New Research Sheds Light on How Mesothelioma Develops

Mesothelioma has been a high-profile disease at the center of several multi-billion-dollar lawsuits, but the disease itself remains a medical mystery. 

The incurable cancer develops on the lining of many internal organs—including the lungs and peritoneum—but its symptoms are often undetectable until about 40 years after initial exposure to asbestos, a common and naturally occurring mineral. This long latency period, as well as cases of mesothelioma in individuals who have no known exposure to asbestos, has made the disease and its origins a longstanding puzzle to doctors and scientists alike. 

Now, an interdisciplinary team of researchers from the University of Maryland may have identified an essential piece of the puzzle. In a paper published online in the journal Environmental Research in January 2023, the team suggests that the key to understanding mesothelioma lies in how immune cells “sense” and interact with particles around them. 

According to the new study, the shape and size of contaminant particles, like asbestos fibers, significantly influence how the immune system responds after exposure—ultimately impacting health outcomes.An asbestos fiber (stained blue) in lung tissue being surrounded by macrophages. Image courtesy of the Centers for Disease Control and Prevention.An asbestos fiber (stained blue) in lung tissue being surrounded by macrophages. Image courtesy of the Centers for Disease Control and Prevention.

“The geometry or size of a particle is more important than its mineral composition when it comes to how likely it is to cause adverse health effects in patients,” explained study co-author and UMD Professor Emerita of Geology Ann Wylie. “Asbestos kicks up an immune response when the immune system is exposed to the right shape and size of particle.”

“We believe that the most dangerous types of fibers—ones that are particularly thin and long—likely cause immune cells called macrophages to recruit other immune cells to asbestos exposure sites within tissue. This response prevents the immune cells from reaching other places where they’re needed, like precancerous lesions,” added study co-author Wolfgang Losert, a professor in the Department of Physics and the Institute for Physical Science and Technology at UMD. “This could cause the immune system to effectively ignore other serious conditions around that organ.”

In a previous study, some members of the research team found that mineral particles with diameters less than 250 nanometers and lengths greater than 5 micrometers were more difficult for the lungs to physically clear out than their shorter counterparts. The longer particles stayed in the lungs longer, further interacting with healthy lung tissues before eventually encountering immune cells like macrophages.

For the new study, the researchers examined particles taken from mineral samples from various geological sites. They found that immune cells used a mechanism called esotaxis to “sense” physical features—such as size, shape and texture—of the particles around them and responded differently to each particle based on that information. 

The researchers observed that when macrophages encountered these small and dangerous types of particles (including smaller asbestos fibers), the macrophages “activated” to recruit other immune cells to the site. However, because these longer particles are less able to be removed physically, activated macrophages continue to call for more immune cells to the same site over a long period of time, dominating immune cell communication.

The researchers hypothesize that this eventual “hijacking” of the immune cell migration system would lead to other nearby regions of an infected organ to be neglected because all immune cells are delegated to a single site. As a result, those other tissues would be deprived of the immune system’s healing abilities—a possible explanation as to why many immunocompromised patients can develop mesothelioma even without known exposure to asbestos fibers.

In essence, a particle’s nanotopography—their surface features formed at a nanoscopic level—indirectly controls the internal machinery that allows immune cells to move.

“This response basically overwhelms the immune cell communication system and diverts the body’s own defenses away from where they’re needed,” explained study co-author John Fourkas, a professor in the UMD Department of Chemistry and Biochemistry and the Institute for Physical Science and Technology. “The physical characteristics of a mineral particle can change the behavior of immune cells in the long term, which could be why mesothelioma symptoms take a minimum of 30 to 40 years to manifest.” 

The team believes that their theory also applies to mineral particles that are similar in size to carcinogenic asbestos fibers, which could provide more insight into other diseases caused by such particles. With rising concerns about the carcinogenic properties of airborne mineral particles like crystalline silica and carbon nanotubes, additional information about esotaxis and its effects on immune responses could be the key to protection. 

“More research about the induction of cancer by minerals is still needed—it’s complicated and requires the expertise of geologists, chemists, physicists and bioscientists,” Wylie said. “But this project and others like it bring us a step closer to figuring out what mechanisms underlie not only mesothelioma but all types of cancer formations.”


Original story:

Additional UMD co-authors on the paper include Shuyao Gu, Abby Bull, Amilee Huang, Matt Hourwitz and Mona Abostate.

