“One of the big challenges we have in the field is that the majority of prostate cancer therapies target hormones — the androgen axis,” says University of Colorado Cancer Center mentored member Cecilia Caino, PhD. “But nearly all patients develop resistance to those drugs and then get a more aggressive disease that starts moving to other parts of the body. It’s been confined to the prostate, but now it might move over to the bones or the liver, or the lungs. That’s really a big problem, because when you start to compromise the vital organs, the patient eventually will die.”

In spring 2021, Caino received an Idea Award from the U.S. Department of Defense’s Peer Reviewed Cancer Research Program to investigate the role of mitochondria — the small energy factories in cells that help to break down food into fuel — in metastatic prostate cancer.

In initial research recently published in the journal Molecular Cancer Research, Caino and her co-investigators discovered that tumor cells use mitochondria to control their growth and detect stress that can destroy a tumor cell if it is not controlled. In addition to the Department of Defense, the research is funded by the American Cancer Society, the Boettcher Foundation, and the National Institute of General Medical Sciences.

“We know that tumor cells are very resistant to stress in general; that’s what makes them so hard to target with therapies,” Caino says. “But when the tumors grow too fast, they start running out of nutrients to keep building. They utilize this mitochondrial pathway that we describe to slow down for a moment, adapt, and expand their capacity to synthesize more blocks to build the cells.”

A compound to target

Caino and her team also found that a mitochondrial protein called MIRO2 is overexpressed in metastatic prostate cancer tumors. Having previously found that MIRO2 works together with two other proteins called GCN1 and GCN2 to help metastatic prostate cancer cells tolerate conditions where growth of normal cells would be prevented, Caino now hypothesizes that targeting this protein compound can inhibit the mitochondrial process that prevents tumor cells from destroying themselves by expanding too quickly.

“Our next step is to treat animal models that have metastases and see if we can eliminate the tumor or prevent the metastasis from even occurring in the first place,” she says. “We’re also learning a lot more about the complex, because we want to know how it’s regulated. That will help us stratify patients who will benefit from the therapy from those who will not.”

The researchers will start out treating the metastasis with an existing drug used to treat acute lymphocytic leukemia, but Caino also hopes to eventually design a drug that would prevent the complex from forming in the first place.

“A lot of times drugs work for a while, then they stop working. You already have to be thinking about what you’re going to do when that drug doesn’t work anymore,” she says. “Hopefully we can come up with a strategy to stop the process farther upstream.”

Milestone research

Caino is especially excited about this research as it represents her first peer-reviewed paper as a senior corresponding author. It also marks 22 years from her first experience in lab research.

“I decided to start a new line of research that did not stem directly from my postdoctoral studies,” she says. “I also chose to begin my lab with a couple of graduate students and a technician, investing in their training while remaining involved in bench work myself. Walking this long, winding road was challenging and called upon every single skill and strength I had.”

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Materials provided by University of Colorado Anschutz Medical Campus. Original written by Greg Glasgow. Note: Content may be edited for style and length.

Despite the name, quantum spin liquids are solid materials in which quantum entanglement and the geometric arrangement of atoms frustrate the natural tendency of electrons to magnetically order themselves in relation to one another. The geometric frustration in a quantum spin liquid is so severe that electrons fluctuate between quantum magnetic states no matter how cold they become.

Theoretical physicists routinely work with quantum mechanical models that manifest quantum spin liquids, but finding convincing evidence that they exist in actual physical materials has been a decadeslong challenge. While a number of 2D or 3D materials have been proposed as possible quantum spin liquids, Rice University physicist Andriy Nevidomskyy said there’s no established consensus among physicists that any of them qualify.

Nevidomskyy is hoping that will change based on the computational sleuthing he and colleagues from Rice, Florida State University and the Max Planck Institute for Physics of Complex Systems in Dresden, Germany, published this month in the open-access journal npj Quantum Materials.

“Based on all the evidence we have today, this work confirms that the single crystals of the cerium pyrochlore identified as candidate 3D quantum spin liquids in 2019 are indeed quantum spin liquids with fractionalized spin excitations,” he said.

The inherent property of electrons that leads to magnetism is spin. Each electron behaves like a tiny bar magnet with a north and south pole, and when measured, individual electron spins always point up or down. In most everyday materials, spins point up or down at random. But electrons are antisocial by nature, and this can cause them to arrange their spins in relation to their neighbors in some circumstances. In magnets, for example, spins are collectively arranged in the same direction, and in antiferromagnets they are arranged in an up-down, up-down pattern.

At very low temperatures, quantum effects become more prominent, and this causes electrons to arrange their spins collectively in most materials, even those where spins would point in random directions at room temperature. Quantum spin liquids are a counterexample where spins do not point in a definite direction — even up or down — no matter how cold the material becomes.

