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Human brain maps are a dime a dozen these days. Maps that detail neurons in a certain region. Maps that draw out functional connections between those cells. Maps that dive deeper into gene expression. Or even meta-maps that combine all of the above.
But have you ever wondered: how well do those maps represent my brain? After all, no two brains are alike. And if we’re ever going to reverse-engineer the brain as a computer simulation—as Europe’s Human Brain Project is trying to do—shouldn’t we ask whose brain they’re hoping to simulate?
Enter a new kind of map: the Julich-Brain, a probabilistic map of human brains that accounts for individual differences using a computational framework. Rather than generating a static PDF of a brain map, the Julich-Brain atlas is also dynamic, in that it continuously changes to incorporate more recent brain mapping results. So far, the map has data from over 24,000 thinly sliced sections from 23 postmortem brains covering most years of adulthood at the cellular level. But the atlas can also continuously adapt to progress in mapping technologies to aid brain modeling and simulation, and link to other atlases and alternatives.
In other words, rather than “just another” human brain map, the Julich-Brain atlas is its own neuromapping API—one that could unite previous brain-mapping efforts with more modern methods.
“It is exciting to see how far the combination of brain research and digital technologies has progressed,” said Dr. Katrin Amunts of the Institute of Neuroscience and Medicine at Research Centre Jülich in Germany, who spearheaded the study.
The Old Dogma
The Julich-Brain atlas embraces traditional brain-mapping while also yanking the field into the 21st century.
First, the new atlas includes the brain’s cytoarchitecture, or how brain cells are organized. As brain maps go, these kinds of maps are the oldest and most fundamental. Rather than exploring how neurons talk to each other functionally—which is all the rage these days with connectome maps—cytoarchitecture maps draw out the physical arrangement of neurons.
Like a census, these maps literally capture how neurons are distributed in the brain, what they look like, and how they layer within and between different brain regions.
Because neurons aren’t packed together the same way between different brain regions, this provides a way to parse the brain into areas that can be further studied. When we say the brain’s “memory center,” the hippocampus, or the emotion center, the “amygdala,” these distinctions are based on cytoarchitectural maps.
Some may call this type of mapping “boring.” But cytoarchitecture maps form the very basis of any sort of neuroscience understanding. Like hand-drawn maps from early explorers sailing to the western hemisphere, these maps provide the brain’s geographical patterns from which we try to decipher functional connections. If brain regions are cities, then cytoarchitecture maps attempt to show trading or other “functional” activities that occur in the interlinking highways.
You might’ve heard of the most common cytoarchitecture map used today: the Brodmann map from 1909 (yup, that old), which divided the brain into classical regions based on the cells’ morphology and location. The map, while impactful, wasn’t able to account for brain differences between people. More recent brain-mapping technologies have allowed us to dig deeper into neuronal differences and divide the brain into more regions—180 areas in the cortex alone, compared with 43 in the original Brodmann map.
The new study took inspiration from that age-old map and transformed it into a digital ecosystem.
A Living Atlas
Work began on the Julich-Brain atlas in the mid-1990s, with a little help from the crowd.
The preparation of human tissue and its microstructural mapping, analysis, and data processing is incredibly labor-intensive, the authors lamented, making it impossible to do for the whole brain at high resolution in just one lab. To build their “Google Earth” for the brain, the team hooked up with EBRAINS, a shared computing platform set up by the Human Brain Project to promote collaboration between neuroscience labs in the EU.
First, the team acquired MRI scans of 23 postmortem brains, sliced the brains into wafer-thin sections, and scanned and digitized them. They corrected distortions from the chopping using data from the MRI scans and then lined up neurons in consecutive sections—picture putting together a 3D puzzle—to reconstruct the whole brain. Overall, the team had to analyze 24,000 brain sections, which prompted them to build a computational management system for individual brain sections—a win, because they could now track individual donor brains too.
Their method was quite clever. They first mapped their results to a brain template from a single person, called the MNI-Colin27 template. Because the reference brain was extremely detailed, this allowed the team to better figure out the location of brain cells and regions in a particular anatomical space.
However, MNI-Colin27’s brain isn’t your or my brain—or any of the brains the team analyzed. To dilute any of Colin’s potential brain quirks, the team also mapped their dataset onto an “average brain,” dubbed the ICBM2009c (catchy, I know).
This step allowed the team to “standardize” their results with everything else from the Human Connectome Project and the UK Biobank, kind of like adding their Google Maps layer to the existing map. To highlight individual brain differences, the team overlaid their dataset on existing ones, and looked for differences in the cytoarchitecture.
