Monday, March 18, 2024

Primatologist Frans de Waal remembered for bringing apes 'a little closer to humans'

Frans de Waal shown overlooking the chimpanzee habitat at the Emory National Primate Research Center.

By Carol Clark

Emory University primatologist Frans de Waal — who pioneered studies of animal cognition while also writing best-selling books that helped popularize the field around the globe — passed away March 14, 2024, from stomach cancer. 

De Waal, Charles Howard Candler Professor Emeritus of Psychology and former director of the Living Links Center for the Advanced Study of Ape and Human Evolution at the Emory National Primate Research Center, was 75. From his groundbreaking 1982 book “Chimpanzee Politics: Power and Sex Among Apes” to 2019’s “Mama’s Last Hug: Animal Emotions and What They Tell Us About Ourselves,” de Waal shattered long-held ideas about what it means to be an animal and a human. 

“One thing that I’ve seen often in my career is claims of human uniqueness that fall away and are never heard from again,” de Waal said in 2014. “We always end up overestimating the complexity of what we do. That’s how you can sum up my career: I’ve brought apes a little closer to humans but I’ve also brought humans down a bit.” 

 Read the full story here by clicking here.

Wednesday, March 6, 2024

Atlanta Science Festival returns to inspire discovery for all ages

A middle-school student experiences an Emory chemistry lab during a recent community outreach event. 

The Atlanta Science Festival returns March 9 to 23, inviting curious kids and adults to explore all things science, technology, engineering and mathematics (STEM). Experts in these fields — including many members of the Emory community — will serve as educational guides for more than 150 interactive events. 

“The Atlanta Science Festival aims to bring the community together through their shared love of science,” says Meisa Salaita, co-founder and co-executive director of Science ATL, the engineers of the festival. “Through these events, we hope to inspire and empower the next generation to pursue their dreams.” 

Participants can take a crash course on the basics of AI, create an herbarium of medicinal plants, go into the field with researchers studying microplastic pollution in a stream, take a behind-the-scenes tour of the latest advances in healthcare technology and even get a taste of the physics of cheese making. 

Now in its 11th year, the Atlanta Science Festival was co-founded by Emory, Georgia Tech and the Metro Atlanta Chamber. 

“We have grown into a mainstay of Atlanta,” says Salaita, noting that many of the events fill up quickly. “The festival is something that people look forward to every spring.” 

Friday, January 26, 2024

Spatial model predicts bumblebee exposure to pesticide use

Field experiments were conducted using yellow-faced bumblebees, a species native to the West Coast and an important pollinator.

By Carol Clark

It has long been known that agricultural pesticides are one of the greatest threats to bees and other essential pollinators. What farmers have lacked is an understanding of how different pesticides, applied at various times on a variety of crops, affect the risk of exposure to bees living near the fields. 

Researchers have drawn from real-world data to try to address this gap, developing and testing a spatial model for predicting pesticide exposure in bumblebees. The journal Science of the Total Environment published the work, based on the interactions of the yellow-faced bumblebee (Bombus vosnesenskii) with crops in California. 

“We were able to explain nearly 75% of the spatial variation in pesticide exposure among the bumblebee hives using our model,” says Eric Lonsdorf, first author of the study and assistant professor in Emory’s Department of Environmental Sciences. 

Relatively simple models were more effective at preventing exposures than the researchers expected.

“Our results suggest that simply data on where and when a pesticide was sprayed is all that you need to make a good prediction for the threat to nearby hives,” Lonsdorf says. 

Including data on how long a particular chemical lingers in the landscape or how attractive the flowers in a particular crop are to the bees did not make a significant difference in the model’s predictive power. 

“We found that even if a crop is not that attractive to the bees, the chemicals from that crop are still going to be found in their pollen,” Lonsdorf says. “The bees may be picking up the chemical due to drift of the pesticide onto nearby weeds where they are foraging.” 

Providing tools for conservation 

Lonsdorf studies natural capital, or nature’s contributions to humans. He translates ecological principles and knowledge into predictive models that enable industry leaders and policymakers to better manage natural resources. 

He’s currently using models he developed to help the U.S. Fish and Wildlife Service identify bee conservation priority areas in the United States. 

More research is needed, Lonsdorf says, to determine whether the bumblebee risk-prediction model will scale up across different landscapes and for different species of bees. The current study also did not delve into how the amount of a particular pesticide found in the pollen translated into toxicity for the bees. 

