A cell contains several hundred thousand tRNA molecules, each of which consists of only 70 to 90 nucleotides folded into a cloverleaf-like pattern. At one end, tRNAs carry one of the twenty amino acids that serve as protein building blocks, while the opposite end pairs with the codon specifying this amino acid in messenger RNA during translation. Although there are only 61 codons for the twenty amino acids, cells from different organisms can contain hundreds of unique tRNA molecules, some of which differ from each other by only a single nucleotide. Many nucleotides in tRNAs are also decorated with chemical modifications, which help tRNAs fold or bind the correct codon.

The levels of individual tRNAs are dynamically regulated in different tissues and during development, and tRNA defects are linked to neurogical diseases and cancer. The molecular origins of these links remain unclear, because quantifying the abundance and modifications of tRNAs in cells has long remained a challenge. The team of Danny Nedialkova at the MPI of Biochemistry has now developed mim-tRNAseq, a method that accurately measures the abundance and modification status of different tRNAs in cells.

Modification roadblocks and resolutions

To measure the levels of multiple RNAs simultaneously, scientists use an enzyme called reverse transcriptase to first rewrite RNA into DNA. Millions of these DNA copies can then be quantified in parallel by high-throughput sequencing. Rewriting tRNAs into DNA has been tremendously hard since many tRNA modifications block the reverse transcriptase, causing it to stop synthesizing DNA.

“Many researches have proposed elegant solutions to this problem, but all of them relieve only a fraction of the modification roadblocks in tRNAs,” explains Danny Nedialkova, Max Planck Research Group Leader at the Max Planck Institute of Biochemistry. “We noticed that one specific reverse transcriptase seemed to be much better at reading through modified tRNA sites. By optimizing the reaction conditions, we could significantly improve the enzyme’s efficiency, enabling it to read through nearly all tRNA modification roadblocks,” adds Nedialkova. This made it possible to construct DNA libraries from full-length tRNA copies and use them for high-throughput sequencing.

The mim-tRNAseq computational toolkit

The analysis of the resulting sequencing data also presented significant challenges. “We identified two major issues: the first one is the extensive sequence similarity between different tRNA transcripts,” explains Andrew Behrens, PhD student in Nedialkova’s group and first author of the paper. “The second one comes from the fact that an incorrect nucleotide (a misincorporation) is introduced at many modified sites during reverse transcription. Both make it extremely challenging to assign each DNA read to the tRNA molecule it originated from,” adds Behrens.

The team tackled these issues with novel computational approaches, including the use of modification annotation to guide accurate read alignment. The resulting comprehensive toolkit is packaged into a freely available pipeline for alignment, analysis and visualization of tRNA-derived sequencing data . Researchers can use mim-tRNAseq to not only measure tRNA abundance, but also to map and quantify tRNA modifications that induce nucleotide misincorporations by the reverse transcriptase. “mim-tRNAseq opens up myriad possibilities moving forward,” says Nedialkova. “We expect it will help us and others to tackle many outstanding questions about tRNA biology in health and disease.”

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The discovery by researchers from Rice University, Austria’s Vienna University of Technology (TU Wien), Switzerland’s Paul Scherrer Institute and Canada’s McMaster University is detailed in a paper in the Proceedings of the National Academy of Sciences. Of interest are both the origins of the effect, which is typically associated with magnetism, and its gigantic magnitude — more than 1,000 times larger than one might observe in simple semiconductors.

Rice study co-author Qimiao Si, a theoretical physicist who has investigated quantum materials for nearly three decades, said, “It’s really topology at work,” referring to the patterns of quantum entanglement that give rise the unorthodox state.

The material, an exotic semimetal of cerium, bismuth and palladium, was created and measured at TU Wien by Silke Bühler-Paschen, a longtime collaborator of Si’s. In late 2017, Si, Bühler-Paschen and colleagues discovered a new type of quantum material they dubbed a “Weyl-Kondo semimetal.” The research laid the groundwork for empirical investigations, but Si said the experiments were challenging, in part because it wasn’t clear “which physical quantity would pick up the effect.”

In April 2018, Bühler-Paschen and TU Wien graduate student Sami Dzsaber, the study’s first author, dropped by Si’s office while attending a workshop at the Rice Center for Quantum Materials (RCQM). When Si saw Dzsaber’s data, he was dubious.

“Upon seeing this, everybody’s first reaction is that it is not possible,” he said.

To appreciate why, it helps to understand both the nature and the 1879 discovery of Edwin Hall, a doctoral student who found that applying a magnetic field at a 90-degree angle to conducting wire produced a voltage difference across the wire, in the direction perpendicular to both the current and the magnetic field. Physicists eventually discovered the source of the Hall effect: The magnetic field deflects the motion of passing electrons, pulling them toward one side of the wire. The Hall effect is a standard tool in physics labs, and devices that make use of it are found in products as diverse as rocket engines and paintball guns. Studies related to the quantum nature of the Hall effect captured Nobel Prizes in 1985 and 1998.

