Tag Archives: University of Chicago

‘Nanotraps’ for catching and destroying coronavirus

‘Nanotraps’ are not vaccines although they do call the immune system into play. They represent a different way for dealing with COVID-19. (This work reminds of my June 24, 2020 posting Tiny sponges lure coronavirus away from lung cells where the researchers have a similar approach with what they call ‘nanosponges’.)

An April 27, 2021 news item on Nanowerk makes the announcement,

Researchers at the Pritzker School of Molecular Engineering (PME) at the University of Chicago have designed a completely novel potential treatment for COVID-19: nanoparticles that capture SARS-CoV-2 viruses within the body and then use the body’s own immune system to destroy it.

These “Nanotraps” attract the virus by mimicking the target cells the virus infects. When the virus binds to the Nanotraps, the traps then sequester the virus from other cells and target it for destruction by the immune system.

In theory, these Nanotraps could also be used on variants of the virus, leading to a potential new way to inhibit the virus going forward. Though the therapy remains in early stages of testing, the researchers envision it could be administered via a nasal spray as a treatment for COVID-19.

A scanning electron microscope image of a nanotrap (orange) binding a simulated SARS-CoV-2 virus (dots in green). Scientists at the University of Chicago created these nanoparticles as a potential treatment for COVID-19. Image courtesy Chen and Rosenberg et al.

An April 27, 2021 University of Chicago news release (also on EurekAlert) by Emily Ayshford, which originated the news item, describes the work in more detail,

“Since the pandemic began, our research team has been developing this new way to treat COVID-19,” said Asst. Prof. Jun Huang, whose lab led the research. “We have done rigorous testing to prove that these Nanotraps work, and we are excited about their potential.”

Designing the perfect trap

To design the Nanotrap, the research team – led by postdoctoral scholar Min Chen and graduate student Jill Rosenberg – looked into the mechanism SARS-CoV-2 uses to bind to cells: a spike-like protein on its surface that binds to a human cell’s ACE2 receptor protein.

To create a trap that would bind to the virus in the same way, they designed nanoparticles with a high density of ACE2 proteins on their surface. Similarly, they designed other nanoparticles with neutralizing antibodies on their surfaces. (These antibodies are created inside the body when someone is infected and are designed to latch onto the coronavirus in various ways).

Both ACE2 proteins and neutralizing antibodies have been used in treatments for COVID-19, but by attaching them to nanoparticles, the researchers created an even more robust system for trapping and eliminating the virus.

Made of FDA [US Food and Drug Administration]-approved polymers and phospholipids, the nanoparticles are about 500 nanometers in diameter – much smaller than a cell. That means the Nanotraps can reach more areas inside the body and more effectively trap the virus.

The researchers tested the safety of the system in a mouse model and found no toxicity. They then tested the Nanotraps against a pseudovirus – a less potent model of a virus that doesn’t replicate – in human lung cells in tissue culture plates and found that they completely blocked entry into the cells.

Once the pseudovirus bound itself to the nanoparticle – which in tests took about 10 minutes after injection – the nanoparticles used a molecule that calls the body’s macrophages to engulf and degrade the Nanotrap. Macrophages will generally eat nanoparticles within the body, but the Nanotrap molecule speeds up the process. The nanoparticles were cleared and degraded within 48 hours.

The researchers also tested the nanoparticles with a pseudovirus in an ex vivo lung perfusion system – a pair of donated lungs that is kept alive with a ventilator – and found that they completely blocked infection in the lungs.

They also collaborated with researchers at Argonne National Laboratory to test the Nanotraps with a live virus (rather than a pseudovirus) in an in vitro system. They found that their system inhibited the virus 10 times better than neutralizing antibodies or soluble ACE2 alone.

A potential future treatment for COVID-19 and beyond

Next the researchers hope to further test the system, including more tests with a live virus and on the many virus variants.

“That’s what is so powerful about this Nanotrap,” Rosenberg said. “It’s easily modulated. We can switch out different antibodies or proteins or target different immune cells, based on what we need with new variants.”

The Nanotraps can be stored in a standard freezer and could ultimately be given via an intranasal spray, which would place them directly in the respiratory system and make them most effective.

The researchers say it is also possible to serve as a vaccine by optimizing the Nanotrap formulation, creating an ultimate therapeutic system for the virus.

“This is the starting point,” Huang said. “We want to do something to help the world.”

The research involved collaborators across departments, including chemistry, biology, and medicine.

Here’s a link to and a citation for the paper,

Nanotraps for the containment and clearance of SARS-CoV-2 by Min Chen, Jillian Rosenberg, Xiaolei Cai, Andy Chao Hsuan Lee, Jiuyun Shi, Mindy Nguyen, Thirushan Wignakumar, Vikranth Mirle, Arianna Joy Edobor, John Fung, Jessica Scott Donington, Kumaran Shanmugarajah, Yiliang Lin, Eugene Chang, Glenn Randall, Pablo Penaloza-MacMaster, Bozhi Tian, Maria Lucia Madariaga, Jun Huang. Matter, April 19, 2021, DOI: https://doi.org/10.1016/j.matt.2021.04.005

This paper appears to be open access.

You mean Fitbit makes mistakes? More accuracy with ‘drawn-on-skin’ electronics

A July 30, 2020 news item on ScienceDaily announces news about more accurate health monitoring with electronics applied directly to your skin,

A team of researchers led by Cunjiang Yu, Bill D. Cook Associate Professor of Mechanical Engineering at the University of Houston, has developed a new form of electronics known as “drawn-on-skin electronics,” allowing multifunctional sensors and circuits to be drawn on the skin with an ink pen.

The advance, the researchers report in Nature Communications, allows for the collection of more precise, motion artifact-free health data, solving the long-standing problem of collecting precise biological data through a wearable device when the subject is in motion.

The imprecision may not be important when your FitBit registers 4,000 steps instead of 4,200, but sensors designed to check heart function, temperature and other physical signals must be accurate if they are to be used for diagnostics and treatment.

A July 30, 2020 University of Houston news release (also on EurekAlert) by Jeannie Kever, which originated the news item, goes on to explain why you might want to have electronics ‘drawn on your skin’,

The drawn-on-skin electronics are able to seamlessly collect data, regardless of the wearer’s movements.  

They also offer other advantages, including simple fabrication techniques that don’t require dedicated equipment.

“It is applied like you would use a pen to write on a piece of paper,” said Yu. “We prepare several electronic materials and then use pens to dispense them. Coming out, it is liquid. But like ink on paper, it dries very quickly.”

Wearable bioelectronics – in the form of soft, flexible patches attached to the skin – have become an important way to monitor, prevent and treat illness and injury by tracking physiological information from the wearer. But even the most flexible wearables are limited by motion artifacts, or the difficulty that arises in collecting data when the sensor doesn’t move precisely with the skin.

The drawn-on-skin electronics can be customized to collect different types of information, and Yu said it is expected to be especially useful in situations where it’s not possible to access sophisticated equipment, including on a battleground.

The electronics are able to track muscle signals, heart rate, temperature and skin hydration, among other physical data, he said. The researchers also reported that the drawn-on-skin electronics have demonstrated the ability to accelerate healing of wounds.

In addition to Yu, researchers involved in the project include Faheem Ershad, Anish Thukral, Phillip Comeaux, Yuntao Lu, Hyunseok Shim, Kyoseung Sim, Nam-In Kim, Zhoulyu Rao, Ross Guevara, Luis Contreras, Fengjiao Pan, Yongcao Zhang, Ying-Shi Guan, Pinyi Yang, Xu Wang and Peng Wang, all from the University of Houston, and Jiping Yue and Xiaoyang Wu from the University of Chicago.

The drawn-on-skin electronics are actually comprised of three inks, serving as a conductor, semiconductor and dielectric.

“Electronic inks, including conductors, semiconductors, and dielectrics, are drawn on-demand in a freeform manner to develop devices, such as transistors, strain sensors, temperature sensors, heaters, skin hydration sensors, and electrophysiological sensors,” the researchers wrote.

This research is supported by the Office of Naval Research and National Institutes of Health.

