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#434792 Extending Human Longevity With ...
Lizards can regrow entire limbs. Flatworms, starfish, and sea cucumbers regrow entire bodies. Sharks constantly replace lost teeth, often growing over 20,000 teeth throughout their lifetimes. How can we translate these near-superpowers to humans?
The answer: through the cutting-edge innovations of regenerative medicine.
While big data and artificial intelligence transform how we practice medicine and invent new treatments, regenerative medicine is about replenishing, replacing, and rejuvenating our physical bodies.
In Part 5 of this blog series on Longevity and Vitality, I detail three of the regenerative technologies working together to fully augment our vital human organs.
Replenish: Stem cells, the regenerative engine of the body
Replace: Organ regeneration and bioprinting
Rejuvenate: Young blood and parabiosis
Let’s dive in.
Replenish: Stem Cells – The Regenerative Engine of the Body
Stem cells are undifferentiated cells that can transform into specialized cells such as heart, neurons, liver, lung, skin and so on, and can also divide to produce more stem cells.
In a child or young adult, these stem cells are in large supply, acting as a built-in repair system. They are often summoned to the site of damage or inflammation to repair and restore normal function.
But as we age, our supply of stem cells begins to diminish as much as 100- to 10,000-fold in different tissues and organs. In addition, stem cells undergo genetic mutations, which reduce their quality and effectiveness at renovating and repairing your body.
Imagine your stem cells as a team of repairmen in your newly constructed mansion. When the mansion is new and the repairmen are young, they can fix everything perfectly. But as the repairmen age and reduce in number, your mansion eventually goes into disrepair and finally crumbles.
What if you could restore and rejuvenate your stem cell population?
One option to accomplish this restoration and rejuvenation is to extract and concentrate your own autologous adult stem cells from places like your adipose (or fat) tissue or bone marrow.
These stem cells, however, are fewer in number and have undergone mutations (depending on your age) from their original ‘software code.’ Many scientists and physicians now prefer an alternative source, obtaining stem cells from the placenta or umbilical cord, the leftovers of birth.
These stem cells, available in large supply and expressing the undamaged software of a newborn, can be injected into joints or administered intravenously to rejuvenate and revitalize.
Think of these stem cells as chemical factories generating vital growth factors that can help to reduce inflammation, fight autoimmune disease, increase muscle mass, repair joints, and even revitalize skin and grow hair.
Over the last decade, the number of publications per year on stem cell-related research has increased 40x, and the stem cell market is expected to increase to $297 billion by 2022.
Rising research and development initiatives to develop therapeutic options for chronic diseases and growing demand for regenerative treatment options are the most significant drivers of this budding industry.
Biologists led by Kohji Nishida at Osaka University in Japan have discovered a new way to nurture and grow the tissues that make up the human eyeball. The scientists are able to grow retinas, corneas, the eye’s lens, and more, using only a small sample of adult skin.
In a Stanford study, seven of 18 stroke victims who agreed to stem cell treatments showed remarkable motor function improvements. This treatment could work for other neurodegenerative conditions such as Alzheimer’s, Parkinson’s, and ALS.
Doctors from the USC Neurorestoration Center and Keck Medicine of USC injected stem cells into the damaged cervical spine of a recently paralyzed 21-year-old man. Three months later, he showed dramatic improvement in sensation and movement of both arms.
In 2019, doctors in the U.K. cured a patient with HIV for the second time ever thanks to the efficacy of stem cells. After giving the cancer patient (who also had HIV) an allogeneic haematopoietic (e.g. blood) stem cell treatment for his Hodgkin’s lymphoma, the patient went into long-term HIV remission—18 months and counting at the time of the study’s publication.
Replace: Organ Regeneration and 3D Printing
Every 10 minutes, someone is added to the US organ transplant waiting list, totaling over 113,000 people waiting for replacement organs as of January 2019.
Countless more people in need of ‘spare parts’ never make it onto the waiting list. And on average, 20 people die each day while waiting for a transplant.
As a result, 35 percent of all US deaths (~900,000 people) could be prevented or delayed with access to organ replacements.
The excessive demand for donated organs will only intensify as technologies like self-driving cars make the world safer, given that many organ donors result from auto and motorcycle accidents. Safer vehicles mean less accidents and donations.