Dzsaber’s experimental data clearly showed a characteristic Hall signal, even though no magnetic field was applied.

“If you don’t apply a magnetic field, the electron is not supposed to bend,” Si said. “So, how could you ever get a voltage drop along the perpendicular direction? That’s why everyone didn’t believe this at first.”

Experiments at the Paul Scherrer Institute ruled out the presence of a tiny magnetic field that could only be detected on a microscopic scale. So the question remained: What caused the effect?

“In the end, all of us had to accept that this was connected to topology,” Si said.

In topological materials, patterns of quantum entanglement produce “protected” states, universal features that cannot be erased. The immutable nature of topological states is of increasing interest for quantum computing. Weyl semimetals, which manifest a quasiparticle known as the Weyl fermion, are topological materials.

So are the Weyl-Kondo semimetals Si, Bühler-Paschen and colleagues discovered in 2018. Those feature both Weyl fermions and the Kondo effect, an interaction between the magnetic moments of electrons attached to atoms inside the metal and the spins of passing conduction electrons.

“The Kondo effect is the quintessential form of strong correlations in quantum materials,” Si said in reference to the correlated, collective behavior of billions upon billions of quantum entangled particles. “It qualifies the Weyl-Kondo semimetal as one of the rare examples of a topological state that’s driven by strong correlations.

“Topology is a defining characteristic of the Weyl-Kondo semimetal, and the discovery of this spontaneous giant Hall effect is really the first detection of topology that’s associated with this kind of Weyl fermion,” Si said.

Experiments showed that the effect arose at the characteristic temperature associated with the Kondo effect, indicating the two are likely connected, Si said.

“This kind of spontaneous Hall effect was also observed in contemporaneous experiments in some layered semiconductors, but our effect is more than 1,000 times larger,” he said. “We were able to show that the observed giant effect is, in fact, natural when the topological state develops out of strong correlations.”

Si said the new observation is likely “a tip of the iceberg” of extreme responses that result from the interplay between strong correlations and topology.

He said the size of the topologically generated Hall effect is also likely to spur investigations into potential uses of the technology for quantum computation.

“This large magnitude, and its robust, bulk nature presents intriguing possibilities for exploitation in topological quantum devices,” Si said.

Si is the Harry C. and Olga K. Wiess Professor in Rice’s Department of Physics and Astronomy and director of RCQM. Bühler-Paschen is a professor at TU Wien’s Institute for Solid State Physics.

Today, Rottinghaus, an associate professor in the University of Missouri College of Education, is helping young people eager to find their place in the world by identifying their strengths and connecting them with careers that match their skillset, interests and personality. As the father of three children, including a daughter soon to enter high school, he wants to ensure they are equipped with the knowledge and skills to succeed as they prepare to enter the modern workforce.

In an effort to fill the United States labor market’s current “skills gap,” Rottinghaus and graduate student Chan Jeong Park collaborated to study how certain tools could better help students to know their strengths. In his study, Rottinghaus partnered with YouScience, a web-based aptitude assessment system, to distribute an online career aptitude test to more than 7,000 high school students across 14 states. The skills gap is defined as the disconnect between the skills employers look for when recruiting potential employees and the number of job-seekers with those skills.

While most career exploration surveys focus mainly on students’ interests, the aptitude test Rottinghaus distributed also inquired about the strengths and skills the students possess, which enabled them to explore more potential careers than they had originally considered. The aptitude assessments helped identify female students with the talent for careers in construction, technical health care, manufacturing and computer technology, areas they may not have previously considered based solely on their interests. The assessments also helped identify males with the talent to pursue jobs in patient-centered health care.

“When you look at rapidly growing employment sectors like manufacturing, computer technology, health care and construction, there is a pipeline concern, as we need more young people equipped with the skills to enter these fields,” Rottinghaus said. “Not only does the aptitude test help high school students identify potential career paths, but it also helps them identify classes they can take now or in college that will strengthen their skillset and potentially open up doors for their future.”

According to Rottinghaus, one approach to mitigating the “skills gap” is to encourage more women and underrepresented groups to pursue high-demand careers in science, technology, engineering and mathematics, or STEM.

“Due to traditional societal norms and gender stereotypes, young women have historically not been as likely to pursue STEM careers,” Rottinghaus said. “But when we looked at their aptitude scores, the system would often indicate many of the young women surveyed have the aptitude to be successful in these areas. We can also help men consider more nontraditional fields, too, such as nursing or health care, which tend to be predominantly female.”