Caption: A new form of electronics known as “drawn-on-skin electronics” allows multifunctional sensors and circuits to be drawn on the skin with an ink pen. Credit: University of Houston

Here’s a link to and a citation for the paper,

Ultra-conformal drawn-on-skin electronics for multifunctional motion artifact-free sensing and point-of-care treatment by Faheem Ershad, Anish Thukral, Jiping Yue, Phillip Comeaux, Yuntao Lu, Hyunseok Shim, Kyoseung Sim, Nam-In Kim, Zhoulyu Rao, Ross Guevara, Luis Contreras, Fengjiao Pan, Yongcao Zhang, Ying-Shi Guan, Pinyi Yang, Xu Wang, Peng Wang, Xiaoyang Wu & Cunjiang Yu. Nature Communications volume 11, Article number: 3823 (2020) DOI: https://doi.org/10.1038/s41467-020-17619-1

This paper is open access.

Touchy robots and prosthetics

I have briefly speculated about the importance of touch elsewhere (see my July 19, 2019 posting regarding BlocKit and blockchain; scroll down about 50% of the way) but this upcoming news bit and the one following it put a different spin on the importance of touch.

Exceptional sense of touch

Robots need a sense of touch to perform their tasks and a July 18, 2019 National University of Singapore press release (also on EurekAlert) announces work on an improved sense of touch,

Robots and prosthetic devices may soon have a sense of touch equivalent to, or better than, the human skin with the Asynchronous Coded Electronic Skin (ACES), an artificial nervous system developed by a team of researchers at the National University of Singapore (NUS).

The new electronic skin system achieved ultra-high responsiveness and robustness to damage, and can be paired with any kind of sensor skin layers to function effectively as an electronic skin.

The innovation, achieved by Assistant Professor Benjamin Tee and his team from the Department of Materials Science and Engineering at the NUS Faculty of Engineering, was first reported in prestigious scientific journal Science Robotics on 18 July 2019.

Faster than the human sensory nervous system

“Humans use our sense of touch to accomplish almost every daily task, such as picking up a cup of coffee or making a handshake. Without it, we will even lose our sense of balance when walking. Similarly, robots need to have a sense of touch in order to interact better with humans, but robots today still cannot feel objects very well,” explained Asst Prof Tee, who has been working on electronic skin technologies for over a decade in hope of giving robots and prosthetic devices a better sense of touch.

Drawing inspiration from the human sensory nervous system, the NUS team spent a year and a half developing a sensor system that could potentially perform better. While the ACES electronic nervous system detects signals like the human sensor nervous system, it is made up of a network of sensors connected via a single electrical conductor, unlike the nerve bundles in the human skin. It is also unlike existing electronic skins which have interlinked wiring systems that can make them sensitive to damage and difficult to scale up.

Elaborating on the inspiration, Asst Prof Tee, who also holds appointments in the NUS Department of Electrical and Computer Engineering, NUS Institute for Health Innovation & Technology (iHealthTech), N.1 Institute for Health and the Hybrid Integrated Flexible Electronic Systems (HiFES) programme, said, “The human sensory nervous system is extremely efficient, and it works all the time to the extent that we often take it for granted. It is also very robust to damage. Our sense of touch, for example, does not get affected when we suffer a cut. If we can mimic how our biological system works and make it even better, we can bring about tremendous advancements in the field of robotics where electronic skins are predominantly applied.”

ACES can detect touches more than 1,000 times faster than the human sensory nervous system. For example, it is capable of differentiating physical contacts between different sensors in less than 60 nanoseconds – the fastest ever achieved for an electronic skin technology – even with large numbers of sensors. ACES-enabled skin can also accurately identify the shape, texture and hardness of objects within 10 milliseconds, ten times faster than the blinking of an eye. This is enabled by the high fidelity and capture speed of the ACES system.

The ACES platform can also be designed to achieve high robustness to physical damage, an important property for electronic skins because they come into the frequent physical contact with the environment. Unlike the current system used to interconnect sensors in existing electronic skins, all the sensors in ACES can be connected to a common electrical conductor with each sensor operating independently. This allows ACES-enabled electronic skins to continue functioning as long as there is one connection between the sensor and the conductor, making them less vulnerable to damage.

Smart electronic skins for robots and prosthetics

ACES’ simple wiring system and remarkable responsiveness even with increasing numbers of sensors are key characteristics that will facilitate the scale-up of intelligent electronic skins for Artificial Intelligence (AI) applications in robots, prosthetic devices and other human machine interfaces.

“Scalability is a critical consideration as big pieces of high performing electronic skins are required to cover the relatively large surface areas of robots and prosthetic devices,” explained Asst Prof Tee. “ACES can be easily paired with any kind of sensor skin layers, for example, those designed to sense temperatures and humidity, to create high performance ACES-enabled electronic skin with an exceptional sense of touch that can be used for a wide range of purposes,” he added.

For instance, pairing ACES with the transparent, self-healing and water-resistant sensor skin layer also recently developed by Asst Prof Tee’s team, creates an electronic skin that can self-repair, like the human skin. This type of electronic skin can be used to develop more realistic prosthetic limbs that will help disabled individuals restore their sense of touch.

Other potential applications include developing more intelligent robots that can perform disaster recovery tasks or take over mundane operations such as packing of items in warehouses. The NUS team is therefore looking to further apply the ACES platform on advanced robots and prosthetic devices in the next phase of their research.

For those who like videos, the researchers have prepared this,

Here’s a link to and a citation for the paper,

A neuro-inspired artificial peripheral nervous system for scalable electronic skins by Wang Wei Lee, Yu Jun Tan, Haicheng Yao, Si Li, Hian Hian See, Matthew Hon, Kian Ann Ng, Betty Xiong, John S. Ho and Benjamin C. K. Tee. Science Robotics Vol 4, Issue 32 31 July 2019 eaax2198 DOI: 10.1126/scirobotics.aax2198 Published online first: 17 Jul 2019:

This paper is behind a paywall.

Picking up a grape and holding his wife’s hand

This story comes from the Canadian Broadcasting Corporation (CBC) Radio with a six minute story embedded in the text, from a July 25, 2019 CBC Radio ‘As It Happens’ article by Sheena Goodyear,

The West Valley City, Utah, real estate agent [Keven Walgamott] lost his left hand in an electrical accident 17 years ago. Since then, he’s tried out a few different prosthetic limbs, but always found them too clunky and uncomfortable.

Then he decided to work with the University of Utah in 2016 to test out new prosthetic technology that mimics the sensation of human touch, allowing Walgamott to perform delicate tasks with precision — including shaking his wife’s hand. 

“I extended my left hand, she came and extended hers, and we were able to feel each other with the left hand for the first time in 13 years, and it was just a marvellous and wonderful experience,” Walgamott told As It Happens guest host Megan Williams. 

Walgamott, one of seven participants in the University of Utah study, was able to use an advanced prosthetic hand called the LUKE Arm to pick up an egg without cracking it, pluck a single grape from a bunch, hammer a nail, take a ring on and off his finger, fit a pillowcase over a pillow and more. 

While performing the tasks, Walgamott was able to actually feel the items he was holding and correctly gauge the amount of pressure he needed to exert — mimicking a process the human brain does automatically.

“I was able to feel something in each of my fingers,” he said. “What I feel, I guess the easiest way to explain it, is little electrical shocks.”

Those shocks — which he describes as a kind of a tingling sensation — intensify as he tightens his grip.

“Different variations of the intensity of the electricity as I move my fingers around and as I touch things,” he said. 

To make that [sense of touch] happen, the researchers implanted electrodes into the nerves on Walgamott’s forearm, allowing his brain to communicate with his prosthetic through a computer outside his body. That means he can move the hand just by thinking about it.

But those signals also work in reverse.

The team attached sensors to the hand of a LUKE Arm. Those sensors detect touch and positioning, and send that information to the electrodes so it can be interpreted by the brain.

For Walgamott, performing a series of menial tasks as a team of scientists recorded his progress was “fun to do.”

“I’d forgotten how well two hands work,” he said. “That was pretty cool.”

But it was also a huge relief from the phantom limb pain he has experienced since the accident, which he describes as a “burning sensation” in the place where his hand used to be.