The study, “Excitable systems: A new perspective on the cellular impact of elongate mineral particles,” was published in Environmental Research on January 23, 2023.

This research was supported by the National Science Foundation (Award No. PHY2014151). This story does not necessarily reflect the views of this organization.

Experiment Demonstrates Continuously Operating Optical Fiber Made of Thin Air

Researchers at the University of Maryland have demonstrated a continuously operating optical fiber made of thin air.

The most common optical fibers are strands of glass that tightly confine light over long distances. However, these fibers are not well-suited for guiding extremely high-power laser beams due to glass damage and scattering of laser energy out of the fiber. Additionally, the need for a physical support structure means that glass fiber must be laid down long in advance of light signal transmission or collection.

Professor Howard Milchberg and his group in the Depts. of Physics, ECE, and the Institute for Research in Electronics and Applied Physics at the University of Maryland have demonstrated an optical guiding method that beats both limitations, using auxiliary ultrashort laser pulses to sculpt fiber optic waveguides in the air itself. These short pulses form a ring of high-intensity light structures called “filaments”, which heat the air molecules to form an extended ring of low-density heated air surrounding a central undisturbed region; this is exactly the refractive index structure of an optical fiber. With air itself as the fiber, very high average powers can potentially be guided. And for collection of remote optical signals for detecting pollutants and radioactive sources, for example, the air waveguide can be arbitrarily “unspooled” and directed at the speed of light in any direction.An unguided continuous wave green laser beam (left), and the same beam guided by an air waveguide generated at 10 Hz (center) and at 1000 Hz (right). The air waveguide on the right is essentially continuously operating.An unguided continuous wave green laser beam (left), and the same beam guided by an air waveguide generated at 10 Hz (center) and at 1000 Hz (right). The air waveguide on the right is essentially continuously operating.

In an experiment published in January in Physical Review X [Physical Review X 13, 011006 (2023)], graduate student Andrew Goffin and colleagues from Milchberg’s group showed that this technique can form 50-meter-long air waveguides that persist for tens of milliseconds until they dissipate from cooling by the surrounding air. Generated using only one watt of average laser power, these waveguides could theoretically guide megawatt average power laser beams, making them exceptional candidates for directed energy. The waveguide method is straightforwardly scalable to 1 kilometer and longer. However, the waveguide-generating laser in that work fired a pulse every 100 milliseconds (repetition rate of 10 Hz), with cooling dissipation over 30 milliseconds, leaving 70 milliseconds between shots with no air waveguide present. This is an impediment to guiding a continuous wave laser or collecting a continuous optical signal.

In a new Memorandum in Optica [Optica 10, 505 (2023)], Andrew Goffin, Andrew Tartaro, and Milchberg show that by increasing the repetition rate of the waveguide-generating pulse up to 1000 Hz (a pulse every millisecond), the air waveguide is continuously maintained by heating and deepening the waveguide faster than the surrounding air can cool it. The result is a continuously operating air waveguide that can guide an injected continuous wave laser beam. Because the waveguide is deepened by repetitive generation, guided light confinement efficiency improves by a factor of three at the highest repetition rate.

Continuous wave optical guiding significantly improves the utility of air waveguides: it increases the maximum average laser power one can transport and maintains the guiding structure for use in continuous collection of remote optical signals. And because kilometer-scale and longer waveguides are wider, cooling is slower and a repetition rate well below 1 kHz will be needed to maintain the guide. This more lenient requirement makes continuous air waveguiding over kilometer and longer ranges easily achievable with existing laser technology and modest power levels.

“With an appropriate laser system for generating the waveguide, long-distance continuous guiding should be easily doable”, says Goffin, “Once we have that, it’s just a matter of time before we’re transmitting high power continuous laser beams and detecting pollutants from miles away.”

(Possibly) Breaking the Standard Model, One Lepton-universality-violating Decay at a Time

Physicists in general, and high energy physicists in particular, like to "break" things. It can be useful to prove again that a well established theory is true, especially if you are probing a yet-untested prediction of the venerable theory. But proving that the theory is wrong--or at least not completely true--that is where the fun is. This is why a series of measurements of b hadron decays that seemingly break the Standard Model (SM) of particle physics is garnering so much excitement.

