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#434854 New Lifelike Biomaterial Self-Reproduces ...
Life demands flux.
Every living organism is constantly changing: cells divide and die, proteins build and disintegrate, DNA breaks and heals. Life demands metabolism—the simultaneous builder and destroyer of living materials—to continuously upgrade our bodies. That’s how we heal and grow, how we propagate and survive.
What if we could endow cold, static, lifeless robots with the gift of metabolism?
In a study published this month in Science Robotics, an international team developed a DNA-based method that gives raw biomaterials an artificial metabolism. Dubbed DASH—DNA-based assembly and synthesis of hierarchical materials—the method automatically generates “slime”-like nanobots that dynamically move and navigate their environments.
Like humans, the artificial lifelike material used external energy to constantly change the nanobots’ bodies in pre-programmed ways, recycling their DNA-based parts as both waste and raw material for further use. Some “grew” into the shape of molecular double-helixes; others “wrote” the DNA letters inside micro-chips.
The artificial life forms were also rather “competitive”—in quotes, because these molecular machines are not conscious. Yet when pitted against each other, two DASH bots automatically raced forward, crawling in typical slime-mold fashion at a scale easily seen under the microscope—and with some iterations, with the naked human eye.
“Fundamentally, we may be able to change how we create and use the materials with lifelike characteristics. Typically materials and objects we create in general are basically static… one day, we may be able to ‘grow’ objects like houses and maintain their forms and functions autonomously,” said study author Dr. Shogo Hamada to Singularity Hub.
“This is a great study that combines the versatility of DNA nanotechnology with the dynamics of living materials,” said Dr. Job Boekhoven at the Technical University of Munich, who was not involved in the work.
Dissipative Assembly
The study builds on previous ideas on how to make molecular Lego blocks that essentially assemble—and destroy—themselves.
Although the inspiration came from biological metabolism, scientists have long hoped to cut their reliance on nature. At its core, metabolism is just a bunch of well-coordinated chemical reactions, programmed by eons of evolution. So why build artificial lifelike materials still tethered by evolution when we can use chemistry to engineer completely new forms of artificial life?
Back in 2015, for example, a team led by Boekhoven described a way to mimic how our cells build their internal “structural beams,” aptly called the cytoskeleton. The key here, unlike many processes in nature, isn’t balance or equilibrium; rather, the team engineered an extremely unstable system that automatically builds—and sustains—assemblies from molecular building blocks when given an external source of chemical energy.
Sound familiar? The team basically built molecular devices that “die” without “food.” Thanks to the laws of thermodynamics (hey ya, Newton!), that energy eventually dissipates, and the shapes automatically begin to break down, completing an artificial “circle of life.”
The new study took the system one step further: rather than just mimicking synthesis, they completed the circle by coupling the building process with dissipative assembly.
Here, the “assembling units themselves are also autonomously created from scratch,” said Hamada.
DNA Nanobots
The process of building DNA nanobots starts on a microfluidic chip.
Decades of research have allowed researchers to optimize DNA assembly outside the body. With the help of catalysts, which help “bind” individual molecules together, the team found that they could easily alter the shape of the self-assembling DNA bots—which formed fiber-like shapes—by changing the structure of the microfluidic chambers.
Computer simulations played a role here too: through both digital simulations and observations under the microscope, the team was able to identify a few critical rules that helped them predict how their molecules self-assemble while navigating a maze of blocking “pillars” and channels carved onto the microchips.
This “enabled a general design strategy for the DASH patterns,” they said.
In particular, the whirling motion of the fluids as they coursed through—and bumped into—ridges in the chips seems to help the DNA molecules “entangle into networks,” the team explained.
These insights helped the team further develop the “destroying” part of metabolism. Similar to linking molecules into DNA chains, their destruction also relies on enzymes.
Once the team pumped both “generation” and “degeneration” enzymes into the microchips, along with raw building blocks, the process was completely autonomous. The simultaneous processes were so lifelike that the team used a metric commonly used in robotics, finite-state automation, to measure the behavior of their DNA nanobots from growth to eventual decay.
“The result is a synthetic structure with features associated with life. These behaviors include locomotion, self-regeneration, and spatiotemporal regulation,” said Boekhoven.
Molecular Slime Molds
Just witnessing lifelike molecules grow in place like the dance move running man wasn’t enough.
In their next experiments, the team took inspiration from slugs to program undulating movements into their DNA bots. Here, “movement” is actually a sort of illusion: the machines “moved” because their front ends kept regenerating, whereas their back ends degenerated. In essence, the molecular slime was built from linking multiple individual “DNA robot-like” units together: each unit receives a delayed “decay” signal from the head of the slime in a way that allowed the whole artificial “organism” to crawl forward, against the steam of fluid flow.
