The research, recently published in the Journal of Glaciology, is the first large-scale study of its kind to compare ice shelf thickness data from ice-penetrating radar measurements to thickness data estimated from contemporary surface elevation measurements.

By juxtaposing vast datasets of 20 of the 300 total separate ice shelf systems that surround about 75% of the Antarctic ice sheet, researchers from The Ohio State University found that on average, the Antarctic ice shelves are nearly 6% thinner than previous studies had assumed, a difference of about 17 meters. This may seem like a small shift in scale, but typical ice shelves can be anywhere from 50 to 600 meters thick.

The study concludes that while prior assumptions about the ice shelves’ thickness were correct on a large scale, their accuracy varied greatly on a small scale, such as for individual structures like valleys or crevasses that are either too narrow or too small to be measured accurately.

Yet as ice shelves play a large role in stabilizing the Antarctic ice sheet as well as Earth’s complex climate system, getting an accurate estimation of their size is essential for calculating how their melt could contribute to sea level rise, said Allison Chartrand, lead author of the study and recent doctoral graduate of the Byrd Polar and Climate Research Center.

“Because the Antarctic ice sheet is so big, a 1% misestimation in how fast it’s melting could mean inches or feet of sea level rise that we’re not accounting for,” she said. “So it’s really important to be as accurate as we can.”

Even the most minute changes to Antarctica’s ice shelves could pose a significant threat to coastal communities, Chartrand said, as a few inches of significantly displaced ice shelf could cause thicker ice to flow into the ocean and potentially cause some coastlines to retreat several feet.

According to Chartrand, she and her co-author, Ian Howat, a glaciologist and a Distinguished University Scholar in earth sciences at Ohio State, first began to investigate ice shelf thickness when examining basal channels — channels in which warmer ocean water melts grooves into the bottom of the ice shelf, accelerating mass loss — during a previous study.

One of the largest discrepancies the study found was that the assumptions used to estimate ice shelf thickness in previous research sometimes exaggerated ice shelf thickness in some areas, and at other times understated it.

While many of these inconsistencies don’t take away much from the big picture, individually, these snapshots are vastly out of focus, said Chartrand. “In comparing the thickness estimate with the radar estimate, we saw that the numbers we had on basal channels and other features like them could be different by up to hundreds of meters, which meant that we could potentially be underestimating or overestimating rates of change,” she said.

Overall, the study concludes that more abundant and accurate data is needed to enable better predictions of ice shelf loss in Antarctica, as the ultimate goal of their work is to improve observations of the processes that contribute to sea level rise, said Chartrand.

“What this research really shows is that we need to be a lot more careful about the assumptions we make to estimate the ice shelf thickness, and about how we account for uncertainties and what they mean for the final result,” she said.

While their work also seeks to inspire others to probe into older datasets, Chartrand hopes that using the past to study the future changes in our environment spurs the development of more advanced technologies, ones that might be able to offer greater aid in the task of assessing the ups and downs of Antarctica’s ever-shifting landscape.

“There’s potential for new discoveries even with data collected anywhere from two to 15 years ago, so we know that a lot still hasn’t been fully explored,” said Chartrand.

This study was supported by NASA and the National Science Foundation.

“Although we finally recognize that environmental chemicals impact women’s health, most studies have focused on men’s reproductive health and very few studies have looked at how these chemicals affect women,” said Jodi Flaws (EIRH co-leader/MME), a professor of comparative biosciences. “Our paper is novel because we are the first to look at this aspect of reproduction.”

For their study, the researchers chose a DiNP dose that humans are exposed to on a daily basis. They exposed pregnant female mice to DiNP orally for their first week of pregnancy, which is analogous to the first trimester in humans.

“I chose this window because most women don’t know from day one that they are pregnant. As a result, they maintain their general lifestyle for a while and may become more careful once they know that they are pregnant. During that time, however, they will continue to be exposed to DiNP,” said Arpita Bhurke, a postdoctoral fellow in the Bagchi lab and the first author of the paper.

In the early stages of pregnancy, the embryo attaches to the uterus and embeds in the maternal tissue, which supports the growth and development of the embryo. The process also stimulates the formation of new blood vessels, ensuring that the embryo has an adequate supply of oxygen and nutrients from the mother. Using tissue-staining techniques, the researchers found that DiNP exposure impairs the formation of blood vessels in both the maternal tissue and the placenta.

