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#431189 Researchers Develop New Tech to Predict ...
It is one of the top 10 deadliest diseases in the United States, and it cannot be cured or prevented. But new studies are finding ways to diagnose Alzheimer’s disease in its earliest stages, while some of the latest research says technologies like artificial intelligence can detect dementia years before the first symptoms occur.
These advances, in turn, will help bolster clinical trials seeking a cure or therapies to slow or prevent the disease. Catching Alzheimer’s disease or other forms of dementia early in their progression can help ease symptoms in some cases.
“Often neurodegeneration is diagnosed late when massive brain damage has already occurred,” says professor Francis L Martin at the University of Central Lancashire in the UK, in an email to Singularity Hub. “As we know more about the molecular basis of the disease, there is the possibility of clinical interventions that might slow or halt the progress of the disease, i.e., before brain damage. Extending cognitive ability for even a number of years would have huge benefit.”
Blood Diamond
Martin is the principal investigator on a project that has developed a technique to analyze blood samples to diagnose Alzheimer’s disease and distinguish between other forms of dementia.
The researchers used sensor-based technology with a diamond core to analyze about 550 blood samples. They identified specific chemical bonds within the blood after passing light through the diamond core and recording its interaction with the sample. The results were then compared against blood samples from cases of Alzheimer’s disease and other neurodegenerative diseases, along with those from healthy individuals.
“From a small drop of blood, we derive a fingerprint spectrum. That fingerprint spectrum contains numerical data, which can be inputted into a computational algorithm we have developed,” Martin explains. “This algorithm is validated for prediction of unknown samples. From this we determine sensitivity and specificity. Although not perfect, my clinical colleagues reliably tell me our results are far better than anything else they have seen.”
Martin says the breakthrough is the result of more than 10 years developing sensor-based technologies for routine screening, monitoring, or diagnosing neurodegenerative diseases and cancers.
“My vision was to develop something low-cost that could be readily applied in a typical clinical setting to handle thousands of samples potentially per day or per week,” he says, adding that the technology also has applications in environmental science and food security.
The new test can also distinguish accurately between Alzheimer’s disease and other forms of neurodegeneration, such as Lewy body dementia, which is one of the most common causes of dementia after Alzheimer’s.
“To this point, other than at post-mortem, there has been no single approach towards classifying these pathologies,” Martin notes. “MRI scanning is often used but is labor-intensive, costly, difficult to apply to dementia patients, and not a routine point-of-care test.”
Crystal Ball
Canadian researchers at McGill University believe they can predict Alzheimer’s disease up to two years before its onset using big data and artificial intelligence. They developed an algorithm capable of recognizing the signatures of dementia using a single amyloid PET scan of the brain of patients at risk of developing the disease.
Alzheimer’s is caused by the accumulation of two proteins—amyloid beta and tau. The latest research suggests that amyloid beta leads to the buildup of tau, which is responsible for damaging nerve cells and connections between cells called synapses.
The work was recently published in the journal Neurobiology of Aging.
“Despite the availability of biomarkers capable of identifying the proteins causative of Alzheimer’s disease in living individuals, the current technologies cannot predict whether carriers of AD pathology in the brain will progress to dementia,” Sulantha Mathotaarachchi, lead author on the paper and an expert in artificial neural networks, tells Singularity Hub by email.
The algorithm, trained on a population with amnestic mild cognitive impairment observed over 24 months, proved accurate 84.5 percent of the time. Mathotaarachchi says the algorithm can be trained on different populations for different observational periods, meaning the system can grow more comprehensive with more data.
“The more biomarkers we incorporate, the more accurate the prediction could be,” Mathotaarachchi adds. “However, right now, acquiring [the] required amount of training data is the biggest challenge. … In Alzheimer’s disease, it is known that the amyloid protein deposition occurs decades before symptoms onset.”
Unfortunately, the same process occurs in normal aging as well. “The challenge is to identify the abnormal patterns of deposition that lead to the disease later on,” he says
One of the key goals of the project is to improve the research in Alzheimer’s disease by ensuring those patients with the highest probability to develop dementia are enrolled in clinical trials. That will increase the efficiency of clinical programs, according to Mathotaarachchi.
