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#439077 How Scientists Grew Human Muscles in Pig ...
The little pigs bouncing around the lab looked exceedingly normal. Yet their adorable exterior hid a remarkable secret: each piglet carried two different sets of genes. For now, both sets came from their own species. But one day, one of those sets may be human.
The piglets are chimeras—creatures with intermingled sets of genes, as if multiple entities were seamlessly mashed together. Named after the Greek lion-goat-serpent monsters, chimeras may hold the key to an endless supply of human organs and tissues for transplant. The crux is growing these human parts in another animal—one close enough in size and function to our own.
Last week, a team from the University of Minnesota unveiled two mind-bending chimeras. One was joyous little piglets, each propelled by muscles grown from a different pig. Another was pig embryos, transplanted into surrogate pigs, that developed human muscles for more than 20 days.
The study, led by Drs. Mary and Daniel Garry at the University of Minnesota, had a therapeutic point: engineering a brilliant way to replace muscle loss, especially for the muscles around our skeletons that allow us to move and navigate the world. Trauma and injury, such as from firearm wounds or car crashes, can damage muscle tissue beyond the point of repair. Unfortunately, muscles are also stubborn in that donor tissue from cadavers doesn’t usually “take” at the injury site. For now, there are no effective treatments for severe muscle death, called volumetric muscle loss.
The new human-pig hybrids are designed to tackle this problem. Muscle wasting aside, the study also points to a clever “hack” that increases the amount of human tissue inside a growing pig embryo.
If further improved, the technology could “provide an unlimited supply of organs for transplantation,” said Dr. Mary Garry to Inverse. What’s more, because the human tissue can be sourced from patients themselves, the risk of rejection by the immune system is relatively low—even when grown inside a pig.
“The shortage of organs for heart transplantation, vascular grafting, and skeletal muscle is staggering,” said Garry. Human-animal chimeras could have a “seismic impact” that transforms organ transplantation and helps solve the organ shortage crisis.
That is, if society accepts the idea of a semi-humanoid pig.
Wait…But How?
The new study took a page from previous chimera recipes.
The main ingredients and steps go like this: first, you need an embryo that lacks the ability to develop a tissue or organ. This leaves an “empty slot” of sorts that you can fill with another set of genes—pig, human, or even monkey.
Second, you need to fine-tune the recipe so that the embryos “take” the new genes, incorporating them into their bodies as if they were their own. Third, the new genes activate to instruct the growing embryo to make the necessary tissue or organs without harming the overall animal. Finally, the foreign genes need to stay put, without cells migrating to another body part—say, the brain.
Not exactly straightforward, eh? The piglets are technological wonders that mix cutting-edge gene editing with cloning technologies.
The team went for two chimeras: one with two sets of pig genes, the other with a pig and human mix. Both started with a pig embryo that can’t make its own skeletal muscles (those are the muscles surrounding your bones). Using CRISPR, the gene-editing Swiss Army Knife, they snipped out three genes that are absolutely necessary for those muscles to develop. Like hitting a bullseye with three arrows simultaneously, it’s already a technological feat.
Here’s the really clever part: the muscles around your bones have a slightly different genetic makeup than the ones that line your blood vessels or the ones that pump your heart. While the resulting pig embryos had severe muscle deformities as they developed, their hearts beat as normal. This means the gene editing cut only impacted skeletal muscles.
Then came step two: replacing the missing genes. Using a microneedle, the team injected a fertilized and slightly developed pig egg—called a blastomere—into the embryo. If left on its natural course, a blastomere eventually develops into another embryo. This step “smashes” the two sets of genes together, with the newcomer filling the muscle void. The hybrid embryo was then placed into a surrogate, and roughly four months later, chimeric piglets were born.
Equipped with foreign DNA, the little guys nevertheless seemed totally normal, nosing around the lab and running everywhere without obvious clumsy stumbles. Under the microscope, their “xenomorph” muscles were indistinguishable from run-of-the-mill average muscle tissue—no signs of damage or inflammation, and as stretchy and tough as muscles usually are. What’s more, the foreign DNA seemed to have only developed into muscles, even though they were prevalent across the body. Extensive fishing experiments found no trace of the injected set of genes inside blood vessels or the brain.