“A quantum spin liquid, by its very nature, is an example of a fractionalized state of matter,” said Nevidomskyy, associate professor of physics and astronomy and a member of both the Rice Quantum Initiative and the Rice Center for Quantum Materials (RCQM). “The individual excitations are not spin flips from up to down or vice versa. They’re these bizarre, delocalized objects that carry half of one spin degree of freedom. It’s like half of a spin.”

Nevidomskyy was part of the 2019 study led by Rice experimental physicist Pengcheng Dai that found the first evidence that cerium zirconium pyrochlore was a quantum spin liquid. The team’s samples were the first of their kind: Pyrochlores because of their 2-to-2-to-7 ratio of cerium, zirconium and oxygen, and single crystals because the atoms inside were arranged in a continuous, unbroken lattice. Inelastic neutron scattering experiments by Dai and colleagues revealed a quantum spin liquid hallmark, a continuum of spin excitations measured at temperatures as low as 35 millikelvin.

“You could argue that they found the suspect and charged him with the crime,” Nevidomskyy said. “Our job in this new study was to prove to the jury that the suspect is guilty.”

Nevidomskyy and colleagues built their case using state-of-the-art Monte Carlo methods, exact diagonalization as well as analytical tools to perform the spin dynamics calculations for an existing quantum mechanical model of cerium zirconium pyrochlore. The study was conceived by Nevidomskyy and Max Planck’s Roderich Moessner, and the Monte Carlo simulations were performed by Florida State’s Anish Bhardwaj and Hitesh Changlani with contributions from Rice’s Han Yan and Max Planck’s Shu Zhang.

“The framework for this theory was known, but the exact parameters, of which there are at least four, were not,” Nevidomskyy said. “In different compounds, these parameters could have different values. Our goal was to find those values for cerium pyrochlore and determine whether they describe a quantum spin liquid.

“It would be like a ballistics expert who is using Newton’s second law to calculate a bullet’s trajectory,” he said. “Newton’s law is known, but it only has predictive power if you supply the initial conditions like the bullet’s mass and initial velocity. Those initial conditions are analogous to these parameters. We had to reverse engineer, or sleuth out, ‘What are those initial conditions inside this cerium material?’ and, ‘Does that match the prediction of this quantum spin liquid?'”

To build a convincing case, the researchers tested the model against thermodynamic, neutron-scattering and magnetization results from previously published experimental studies of cerium zirconium pyrochlore.

“If you just have one piece of evidence, you might inadvertently find several models that still fit the description,” Nevidomskyy said. “We actually matched not one, but three different pieces of evidence. So, a single candidate had to match all three experiments.”

Some studies have implicated the same type of quantum magnetic fluctuations that arise in quantum spin liquids as a possible cause for unconventional superconductivity. But Nevidomskyy said the computational findings are primarily of fundamental interest to physicists.

“This satisfies our innate desire, as physicists, to find out how nature works,” he said. “There’s no application I know of that might benefit. It’s not immediately tied to quantum computing, although ideas exist for using fractionalized excitations as a platform for logical qubits.”

He said one particularly interesting point for physicists is the deep connection between quantum spin liquids and the experimental realization of magnetic monopoles, theoretical particles whose potential existence is still debated by cosmologists and high-energy physicists.

“When people talk about fractionalization, what they mean is the system behaves as if a physical particle, like an electron, splits into two halves that kind of wander around and then recombine somewhere later,” Nevidomskyy said. “And in pyrochlore magnets such as the one we studied, these wandering objects moreover behave like quantum magnetic monopoles.”

Magnetic monopoles can be visualized as isolated magnetic poles like either the upward or downward facing pole of a single electron.

“Of course, in classical physics one can never isolate just one end of a bar magnet,” he said. “The north and south monopoles always come in pairs. But in quantum physics, magnetic monopoles can hypothetically exist, and quantum theorists constructed these almost 100 years ago to explore fundamental questions about quantum mechanics.

“As far as we know, magnetic monopoles don’t exist in a raw form in our universe,” Nevidomskyy said. “But it turns out that a fancy version of monopoles does exist in these cerium pyrochlore quantum spin liquids. A single spin flip creates two fractionalized quasiparticles called spinons that behave like monopoles and wander around the crystal lattice.”

The study also found evidence that monopole-like spinons were created in an unusual way in cerium zirconium pyrochlore. Due to the tetrahedral arrangement of magnetic atoms in the pyrochlore, the study suggests they develop octupolar magnetic moments — spin-like magnetic quasiparticles with eight poles — at low temperatures. The research showed spinons in the material were produced from both these octupolar sources and more conventional, dipolar spin moments.

“Our modeling established the exact proportions of interactions of these two components with one another,” Nevidomskyy said. “It opens a new chapter in the theoretical understanding of not only the cerium pyrochlore materials but of octupolar quantum spin liquids in general.”