A July 24, 2019 University of Utah news release (also on EurekAlert) provides more detail about the research,

Keven Walgamott had a good “feeling” about picking up the egg without crushing it.

What seems simple for nearly everyone else can be more of a Herculean task for Walgamott, who lost his left hand and part of his arm in an electrical accident 17 years ago. But he was testing out the prototype of a high-tech prosthetic arm with fingers that not only can move, they can move with his thoughts. And thanks to a biomedical engineering team at the University of Utah, he “felt” the egg well enough so his brain could tell the prosthetic hand not to squeeze too hard.

That’s because the team, led by U biomedical engineering associate professor Gregory Clark, has developed a way for the “LUKE Arm” (so named after the robotic hand that Luke Skywalker got in “The Empire Strikes Back”) to mimic the way a human hand feels objects by sending the appropriate signals to the brain. Their findings were published in a new paper co-authored by U biomedical engineering doctoral student Jacob George, former doctoral student David Kluger, Clark and other colleagues in the latest edition of the journal Science Robotics. A copy of the paper may be obtained by emailing robopak@aaas.org.

“We changed the way we are sending that information to the brain so that it matches the human body. And by matching the human body, we were able to see improved benefits,” George says. “We’re making more biologically realistic signals.”

That means an amputee wearing the prosthetic arm can sense the touch of something soft or hard, understand better how to pick it up and perform delicate tasks that would otherwise be impossible with a standard prosthetic with metal hooks or claws for hands.

“It almost put me to tears,” Walgamott says about using the LUKE Arm for the first time during clinical tests in 2017. “It was really amazing. I never thought I would be able to feel in that hand again.”

Walgamott, a real estate agent from West Valley City, Utah, and one of seven test subjects at the U, was able to pluck grapes without crushing them, pick up an egg without cracking it and hold his wife’s hand with a sensation in the fingers similar to that of an able-bodied person.

“One of the first things he wanted to do was put on his wedding ring. That’s hard to do with one hand,” says Clark. “It was very moving.”

Those things are accomplished through a complex series of mathematical calculations and modeling.

The LUKE Arm

The LUKE Arm has been in development for some 15 years. The arm itself is made of mostly metal motors and parts with a clear silicon “skin” over the hand. It is powered by an external battery and wired to a computer. It was developed by DEKA Research & Development Corp., a New Hampshire-based company founded by Segway inventor Dean Kamen.

Meanwhile, the U’s team has been developing a system that allows the prosthetic arm to tap into the wearer’s nerves, which are like biological wires that send signals to the arm to move. It does that thanks to an invention by U biomedical engineering Emeritus Distinguished Professor Richard A. Normann called the Utah Slanted Electrode Array. The array is a bundle of 100 microelectrodes and wires that are implanted into the amputee’s nerves in the forearm and connected to a computer outside the body. The array interprets the signals from the still-remaining arm nerves, and the computer translates them to digital signals that tell the arm to move.

But it also works the other way. To perform tasks such as picking up objects requires more than just the brain telling the hand to move. The prosthetic hand must also learn how to “feel” the object in order to know how much pressure to exert because you can’t figure that out just by looking at it.

First, the prosthetic arm has sensors in its hand that send signals to the nerves via the array to mimic the feeling the hand gets upon grabbing something. But equally important is how those signals are sent. It involves understanding how your brain deals with transitions in information when it first touches something. Upon first contact of an object, a burst of impulses runs up the nerves to the brain and then tapers off. Recreating this was a big step.

“Just providing sensation is a big deal, but the way you send that information is also critically important, and if you make it more biologically realistic, the brain will understand it better and the performance of this sensation will also be better,” says Clark.

To achieve that, Clark’s team used mathematical calculations along with recorded impulses from a primate’s arm to create an approximate model of how humans receive these different signal patterns. That model was then implemented into the LUKE Arm system.

Future research

In addition to creating a prototype of the LUKE Arm with a sense of touch, the overall team is already developing a version that is completely portable and does not need to be wired to a computer outside the body. Instead, everything would be connected wirelessly, giving the wearer complete freedom.

Clark says the Utah Slanted Electrode Array is also capable of sending signals to the brain for more than just the sense of touch, such as pain and temperature, though the paper primarily addresses touch. And while their work currently has only involved amputees who lost their extremities below the elbow, where the muscles to move the hand are located, Clark says their research could also be applied to those who lost their arms above the elbow.

Clark hopes that in 2020 or 2021, three test subjects will be able to take the arm home to use, pending federal regulatory approval.

The research involves a number of institutions including the U’s Department of Neurosurgery, Department of Physical Medicine and Rehabilitation and Department of Orthopedics, the University of Chicago’s Department of Organismal Biology and Anatomy, the Cleveland Clinic’s Department of Biomedical Engineering and Utah neurotechnology companies Ripple Neuro LLC and Blackrock Microsystems. The project is funded by the Defense Advanced Research Projects Agency and the National Science Foundation.

“This is an incredible interdisciplinary effort,” says Clark. “We could not have done this without the substantial efforts of everybody on that team.”

Here’s a link to and a citation for the paper,

Biomimetic sensory feedback through peripheral nerve stimulation improves dexterous use of a bionic hand by J. A. George, D. T. Kluger, T. S. Davis, S. M. Wendelken, E. V. Okorokova, Q. He, C. C. Duncan, D. T. Hutchinson, Z. C. Thumser, D. T. Beckler, P. D. Marasco, S. J. Bensmaia and G. A. Clark. Science Robotics Vol. 4, Issue 32, eaax2352 31 July 2019 DOI: 10.1126/scirobotics.aax2352 Published online first: 24 Jul 2019

This paper is definitely behind a paywall.

The University of Utah researchers have produced a video highlighting their work,

The roles mathematics and light play in cellular communication

These are two entirely different types of research but taken together they help build a picture about how the cells in our bodies function.

Cells and light

An April 30, 2018 news item on phys.org describes work on controlling biology with light,

Over the past five years, University of Chicago chemist Bozhi Tian has been figuring out how to control biology with light.

A longterm science goal is devices to serve as the interface between researcher and body—both as a way to understand how cells talk among each other and within themselves, and eventually, as a treatment for brain or nervous system disorders [emphasis mine] by stimulating nerves to fire or limbs to move. Silicon—a versatile, biocompatible material used in both solar panels and surgical implants—is a natural choice.

In a paper published April 30 in Nature Biomedical Engineering, Tian’s team laid out a system of design principles for working with silicon to control biology at three levels—from individual organelles inside cells to tissues to entire limbs. The group has demonstrated each in cells or mice models, including the first time anyone has used light to control behavior without genetic modification.

“We want this to serve as a map, where you can decide which problem you would like to study and immediately find the right material and method to address it,” said Tian, an assistant professor in the Department of Chemistry.

Researchers built this thin layer of silicon lace to modulate neural signals when activated by light. Courtesy of Yuanwen Jiang and Bozhi Tian

An April 30, 2018 University of Chicago news release by Louise Lerner, which originated the news item, describes the work in greater detail,

The scientists’ map lays out best methods to craft silicon devices depending on both the intended task and the scale—ranging from inside a cell to a whole animal.

For example, to affect individual brain cells, silicon can be crafted to respond to light by emitting a tiny ionic current, which encourages neurons to fire. But in order to stimulate limbs, scientists need a system whose signals can travel farther and are stronger—such as a gold-coated silicon material in which light triggers a chemical reaction.

The mechanical properties of the implant are important, too. Say researchers would like to work with a larger piece of the brain, like the cortex, to control motor movement. The brain is a soft, squishy substance, so they’ll need a material that’s similarly soft and flexible, but can bind tightly against the surface. They’d want thin and lacy silicon, say the design principles.

The team favors this method because it doesn’t require genetic modification or a power supply wired in, since the silicon can be fashioned into what are essentially tiny solar panels. (Many other forms of monitoring or interacting with the brain need to have a power supply, and keeping a wire running into a patient is an infection risk.)

They tested the concept in mice and found they could stimulate limb movements by shining light on brain implants. Previous research tested the concept in neurons.

“We don’t have answers to a number of intrinsic questions about biology, such as whether individual mitochondria communicate remotely through bioelectric signals,” said Yuanwen Jiang, the first author on the paper, then a graduate student at UChicago and now a postdoctoral researcher at Stanford. “This set of tools could address such questions as well as pointing the way to potential solutions for nervous system disorders.”

