Graduate students Ali Kiaghadi and S. Zohreh Homayounfar, with their professors Trisha L. Andrew, a materials chemist, and computer scientist Deepak Ganesan, will introduce their health-monitoring sleepwear at the Ubicomp 2019 conference this week in London, U.K. A paper detailing the work has been chosen for publication in the Proceedings of the ACM on Interactive, Mobile, Wearable and Ubiquitous Technologies (IMWUT).

As Andrew explains, “The challenge we faced was how to obtain useful signals without changing the aesthetics or feel of the textile. Generally, people assume that smart textiles refer to tightly worn clothing that has various sensors embedded in it for measuring physiological and physical signals, but this is clearly not a solution for everyday clothing and, in particular, sleepwear.”

Ganesan adds, “Our insight was that even though sleepwear is worn loosely, there are several parts of such a textile that are pressed against the body due to our posture and contact with external surfaces. This includes pressure exerted by the torso against a chair or bed, pressure when the arm rests on the side of the body while sleeping, and light pressure from a blanket over the sleepwear.”

“Such pressured regions of the textile are potential locations where we can measure ballistic movements caused by heartbeats and breathing,” he explains, “and these can be used to extract physiological variables.” The difficulty is that these signals can be individually unreliable, particularly in loose-fitting clothing, but signals from many sensors placed across different parts of the body can be intelligently combined to get a more accurate composite reading.

Andrew, Ganesan and colleagues explain that their team had to come up with several new ideas to make their vision a reality. They realized that there is no existing fabric-based method to sense continuous and dynamic changes in pressure, particularly given the small signals that they needed to measure. So they designed a new fabric-based pressure sensor and combined that with a triboelectric sensor — one activated by a change in physical contact — to develop a distributed sensor suite that could be integrated into loose-fitting clothing like pajamas. They also developed data analytics to fuse signals from many points that took into account the quality of the signal coming in from each location.

The authors report that this combination allowed them to detect physiological signals across many different postures. They performed multiple user studies in both controlled and natural settings and showed that they can extract heartbeat peaks with high accuracy, breathing rate with less than one beat per minute error, and perfectly predict sleep posture.

“We expect that these advances can be particularly useful for monitoring elderly patients, many of whom suffer from sleep disorders,” says Andrew. “Current generation wearables, like smartwatches, are not ideal for this population since elderly individuals often forget to consistently wear or are resistant to wearing additional devices, while sleepwear is already a normal part of their daily life. More than that, your watch can’t tell you which position you sleep in, and whether your sleep posture is affecting your sleep quality; our Phyjama can.”

This work was enhanced by Ganesan and Andrew’s affiliation with UMass Amherst’s Institute of Applied Life Sciences (IALS), which focuses on translating life science research into products that improve human health. Director Peter Reinhart at IALS says, “It’s exciting to see the next generation of wearable technology that is zero effort and addresses the issue of comfort and unobtrusiveness head-on. The data generated by fabric-based sensors have the potential to improve health and well-being, and could possibly contribute to the early diagnosis of multiple disorders.”

The new comet, C/2019 Q4, is still inbound toward the Sun, but it will remain farther than the orbit of Mars and will approach no closer to Earth than about 190 million miles (300 million kilometers).

After the initial detections of the comet, Scout system, which is located at NASA’s Jet Propulsion Laboratory in Pasadena, California, automatically flagged the object as possibly being interstellar. Davide Farnocchia of NASA’s Center for Near-Earth Object Studies at JPL worked with astronomers and the European Space Agency’s Near-Earth Object Coordination Center in Frascati, Italy, to obtain additional observations. He then worked with the NASA-sponsored Minor Planet Center in Cambridge, Massachusetts, to estimate the comet’s precise trajectory and determine whether it originated within our solar system or came from elsewhere in the galaxy.

The comet is currently 260 million miles (420 million kilometers) from the Sun and will reach its closest point, or perihelion, on Dec. 8, 2019, at a distance of about 190 million miles (300 million kilometers).

