known as “artificial intelligence,” or AI.

Their insights and persistence were rewarded Wednesday with the Turing Award, an honor that has become known as technology industry’s version of the Nobel Prize. It comes with a $1 million prize funded by Google, a company where AI has become part of its DNA.

The award marks the latest recognition of the instrumental role that artificial intelligence will likely play in redefining the relationship between humanity and technology in the decades ahead.

Artificial intelligence is now one of the fastest-growing areas in all of science and one of the most talked-about topics in society,” said Cherri Pancake, president of the Association for Computing Machinery, the group behind the Turing Award.

Although they have known each other for than 30 years, Bengio, Hinton and LeCun have mostly worked separately on technology known as neural networks. These are the electronic engines that power tasks such as facial and speech recognition, areas where computers have made enormous strides over the past decade. Such neural networks also are a critical component of robotic systems that are automating a wide range of other human activity, including driving.

Their belief in the power of neural networks was once mocked by their peers, Hinton said. No more. He now works at Google as a vice president and senior fellow while LeCun is chief AI scientist at Facebook. Bengio remains immersed in academia as a University of Montreal professor in addition to serving as scientific director at the Artificial Intelligence Institute in Quebec.

“For a long time, people thought what the three of us were doing was nonsense,” Hinton said in an interview with The Associated Press. “They thought we were very misguided and what we were doing was a very surprising thing for apparently intelligent people to waste their time on. My message to young researchers is, don’t be put off if everyone tells you what are doing is silly.” Now, some people are worried that the results of the researchers’ efforts might spiral out of control.

While the AI revolution is raising hopes that computers will make most people’s lives more convenient and enjoyable, it’s also stoking fears that humanity eventually will be living at the mercy of machines.

Bengio, Hinton and LeCun share some of those concerns especially the doomsday scenarios that envision AI technology developed into weapons systems that wipe out humanity.

But they are far more optimistic about the other prospects of AI empowering computers to deliver more accurate warnings about floods and earthquakes, for instance, or detecting health risks, such as cancer and heart attacks, far earlier than human doctors.

“One thing is very clear, the techniques that we developed can be used for an enormous amount of good affecting hundreds of millions of people,” Hinton said.

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Lamborghini’s latest Huracán is a supercar with a supercomputer

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Over the past few decades, technology has made vehicles safer and easier to drive. Anti-lock brakes, traction control, torque vectoring and other bits of tech keep cars on the road instead of flying into a ditch when things get hairy. It’s why newer cars typically handle corners better than older cars.

At Lamborghini, they’ve taken things further with their new Lamborghini Dinamica Veicolo Integrata or LDVI system. The Engine Control Unit (ECU) takes data from the entire car and uses it to adjust how the new Huracán EVO Spyder drives in real time (actually in less than 20 milliseconds. But that’s about as close as you can get to real time). Cars have been doing some form of this for a while but the Italian automaker needs to be able to do this at incredible speeds and in environments your typical sedan or SUV doesn’t encounter.

At Lamborghini, they’ve taken things further with their new Lamborghini Dinamica Veicolo Integrata or LDVI system. The Engine Control Unit (ECU) takes data from the entire car and uses it to adjust how the new Huracán EVO Spyder drives in real time (actually in less than 20 milliseconds. But that’s about as close as you can get to real time). Cars have been doing some form of this for a while but the Italian automaker needs to be able to do this at incredible speeds and in environments your typical sedan or SUV doesn’t encounter.

With this technology, Lamborghini is able to take the raw power of an all-wheel-drive supercar with a V10 engine and 630 horsepower and tame it, just enough, so your average driver (who can shell out $287,400) can enjoy themselves behind the wheel of the all-wheel-steering vehicle without, you know, flying into a ditch.

To achieve this, the LVDI is actually a super fast central processing unit that takes in data about the road surface, the car’s setup, the tires and how the driver is driving the vehicle. It then uses that info to control various aspects of the Huracan.

The system works in concert with the Lamborghini Piattaforma Inerziale (LPI) version 2.0 hardware sensors. This system uses gyroscopes and accelerometers located at the car’s center of gravity. It measures the vehicle’s movements and shares that data with the LVDI computer.

Lamborghini says the system is so in tune with all aspects of a drive that it can actually predict the best driving setup for the next moment. In other words, if you’re behind the wheel flying around corners on a back road, the system will recognize your behavior as you enter a corner and adjust itself.

“Where it’s possible to do a bigger jump in the future is with the intelligent use of four-wheel drive and four-wheel steering and the movement and control of the torque wheel by wheel in a way that can be more predictable and that is what we have with the Huracan EVO,” said Maurizio Reggiani, chief technology officer of Automobili Lamborghini.