Co-authors of the paper include Neal Williams from the University of California, Davis, and Maj Rundlöf and Charlie Nicholson, who are affiliated with the University of California, Davis, and Lund University in Sweden. 

Drawing from fine-scaled data 

The researchers began with experiments set amid a variety of crops in northern California’s Yolo County. Fourteen pairs of yellow-faced bumblebee colonies were placed around the agricultural landscape. This species of bumblebee is native to the West Coast and the most abundant wild species of bee in this range, found in both urban and agricultural areas. 

Pollen that bees in each hive collected were sampled at six different times during the growing season. The pollen samples were then assessed for exposure to 52 different active ingredients encompassing a range of pesticides. 

Data from these experiments were combined with field-level data from the California Department of Pesticide Regulation on what pesticides were sprayed and what days they were sprayed. 

“California is unique in providing such fine-scaled, public data,” Lonsdorf says. “In most places in the United States, information on what pesticides are being sprayed is only collected at the county level and summarized on an annual basis.” 

The detailed data allowed the researchers to consider a range of factors in their predictive model to identify those factors with the most predictive power. 

“Our risk-prediction model marks another step toward evaluating pollinator-conservation issues to help guide policies for pollinator landscapes,” Lonsdorf says. “The next step is to do a field-toxicity assessment to get a better understanding of how pesticides are affecting bee health.” 

He and colleagues are now conducting such a study with honeybees, he adds. 

The current paper was supported by the National Science Foundation, California Department of Food and Agriculture, Almond Board of California, KIND Foundation Fund for Pollinator Health and the Swedish Research Council.

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Wednesday, January 24, 2024

Computer scientists create simple method to speed cache sifting

"Computer performance fascinates me," says Emory graduate student Yazhuo Zhang, co-first author of the discovery, shown on a visit to Switzerland. Set to receive her PhD in May,Zhang accepted a post-doctroal fellowship at the Federal Institute of Technology Zurich (ETH Zurich).

By Carol Clark

Computer scientists have invented a highly effective, yet incredibly simple, algorithm to decide which items to toss from a web cache to make room for new ones. Known as SIEVE, the new open-source algorithm holds the potential to transform the management of web traffic on a large scale. 

SIEVE is a joint project of computer scientists at Emory University, Carnegie Mellon University and the Pelikan Foundation. The team’s paper on SIEVE will be presented at the 21st USENIX Symposium on Networked Systems Design and Implementation (NSDI) in Santa Clara, California, in April. 

A preprint of the paper is already making waves. SIEVE became a hot topic on Hacker News and the subject of a feature in the influential tech newsletter TLDR, driving tens of thousands of visits to the SIEVE website. 

“SIEVE is bigger and greater than just us,” says Yazhuo Zhang, an Emory PhD student and co-first author of the paper. “It is already performing well but we are getting a lot of good suggestions to make it even better. That’s the beauty of the open-source world.” 

Zhang shares first authorship of the paper with Juncheng (Jason) Yang, who received his master’s degree in computer science at Emory and is now a PhD candidate at Carnegie Mellon. 

“SIEVE is an easy improvement of a tried-and-true cache-eviction algorithm that’s been in use for decades — which is literally like centuries in the world of computing,” says Ymir Vigfusson, associate professor in Emory’s Department of Computer Science. 

Vigfusson is co-senior author of the paper, along with Rashmi Vinayak, an associate professor in Carnegie Mellon’s computer science department. Yao Yue, a computer engineer at the Pelikan Foundation, is also a co-author. 

In addition to its speed and effectiveness, a key factor sparking interest in SIEVE is its simplicity, lending it scalability. 

“Simplicity is the ultimate sophistication,” Vigfusson says. “The simpler the pieces are within a system designed to serve billions of people within a fraction of a second, the easier it is to efficiently implement and maintain that system.” 

Keeping ‘hot objects’ handy 

Many people understand the value of regularly reorganizing their clothing closet. Items that are never used can be tossed and those that are rarely used can be moved to the attic or some other remote location. That leaves the items most commonly worn within easy reach so they can be found quickly, without rummaging around. 

A cache is like a well-organized closet for computer data. The cache is filled with copies of the most popular objects requested by users, or “hot objects” in IT terminology. The cache maintains this small collection of hot objects separately from a computer network’s main database, which is like a vast warehouse filled with all the information that could be served by the system. 

Caching hot objects allows a networked system to run more efficiently, rapidly responding to requests from users. A web application can effectively handle more traffic by popping into a handy closet to grab most of the objects users want rather than traveling down to the warehouse and searching through a massive database for each request. 