“The comet’s current velocity is high, about 93,000 mph [150,000 kph], which is well above the typical velocities of objects orbiting the Sun at that distance,” said Farnocchia. “The high velocity indicates not only that the object likely originated from outside our solar system, but also that it will leave and head back to interstellar space.”

Currently on an inbound trajectory, comet C/2019 Q4 is heading toward the inner solar system and will enter it on Oct. 26 from above at roughly a 40-degree angle relative to the ecliptic plane. That’s the plane in which the Earth and planets orbit the Sun.

C/2019 Q4 was established as being cometary due to its fuzzy appearance, which indicates that the object has a central icy body that is producing a surrounding cloud of dust and particles as it approaches the Sun and heats up. Its location in the sky (as seen from Earth) places it near the Sun — an area of sky not usually scanned by the large ground-based asteroid surveys or NASA’s asteroid-hunting NEOWISE spacecraft.

C/2019 Q4 can be seen with professional telescopes for months to come. “The object will peak in brightness in mid-December and continue to be observable with moderate-size telescopes until April 2020,” said Farnocchia. “After that, it will only be observable with larger professional telescopes through October 2020.”

Observations completed by Karen Meech and her team at the University of Hawaii indicate the comet nucleus is somewhere between 1.2 and 10 miles (2 and 16 kilometers) in diameter. Astronomers will continue collect observations to further characterize the comet’s physical properties (size, rotation, etc.) and also continue to better identify its trajectory.

The Minor Planet Center is hosted by the Harvard-Smithsonian Center for Astrophysics and is a sub-node of NASA’s Planetary Data System Small Bodies Node at the University of Maryland. JPL hosts the Center for Near-Earth Object Studies. All are projects of NASA’s Near-Earth Object Observations Program and elements of the agency’s Planetary Defense Coordination Office within NASA’s Science Mission Directorate.

More information about asteroids and near-Earth objects can be found at:

https://cneos.jpl.nasa.gov

https://www.jpl.nasa.gov/asteroidwatch

For more information about NASA’s Planetary Defense Coordination Office, visit:

https://www.nasa.gov/planetarydefense

For asteroid and comet news and updates, follow AsteroidWatch on Twitter:

twitter.com/AsteroidWatch

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Those questions led PhD candidate Golnaz Morad, DDS, and her mentor Marsha Moses, PhD, to conduct an in-depth investigation of exosomes, also known as extracellular vesicles or EVs, and their role in breast-to-brain metastasis. Their surprising findings appear in the journal ACS Nano.

“Golnaz was able to identify the mechanism by which EVs pass through the blood brain barrier and provide a ‘niche’ so that breast cancer cells can metastasize to brain,” says Moses, who directs the Vascular Biology Program at Boston Children’s Hospital and whose lab is interested in women’s cancers.

Now that they know the mechanism, Moses and Morad hope to identify therapeutic targets that could stop brain metastases from happening.

EVs and cancer

Simply put, EVs are tiny bubbles released by cells, encapsulating chemical messages they wish to convey. In the case of cancer cells, EVs carry factors that help create a more hospitable environment for both the primary tumor and its metastases, as Moses and Morad detailed recently in a review article. Primary tumors can secrete EVs into the circulation, allowing them to travel to distant organs and help spread the cancer.

“The main question we had was, how can EVs reach the brain in the first place?” says Morad. “The blood brain barrier doesn’t allow anything larger than 400 daltons to passively get into brain tissue. Exosomes are more than two thousand times larger than the size cutoff limit.”

Hijacking transcytosis

The blood brain barrier (BBB) is a complex structure made up of three kinds of cells. EVs traveling in the blood first encounter tightly joined brain endothelial cells. Pericytes comprise the next layer, followed by astrocytes (the “feet,” which connect to the cell bodies). Crosstalk between the cells circles the wagons even tighter: Astrocytes and pericytes send cues to the endothelial cells to tighten up the junctions.