Clearly, replacement and regenerative medicine represent a massive opportunity.
Organ Entrepreneurs
Enter United Therapeutics CEO, Dr. Martine Rothblatt. A one-time aerospace entrepreneur (she was the founder of Sirius Satellite Radio), Rothblatt changed careers in the 1990s after her daughter developed a rare lung disease.
Her moonshot today is to create an industry of replacement organs. With an initial focus on diseases of the lung, Rothblatt set out to create replacement lungs. To accomplish this goal, her company United Therapeutics has pursued a number of technologies in parallel.
3D Printing Lungs
In 2017, United teamed up with one of the world’s largest 3D printing companies, 3D Systems, to build a collagen bioprinter and is paying another company, 3Scan, to slice up lungs and create detailed maps of their interior.
This 3D Systems bioprinter now operates according to a method called stereolithography. A UV laser flickers through a shallow pool of collagen doped with photosensitive molecules. Wherever the laser lingers, the collagen cures and becomes solid.
Gradually, the object being printed is lowered and new layers are added. The printer can currently lay down collagen at a resolution of around 20 micrometers, but will need to achieve resolution of a micrometer in size to make the lung functional.
Once a collagen lung scaffold has been printed, the next step is to infuse it with human cells, a process called recellularization.
The goal here is to use stem cells that grow on scaffolding and differentiate, ultimately providing the proper functionality. Early evidence indicates this approach can work.
In 2018, Harvard University experimental surgeon Harald Ott reported that he pumped billions of human cells (from umbilical cords and diced lungs) into a pig lung stripped of its own cells. When Ott’s team reconnected it to a pig’s circulation, the resulting organ showed rudimentary function.
Humanizing Pig Lungs
Another of Rothblatt’s organ manufacturing strategies is called xenotransplantation, the idea of transplanting an animal’s organs into humans who need a replacement.
Given the fact that adult pig organs are similar in size and shape to those of humans, United Therapeutics has focused on genetically engineering pigs to allow humans to use their organs. “It’s actually not rocket science,” said Rothblatt in her 2015 TED talk. “It’s editing one gene after another.”
To accomplish this goal, United Therapeutics made a series of investments in companies such as Revivicor Inc. and Synthetic Genomics Inc., and signed large funding agreements with the University of Maryland, University of Alabama, and New York Presbyterian/Columbia University Medical Center to create xenotransplantation programs for new hearts, kidneys, and lungs, respectively. Rothblatt hopes to see human translation in three to four years.
In preparation for that day, United Therapeutics owns a 132-acre property in Research Triangle Park and built a 275,000-square-foot medical laboratory that will ultimately have the capability to annually produce up to 1,000 sets of healthy pig lungs—known as xenolungs—from genetically engineered pigs.
Lung Ex Vivo Perfusion Systems
Beyond 3D printing and genetically engineering pig lungs, Rothblatt has already begun implementing a third near-term approach to improve the supply of lungs across the US.
Only about 30 percent of potential donor lungs meet transplant criteria in the first place; of those, only about 85 percent of those are usable once they arrive at the surgery center. As a result, nearly 75 percent of possible lungs never make it to the recipient in need.
What if these lungs could be rejuvenated? This concept informs Dr. Rothblatt’s next approach.
In 2016, United Therapeutics invested $41.8 million in TransMedics Inc., an Andover, Massachusetts company that develops ex vivo perfusion systems for donor lungs, hearts, and kidneys.
The XVIVO Perfusion System takes marginal-quality lungs that initially failed to meet transplantation standard-of-care criteria and perfuses and ventilates them at normothermic conditions, providing an opportunity for surgeons to reassess transplant suitability.
Rejuvenate Young Blood and Parabiosis
In HBO’s parody of the Bay Area tech community, Silicon Valley, one of the episodes (Season 4, Episode 5) is named “The Blood Boy.”
In this installment, tech billionaire Gavin Belson (Matt Ross) is meeting with Richard Hendricks (Thomas Middleditch) and his team, speaking about the future of the decentralized internet. A young, muscled twenty-something disrupts the meeting when he rolls in a transfusion stand and silently hooks an intravenous connection between himself and Belson.
Belson then introduces the newcomer as his “transfusion associate” and begins to explain the science of parabiosis: “Regular transfusions of the blood of a younger physically fit donor can significantly retard the aging process.”