The microscopic architecture of neurons change between two areas (dotted line), forming the basis of different identifiable brain regions. To account for individual differences, the team also calculated a probability map (right hemisphere). Image credit: Forschungszentrum Juelich / Katrin Amunts
Based on structure alone, the brains were both remarkably different and shockingly similar at the same time. For example, the cortexes—the outermost layer of the brain—were physically different across donor brains of different age and sex. The region especially divergent between people was Broca’s region, which is traditionally linked to speech production. In contrast, parts of the visual cortex were almost identical between the brains.
The Brain-Mapping Future
Rather than relying on the brain’s visible “landmarks,” which can still differ between people, the probabilistic map is far more precise, the authors said.
What’s more, the map could also pool yet unmapped regions in the cortex—about 30 percent or so—into “gap maps,” providing neuroscientists with a better idea of what still needs to be understood.
“New maps are continuously replacing gap maps with progress in mapping while the process is captured and documented … Consequently, the atlas is not static but rather represents a ‘living map,’” the authors said.
Thanks to its structurally-sound architecture down to individual cells, the atlas can contribute to brain modeling and simulation down the line—especially for personalized brain models for neurological disorders such as seizures. Researchers can also use the framework for other species, and they can even incorporate new data-crunching processors into the workflow, such as mapping brain regions using artificial intelligence.
Fundamentally, the goal is to build shared resources to better understand the brain. “[These atlases] help us—and more and more researchers worldwide—to better understand the complex organization of the brain and to jointly uncover how things are connected,” the authors said.
Image credit: Richard Watts, PhD, University of Vermont and Fair Neuroimaging Lab, Oregon Health and Science University Continue reading
OpenAI’s Latest Breakthrough Is Astonishingly Powerful, But Still Fighting Its Flaws
James Vincent | The Verge
“What makes GPT-3 amazing, they say, is not that it can tell you that the capital of Paraguay is Asunción (it is) or that 466 times 23.5 is 10,987 (it’s not), but that it’s capable of answering both questions and many more beside simply because it was trained on more data for longer than other programs. If there’s one thing we know that the world is creating more and more of, it’s data and computing power, which means GPT-3’s descendants are only going to get more clever.”
I Tried to Live Without the Tech Giants. It Was Impossible.
Kashmir Hill | The New York Times
“Critics of the big tech companies are often told, ‘If you don’t like the company, don’t use its products.’ My takeaway from the experiment was that it’s not possible to do that. It’s not just the products and services branded with the big tech giant’s name. It’s that these companies control a thicket of more obscure products and services that are hard to untangle from tools we rely on for everything we do, from work to getting from point A to point B.”
Meet the Engineer Who Let a Robot Barber Shave Him With a Straight Razor
Luke Dormehl | Digital Trends
“No, it’s not some kind of lockdown-induced barber startup or a Jackass-style stunt. Instead, Whitney, assistant professor of mechanical and industrial engineering at Northeastern University School of Engineering, was interested in straight-razor shaving as a microcosm for some of the big challenges that robots have faced in the past (such as their jerky, robotic movement) and how they can now be solved.”
Can Trees Live Forever? New Kindling in an Immortal Debate
Cara Giaimo | The New York Times
“Even if a scientist dedicated her whole career to very old trees, she would be able to follow her research subjects for only a small percentage of their lives. And a long enough multigenerational study might see its own methods go obsolete. For these reasons, Dr. Munné-Bosch thinks we will never prove’ whether long-lived trees experience senescence…”
There’s No Such Thing as Family Secrets in the Age of 23andMe
Caitlin Harrington | Wired
“…technology has a way of creating new consequences for old decisions. Today, some 30 million people have taken consumer DNA tests, a threshold experts have called a tipping point. People conceived through donor insemination are matching with half-siblings, tracking down their donors, forming networks and advocacy organizations.”
The Problems AI Has Today Go Back Centuries
Karen Hao | MIT Techology Review
“In 2018, just as the AI field was beginning to reckon with problems like algorithmic discrimination, [Shakir Mohamed, a South African AI researcher at DeepMind], penned a blog post with his initial thoughts. In it he called on researchers to ‘decolonise artificial intelligence’—to reorient the field’s work away from Western hubs like Silicon Valley and engage new voices, cultures, and ideas for guiding the technology’s development.”
