In a study online this week in the American Physical Society journal Physical Review X (PRX), physicist Ming Yi and colleagues offer up a band structure map for iron selenide, a material that has long puzzled physicists because of its structural simplicity and behavioral complexity. The map, which details the electronic states of the material, is a visual summary of data gathered from measurements of a single crystal of iron selenide as it was cooled to the point of superconductivity.

“It’s very much like a traffic map,” said Yi, who joined Rice’s faculty and Center for Quantum Materials (RCQM) early this year. “In the quantum mechanical world, there are all kinds of interesting rules electrons must obey as they move through a crystal. Some materials have fast lanes and slow lanes, and electrons can only cross and change lanes under special circumstances. Other materials have traffic circles where U-turns are forbidden because electrons can move counterclockwise but not clockwise.”

Yi began the angle-resolved photoemission spectroscopy experiments for the study during a postdoctoral stint at the University of California, Berkeley. The technically challenging experiments used powerful synchrotron light from the Stanford Synchrotron Radiation Lightsource (SSRL) to coax the crystal to emit electrons.

“In a sense, these measurements are like taking photographs of electrons that are flying out of the material,” she said. “Each photograph tells the lives the electrons were living right before being kicked out of the material by photons. By analyzing all the photos, we can piece together the underlying physics that explains all of their stories.”

Red-light cameras for electrons

The electron detector tracked both the speed and direction that electrons were traveling when emitted from the crystal. That information contained important clues about the quantum mechanical laws that dictated the traffic patterns at a larger, microscopic scale, where key aspects of superconductivity are believed to arise.

“The fun aspect of our experimental work is making observations of different types of exotic materials and figuring out the quantum mechanical rules that govern electron behavior in those materials,” she said. “Ultimately, we hope those rules will guide physicists to new classes and new kinds of materials, hopefully with amazing properties that improve the world.”

These rules are encoded in a material’s electronic structure, Yi said.

“They’re like an electronic fingerprint of a material,” she said. “Each material has its own unique fingerprint, which describes the allowed energy states electrons can occupy based on quantum mechanics. The electronic structure helps us decide, for example, whether something will be a good conductor or a good insulator or a superconductor.”

When things go sideways

Electrical resistance is what causes wires, smartphones and computers to heat up during use, and it costs billions of dollars each year in lost power on electric grids and cooling bills for data centers. Superconductivity, the zero-resistance flow of electricity, could eliminate that waste, but physicists have struggled to understand and explain the behavior of unconventional superconductors like iron selenide.

Yi was in graduate school when the first iron-based superconductors were discovered in 2008, and she’s spent her career studying them. In each of these, an atom-thick layer of iron is sandwiched between other elements. At room temperature, the atoms in this iron layer are arranged in checkerboard squares. But when the materials are cooled near the point of superconductivity, the iron atoms shift and the squares become rectangular. This change brings about direction-dependent behavior, or nematicity, which is believed to play an important but undetermined role in superconductivity.

“Iron selenide is special because in all of the other iron-based materials, nematicity appears together with magnetic order,” Yi said. “If you have two orders forming together, it is very difficult to tell which is more important, and how each one affects superconductivity. In iron selenide, you only have nematicity, so it gives us a unique chance to study how nematicity contributes to superconductivity by itself.”

Performing under pressure

The upshot of nematicity is that the traffic patterns of electrons — and the quantum rules that cause the patterns — may be quite different for electrons flowing right-to-left, along the long axis of the rectangles, than for the electrons flowing up-and-down along the short axis. But getting a clear look at those traffic patterns in iron selenide has been challenging because of twinning, a property of the crystals that causes the rectangles to randomly change orientation by 90 degrees. Twinning means that long-axis rectangles will run left-to-right about half of the time and up-and-down the other half.

Twinning in iron selenide made it impossible to obtain clear, whole-sample measurements of nematic order in the material until Rice physicists Pengcheng Dai and Tong Chen published a clever solution to the problem in May. Building on a detwinning technique developed by Dai and colleagues in 2014, Chen found he could detwin fragile crystals of iron selenide by gluing them atop a sturdier layer of barium iron arsenide and turning a screw to apply a bit of pressure. The technique causes all the nematic layers in the iron selenide to snap into alignment.

Dai and Chen were co-authors on the PRX paper, and Yi said the detwinning technique was key to getting clear data about the impact of nematicity on iron selenide’s electronic behavior.

“This study would not have been possible without the detwinning technique that Pengcheng and Tong developed,” Yi said. “It allowed us to take a peek at the arrangements of electronic states as the material system gets ready for superconductivity. We were able to make precise statements about the availability of electrons belonging to different orbitals that could participate in superconductivity when nematic rules have to be obeyed.”