A Better Human-Pig Hybrid
Confident in their recipe, the team next repeated the experiment with human cells, with a twist. Instead of using controversial human embryonic stem cells, which are obtained from aborted fetuses, they relied on induced pluripotent stem cells (iPSCs). These are skin cells that have been reverted back into a stem cell state.
Unlike previous attempts at making human chimeras, the team then scoured the genetic landscape of how pig and human embryos develop to find any genetic “brakes” that could derail the process. One gene, TP53, stood out, which was then promptly eliminated with CRISPR.
This approach provides a way for future studies to similarly increase the efficiency of interspecies chimeras, the team said.
The human-pig embryos were then carefully grown inside surrogate pigs for less than a month, and extensively analyzed. By day 20, the hybrids had already grown detectable human skeletal muscle. Similar to the pig-pig chimeras, the team didn’t detect any signs that the human genes had sprouted cells that would eventually become neurons or other non-muscle cells.
For now, human-animal chimeras are not allowed to grow to term, in part to stem the theoretical possibility of engineering humanoid hybrid animals (shudder). However, a sentient human-pig chimera is something that the team specifically addressed. Through multiple experiments, they found no trace of human genes in the embryos’ brain stem cells 20 and 27 days into development. Similarly, human donor genes were absent in cells that would become the hybrid embryos’ reproductive cells.
Despite bioethical quandaries and legal restrictions, human-animal chimeras have taken off, both as a source of insight into human brain development and a well of personalized organs and tissues for transplant. In 2019, Japan lifted its ban on developing human brain cells inside animal embryos, as well as the term limit—to global controversy. There’s also the question of animal welfare, given that hybrid clones will essentially become involuntary organ donors.
As the debates rage on, scientists are nevertheless pushing the limits of human-animal chimeras, while treading as carefully as possible.
“Our data…support the feasibility of the generation of these interspecies chimeras, which will serve as a model for translational research or, one day, as a source for xenotransplantation,” the team said.
Image Credit: Christopher Carson on Unsplash Continue reading
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#438553 New Drone Software Handles Motor ...
Good as some drones are becoming at obstacle avoidance, accidents do still happen. And as far as robots go, drones are very much on the fragile side of things. Any sort of significant contact between a drone and almost anything else usually results in a catastrophic, out-of-control spin followed by a death plunge to the ground. Bad times. Bad, expensive times.
A few years ago, we saw some interesting research into software that can keep the most common drone form factor, the quadrotor, aloft and controllable even after the failure of one motor. The big caveat to that software was that it relied on GPS for state estimation, meaning that without a GPS signal, the drone is unable to get the information it needs to keep itself under control. In a paper recently accepted to RA-L, researchers at the University of Zurich report that they have developed a vision-based system that brings state estimation completely on-board. The upshot: potentially any drone with some software and a camera can keep itself safe even under the most challenging conditions.
A few years ago, we wrote about first author Sihao Sun’s work on high speed controlled flight of a quadrotor with a non-functional motor. But that innovation relied on an external motion capture system. Since then, Sun has moved from Tu Delft to Davide Scaramuzza’s lab at UZH, and it looks like he’s been able to combine his work on controlled spinning flight with the Robotics and Perception Group’s expertise in vision. Now, a downward-facing camera is all it takes for a spinning drone to remain stable and controllable:
Remember, this software isn’t just about guarding against motor failure. Drone motors themselves don’t just up and fail all that often, either with respect to their software or hardware. But they do represent the most likely point of failure for any drone, usually because when you run into something, what ultimately causes your drone to crash is damage to a motor or a propeller that causes loss of control.
The reason that earlier solutions relied on GPS was because the spinning drone needs a method of state estimation—that is, in order to be closed-loop controllable, the drone needs to have a reasonable understanding of what its position is and how that position is changing over time. GPS is an easy way to take care of this, but GPS is also an external system that doesn’t work everywhere. Having a state estimation system that’s completely internal to the drone itself is much more fail safe, and Sun got his onboard system to work through visual feature tracking with a downward-facing camera, even as the drone is spinning at over 20 rad/s.