You see, the SM is the most well established theory of them all, the only one with predictions corroborated to the 11th digit (see the anomalous magnetic moment of the electron). It was fully fleshed out in the 70's, and since then it has racked up success after success. Its crowning achievement came in 2012 when the long-predicted Higgs boson was finally confirmed to be alive and well. Despite this resiliency, the SM is not the end of it all. It can't explain why the mass of the Higgs is so low, what the nature of dark matter is, or why there is so much more matter than antimatter in the universe. Finding answers to these questions will thus require breaking, or extending, the SM.

Enter Lepton Flavor Universality (LFU) violation. LFU is a fundamental assumption within the SM involving the three lepton flavors: electron, muon, and tau. All SM interactions other than the Higgs are assumed to be flavor universal, and this has been shown to be true in numerous measurements. Since 2012, however, an intriguing pattern has emerged in decays of b hadrons (particles with a b quark inside) to final states with a c quark, a tau lepton τ, and a neutrino ν. When results involving a tau lepton and a neutrino are compared to decays involving a muon or an electron and a neutrino, they tend to be higher than we'd expect from SM calculations. This is shown in the nearby figure by all the measurements keeping their distance from the theoretical predictions in blue. Measurements that measured the two LFU quantities RD and RD* are shown as Artistic representation of a proton-proton collision resulting in a B meson that subsequently decays to a charmed D0 or D* meson, a tau lepton, as well as a smaller antineutrino. Credit: Greg Stewart, SLAC National Accelerator Laboratory/BaBar and Manuel Franco Sevilla.Artistic representation of a proton-proton collision resulting in a B meson that subsequently decays to a charmed D0 or D* meson, a tau lepton, as well as a smaller antineutrino. Credit: Greg Stewart, SLAC National Accelerator Laboratory/BaBar and Manuel Franco Sevilla.ellipses while measurements of RD* alone are shown as markers with uncertainties.
None of these results on their own rises to what is typically known as an "observation" (5σ statistical significance), and it could very well go away. For instance, a similar pattern that had appeared when comparing decays involving a kaon and two muons to decays with a pair of electrons was recently shown to be an artifact  of an underestimated background. But the consistency among results that share the same b→ cτν underlying process is very suggestive. Multiple explanations have been proposed that would explain all of these with physics beyond the SM (BSM). A particularly neat solution postulates a new kind of exotic particle that interacts with both leptons and quarks: a vector leptoquark. 
In an article published last year in Review of Modern Physics ("Semitauonic b-hadron decays: A lepton flavor universality laboratory"), my co-authors and I comprehensively described these results, delved into the main sources of uncertainty, and mapped out the future measurements. Spoiler alert: while we do not know whether BSM physics will be discovered, we are rather confident that we will know whether these results are due to BSM physics or not within 5-10 years. 
And the first of these new results was just submitted to Physical Review Letters  Professor Hassan Jawahery and Dr. Phoebe Hamilton, together with Dr. Greg Ciezarek from CERN, measured for the first time RD and RD* simultaneously at LHCb. The uncertainties are still large, so it is hard to say whether the discrepancy will be proven true. But this result sets the stage for another meaThe results reflect analysis of two years of data by Phoebe Hamilton and Hassan Jawahery and their CERN collaborator, Greg Ciezarek.The results reflect analysis of two years of data by Phoebe Hamilton and Hassan Jawahery and their CERN collaborator, Greg Ciezarek.surement based on the same techniques that uses a data sample more than 6 times larger. This work, carried out by the all-UMD team Professor Manuel Franco Sevilla, Dr. Hamilton, Dr. Christos Hadjivasiliou, Yipeng Sun, and Alex Fernez, is now fairly advanced. So stay tuned, there's potential for SM-breaking ahead!

 --Manuel Franco Sevilla



UMD Physicists Hope to Strike Gold by Finding Dark Matter in an Old Mine

Nestled in the mountains of western South Dakota is the little town of Lead, which bills itself as “quaint” and “rough around the edges.” Visitors driving past the hair salon or dog park may never guess that an unusual—even otherworldly—experiment is happening a mile below the surface.

A research team that includes University of Maryland physics faculty members and graduate students hopes to lure a hypothesized particle from outer space to the town’s Sanford Underground Research Facility, housed in a former gold mine that operated at the height of the 1870s gold rush. 

More specifically, they are searching for WIMPs—weakly interacting massive particles which are thought to have formed when the universe was just a microsecond old. The research facility suits this type of search because the depth allows the absorption of cosmic rays, which would otherwise interfere with experiments.

