Why do viruses like the coronavirus sometimes steal our sense of smell?

When you catch a severe cold, your nose stuffs up, you can’t smell anything and food tastes funny. Fortunately, most people regain their sense of smell once the cold runs its course. But for others, the complete (anosmia) or partial (hyposmia) loss of the sense of smell is permanent.

I spoke with Zara Patel, MD, a Stanford associate professor of otolaryngology, head and neck surgery, and director of endoscopic skull base surgery, to learn more about her research on olfactory disorders. In particular, we discussed her recent study on the possible association between post-viral olfactory loss and other cranial neuropathies, which are disorders that impair your nerves and ultimately your ability to feel or move. She also described how her work pertains to the COVID-19 pandemic.  

How does a virus impair someone’s sense of smell?

A variety of viruses can attack the cranial nerves related to smell or the mucosal tissue that surrounds those nerves. Cranial nerves control things in our head and neck — such as the nerves that allow us to speak by using our vocal cords, control our facial motion, hear and smell.

For example, COVID-19 is just one type of disease caused by a coronavirus. There are many other types of coronaviruses that cause colds and upper respiratory illnesses, as well as rhinoviruses and influenza viruses. Any of these viruses are known to cause inflammation, either directly around the nerve in the nasal lining or within the nerve itself. When the nerve is either surrounded by inflammatory molecules or has a lot of inflammation within the nerve cell body, it cannot function correctly — and that is what causes the loss or dysfunction of smell. And it can happen to anyone: young and old, healthy and sick.

How did your study investigate olfactory loss?

In my practice, I see patients who have smell dysfunction. But I’m also a sinus and skull base surgeon, so I have a whole host of other patients with sinus problems and skull-based tumors who don’t have an olfactory loss. So we did a case-control study to compare the incidence of cranial neuropathies — conditions in which nerves in the brain or brain stem are damaged — in two patient groups. Ninety-one patients had post-viral olfactory loss and 100 were controls; and they were matched as closely as possible for age and gender.

We also looked at family history of neurologic diseases — such as Alzheimer’s disease, Parkinson’s disease and stroke.

What did you find?

Patients with post-viral olfactory loss had six-times higher odds of having other cranial neuropathies than the control group — with an incidence rate of other cranial nerve deficits of 11% and 2%, respectively. Family history of neurologic diseases was associated with more than two-fold greater odds of having a cranial nerve deficit. Although we had a small sample size, the striking difference between the groups implies that it is worthwhile to research this with a larger population.

Our findings suggest that patients experiencing these pathologies may have inherent vulnerabilities to neural damage or decreased ability of nerve recovery — something beyond known risk factors like age, body mass index, co-morbidities and the duration of the loss before intervention. For example, there may be a genetic predisposition, but that is just an untested theory at this point.

How does this work pertain to COVID-19?

Smell loss can be one of the earliest signs of a COVID-19 infection. It can sometimes be the only sign. Or it can present after other symptoms. Although it may not affect every patient with COVID-19, loss of smell and taste is definitely associated with the disease. In some countries, including France, they’ve used this as a triage mechanism. People need to know that these symptoms can be related to the COVID-19 disease process so they aren’t going about their lives like normal and spreading the virus.

The pandemic also might impact how we treat patients with olfactory dysfunction in general. When someone has a viral-induced inflammation of the nerve, we sometimes treat it with steroids to decrease the inflammation. But treating COVID-19 patients with steroids might be a bad idea because of its effect on the inflammatory processes going on in their heart and lungs.

What advice do you have for people who have an impaired sense of smell?  

First, if you lose your sense of smell and it isn’t coming back after all the other symptoms have gone away, seek care as soon as possible. If you wait too long, there is much less that we can do to help you. Interventions, including olfactory training and medications, are more effective when you are treated early.

Second, if you lose your sense of smell or taste during this pandemic and you don’t have any other symptoms, contact your doctor. The doctor can decide whether you need to be tested for COVID-19 or whether you need to self-isolate to avoid being a vector of the virus in your family or community.

Image by carles

This is a reposting of my Scope story, courtesy of Stanford School of Medicine.

Harnessing AMReX for Wind Turbine Simulations

ECP ExaWind Project Taps Bereley Lab’s AMReX to Help Model Next-Generation Wind Farms

Driving along Highway 580 over the Altamont Pass in Northern California, you can’t help but marvel at the 4,000+ wind turbines slowly spinning on the summer-golden hillsides. Home to one of the earliest wind farms in the United States, Altamont Pass today remains one of the largest concentrations of wind turbines in the world. It is also a symbol of the future of clean energy.