While the system works well enough with a regular downward-facing camera—something that many consumer drones are equipped with for stabilization purposes—replacing it with an event camera (you remember event cameras, right?) makes the performance even better, especially in low light.
For more details on this, including what you’re supposed to do with a rapidly spinning partially disabled quadrotor (as well as what it’ll take to make this a standard feature on consumer hardware), we spoke with Sihao Sun via email.
IEEE Spectrum: what usually happens when a drone spinning this fast lands? Is there any way to do it safely?
Sihao Sun: Our experience shows that we can safely land the drone while it is spinning. When the range sensor measurements are lower than a threshold (around 10 cm, indicating that the drone is close to the ground), we switch off the rotors. During the landing procedure, despite the fast spinning motion, the thrust direction oscillates around the gravity vector, thus the drone touches the ground with its legs without damaging other components.
Can your system handle more than one motor failure?
Yes, the system can also handle the failure of two opposing rotors. However, if two adjacent rotors or more than two rotors fail, our method cannot save the quadrotor. Some research has shown that it is possible to control a quadrotor with only one remaining rotor. But the drone requires a very special inertial property, which is hard to satisfy in real applications.
How different is your system's performance from a similar system that relies on GPS, in a favorable environment?
In a favorable environment, our system outperforms those relying on GPS signals because it obtains better position estimates. Since a damaged quadrotor spins fast, the accelerometer readings are largely affected by centrifugal forces. When the GPS signal is lost or degraded, a drone relying on GPS needs to integrate these biased accelerometer measurements for position estimation, leading to large position estimation errors. Feeding these erroneous estimates to the flight controller can easily crash the drone.
When you say that your solution requires “only onboard sensors and computation,” are those requirements specialized, or would they be generally compatible with the current generation of recreational and commercial quadrotors?
We use an NVIDIA Jetson TX2 to run our solution, which includes two parts: the control algorithm and the vision-based state estimation algorithm. The control algorithm is lightweight; thus, we believe that it is compatible with the current generation of quadrotors. On the other hand, the vision-based state estimation requires relatively more computational resources, which may not be affordable for cheap recreational platforms. But this is not an issue for commercial quadrotors because many of them have more powerful processors than a TX2.
What else can event cameras be used for, in recreational or commercial applications?
Many drone applications can benefit from event cameras, especially those in high-speed or low-light conditions, such as autonomous drone racing, cave exploration, drone delivery during night time, etc. Event cameras also consume very little power, which is a significant advantage for energy-critical missions, such as planetary aerial vehicles for Mars explorations. Regarding space applications, we are currently collaborating with JPL to explore the use of event cameras to address the key limitations of standard cameras for the next Mars helicopter.
[ UZH RPG ] Continue reading
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#437924 How a Software Map of the Entire Planet ...
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“3D map data is the scaffolding of the 21st century.”
–Edward Miller, Founder, Scape Technologies, UK
Covered in cameras, sensors, and a distinctly spaceship looking laser system, Google’s autonomous vehicles were easy to spot when they first hit public roads in 2015. The key hardware ingredient is a spinning laser fixed to the roof, called lidar, which provides the car with a pair of eyes to see the world. Lidar works by sending out beams of light and measuring the time it takes to bounce off objects back to the source. By timing the light’s journey, these depth-sensing systems construct fully 3D maps of their surroundings.
3D maps like these are essentially software copies of the real world. They will be crucial to the development of a wide range of emerging technologies including autonomous driving, drone delivery, robotics, and a fast-approaching future filled with augmented reality.
Like other rapidly improving technologies, lidar is moving quickly through its development cycle. What was an expensive technology on the roof of a well-funded research project is now becoming cheaper, more capable, and readily available to consumers. At some point, lidar will come standard on most mobile devices and is now available to early-adopting owners of the iPhone 12 Pro.
Consumer lidar represents the inevitable shift from wealthy tech companies generating our world’s map data, to a more scalable crowd-sourced approach. To develop the repository for their Street View Maps product, Google reportedly spent $1-2 billion sending cars across continents photographing every street. Compare that to a live-mapping service like Waze, which uses crowd-sourced user data from its millions of users to generate accurate and real-time traffic conditions. Though these maps serve different functions, one is a static, expensive, unchanging map of the world while the other is dynamic, real-time, and constructed by users themselves.