If WIMPs are observed, they could hold clues to the nature of dark matter and structure of the universe, which remain some of the most perplexing problems in physics.

Just getting started
The UMD team is led by Physics Professor Carter Hall, who has been looking for dark matter for 15 years. Excited by the prospect of observing unexplained physical phenomena, Hall joined the Large Underground Xenon (LUX) experiment, an earlier instrument at the Sanford Lab that attempted to detect dark matter from 2012 to 2016.

LUX was the most sensitive WIMP dark matter detector in the world until 2018. Its successor at Sanford, the new and improved LUX-ZEPLIN (LZ) experiment, launched last year. Hall believes LZ has even better odds of detecting or ruling out dark matter due to its significantly larger target. It’s specifically designed to search for WIMPs—a strong candidate for dark matter that, if proven to exist, could help account for the missing 85% of the universe’s mass.

Unlike experiments conducted at particle smashers like the Large Hadron Collider (LHC) in Switzerland, the LZ attempts to directly observe—rather than manufacture—dark matter. Anwar Bhatti, a research professor in UMD’s Department of Physics, said there are pros and cons to both approaches. He worked at the LHC from 2005 to 2013 and is now part of the LZ team at UMD.

Bhatti said the odds of finding irrefutable proof of WIMPs are slim, but he hopes previously undiscovered particles will show up in their experiment, leaving a trail of clues in their wake.

“There’s a chance we will see hints of dark matter, but whether it’s conclusive remains to be seen,” Bhatti said. 

UMD physics graduate students John Armstrong, Eli Mizrachi, and John Silk are also part of this experiment, and the team published its first set of results in July 2022 following a few months of data collection. No dark matter was detected, but their results show that the experiment is running smoothly. Researchers expect to continue collecting data for up to five years.

“That was just a little taste of the data,” Hall said. “It convinced us that the experiment is working well, and we were able to rule out certain types of WIMPs that had not been explored before. We’re currently the world’s most sensitive WIMP search.”

Sparks in the dark

These direct searches for dark matter can only be conducted underground because researchers need to eliminate surface-level cosmic radiation, which can muddle dark matter signals and make them easier to miss. 

“Here, on the surface of the Earth, we’re constantly being bathed in cosmic particles that are raining down upon us. Some of them have come from across the galaxy and some of them have come across the universe,” Hall explained. “Our experiment is about a mile underground, and that mile of rock absorbs almost all of those conventional cosmic rays. That means that we can look for some exotic component which doesn’t interact very much and would not be absorbed by the rock.”

In the LZ experiment, bursts of light are produced by particle collisions. Researchers then work backward, using the characteristics of these flashes of light to determine the type of particle.

The UMD research group calibrates the instrument that powers the LZ experiment, which involves preparing and injecting tritium—a radioactive form of hydrogen—into a liquefied form of xenon, an extremely dense gas. Once mixed, the radioactive mixture is pumped throughout the instrument, which is where the particle collisions can be observed.

The researchers then analyze the mixture’s decay to determine how the instrument responds to background events that are not dark matter. By process of elimination, the researchers learn the types of interactions are—and aren’t—important.

“That tells us what dark matter does not look like, so what we’re going to be looking for in the dark matter search data are events that don’t fit that pattern,” Hall said.

The UMD team also built, and now operates, two mass spectrometry systems that monitor xenon to ensure it isn’t poisoned by impurities like krypton, a gas found in the atmosphere. To detect dark matter scatterings, xenon must be extremely pure with no more than 100 parts per quadrillion of krypton.

Rewriting the physics playbook

The researchers will not know if they found dark matter until their next data set is released. This could take at least a year because they want the sensitivity of the second data set to significantly exceed that of the first, which requires a larger amount of data overall.

If detected, these WIMP particles would prompt a massive overhaul of the Standard Model of particle physics, which explains the fundamental forces of the universe. While this experiment could answer pressing questions about the universe, there is a good chance it will also create new ones. Hall thinks up-and-coming physicists will welcome that challenge. 

“It would mean that a lot of our basic ideas about the fundamental constituents of nature would need to be revised in one way or another,” Hall said. “Understanding how that would fit into particle physics as we know it would immediately become the big challenge for the next generation of particle physicists.”

Written by Emily Nunez

Twisting Up Atoms Through Space and Time