Other UChicago authors were Assoc. Profs. Chin-Tu Chen and Chien-Min Kao, Asst. Prof Xiaoyang, postdoctoral researchers Jaeseok Yi, Yin Fang, Xiang Gao, Jiping Yue, Hsiu-Ming Tsai, Bing Liu and Yin Fang, graduate students Kelliann Koehler, Vishnu Nair, and Edward Sudzilovsky, and undergraduate student George Freyermuth.

Other researchers on the paper hailed from Northwestern University, the University of Illinois at Chicago and Hong Kong Polytechnic University.

The researchers have also made this video illustrating their work,

via Gfycat Tiny silicon nanowires (in blue), activated by light, trigger activity in neurons. (Courtesy Yuanwen Jiang and Bozhi Tian)

Here’s a link to and a citation for the paper,

Rational design of silicon structures for optically controlled multiscale biointerfaces by Yuanwen Jiang, Xiaojian Li, Bing Liu, Jaeseok Yi, Yin Fang, Fengyuan Shi, Xiang Gao, Edward Sudzilovsky, Ramya Parameswaran, Kelliann Koehler, Vishnu Nair, Jiping Yue, KuangHua Guo, Yin Fang, Hsiu-Ming Tsai, George Freyermuth, Raymond C. S. Wong, Chien-Min Kao, Chin-Tu Chen, Alan W. Nicholls, Xiaoyang Wu, Gordon M. G. Shepherd, & Bozhi Tian. Nature Biomedical Engineering (2018) doi:10.1038/s41551-018-0230-1 Published: 30 April 2018

This paper is behind a paywall.

Mathematics and how living cells ‘think’

This May 2, 2018 Queensland University of Technology (QUT; Australia) press release is also on EurekAlert,

How does the ‘brain’ of a living cell work, allowing an organism to function and thrive in changing and unfavourable environments?

Queensland University of Technology (QUT) researcher Dr Robyn Araujo has developed new mathematics to solve a longstanding mystery of how the incredibly complex biological networks within cells can adapt and reset themselves after exposure to a new stimulus.

Her findings, published in Nature Communications, provide a new level of understanding of cellular communication and cellular ‘cognition’, and have potential application in a variety of areas, including new targeted cancer therapies and drug resistance.

Dr Araujo, a lecturer in applied and computational mathematics in QUT’s Science and Engineering Faculty, said that while we know a great deal about gene sequences, we have had extremely limited insight into how the proteins encoded by these genes work together as an integrated network – until now.

“Proteins form unfathomably complex networks of chemical reactions that allow cells to communicate and to ‘think’ – essentially giving the cell a ‘cognitive’ ability, or a ‘brain’,” she said. “It has been a longstanding mystery in science how this cellular ‘brain’ works.

“We could never hope to measure the full complexity of cellular networks – the networks are simply too large and interconnected and their component proteins are too variable.

“But mathematics provides a tool that allows us to explore how these networks might be constructed in order to perform as they do.

“My research is giving us a new way to look at unravelling network complexity in nature.”

Dr Araujo’s work has focused on the widely observed function called perfect adaptation – the ability of a network to reset itself after it has been exposed to a new stimulus.

“An example of perfect adaptation is our sense of smell,” she said. “When exposed to an odour we will smell it initially but after a while it seems to us that the odour has disappeared, even though the chemical, the stimulus, is still present.

“Our sense of smell has exhibited perfect adaptation. This process allows it to remain sensitive to further changes in our environment so that we can detect both very feint and very strong odours.

“This kind of adaptation is essentially what takes place inside living cells all the time. Cells are exposed to signals – hormones, growth factors, and other chemicals – and their proteins will tend to react and respond initially, but then settle down to pre-stimulus levels of activity even though the stimulus is still there.

“I studied all the possible ways a network can be constructed and found that to be capable of this perfect adaptation in a robust way, a network has to satisfy an extremely rigid set of mathematical principles. There are a surprisingly limited number of ways a network could be constructed to perform perfect adaptation.

“Essentially we are now discovering the needles in the haystack in terms of the network constructions that can actually exist in nature.

“It is early days, but this opens the door to being able to modify cell networks with drugs and do it in a more robust and rigorous way. Cancer therapy is a potential area of application, and insights into how proteins work at a cellular level is key.”

Dr Araujo said the published study was the result of more than “five years of relentless effort to solve this incredibly deep mathematical problem”. She began research in this field while at George Mason University in Virginia in the US.

Her mentor at the university’s College of Science and co-author of the Nature Communications paper, Professor Lance Liotta, said the “amazing and surprising” outcome of Dr Araujo’s study is applicable to any living organism or biochemical network of any size.

“The study is a wonderful example of how mathematics can have a profound impact on society and Dr Araujo’s results will provide a set of completely fresh approaches for scientists in a variety of fields,” he said.

“For example, in strategies to overcome cancer drug resistance – why do tumours frequently adapt and grow back after treatment?

“It could also help understanding of how our hormone system, our immune defences, perfectly adapt to frequent challenges and keep us well, and it has future implications for creating new hypotheses about drug addiction and brain neuron signalling adaptation.”

Hre’s a link to and a citation for the paper,

The topological requirements for robust perfect adaptation in networks of any size by Robyn P. Araujo & Lance A. Liotta. Nature Communicationsvolume 9, Article number: 1757 (2018) doi:10.1038/s41467-018-04151-6 Published: 01 May 2018

This paper is open access.

Quantum entanglement in near-macroscopic objects

Researchers at Finland’s Aalto University seem excited in an April 25, 2018 news item on phys.org,

Perhaps the strangest prediction of quantum theory is entanglement, a phenomenon whereby two distant objects become intertwined in a manner that defies both classical physics and a common-sense understanding of reality. In 1935, Albert Einstein expressed his concern over this concept, referring to it as “spooky action at a distance.”

Today, entanglement is considered a cornerstone of quantum mechanics, and it is the key resource for a host of potentially transformative quantum technologies. Entanglement is, however, extremely fragile, and it has previously been observed only in microscopic systems such as light or atoms, and recently in superconducting electric circuits.

In work recently published in Nature, a team led by Prof. Mika Sillanpää at Aalto University in Finland has shown that entanglement of massive objects can be generated and detected.

The researchers managed to bring the motions of two individual vibrating drumheads—fabricated from metallic aluminium on a silicon chip—into an entangled quantum state. The macroscopic objects in the experiment are truly massive compared to the atomic scale—the circular drumheads have a diametre similar to the width of a thin human hair.

An April 20,2018 Aalto University press release (also on EurekAlert), which originated the news item, provides more detail,

‘The vibrating bodies are made to interact via a superconducting microwave circuit. The electromagnetic fields in the circuit carry away any thermal disturbances, leaving behind only the quantum mechanical vibrations’, says Professor Sillanpää, describing the experimental setup.

Eliminating all forms of external noise is crucial for the experiments, which is why they have to be conducted at extremely low temperatures near absolute zero, at –273 °C. Remarkably, the experimental approach allows the unusual state of entanglement to persist for long periods of time, in this case up to half an hour. In comparison, measurements on elementary particles have witnessed entanglement to last only tiny fractions of a second.

‘These measurements are challenging but extremely fascinating. In the future, we will attempt to teleport the mechanical vibrations. In quantum teleportation, properties of physical bodies can be transmitted across arbitrary distances using the channel of “spooky action at a distance”. We are still pretty far from Star Trek, though,’ says Dr. Caspar Ockeloen-Korppi, the lead author on the work, who also performed the measurements.

The results demonstrate that it is now possible to have control over the most delicate properties of objects whose size approaches the scale of our daily lives. The achievement opens doors for new kinds of quantum technologies, where the entangled drumheads could be used as routers or sensors. The finding also enables new studies of fundamental physics in, for example, the poorly understood interplay of gravity and quantum mechanics.

The team also included scientists from the University of New South Wales in Australia, the University of Chicago in the USA, and the University of Jyväskylä in Finland, whose theoretical innovations paved the way for the laboratory experiment.