A path forward

Yi said the data show that the magnitude of nematic shifts in iron selenide are comparable to the shifts measured in more complicated iron-based superconductors that also feature magnetic order. She said that suggests the nematicity that’s observed in iron selenide could be a universal feature of all iron-based superconductors, regardless of the presence of long-range magnetism. And she hopes that her data allow theorists to explore that possibility and others.

“This set of measurements will provide precise guidance for theoretical models that aim to describe the nematic superconducting state in iron-based superconductors,” she said. “That’s important because nematicity plays a role in bringing about superconductivity in all of these materials.”

Cesarean or C-section deliveries have soared in recent years, from 6.7 percent globally in 1990 to around 19.1 percent in 2014, according to earlier reports. The jump has sparked intense research into the long-term consequences of C-section on offspring health, and several studies have linked cesarean deliveries with increased risks for asthma, various allergies and obesity. The association with obesity has, however, mainly been confirmed in smaller studies that were unable to account for a wide array of possible confounders or differentiate between types of C-sections.

The researchers in this study set out to investigate if indeed increased C-section births could explain part of the rise in obesity also seen in the last decades, and whether this potential association held true once they accounted for maternal and prenatal factors known to impact offspring weight. They compared the body-mass index (BMI) of nearly 100,000 male 18-year-olds and divided them into categories depending on whether they were born through vaginal delivery, elective C-section or non-elective C-section.

According to the data, 5.5 and 5.6 percent of the men delivered through elective and non-elective C-section, respectively, were obese compared to 4.9 percent of the men delivered vaginally. But after accounting for other factors known to impact offspring weight — including pre-pregnancy BMI, maternal and gestational age and the presence of diabetes, hypertension, smoking and preeclampsia in the mother — the researchers concluded that the method of childbirth did not play a significant role in determining the risk of obesity in the offspring.

“We found no evidence to support a link between C-sections and the development of obesity,” says Daniel Berglind, researcher at the Department of Global Public Health at Karolinska Institutet. “This tells us that how women give birth may not be an important factor in the origins of the global obesity epidemic.”

The researchers also identified nearly 10,000 full brothers and concluded that sibling analysis, accounting for genetic and environmental factors, did not alter the overall findings.

The strongest confounder in the association between mode of delivery and obesity was how much the mother weighed before she became pregnant. This is consistent with previous reports on the heritability of obesity and the influence of maternal obesity on fetal health.

“Most of the association between C-section and obesity could be explained by maternal pre-pregnancy BMI,” says Viktor H. Ahlqvist, researcher at the Department of Global Public Health. “This suggests that heritability and fetal exposure to obese-causing factors in the womb are more important when assessing the risk of obesity in the offspring than the mode of delivery.”

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Their findings were published today in Science Advances.

“Usually, you have sacrifice either size or image quality. We’ve been able to achieve both with our microendoscope,” says Mark Foster, an associate professor of electrical and computer engineering at The Johns Hopkins University and the study’s corresponding author.

Intended for examining neurons firing off in the brains of animals such as mice and rats, an ideal microendoscope should be small to minimize brain tissue damage yet powerful enough to produce a clear image.

Currently, standard microendoscopes are about half a millimeter to a few millimeters in diameter, and require larger, more invasive lenses for better imaging. While lensless microendoscopes exist, the optical fiber within that scans an area pixel by pixel frequently bends and loses imaging ability when moved.

In their new study, Foster and colleagues created a lens-free ultra-miniaturized microendoscope that, compared to a conventional lens-based microendoscope, increases the amount researchers can see and improves image quality.

The researchers achieved this by using a coded aperture, or a flat grid that randomly blocks light creating a projection in a known pattern akin to randomly poking a piece of aluminum foil and letting light through all of the small holes. This creates a messy image, but one that provides a bounty of information about where the light originates, and that information can be computationally reconstructed into a clearer image. In their experiments, Foster’s team looked at beads in different patterns on a slide.

“For thousands of years, the goal has been to make an image as clear as possible. Now, thanks to computational reconstruction, we can purposefully capture something that looks awful and counterintuitively end up with a clearer final image,” says Foster.

Additionally, Foster and team’s microendoscope doesn’t require movement to focus on objects at different depths; they use computational refocusing to determine where the light originated from in 3 dimensions. This allows the endoscope to be much smaller than a traditional one that requires moving the endoscope around to focus.

Looking forward, the research team will test their microendoscope with fluorescent labeling procedures in which active brain neurons would be tagged and illuminated, to determine how accurately the endoscope can image neural activity.