“Caching is everywhere,” Zhang says. “It’s important to every company, big or small, that is using web applications. Every website needs a cache system.” 

And yet, caching is relatively understudied in the computer science field. 

A logo for SIEVE, designed by Zhang, portrays hotter objects in shades of red and colder objects in shades of blue. Zhang also designed a web site for SIEVE, including a motion graphic demonstrating how it works.

A sense of wonder 

Zhang, who received her undergraduate and master’s degrees at universities in her hometown of Guangzhou, China, started off majoring in software engineering. “It’s fun to code and to make a website,” she says, “but it’s not fundamentally challenging once you learn how to do it. I wanted to gain more understanding of the backbone of technology. Computer performance fascinates me.” 

Zhang applied to Emory to work with Vigfusson given his focus on fundamental topics such as computer security and caching, and his skill at talking about them in simple terms. “It’s important to make complex ideas easy to understand,” she says. 

In turn, Vigfusson appreciates how Zhang approaches intractable problems with a sense of wonder. “She’s doing science for all the right reasons,” he says. “She is delighted by the process of exploration and by traversing the frontiers of the unknown.” 

In 2016, Vigfusson received a National Science Foundation Faculty Early Career Development Program (CAREER) grant to explore cache systems. Yang took the lead on the project while he was an Emory master’s student. As a PhD student at Carnegie Mellon, Yang continued to collaborate with Vigfusson and helped to mentor Zhang when she arrived at Emory in 2019. 

How caching works 

While caching can be thought of as a well-organized closet for a computer, it is difficult to know what should go into that closet when millions of people, with constantly changing needs, are using it. 

The fast memory of the cache is expensive to run yet critical to a good experience for web users. The goal is to keep the most useful, future information within the cache. Other objects must be continuously winnowed out, or “evicted” in tech terminology, to make room for the changing array of hot objects.

Cache-eviction algorithms determine what objects to toss and when to do so. 

FIFO, or “first-in, first-out,” is a classic eviction algorithm developed in the 1960s. Imagine objects lined up on a conveyor belt. Newly requested objects enter on the left and the oldest objects get evicted when they reach the end of the line on the right. 

In the LRU, or “least recently used,” algorithm the objects also move along the line towards eviction at the end. However, if an object is requested again while it moves down the conveyor belt, it gets moved back to the head of the line. 

Hundreds of variations of eviction algorithms exist but they have tended to take on greater complexity to gain efficiency. That generally means they are opaque to reason about and require high maintenance, especially when dealing with massive workloads. 

“If an algorithm is very complicated, it tends to have more bugs, and all of those bugs need to be fixed,” Zhang explains. 

A simple idea 

Like LRU and some other algorithms, SIEVE makes a simple tweak on the basic FIFO scheme. 

SIEVE initially labels a requested object as a “zero.” If the object is requested again as it moves down the belt, its status changes to “one.” When an object labeled “one” makes it to the end of the line it is automatically reset to “zero” and evicted. 

A pointer, or “moving hand,” also scans the objects as they travel down the line. The pointer starts at the end of the line and then jumps to the head, moving in a continuous circle. Anytime the pointer hits an object labeled “zero,” the object is evicted. 

“It’s important to evict unpopular objects as quickly as possible, and SIEVE is very fast at this task,” Zhang says. 

In addition to this quick demotion of objects, SIEVE manages to maintain popular objects in the cache with minimal computational effort, known as “lazy promotion” in computer terminology. The researchers believe that SIEVE is the simplest cache-eviction algorithm to effectively achieve both quick demotion and lazy promotion. 

A lower miss ratio 

The purpose of caching is to achieve a low miss ratio — the fraction of requested objects that must be fetched from “the warehouse.” 

To evaluate SIEVE, the researchers conducted experiments on open-source web-cache traces from Meta, Wikimedia, X and four other large datasets. The results showed that SIEVE achieves a lower miss ratio than nine state-of-the-art algorithms on more than 45% of the traces. The next best algorithm has a lower miss ratio on only 15%. 

The ease and simplicity of SIEVE raise the question of why no one came up with the method before. The SIEVE team’s focus on how patterns of web traffic have changed in recent years may have made the difference, Zhang theorizes. 

“For example,” she says, “new items now become ‘hot’ quickly but also disappear quickly. People continuously lose interest in things because new things keep coming up.” 