AI-Generated Text Is the Scariest Deepfake of All
Renee DiResta | Wired
“In the future, deepfake videos and audiofakes may well be used to create distinct, sensational moments that commandeer a press cycle, or to distract from some other, more organic scandal. But undetectable textfakes—masked as regular chatter on Twitter, Facebook, Reddit, and the like—have the potential to be far more subtle, far more prevalent, and far more sinister.”
Image credit: Adrien Olichon / Unsplash Continue reading
When Deep Blue defeated world chess champion Garry Kasparov in 1997, it may have seemed artificial intelligence had finally arrived. A computer had just taken down one of the top chess players of all time. But it wasn’t to be.
Though Deep Blue was meticulously programmed top-to-bottom to play chess, the approach was too labor-intensive, too dependent on clear rules and bounded possibilities to succeed at more complex games, let alone in the real world. The next revolution would take a decade and a half, when vastly more computing power and data revived machine learning, an old idea in artificial intelligence just waiting for the world to catch up.
Today, machine learning dominates, mostly by way of a family of algorithms called deep learning, while symbolic AI, the dominant approach in Deep Blue’s day, has faded into the background.
Key to deep learning’s success is the fact the algorithms basically write themselves. Given some high-level programming and a dataset, they learn from experience. No engineer anticipates every possibility in code. The algorithms just figure it.
Now, Alphabet’s DeepMind is taking this automation further by developing deep learning algorithms that can handle programming tasks which have been, to date, the sole domain of the world’s top computer scientists (and take them years to write).
In a paper recently published on the pre-print server arXiv, a database for research papers that haven’t been peer reviewed yet, the DeepMind team described a new deep reinforcement learning algorithm that was able to discover its own value function—a critical programming rule in deep reinforcement learning—from scratch.
Surprisingly, the algorithm was also effective beyond the simple environments it trained in, going on to play Atari games—a different, more complicated task—at a level that was, at times, competitive with human-designed algorithms and achieving superhuman levels of play in 14 games.
DeepMind says the approach could accelerate the development of reinforcement learning algorithms and even lead to a shift in focus, where instead of spending years writing the algorithms themselves, researchers work to perfect the environments in which they train.
Pavlov’s Digital Dog
First, a little background.
Three main deep learning approaches are supervised, unsupervised, and reinforcement learning.
The first two consume huge amounts of data (like images or articles), look for patterns in the data, and use those patterns to inform actions (like identifying an image of a cat). To us, this is a pretty alien way to learn about the world. Not only would it be mind-numbingly dull to review millions of cat images, it’d take us years or more to do what these programs do in hours or days. And of course, we can learn what a cat looks like from just a few examples. So why bother?
While supervised and unsupervised deep learning emphasize the machine in machine learning, reinforcement learning is a bit more biological. It actually is the way we learn. Confronted with several possible actions, we predict which will be most rewarding based on experience—weighing the pleasure of eating a chocolate chip cookie against avoiding a cavity and trip to the dentist.
In deep reinforcement learning, algorithms go through a similar process as they take action. In the Atari game Breakout, for instance, a player guides a paddle to bounce a ball at a ceiling of bricks, trying to break as many as possible. When playing Breakout, should an algorithm move the paddle left or right? To decide, it runs a projection—this is the value function—of which direction will maximize the total points, or rewards, it can earn.
Move by move, game by game, an algorithm combines experience and value function to learn which actions bring greater rewards and improves its play, until eventually, it becomes an uncanny Breakout player.
Learning to Learn (Very Meta)
So, a key to deep reinforcement learning is developing a good value function. And that’s difficult. According to the DeepMind team, it takes years of manual research to write the rules guiding algorithmic actions—which is why automating the process is so alluring. Their new Learned Policy Gradient (LPG) algorithm makes solid progress in that direction.
LPG trained in a number of toy environments. Most of these were “gridworlds”—literally two-dimensional grids with objects in some squares. The AI moves square to square and earns points or punishments as it encounters objects. The grids vary in size, and the distribution of objects is either set or random. The training environments offer opportunities to learn fundamental lessons for reinforcement learning algorithms.
Only in LPG’s case, it had no value function to guide that learning.
Instead, LPG has what DeepMind calls a “meta-learner.” You might think of this as an algorithm within an algorithm that, by interacting with its environment, discovers both “what to predict,” thereby forming its version of a value function, and “how to learn from it,” applying its newly discovered value function to each decision it makes in the future.
Prior work in the area has had some success, but according to DeepMind, LPG is the first algorithm to discover reinforcement learning rules from scratch and to generalize beyond training. The latter was particularly surprising because Atari games are so different from the simple worlds LPG trained in—that is, it had never seen anything like an Atari game.