An illustration has been made available,

An illustration of the 15-micrometre-wide drumheads prepared on silicon chips used in the experiment. The drumheads vibrate at a high ultrasound frequency, and the peculiar quantum state predicted by Einstein was created from the vibrations. Image: Aalto University / Petja Hyttinen & Olli Hanhirova, ARKH Architects.

Here’s a link to and a citation for the paper,

Stabilized entanglement of massive mechanical oscillators by C. F. Ockeloen-Korppi, E. Damskägg, J.-M. Pirkkalainen, M. Asjad, A. A. Clerk, F. Massel, M. J. Woolley & M. A. Sillanpää. Nature volume 556, pages478–482 (2018) doi:10.1038/s41586-018-0038-x Published online: 25 April 2018

This paper is behind a paywall.

Why don’t you CRISPR yourself?

It must have been quite the conference. Josiah Zayner plunged a needle into himself and claimed to have changed his DNA (deoxyribonucleic acid) while giving his talk. (*Segue: There is some Canadian content if you keep reading.*) From an Oct. 10, 2017 article by Adele Peters for Fast Company (Note: A link has been removed),

“What we’ve got here is some DNA, and this is a syringe,” Josiah Zayner tells a room full of synthetic biologists and other researchers. He fills the needle and plunges it into his skin. “This will modify my muscle genes and give me bigger muscles.”

Zayner, a biohacker–basically meaning he experiments with biology in a DIY lab rather than a traditional one–was giving a talk called “A Step-by-Step Guide to Genetically Modifying Yourself With CRISPR” at the SynBioBeta conference in San Francisco, where other presentations featured academics in suits and the young CEOs of typical biotech startups. Unlike the others, he started his workshop by handing out shots of scotch and a booklet explaining the basics of DIY [do-it-yourwelf] genome engineering.

If you want to genetically modify yourself, it turns out, it’s not necessarily complicated. As he offered samples in small baggies to the crowd, Zayner explained that it took him about five minutes to make the DNA that he brought to the presentation. The vial held Cas9, an enzyme that snips DNA at a particular location targeted by guide RNA, in the gene-editing system known as CRISPR. In this case, it was designed to knock out the myostatin gene, which produces a hormone that limits muscle growth and lets muscles atrophy. In a study in China, dogs with the edited gene had double the muscle mass of normal dogs. If anyone in the audience wanted to try it, they could take a vial home and inject it later. Even rubbing it on skin, Zayner said, would have some effect on cells, albeit limited.

Peters goes on to note that Zayner has a PhD in molecular biology and biophysics and worked for NASA (US National Aeronautics and Space Administration). Zayner’s Wikipedia entry fills in a few more details (Note: Links have been removed),

Zayner graduated from the University of Chicago with a Ph.D. in biophysics in 2013. He then spent two years as a researcher at NASA’s Ames Research Center,[2] where he worked on Martian colony habitat design. While at the agency, Zayner also analyzed speech patterns in online chat, Twitter, and books, and found that language on Twitter and online chat is closer to how people talk than to how they write.[3] Zayner found NASA’s scientific work less innovative than he expected, and upon leaving in January 2016, he launched a crowdfunding campaign to provide CRISPR kits to let the general public experiment with editing bacterial DNA. He also continued his grad school business, The ODIN, which sells kits to let the general public experiment at home. As of May 2016, The ODIN had four employees and operates out of Zayner’s garage.[2]

He refers to himself as a biohacker and believes in the importance in letting the general public participate in scientific experimentation, rather than leaving it segregated to labs.[2][4][1] Zayner found the biohacking community exclusive and hierarchical, particularly in the types of people who decide what is “safe”. He hopes that his projects can let even more people experiment in their homes. Other scientists responded that biohacking is inherently privileged, as it requires leisure time and money, and that deviance from the safety rules of concern would lead to even harsher regulations for all.[5] Zayner’s public CRISPR kit campaign coincided with wider scrutiny over genetic modification. Zayner maintained that these fears were based on misunderstandings of the product, as genetic experiments on yeast and bacteria cannot produce a viral epidemic.[6][7] In April 2015, Zayner ran a hoax on Craigslist to raise awareness about the future potential of forgery in forensics genetics testing.[8]

In February 2016, Zayner performed a full body microbiome transplant on himself, including a fecal transplant, to experiment with microbiome engineering and see if he could cure himself from gastrointestinal and other health issues. The microbiome from the donors feces successfully transplanted in Zayner’s gut according to DNA sequencing done on samples.[2] This experiment was documented by filmmakers Kate McLean and Mario Furloni and turned into the short documentary film Gut Hack.[9]

In December 2016, Zayner created a fluorescent beer by engineering yeast to contain the green fluorescent protein from jellyfish. Zayner’s company, The ODIN, released kits to allow people to create their own engineered fluorescent yeast and this was met with some controversy as the FDA declared the green fluorescent protein can be seen as a color additive.[10] Zayner, views the kit as a way that individual can use genetic engineering to create things in their everyday life.[11]

I found the video for Zayner’s now completed crowdfunding campaign,

I also found The ODIN website (mentioned in the Wikipedia essay) where they claim to be selling various gene editing and gene engineering kits including the CRISPR editing kits mentioned in Peters’ article,

In 2016, he [Zayner] sold $200,000 worth of products, including a kit for yeast that can be used to brew glowing bioluminescent beer, a kit to discover antibiotics at home, and a full home lab that’s roughly the cost of a MacBook Pro. In 2017, he expects to double sales. Many kits are simple, and most buyers probably aren’t using the supplies to attempt to engineer themselves (many kits go to classrooms). But Zayner also hopes that as people using the kits gain genetic literacy, they experiment in wilder ways.

Zayner sells a full home biohacking lab that’s roughly the cost of a MacBook Pro. [Photo: The ODIN]

He questions whether traditional research methods, like randomized controlled trials, are the only way to make discoveries, pointing out that in newer personalized medicine (such as immunotherapy for cancer, which is personalized for each patient), a sample size of one person makes sense. At his workshop, he argued that people should have the choice to self-experiment if they want to; we also change our DNA when we drink alcohol or smoke cigarettes or breathe in dirty city air. Other society-sanctioned activities are more dangerous. “We sacrifice maybe a million people a year to the car gods,” he said. “If you ask someone, ‘Would you get rid of cars?’–no.” …

US researchers both conventional and DIY types such as Zayner are not the only ones who are editing genes. The Chinese study mentioned in Peters’ article was written up in an Oct. 19, 2015 article by Antonio Regalado for the MIT [Massachusetts Institute of Technology] Technology Review (Note: Links have been removed),

Scientists in China say they are the first to use gene editing to produce customized dogs. They created a beagle with double the amount of muscle mass by deleting a gene called myostatin.

The dogs have “more muscles and are expected to have stronger running ability, which is good for hunting, police (military) applications,” Liangxue Lai, a researcher with the Key Laboratory of Regenerative Biology at the Guangzhou Institutes of Biomedicine and Health, said in an e-mail.

Lai and 28 colleagues reported their results last week in the Journal of Molecular Cell Biology, saying they intend to create dogs with other DNA mutations, including ones that mimic human diseases such as Parkinson’s and muscular dystrophy. “The goal of the research is to explore an approach to the generation of new disease dog models for biomedical research,” says Lai. “Dogs are very close to humans in terms of metabolic, physiological, and anatomical characteristics.”

Lai said his group had no plans breed to breed the extra-muscular beagles as pets. Other teams, however, could move quickly to commercialize gene-altered dogs, potentially editing their DNA to change their size, enhance their intelligence, or correct genetic illnesses. A different Chinese Institute, BGI, said in September it had begun selling miniature pigs, created via gene editing, for $1,600 each as novelty pets.

People have been influencing the genetics of dogs for millennia. By at least 36,000 years ago, early humans had already started to tame wolves and shape the companions we have today. Charles Darwin frequently cited dog breeding in The Origin of Species to demonstrate how evolution gradually occurs by a process of selection. With CRISPR, however, evolution is no longer gradual or subject to chance. It is immediate and under human control.

