Thursday, March 15, 2018

Biologists unravel another mystery of what makes DNA go 'loopy'

Interior of a cell showing the nucleus with the chromatin fiber (yellow) arranged in the three-dimensional space by loops formed by the CTCF protein (shown in pink). DNA is represented by thin blue lines on the chromatin. Graphic by Victor Corces. 

By Carol Clark

Scientists discovered another key to how DNA forms loops and wraps inside the cell nucleus — a precise method of “packing” that may affect gene expression.

The journal Science published the research by biologists at Emory University, showing that a process known as hemimethylation plays a role in looping DNA in a specific way. The researchers also demonstrated that hemimethylation is maintained deliberately — not through random mistakes as previously thought — and is passed down through human cell generations.

“In order for a protein called CTCF to make loops in the DNA, we discovered that it needs to have hemimethylated DNA close by,” says Emory biologist Victor Corces, whose lab conducted the research. “Nobody had previously seen that hemimethylated DNA has a function.”

Chromatin is made up of CTCF and other proteins, along with DNA and RNA. One role of chromatin is to fold and package DNA into more compact shapes. Growing evidence suggests that this folding process is not just important to fit DNA into a cell nucleus — it also plays a role in whether genes are expressed normally or malfunction.

The Corces lab specializes in epigenetics: The study of heritable changes in gene function — including chromatin folding — that do not involve changes in the DNA sequence.

DNA methylation, for example, can modify the activity of DNA by adding methyl groups to both strands of the double helix at the site of particular base pairs. The process can be reversed through demethylation.

As cells divide they make a copy of their DNA. In order to do so, they have to untangle the two strands of DNA and split them apart. Each parental strand then replicates a daughter strand.

“When cells divide, it’s important that they keep the methylation the same for both strands,” Corces says, noting that altered patterns of methylation are associated with cancer and other diseases.

Hemimethylation involves the addition of a methyl group to one strand of the DNA helix but not the other. Some researchers observing hemimethylation have hypothesized that they were catching it right after cell division, before the cell had time to fully replicate to form a daughter strand. Another theory was that hemimethylation was the result of random mistakes in the methylation process.

Chenhuan Xu, a post-doctoral fellow in the Corces lab, developed new experimental methods for DNA methylome mapping to conduct the research for the Science paper. These methods allowed the researchers to observe hemimethylation on DNA in human cells in real-time before, during and after cell division. They also mapped it as the cells continued to replicate.

“If the parental DNA was hemimethylated, the daughter DNA was also hemimethylated at the same place in the genome,” Corces says. “The process is not random and it’s maintained from one cell generation to the next over weeks.”

The researchers found that hemimethlyation only occurs near the binding sites of CTCF — the main protein involved in organizing DNA into loops.

“If we got rid of the hemimethlyation, CTCF did not make loops,” Corces says. “Somehow, hemimethylation is allowing CTCF to make loops.”

And when CTCF makes a loop, it does so by binding ahead, going forward in the DNA sequence, they observed.

“Research suggests that some disorders are associated with CTCF binding — either mutations in the protein itself or with the DNA sequence where the protein binds,” Corces says. “It comes back to the story of how important these loops are to the three-dimensional organization of chromatin, and how that organization affects the gene expression.”

Small steps lead to big career
Teen scientists bloom in lab
Epigenetics zeroes in on nature vs. nurture

Monday, March 12, 2018

Biophysicists discover how small populations of bacteria survive treatment

"We showed that by tuning the growth and death rate of bacterial cells, you can clear small populations of even antibiotic-resistant bacteria using low antibiotic concentrations," says biophysicist Minsu Kim. His lab conducted experiments with E. coli bacteria (above).

By Carol Clark

Small populations of pathogenic bacteria may be harder to kill off than larger populations because they respond differently to antibiotics, a new study by Emory University finds.

The journal eLife published the research, showing that a population of bacteria containing 100 cells or less responds to antibiotics randomly — not homogeneously like a larger population.

“We’ve shown that there may be nothing special about bacterial cells that aren’t killed by drug therapy — they survive by random chance,” says lead author Minsu Kim, an assistant professor in the Department of Physics and a member of Emory’s Antibiotic Resistance Center.

