Scientists at Sandia National Laboratories and the Max Planck Institute for the Science of Light have reported on a device that could replace a roomful of equipment to link photons in a bizarre quantum effect called entanglement. This device — a kind of nano-engineered material called a metasurface — paves the way for entangling photons in complex ways that have not been possible with compact technologies.

When scientists say photons are entangled, they mean they are linked in such a way that actions on one affect the other, no matter where or how far apart the photons are in the universe. It is an effect of quantum mechanics, the laws of physics that govern particles and other very tiny things.

Although the phenomenon might seem odd, scientists have harnessed it to process information in new ways. For example, entanglement helps protect delicate quantum information and correct errors in quantum computing, a field that could someday have sweeping impacts in national security, science and finance. Entanglement is also enabling new, advanced encryption methods for secure communication.

Research for the groundbreaking device, which is a hundred times thinner than a sheet of paper, was performed, in part, at the Center for Integrated Nanotechnologies, a Department of Energy Office of Science user facility operated by Sandia and Los Alamos national laboratories. Sandia’s team received funding from the Office of Science, Basic Energy Sciences program.

Light goes in, entangled photons come out

The new metasurface acts as a doorway to this unusual quantum phenomenon. In some ways, it’s like the mirror in Lewis Carrol’s “Through the Looking-Glass,” through which the young protagonist Alice experiences a strange, new world.

Instead of walking through their new device, scientists shine a laser through it. The beam of light passes through an ultrathin sample of glass covered in nanoscale structures made of a common semiconductor material called gallium arsenide.

“It scrambles all the optical fields,” said Sandia senior scientist Igal Brener, an expert in a field called nonlinear optics who led the Sandia team. Occasionally, he said, a pair of entangled photons at different wavelengths emerge from the sample in the same direction as the incoming laser beam.

Brener said he is excited about this device because it is designed to produce complex webs of entangled photons — not just one pair at a time, but several pairs all entangled together, and some that can be indistinguishable from each other. Some technologies need these complex varieties of so-called multi-entanglement for sophisticated information processing schemes.

Other miniature technologies based on silicon photonics can also entangle photons but without the much-needed level of complex, multi-entanglement. Until now, the only way to produce such results was with multiple tables full of lasers, specialized crystals and other optical equipment.

“It is quite complicated and kind of intractable when this multi-entanglement needs more than two or three pairs,” Brener said. “These nonlinear metasurfaces essentially achieve this task in one sample when before it would have required incredibly complex optical setups.”

The Science paper outlines how the team successfully tuned their metasurface to produce entangled photons with varying wavelengths, a critical precursor to generating several pairs of intricately entangled photons simultaneously.

However, the researchers note in their paper that the efficiency of their device — the rate at which they can generate groups of entangled photons — is lower than that of other techniques and needs to be improved.

What is a metasurface?

A metasurface is a synthetic material that interacts with light and other electromagnetic waves in ways conventional materials can’t. Commercial industries, said Brener, are busy developing metasurfaces because they take up less space and can do more with light than, for instance, a traditional lens.

“You now can replace lenses and thick optical elements with metasurfaces,” Brener said. “Those types of metasurfaces will revolutionize consumer products.”

Sandia is one of the leading institutions in the world performing research in metasurfaces and metamaterials. Between its Microsystems Engineering, Science and Applications complex, which manufactures compound semiconductors, and the nearby Center for Integrated Nanotechnologies, researchers have access to all the specialized tools they need to design, fabricate and analyze these ambitious new materials.

“The work was challenging as it required precise nanofabrication technology to obtain the sharp, narrowband optical resonances that seeds the quantum process of the work,” said Sylvain Gennaro, a former postdoctoral researcher at Sandia who worked on several aspects of the project.

The device was designed, fabricated and tested through a partnership between Sandia and a research group led by physicist Maria Chekhova, an expert in the quantum entanglement of photons at the Max Planck Institute for the Science of Light.

“Metasurfaces are leading to a paradigm shift in quantum optics, combining ultrasmall sources of quantum light with far reaching possibilities for quantum state engineering,” said Tomás Santiago-Cruz, a member of the Max Plank team and first author on the paper.

Brener, who has studied metamaterials for more than a decade, said this newest research could possibly spark a second revolution — one that sees these materials developed not just as a new kind of lens, but as a technology for quantum information processing and other new applications.