Soon millions of people may be scanning everything from bedrooms to neighborhoods, resulting in 3D maps of significant quality. An online search for lidar room scans demonstrates just how richly textured these three-dimensional maps are compared to anything we’ve had before. With lidar and other depth-sensing systems, we now have the tools to create exact software copies of everywhere and everything on earth.
At some point, likely aided by crowdsourcing initiatives, these maps will become living breathing, real-time representations of the world. Some refer to this idea as a “digital twin” of the planet. In a feature cover story, Kevin Kelly, the cofounder of Wired magazine, calls this concept the “mirrorworld,” a one-to-one software map of everything.
So why is that such a big deal? Take augmented reality as an example.
Of all the emerging industries dependent on such a map, none are more invested in seeing this concept emerge than those within the AR landscape. Apple, for example, is not-so-secretly developing a pair of AR glasses, which they hope will deliver a mainstream turning point for the technology.
For Apple’s AR devices to work as anticipated, they will require virtual maps of the world, a concept AR insiders call the “AR cloud,” which is synonymous with the “mirrorworld” concept. These maps will be two things. First, they will be a tool that creators use to place AR content in very specific locations; like a world canvas to paint on. Second, they will help AR devices both locate and understand the world around them so they can render content in a believable way.
Imagine walking down a street wanting to check the trading hours of a local business. Instead of pulling out your phone to do a tedious search online, you conduct the equivalent of a visual google search simply by gazing at the store. Albeit a trivial example, the AR cloud represents an entirely non-trivial new way of managing how we organize the world’s information. Access to knowledge can be shifted away from the faraway monitors in our pocket, to its relevant real-world location.
Ultimately this describes a blurring of physical and digital infrastructure. Our public and private spaces will thus be comprised equally of both.
No example demonstrates this idea better than Pokémon Go. The game is straightforward enough; users capture virtual characters scattered around the real world. Today, the game relies on traditional GPS technology to place its characters, but GPS is accurate only to within a few meters of a location. For a car navigating on a highway or locating Pikachus in the world, that level of precision is sufficient. For drone deliveries, driverless cars, or placing a Pikachu in a specific location, say on a tree branch in a park, GPS isn’t accurate enough. As astonishing as it may seem, many experimental AR cloud concepts, even entirely mapped cities, are location specific down to the centimeter.
Niantic, the $4 billion publisher behind Pokémon Go, is aggressively working on developing a crowd-sourced approach to building better AR Cloud maps by encouraging their users to scan the world for them. Their recent acquisition of 6D.ai, a mapping software company developed by the University of Oxford’s Victor Prisacariu through his work at Oxford’s Active Vision Lab, indicates Niantic’s ambition to compete with the tech giants in this space.
With 6D.ai’s technology, Niantic is developing the in-house ability to generate their own 3D maps while gaining better semantic understanding of the world. By going beyond just knowing there’s a temporary collection of orange cones in a certain location, for example, the game may one day understand the meaning behind this; that a temporary construction zone means no Pokémon should spawn here to avoid drawing players to this location.
Niantic is not the only company working on this. Many of the big tech firms you would expect have entire teams focused on map data. Facebook, for example, recently acquired the UK-based Scape technologies, a computer vision startup mapping entire cities with centimeter precision.
As our digital maps of the world improve, expect a relentless and justified discussion of privacy concerns as well. How will society react to the idea of a real-time 3D map of their bedroom living on a Facebook or Amazon server? Those horrified by the use of facial recognition AI being used in public spaces are unlikely to find comfort in the idea of a machine-readable world subject to infinite monitoring.
The ability to build high-precision maps of the world could reshape the way we engage with our planet and promises to be one of the biggest technology developments of the next decade. While these maps may stay hidden as behind-the-scenes infrastructure powering much flashier technologies that capture the world’s attention, they will soon prop up large portions of our technological future.
Keep that in mind when a car with no driver is sharing your road.