“This randomness is a double-edged sword,” Kim adds. “On the surface, it makes it more difficult to predict a treatment outcome. But we found a way to manipulate this inherent randomness in a way that clears a small population of bacteria with 100 percent probability. By tuning the growth and death rate of bacterial cells, you can clear small populations of even antibiotic-resistant bacteria using low antibiotic concentrations.”

The researchers developed a treatment model using a cocktail of two different classes of antibiotic drugs. They first demonstrated the effectiveness of the model in laboratory experiments on a small population of E. coli bacteria without antibiotic-drug resistance. In later experiments, they found that the model also worked on a small population of clinically-isolated antibiotic-resistant E. coli.

“We hope that our model can help in the development of more sophisticated antibiotic drug protocols — making them more effective at lower doses for some infections,” Kim says. “It’s important because if you treat a bacterial infection and fail to kill it entirely, that can contribute to antibiotic resistance.”

Antibiotic resistance is projected to lead to 300 million premature deaths annually and a global healthcare burden of $100 trillion by 2050, according to the 2014 Review on Antimicrobial Resistance. The epidemic is partly driven by the inability to reliably eradicate infections of antibiotic-susceptible bacteria.

For decades, it was thought that simply reducing the population size of the bacteria to a few hundred cells would be sufficient because the immune system of an infected person can clear out the remaining bacteria.

“More recently, it became clear that small populations of bacteria really matter in the course of an infection,” Kim says. “The infectious dose — the number of bacterial cells needed to initiate an infection — turned out to be a few or tens of cells for some species of bacteria and, for others, as low as one cell.”

It was not well understood, however, why treatment of bacteria with antibiotics sometimes worked and sometimes failed. Contributing factors may include variations in the immune responses of infected people and possible mutations of bacterial cells to become more virulent.

Kim suspected that something more fundamental was a factor. Research has shown unexpected treatment failure for antibiotic-susceptible infections even in a simple organism like the C. celegans worm, a common model for the study of bacterial virulence.

By focusing on small bacteria populations, the Emory team discovered how the dynamics were different from large ones. Antibiotics induce the concentrations of bacterial cells to fluctuate. When the growth rate topped the death rate by random chance, clearance of the bacteria failed.

The researchers used this knowledge to develop a low-dose cocktail drug therapy of two different kinds of antibiotics. They combined a bactericide (which kills bacteria) and a bacteriostat (which slows the growth of bacteria) to manipulate the random fluctuation in the number of cells and boost the probability of the cell death rate topping the growth rate.

Not all antibiotics fit the model and more research is needed to refine the method for applications in a clinical setting.

 “We showed that the successful treatment of a bacterial infection with antibiotics is even more complicated than we thought,” Kim says. “We hope this knowledge leads to new strategies to fight against infections caused by antibiotic-resistant bacteria.”

CDC funds Emory project to automate analysis of mixed strains of antibiotic-resistant bacteria
Brazilian peppertree packs power to knock out antibiotic-resistant bacteria

Mathematician works to improve artificial intelligence

Emory mathematician Lars Ruthotto is pioneering a new field that applies the logic of differential equations to refine the chaos of deep learning. (Emory Photo/Video)

By April Hunt
Emory Report

 If you’ve ever told Siri to call your friend Bob and she answers with, “Calling cops,” you’ve seen the instability of artificial intelligence (AI) in action.

Those mistakes are the limitation of the AI technology known as deep learning. They arise from the design of the deep neural network, as well as the network’s “training,” which applies mathematical optimization methods to massive amounts of data rather than hand-crafting rules to accomplish a specific task.

Emory mathematician Lars Ruthotto has dedicated his research to modeling and solving such 21st century problems with the innovative use of differential equations that date back to the late 1600s. The National Science Foundation has rewarded his efforts with a CAREER Award, its most prestigious honor for junior faculty.

Put simply, Ruthotto is pioneering a new field — combining applied math, engineering and computer science — that applies the logic of differential equations to refine the chaos of deep learning.