“In mice, these maternal blood vessels are formed after the first week of pregnancy and they have been exposed to DiNP before this development happens,” said Indrani Bagchi (EIRH co-leader), a Billie Field Professor of Reproductive Biology. “As a result, the tissue formation is effected and it creates a ripple effect, impairing embryo growth.”

The impact of DiNP on the placenta had several consequences later on in the pregnancy. The researchers found that pregnant mice that had been exposed to DiNP had smaller litter sizes and shorter gestation periods. Mice that were fed corn oil instead of DiNP produced an average of 16 pups per litter, whereas DiNP-fed mice produced 11 pups, and on average the pups weighed less. Additionally, instead of delivering their litter in 20 days, DiNP-fed mice were giving birth 18-24 hours earlier.

“We know that DiNP causes defects in the formation of the placenta. However, it is unclear whether this is due to the effect of DiNP on the embryo or on the maternal tissue or both. We want to address this question in our future work,” Bagchi said.

The researchers are also interested in deciphering how the chemicals impact the uterine tissue and litter birth. “I will focus on cell culture systems because we want to distinguish between the embryo and the maternal tissue effects. By using just the cells, we can better understand how DiNP is impacting the placenta in both early and late stages of pregnancy,” Bhurke said.

It’s an issue in the news, as toxic mold spawned by the moisture left behind by flood waters from Hurricane Idalia could lead to severe health problems for people who suffer from chemical intolerance. This mold also could initiate the condition in some individuals.

“Everyone should avoid prolonged exposure to mold whenever possible,” said physician-researcher Claudia Miller, MD, MS, from The University of Texas Health Science Center at San Antonio, also called UT Health San Antonio. “Research has increasingly shown that toxic mold is much more dangerous than was previously recognized.”

In the survey, published in the journal Environmental Sciences Europe, 17.5% of participants who attributed their illness to an initiating event cited mold exposure as the perceived cause of their chemical intolerance. CI is estimated to afflict up to 20% to 30% of Americans, Miller, senior author of the study, said.

Participants were queried about antibiotic use, as well. According to the results, prolonged courses of antibiotics were associated with an increased risk of CI.

The survey data also indicate that with each additional initiating exposure respondents can recall, the odds of their reporting CI nearly triple.

“With climate change contributing to more severe storms and more intense flooding worldwide, the danger posed by toxic mold is likely to increase dramatically in the near future,” Miller said. “As mold exposure is known to be a major initiator, the likelihood of more and more people with chemical intolerance is also unfortunately on the rise.”

TILT

The study furthers understanding about how a two-stage disease process called TILT (toxicant-induced loss of tolerance) begins. The survey asked 10,981 people to state their self-perceptions about the events that began the downward spiral through TILT and into chemical intolerance.

“TILT can develop rapidly, for instance after a pesticide exposure, or gradually if someone is working or living in a setting such as a moldy building,” Miller said. She first proposed TILT in 1996 and is professor emerita of family and community medicine at UT Health San Antonio.

Unknown origins

“Initiating events commonly go unrecognized and therefore unreported, leaving triggers and symptoms as the only documented components,” Miller said. “This has thwarted our understanding of the actual causes of TILT.”

Participants completed an 80-question online survey called the Personal Exposure Inventory. It included items concerning individuals’ medical diagnoses and personal exposures including antibiotic use.

Chemical intolerance was assessed using the Quick Environmental Exposure and Sensitivity Inventory (QEESI©) developed by Miller 25 years ago. It is a validated, self-administered questionnaire now used worldwide to differentiate individuals with CI from the general population. One-fifth of survey respondents met the QEESI criteria for chemical intolerance.

Toxic mold

Exposure to mold was the most frequently mentioned initiating event on the Personal Exposure Inventory. “In recent years, global warming has led to more rainfall, floods, hurricanes, roof leaks and water intrusion, resulting in increased mold growth indoors,” said paper co-author Raymond F. Palmer, PhD, a biostatistician and professor of family and community medicine at UT Health San Antonio.

Mold was followed in rank order by exposures to pesticides (cited by 13.8% of respondents), medical/surgical procedures (12.6%), remodeling/new construction (12.0%), fires/combustion products (7.2%) and breast implants (1.8%).