“One of the most important outcomes from our study was the pilot, online, real-time prediction tool,” he says. “This can be used as a framework for patient screening before recruiting for clinical trials. … If a disease-modifying therapy becomes available for patients, a predictive tool might have clinical applications as well, by providing to the physician information regarding clinical progression.”
Pixel by Pixel Prediction
Private industry is also working toward improving science’s predictive powers when it comes to detecting dementia early. One startup called Darmiyan out of San Francisco claims its proprietary software can pick up signals before the onset of Alzheimer’s disease by up to 15 years.
Darmiyan didn’t respond to a request for comment for this article. Venture Beat reported that the company’s MRI-analyzing software “detects cell abnormalities at a microscopic level to reveal what a standard MRI scan cannot” and that the “software measures and highlights subtle microscopic changes in the brain tissue represented in every pixel of the MRI image long before any symptoms arise.”
Darmiyan claims to have a 90 percent accuracy rate and says its software has been vetted by top academic institutions like New York University, Rockefeller University, and Stanford, according to Venture Beat. The startup is awaiting FDA approval to proceed further but is reportedly working with pharmaceutical companies like Amgen, Johnson & Johnson, and Pfizer on pilot programs.
“Our technology enables smarter drug selection in preclinical animal studies, better patient selection for clinical trials, and much better drug-effect monitoring,” Darmiyan cofounder and CEO Padideh Kamali-Zare told Venture Beat.
Conclusions
An estimated 5.5 million Americans have Alzheimer’s, and one in 10 people over age 65 have been diagnosed with the disease. By mid-century, the number of Alzheimer’s patients could rise to 16 million. Health care costs in 2017 alone are estimated to be $259 billion, and by 2050 the annual price tag could be more than $1 trillion.
In sum, it’s a disease that cripples people and the economy.
Researchers are always after more data as they look to improve outcomes, with the hope of one day developing a cure or preventing the onset of neurodegeneration altogether. If interested in seeing this medical research progress, you can help by signing up on the Brain Health Registry to improve the quality of clinical trials.
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Posted in Human Robots
#431159 How Close Is Turing’s Dream of ...
The quest for conversational artificial intelligence has been a long one.
When Alan Turing, the father of modern computing, racked his considerable brains for a test that would truly indicate that a computer program was intelligent, he landed on this area. If a computer could convince a panel of human judges that they were talking to a human—if it could hold a convincing conversation—then it would indicate that artificial intelligence had advanced to the point where it was indistinguishable from human intelligence.
This gauntlet was thrown down in 1950 and, so far, no computer program has managed to pass the Turing test.
There have been some very notable failures, however: Joseph Weizenbaum, as early as 1966—when computers were still programmed with large punch-cards—developed a piece of natural language processing software called ELIZA. ELIZA was a machine intended to respond to human conversation by pretending to be a psychotherapist; you can still talk to her today.
Talking to ELIZA is a little strange. She’ll often rephrase things you’ve said back at you: so, for example, if you say “I’m feeling depressed,” she might say “Did you come to me because you are feeling depressed?” When she’s unsure about what you’ve said, ELIZA will usually respond with “I see,” or perhaps “Tell me more.”
For the first few lines of dialogue, especially if you treat her as your therapist, ELIZA can be convincingly human. This was something Weizenbaum noticed and was slightly alarmed by: people were willing to treat the algorithm as more human than it really was. Before long, even though some of the test subjects knew ELIZA was just a machine, they were opening up with some of their deepest feelings and secrets. They were pouring out their hearts to a machine. When Weizenbaum’s secretary spoke to ELIZA, even though she knew it was a fairly simple computer program, she still insisted Weizenbaum leave the room.
Part of the unexpected reaction ELIZA generated may be because people are more willing to open up to a machine, feeling they won’t be judged, even if the machine is ultimately powerless to do or say anything to really help. The ELIZA effect was named for this computer program: the tendency of humans to anthropomorphize machines, or think of them as human.
Weizenbaum himself, who later became deeply suspicious of the influence of computers and artificial intelligence in human life, was astonished that people were so willing to believe his script was human. He wrote, “I had not realized…that extremely short exposures to a relatively simple computer program could induce powerful delusional thinking in quite normal people.”