“Focusing on this research question can impact specific areas of deep learning now as well as emerging technology,” says Ruthotto, an assistant professor in mathematics and computer science. “It’s uncharted territory, and my students and I will be at the forefront exploring it.”

The award is recognition of the new knowledge Ruthotto and his students are creating in the emerging field and also a hint of what’s to come, says Vaidy Sunderam, chair of Emory's Department of Math and Computer Science.

 “This grant establishes Emory as a research and education pioneer in innovative methods for robust deep learning, a key technology in the coming AI decade,” Sunderam says.

Read more in Emory Report.

Emory team vies for best social bot via Amazon's Alexa Prize 
CDC funds Emory project to automate analysis of mixed strains of antibiotic-resistant bacteria

Wednesday, February 28, 2018

Emory team vies for best social bot via Amazon's Alexa Prize

Faculty advisor Eugene Agichtein (far right) with the Mathematics and Computer Science Alexa Prize team (clockwise from top left): Ali Ahmadvand, Mingyang Sun, Jason Choi, Sergey Volokhin, Zihao Wang and Harshita Sahijwani. (Photo by Ann Borden, Emory Photo/Video)

By Carol Clark

“Alexa, when will you learn to chat with me like people I might meet at a party or a pub?”

“I couldn’t say.”

Alexa may be a popular talking bot, but she has not yet acquired the “social” skills to turn that query into a conversation.

A team of Emory students from the Department of Mathematics and Computer Science are trying to help her develop those skills sooner, rather than later. They are among eight university teams selected from around the world to create a social bot and compete for this year’s Alexa Prize. Amazon is sponsoring the $3.5 million university challenge in order to advance the conversational capabilities of bots such as Alexa — Amazon’s “personal assistant” software that responds to voice commands through a growing list of devices.

“Conversational AI is one of the most difficult problems in the field of artificial intelligence,” says Zihao Wang, a graduate student and the leader of the Emory team. “Human language is so rich. We use combinations of words to form different expressions and idioms. It’s difficult to represent them in computer language.”

Wang’s teammates include Ali Ahmadvand, Jason Choi, Harshita Sahijwani and Sergey Volokhin — all graduate students — and senior Mingyang Sun. The team’s faculty advisor is Eugene Agichtein, an associate professor of Mathematics and Computer Science.

Each of the university teams received a $250,000 research grant, Alexa-enabled devices, and other tools, data and support from Amazon. A $500,000 prize will be given next November to the team that creates the best social bot, while second- and third-place teams will receive $100,000 and $50,000.

Additionally, a $1 million research grant will be awarded to the winning team’s university if their social bot achieves the grand challenge — conversing coherently and engagingly with humans for 20 minutes with a user rating of 4.0 or higher.

“The contest is a wonderful way for students to get hands-on experience developing a social bot using state-of-the-art technology,” Agichtein says. “Their work will be tested out by millions of real-world consumers through Amazon. And Amazon provides support and training so they can get experience with data and computing environments that are usually only accessible to those within major corporations.”

Agichtein’s IR Lab is developing new techniques for intelligent information access, including Web search and automated question answering. Conversational search capabilities are a key emerging trend, he says.

He notes that his children love asking Alexa trivia questions or about music and sports. “It’s natural for them to talk to devices instead of having to type in a question because they’re growing up amid this technology,” Agichtein says. “And as time goes on, it’s clear that voice-based communication devices are going to keep improving and become more ubiquitous.”

Wang is a native of China who earned his master’s in civil engineering at Carnegie Mellon University. A robotics project sparked his interest in information retrieval powered by machine learning, leading him to Emory and Agichtein’s lab to work on his PhD.

“Machine learning is widely applied in the real world,” Wang says. “It’s changing peoples’ lives in every way.”

Autonomous vehicles, drones, online shopping mechanisms and robots designed to detect and remove dangerous objects are just a few examples of how machine learning is being applied.

 “The idea is to train an algorithm to ‘learn’ patterns embedded in data,” Wang explains.

While a machine learning algorithm to simulate natural, human conversation is a difficult challenge, Wang says it’s one well worth pursuing.