It is precisely that power that is stirring wide debate and concern over CRISPR. Yet at least some researchers think that gene-edited dogs could put a furry, friendly face on the technology. In an interview this month, George Church, a professor at Harvard University who leads a large effort to employ CRISPR editing, said he thinks it will be possible to augment dogs by using DNA edits to make them live longer or simply make them smarter.

Church said he also believed the alteration of dogs and other large animals could open a path to eventual gene editing of people. “Germline editing of pigs or dogs offers a line into it,” he said. “People might say, ‘Hey, it works.’ ”

In the meantime, Zayner’s ideas are certainly thought provoking. I’m not endorsing either his products or his ideas but it should be noted that early science pioneers such as Humphrey Davy and others experimented on themselves. For anyone unfamiliar with Davy, (from the Humphrey Davy Wikipedia entry; Note: Links have been removed),

Sir Humphry Davy, 1st Baronet PRS MRIA FGS (17 December 1778 – 29 May 1829) was a Cornish chemist and inventor,[1] who is best remembered today for isolating a series of substances for the first time: potassium and sodium in 1807 and calcium, strontium, barium, magnesium and boron the following year, as well as discovering the elemental nature of chlorine and iodine. He also studied the forces involved in these separations, inventing the new field of electrochemistry. Berzelius called Davy’s 1806 Bakerian Lecture On Some Chemical Agencies of Electricity[2] “one of the best memoirs which has ever enriched the theory of chemistry.”[3] He was a Baronet, President of the Royal Society (PRS), Member of the Royal Irish Academy (MRIA), and Fellow of the Geological Society (FGS). He also invented the Davy lamp and a very early form of incandescent light bulb.

Canadian content*

A Nov. 11, 2017 posting on the Canadian Broadcasting Corporation’s (CBC) Quirks and Quarks blog notes that self-experimentation has a long history and goes on to describe Zayner’s and others biohacking exploits before describing the legality of biohacking in Canada,

With biohackers entering into the space traditionally held by scientists and clinicians, it begs questions. Professor Timothy Caulfield, a Canada research chair in health, law and policy at the University of Alberta, says when he hears of somebody giving themselves biohacked gene therapy, he wonders: “Is this legal? Is this safe? And if it’s not safe, is there anything that we can do about regulating it? And to be honest with you that’s a tough question and I think it’s an open question.”

In Canada, Caulfield says, Health Canada focuses on products. “You have to have something that you are going to regulate or you have to have something that’s making health claims. So if there is a product that is saying I can cure X, Y, or Z, Health Canada can say, ‘Well let’s make sure the science really backs up that claim.’ The problem with these do-it-yourself approaches is there isn’t really a product. You know these people are experimenting on themselves with something that may or may not be designed for health purposes.”

According to Caufield, if you could buy a gene therapy kit that was being marketed to you to biohack yourself, that would be different. “Health Canada could jump in. But right here that’s not the case,” he says.

There are places in the world that do regulate biohacking, says Caulfield. “Germany, for example, they have specific laws for it. And here in Canada we do have a regulatory framework that says that you cannot do gene therapy that will alter the germ line. In other words, you can’t do gene therapy or any kind of genetic editing that will create a change that you will pass on to your offspring. So that would be illegal, but that’s not what’s happening here. And I don’t think there’s a regulatory framework that adequately captures it.”

Infectious disease and policy experts aren’t that concerned yet about the possibility of a biohacker unleashing a genetically modified super germ into the population.

“I think in the future that could be a problem,”says Caulfield, “but this isn’t something that would be easy to do in your garage. I think it’s complicated science. But having said that, the science is moving quickly. We need to think about how we are going to control the potential harms.”

You can find out more about the ‘wild’ people (mostly men) of early science in Richard Holmes’ 2008 book, The Age of Wonder: How the Romantic Generation Discovered the Beauty and Terror of Science.

Finally, should you be interested in connecting with synthetic biology enthusiasts, entrepreneurs, and others, SynBioBeta is more than a conference; it’s also an activity hub.

ETA January 25, 2018 (five minutes later): There are some CRISPR/CAS9 events taking place in Toronto, Canada on January 24 and 25, 2018. One is a workshop with Portuguese artist, Marta de Menezes, and the other is a panel discussion. See my January 10, 2018 posting for more details.

*’Segue: There is some Canadian content if you keep reading.’ and ‘Canadian content’ added January 25, 2018 six minutes after first publication.

ETA February 20, 2018: Sarah Zhang’s Feb. 20, 2018 article for The Atlantic revisits Josiah Zayner’s decision to inject himself with CRISPR,

When Josiah Zayner watched a biotech CEO drop his pants at a biohacking conference and inject himself with an untested herpes treatment, he realized things had gone off the rails.

Zayner is no stranger to stunts in biohacking—loosely defined as experiments, often on the self, that take place outside of traditional lab spaces. You might say he invented their latest incarnation: He’s sterilized his body to “transplant” his entire microbiome in front of a reporter. He’s squabbled with the FDA about selling a kit to make glow-in-the-dark beer. He’s extensively documented attempts to genetically engineer the color of his skin. And most notoriously, he injected his arm with DNA encoding for CRISPR that could theoretically enhance his muscles—in between taking swigs of Scotch at a live-streamed event during an October conference. (Experts say—and even Zayner himself in the live-stream conceded—it’s unlikely to work.)

So when Zayner saw Ascendance Biomedical’s CEO injecting himself on a live-stream earlier this month, you might say there was an uneasy flicker of recognition.

“Honestly, I kind of blame myself,” Zayner told me recently. He’s been in a soul-searching mood; he recently had a kid and the backlash to the CRISPR stunt in October [2017] had been getting to him. “There’s no doubt in my mind that somebody is going to end up hurt eventually,” he said.

Yup, it’s one of the reasons for rules; people take things too far. The trick is figuring out how to achieve balance between risk taking and recklessness.

Machine learning programs learn bias

The notion of bias in artificial intelligence (AI)/algorithms/robots is gaining prominence (links to other posts featuring algorithms and bias are at the end of this post). The latest research concerns machine learning where an artificial intelligence system trains itself with ordinary human language from the internet. From an April 13, 2017 American Association for the Advancement of Science (AAAS) news release on EurekAlert,

As artificial intelligence systems “learn” language from existing texts, they exhibit the same biases that humans do, a new study reveals. The results not only provide a tool for studying prejudicial attitudes and behavior in humans, but also emphasize how language is intimately intertwined with historical biases and cultural stereotypes. A common way to measure biases in humans is the Implicit Association Test (IAT), where subjects are asked to pair two concepts they find similar, in contrast to two concepts they find different; their response times can vary greatly, indicating how well they associated one word with another (for example, people are more likely to associate “flowers” with “pleasant,” and “insects” with “unpleasant”). Here, Aylin Caliskan and colleagues developed a similar way to measure biases in AI systems that acquire language from human texts; rather than measuring lag time, however, they used the statistical number of associations between words, analyzing roughly 2.2 million words in total. Their results demonstrate that AI systems retain biases seen in humans. For example, studies of human behavior show that the exact same resume is 50% more likely to result in an opportunity for an interview if the candidate’s name is European American rather than African-American. Indeed, the AI system was more likely to associate European American names with “pleasant” stimuli (e.g. “gift,” or “happy”). In terms of gender, the AI system also reflected human biases, where female words (e.g., “woman” and “girl”) were more associated than male words with the arts, compared to mathematics. In a related Perspective, Anthony G. Greenwald discusses these findings and how they could be used to further analyze biases in the real world.

There are more details about the research in this April 13, 2017 Princeton University news release on EurekAlert (also on ScienceDaily),

In debates over the future of artificial intelligence, many experts think of the new systems as coldly logical and objectively rational. But in a new study, researchers have demonstrated how machines can be reflections of us, their creators, in potentially problematic ways. Common machine learning programs, when trained with ordinary human language available online, can acquire cultural biases embedded in the patterns of wording, the researchers found. These biases range from the morally neutral, like a preference for flowers over insects, to the objectionable views of race and gender.

Identifying and addressing possible bias in machine learning will be critically important as we increasingly turn to computers for processing the natural language humans use to communicate, for instance in doing online text searches, image categorization and automated translations.