The research was funded by the National Science Foundation’s Division of Materials Research (1917511, 1644779, 2046570, 1742928, 1748958, 1607611), the Welch Foundation (C-1818) and the German Research Foundation (SFB-1143-247310070, EXC-2147-390858490). The scientists thank the Kavli Institute for Theoretical Physics and Aspen Center for Physics where a portion of the research was performed.

RCQM leverages global partnerships and the strengths of more than 20 Rice research groups to address questions related to quantum materials. RCQM is supported by Rice’s offices of the provost and the vice provost for research, the Wiess School of Natural Sciences, the Brown School of Engineering, the Smalley-Curl Institute and the departments of Physics and Astronomy, Electrical and Computer Engineering, and Materials Science and NanoEngineering.

UAVs are occupying an ever-growing space in aviation circles. In a new paper published in the journal Composite Structures, Suong Hoa and his student co-authors present a method to make UAV wings cheaper to manufacture and more efficient in flight.

Hoa is a professor of mechanical, industrial and aerospace engineering at the Gina Cody School of Engineering and Computer Science. Using a technique Hoa pioneered known as 4D printing of composites, the authors performed a feasibility study on the application of a new way to manufacture adaptive compliant trailing edge (ACTE) morphing wings. The experimental technology replaces the commonly used hinged wing flap with one that is attached to the main wing body but can bend up to 20 degrees.

“Our paper shows that a UAV using this kind of wing can support a good amount of load for small or medium-sized vehicles,” says Hoa, director of the Concordia Centre for Composites.

Using material reactions

4D printing is similar to 3D printing except that it changes materials from location to location. The separate material is used because it is reactive to a particular stimulus: water, cold or heat, for instance. Initial printing is done on a flat surface that is then exposed to the stimulus, causing a reaction, and changing the surface shape. The fourth dimension refers to the altered configuration of the once-flat material.

Composite 4D printing is more complex. Rather than using a soft, dough-like substance commonly used by 3D and 4D printers, it relies on a sinewy combination of long, fine filaments held in place by a resin. Each filament is only 10 microns thick — about 1/10th the diameter of a human hair. The 4D composite printer unrolls its filament-resin mixture in ultra-thin layers at 90-degree angles from each other. The layers are then compacted together and cured in an oven at 180˚C, and then cooled down to 0˚C, creating an object that is stiff but not brittle.

As the authors explain in their paper, this allows them to create a section of material with a uniform curvature that is sandwiched in between the wing flap’s upper and lower surfaces. It is flexible and strong enough to support the 20-degree deformation the wing requires for flight maneuverability.

“The idea is to have a wing that can change its shape easily during flight, which would be a great benefit as compared to fixed-wing aircraft,” Hoa explains.

He believes the composite 4D technology has great potential for all manner of applications. Its products’ transportability, he says, is a major draw.

“Because it is flat, it is easy to package to send to remote areas, from Canada’s Far North to outer space.”

Video of Suong Hoa discussing 4D printing of composites: https://youtu.be/j7k-ZjG0qPE

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Materials provided by Concordia University. Original written by Patrick Lejtenyi. Note: Content may be edited for style and length.

Cognitive tests that rely on vision-dependent tasks could be skewing results in up to a quarter of people aged over 50 who have undiagnosed visual problems such as cataracts or age-related macular degeneration (AMD).

Age-related macular degeneration is a leading cause of vision loss for older people. It doesn’t cause complete vision loss, but severely impacts people’s ability to read, drive, cook, and even recognise faces. It has no bearing on cognition.

UniSA researchers recruited 24 participants with normal vision to complete two cognitive tests — one involving vision-dependent reactive tasks and the other based on verbal fluency.

Using a set of goggles to simulate AMD, the participants scored far lower on the cognitive test involving reaction time tasks than without the goggles. There was no statistical difference with verbal fluency tests when using the goggles.

The study has been published in Scientific Reports.

UniSA PhD candidate Anne Macnamara, who led the study, says the results are a stark reminder that visual impairments — which affect approximately 200 million people worldwide over the age of 50 — unfairly affect cognitive scores when tests involve visual abilities.

“A mistaken score in cognitive tests could have devastating ramifications, leading to unnecessary changes to a person’s living, working, financial or social circumstances,” Macnamara says.

“For example, if a mistaken score contributed to a diagnosis of mild cognitive impairment, it could trigger psychological problems including depression and anxiety.

“People with AMD are already experiencing multiple issues due to vision loss and an inaccurate cognitive assessment is an additional burden they don’t need.”

Visual impairments are often overlooked in research and clinical settings, the UniSA researchers say, with reduced vision underestimated in up to 50 per cent of older adults.

And with this figure expected to increase in line with an ageing population, it is critical that neuro-degenerative researchers control for vision when assessing people’s cognition.

“Mobile apps can now be used to overlay simulated visual impairments onto test materials when piloting their stimuli,” Macnamara says.

“Also, researchers can incorporate quick and simple screening tasks before getting people to do cognitive tests. Verbal tasks should always be part of the assessment, too.”

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