“This case study shows that it is possible to use these neural control technologies, in which devices respond to electrical signals from a patient’s muscles, to help patients using robotic prosthetic ankles move more naturally and intuitively,” says Helen Huang, corresponding author of the study. Huang is the Jackson Family Distinguished Professor in the Joint Department of Biomedical Engineering at NC State and UNC.

“This work demonstrates that these technologies can give patients the ability to do more than we previously thought possible,” says Aaron Fleming, first author of the study and a Ph.D. candidate in the joint biomedical engineering department.

Most of the existing research on robotic prosthetic ankles has focused solely on walking using autonomous control. Autonomous control, in this context, means that while the person wearing the prosthesis decides whether to walk or stand still, the fine movements involved in those movements happen automatically — rather than because of anything the wearer is doing.

Huang, Fleming and their collaborators wanted to know what would happen if an amputee, working with a physical therapist, trained with a neurally controlled powered prosthetic ankle on activities that are challenging with typical prostheses. Would it be possible for amputees to regain a fuller range of control in the many daily motions that people make with their ankles in addition to walking?

The powered prosthesis in this study reads electrical signals from two residual calf muscles. Those calf muscles are responsible for controlling ankle motion. The prosthetic technology uses a control paradigm developed by the researchers to convert electrical signals from those muscles into commands that control the movement of the prosthesis.

The researchers worked with a study participant who had lost one leg about halfway between the knee and the ankle. The participant was fitted with the powered prosthetic ankle and did an initial evaluation. The patient then had five training sessions with a physical therapist, each lasting about two hours, over the course of two-and-a-half weeks. After the training was completed, the participant did a second evaluation.

After training, the study participant was able to do a variety of tasks that had been difficult before, such as going from sitting to standing without any external assistance or squatting to pick something up off the ground without compensating for the movement with other body parts. But one of the most pronounced differences was the study participant’s stability, whether standing or moving. This was reflected in both empirical evaluations — such as testing the patient’s stability when standing on foam — and in the patient’s level of confidence in his own stability.

“The concept of mimicking natural control of the ankle is very straightforward,” Huang says. “But implementation of this concept is more complicated. It requires training people to use residual muscles to drive new prosthetic technologies. The results in this case study were dramatic. This is just one study, but it shows us what is feasible.”

“There is also a profound emotional impact when people use powered prosthetic devices that are controlled by reading the electrical signals that their bodies are making,” Fleming says. “It is much more similar to the way people move intuitively, and that can make a big difference in how people respond to using a prosthesis at all.”

The researchers are already having more people go through the training paradigm and are expanding their testing to assess the results of that training.

Before making this technology more widely available, the researchers also want to engage in real-world beta testing — with people using the robotic prosthesis during their daily routines.

“As with any prosthetic device for lower limbs, you have to make sure the device is consistent and reliable, so that it doesn’t fail when people are using it,” Huang says.

“Powered prostheses that exist now are very expensive and are not covered by insurance,” Fleming says. “So there are issues related to access to these technologies. By attempting to restore normal control of these type of activities, this technology stands to really improve quality of life and community participation for individuals with amputation. This would make these expensive devices more likely to be covered by insurance in the future if it means improving the overall health of the individual.”

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Materials provided by North Carolina State University. Original written by Matt Shipman. Note: Content may be edited for style and length.

Doctoral student Jonatan Jungmalm recruited a little over 200 recreational runners from the list of entrants for the Göteborgsvarvet Half Marathon and monitored them over a period of one year. To take part in the study, they had to have been running for at least a year, have run an average of at least 15 km per week over the past year and have been injury free for at least six months. The participants were men and women in the age range 18-55.

Calculation shows injury for half of runners

Over the year of the study, the recreational runners filled in a training diary, entering information about how far they ran each day and whether they felt any pain. Those who suffered sudden injury or felt pain for a prolonged period were examined by a sports doctor.

“A third of the participants were injured over the course of the study. But if you also take account of the participants who dropped out of the study, it is reasonable to assume that almost half of all recreational runners injure themselves in a year,” states Jonatan Jungmalm.