Before utility grids can achieve wide-scale deployment of wind energy, however, they need more efficient wind plants. This requires advancing our fundamental understanding of the flow physics governing wind-plant performance.

ExaWind, a U.S. Department of Energy (DOE) Exascale Computing Project, is tackling this challenge by developing new simulation capabilities to more accurately predict the complex flow physics of wind farms. The project entails a collaboration between the National Renewable Energy Laboratory (NREL), Sandia National Laboratories, Oak Ridge National Laboratory, the University of Texas at Austin, Parallel Geometric Algorithms, and — as of a few months ago — Lawrence Berkeley National Laboratory (Berkeley Lab).

“Our ExaWind challenge problem is to simulate the air flow of nine wind turbines arranged as a three-by-three array inside a space five kilometers by five kilometers on the ground and a kilometer high,” said Shreyas Ananthan, a research software engineer at NREL and lead technical expert on the project. “And we need to run about a hundred seconds of real-time simulation.” 

By developing this virtual test bed, the researchers hope to revolutionize the design, operational control, and siting of wind plants, plus facilitate reliable grid integration. And this requires a combination of advanced supercomputers and unique simulation codes.

Unstructured + Structured Calculations

The principle behind a wind turbine is simple: energy in the wind turns the turbine blades, which causes an internal gearbox to rotate and spin a generator that produces electricity. But simulating this is complicated. The flexible turbine blades rotate, bend, and twist as the wind shifts direction and speed. The yaw and pitch of these blades are controlled in real time to extract as much energy as possible from a wind event. The air flow also entails complex dynamics  — such as influences from the ground terrain, formation of a turbulent wakefield downstream from the blades, and turbine-turbine interactions.

To improve on current simulations, scientists need more computing power and higher resolution models that better capture the crucial dynamics. The ExaWind team is developing a predictive, physics-based, and high-resolution computational model — progressively building from petascale simulations of a single turbine toward exascale simulations of a nine-turbine array in complex terrain.

A Nalu-Wind solution to the differential equations of motion for a wind turbine operating in uniform air flow (moving from left to right). Two of the three wind turbine’s blades are pictures (think blue rectangles on left). The slice in the background represents the contours of the whirling air’s motion, showing the vertical direction of the wake structure behind the turbine blades (red indicates swirl in counterclockwise direction and blue clockwise direction around blade tip).

“We want to know things like the air velocity and air temperature across a big three-dimensional space,” said Ann Almgren, who leads the Center for Computational Sciences and Engineering in Berkeley Lab’s Computational Research Division. “But we care most about what’s happening right at the turbines where things are changing quickly. We want to focus our resources near these turbines, without neglecting what’s going on in the larger space.”

To achieve the desired accuracy, the researchers are solving fluid dynamics equations near the turbines using a computational code called Nalu-Wind, a fully unstructured code that gives users the flexibility to more accurately describe the complex geometries near the turbines, Ananthan explained.

But this flexibility comes at a price. Unstructured mesh calculations have to store information not just about the location of all the mesh points but also about which points are connected to which. Structured meshes, meanwhile, are “logically rectangular,” which makes a lot of operations much simpler and faster.

“Originally, ExaWind planned to use Nalu-Wind everywhere, but coupling Nalu-Wind with a structured grid code may offer a much faster time-to-solution,” Almgren said.

Enter AMReX

Luckily, Ananthan knew about Berkeley Lab’s AMReX, a C++ software framework that supports block-structured adaptive-mesh algorithms for solving systems of partial differential equations. AMReX supports simulations on a structured mesh hierarchy; at each level the mesh is made up of regular boxes, but the different levels have different spatial resolution.

Ananthan explained they actually want the best of both worlds: unstructured mesh near the turbines and structured mesh elsewhere in the domain. The unstructured mesh and structured mesh have to communicate with each other, so the ExaWind team validated an overset mesh approach with an unstructured mesh near the turbines and a background structured mesh. That’s when they reached out to Almgren to collaborate.

“AMReX allows you to zoom in to get fine resolution in the regions you care about but have coarse resolution everywhere else,” Almgren said. The plan is for ExaWind to use an AMReX-based code (AMR-Wind) to resolve the entire domain except right around the turbines, where the researchers will use Nalu-Wind. AMR-Wind will generate finer and finer cells as they get closer to the turbines, basically matching the Nalu-Wind resolution where the codes meet. Nalu-Wind and AMR-Wind will talk to each other using a coupling code called TIOGA.

Even with this strategy, the team needs high performance computing. Ananthan’s initial performance studies were conducted on up to 1,024 Cori Haswell nodes at Berkeley Lab’s National Energy Research Scientific Computing Center (NERSC) and 49,152 Mira nodes at the Argonne Leadership Computing Facility.