“Consciously, you know you’re talking to a big block of code stored somewhere out there in the ether. But subconsciously, you might feel like you’re interacting with a human.”
The ELIZA effect may have disturbed Weizenbaum, but it has intrigued and fascinated others for decades. Perhaps you’ve noticed it in yourself, when talking to an AI like Siri, Alexa, or Google Assistant—the occasional response can seem almost too real. Consciously, you know you’re talking to a big block of code stored somewhere out there in the ether. But subconsciously, you might feel like you’re interacting with a human.
Yet the ELIZA effect, as enticing as it is, has proved a source of frustration for people who are trying to create conversational machines. Natural language processing has proceeded in leaps and bounds since the 1960s. Now you can find friendly chatbots like Mitsuku—which has frequently won the Loebner Prize, awarded to the machines that come closest to passing the Turing test—that aim to have a response to everything you might say.
In the commercial sphere, Facebook has opened up its Messenger program and provided software for people and companies to design their own chatbots. The idea is simple: why have an app for, say, ordering pizza when you can just chatter to a robot through your favorite messenger app and make the order in natural language, as if you were telling your friend to get it for you?
Startups like Semantic Machines hope their AI assistant will be able to interact with you just like a secretary or PA would, but with an unparalleled ability to retrieve information from the internet. They may soon be there.
But people who engineer chatbots—both in the social and commercial realm—encounter a common problem: the users, perhaps subconsciously, assume the chatbots are human and become disappointed when they’re not able to have a normal conversation. Frustration with miscommunication can often stem from raised initial expectations.
So far, no machine has really been able to crack the problem of context retention—understanding what’s been said before, referring back to it, and crafting responses based on the point the conversation has reached. Even Mitsuku will often struggle to remember the topic of conversation beyond a few lines of dialogue.
“For everything you say, there could be hundreds of responses that would make sense. When you travel a layer deeper into the conversation, those factors multiply until you end up with vast numbers of potential conversations.”
This is, of course, understandable. Conversation can be almost unimaginably complex. For everything you say, there could be hundreds of responses that would make sense. When you travel a layer deeper into the conversation, those factors multiply until—like possible games of Go or chess—you end up with vast numbers of potential conversations.
But that hasn’t deterred people from trying, most recently, tech giant Amazon, in an effort to make their AI voice assistant, Alexa, friendlier. They have been running the Alexa Prize competition, which offers a cool $500,000 to the winning AI—and a bonus of a million dollars to any team that can create a ‘socialbot’ capable of sustaining a conversation with human users for 20 minutes on a variety of themes.
Topics Alexa likes to chat about include science and technology, politics, sports, and celebrity gossip. The finalists were recently announced: chatbots from universities in Prague, Edinburgh, and Seattle. Finalists were chosen according to the ratings from Alexa users, who could trigger the socialbots into conversation by saying “Hey Alexa, let’s chat,” although the reviews for the socialbots weren’t always complimentary.
By narrowing down the fields of conversation to a specific range of topics, the Alexa Prize has cleverly started to get around the problem of context—just as commercially available chatbots hope to do. It’s much easier to model an interaction that goes a few layers into the conversational topic if you’re limiting those topics to a specific field.
Developing a machine that can hold almost any conversation with a human interlocutor convincingly might be difficult. It might even be a problem that requires artificial general intelligence to truly solve, rather than the previously-employed approaches of scripted answers or neural networks that associate inputs with responses.
But a machine that can have meaningful interactions that people might value and enjoy could be just around the corner. The Alexa Prize winner is announced in November. The ELIZA effect might mean we will relate to machines sooner than we’d thought.
So, go well, little socialbots. If you ever want to discuss the weather or what the world will be like once you guys take over, I’ll be around. Just don’t start a therapy session.
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#430830 Biocomputers Made From Cells Can Now ...
When it comes to biomolecules, RNA doesn’t get a lot of love.
Maybe you haven’t even heard of the silent workhorse. RNA is the cell’s de facto translator: like a game of telephone, RNA takes DNA’s genetic code to a cellular factory called ribosomes. There, the cell makes proteins based on RNA’s message.
But RNA isn’t just a middleman. It controls what proteins are formed. Because proteins wiz around the cell completing all sorts of important processes, you can say that RNA is the gatekeeper: no RNA message, no proteins, no life.