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A report on their work appears in the Dec. 6 issue of Science Advances.

“Most medicines spread throughout the body in an indiscriminate way and don’t target a specific cell,” says biomedical engineer Jordan Green, Ph.D., leader of the research team. “Some medicines, such as antibodies, latch on to targets on the cell’s surface receptors, but we don’t have good systems for delivering biological medicines straight to the inside of a cell, which is where therapies would have the best chance at working properly and with fewer side effects.”

Many academic and commercial scientists have long sought better transit systems for therapies, says Green, professor of biomedical engineering, ophthalmology, oncology, neurosurgery, materials science and engineering, and chemical and biomolecular engineering at the Johns Hopkins University School of Medicine, and a member of the Bloomberg~Kimmel Institute for Cancer Immunotherapy at Johns Hopkins.

Some commercially available techniques use stripped down forms of viruses — known for their ability to “infect” cells directly — to deliver therapies, although the noninfectious versions of these delivery systems can unleash an unwanted immune system response. Other therapies aimed at diseased blood cells, for example, are more cumbersome, requiring patients’ blood to be removed, then zapped with an electric current that opens pores in the cell membrane to gain entry.

The nanosize container that Green and his team developed at Johns Hopkins borrows an idea from the properties of viruses, many of which are nearly spherical in shape and carry both negative and positive charges. With a more neutral overall charge, viruses can get close to cells. That’s not the case with many biological medicines, which consist of highly charged, large proteins and nucleic acids that tend to repel off cells.

To overcome this, graduate student Yuan Rui developed a new biodegradable polymer material. Polymer is the general term for a substance made up of many molecules. To make the polymer, Rui strung together — like the branches of a tree — four component molecules that, over time, break down and dissolve in water. The molecules contain both positive and negative charges.

With a balance of positive and negative charges, the molecules push and pull according to their charge and their hydrogen atoms bond with a biological therapy in the vicinity. The result is a nano-structure containing the biological therapy.

The nanosize container’s positive charges interact with the membrane of a cell, and the container is engulfed in a cellular package called an endosome.

Once inside, the nanosize container breaks open the endosome, and the polymers degrade, leaving the medicine to work inside the cell.

To test their invention, Rui made a nanocontainer of a small protein and fed it to mouse kidney cells in culture dishes. She attached a green fluorescent tag to the small protein and saw bright green splashes throughout most of the cells, indicating that the protein was successfully delivered.

Then, Rui packaged a bigger protein: human immunoglobulin, a therapy typically used to strengthen the immune system and a model for antibody therapies. This time, she found that 90% of the kidney cells she treated lit up with the green fluorescent tag attached to the immunoglobulin.

“When nanoparticles enter a cell, they often get sequestered into endosomes, which degrade its contents, but our experiments show the protein packages uniformly spread throughout most of the cells and were not stuck in the endosomes,” says Rui.

For an even greater challenge, Rui created a nanopackage containing a CRISPR-based protein and nucleic acid complex that could turn off a green fluorescence signal or cause the cells to glow red when the CRISPR compound cut part of a cell’s genome. The researchers saw that the gene editing to disable a gene worked in up to 77% of cells grown in the laboratory and to add or repair a gene in about 4% of cells.

“That’s pretty effective considering, with other gene editing systems, you might get the correct gene-cutting result less than 10 percent of the time,” said Rui. CRISPR-based therapies have the potential to make medicines far more precise with their ability to precisely target genetic flaws that contribute to disease. Some CRISPR therapies are being tested in clinical trials.

In a final experiment, Rui and her colleagues implanted brain cancer cells into the brains of mice. She injected the nanocontainers with gene editing components directly into the mouse brains and analyzed their cells for a red glow indicating successful gene editing. She found brain cancer cells that glowed red several millimeters away from where she injected them.

‘When I first started this project five years ago, scientists didn’t think that you could use something other than a virus to deliver these therapies into cells,” says Rui. “Developing new technologies can help us understand more about disease, but also more about making new drugs.”

Rui and Green are trying to make the nanocontainers more stable so they can be injected into the bloodstream and targeted to cells with certain genetic signatures.

The scientists are filing for patents related to this work.

Funding for the research was provided by the National Science Foundation, the Johns Hopkins University School of Medicine, the National Institutes of Health (R01CA228133, R01EB022148 and P30 EY001765), the Bloomberg~Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, and the Research to Prevent Blindness James and Carole Free Catalyst Award.

Other scientists who contributed to the work include David Wilson, John Choi, Mahita Varanasi, Katie Sanders, Johan Karlsson and Michael Lim from Johns Hopkins.