“Questions about fairness and bias in machine learning are tremendously important for our society,” said researcher Arvind Narayanan, an assistant professor of computer science and an affiliated faculty member at the Center for Information Technology Policy (CITP) at Princeton University, as well as an affiliate scholar at Stanford Law School’s Center for Internet and Society. “We have a situation where these artificial intelligence systems may be perpetuating historical patterns of bias that we might find socially unacceptable and which we might be trying to move away from.”

The paper, “Semantics derived automatically from language corpora contain human-like biases,” published April 14  [2017] in Science. Its lead author is Aylin Caliskan, a postdoctoral research associate and a CITP fellow at Princeton; Joanna Bryson, a reader at University of Bath, and CITP affiliate, is a coauthor.

As a touchstone for documented human biases, the study turned to the Implicit Association Test, used in numerous social psychology studies since its development at the University of Washington in the late 1990s. The test measures response times (in milliseconds) by human subjects asked to pair word concepts displayed on a computer screen. Response times are far shorter, the Implicit Association Test has repeatedly shown, when subjects are asked to pair two concepts they find similar, versus two concepts they find dissimilar.

Take flower types, like “rose” and “daisy,” and insects like “ant” and “moth.” These words can be paired with pleasant concepts, like “caress” and “love,” or unpleasant notions, like “filth” and “ugly.” People more quickly associate the flower words with pleasant concepts, and the insect terms with unpleasant ideas.

The Princeton team devised an experiment with a program where it essentially functioned like a machine learning version of the Implicit Association Test. Called GloVe, and developed by Stanford University researchers, the popular, open-source program is of the sort that a startup machine learning company might use at the heart of its product. The GloVe algorithm can represent the co-occurrence statistics of words in, say, a 10-word window of text. Words that often appear near one another have a stronger association than those words that seldom do.

The Stanford researchers turned GloVe loose on a huge trawl of contents from the World Wide Web, containing 840 billion words. Within this large sample of written human culture, Narayanan and colleagues then examined sets of so-called target words, like “programmer, engineer, scientist” and “nurse, teacher, librarian” alongside two sets of attribute words, such as “man, male” and “woman, female,” looking for evidence of the kinds of biases humans can unwittingly possess.

In the results, innocent, inoffensive biases, like for flowers over bugs, showed up, but so did examples along lines of gender and race. As it turned out, the Princeton machine learning experiment managed to replicate the broad substantiations of bias found in select Implicit Association Test studies over the years that have relied on live, human subjects.

For instance, the machine learning program associated female names more with familial attribute words, like “parents” and “wedding,” than male names. In turn, male names had stronger associations with career attributes, like “professional” and “salary.” Of course, results such as these are often just objective reflections of the true, unequal distributions of occupation types with respect to gender–like how 77 percent of computer programmers are male, according to the U.S. Bureau of Labor Statistics.

Yet this correctly distinguished bias about occupations can end up having pernicious, sexist effects. An example: when foreign languages are naively processed by machine learning programs, leading to gender-stereotyped sentences. The Turkish language uses a gender-neutral, third person pronoun, “o.” Plugged into the well-known, online translation service Google Translate, however, the Turkish sentences “o bir doktor” and “o bir hem?ire” with this gender-neutral pronoun are translated into English as “he is a doctor” and “she is a nurse.”

“This paper reiterates the important point that machine learning methods are not ‘objective’ or ‘unbiased’ just because they rely on mathematics and algorithms,” said Hanna Wallach, a senior researcher at Microsoft Research New York City, who was not involved in the study. “Rather, as long as they are trained using data from society and as long as society exhibits biases, these methods will likely reproduce these biases.”

Another objectionable example harkens back to a well-known 2004 paper by Marianne Bertrand of the University of Chicago Booth School of Business and Sendhil Mullainathan of Harvard University. The economists sent out close to 5,000 identical resumes to 1,300 job advertisements, changing only the applicants’ names to be either traditionally European American or African American. The former group was 50 percent more likely to be offered an interview than the latter. In an apparent corroboration of this bias, the new Princeton study demonstrated that a set of African American names had more unpleasantness associations than a European American set.

Computer programmers might hope to prevent cultural stereotype perpetuation through the development of explicit, mathematics-based instructions for the machine learning programs underlying AI systems. Not unlike how parents and mentors try to instill concepts of fairness and equality in children and students, coders could endeavor to make machines reflect the better angels of human nature.

“The biases that we studied in the paper are easy to overlook when designers are creating systems,” said Narayanan. “The biases and stereotypes in our society reflected in our language are complex and longstanding. Rather than trying to sanitize or eliminate them, we should treat biases as part of the language and establish an explicit way in machine learning of determining what we consider acceptable and unacceptable.”

Here’s a link to and a citation for the Princeton paper,

Semantics derived automatically from language corpora contain human-like biases by Aylin Caliskan, Joanna J. Bryson, Arvind Narayanan. Science  14 Apr 2017: Vol. 356, Issue 6334, pp. 183-186 DOI: 10.1126/science.aal4230

This paper appears to be open access.

Links to more cautionary posts about AI,

Aug 5, 2009: Autonomous algorithms; intelligent windows; pretty nano pictures

June 14, 2016:  Accountability for artificial intelligence decision-making

Oct. 25, 2016 Removing gender-based stereotypes from algorithms

March 1, 2017: Algorithms in decision-making: a government inquiry in the UK

There’s also a book which makes some of the current use of AI programmes and big data quite accessible reading: Cathy O’Neil’s ‘Weapons of Math Destruction: How Big Data Increases Inequality and Threatens Democracy’.

Regrowing bone

The ability to grow bone or bone-like material could change life substantially for people with certain kinds of injuries. Scientists at Northwestern University and the University of Chicago have been able to regrow bone in a skull (according to a March 8, 2017 Northwestern University news release (also on EurekAlert),

A team of researchers repaired a hole in a mouse’s skull by regrowing “quality bone,” a breakthrough that could drastically improve the care of people who suffer severe trauma to the skull or face.

The work by a joint team of Northwestern Engineering and University of Chicago researchers was a resounding success, showing that a potent combination of technologies was able to regenerate the skull bone with supporting blood vessels in just the discrete area needed without developing scar tissue — and more rapidly than with previous methods.

“The results are very exciting,” said Guillermo Ameer, professor of biomedical engineering at Northwestern’s McCormick School of Engineering, and professor of surgery at Feinberg School of Medicine.

Supported by the China Scholarship Council, National Institute of Dental and Craniofacial Research, Chicago Community Trust, and National Center for Advancing Translational Sciences, the research was published last week in the journal PLOS One. Russell Reid, associate professor of surgery at the University of Chicago Medical Center, is the article’s corresponding author. Reid, his long-time collaborator Dr. Tong-Chuan He, and colleagues in Hyde Park brought the surgical and biological knowledge and skills. Zari P. Dumanian, affiliated with the medical center’s surgery department, was the paper’s first author.

“This project was a true collaborative team effort in which our Regenerative Engineering Laboratory provided the biomaterials expertise,” Ameer said.

Injuries or defects in the skull or facial bones are very challenging to treat, often requiring the surgeon to graft bone from the patient’s pelvis, ribs, or elsewhere, a painful procedure in itself. Difficulties increase if the injury area is large or if the graft needs to be contoured to the angle of the jaw or the cranial curve.

But if all goes well with this new approach, it may make painful bone grafting obsolete.

In the experiment, the researchers harvested skull cells from the mouse and engineered them to produce a potent protein to promote bone growth. They then used Ameer’s hydrogel, which acted like a temporary scaffolding, to deliver and contain these cells to the affected area. It was the combination of all three technologies that proved so successful, Ameer said.

Using calvaria or skull cells from the subject meant the body didn’t reject those cells.

The protein, BMP9, has been shown to promote bone cell growth more rapidly than other types of BMPs. Importantly, BMP9 also appeared to improve the creation of blood vessels in the area. Being able to safely deliver skull cells that are capable of rapidly regrowing bone in the affected site, in vivo as opposed to using them to grow bone in the laboratory, which would take a very long time, promises a therapy that might be more “surgeon friendly, if you will, and not too complicated to scale up for the patients,” Ameer said.