Morad, Moses, and colleagues worked with several models of the BBB, including in vitro microfluidic models of the BBB (“BBB on a chip”), as well as static in vitro models and live zebrafish and mouse models. The labs of Donald Ingber, MD, PhD, and Leonard Zon, MD, collaborated in the development of the BBB-on-a-chip and zebrafish models, respectively. The Moses Lab also collaborated with the lab of Christopher Carman, PhD, of Harvard’s T.H. Chan School of Public Health for the high-resolution imaging conducted in this study.

Each model and technique provided its own insights. Bottom line, Morad and Moses showed, for the first time, that rather than squeezing in between the cells in the BBB to get into the brain, the EVs trick the endothelial cells into taking them up. Using a standard biological pathway called transcytosis, the cells simply engulfed the EVs, bringing them inside and releasing them into brain tissue like so many Trojan horses.

“EVs can also manipulate endothelial cells to facilitate their own transport across the BBB,” says Morad. “They hijack the pathways involved in the uptake and sorting of molecules and change regulation of the pathways.”

Ongoing work in the Moses Lab shows that once the EVs have breached the barrier, they trick astrocytes into sending signals to the surrounding environment, making it more receptive to tumor growth. An inventory of these signals, using mass spectrometry and other techniques, identified some that are known to degrade the network of proteins providing structural and biochemical support to brain cells.

EVs as anticancer delivery vehicles?

For the study, Morad had to develop special methods to harvest the EVs in quantity and to verify their identity.

“They are remarkable little vehicles, but it is very challenging to get enough of them,” says Moses.

Having discovered what EVs do to help breast cancer metastasize to the brain, the Moses Lab hopes to turn the tables — and use EVs (or synthetic versions) to deliver anticancer drugs that home to the metastatic site. That work is ongoing.

The work, for which the investigators have filed patents, was supported by the Breast Cancer Research Foundation, the National Institutes of Health (R01 CA185530, K01 DK111790), and the Advanced Medical Foundation. 

In western lowland gorillas, groups consist of several females and only one adult male, the silverback. With his impressive body size, he protects his group against predators and other adult males. Females rely on this protection and never travel alone, however they may change groups multiple times during their lives. “Female gorillas seem to have different strategies when it comes to reproduction and transfer,” says Marie Manguette, first author of the study. “We have observed females transferring to another group after every weaned offspring and therefore up to six times in their lives, while others have stayed and bred with the same male for 20 years.”

Manguette and her colleagues found that a high percentage of infants die if they are born when the male is old and has reached the end of his reproductive years. “When a silverback dies, all females leave to join a new male,” says Manguette. “If at that point a female has a suckling infant, the new silverback will most likely kill it to breed with the female right away and raise his own offspring.” Female lowland gorillas can prevent this from happening by transferring to a new group right after her offspring stops suckling, leaving the infant behind with its father.

Yet when females leave to join another male, they have longer intervals between births and hence fewer births over their lifetime. These delays can be substantial: females that transferred four times during their life took approximately ten years longer to produce a surviving offspring compared to females that never transferred. “Given the high costs of transfer, a female finds herself in a dilemma when she is with an older male: does she stay, breed with him again and risk losing the infant if he dies, or does she leave and suffer the reproductive costs,” says Manguette.

The study shows that females suffer the highest cost if they lose an offspring. “Therefore females should leave a male if they fear he is weak and will not survive long enough for her to carry and wean a new infant.” Yet how do females know when to leave? “Many females leave a male long before he dies, suggesting that they may be able to determine when he is getting weaker, potentially using the outcome of aggressive displays between males when they meet as a hint,” says Manguette. “Whether females really leave an old male to transfer to a younger and stronger male still remains to be determined, but our results suggest that they should.”

The authors further emphasize the importance of long-term studies for the understanding of slow reproducing species such as gorillas. The information they provide on the live and behavior of gorillas is desperately needed to improve conservation efforts for this threatened species. “We need to do whatever it takes to protect these endangered animals in their natural habitat before it is too late,” say the authors.