Antibiotics

Respondents answered questions pertaining to how many courses of antibiotics they had completed for specific types of infections. Antibiotics prescribed for infections categorized as skin, tonsil, gastrointestinal, prostate, sinus, wound and pneumonia were most strongly associated with chemical intolerance.

“Our search for the underlying causes of CI represents a much-needed addition to the CI/TILT literature, whose principal focus has been on triggers that elicit CI symptoms from day to day with no attempt to determine what initiated TILT,” Miller said.

‘A cohesive narrative’

“Taken together, our data support the idea that the person who reports multiple symptoms, multiple intolerances and recurrent infections as well as a history of exposure events is sharing a cohesive narrative, one that points to physiological (as opposed to psychosomatic) explanations of their oft-confusing complaints,” she said.

Although certain exposures such as medical/surgical procedures may be difficult to avoid, reducing exposures to contaminants related to pesticide use, new construction/remodeling and mold is possible and should be the focus of efforts to prevent future CI/TILT, the authors wrote.

Digging in

Finally, they encourage practitioners who see patients with medically unexplained symptoms — currently one in four primary care patients — to consider administering the QEESI. “‘TILTed’ individuals who report brain fog, memory, mood and concentration difficulties often receive referrals to psychiatrists, psychologists or social workers who explore their psychosocial environments but do not ask about changes in their actual — physical and chemical — environments,” Miller said. “If initiating exposures such as pesticides, toxic mold, implants and combustion products are not stopped, sensitivities can spiral out of control.”

Teaching in schools of medicine, public health, architecture and engineering has not kept pace with these toxicants, many of which are new to the planet since World War ll, Miller noted. This is exacerbated by energy conservation efforts that have increased exposures to indoor air toxicants, she said.

Marilyn Brachman Hoffman

In their acknowledgments, the authors “thank the Marilyn Brachman Hoffman Foundation for generously funding this study and Marilyn Hoffman for her prescient bequest prioritizing research on toxicant-induced loss of tolerance. We are deeply grateful to the patients who participated in this groundbreaking study.”

Hoffman’s bequest specified research on TILT. “She suffered terribly from chemical, food and drug intolerances herself, but especially from not being believed by family members and her doctors,” Miller said. “She was a citizen-scientist who read all my papers and book, “Chemical Exposures: Low Levels and High Stakes,” co-authored with Nicholas Ashford, PhD, JD, of the Massachusetts Institute of Technology.

“More than anything, Mrs. Hoffman wanted to discover the biomechanism for TILT,” Miller said. “She knew that it was essential for helping patients like herself. Her bequest has led to publication of the biomechanism for TILT in a series of papers over the past two years in Environmental Sciences Europe, a journal read by regulatory toxicologists around the world.”

If you suspect that you or a loved one has developed chemical intolerance or TILT, answer this brief, three yes-or-no question screening test, called BREESI. A positive response to any of the questions should lead to taking the more extensive, validated diagnostic questionnaire, the QEESI, or Quick Environmental Exposure and Sensitivity Inventory. People who have high scores on the QEESI are seen as likely to be chemically intolerant and are encouraged to share the information with their health care providers.

In people with tumors that originated in other parts of the body but spread to the brain, treatment with a type of immunotherapy called immune checkpoint blockade appears to elicit a significant increase in both active and exhausted T cells — signs that the T cells have been triggered to fight the cancer. The reason the same thing doesn’t occur in people with glioblastoma is that anti-tumor immune responses are best initiated in draining lymph nodes outside of the brain, and that process does not occur very effectively in glioblastoma cases.

To date, immunotherapy has not been effective in treating glioblastoma, but it has been shown to slow or even eradicate other types of cancer, such as melanoma, which frequently metastasizes to the brain.

The new research, published in the Journal of Clinical Investigation, could help improve the effectiveness of immunotherapy for people with brain tumors and it could suggest new paths in the effort to help develop more effective therapies.

“If we’re going to try to develop new therapies for solid tumors, like glioblastoma, which are not typically responsive, we need to understand the tumor types that are responsive, and learn the mechanisms by which that happens,” said the study’s senior author, Robert Prins, a professor of molecular and medical pharmacology and of neurosurgery at the David Geffen School of Medicine at UCLA.