Here’s the fun part: the team eventually engineered two molecular slime bots and pitted them against each other, Mario Kart-style. In these experiments, the faster moving bot alters the state of its competitor to promote “decay.” This slows down the competitor, allowing the dominant DNA nanoslug to win in a race.
Of course, the end goal isn’t molecular podracing. Rather, the DNA-based bots could easily amplify a given DNA or RNA sequence, making them efficient nano-diagnosticians for viral and other infections.
The lifelike material can basically generate patterns that doctors can directly ‘see’ with their eyes, which makes DNA or RNA molecules from bacteria and viruses extremely easy to detect, the team said.
In the short run, “the detection device with this self-generating material could be applied to many places and help people on site, from farmers to clinics, by providing an easy and accurate way to detect pathogens,” explained Hamaga.
A Futuristic Iron Man Nanosuit?
I’m letting my nerd flag fly here. In Avengers: Infinity Wars, the scientist-engineer-philanthropist-playboy Tony Stark unveiled a nanosuit that grew to his contours when needed and automatically healed when damaged.
DASH may one day realize that vision. For now, the team isn’t focused on using the technology for regenerating armor—rather, the dynamic materials could create new protein assemblies or chemical pathways inside living organisms, for example. The team also envisions adding simple sensing and computing mechanisms into the material, which can then easily be thought of as a robot.
Unlike synthetic biology, the goal isn’t to create artificial life. Rather, the team hopes to give lifelike properties to otherwise static materials.
“We are introducing a brand-new, lifelike material concept powered by its very own artificial metabolism. We are not making something that’s alive, but we are creating materials that are much more lifelike than have ever been seen before,” said lead author Dr. Dan Luo.
“Ultimately, our material may allow the construction of self-reproducing machines… artificial metabolism is an important step toward the creation of ‘artificial’ biological systems with dynamic, lifelike capabilities,” added Hamada. “It could open a new frontier in robotics.”
Image Credit: A timelapse image of DASH, by Jeff Tyson at Cornell University. Continue reading
Posted in Human Robots
#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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Posted in Human Robots
#434701 3 Practical Solutions to Offset ...
In recent years, the media has sounded the alarm about mass job loss to automation and robotics—some studies predict that up to 50 percent of current jobs or tasks could be automated in coming decades. While this topic has received significant attention, much of the press focuses on potential problems without proposing realistic solutions or considering new opportunities.
The economic impacts of AI, robotics, and automation are complex topics that require a more comprehensive perspective to understand. Is universal basic income, for example, the answer? Many believe so, and there are a number of experiments in progress. But it’s only one strategy, and without a sustainable funding source, universal basic income may not be practical.
As automation continues to accelerate, we’ll need a multi-pronged approach to ease the transition. In short, we need to update broad socioeconomic strategies for a new century of rapid progress. How, then, do we plan practical solutions to support these new strategies?
Take history as a rough guide to the future. Looking back, technology revolutions have three themes in common.
First, past revolutions each produced profound benefits to productivity, increasing human welfare. Second, technological innovation and technology diffusion have accelerated over time, each iteration placing more strain on the human ability to adapt. And third, machines have gradually replaced more elements of human work, with human societies adapting by moving into new forms of work—from agriculture to manufacturing to service, for example.
Public and private solutions, therefore, need to be developed to address each of these three components of change. Let’s explore some practical solutions for each in turn.
Figure 1. Technology’s structural impacts in the 21st century. Refer to Appendix I for quantitative charts and technological examples corresponding to the numbers (1-22) in each slice.
Solution 1: Capture New Opportunities Through Aggressive Investment
The rapid emergence of new technology promises a bounty of opportunity for the twenty-first century’s economic winners. This technological arms race is shaping up to be a global affair, and the winners will be determined in part by who is able to build the future economy fastest and most effectively. Both the private and public sectors have a role to play in stimulating growth.
At the country level, several nations have created competitive strategies to promote research and development investments as automation technologies become more mature.
Germany and China have two of the most notable growth strategies. Germany’s Industrie 4.0 plan targets a 50 percent increase in manufacturing productivity via digital initiatives, while halving the resources required. China’s Made in China 2025 national strategy sets ambitious targets and provides subsidies for domestic innovation and production. It also includes building new concept cities, investing in robotics capabilities, and subsidizing high-tech acquisitions abroad to become the leader in certain high-tech industries. For China, specifically, tech innovation is driven partially by a fear that technology will disrupt social structures and government control.