In a new study published in Nature, RNA finally took center stage. By adding bits of genetic material to the E. Coli bacteria, a team of biohackers at the Wyss Institute hijacked the organism’s RNA messengers so that they only spring into action following certain inputs.
The result? A bacterial biocomputer capable of performing 12-input logic operations—AND, OR, and NOT—following specific inputs. Rather than outputting 0s and 1s, these biocircuits produce results based on the presence or absence of proteins and other molecules.
“It’s the greatest number of inputs in a circuit that a cell has been able to process,” says study author Dr. Alexander Green at Arizona State University. “To be able to analyze those signals and make a decision is the big advance here.”
When given a specific set of inputs, the bacteria spit out a protein that made them glow neon green under fluorescent light.
But synthetic biology promises far more than just a party trick—by tinkering with a cell’s RNA repertoire, scientists may one day coax them to photosynthesize, produce expensive drugs on the fly, or diagnose and hunt down rogue tumor cells.
Illustration of an RNA-based ‘ribocomputing’ device that makes logic-based decisions in living cells. The long gate RNA (blue) detects the binding of an input RNA (red). The ribosome (purple/mauve) reads the gate RNA to produce an output protein. Image Credit: Alexander Green / Arizona State University
The software of life
This isn’t the first time that scientists hijacked life’s algorithms to reprogram cells into nanocomputing systems. Previous work has already introduced to the world yeast cells that can make anti-malaria drugs from sugar or mammalian cells that can perform Boolean logic.
Yet circuits with multiple inputs and outputs remain hard to program. The reason is this: synthetic biologists have traditionally focused on snipping, fusing, or otherwise arranging a cell’s DNA to produce the outcomes they want.
But DNA is two steps removed from proteins, and tinkering with life’s code often leads to unexpected consequences. For one, the cell may not even accept and produce the extra bits of DNA code. For another, the added code, when transformed into proteins, may not act accordingly in the crowded and ever-changing environment of the cell.
What’s more, tinkering with one gene is often not enough to program an entirely new circuit. Scientists often need to amp up or shut down the activity of multiple genes, or multiple biological “modules” each made up of tens or hundreds of genes.
It’s like trying to fit new Lego pieces in a specific order into a room full of Lego constructions. Each new piece has the potential to wander off track and click onto something it’s not supposed to touch.
Getting every moving component to work in sync—as you might have guessed—is a giant headache.
The RNA way
With “ribocomputing,” Green and colleagues set off to tackle a main problem in synthetic biology: predictability.
Named after the “R (ribo)” in “RNA,” the method grew out of an idea that first struck Green back in 2012.
“The synthetic biological circuits to date have relied heavily on protein-based regulators that are difficult to scale up,” Green wrote at the time. We only have a limited handful of “designable parts” that work well, and these circuits require significant resources to encode and operate, he explains.
RNA, in comparison, is a lot more predictable. Like its more famous sibling DNA, RNA is composed of units that come in four different flavors: A, G, C, and U. Although RNA is only single-stranded, rather than the double helix for which DNA is known for, it can bind short DNA-like sequences in a very predictable manner: Gs always match up with Cs and As always with Us.
Because of this predictability, it’s possible to design RNA components that bind together perfectly. In other words, it reduces the chance that added RNA bits might go rogue in an unsuspecting cell.
Normally, once RNA is produced it immediately rushes to the ribosome—the cell’s protein-building factory. Think of it as a constantly “on” system.
However, Green and his team found a clever mechanism to slow them down. Dubbed the “toehold switch,” it works like this: the artificial RNA component is first incorporated into a chain of A, G, C, and U folded into a paperclip-like structure.
This blocks the RNA from accessing the ribosome. Because one RNA strand generally maps to one protein, the switch prevents that protein from ever getting made.
In this way, the switch is set to “off” by default—a “NOT” gate, in Boolean logic.
To activate the switch, the cell needs another component: a “trigger RNA,” which binds to the RNA toehold switch. This flips it on: the RNA grabs onto the ribosome, and bam—proteins.
BioLogic gates
String a few RNA switches together, with the activity of each one relying on the one before, and it forms an “AND” gate. Alternatively, if the activity of each switch is independent, that’s an “OR” gate.