While the sitcom is fiction, that science has merit, and the scenario portrayed in the episode is already happening today.
On the first point, research at Stanford and Harvard has demonstrated that older animals, when transfused with the blood of young animals, experience regeneration across many tissues and organs.
The opposite is also true: young animals, when transfused with the blood of older animals, experience accelerated aging. But capitalizing on this virtual fountain of youth has been tricky.
Ambrosia
One company, a San Francisco-based startup called Ambrosia, recently commenced one of the trials on parabiosis. Their protocol is simple: Healthy participants aged 35 and older get a transfusion of blood plasma from donors under 25, and researchers monitor their blood over the next two years for molecular indicators of health and aging.
Ambrosia’s founder Jesse Karmazin became interested in launching a company around parabiosis after seeing impressive data from animals and studies conducted abroad in humans: In one trial after another, subjects experience a reversal of aging symptoms across every major organ system. “The effects seem to be almost permanent,” he said. “It’s almost like there’s a resetting of gene expression.”
Infusing your own cord blood stem cells as you age may have tremendous longevity benefits. Following an FDA press release in February 2019, Ambrosia halted its consumer-facing treatment after several months of operation.
Understandably, the FDA raised concerns about the practice of parabiosis because to date, there is a marked lack of clinical data to support the treatment’s effectiveness.
Elevian
On the other end of the reputability spectrum is a startup called Elevian, spun out of Harvard University. Elevian is approaching longevity with a careful, scientifically validated strategy. (Full Disclosure: I am both an advisor to and investor in Elevian.)
CEO Mark Allen, MD, is joined by a dozen MDs and Ph.Ds out of Harvard. Elevian’s scientific founders started the company after identifying specific circulating factors that may be responsible for the “young blood” effect.
One example: A naturally occurring molecule known as “growth differentiation factor 11,” or GDF11, when injected into aged mice, reproduces many of the regenerative effects of young blood, regenerating heart, brain, muscles, lungs, and kidneys.
More specifically, GDF11 supplementation reduces age-related cardiac hypertrophy, accelerates skeletal muscle repair, improves exercise capacity, improves brain function and cerebral blood flow, and improves metabolism.
Elevian is developing a number of therapeutics that regulate GDF11 and other circulating factors. The goal is to restore our body’s natural regenerative capacity, which Elevian believes can address some of the root causes of age-associated disease with the promise of reversing or preventing many aging-related diseases and extending the healthy lifespan.
Conclusion
In 1992, futurist Leland Kaiser coined the term “regenerative medicine”:
“A new branch of medicine will develop that attempts to change the course of chronic disease and in many instances will regenerate tired and failing organ systems.”
Since then, the powerful regenerative medicine industry has grown exponentially, and this rapid growth is anticipated to continue.
A dramatic extension of the human healthspan is just over the horizon. Soon, we’ll all have the regenerative superpowers previously relegated to a handful of animals and comic books.
What new opportunities open up when anybody, anywhere, and at anytime can regenerate, replenish, and replace entire organs and metabolic systems on command?
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#433852 How Do We Teach Autonomous Cars To Drive ...
Autonomous vehicles can follow the general rules of American roads, recognizing traffic signals and lane markings, noticing crosswalks and other regular features of the streets. But they work only on well-marked roads that are carefully scanned and mapped in advance.
Many paved roads, though, have faded paint, signs obscured behind trees and unusual intersections. In addition, 1.4 million miles of U.S. roads—one-third of the country’s public roadways—are unpaved, with no on-road signals like lane markings or stop-here lines. That doesn’t include miles of private roads, unpaved driveways or off-road trails.
What’s a rule-following autonomous car to do when the rules are unclear or nonexistent? And what are its passengers to do when they discover their vehicle can’t get them where they’re going?
Accounting for the Obscure
Most challenges in developing advanced technologies involve handling infrequent or uncommon situations, or events that require performance beyond a system’s normal capabilities. That’s definitely true for autonomous vehicles. Some on-road examples might be navigating construction zones, encountering a horse and buggy, or seeing graffiti that looks like a stop sign. Off-road, the possibilities include the full variety of the natural world, such as trees down over the road, flooding and large puddles—or even animals blocking the way.