The researchers studied the immune cells obtained from nine people with metastatic brain tumors who had been treated with immune checkpoint blockade — which works by harnessing the body’s immune system to destroy cancer cells — and compared their observations with immune cells taken from 19 patients with brain metastases that not been treated with immunotherapy.

They used a technique called single-cell RNA sequencing to examine the genetic material in both sets of samples, and then compared the data to previously published analyses of 25 recurrent glioblastoma tumors to better understand the effect the immunotherapy had on T cells.

“We really were trying to figure out which immune cells are changing in the more responsive tumors in order to better explain the higher response rate to the treatment,” said the study’s co-first author, Lu Sun, a project scientist in the Geffen School of Medicine’s neurosurgery department. “No study has comprehensively examined the differential effect of immune checkpoint blockade treatment on these two types of brain tumors before.”

In the tumors that had spread to the brain, the researchers saw that the T cells had specific characteristics associated with fighting tumors entering the brain, most likely due to a more effective priming step that occurs outside of the brain.

Before traveling to the brain, T cells are first activated in the lymph nodes. During this process, a type of immune cells called dendritic cells share information about the tumor to T cells so they can better attack the tumor. This priming process, however, doesn’t work very effectively when doctors attempt to use immune checkpoint blockade for treating glioblastoma.

The researchers also found that a specific subgroup of those exhausted T cells was associated with longer overall survival in people whose cancer had metastasized to the brain.

“We found quite a significant difference between the two types of brain tumors and how they respond to immunotherapies,” said study author Dr. Won Kim, surgical director of UCLA Health’s brain metastasis program and a member of the Jonsson Cancer Center. “There was a tremendous number of T cell lymphocytes that were found within brain metastases following immunotherapy, and while the number of T cell lymphocytes also increased in glioblastoma patients, it wasn’t anywhere near the same extent.”

Prins, who is also a researcher at the Jonsson Cancer Center, said that finding “suggests that enhancing the activation and presentation of T cells by dendritic cells could be a potential treatment strategy.”

In future studies, the researchers plan to analyze data from a larger, more uniform group of people who were diagnosed with melanoma that had spread to the brain.

The study’s other co-first author is Jenny Kienzler, who was a UCLA fellow in neurosurgery when the research was conducted. Other UCLA authors are Jeremy Reynoso, Alexander Lee, Eileen Shiuan, Shanpeng Li, Jiyoon Kim, Lizhong Ding, Amber Monteleone, Geoffrey Owens, Dr. Richard Everson, David Nathanson, Dr. Timothy Cloughesy, Gang Li, Dr. Linda Liau and Willy Hugo.

The research was supported by grants from the National Institutes of Health Specialized Programs of Research Excellence in Brain Cancer, National Cancer Institute, National Institutes of Health National Center for Advancing Translational Science, Parker Institute for Cancer Immunotherapy, Brain Tumor Funder’s Collaborative and Cancer Research Institute.

Mutation rate is a key parameter in genetics and genomics, where it is used to determine rates of evolution and adaptation. It is also used to derive the number of whales in the oceans before they were decimated by large-scale commercial whaling. However, estimating the rate at which new mutations appear in whales, or in any wild species, is difficult.

Pedigree method

For a long time, the phylogenetic method was used to measure mutation rates. This method uses fossil data from different species to estimate when they diverged. Subsequently, DNA from those species is compared to infer how many mutations must have occurred since the divergence. ‘However, the fossil record is not that exact. And some mutations may have disappeared over time,’ says Per Palsbøll, Professor of Marine Evolution and Conservation at the University of Groningen. He has studied whales since the late 1980s and is a corresponding author of the Science paper.

A more recent approach is the pedigree method, which uses the genomes of a pair of parents and their offspring to identify new mutations in the offspring. This more direct method relies on very few assumptions and is ideal for comparing mutation rates among different species, such as whales and humans.

Especially in wild species, the challenge is to obtain tissue samples from both parents and their offspring. First author Marcos Suárez-Menéndez: ‘The method has only been used on a handful of animals that are living in the wild, such as a single wolf pair and their cubs. It has also been used to estimate mutation rates in zoo animals, although it is uncertain if this reflects the mutation rates in the wild where the conditions are very different.’ However, the team, comprising scientists from the Netherlands, USA, Greenland, Denmark, Canada, and the UK, were able to use skin biopsy samples collected from whales during a collaboration that has been ongoing for more than thirty years.