Jonatan used a particular statistical method to calculate the proportion of injured runners, taking into account the rate of dropout that is common in studies based on voluntary participation.

Injuries to knee, calf and Achilles tendon

Of those hit by injury, half had problems with their knees, calves or Achilles tendons.

“Few of the injuries were long-lasting. But all the injuries prevented the runners from exercising as usual,” says Jonatan.

No difference was found in terms of gender, age, running experience or weight between those who injured themselves and those who did not.

“However, those who had previously been injured were more likely to be affected again.”

Multiple physical tests

All the participants were put through a series of physical tests before the study, ranging from strength tests and mobility tests to tests of running style.

“Those who had relatively weak outer thighs faced a higher risk of injury. Those with late pronation in their running gait were also at higher risk. However, having a weak torso or limited muscle flexibility was of no great significance.”

Link to sport science thesis “Running-related injuries among recreational runners. How many, who, and why?”: http://hdl.handle.net/2077/67446

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Materials provided by University of Gothenburg. Note: Content may be edited for style and length.

Using EMBL Hamburg’s world-class beamline P12 at DESY’s PETRA III synchrotron, a team of Slovenian researchers, in collaboration with EMBL’s Svergun group, directed powerful X-ray beams at artificial proteins called coiled-coil origami. The proteins were designed to fold into a particular shape based on short modules that interact in pairs. By determining their molecular structure at the EMBL beamline, the researchers confirmed that the proteins folded into the desired shape and then studied the self-assembly process step by step. These findings advance understanding of how synthetic origami-like protein folding could potentially convey therapeutics, making it possible to more precisely target medication, minimising side-effects and maximising effectiveness.

“Recently scientists realised that natural proteins represent only a tiny fraction of possible protein shapes and that we can use design principles distinct from natural proteins. We can tailor designed proteins to make new materials, deliver drugs and vaccines, and much more,” says Roman Jerala, a synthetic biologist at the National Institute of Chemistry in Ljubljana, Slovenia, who led the work to design and build a bipyramid (a diamond shape made of two conjoined triangular pyramids) from different types of artificial protein chains.

While scientists first attempted origami using DNA, proteins lend themselves more to potential applications. Proteins are the molecular machines of life, containing long chains of amino acids that fold into shapes specific to the functions they serve. That can mean bolstering immunity, talking to other cells, or carrying out other tasks to keep the body healthy. The proteins used in this study were folded into braided ropes called coiled coils, which readily bind to other parts of the same chain or to other molecules. This makes them a particularly good building material for creating custom-made nanostructures.

Roman’s team first succeeded in this quest with a simpler origami structure — a single pyramid with a triangular base. They checked one chain of protein built of amino acids in a specific order and saw how it self-assembles. Then it was time to transform it from one structure to another, as if an origami lotus could transform into a crane. They put together two different chains of amino acids carrying a signal for a scissor enzyme called a protease, informing it where to make a cut in the origami protein. By doing so, they managed to force the protein to perform its origami transformation into a different shape.

Shining a light on protein solutions

To do this kind of work, the researchers need high-tech tools. EMBL Hamburg’s beamline P12 is particularly suited for this purpose, and EMBL’s Svergun group is known for its expertise in a technique called small-angle X-ray scattering (SAXS). Since 2018, EMBL scientists have been collaborating with the group from Slovenia, supporting them in using SAXS to study the structure of origami proteins.

“In SAXS, we shine X-rays at a glass capillary that contains the protein solutions. As the X-rays scatter as they pass through the solution, we have a way to interpret the structures,” says group leader Dmitri Svergun. “Here, most data collection work is automated, and we also provide important software and analysis support in collaborations like this one.”

Using the EMBL beamline, together with electron microscopy, calorimetry, computational modelling, and other methods, the researchers assembled the data needed to identify the structures of the origami proteins and confirm that the shapes would fit into their overall origami design.

“It’s our job to obtain the best signal from the beamline and create the optimal conditions for getting data,” says Stefano Da Vela, a postdoc in the Svergun group. “We provide tools to help make sense of the SAXS experimental data and create 3D models from the data.”