Web-cache workloads tend to follow what are known as generalized Zipfian distributions, where a small subset of objects account for a large proportion of requests. SIEVE may have hit a Zipfian sweet spot for current workloads. 

“It is clearly a transformative moment for our understanding of web-cache eviction,” Vigfusson says. “It changes a construct that’s been used blindly for so long.” 

Marquee companies that manage massive amounts of web traffic are making inquiries, he notes, adding, “Even a tiny improvement in a web-caching system can save millions of dollars at a major data center.”

Zhang and Yang are on track to receive their PhDs in May. 

“They are doing incredible work,” Vigfusson says. “It’s safe to say that both of them are now among the world experts on web-cache eviction.”

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Tuesday, December 12, 2023

New tool to analyze blood platelets holds major medical potential

Graphic image shows a blood clot forming in an artery. The white, spikey platelets are amid red and white blood cells. Activated platelets use their spkes like "arms" to grip onto one another and to stringy chains of proteins in the blood called fibrin, forming clumps that also bind up red and white blood cells.

By Carol Clark

A novel technique to test platelet function within a person’s blood sample is faster, easier and more precise than methods currently in use, an experimental study shows. 

Nature Biomedical Engineering published the research, led by scientists at Emory University. The researchers demonstrated the proof-of-concept for the technique, which provides the first detailed look at the molecular forces generated by activated platelets in patient blood samples. 

The study results show that the technology holds the potential to assess the effects of antiplatelet drugs on individuals and to gain a clearer picture of bleeding risks for patients undergoing cardiopulmonary bypass surgery. 

The technique requires only about a drop of blood to run tests, compared to the tablespoon needed for current assays. This ultrasensitivity may make the technology a valuable tool for the diagnosis of babies suffering from rare, congenital platelet disorders. 

The breakthrough is based on synthetic-DNA tension probes developed more than a decade ago in the laboratory of Khalid Salaita, professor in Emory’s Department of Chemistry and in the Wallace H. Coulter Department of Biomedical Engineering at Emory and Georgia Tech. 

‘A scientist’s dream’ 

The tension probes can detect cellular forces on the magnitude of just a few piconewtons, or about a billion times less than the weight of a paper clip. The researchers found a way to amplify the signal of the probes by tapping the power of an enzyme known as CRISPR-associated 12a. The mechanical signal is then detected using a plate-reader, a tool already routinely used in clinical testing. 

“This project started out of basic curiosity,” says Salaita, co-corresponding author. “We wanted to know whether we could measure the tiniest forces exerted by cells. It’s exciting that we are now building on this basic curiosity to develop diagnostic tools to help patients. It’s a scientist’s dream.” 

First author of the paper is Yuxin Duan, an American Heart Association postdoctoral fellow in the Salaita lab. 

Roman Sniecinski, a professor in Emory School of Medicine’s Department of Anesthesiology and a leading expert in the field of perioperative coagulation, is co-corresponding author of the paper.

“Platelet function in general is important and yet the current tools that we have to measure it are relatively primitive,” Sniecinski says. “This new technique offers an easier, faster and cheaper way to measure platelet function, while also providing us with key information that we didn’t have before.” 

Co-authors include: Fania Szlam, a senior associate in the Sniecinski lab; Yuesong Hu, a graduate student in the Salaita lab; Renhao Li, a professor in Emory School of Medicine’s Department of Pediatrics, Hematology/Oncology; Wenchun Chen, a postdoctoral fellow in Emory School of Medicine; and Yonggang Ke, an associate professor in the Coulter Department of Biomedical Engineering at Emory and Georgia Tech. 

The importance of platelets 

Platelets are colorless, disc-shaped blood-cell fragments whose job is to bind at the site of an injured blood vessel to stop the bleeding. In some cases, however, platelets may not function optimally. When platelets are weak, or less active than optimal, the blood may not clot properly leading to uncontrolled bleeding. But if platelets are “hyperactive” they may become too sticky and cause spontaneous blood clots that can lead to heart attack or stroke. 

Regulating platelet function is especially critical to people at higher risk for some conditions. Antiplatelet drugs, such as clopidogrel, ticagrelor and even aspirin, are among the most commonly prescribed medications in the United States. In some patients, however, these drugs may not work well and adjustments in doses or changing to another drug might better help prevent heart attacks. 

During cardiac surgery, platelet function becomes even more dysregulated. The operating-room team must perform a balancing act of making blood not clot during cardiopulmonary bypass, then using procoagulant interventions, including transfusions of platelets, to stop the bleeding when the surgical procedure is finished. This can be difficult because the use of the cardiopulmonary bypass machine can stress and weaken blood platelets. 