Time to Hand Over the Reins? Not Just Yet
LPG is still behind advanced human-designed algorithms, the researchers said. But it outperformed a human-designed benchmark in training and even some Atari games, which suggests it isn’t strictly worse, just that it specializes in some environments.
This is where there’s room for improvement and more research.
The more environments LPG saw, the more it could successfully generalize. Intriguingly, the researchers speculate that with enough well-designed training environments, the approach might yield a general-purpose reinforcement learning algorithm.
At the least, though, they say further automation of algorithm discovery—that is, algorithms learning to learn—will accelerate the field. In the near term, it can help researchers more quickly develop hand-designed algorithms. Further out, as self-discovered algorithms like LPG improve, engineers may shift from manually developing the algorithms themselves to building the environments where they learn.
Deep learning long ago left Deep Blue in the dust at games. Perhaps algorithms learning to learn will be a winning strategy in the real world too.
Image credit: Mike Szczepanski / Unsplash Continue reading
The causes of aging are extremely complex and unclear. But with longevity clinical trials increasing, more answers—and questions—are emerging than ever before.
With the dramatic demonetization of genome reading and editing over the past decade, and Big Pharma, startups, and the FDA starting to face aging as a disease, we are starting to turn those answers into practical ways to extend our healthspan.
In this article, I’ll explore how genome sequencing and editing, along with new classes of anti-aging drugs, are augmenting our biology to further extend our healthy lives.
Genome Sequencing and Editing
Your genome is the software that runs your body. A sequence of 3.2 billion letters makes you “you.” These base pairs of A’s, T’s, C’s, and G’s determine your hair color, your height, your personality, your propensity for disease, your lifespan, and so on.
Until recently, it’s been very difficult to rapidly and cheaply “read” these letters—and even more difficult to understand what they mean. Since 2001, the cost to sequence a whole human genome has plummeted exponentially, outpacing Moore’s Law threefold. From an initial cost of $3.7 billion, it dropped to $10 million in 2006, and to $1,500 in 2015.
Today, the cost of genome sequencing has dropped below $600, and according to Illumina, the world’s leading sequencing company, the process will soon cost about $100 and take about an hour to complete.
This represents one of the most powerful and transformative technology revolutions in healthcare. When we understand your genome, we’ll be able to understand how to optimize “you.”
We’ll know the perfect foods, the perfect drugs, the perfect exercise regimen, and the perfect supplements, just for you.
We’ll understand what microbiome types, or gut flora, are ideal for you (more on this in a later article).
We’ll accurately predict how specific sedatives and medicines will impact you.
We’ll learn which diseases and illnesses you’re most likely to develop and, more importantly, how to best prevent them from developing in the first place (rather than trying to cure them after the fact).
CRISPR Gene Editing
In addition to reading the human genome, scientists can now edit a genome using a naturally occurring biological system discovered in 1987 called CRISPR/Cas9.
Short for Clustered Regularly Interspaced Short Palindromic Repeats and CRISPR-associated protein 9, the editing system was adapted from a naturally-occurring defense system found in bacteria.
Here’s how it works. The bacteria capture snippets of DNA from invading viruses (or bacteriophage) and use them to create DNA segments known as CRISPR arrays. The CRISPR arrays allow the bacteria to “remember” the viruses (or closely related ones), and defend against future invasions. If the viruses attack again, the bacteria produce RNA segments from the CRISPR arrays to target the viruses’ DNA. The bacteria then use Cas9 to cut the DNA apart, which disables the virus.
Most importantly, CRISPR is cheap, quick, easy to use, and more accurate than all previous gene editing methods. As a result, CRISPR/Cas9 has swept through labs around the world as the way to edit a genome. A short search in the literature will show an exponential rise in the number of CRISPR-related publications and patents.
2018: Filled With CRISPR Breakthroughs
Early results are impressive. Researchers have used CRISPR to genetically engineer cocaine resistance into mice, reverse the gene defect causing Duchenne muscular dystrophy (DMD) in dogs, and reduce genetic deafness in mice.
Already this year, CRISPR-edited immune cells have been shown to successfully kill cancer cells in human patients. Researchers have discovered ways to activate CRISPR with light and use the gene-editing technology to better understand Alzheimer’s disease progression.
With great power comes great responsibility, and the opportunity for moral and ethical dilemmas. In 2015, Chinese scientists sparked global controversy when they first edited human embryo cells in the lab with the goal of modifying genes that would make the child resistant to smallpox, HIV, and cholera. Three years later, in November 2018, researcher He Jiankui informed the world that the first set of CRISPR-engineered female twins had been delivered.