Crossbow

Palsbøll collected his first whale biopsy samples amongst icebergs in the waters off West Greenland in 1988. ‘To do this, we had to sail very close to a whale and then fire a dart with a hollow point using a crossbow.’ The dart punches out a sample and bounces back into the water from where it is collected.

Finding both parents of a whale calf is the first step in measuring the mutation rate using the pedigree method. This is where large-scale DNA analyses come in. Suárez-Menéndez analyzed data that were generated by the other first author, Martine Bérubé, from microsatellite markers in DNA. This DNA was extracted from a large archive of whale biopsy samples and used to create a genetic fingerprint of individuals. ‘I sifted through the microsatellite data to find individuals that were related as mother and calf. Next, I looked for possible fathers in the database.’

In this way, he managed to identify 212 putative parent and offspring trios in four different whale species. The DNA of eight trios was then sent off for genome sequencing. After a final paternity check, Suárez-Menéndez and his colleagues estimated the number of new mutations in the calf and the average mutation rate in whales.

Industrial whaling

The results showed that the mutation rates in whales are similar to the rates seen in pedigrees in smaller mammals such as humans, apes, and dolphins. In contrast, earlier estimates in whales using the phylogenetic method were much lower compared to these smaller mammals. Suárez-Menéndez: ‘And just like in humans, most new mutations originate from the father. So, whales are very similar to us in this respect.’

The team also used a slightly different maternal pedigree method to estimate the mutation rates in DNA from mitochondria, the cell’s power plants. This method has so far only been used in penguins. Mitochondria and their DNA are passed on through the maternal line and Suárez-Menéndez took advantage of four decades of sighting data of humpback cow and calf pairs in the Gulf of Maine, directed by senior author Jooke Robbins at the Center for Coastal Studies. ‘Our study revealed that the mutation rate in whale mitochondrial DNA is also much higher than earlier estimates based on the phylogenetic method,’ explains Suárez-Menéndez.

The newly determined, higher mutation rates were used to infer that the number of whales in the North Atlantic before industrial whaling. The result was 86 percent lower than earlier reported estimates based on phylogenetic mutation rates. ‘Our new mutation rates suggested that some 20,000 humpback whales lived in the North Atlantic before commercial whaling, in contrast to the previous estimate of 150,000,’ says Palsbøll. This is important information, not only for the conservation of whales but also for our understanding of the state of the oceans before whaling. Palsbøll: ‘Another conclusion of wide-ranging consequences is that our study shows that it is entirely feasible to estimate the mutation rate in wild animals.’

Cancer

The human-like mutation rates in whales also led the authors to reject one possible cause of Peto’s paradox. This is the observation that, at the species level, the incidence of cancer does not appear to correlate with the number of cells in an organism. Whales have a hundred to a thousand times more cells than, for example, humans, so if they have the same cancer rate as humans, they should get cancer very early in life. Several mechanisms have been proposed for protecting these large sea mammals against cancer. One of those is a slower mutation rate as a consequence of whales having much lower metabolic rates. The discovery that this is not the case, implies that other mechanisms are probably at play in whales, such as an increase in the number of copies of the p53 gene which protects against cancer.

Finally, as the study relied on a large number of tissue samples that have been collected over several decades, the Science paper highlights the importance of long-term ecological research projects. Palsbøll: ‘It is difficult to acquire sustained funding for these kinds of long-term ecological studies. However, we wouldn’t have been able to do this research without the sustained commitment and dedication of the many colleagues who recorded all the sightings and collected the samples that our study relied on.’

In the study, published today in Science Translational Medicine, the researchers used engineered CAR T cells to target CD45 — a surface marker found on nearly all blood cells, including nearly all blood cancer cells. Because CD45 is found on healthy blood cells too, the research team used CRISPR base-editing to develop a method called “epitope editing” to overcome the challenges of an anti-CD45 strategy, which would otherwise result in low blood counts, with potentially life-threating side effects. The early results represent a proof-of-concept for epitope editing, which involves changing a small piece of the target CD45 molecule just enough so that the CAR T cells don’t recognize it, but it can still function normally within the blood immune system.