“For decades, people have written in the scientific literature about this problem of platelet dysfunction during cardiac surgery,” Sniecinski says, “but it’s really difficult to measure it with the tools that we’ve been using. And since we haven’t been able to measure platelet function well, that’s made it difficult to study it in effective ways.” 

‘A small part of the picture’ 

Aggregometry is a standard tool currently used to assess platelet function. It measures the speed and degree at which platelets in a blood sample clump together, or aggregate. 

“This data provides only a small part of the picture of platelet function and it’s not the most interesting part,” Sniecinski says. 

When a platelet gets activated, he explains, it changes its morphology and grows tiny pseudo “arms.” Platelets use these arms to grip onto chains of proteins in the blood called fibrinogen to form clots. 

“Aggregometry tells you that platelets are clumping together,” Sniecinski says. “But it doesn’t tell you about their level of activation — the amount of force they’re using to hold on to other coagulation proteins, as well as each other.” 

Amplifying the signal 

The Salaita lab is a leader in visualizing and measuring the mechanical forces applied by cells using tension probes made from synthetic strands of double-stranded DNA tethered to a surface. 

The double-strands of DNA can be programmed to bind to platelet cells. When the cells bind and apply force to the anchored DNA, the DNA splits into two strands, leaving one strand stuck to the surface. The resulting physical tug is converted into a fluorescent signal. 

A major challenge to reading this signal, however, is that these physical tugs are faint, fleeting and infrequent. They require a microscope to detect them. 

During the COVID-19 pandemic , the enzyme CRISPR 12a, or Cas12a, came to the fore as a diagnostic tool for SARS-CoV-2 virus. Bacteria use Cas12a to defend against phages, or viruses that attack bacteria. The Cas12a enzyme can be loaded with single-stranded “guide” RNA that is programmed to bind to a complementary single-stranded DNA. The enzyme then reacts to the single-stranded DNA by destroying other single-stranded DNA surrounding it. 

The Salaita lab decided to combine Cas12a with its tension probes to see if the enzyme would amplify the signal for the mechanical forces exerted by blood platelets. The lab developed what it calls the Mechano-Cas12a Assisted Tension Sensor, or MCATS. 

“It worked like gangbusters,” Salaita says. 

“Cas12a is quiet and inactive if it doesn’t see its target,” he explains. “But as soon as it sees a specific single-strand DNA, it goes bananas and starts destroying any single-stranded DNA it comes across. This activation generates a massive fluorescence signal output.” 

MCATS is precise and ultrasensitive, able to measure cellular traction forces generated by as few as 2,000 platelets within a sample. And the resulting signal is robust enough to measure via a conventional fluorometer — a tool commonly used in routine blood tests. 

MCATS also works with a plate reader, an instrument designed to handle dozens of samples simultaneously, for the kind of high-throughput readout needed to conduct research. 

Testing its clinical potential 

To test the efficacy of MCATS at measuring the activity of platelet function, the researchers drew blood samples from healthy volunteer donors. They first validated that the MCATS response was sensitive to the mechanical forces of platelets. 

They next added to the healthy blood samples different antiplatelet drugs, ranging from over-the-counter aspirin to a panel of different prescription medications. The MCATS results showed that the antiplatelet therapies reduced the mechanical activity of platelets by an amount similar to the reduction observed in aggregometry. 

The researchers also received permission to take blood samples for investigation from seven patients pre- and post-cardiopulmonary bypass surgery. The results showed that the MCATS readings for the platelet activity of each individual patient’s sample correlated to their likelihood to need platelet transfusions to minimize bleeding after surgery. 

The researchers are now enrolling participants in a prospective study to further explore MCATS as a diagnostic tool. People diagnosed with a platelet disorder will have their blood samples tested pre- and post-treatment to assess how well a therapy is working. 

“The bottom line is that MCATS is a whole new way to measure platelet function using a really tiny sample,” Sniecinski says. “It’s telling us something specific that we haven’t been able to measure before and that can give us a new way to understand what’s going on with platelet dysfunction and the best methods for controlling it.” 

“Blood work up gives you a basic readout of your health based on data like platelet count and metabolic concentrations,” Salaita adds. “Now we’re adding information about the mechanics of platelets. That’s like getting a whole new dial on your dashboard for monitoring your health.” 

Work on the current paper was funded by the National Institutes of Health, the National Science Foundation and the American Heart Association.

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