The researchers observed that their synthetic proteins assemble ‘bottom up’, which means that small, detailed bits form first and then assemble together into a bigger structure. Understanding this will help researchers construct more complex protein origami structures with more precision. “SAXS analysis was crucial in identifying which design leads to the desired shapes, and the superb tools developed at EMBL allowed us to detect unique features of our designed cages,” says Fabio Lapenta, a postdoc at the National Institute of Chemistry and the lead author of their recent paper in Nature Communications that described this work. “Coiled coils are excellent tools that can be used in cells as well as in isolated proteins. We think we can expand the potential of coiled-coil protein origami to design many new protein folds and introduce interesting functionalities.”

Why is sugar not transparent? Because light that penetrates a piece of sugar is scattered, altered and deflected in a highly complicated way. However, as a research team from TU Wien (Vienna) and Utrecht University (Netherlands) has now been able to show, there is a class of very special light waves for which this does not apply: for any specific disordered medium — such as the sugar cube you may just have put in your coffee — tailor-made light beams can be constructed that are practically not changed by this medium, but only attenuated. The light beam penetrates the medium, and a light pattern arrives on the other side that has the same shape as if the medium were not there at all.

This idea of “scattering-invariant modes of light” can also be used to specifically examine the interior of objects. The results have now been published in the journal Nature Photonics.

Astronomically many possible wave forms

The waves on a turbulent water surface can take on an infinite number of different shapes — and in a similar way, light waves can also be made in countless different forms. “Each of these light wave patterns is changed and deflected in a very specific way when you send it through a disordered medium,” explains Prof. Stefan Rotter from the Institute of Theoretical Physics at TU Wien.

Together with his team, Stefan Rotter is developing mathematical methods to describe such light scattering effects. The expertise to produce and characterise such complex light fields was contributed by the team around Prof. Allard Mosk at Utrecht University. “As a light-scattering medium, we used a layer of zinc oxide — an opaque, white powder of completely randomly arranged nanoparticles,” explains Allard Mosk, the head of the experimental research group.

First, you have to characterise this layer precisely. You shine very specific light signals through the zinc oxide powder and measure how they arrive at the detector behind it. From this, you can then conclude how any other wave is changed by this medium — in particular, you can calculate specifically which wave pattern is changed by this zinc oxide layer exactly as if wave scattering was entirely absent in this layer.

“As we were able to show, there is a very special class of light waves — the so-called scattering-invariant light modes, which produce exactly the same wave pattern at the detector, regardless of whether the light wave was only sent through air or whether it had to penetrate the complicated zinc oxide layer,” says Stefan Rotter. “In the experiment, we see that the zinc oxide actually does not change the shape of these light waves at all — they just get a little weaker overall,” explains Allard Mosk.

A stellar constellation at the light detector

As special and rare as these scattering-invariant light modes may be, with the theoretically unlimited number of possible light waves, one can still find many of them. And if you combine several of these scattering-invariant light modes in the right way, you get a scattering-invariant waveform again.

“In this way, at least within certain limits, you are quite free to choose which image you want to send through the object without interference,” says Jeroen Bosch, who worked on the experiment as a Ph.D. student. “For the experiment we chose a constellation as an example: The Big Dipper. And indeed, it was possible to determine a scattering-invariant wave that sends an image of the Big Dipper to the detector, regardless of whether the light wave is scattered by the zinc oxide layer or not. To the detector, the light beam looks almost the same in both cases.”

A look inside the cell

This method of finding light patterns that penetrate an object largely undisturbed could also be used for imaging procedures. “In hospitals, X-rays are used to look inside the body — they have a shorter wavelength and can therefore penetrate our skin. But the way a light wave penetrates an object depends not only on the wavelength, but also on the waveform,” says Matthias Kühmayer, who works as a Ph.D. student on computer simulations of wave propagation. “If you want to focus light inside an object at certain points, then our method opens up completely new possibilities. We were able to show that using our approach the light distribution inside the zinc oxide layer can also be specifically controlled.” This could be interesting for biological experiments, for example, where you want to introduce light at very specific points in order to look deep inside cells.

What the joint publication of the scientists from the Netherlands and Austria shows already is how important international cooperation between theory and experiment is for achieving progress in this area of research.