“There was one wave with metasurfaces that is already well established and on its way. Maybe there is a second wave of innovative applications coming,” he said

Sandia National Laboratories is a multimission laboratory operated by National Technology and Engineering Solutions of Sandia LLC, a wholly owned subsidiary of Honeywell International Inc., for the U.S. Department of Energy’s National Nuclear Security Administration. Sandia Labs has major research and development responsibilities in nuclear deterrence, global security, defense, energy technologies and economic competitiveness, with main facilities in Albuquerque, New Mexico, and Livermore, California.

People with diabetes may experience damage to the small blood vessels in various organs. The reasons for this are unclear, but it has been known since the 1990s that good control of blood sugar levels reduces the risk of complications. It has, however, not been clear what level of long-term sugar, HbA_1c, people with type 1 diabetes should have in order to avoid serious damage to blood vessels in the eyes and kidneys.

“Our study determines accurately the levels of long-term sugar that can avoid complications. This knowledge can increase a person’s motivation to keep their blood sugar level under control,” says Hans Arnqvist, professor emeritus at Linköping University and leader of the study.

Researchers in the current study, known as VISS (Vascular Diabetic Complications in Southeast Sweden), have followed all children and adults younger than 35 years who developed type 1 diabetes during the period 1983-1987, and who received care in the South-East Healthcare Region of Sweden. All 447 newly diagnosed persons in the region during this period were included in the study. The researchers have followed the patients’ HbA_1c values, which reflect their average blood sugar levels during a longer period. They have also monitored the development of eye- and kidney damage in these patients for a period of between 32 and 36 years after diagnosis.

The small blood vessels in the eye are particularly susceptible to damage in type 1 diabetes. Nearly all patients experience small haemorrhages in the eye that do not affect their vision. In some cases, new blood vessels develop in the retina. The latter is known as ‘proliferative retinopathy’, and can lead to blindness. Another effect of diabetes concerns the area known as the ‘macula’ of the retina, where high-focus vision is located. Damage here leads to blurred vision.

The kidneys are not as sensitive to high blood sugar levels as the eye, but the important small blood vessels here can also be damaged. One consequence of such damage is the excretion of blood proteins in the urine. Albumin is the protein with highest concentration in the blood, and when it is present in the urine the condition is known as ‘albuminuria’. The damage to the kidneys eventually leads to impaired kidney function and, in serious cases, kidney failure. This is a fatal condition if untreated, and the patient must either undergo dialysis or receive a kidney transplant.

The blood sugar level in a healthy person is very closely controlled, with a maximum HbA_1c level of 42 mmol/mol (6.0%).

“The results of our study show that people with type 1 diabetes for at least 32 years should keep their mean long-term sugar level below 53 mmol/mol (7.0%), if they are to completely avoid serious damage. The risk of eye- and kidney complications increases as the level increases. Our conclusions relate to avoiding complications arising from blood vessel damage. But if a patient has problems with low blood sugar, hypoglycaemia, it’s not possible to control the blood sugar level so strictly,” says Hans Arnqvist.

The target level for HbA_1c that is suggested by the results of the VISS study agrees with the individual targets recommended by the American Diabetes Association. In Sweden, target levels are given for groups, rather than individuals.

The previous follow-up by the research group was conducted 20 years after the onset of disease. Now after 30 years, the results show that damage has arisen at lower blood sugar levels than was the case after 20 years. More patients have experienced damage, despite having blood sugar levels that are not higher than those they have previously had. In other words, it seems that the threshold for developing complications falls gradually with time. This means that the study does not allow any conclusions for the recommended blood sugar levels of people with type 1 diabetes longer than 30 years after diagnosis.

The VISS study has received funding from the Swedish Child Diabetes Foundation and the Foundation Funds of Region Östergötland.

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Materials provided by Linköping University. Original written by Karin Söderlund Leifler. Note: Content may be edited for style and length.

“When I first saw a video of the cockatoos opening the bins I thought it was such an interesting and unique behavior and I knew we needed to look into it,” says lead author Barbara Klump, a behavioral ecologist at the Max Planck Institute of Animal Behavior.

The cockatoos’ motivation is food waste. “They really like bread,” she says. “Once one gets a bin open all the cockatoos in the vicinity will come and try to get something nice to eat.”

The birds typically pry the bins open with their beaks and then maneuver themselves onto a small rim and flip the lid open. It’s a community affair. “We could actually show that this is a cultural trait,” says Klump. “The cockatoos learn the behavior from observing other cockatoos and within each group they sort of have their own special technique, so across a wide geographic range the techniques are more dissimilar.”