“This study of a long-term data set from wild gorillas contributes to our understanding of the costs and benefits of social living. Male and females form long term social bonds and can live together for long periods of time. This study sheds light on the mechanisms driving the grouping patterns in gorillas and the dynamic nature of their social groups, which in turn, contributes to our understanding of human sociality,” says Martha Robbins, senior author of the study.

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Materials provided by Max Planck Institute for Evolutionary Anthropology. Note: Content may be edited for style and length.

The decision to use the drug, sorafenib, was made after pathologists identified a unique mutation in the form of two genes being fused together instead of on separate chromosomes — according to a case study publishing in the journal Leukemia on Sept. 11, 2019.

The patient, now a thriving toddler, personifies a growing shift in cancer treatment: the genes fueling the cancer, rather than the type of cancer itself, may determine optimal therapy, say researchers, led by senior author Elliot Stieglitz, MD, a physician scientist in the UCSF Division of Pediatric Hematology/Oncology and the Helen Diller Family Comprehensive Cancer Center.

The authors report that the infant presented with the hallmarks of leukemia, including enlargement of the liver and spleen, and elevated white blood cell counts.

The child was believed to have JMML, or juvenile myelomonocytic leukemia, an aggressive type of blood cancer most commonly affecting infants and toddlers, and occurring in about 1.2 children per million, per year. JMML is treated with a stem cell transplant, in which intense chemotherapy is given to wipe out JMML cells, followed by a transplant of donated stem cells from a closely matched donor into the recipient’s bone marrow, where they produce healthy blood cells. However, up to 50 percent of JMML patients relapse after transplantation.

Live-Saving Treatment Stalled When Infant’s Condition Declined

Chemotherapy was initiated in an attempt to reduce the disease burden before stem cell transplant, said Stieglitz. “Unfortunately, the patient did not respond to chemotherapy and his symptoms worsened. The stem cell transplant was no longer an option.”

Facing shrinking options, Stieglitz’s team conducted molecular profiling of the child’s cancer cells, in the hope that mutations could be identified and matched with targeted therapies. They used both UCSF 500, a cancer gene panel that sequences DNA from a patient’s cancer cells and compares them to normal tissue, and a second tool that analyzes RNA, which offers a more sensitive measurement of gene expression and may identify novel features, including fusion genes. None of the mutations associated with JMML were found. However, the pathologists were surprised to discover a mutation known as an FLT3 fusion — something that had never before been reported in a pediatric malignancy, the authors said.

“We know that fusions are more likely to respond to targeted therapies than other types of mutations,” said Mignon Loh, MD, a co-author and Chair in Pediatric Molecular Oncology, who was involved in the patient’s care. “Sorafenib, which was developed at UCSF, is a type of targeted therapy known as a kinase inhibitor that works by blocking the action of an abnormal protein that signals cancer cells to multiply.”

After two weeks on sorafenib, the patient’s white blood cell counts plummeted to within the normal range. After 10 weeks’ treatment, the infant was well enough to undergo a stem cell transplant. Sorafenib was stopped after nearly two years. The patient remains in remission months later.

“The patient’s history reveals that the one-size-fits-all treatment approach does not work well for all children with JMML,” said Stieglitz. “The course of JMML is highly variable. In rare cases, children spontaneously go into remission with minimal treatment, while half of all patients suffer from a highly aggressive form of the disease that fails to respond to stem cell transplant.”

Most JMML patients present with genes that hyperactivate the Ras pathway, said Stieglitz, referring to a chain of proteins within the cell that communicates a signal from a receptor to the DNA in the nucleus.

“Recently there have been reports of JMML patients who have lacked these Ras mutations, but have fusions like our patient,” he said. “We recommend that all patients without Ras mutations undergo RNA sequencing to identify any fusions that might be treated with targeted therapies.”

Funding: The study was supported by funding from the National Cancer Institute, National Heart, Lung and Blood Institute, Alex’s Lemonade Stand Center of Excellence program, Frank A. Campini Foundation and the Damon Runyon-Richard Lumsden Foundation.

DSmith received research funding from FujiFilm and Astellas Pharma; Chao received an honorarium from Bio-Rad.