“For the last three years, we’ve been using NERSC’s Cori heavily, as well as NREL’s Peregrine and Eagle,” said Ananthan. Moving forward, they’ll also be using the Summit system at the Oak Ridge Leadership Computing Facility and, ultimately, the Aurora and Frontier exascale supercomputers — all of which feature different types of GPUs: NVIDIA on Summit (and NERSC’s next-generation Perlmutter system), Intel on Aurora, and AMD on Frontier. 

Although Berkeley Lab just started partnering with the ExaWind team this past fall, the collaboration has already made a lot of progress. “Right now we’re still doing proof-of-concept testing for coupling the AMR-Wind and Nalu-Wind codes, but we expect to have the coupled software running on the full domain by the end of FY20,” said Almgren.

NERSC is a DOE Office of Science user facility.

Top figure: Some of the 4000+ wind turbines in Northern California’s Altamont Pass wind farm. Credit: David Laporte

This is a reposting of my news feature, courtesy of Berkeley Lab.

Hydrogel elicits switchable, reversible, and controllable self-trapping light beams

The next generation of optoelectronic and photonic systems — with wide-ranging potential applications in image transmission, light-guiding-light signal processing, logic gates for computing, and medicine — may be realized through the invention of circuitry-free, rapidly reconfigurable systems powered by solitons. Optical spatial solitons are self-trapped optical beams of finite spatial cross section that travel without diverging like freely diffracting beams. These nonlinear waves propagate in photoresponsive materials through self-inscribed waveguides, which are generated when the materials locally change their refractive index in response to light intensity. In conventional nonlinear materials, self-trapping requires high-powered lasers or external electric fields.

Now, a team of researchers from the University of Pittsburgh, Harvard University, and McMaster University have developed a pH-responsive poly(acrylamide-co-acrylic acid) hydrogel, a hydrophilic three-dimensionally connected polymer network, in which light self-trapping can be turned rapidly on and off many times in a controllable and reversible way using a low-intensity visible laser. They reported their work in a recent issue of Proceedings of the National Academy of Sciences.

Developed by Joanna Aizenberg’s group at Harvard University, the hydrogel contains critical covalently-tethered chromophores that absorb specific wavelengths of visible light and thereby transform their structure. In the absence of light, the gel is relaxed and the chromophores are predominantly in a ring-open merocyanine form. When the hydrogel is irradiated with visible light, the isomerization of merocyanine to its closed-ring spiropyran form triggers a local expulsion of water, a contraction of the hydrogel, and ultimately an increase in the refractive index along the irradiated path.

The novelty of this work is that this isomerization process is reversible. In the absence of light, the hydrogel reverts back to its original state.

The researchers demonstrated the reversible self-trapping process with experiments led by Kalaichelvi Saravanamuttu’s team at McMaster University—measuring the diameter and peak intensity of the beam over time using a 532 nm laser, optical lenses, neutral density filters, and a CCD camera. They also performed a series of control experiments, such as testing the hydrogel matrix without chromophores, to determine which parameters are critical for self-trapping.

“We determined it was important to have a hydrogel matrix that became more hydrophobic in the presence of light. It was important to have the chromophores covalently-tethered to the three-dimensional matrix to localize the refractive index change. And photoisomerization was critical in triggering this sequence of events,” says Saravanamuttu, an associate professor of chemistry and chemical biology and a senior author on the paper.

More surprising, when the researchers irradiated the hydrogel with two parallel lasers, the self-trapping beams interacted with each other when separated by distances up to 10 times the beam width. “They modulated each other, reducing their self-trapping efficiency, at remote distances through the interconnected and flexible network of the hydrogel,” Saravanamuttu says.

Being able to reversibly, predictably, and remotely control one self-trapped beam with another opens up the possibility of applications like all-optical computing using beams of ambient light. Traditional computations are performed using hard materials such as wires, semiconductors and photodiodes to couple electronics to light. Instead, the team hopes to control light with light. So far, they have already used the interactions of self-trapped beams to do basic binary arithmetic, says Saravanuamuttu.

These experimental results were confirmed by numerical simulations developed by senior authors Aizenberg, a professor of materials science and of chemistry and chemical biology at Harvard University, and Anna Balazs, a professor of chemical and petroleum engineering at the University of Pittsburgh, and their groups. Their model dynamically calculated the spatial and temporal evolution of the optical field as it propagated through the hydrogel, whose index of refraction was changing. Consistent with experiments, the model accurately captured the self-trapping dynamics and efficiency when using the single or double laser beams.