Possible healthcare uses for conversational social bots include providing companionship to isolated seniors, serving as therapeutic agents for people suffering from depression and conducting patient interviews to streamline admissions to a medical clinic.

Wang also led an Emory team in the inaugural Alexa contest last year, but the team did not make it to the finals. “We learned a lot from the experience,” he says.

The working title for the Emory social bot this year is IRIS, which stands for information retrieval and informative suggestion agent. “Our focus will be on the accuracy and usefulness of information that we provide to users,” Wang says. “And we will add conversational functionality to our design to make the responses as natural and engaging as possible.”

IRIS will incorporate “ideas from each member of the team,” he adds. “That’s one of the most fun things about the contest, is working as a team.”

Starting in May, the public can access competing bots to provide feedback and rate them by saying, “Alexa, lets chat,” to an Echo device, or to the Amazon mobile app. The bots will be randomly assigned and remain anonymous, so that people providing feedback cannot identify the university that generated them.

By August, Amazon will have used this feedback to winnow the contestants down to three finalists that will continue to get more consumer feedback until the winner is announced in November.

Other university teams competing this year include: Heriot-Watt University in Edinburgh, Scotland, Czech Technical University in Prague, Brigham Young University, UC Davis, KTH Royal Institute of Technology in Stockholm, Sweden, UC Santa Cruz, and Carnegie Mellon.

Raising IQ of web searches
Mouse trail leads to online shoppers

Monday, February 26, 2018

Ecosystems hanging by a thread

Emory disease ecologist Thomas Gillespie served on an international committee that developed best practice guidelines for health monitoring and disease control in great ape populations, part of a growing public education effort.

By Tony Rehagen
Emory Magazine

Thomas Gillespie’s parents and teachers always wanted him to go into medicine.

“Growing up in Rockford, Illinois, if you were smart and interested in biology, you were supposed to be a doctor,” he says.

Gillespie, meanwhile, was always more interested in primates. In seventh grade, he phoned animal psychologist Penny Patterson, famous for teaching the gorilla Koko how to use sign language, and interviewed the scientist about Koko’s diet while punching out notes on a typewriter. He was premed at the University of Illinois, but spent his internship at the Brookfield Zoo in Chicago, working in the “Tropic World” primate exhibit. His favorite undergrad course was biological anthropology, the study of biological and behavioral aspects of humans and nonhuman primates, looking at our closest relatives to better understand ourselves.

Gillespie eventually took a year off before graduate school to work with primate communities in the Peruvian Amazon. The apes finally won out — Gillespie would choose a doctorate in zoology over medical school.

But it wasn’t long before the two fields of study collided. While monitoring the group behavior of colobine monkeys in Africa, Gillespie observed that some of the animals were eating bark from the African cherry tree — not a typical food source for them. When he dug deeper, Gillespie learned that human doctors in the region used that same bark to treat parasites in their patients. The monkeys, he realized, were self-medicating.

“That discovery in these monkeys brought me back toward the health science side of biology,” says Gillespie.

Gillespie’s return to a medical approach to zoology came not a moment too soon—for the sake of the primates and maybe even all of humankind. As an associate professor in Emory’s Department of Environmental Sciences specializing in the disease ecology of primates, Gillespie and his team of researchers have helped uncover a crisis among our nearest taxonomic neighbors. According to an article coauthored by Gillespie and thirty other experts and published in the journal Science Advances, 75 percent of the world’s five-hundred-plus primate species are declining in population, and a whopping 60 percent face extinction, largely due to human encroachment.

Read more in Emory Magazine.

Experts warn of impending extinction of many of the world's primates
Chimpanzee studies highlight disease risks to all endangered wildlife

Thursday, February 22, 2018

Frankenstein and robots rise up for Atlanta Science Festival

Hair-raising, spine-tingling fun: A young visitor to the Emory campus during last year's Atlanta Science Festival experiences the thrill of static electricity.

By Carol Clark

From the lumbering, 200-year-old Frankenstein to sleek, modern-day robots, this year’s Atlanta Science Festival — set for March 9 to 24 — highlights creations that spark wonder and fun, giving glimpses of the past and the future.