Human residents trying to keep the cockatoos out can’t simply secure the bin lids completely closed because the lids need to open when tipped by an automated arm on the garbage truck. A survey given by the researchers found that people put bricks and stones on their bin lids, strap water bottles to the top, rig ropes to prevent the lid from flipping, use sticks to block the hinges, and switch tactics once the cockatoos figure them out. “There are even commercially available cockatoo locks for bins,” says Klump.

“It’s not just a social learning on the cockatoo side, but it’s also social learning on the human side,” she says. “People come up with new protection methods on their own, but a lot of people actually learn it from their neighbors or people on their street, so they get their inspiration from someone else.”

Klump won’t say who she expects to win the race for control of the bins, but she and her colleagues plan to look at how the cockatoos’ behavior varies from season to season.

Klump expects we will see more of these kinds of human-wildlife interactions in the future. “As cities expand, we will have more interactions with wildlife,” she says. “I’m hoping that there will be a better understanding and more tolerance for the animals that we share our lives with.”

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In a new study, researchers led by Serge Y. Fuchs of the School of Veterinary Medicine, have uncovered a detailed mechanism by which tumors can skirt both the immune system and cancer therapies that leverage its power, such as genetically engineered CAR T cells.

Their investigation, published in the journal Cell Metabolism, revealed how tumor-derived factors stimulate trogocytosis — a process derived from the Greek word trogo, which means “to gnaw” or “to chew.” When T cells interact with cancer cells, they can sometimes “nibble” a piece of the cancer cell membrane. When that membrane segment includes an antigen, a molecule specific to the cancer, the T cells may then begin expressing that antigen on their own cell surface, making it appear to other T cells like a cancer cell.

Trogocytosis can affect a patient’s own T cells and those modified to become CAR T cells, an approach in which a patient’s T cells are genetically engineered to specifically target cancer cells, grown in a lab, and then delivered back to the patient.

“Trogocytosis can lead to three different things, and all three are bad for a person with a tumor,” says Fuchs, the senior author on the work. “First of all, the tumor cell did not get killed and has lost an antigen, which may mean that even if another, better equipped T cell comes along, it will not recognize it, giving cancer cells a window of opportunity to grow unchecked. The second problem is, for reasons we still don’t understand, once a T cell takes a piece of the tumor cell membrane, it becomes much less active. And the third problem is very ironic. Because now, a T cell that displays tumor antigen, this ‘sheep in wolf’s clothing,’ may then become victim to ‘fratricide,’ killed by another T cell.” Overall, the result is a decline in killer T cell numbers and activity and a bump in opportunities for the cancer cells to escape detection and grow.

“What we see is that only a small number of cells undergo trogocytosis and then they disappear quickly because they’re killed. So we’re studying a vanishing act. It is hard to do — very expensive and very tedious — but it appears to be very important,” says Fuchs.

With a longstanding interest in how receptors on the surface of immune cells guide anti-cancer immunity, Fuchs and colleagues have made a variety of discoveries showing how tumors can manipulate T cells to escape being targeted and killed.

A particular area of interest is what’s known as tumor-derived factors, or the concoction of proteins, lipids, and other materials that cancer cells secrete into the body. In the current study, the Penn researchers found that collecting these secretions and exposing the resulting solution to T cells hampered the cells’ ability to do their cancer-fighting job.

“Just exposing them to this tumor-conditioned media caused them to kill fewer cancer cells, trogocytose more, and get killed more,” Fuchs says.

Trogocytosis was previously believed to have something to do with cancer’s ability to hinder anti-cancer immunity, but the Penn-led team pinned down the mechanism, showing that T cells exposed to tumor-derived factors experienced a notable decline in levels of the gene CH25H. This gene is known to be involved in altering cell’s lipid membranes and can inhibit two cell membranes from fusing together — an essential process for trogocytosis to occur. When they added back a metabolite produced by CH25H, they could block trogocytosis.

“That was an ‘aha’ moment,” Fuchs says.

Further characterization of the pathway helped the team identify another player, the gene ATF3, which opposes the activity of CH25H. Eliminating AFT3 prevented trogocytosis from occurring and restored the ability of T cells to kill tumor cells.