“This paper marks an interesting step forward that is indicative of the potential of one disruptive technology,” says John Sheridan, a professor of electrical and electronic engineering at the University College of Dublin, who was not involved in the research. “Technologies like this will provide core hardware components enabling the three-dimensional, all-optical connection and switching hardware needed for ‘Internet of things’ data integration and the 5G/6G telecommunications systems of the future.”

Currently, the speed of the waveguide formation and switching happens in seconds, though, rather than the nanoseconds typical of optoelectronic switches. So the researchers plan to investigate what parameters are slowing down the process and how to change them. For example, they will explore making the hydrogel more flexible to give the chromophores greater freedom to undergo isomerization in hopes of eliciting a faster response. They will also look at different types of isomerizable chromophores.

However, Saravanamuttu emphasizes they are not trying to replace digital computers that use conventional electronics, so speed may not be critical. Other potential applications include autonomous stimuli-responsive soft robotic systems for drug delivery or dynamic optics.

“This is particularly exciting because we see it as a material that can reciprocally interact with an environmental stimulus. It isn’t just turned on and off, but it actually changes its behavior in a dynamic way,” she says.

Read the article in Proceedings of the National Academy of Sciences

Figure caption: (a) Schematic illustration of the experimental setup used to probe laser self-trapping due to photoinduced local contraction of the hydrogel. A 532 nm laser beam is focused onto the entrance face of the hydrogel, propagated through the material, and imaged onto a CCD camera. (b) Illustration of beam-induced contraction of the hydrogel when continuously irradiated with a 532 nm laser beam. Credit: Saravanamuttu group, McMaster University, Aizenberg Group, Harvard University, Balazs Group, University of Pittsburgh; PNAS doi.org/10.1073/pnas.1902872117

This is a reposting of my MRS news brief, courtesy of the Materials Research Society.

Defend or delay? Grad students must decide whether to present their thesis virtually

Graduate students who are trying to finish their degrees amid the COVID-19 pandemic are finding, after years of research and months of preparation, that the big day of defending their thesis has to be delayed or done remotely.

Faced with a new order to shelter at her off-campus home, Anjali Bisaria, a graduate student in chemical and systems biology at Stanford, decided to forge ahead. She works in the lab of Tobias Meyer, PhD,  where they study how human cells move and divide to build, maintain and repair tissues and organs.

On the scheduled date and time, Bisaria logged into a Zoom session and defended her research to a virtual audience of advisors, classmates, friends and family members. She then virtually met with just her faculty examinees. After being declared a doctor, she celebrated with her lab via yet another Zoom session.

“I know it was the right thing to do to keep the community safe,” she said in a Stanford news story. “But it was a little bit sad because this is likely my last quarter on campus. So to not be able to interact with my classmates and not be able to enjoy that honeymoon phase of grad school felt unceremonious.”

Soon, microbiology and immunology graduate student Kali Pruss will face the same decision. Her in-person PhD oral is currently scheduled for May 22 at Munzer Auditorium on Stanford campus.

“I haven’t yet decided whether I’ll proceed with my defense via Zoom or delay my defense to later in the summer, in hopes that I would be able to have an in-person defense,” Pruss told me. “I was planning on staying through the summer, taking a writing quarter anyway. Thankfully, this gives me some flexibility in terms of timing.”

As a member of the lab run by Justin Sonnenburg, PhD, Pruss studies how Clostridium difficile — a bacteria that commonly causes diarrhea and colitis — adapts to the inflammation that it generates, she said.

Pruss is currently writing a paper on her research, but the pandemic is impacting that too. She told me that she’s doing more data analysis and relying less on experiments than she normally would — and she’s a bit worried about how this approach will be received.

“I’m concerned with how this is going to affect the review process, and whether I’ll be able to successfully address reviewer comments asking for additional experiments for my papers,” she said.

She added, “Ultimately, though, I feel incredibly privileged and grateful to be able to continue working remotely towards my dissertation. The question of how my research is being impacted, and whether to postpone my defense, has been a minor concern in the scope of what is currently happening at Stanford and around the world.”

Given the extension of the Bay Area’s shelter-at-home order to last through at least May 3, Pruss’s hopes of defending in-person on May 22 may not be realized. So, her extended family — from Wisconsin, Indiana and Illinois — canceled their travel arrangements. They hope to come in late summer if she delays her defense and sheltering orders have been lifted.  

Regardless of how she defends her thesis, she plans to celebrate her upcoming educational milestone.

“This is the one time we, as PhD students, get to celebrate our time in grad school as an accomplishment,” she said.

After graduation, Pruss plans to join Jeffrey Gordon’s lab at Washington University School of Medicine in St. Louis as a postdoc. Ultimately, she plans to run her own academic lab.

Photo by Anjali Bisaria

This is a reposting of my Scope story, courtesy of Stanford School of Medicine.