The five-year-old festival expanded to more than two weeks, encompassing 120 events sponsored by 90 different partners at 70 venues across metro Atlanta, including many on the Emory campus. The festival culminates with a day-long “Exploration Expo” on Saturday, March 24, set in Piedmont Park.

“Rise Up, Robots!” kicks off the festival on the evening of Friday, March 9 at the Ferst Center, when three robots and their inventors will take the stage.

“We thought about how we could possibly top last year’s featured speaker, astronaut Mark Kelly — someone so inspirational to children and adults all over the planet,” says Meisa Salaita, co-director of the Atlanta Science Festival. “We finally realized that no human could match him, and we would have to resort to artificial intelligence.”

Heather Knight, professor of robotics at Oregon State University, will demonstrate the interactive quips of “Data,” the world’s first robotic comedian. Georgia Tech’s Gil Weinberg will jam with “Shimon,” a marimba playing robotic musician. And Stewart Coulter, from DEKA Research and Development, will show how a bionic arm named LUKE (Life Under Kinetic Evolution) changed an amputee’s life.

Tickets are required for the event, which starts at 7 pm. Door open early with an Interactive Robotic Petting Zoo, starting at 6 pm.

Frankenstein rises up on the Emory campus on Thursday, March 22. Three Atlanta playwrights will reanimate Mary Shelley’s creation, which turns 200 this year, in the context of scientific research ongoing at Emory. Following the short plays join ethicists, scientists and the playwrights to discuss the work over refreshments. The event, titled “Frankenstein Goes Back to the Lab,” begins at 5:30 pm in Emory’s Science Commons.

On Friday, March 23, from 3:30 to 7 pm, Emory will host “Chemistry Carnival,” where visitors can join scientists in carnival games like Peptide Jenga and Bacterial Telepathy, in the Atwood Chemistry Center. On the same day and time, the ever-popular “Physics Live!” will again feature giant soap bubbles and liquid nitrogen ice cream, among other treats in the Math and Science Center.

A new Emory event this year, “Science.Art.Wonder,” will run concurrently with the chemistry and physics events, in the same venues. For the past year, the program has paired local artists and scientists to explore ideas of research through the visual arts. You can stroll through an exhibit of the resulting artwork and meet some of the artists and scientists involved in the project.

Adult fare is featured on Monday, March 19, including “The Science of ‘Motherese,’” an overview of early vocal development in infants at the Marcus Autism Center, and “CDC in the Scene,” which features CDC scientists sorting fact from fiction surrounding movies like “Outbreak,” in the Mathematics and Science Center.

On Tuesday, March 20, “Become an Archeologist” lets you in on secrets revealed by ancient skeletons and artifacts, while “Mock Climate Change Negotiation” turns you into an international policymaker for a day.

During “Unveiling the Internet,” on Wednesday, March 21, Emory computer scientists will give interactive lessons on everything from the workings of YouTube to Snapchat.

“STEM Gems: Giving Girls Role Models in STEM Careers,” on Saturday, March 10, is an interactive discussion where panelists offer advice and guidance specific to girls and young women intrigued by science, technology, engineering and math. “Women and Minorities in STEM: Surprises, Setbacks and Successes,” set for the evening of Thursday, March 22 at the Oxford campus, is a panel discussion with voices from a diverse set of scientific fields who will share their stories and take questions.

Click here for more details of Emory campus events, and events throughout the city featuring members of the Emory community.

Among the dozen Emory booths at “Exploration Expo” will be chemistry students running their non-Newtonian fluid dance pit. The Center for the Study of Human Health will explore the human gut microbiome in a booth called “Your Hundred Trillion Best Friends.” And the “Science.Art.Wonder” team will display art from the program and invite you to help create a mural.

The Atlanta Science Festival was founded by Emory, Georgia Tech and the Metro Atlanta Chamber and is a collaboration among diverse community partners and sponsors.

'The Enlightened Gene' bridges Buddhism and biology

Tibetan monk Geshe Yungdrung Konchok (left) and Emory biologist Arri Eisen (right) pose with the Dalai Lama, who wrote an introduction for their new book, "The Enlightened Gene." The book explores how dialogue between scientists and monastics enriches understandings of biology, physics and other sciences. 