Rottinghaus believes providing aptitude tests to young students and having a trained counselor review the results with them can help in overcoming gender stereotypes. He encourages his own children to expand their career possibilities by exploring fields not traditionally considered in the past.

“I don’t want my daughter to feel constricted in her career exploration by only considering fields traditionally held by women. I want her to consider a full array of opportunities,” Rottinghaus said. “My overall goal is to help people intentionally identify aptitudes and interests to find their fit with educational pathways and labor market needs so they can be happy and productive members of society. There are also implications for institutions of higher education, as students who don’t know what they want to major in are more likely to drop out before graduation.”

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But for practical applications, such two-dimensional materials must at some point connect with the ordinary world of 3D materials. An international team led by MIT researchers has now come up with a way of imaging what goes on at these interfaces, down to the level of individual atoms, and of correlating the moiré patterns at the 2D-3D boundary with the resulting changes in the material’s properties.

The new findings are described today in the journal Nature Communications, in a paper by MIT graduate students Kate Reidy and Georgios Varnavides, professors of materials science and engineering Frances Ross, Jim LeBeau, and Polina Anikeeva, and five others at MIT, Harvard University, and the University of Victoria in Canada.

Pairs of two-dimensional materials such as graphene or hexagonal boron nitride can exhibit amazing variations in their behavior when the two sheets are just slightly twisted relative to each other. That causes the chicken-wire-like atomic lattices to form moiré patterns, the kinds of odd bands and blobs that sometimes appear when taking a picture of a printed image, or through a window screen. In the case of 2D materials, “it seems like anything, every interesting materials property you can think of, you can somehow modulate or change by twisting the 2D materials with respect to each other,” says Ross, who is the Ellen Swallow Richards Professor at MIT.

While these 2D pairings have attracted scientific attention worldwide, she says, little has been known about what happens where 2D materials meet regular 3D solids. “What got us interested in this topic,” Ross says, was “what happens when a 2D material and a 3D material are put together. Firstly, how do you measure the atomic positions at, and near, the interface? Secondly, what are the differences between a 3D-2D and a 2D-2D interface? And thirdly, how you might control it — is there a way to deliberately design the interfacial structure” to produce desired properties?

Figuring out exactly what happens at such 2D-3D interfaces was a daunting challenge because electron microscopes produce an image of the sample in projection, and they’re limited in their ability to extract depth information needed to analyze details of the interface structure. But the team figured out a set of algorithms that allowed them to extrapolate back from images of the sample, which look somewhat like a set of overlapping shadows, to figure out which configuration of stacked layers would yield that complex “shadow.”

The team made use of two unique transmission electron microscopes at MIT that enable a combination of capabilities that is unrivalled in the world. In one of these instruments, a microscope is connected directly to a fabrication system so that samples can be produced onsite by deposition processes and immediately fed straight into the imaging system. This is one of only a few such facilities worldwide, which use an ultrahigh vacuum system that prevents even the tiniest of impurities from contaminating the sample as the 2D-3D interface is being prepared. The second instrument is a scanning transmission electron microscope located in MIT’s new research facility, MIT.nano. This microscope has outstanding stability for high-resolution imaging, as well as multiple imaging modes for collecting information about the sample.

Unlike stacked 2D materials, whose orientations can be relatively easily changed by simply picking up one layer, twisting it slightly, and placing it down again, the bonds holding 3D materials together are much stronger, so the team had to develop new ways of obtaining aligned layers. To do this, they added the 3D material onto the 2D material in ultrahigh vacuum, choosing growth conditions where the layers self-assembled in a reproducible orientation with specific degrees of twist. “We had to grow a structure that was going to be aligned in a certain way,” Reidy says.

Having grown the materials, they then had to figure out how to reveal the atomic configurations and orientations of the different layers. A scanning transmission electron microscope actually produces more information than is apparent in a flat image; in fact, every point in the image contains details of the paths along which the electrons arrived and departed (the process of diffraction), as well as any energy that the electrons lost in the process. All these data can be separated out so that the information at all points in an image can be used to decode the actual solid structure. This process is only possible for state-of-the-art microscopes, such as that in MIT.nano, which generates a probe of electrons that is unusually narrow and precise.

The researchers used a combination of techniques called 4D STEM and integrated differential phase contrast to achieve that process of extracting the full structure at the interface from the image. Then, Varnavides says, they asked, “Now that we can image the full structure at the interface, what does this mean for our understanding of the properties of this interface?” The researchers showed through modeling that electronic properties are expected to be modified in a way that can only be understood if the full structure of the interface is included in the physical theory. “What we found is that indeed this stacking, the way the atoms are stacked out-of-plane, does modulate the electronic and charge density properties,” he says.