“Basically, the toehold switches performed so well that we wanted to find a way to best exploit them for cellular applications,” says Green. They’re “kind of the equivalent of your first transistors,” he adds.
Once the team optimized the designs for different logic gates, they carefully condensed the switches into “gate RNA” molecules. These gate RNAs contain both codes for proteins and the logic operations needed to kickstart the process—a molecular logic circuit, so to speak.
If you’ve ever played around with an Arduino-controlled electrical circuit, you probably know the easiest way to test its function is with a light bulb.
That’s what the team did here, though with a biological bulb: green fluorescent protein, a light-sensing protein not normally present in bacteria that—when turned on—makes the microbugs glow neon green.
In a series of experiments, Green and his team genetically inserted gate RNAs into bacteria. Then, depending on the type of logical function, they added different combinations of trigger RNAs—the inputs.
When the input RNA matched up with its corresponding gate RNA, it flipped on the switch, causing the cell to light up.
Their most complex circuit contained five AND gates, five OR gates, and two NOTs—a 12-input ribocomputer that functioned exactly as designed.
That’s quite the achievement. “Everything is interacting with everything else and there are a million ways those interactions could flip the switch on accident,” says RNA researcher Dr. Julies Lucks at Northwestern University.
The specificity is thanks to RNA, the authors explain. Because RNAs bind to others so predictably, we can now design massive libraries of gate and trigger units to mix-and-match into all types of nano-biocomputers.
RNA BioNanobots
Although the technology doesn’t have any immediate applications, the team has high hopes.
For the first time, it’s now possible to massively scale up the process of programming new circuits into living cells. We’ve expanded the library of available biocomponents that can be used to reprogram life’s basic code, the authors say.
What’s more, when freeze-dried onto a piece of tissue paper, RNA keeps very well. We could potentially print RNA toehold switches onto paper that respond to viruses or to tumor cells, the authors say, essentially transforming the technology into highly accurate diagnostic platforms.
But Green’s hopes are even wilder for his RNA-based circuits.
“Because we’re using RNA, a universal molecule of life, we know these interactions can also work in other cells, so our method provides a general strategy that could be ported to other organisms,” he says.
Ultimately, the hope is to program neural network-like capabilities into the body’s other cells.
Imagine cells endowed with circuits capable of performing the kinds of computation the brain does, the authors say.
Perhaps one day, synthetic biology will transform our own cells into fully programmable entities, turning us all into biological cyborgs from the inside. How wild would that be?
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Posted in Human Robots
#430761 How Robots Are Getting Better at Making ...
The multiverse of science fiction is populated by robots that are indistinguishable from humans. They are usually smarter, faster, and stronger than us. They seem capable of doing any job imaginable, from piloting a starship and battling alien invaders to taking out the trash and cooking a gourmet meal.
The reality, of course, is far from fantasy. Aside from industrial settings, robots have yet to meet The Jetsons. The robots the public are exposed to seem little more than over-sized plastic toys, pre-programmed to perform a set of tasks without the ability to interact meaningfully with their environment or their creators.
To paraphrase PayPal co-founder and tech entrepreneur Peter Thiel, we wanted cool robots, instead we got 140 characters and Flippy the burger bot. But scientists are making progress to empower robots with the ability to see and respond to their surroundings just like humans.
Some of the latest developments in that arena were presented this month at the annual Robotics: Science and Systems Conference in Cambridge, Massachusetts. The papers drilled down into topics that ranged from how to make robots more conversational and help them understand language ambiguities to helping them see and navigate through complex spaces.
Improved Vision
Ben Burchfiel, a graduate student at Duke University, and his thesis advisor George Konidaris, an assistant professor of computer science at Brown University, developed an algorithm to enable machines to see the world more like humans.
In the paper, Burchfiel and Konidaris demonstrate how they can teach robots to identify and possibly manipulate three-dimensional objects even when they might be obscured or sitting in unfamiliar positions, such as a teapot that has been tipped over.
The researchers trained their algorithm by feeding it 3D scans of about 4,000 common household items such as beds, chairs, tables, and even toilets. They then tested its ability to identify about 900 new 3D objects just from a bird’s eye view. The algorithm made the right guess 75 percent of the time versus a success rate of about 50 percent for other computer vision techniques.