By April Hunt, Emory Report

For nearly a decade, the Emory-Tibet Science Initiative has done more than challenge the idea that religion and science don’t mix by developing and successfully launching a comprehensive science curriculum for thousands of Tibetan monks and nuns.

The first major change to Tibetan Buddhist monastic education in six centuries also demonstrated how insights and information from both the monastics and professors could enrich each other’s understanding of biology, physics and other sciences.

Arri Eisen, an Emory College professor of pedagogy in biology and the Institute for Liberal Arts, explores those connections in “The Enlightened Gene,” a book he co-wrote with one of the monks, Geshe Yungdrung Konchok.

“He grew up on the Tibetan plateau herding yaks. I grew up one of about five Jewish guys in North Carolina in the 1970s,” Eisen says. “We had different experiences, but we could use them to develop a common approach, to try to better understand our world.”

Emory has woven Western and Tibetan Buddhist intellectual traditions together since founding the Emory-Tibet Partnership in 1998. His Holiness the Dalai Lama has been a Presidential Distinguished Professor at Emory since 2007.

Read more in Emory Report.

Emory Tibet Science Initiative rolls out bridges to inner and outer worlds

Friday, February 16, 2018

'Divine Felines' showcases Egypt's exaltation of cats

From ancient Egypt to modern times, cats rule many peoples' lives. Photo by Stephen Nowland, Emory Photo/Video.

By Leslie King
Emory Report

“In ancient Egypt, cats and dogs were gods, and they have not forgotten this!” says Melinda Hartwig, curator of Ancient Egyptian, Nubian and Near Eastern Art at the Michael C. Carlos Museum.

That exalted stature is illuminated in the exhibition “Divine Felines: Cats of Ancient Egypt,” which opened Feb. 10 at the museum and will be on view through Nov. 11.

The exhibit showcases cats and lions, plus dogs and jackals, as domesticated pets, creatures of the wild or mythic symbols of divinities, in ancient Egyptian mythology, kingship and everyday life. Animal burial practices and luxury items decorated with feline and canine features are also on display.

“Cats and dogs reveal so much about ancient Egyptian culture,” says Hartwig. “These animals were just as important to the ancient Egyptians as they are to us today.”

The kings of Egypt were associated with the lion, thus, the human head on the lion’s body or the sphinx.

“Cats were first domesticated in Egypt around 4000 BC. They were lovable pets, hunters of vermin and divine embodiments of fertility and protection. Lions and jungle cats were admired for their power, and were linked with royalty and divinity,” Hartwig continues. “Dogs were also kept as pets. Their loyalty and hunting abilities were keenly valued. Often found roaming the ancient necropolises, dogs and jackals became embodiments of the gods who protected the dead.”

Read more in Emory Report.

Monday, February 5, 2018

Twitter reveals how future-thinking Americans are and how that affects their decisions

By Carol Clark

Individuals who tend to think further into the future are more likely to invest money and to avoid risks, finds a new paper by psychologists at Emory University. The Proceedings of the National Academy of Sciences (PNAS) published the research, which tapped big data tools to conduct text analyses of nearly 40,000 Twitter users, and to run online experiments of behavior of people who provided their Twitter handles.

The researchers also found an association between longer future-sightedness and less risky decision-making at a U.S. state population level.

“Twitter is like a microscope for psychologists,” says co-author Phillip Wolff, an Emory associate professor of psychology. “Naturalistic data mined from tweets appears to give insights not just into tweeters’ thoughts at a particular time, but into a relatively stable cognitive process. Using social media and big-data analytical tools opens up a new paradigm in the way we study human behavior.”

Co-author Robert Thorstad, an Emory PhD candidate in the Wolff lab, came up with the idea for the research, worked on the design and analyses, and conducted the experiments.

“I'm fascinated by how peoples’ everyday behavior can give away a lot of information about their psychology,” Thorstad says. “Much of our work was automated, so we were able to analyze millions of Tweets from thousands of individuals’ day-to-day lives.”

The future-sightedness found in individuals’ tweets was short, usually just a few days, which differs from prior research suggesting future-sightedness on the order of years.