Such opportunities are not limited to existing economic powers. Estonia’s progress after the breakup of the Soviet Union is a good case study in transitioning to a digital economy. The nation rapidly implemented capitalistic reforms and transformed itself into a technology-centric economy in preparation for a massive tech disruption. Internet access was declared a right in 2000, and the country’s classrooms were outfitted for a digital economy, with coding as a core educational requirement starting at kindergarten. Internet broadband speeds in Estonia are among the fastest in the world. Accordingly, the World Bank now ranks Estonia as a high-income country.
Solution 2: Address Increased Rate of Change With More Nimble Education Systems
Education and training are currently not set for the speed of change in the modern economy. Schools are still based on a one-time education model, with school providing the foundation for a single lifelong career. With content becoming obsolete faster and rapidly escalating costs, this system may be unsustainable in the future. To help workers more smoothly transition from one job into another, for example, we need to make education a more nimble, lifelong endeavor.
Primary and university education may still have a role in training foundational thinking and general education, but it will be necessary to curtail rising price of tuition and increase accessibility. Massive open online courses (MooCs) and open-enrollment platforms are early demonstrations of what the future of general education may look like: cheap, effective, and flexible.
Georgia Tech’s online Engineering Master’s program (a fraction of the cost of residential tuition) is an early example in making university education more broadly available. Similarly, nanodegrees or microcredentials provided by online education platforms such as Udacity and Coursera can be used for mid-career adjustments at low cost. AI itself may be deployed to supplement the learning process, with applications such as AI-enhanced tutorials or personalized content recommendations backed by machine learning. Recent developments in neuroscience research could optimize this experience by perfectly tailoring content and delivery to the learner’s brain to maximize retention.
Finally, companies looking for more customized skills may take a larger role in education, providing on-the-job training for specific capabilities. One potential model involves partnering with community colleges to create apprenticeship-style learning, where students work part-time in parallel with their education. Siemens has pioneered such a model in four states and is developing a playbook for other companies to do the same.
Solution 3: Enhance Social Safety Nets to Smooth Automation Impacts
If predicted job losses to automation come to fruition, modernizing existing social safety nets will increasingly become a priority. While the issue of safety nets can become quickly politicized, it is worth noting that each prior technological revolution has come with corresponding changes to the social contract (see below).
The evolving social contract (U.S. examples)
– 1842 | Right to strike
– 1924 | Abolish child labor
– 1935 | Right to unionize
– 1938 | 40-hour work week
– 1962, 1974 | Trade adjustment assistance
– 1964 | Pay discrimination prohibited
– 1970 | Health and safety laws
– 21st century | AI and automation adjustment assistance?
Figure 2. Labor laws have historically adjusted as technology and society progressed
Solutions like universal basic income (no-strings-attached monthly payout to all citizens) are appealing in concept, but somewhat difficult to implement as a first measure in countries such as the US or Japan that already have high debt. Additionally, universal basic income may create dis-incentives to stay in the labor force. A similar cautionary tale in program design was the Trade Adjustment Assistance (TAA), which was designed to protect industries and workers from import competition shocks from globalization, but is viewed as a missed opportunity due to insufficient coverage.
A near-term solution could come in the form of graduated wage insurance (compensation for those forced to take a lower-paying job), including health insurance subsidies to individuals directly impacted by automation, with incentives to return to the workforce quickly. Another topic to tackle is geographic mismatch between workers and jobs, which can be addressed by mobility assistance. Lastly, a training stipend can be issued to individuals as means to upskill.
Policymakers can intervene to reverse recent historical trends that have shifted incomes from labor to capital owners. The balance could be shifted back to labor by placing higher taxes on capital—an example is the recently proposed “robot tax” where the taxation would be on the work rather than the individual executing it. That is, if a self-driving car performs the task that formerly was done by a human, the rideshare company will still pay the tax as if a human was driving.
Other solutions may involve distribution of work. Some countries, such as France and Sweden, have experimented with redistributing working hours. The idea is to cap weekly hours, with the goal of having more people employed and work more evenly spread. So far these programs have had mixed results, with lower unemployment but high costs to taxpayers, but are potential models that can continue to be tested.
We cannot stop growth, nor should we. With the roles in response to this evolution shifting, so should the social contract between the stakeholders. Government will continue to play a critical role as a stabilizing “thumb” in the invisible hand of capitalism, regulating and cushioning against extreme volatility, particularly in labor markets.
However, we already see business leaders taking on some of the role traditionally played by government—thinking about measures to remedy risks of climate change or economic proposals to combat unemployment—in part because of greater agility in adapting to change. Cross-disciplinary collaboration and creative solutions from all parties will be critical in crafting the future economy.
Note: The full paper this article is based on is available here.
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Posted in Human Robots