Lamborghini is thinking about a world beyond a completely gas-powered engine though — it has a pipeline for hybrid and electric vehicles. But Reggiani notes that Lamborghini will probably be the last automaker to leave behind a large growling power plant.

Putting all that power to the ground in a controllable way requires an incredible amount of technology — that’s where LVDI and other pieces of technology come in. The automaker believes the result is a driving experience that matches exactly what the driver wants, regardless of the mode the car is in. Whether it be Strada, Sport, or the track ready Corsa, the vehicle (in a controlled way) should deliver.

That control allows a driver to do something that typically takes months if not years to master: drifting. It goes against what the car wants to do — lose traction. But in Sport mode it’s possible. To do that, the vehicle has to figure out (in real time and safely) things like what angle it wants to slide. The Huracán EVO Spyder has to understand that you want to drift and not fight that. If it does, it will jerk the car (and driver) back into alignment.

Lamborghini Huracan EVO Spyder

To relive your Fast and Furious dreams, the automaker started where lots of companies start with new technology: In the simulator. But a computer can’t faithfully reproduce the real world. Mostly that has to do with tires, a variable that’s tough to predict because of the density of the rubber’s compound and its wear.

Then, of course, there’s the driver. We all drive differently but the experience must be the same for everyone. It’s important that even with all that technology, it’s still a driving experience. “We don’t want to have something that substitutes the driver. We want to have a car that is able to understand what the driver wants to do,” Reggiani said.

Lamborghini is known for large engines, intense growls, striking design and bank-busting prices. But the reality is all that power would be useless if drivers couldn’t actually control the car. The automaker’s latest system makes that possible for everyone. Sure, only a select few can own a Lamborghini, but everyone can appreciate a system that makes driving safer while simultaneously more fun.

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This device makes it easy for the elderly to stay in touch with their loved ones

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Only 20 percent of over-75s in the UK have a smartphone compared to 95 percent of 16-to-24-year-olds. Digital technologies change fast, become obsolete quickly and usually need you to spend a bit of time learning how to use them.

This helps explain why most older adults tend to use what they know best when it comes to communicating, which usually means a phone call via a landline or basic mobile, instead of a quick text or social media update.

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But it doesn’t have to be this way. My colleague Massimo Micocci and I have recently designed a more modern device we hope will help older people stay in more frequent touch with instant updates, but that has a familiar feel to it. By drawing on smart materials and what we call “design metaphors”, we hope to make new technology more accessible.

When older people don’t have access to instant messaging, a phone call or a visit may be the only way for friends and family to check their loved ones are well. And doing so more than (or even) once a day might not be feasible or wanted.

Similarly, older people might feel that ringing their relatives morning and night just to let them know they’re OK would be an inconvenience. And while you can buy specialized monitoring devices that record people’s movements around their home, these often feel like an invasion of privacy.

With this in mind, we developed something that lets older people broadcast their status to their families like a social media update. Our device (which is designed for research purposes rather than commercial development) looks like an analogue radio. But it lets users transmit information about their activity captured from a wearable heartbeat sensor in a way that is entertaining and intuitive, and only shared with selected group of followers.

The keep-in-touch. Author provided

The information includes how energetic their current activity is, for example whether they are conducting an active task such as gardening, or a relaxing and restful one such as reading a book.

By designing the device to evoke technology with which people will feel instantly familiar, we’re using the principle of design metaphor. Most people find it easier to interact with devices that resemble products they have already used.

In cognitive psychology, this is known as inferential learning, referring to when someone applies established knowledge in their brain to a new context. The design of our “radio” device makes it easier for users to work out how to use it, based on their previous interactions with traditional radios – even though it has a very different function.

Giving users control

There are plenty of systems that enable people to monitor older family members. But usually these are fully passive, where the older adults are observed directly through cameras and sensors around their homes. Or they are fully active, for example mobile phones that require the older adults to stop what they’re doing and respond right away.

Instead, our device lets people choose the level of communication they want. It runs in the background and doesn’t transmit detailed information such as images of people in their homes. This makes it a much less intrusive way of letting someone know you’re OK.

We also wanted to make the device very easy to understand, interpret and remember. So rather than having an information screen that showed text or images, we wanted to create a display that used so-called smart materials to convey what the user was doing.

In this context, smart materials are those that can change color, shape, viscosity or how much light they emit. Our research showed that light-emitting materials were the best way of conveying messages without words for both under and over-60s.

The “radio” is just a research prototype but it has allowed us to understand that the combination of innovative materials and familiar artefacts can be a successful way to encourage aging users to adopt new technologies. In this way, smart materials and design metaphors could help bridge the digital gap and promote innovation among older consumers.

This article is republished from The Conversation by Gabriella Spinelli, Reader in Design Innovation, Brunel University London under a Creative Commons license. Read the original article.

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