In an email interview with Singularity Hub, Burchfiel notes his research is not the first to train machines on 3D object classification. How their approach differs is that they confine the space in which the robot learns to classify the objects.
“Imagine the space of all possible objects,” Burchfiel explains. “That is to say, imagine you had tiny Legos, and I told you [that] you could stick them together any way you wanted, just build me an object. You have a huge number of objects you could make!”
The infinite possibilities could result in an object no human or machine might recognize.
To address that problem, the researchers had their algorithm find a more restricted space that would host the objects it wants to classify. “By working in this restricted space—mathematically we call it a subspace—we greatly simplify our task of classification. It is the finding of this space that sets us apart from previous approaches.”
Following Directions
Meanwhile, a pair of undergraduate students at Brown University figured out a way to teach robots to understand directions better, even at varying degrees of abstraction.
The research, led by Dilip Arumugam and Siddharth Karamcheti, addressed how to train a robot to understand nuances of natural language and then follow instructions correctly and efficiently.
“The problem is that commands can have different levels of abstraction, and that can cause a robot to plan its actions inefficiently or fail to complete the task at all,” says Arumugam in a press release.
In this project, the young researchers crowdsourced instructions for moving a virtual robot through an online domain. The space consisted of several rooms and a chair, which the robot was told to manipulate from one place to another. The volunteers gave various commands to the robot, ranging from general (“take the chair to the blue room”) to step-by-step instructions.
The researchers then used the database of spoken instructions to teach their system to understand the kinds of words used in different levels of language. The machine learned to not only follow instructions but to recognize the level of abstraction. That was key to kickstart its problem-solving abilities to tackle the job in the most appropriate way.
The research eventually moved from virtual pixels to a real place, using a Roomba-like robot that was able to respond to instructions within one second 90 percent of the time. Conversely, when unable to identify the specificity of the task, it took the robot 20 or more seconds to plan a task about 50 percent of the time.
One application of this new machine-learning technique referenced in the paper is a robot worker in a warehouse setting, but there are many fields that could benefit from a more versatile machine capable of moving seamlessly between small-scale operations and generalized tasks.
“Other areas that could possibly benefit from such a system include things from autonomous vehicles… to assistive robotics, all the way to medical robotics,” says Karamcheti, responding to a question by email from Singularity Hub.
More to Come
These achievements are yet another step toward creating robots that see, listen, and act more like humans. But don’t expect Disney to build a real-life Westworld next to Toon Town anytime soon.
“I think we’re a long way off from human-level communication,” Karamcheti says. “There are so many problems preventing our learning models from getting to that point, from seemingly simple questions like how to deal with words never seen before, to harder, more complicated questions like how to resolve the ambiguities inherent in language, including idiomatic or metaphorical speech.”
Even relatively verbose chatbots can run out of things to say, Karamcheti notes, as the conversation becomes more complex.
The same goes for human vision, according to Burchfiel.
While deep learning techniques have dramatically improved pattern matching—Google can find just about any picture of a cat—there’s more to human eyesight than, well, meets the eye.
“There are two big areas where I think perception has a long way to go: inductive bias and formal reasoning,” Burchfiel says.
The former is essentially all of the contextual knowledge people use to help them reason, he explains. Burchfiel uses the example of a puddle in the street. People are conditioned or biased to assume it’s a puddle of water rather than a patch of glass, for instance.
“This sort of bias is why we see faces in clouds; we have strong inductive bias helping us identify faces,” he says. “While it sounds simple at first, it powers much of what we do. Humans have a very intuitive understanding of what they expect to see, [and] it makes perception much easier.”
Formal reasoning is equally important. A machine can use deep learning, in Burchfiel’s example, to figure out the direction any river flows once it understands that water runs downhill. But it’s not yet capable of applying the sort of human reasoning that would allow us to transfer that knowledge to an alien setting, such as figuring out how water moves through a plumbing system on Mars.
“Much work was done in decades past on this sort of formal reasoning… but we have yet to figure out how to merge it with standard machine-learning methods to create a seamless system that is useful in the actual physical world.”
Robots still have a lot to learn about being human, which should make us feel good that we’re still by far the most complex machines on the planet.
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Posted in Human Robots