At Mississippi State University’s Center for Advanced Vehicular Systems, we have taken up the challenge of training algorithms to respond to circumstances that almost never happen, are difficult to predict and are complex to create. We seek to put autonomous cars in the hardest possible scenario: driving in an area the car has no prior knowledge of, with no reliable infrastructure like road paint and traffic signs, and in an unknown environment where it’s just as likely to see a cactus as a polar bear.
Our work combines virtual technology and the real world. We create advanced simulations of lifelike outdoor scenes, which we use to train artificial intelligence algorithms to take a camera feed and classify what it sees, labeling trees, sky, open paths and potential obstacles. Then we transfer those algorithms to a purpose-built all-wheel-drive test vehicle and send it out on our dedicated off-road test track, where we can see how our algorithms work and collect more data to feed into our simulations.
Starting Virtual
We have developed a simulator that can create a wide range of realistic outdoor scenes for vehicles to navigate through. The system generates a range of landscapes of different climates, like forests and deserts, and can show how plants, shrubs and trees grow over time. It can also simulate weather changes, sunlight and moonlight, and the accurate locations of 9,000 stars.
The system also simulates the readings of sensors commonly used in autonomous vehicles, such as lidar and cameras. Those virtual sensors collect data that feeds into neural networks as valuable training data.
Simulated desert, meadow and forest environments generated by the Mississippi State University Autonomous Vehicle Simulator. Chris Goodin, Mississippi State University, Author provided.
Building a Test Track
Simulations are only as good as their portrayals of the real world. Mississippi State University has purchased 50 acres of land on which we are developing a test track for off-road autonomous vehicles. The property is excellent for off-road testing, with unusually steep grades for our area of Mississippi—up to 60 percent inclines—and a very diverse population of plants.
We have selected certain natural features of this land that we expect will be particularly challenging for self-driving vehicles, and replicated them exactly in our simulator. That allows us to directly compare results from the simulation and real-life attempts to navigate the actual land. Eventually, we’ll create similar real and virtual pairings of other types of landscapes to improve our vehicle’s capabilities.
A road washout, as seen in real life, left, and in simulation. Chris Goodin, Mississippi State University, Author provided.
Collecting More Data
We have also built a test vehicle, called the Halo Project, which has an electric motor and sensors and computers that can navigate various off-road environments. The Halo Project car has additional sensors to collect detailed data about its actual surroundings, which can help us build virtual environments to run new tests in.
The Halo Project car can collect data about driving and navigating in rugged terrain. Beth Newman Wynn, Mississippi State University, Author provided.
Two of its lidar sensors, for example, are mounted at intersecting angles on the front of the car so their beams sweep across the approaching ground. Together, they can provide information on how rough or smooth the surface is, as well as capturing readings from grass and other plants and items on the ground.
Lidar beams intersect, scanning the ground in front of the vehicle. Chris Goodin, Mississippi State University, Author provided
We’ve seen some exciting early results from our research. For example, we have shown promising preliminary results that machine learning algorithms trained on simulated environments can be useful in the real world. As with most autonomous vehicle research, there is still a long way to go, but our hope is that the technologies we’re developing for extreme cases will also help make autonomous vehicles more functional on today’s roads.
Matthew Doude, Associate Director, Center for Advanced Vehicular Systems; Ph.D. Student in Industrial and Systems Engineering, Mississippi State University; Christopher Goodin, Assistant Research Professor, Center for Advanced Vehicular Systems, Mississippi State University, and Daniel Carruth, Assistant Research Professor and Associate Director for Human Factors and Advanced Vehicle System, Center for Advanced Vehicular Systems, Mississippi State University
This article is republished from The Conversation under a Creative Commons license. Read the original article.
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#428053 Omnidirectional Mobile Robot Has Just ...
Spherical Induction Motor Eliminates Robot’s Mechanical Drive System
PITTSBURGH— More than a decade ago, Ralph Hollis invented the ballbot, an elegantly simple robot whose tall, thin body glides atop a sphere slightly smaller than a bowling ball. The latest version, called SIMbot, has an equally elegant motor with just one moving part: the ball.
The only other active moving part of the robot is the body itself.