To accomplish his goal, Jiankui deleted a region of a receptor on the surface of white blood cells known as CCR5, introducing a rare, natural genetic variation that makes it more difficult for HIV to infect its favorite target, white blood cells. Because Jiankui forged ethical review documents and misled doctors in the process, he was sentenced to three years in prison and fined $429,000 last December.
Coupled with significant ethical conversations necessary for progress, CRISPR will soon provide us the tools to eliminate diseases, create hardier offspring, produce new environmentally resistant crops, and even wipe out pathogens.
Senolytics, Nutraceuticals, and Pharmaceuticals
Over the arc of your life, the cells in your body divide until they reach what is known as the Hayflick limit, or the number of times a normal human cell population will divide before cell division stops, which is typically about 50 divisions.
What normally follows next is programmed cell death or destruction by the immune system. A very small fraction of cells, however, become senescent cells and evade this fate to linger indefinitely. These lingering cells secrete a potent mix of molecules that triggers chronic inflammation, damages the surrounding tissue structures, and changes the behavior of nearby cells for the worse. Senescent cells appear to be one of the root causes of aging, causing everything from fibrosis and blood vessel calcification to localized inflammatory conditions such as osteoarthritis to diminished lung function.
Fortunately, both the scientific and entrepreneurial communities have begun to work on senolytic therapies, moving the technology for selectively destroying senescent cells out of the laboratory and into a half-dozen startup companies.
Prominent companies in the field include the following:
Unity Biotechnology is developing senolytic medicines to selectively eliminate senescent cells with an initial focus on delivering localized therapy in osteoarthritis, ophthalmology, and pulmonary disease.
Oisin Biotechnologies is pioneering a programmable gene therapy that can destroy cells based on their internal biochemistry.
SIWA Therapeutics is working on an immunotherapy approach to the problem of senescent cells.
In recent years, researchers have identified or designed a handful of senolytic compounds that can curb aging by regulating senescent cells. Two of these drugs that have gained mainstay research traction are rapamycin and metformin.
Originally extracted from bacteria found on Easter Island, rapamycin acts on the m-TOR (mechanistic target of rapamycin) pathway to selectively block a key protein that facilitates cell division. Currently, rapamycin derivatives are widely used for immunosuppression in organ and bone marrow transplants. Research now suggests that use results in prolonged lifespan and enhanced cognitive and immune function.
PureTech Health subsidiary resTORbio (which went public in 2018) is working on a rapamycin-based drug intended to enhance immunity and reduce infection. Their clinical-stage RTB101 drug works by inhibiting part of the mTOR pathway.
Results of the drug’s recent clinical trial include decreased incidence of infection, improved influenza vaccination response, and a 30.6 percent decrease in respiratory tract infection.
Impressive, to say the least.
Metformin is a widely-used generic drug for mitigating liver sugar production in Type 2 diabetes patients. Researchers have found that metformin also reduces oxidative stress and inflammation, which otherwise increase as we age. There is strong evidence that metformin can augment cellular regeneration and dramatically mitigate cellular senescence by reducing both oxidative stress and inflammation.
Over 100 studies registered on ClinicalTrials.gov are currently following up on strong evidence of metformin’s protective effect against cancer.
(3) Nutraceuticals and NAD+
Beyond cellular senescence, certain critical nutrients and proteins tend to decline as a function of age. Nutraceuticals combat aging by supplementing and replenishing these declining nutrient levels.
NAD+ exists in every cell, participating in every process from DNA repair to creating the energy vital for cellular processes. It’s been shown that NAD+ levels decline as we age.
The Elysium Health Basis supplement aims to elevate NAD+ levels in the body to extend one’s lifespan. Elysium’s first clinical study reports that Basis increases NAD+ levels consistently by a sustained 40 percent.
These are just a taste of the tremendous momentum that longevity and aging technology has right now. As artificial intelligence and quantum computing transform how we decode our DNA and how we discover drugs, genetics and pharmaceuticals will become truly personalized.
The next article in this series will demonstrate how artificial intelligence is converging with genetics and pharmaceuticals to transform how we approach longevity, aging, and vitality.
We are edging closer toward a dramatically extended healthspan—where 100 is the new 60. What will you create, where will you explore, and how will you spend your time if you are able to add an additional 40 healthy years to your life?
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This article originally appeared on diamandis.com. Read the original article here.
Image Credit: Arek Socha from Pixabay Continue reading