Ross says the findings could help lead to improved kinds of junctions in some microchips, for example. “Every 2D material that’s used in a device has to exist in the 3D world, and so it has to have a junction somehow with three-dimensional materials,” she says. So, with this better understanding of those interfaces, and new ways to study them in action, “we’re in good shape for making structures with desirable properties in a kind of planned rather than ad hoc way.”

“The methodology used has the potential to calculate from the acquired local diffraction patterns the modulation of the local electron momentum,” he says, adding that “the methodology and research shown here has an outstanding future and high interest for the materials science community.”

“Our study focuses on light propagation in cold atomic gases, in which atoms hardly move. On their way out of the gas, photons undergo multiple scattering by the atoms,” Bellando says. “Roughly speaking, the greater the number of these scattering events? — ?the longer it takes the photons to leave the gas, and thus the smaller their escape rates. This classical description fits the so-called radiation trapping, which occurs, for example, when light undergoes a random walk in a glass of milk.”

When taking into account interference and quantum mechanical effects, two mechanisms affect these escape rates: Anderson localisation arising from interference effects in the presence of disorder, and Dicke’s superradiance? — ??cooperative effects stemming from light-mediated interactions between the atoms.

Numerically studying photon escape rates from a three-dimensional cloud of cold atoms allowed the team to consider if there were any marked differences between the behaviour in the simple scalar case? — ?giving a single value to every point in a region — and the more complex vector case that assigns magnitude and direction to every point in a given area.

One of the biggest surprises encountered by the researchers as they collected their results was how well vector field observations agreed with scalar field tests. “Surprisingly, we found no significant difference between the scalar and vectorial models, and in both cases, the dominant mechanism was cooperativity,” says Bellando. “Now we know that the scalar model constitutes an excellent approximation when considering photon escape rates from atomic gases.”

Because the scalar model is much simpler than the vectorial one, the similarity between the two means that in the case of photon escape rates models can use scalar fields rather than vector fields without the risk of losing substantial information.

“Light-matter interaction is an exciting field of research, both theoretically and experimentally,” Bellando concludes. “Advances in this area may have a significant impact on other emerging fields, such as quantum computing.”

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The technology, which uses organic light-emitting diodes (OLEDs), is applied in the same way as water transfer tattoos. That is, the OLEDs are fabricated on to temporary tattoo paper and transferred to a new surface by being pressed on to it and dabbed with water.

The researchers, who described the process in a new paper in the journal Advanced Electronic Materials, say it could be combined with other tattoo electronics to, for instance emit light when an athlete is dehydrated, or when we need to get out of the sun to avoid sunburn. OLEDs could be tattooed on packaging or fruit to signal when a product has passed its expiry date or will soon become inedible, or used for fashion in the form of glowing tattoos.

Professor Franco Cacialli (UCL Physics & Astronomy), senior author of the paper, said: “The tattooable OLEDs that we have demonstrated for the first time can be made at scale and very cheaply. They can be combined with other forms of tattoo electronics for a very wide range of possible uses. These could be for fashion — for instance, providing glowing tattoos and light-emitting fingernails. In sports, they could be combined with a sweat sensor to signal dehydration.

“In healthcare they could emit light when there is a change in a patient’s condition — or, if the tattoo was turned the other way into the skin, they could potentially be combined with light-sensitive therapies to target cancer cells, for instance.

“Our proof-of-concept study is the first step. Future challenges will include encapsulating the OLEDs as much as possible to stop them from degrading quickly through contact with air, as well as integrating the device with a battery or supercapacitor.”

The OLED device the researchers developed is 2.3 micrometres thick in total (less than one 400th of a millimetre) — about a third of the length of a single red blood cell. It consists of an electroluminescent polymer (a polymer that emits light when an electric field is applied) in between electrodes. An insulating layer is placed in between the electrodes and the commercial tattoo paper.

The light-emitting polymer is 76 nanometres thick (a nanometre is a millionth of a millimetre) and was created using a technique called spin coating, where the polymer is applied to a substrate which is spun at high speed, producing an extremely thin and even layer.

Once they had built the technology, the team applied the tattooable OLEDs, which emitted green light, on to a pane of glass, a plastic bottle, an orange, and paper packaging.

Senior author Professor Virgilio Mattoli, researcher at Italian Institute of Technology said: “Tattoo electronics is a fast-growing field of research. At the Italian Institute of Technology we have previously pioneered electrodes that we have tattooed onto people’s skin that can be used to perform diagnostic tests such as electrocardiograms. The advantage of this technology is that it is low-cost, easy to apply and use, and washes off easily with soap and water.”

OLEDs were first used in a flatscreen TV 20 years ago. Among the advantages of the technology are that they can be used on flexible, bendy surfaces, and that they can be made from liquid solvents. This means they are printable, providing a cheap way to create bespoke new OLED designs.

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