The scaffolding developed in Ameer’s laboratory, which is a material based on citric acid and called PPCN-g, is a liquid that when warmed to body temperature becomes a gel-like elastic material. “When applied, the liquid, which contains cells capable of producing bone, will conform to the shape of the bone defect to make a perfect fit,” Ameer said. “It then stays in place as a gel, localizing the cells to the site for the duration of the repair.” As the bone regrows, the PPCN-g is reabsorbed by the body.

“What we found is that these cells make natural-looking bone in the presence of the PPCN-g,” Ameer said. “The new bone is very similar to normal bone in that location.”

In fact, the three-part method was successful on a number of fronts: The regenerated bone was better quality, the bone growth was contained to the area defined by the scaffolding, the area healed much more quickly, and the new and old bone were continuous with no scar tissue.

The potential, if the procedure can be adapted to treat people that suffered trauma from car accidents or aggressive cancers that have affected the skull or face, would be huge, and give surgeons a much-sought-after option.

“The reconstruction procedure is a lot easier when you can harvest a few cells, make them produce the BMP9 protein, mix them in the PPCN-g solution, and apply it to the bone defect site to jump-start the new bone growth process where you want it.” Ameer said.

Ameer cautioned that the technology is years away to being used in humans, but added, “We did show proof of concept that we can heal large defects in the skull that would normally not heal on their own using a protein, cells and a new material that come together in a completely new way. Our team is very excited about these findings and the future of reconstructive surgery.”

Here’s a link and a citation for the paper,

Repair of critical sized cranial defects with BMP9-transduced calvarial cells delivered in a thermoresponsive scaffold by Zari P. Dumanian, Viktor Tollemar, Jixing Ye, Minpeng Lu, Yunxiao Zhu, Junyi Liao, Guillermo A. Ameer, Tong-Chuan He, Russell R. Reid. PLOS http://dx.doi.org/10.1371/journal.pone.0172327 Published: March 1, 2017

This is an open access paper.

Nanotechnology and Pakistan

I don’t often get information about nanotechnology in Pakistan so this March 6, 2017 news article by Mrya Imran on the TheNews.com website provides some welcome insight,

Pakistan has the right level of expert human resource and scientific activity in the field of nanotechnology. A focused national strategy and sustainable funding can make Pakistan one of the leaders in this sector.

These views were expressed by Professor of Physics in University of Illinois and Founder and President of NanoSi Advanced Technology, Inc. Dr Munir H. Nayfeh.  Dr Nayfeh, along with Executive Director, Centre for Nanoscale Science and Technology, and Research Faculty, Department of Agricultural and Biological Engineering, University of Illinois, Dr. Irfan Ahmad and Associate Professor and Director of Medical Physics Programme, Pritzker School of Medicine, University of Chicago, Dr. Bulent Aydogan were invited by COMSATS Institute of Information Technology (CIIT) to deliver lectures on nanotechnology research and entrepreneurship with special focus on cancer nanomedicine.

The objective of the visit was to motivate and mentor faculty and students at COMSATS and also to provide feedback to campus administration and the Federal Ministry of Science and Technology on strategic initiatives to help develop the next generation of science and engineering workforce in Pakistan.

A story of success for the Muslim youth from areas affected by conflict and war, Dr Nayfeh, a Palestinian by origin, was brought up in a conflict area by a mother who did not know how to read and write. For him, the environment was actually a motivator to work hard and study. “My mother was uneducated but she always wanted her children to get the highest degree possible and both my parents supported us in whatever way possible to achieve our dreams,” he recalled.

Comparing Pakistan with other developing countries in scientific research enterprise, he said that despite lack of resources, he has observed some decent amount of research outcome from the existing setups. About their visits to different labs, he said that they found faculty members and researchers in need of for more and more funds. “I don’t blame them as I am also looking for more and more fund even in America. This is a positive sign which shows that these set ups are alive and want to do more.”

Dr. Nayfeh is greatly impressed with the number of women researchers and students in Pakistan. “In Tunisia and Algeria, there were decent number of women in this field but Pakistan has the most and there are more publications coming out of Pakistan as compared to other developing countries.”

If you have the time, I suggest you read the article in its entirety.

Would you like to invest in the Argonne National Laboratory’s reusable oil spill sponge?

A March 7, 2017 news item on phys.org describes some of the US Argonne National Laboratory’s research into oil spill cleanup technology,

When the Deepwater Horizon drilling pipe blew out seven years ago, beginning the worst oil spill [BP oil spill in the Gulf of Mexico] in U.S. history, those in charge of the recovery discovered a new wrinkle: the millions of gallons of oil bubbling from the sea floor weren’t all collecting on the surface where it could be skimmed or burned. Some of it was forming a plume and drifting through the ocean under the surface.

Now, scientists at the U.S. Department of Energy’s (DOE) Argonne National Laboratory have invented a new foam, called Oleo Sponge, that addresses this problem. The material not only easily adsorbs oil from water, but is also reusable and can pull dispersed oil from the entire water column—not just the surface.

A March 6, 2017 Argonne National Laboratory news release (also on EurekAlert) by Louise Lerner, which originated the news item, provides more information about the work,

“The Oleo Sponge offers a set of possibilities that, as far as we know, are unprecedented,” said co-inventor Seth Darling, a scientist with Argonne’s Center for Nanoscale Materials and a fellow of the University of Chicago’s Institute for Molecular Engineering.

We already have a library of molecules that can grab oil, but the problem is how to get them into a useful structure and bind them there permanently.

The scientists started out with common polyurethane foam, used in everything from furniture cushions to home insulation. This foam has lots of nooks and crannies, like an English muffin, which could provide ample surface area to grab oil; but they needed to give the foam a new surface chemistry in order to firmly attach the oil-loving molecules.

Previously, Darling and fellow Argonne chemist Jeff Elam had developed a technique called sequential infiltration synthesis, or SIS, which can be used to infuse hard metal oxide atoms within complicated nanostructures.

After some trial and error, they found a way to adapt the technique to grow an extremely thin layer of metal oxide “primer” near the foam’s interior surfaces. This serves as the perfect glue for attaching the oil-loving molecules, which are deposited in a second step; they hold onto the metal oxide layer with one end and reach out to grab oil molecules with the other.

The result is Oleo Sponge, a block of foam that easily adsorbs oil from the water. The material, which looks a bit like an outdoor seat cushion, can be wrung out to be reused—and the oil itself recovered.

Oleo Sponge

At tests at a giant seawater tank in New Jersey called Ohmsett, the National Oil Spill Response Research & Renewable Energy Test Facility, the Oleo Sponge successfully collected diesel and crude oil from both below and on the water surface.

“The material is extremely sturdy. We’ve run dozens to hundreds of tests, wringing it out each time, and we have yet to see it break down at all,” Darling said.

Oleo Sponge could potentially also be used routinely to clean harbors and ports, where diesel and oil tend to accumulate from ship traffic, said John Harvey, a business development executive with Argonne’s Technology Development and Commercialization division.

Elam, Darling and the rest of the team are continuing to develop the technology.

“The technique offers enormous flexibility, and can be adapted to other types of cleanup besides oil in seawater. You could attach a different molecule to grab any specific substance you need,” Elam said.

The team is actively looking to commercialize [emphasis mine] the material, Harvey said; those interested in licensing the technology or collaborating with the laboratory on further development may contact partners@anl.gov.

Here’s a link to and a citation for the paper,

Advanced oil sorbents using sequential infiltration synthesis by Edward Barry, Anil U. Mane, Joseph A. Libera, Jeffrey W. Elam, and Seth B. Darling. J. Mater. Chem. A, 2017,5, 2929-2935 DOI: 10.1039/C6TA09014A First published online 11 Jan 2017

This paper is behind a paywall.

The two most recent posts here featuring oil spill technology are my Nov. 3, 2016 piece titled: Oil spill cleanup nanotechnology-enabled solution from A*STAR and my Sept. 15, 2016 piece titled: Canada’s Ingenuity Lab receives a $1.7M grant to develop oil recovery system for oil spills. I hope that one of these days someone manages to commercialize at least one of the new oil spill technologies. It seems that there hasn’t been much progress since the BP (Deepwater Horizon) oil spill. If someone has better information than I do about the current state of oil spill cleanup technologies, please do leave a comment.