Not only do the new insights suggest novel targets for anti-cancer therapies, but they may have immediate significance for CAR T therapy. Since trogocytosis could impair the effectiveness of the engineered T cells delivered in CAR T, the researchers surmised that blocking this could improve CAR T performance. “We figured, why don’t we use what is cleverly known as an ‘armored CAR’ approach, and co-express CH25H in the CAR T,” Fuchs says. “This turned out to be more efficient than the old CAR T cells.”

Indeed, delivering the CAR T cells adorned with CH25H improved the survival of mice with cancer compared to the unarmored CAR T cells.

Though only a small percentage of T cells are involved in trogocytosis, Fuchs says it may be an underappreciated process when it comes to cancer immunity and other processes, such as those involved in autoimmunity. With future work, he and colleagues intend to explore the roles of ATF3 and CH25H and other molecules in trogocytosis. And he’s hopeful that other researchers will pick up on these lines of work, bringing the findings closer to clinical application.

“I can see this going into use in CAR T therapy quickly,” Fuchs says. “It’s ready to play.”

Serge Fuchs is the Elizabeth and William Whitney Clark Professor of Oncology at the University of Pennsylvania School of Veterinary Medicine.

Fuchs’ coauthors on the work were Penn Vet’s Zhen Lu, Noreen McBrearty, Jinyun Chen, Vivek S. Tomar, Hongru Zhang, Gianluca De Rosa, and Daniel P. Beiting; the Perelman School of Medicine’s Aiwen Tan, Aalim M. Weljie, Zhen Miao, Subin S. George, and Constantinos Koumensis; Takeda Development Center’s Allison Berger and Gurpanna Saggu; and Case Western Reserve University’s J. Alan Diehl.

The study was supported in part by the National Institutes of Health (grants CA247803, CA240814, CA165997, and CA115299).

The 10^th oocyte collection in northern white rhinos (NWR) was performed by a team of scientists and conservationists from the Leibniz Institute for Zoo and Wildlife Research (Leibniz-IZW), Ol Pejeta Conservancy, Safari Park Dvůr Králové, Kenya Wildlife Service (KWS) & Wildlife Research and Training Institute (WRTI) on July 28, 2022, at Ol Pejeta Conservancy in Kenya. The BioRescue team was able to collect 23 oocytes from Fatu, the younger of the two remaining NWR females. Oocyte collections from Najin, Fatu’s mother, were ceased in 2021 following an in-depth ethical risk assessment. The oocytes were immediately air-lifted to the Avantea laboratory in Cremona, Italy. Following maturation, 7 of the oocytes were fertilized using cryopreserved, thawed semen from the deceased NWR male Angalifu. Eventually, 5 embryos of Fatu were successfully produced and cryopreserved in liquid nitrogen.

This collection followed on from the 9^th oocyte collection held at the same location and by the same team on April 24^th. Out of 16 collected oocytes, 3 embryos were produced in the Avantea laboratory, again using the semen of Angalifu. Successful results of both procedures raised the total number of NWR embryos produced to 22 — all of them from female Fatu, with half of them sired by the deceased male Suni who was born in Safari Park Dvůr Králové, Czech Republic, and the other half sired by Angalifu who lived in San Diego Zoo Safari Park, USA.

Once the protocol to transfer the embryos to surrogate southern white rhino (SWR) female recipients is optimized, the embryos will be the foundation of a new NWR population, eventually destined to step back into their ecological role as keystone grazers in Central Africa.

To set up suitable conditions for a successful embryo transfer, the team has been carefully following the interactions of the sterilized SWR bull Owuan, who serves as the oestrus detector, with the possible surrogate females that share an enclosure with him. Once the conditions allow it, the BioRescue team will attempt to conduct an embryo transfer — first with SWR embryos to demonstrate that the whole procedure works properly before the team uses the extremely valuable NWR embryos. The team is currently considering whether adding more SWR females to the program might increase the chance of achieving the first successful embryo transfer.

Thomas Hildebrandt, BioRescue project leader and head of Department of Reproduction Management at Leibniz-IZW: “In 2019, one day before our worldwide first oocyte collection in NWR I said — tomorrow we will change the world. Today I can say, we did: The 5 new NWR embryos created in one set of procedures are a new record in our mission to save the NWR from the brink of extinction. In total, we managed to produce and cryopreserve 22 pure NWR embryos from 158 oocytes collected during 10 collections: 148 from Fatu and 10 from Nájin. Our next aim is to successfully produce viable offspring by inventing and using new scientific embryo transfer methods and techniques. The ground breaking scientific work we are establishing here will lay the groundwork for future conservation rescue initiatives.”

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