The spherical induction motor (SIM) invented by Hollis, a research professor in Carnegie Mellon University’s Robotics Institute, and Masaaki Kumagai, a professor of engineering at Tohoku Gakuin University in Tagajo, Japan, eliminates the mechanical drive systems that each used on previous ballbots. Because of this extreme mechanical simplicity, SIMbot requires less routine maintenance and is less likely to suffer mechanical failures.
The new motor can move the ball in any direction using only electronic controls. These movements keep SIMbot’s body balanced atop the ball.
Early comparisons between SIMbot and a mechanically driven ballbot suggest the new robot is capable of similar speed — about 1.9 meters per second, or the equivalent of a very fast walk — but is not yet as efficient, said Greg Seyfarth, a former member of Hollis’ lab who recently completed his master’s degree in robotics.
Induction motors are nothing new; they use magnetic fields to induce electric current in the motor’s rotor, rather than through an electrical connection. What is new here is that the rotor is spherical and, thanks to some fancy math and advanced software, can move in any combination of three axes, giving it omnidirectional capability. In contrast to other attempts to build a SIM, the design by Hollis and Kumagai enables the ball to turn all the way around, not just move back and forth a few degrees.
Though Hollis said it is too soon to compare the cost of the experimental motor with conventional motors, he said long-range trends favor the technologies at its heart.
“This motor relies on a lot of electronics and software,” he explained. “Electronics and software are getting cheaper. Mechanical systems are not getting cheaper, or at least not as fast as electronics and software are.”
SIMbot’s mechanical simplicity is a significant advance for ballbots, a type of robot that Hollis maintains is ideally suited for working with people in human environments. Because the robot’s body dynamically balances atop the motor’s ball, a ballbot can be as tall as a person, but remain thin enough to move through doorways and in between furniture. This type of robot is inherently compliant, so people can simply push it out of the way when necessary. Ballbots also can perform tasks such as helping a person out of a chair, helping to carry parcels and physically guiding a person.
Until now, moving the ball to maintain the robot’s balance has relied on mechanical means. Hollis’ ballbots, for instance, have used an “inverse mouse ball” method, in which four motors actuate rollers that press against the ball so that it can move in any direction across a floor, while a fifth motor controls the yaw motion of the robot itself.
“But the belts that drive the rollers wear out and need to be replaced,” said Michael Shomin, a Ph.D. student in robotics. “And when the belts are replaced, the system needs to be recalibrated.” He said the new motor’s solid-state system would eliminate that time-consuming process.
The rotor of the spherical induction motor is a precisely machined hollow iron ball with a copper shell. Current is induced in the ball with six laminated steel stators, each with three-phase wire windings. The stators are positioned just next to the ball and are oriented slightly off vertical.
The six stators generate travelling magnetic waves in the ball, causing the ball to move in the direction of the wave. The direction of the magnetic waves can be steered by altering the currents in the stators.
Hollis and Kumagai jointly designed the motor. Ankit Bhatia, a Ph.D. student in robotics, and Olaf Sassnick, a visiting scientist from Salzburg University of Applied Sciences, adapted it for use in ballbots.
Getting rid of the mechanical drive eliminates a lot of the friction of previous ballbot models, but virtually all friction could be eliminated by eventually installing an air bearing, Hollis said. The robot body would then be separated from the motor ball with a cushion of air, rather than passive rollers.
“Even without optimizing the motor’s performance, SIMbot has demonstrated impressive performance,” Hollis said. “We expect SIMbot technology will make ballbots more accessible and more practical for wide adoption.”
The National Science Foundation and, in Japan, Grants-in-Aid for Scientific Research (KAKENHI) supported this research. A report on the work was presented at the May IEEE International Conference on Robotics and Automation in Stockholm, Sweden.
Video by: Carnegie Mellon University
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About Carnegie Mellon University: Carnegie Mellon (www.cmu.edu) is a private, internationally ranked research university with programs in areas ranging from science, technology and business, to public policy, the humanities and the arts. More than 13,000 students in the university’s seven schools and colleges benefit from a small student-to-faculty ratio and an education characterized by its focus on creating and implementing solutions for real problems, interdisciplinary collaboration and innovation.
Communications Department
Carnegie Mellon University
5000 Forbes Ave.
Pittsburgh, PA 15213
412-268-2900
Fax: 412-268-6929
Contact: Byron Spice For immediate release:
412-268-9068 October 4, 2016
bspice@cs.cmu.edu
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