“Up to this point, we haven’t had the tools to create a targeted cell therapy approach that could work across all different forms of blood and bone marrow cancers,” said senior corresponding author Saar Gill, MD, PhD, an associate professor of Hematology-Oncology. “We’re excited to create a new solution that could solve a major issue in immunotherapy, which is the inability to target surface markers that are found on both cancer cells and healthy cells.”

Each of the currently available cell-based immunotherapies for blood cancer is designed to work against a narrow range of malignancies based on their target antigens. For example, the first CAR T cell therapy, developed at Penn by Carl June, MD, the Richard W. Vague Professor in Immunotherapy, targets the CD19 protein marker on B cells, to treat B-cell lymphomas and leukemias. Four of the six CAR T cell therapies currently approved to treat blood cancers target CD19. The other two target the BCMA protein marker to treat multiple myeloma. While CAR T cell therapy has been remarkably successful, researchers at Penn and across the world are working to make it even more effective for more patients.

“One drawback of the current approach to CAR T cell therapy is that each therapy must be developed individually based on the targets for that cancer type,” said June, co-senior author of the study, who also directs the Center for Cellular Immunotherapies at Penn. “This study lays the groundwork for a more universal approach that could potentially expand CAR T cell therapy to all blood cancers.”

Because CD45 is found on nearly all blood cells — and is usually highly expressed on blood cancer cells — a treatment that wipes out all CD45-bearing cells would leave patients without any blood cells, including red blood cells, platelets, plasma, and even the marrow-based stem cells that generate new blood cells. Furthermore, since T cells are blood cells and normally express CD45, CAR T cells targeting CD45 effectively would kill each other before they could be infused into patients.

The team built on previous work to overcome this challenge, using CRISPR base-editing to develop a new strategy called epitope editing. This involves the genetic modification of both the CAR T cells and blood stem cells to alter a small piece of the CD45 structure or “epitope” where the CAR T cells bind to the CD45 molecule. The altered version of CD45 still works but differs enough from normal CD45 that the anti-CD45 CAR T cells do not recognize and attack it.

“It’s essentially a blood stem cell transplant paired with CAR T cell therapy,” said lead author Nils Wellhausen, a graduate student in Pharmacology and a member of Gill and June’s labs. “The idea is that when the engineered cells are infused, the CAR T cells kill the cancer cells that bear normal CD45, but don’t kill each other or the newly engineered blood stem cells. This allows the engineered blood stem cells to begin making new blood cells.”

Because the strategy results in replacing the stem cells that create new blood cells, it also has potential use as a milder form of chemotherapy conditioning, which is given to patients before a bone marrow transplant to suppress the immune system.

The researchers tested the strategy in an extensive set of experiments in cell culture and mice models. They showed that the new approach not only keeps anti-CD45 CAR T cells from attacking each other or stem cells, but also enables swift destruction of blood cell cancers. In one test, the anti-CD45 CAR T cells eliminated leukemia cells within three weeks of infusion and were still present and capable of killing leukemia cells more than two months later.

Further toxicology studies and additional modeling studies are currently underway in preparation for an investigational new drug application before it can move into Phase I clinical trials.

Funding for the study was provided by the National Institutes of Health (P01CA214278-05, U54-CA-244711 25, P01CA214278-05, R01 CA177684 06A1, U54 CA 244711) and the Parker Institute for Cancer Immunotherapy.

However, interdevice synchronization remains a persistent problem in cloud gaming and the broader field of networking. In cloud gaming, video, audio, and haptic feedback are streamed from one central source to multiple devices, such as a player’s screen and controller, which typically operate on separate networks. These networks aren’t synchronized, leading to a lag between these two separate streams. A player might see something happen on the screen and then hear it on their controller a half second later.

Inspired by this problem, scientists from MIT and Microsoft Research took a unique approach to synchronizing streams transmitted to two devices. Their system, called Ekho, adds inaudible white noise sequences to the game audio streamed from the cloud server. Then it listens for those sequences in the audio recorded by the player’s controller.

Ekho uses the mismatch between these noise sequences to continuously measure and compensate for the interstream delay.