Image credit: sergio souza / Pexels Continue reading
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#437820 In-Shoe Sensors and Mobile Robots Keep ...
In shoe sensor
Researchers at Stevens Institute of Technology are leveraging some of the newest mechanical and robotic technologies to help some of our oldest populations stay healthy, active, and independent.
Yi Guo, professor of electrical and computer engineering and director of the Robotics and Automation Laboratory, and Damiano Zanotto, assistant professor of mechanical engineering, and director of the Wearable Robotic Systems Laboratory, are collaborating with Ashley Lytle, assistant professor in Stevens’ College of Arts and Letters, and Ashwini K. Rao of Columbia University Medical Center, to combine an assistive mobile robot companion with wearable in-shoe sensors in a system designed to help elderly individuals maintain the balance and motion they need to thrive.
“Balance and motion can be significant issues for this population, and if elderly people fall and experience an injury, they are less likely to stay fit and exercise,” Guo said. “As a consequence, their level of fitness and performance decreases. Our mobile robot companion can help decrease the chances of falling and contribute to a healthy lifestyle by keeping their walking function at a good level.”
The mobile robots are designed to lead walking sessions and using the in-shoe sensors, monitor the user’s gait, indicate issues, and adjust the exercise speed and pace. The initiative is part of a four-year National Science Foundation research project.
“For the first time, we’re integrating our wearable sensing technology with an autonomous mobile robot,” said Zanotto, who worked with elderly people at Columbia University Medical Center for three years before coming to Stevens in 2016. “It’s exciting to be combining these different areas of expertise to leverage the strong points of wearable sensing technology, such as accurately capturing human movement, with the advantages of mobile robotics, such as much larger computational powers.”
The team is developing algorithms that fuse real-time data from smart, unobtrusive, in-shoe sensors and advanced on-board sensors to inform the robot’s navigation protocols and control the way the robot interacts with elderly individuals. It’s a promising way to assist seniors in safely doing walking exercises and maintaining their quality of life.
Bringing the benefits of the lab to life
Guo and Zanotto are working with Lytle, an expert in social and health psychology, to implement a social connectivity capability and make the bi-directional interaction between human and robot even more intuitive, engaging, and meaningful for seniors.
“Especially during COVID, it’s important for elderly people living on their own to connect socially with family and friends,” Zanotto said, “and the robot companion will also offer teleconferencing tools to provide that interaction in an intuitive and transparent way.”
“We want to use the robot for social connectedness, perhaps integrating it with a conversation agent such as Alexa,” Guo added. “The goal is to make it a companion robot that can sense, for example, that you are cooking, or you’re in the living room, and help with things you would do there.”
It’s a powerful example of how abstract concepts can have meaningful real-life benefits.
“As engineers, we tend to work in the lab, trying to optimize our algorithms and devices and technologies,” Zanotto noted, “but at the end of the day, what we do has limited value unless it has impact on real life. It’s fascinating to see how the devices and technologies we’re developing in the lab can be applied to make a difference for real people.”
Maintaining balance in a global pandemic
Although COVID-19 has delayed the planned testing at a senior center in New York City, it has not stopped the team’s progress.
“Although we can’t test on elderly populations yet, our students are still testing in the lab,” Guo said. “This summer and fall, for the first time, the students validated the system’s real-time ability to monitor and assess the dynamic margin of stability during walking—in other words, to evaluate whether the person following the robot is walking normally or has a risk of falling. They’re also designing parameters for the robot to give early warnings and feedback that help the human subjects correct posture and gait issues while walking.”
Those warnings would be literally underfoot, as the in-shoe sensors would pulse like a vibrating cell phone to deliver immediate directional information to the subject.
“We’re not the first to use this vibrotactile stimuli technology, but this application is new,” Zanotto said.
So far, the team has published papers in top robotics publication venues including IEEE Transactions on Neural Systems and Rehabilitation Engineering and the 2020 IEEE International Conference on Robotics and Automation (ICRA). It’s a big step toward realizing the synergies of bringing the technical expertise of engineers to bear on the clinical focus on biometrics—and the real lives of seniors everywhere. Continue reading
Posted in Human Robots