In real cloud gaming sessions, the researchers showed that Ekho is highly reliable. The system can keep streams synchronized to within less than 10 milliseconds of each other, most of the time. Other synchronization methods resulted in consistent delays of more than 50 milliseconds.

And while Ekho was designed for cloud gaming, this technique could be used more broadly to synchronize media streams traveling to different devices, such as in training situations that utilize multiple augmented or virtual reality headsets.

“Sometimes, all it takes for a good solution to come out is to think outside what has been defined for you. The entire community has been fixed on how to solve this problem by synchronizing through the network. Synchronizing two streams by listening to the audio in the room sounded crazy, but it turned out to be a very good solution,” says Pouya Hamadanian, an electrical engineering and computer science (EECS) graduate student and lead author of a paper describing Ekho.

Hamadanian is joined on the paper by Doug Gallatin, a software developer at Microsoft; Mohammad Alizadeh, an associate professor of electrical engineering and computer science and a member of the Computer Science and Artificial Intelligence Laboratory (CSAIL); and senior author Krishna Chintalapudi, a principal researcher at Microsoft Research. The paper will be presented at the ACM SIGCOMM conference.

Off the clock

At the heart of interstream delay in cloud gaming is a fundamental problem in networking known as clock synchronization.

“If the controller and the screen could look at their watches and at the same time see the same thing, then we could synchronize everything to the clock. But a lot of theoretical work on clock synchronization shows that there are certain bounds you can never overcome,” Hamadanian says.

Many approaches attempt clock synchronization by ping-pong messaging, where a device sends a ping message to the server, which sends a pong message back. The device counts how long it takes the message to return, and cuts that value in half to calculate the network delay.

But the path over the network is likely asymmetric, so it may take more time for the message to reach the server than it does for the return message. Therefore, this method is unreliable and can introduce hundreds of milliseconds of error. Humans can typically perceive interstream delay once it reaches 10 milliseconds.

“So if something happens on the screen, we want it to happen within 10 milliseconds on the controller, as well,” Hamadanian explains.

He and his collaborators decided to try listening to game audio to synchronize these separate streams.

In cloud gaming, the microphone on the player’s controller records audio in the room, including game audio played by the speakers on the screen, which it sends back to the server. But using this for synchronization is unreliable because the room audio contains background noise.

So they designed Ekho to add identical sequences of extremely low-volume white noise, known as pseudo noise, to the game audio before it is streamed to the player’s screen. It uses these pseudo-noise segments for synchronization.

Before building Ekho, the researchers conducted a user study to prove that players could not hear the pseudo noise in the game audio. These noise sequences are also resilient to compression, which is important because audio sent from the controller is highly compressed to speed the data transfer.

Pseudo noise, real success

The Ekho-Estimator module adds pseudo-noise sequences to the game audio. When it receives the recorded game audio from the controller, it listens for those markers and tries to line up the streams. This enables it to precisely calculate the inter-stream delay.

The Ekho-Estimator sends that information to the Ekho-Compensator module, which either skips a few milliseconds of sound or adds a few milliseconds of silence to the game audio being sent by the server, which synchronizes the streams.

They tested Ekho on real cloud streaming sessions and found that it was superior to other synchronization methods, even when the microphone quality was poor or background noise was picked up by the recording.

Ekho limited interstream delay to less than 10 milliseconds for nearly 87 percent of the time during streams. No other method the team tested was able to cut that delay to less than 50 milliseconds.

“The traditional way of doing this, which involves trying to measure the synchronization error using the underlying network, the errors are significantly larger. When we started this project, were weren’t sure whether this could even be done. But the accuracy we can get down to with Ekho, at sub-millisecond levels, it is unheard of,” says Chintalapudi.

Impressed by these results, the researchers want to see how well Ekho performs in more complex situations, such as synchronizing five controllers to the same screen device. Also, since Ekho was targeted for cloud gaming, it has range limitations. Future work could seek to enhance Ekho so it can synchronize devices at either end of a very large room, like a concert hall.

“Using inaudible white noise as a sort of ‘timekeeper’ is a great example of how out-of-the-box thinking can produce unexpected results,” says Alizadeh. “The technique could improve user experience, not just in cloud gaming but potentially in any multidevice streaming scenario.”