“One possible interpretation is that the difference is due to a feature of social media,” Wolff says. Another possible reason, he adds, is that prior studies explicitly asked individuals how far they thought into the future while the PNAS paper used the implicit measure of previous tweets.

While the relationship between future-sightedness and decision-making may seem obvious, the researchers note that previous findings on the subject have not been consistent. Those inconsistencies may be due to factors such as observer bias in a laboratory setting and small sample sizes.

The PNAS paper used a suite of methods (such as the Stanford CoreNLP natural language processing toolkit and SUTime, a rule-based temporal tagger built on regular expression patterns) to automatically analyze Twitter text trails previously left by individual subjects. Experimental data was gathered using the Amazon crowdsourcing tool Mechanical Turk, a web site where individuals can complete psychology experiments and other internet-based tasks. Participants in the Mechanical Turk experiments were asked to supply their Twitter handles.

In one experiment for the PNAS paper, Mechanical Turk participants answered a classic delay discounting question, such as: Would you prefer $60 today or $100 in six months? The participants’ Tweets were also analyzed. Future orientation was measured by the tendency of participants to tweet about the future compared to the past. Future-sightedness was measured based on how often tweets referred to the future, and how far into the future.

The results showed that future orientation was not associated with investment behavior, but that individuals with far future-sightedness were more likely to choose to wait for future rewards than those with near future-sightedness. That indicates that investment behavior depends on how far individuals think into the future and not their tendency to think about the future in general.

A second Mechanical Turk experiment used a digital Balloon Analogue Risk Task (BART). Participants’ could earn real money every time they inflated a balloon, but each inflation could lead to the balloon popping, resulting in no money earned for that trial. If participants stopped inflating before the balloon popped, they could bank the money that they have earned and proceed to the next trial.

The BART participants’ tweets were also analyzed. The results showed that those with longer future-sightedness were less likely to take the risk of fully inflating the balloon.

Another study in the PNAS paper focused on Twitter users whose profiles tied them to a particular state. About eight million of their tweets were analyzed for future-sightedness.

The researchers measured a state’s risk-taking behaviors at the population level using the proxy of publicly available statistics, such as seat-belt compliance rates, drunken driving rates and teen-aged pregnancy rates. The results showed that shorter future-sightedness measures for tweets from individual states correlated closely to higher rates of risky behaviors, in a pattern similar to the results of the individual experimental studies.

To measure a state’s investment behavior, the researchers used state statistics for spending on state parks, pre-kindergarten education, highways and per-pupil education. The researchers found that states that invested more in these areas were associated with tweets from individuals with longer future-sightedness, but not at a statistically significant level.

The researchers controlled for state demographics such as political orientation, per capita income, household income and GDP. “We found that, while demographics are important, they couldn’t explain away the effects of future-thinking,” Wolff says.

The estimated 21 percent of American adults who use Twitter tend to be younger and more technologically literate than the general population, Thorstad concedes. But he adds that Twitter’s demographics are not that far off from the general population in terms of gender, economic status and education levels. And the percentages of Twitter users living in rural, urban and suburban areas are virtually the same.

“Twitter can provide a much broader participant pool than many psychology experiments that primarily use undergraduates as subjects,” Thorstad notes. “Big-data methods may ultimately improve generalizability for psychology results.”

“Through social media, we’re amassing huge amounts of data on ourselves, behaviorally and over time, that is leaving behind a kind of digital phenotype,” Wolff adds. “We’re now in an age where we have big-data analytical tools that can extract information to tell us something indirectly about an individual’s cognitive life, and to predict what an individual might do in the future.”

Monday, January 29, 2018

New method calculates equilibrium constant at the small scale

Mixing computational chemistry and theoretical math proved a winning formula for Emory chemist James Kindt (center), his graduate students (from left) Xiaokun Zhang and Lara Patel, and mathematics graduate students Olivia Beckwith and Robert Schneider. Photo by Stephen Nowland, Emory Photo/Video.

By Carol Clark

Computational chemists and mathematicians have developed a new, fast method to calculate equilibrium constants using small-scale simulations — even when the Law of Mass Action does not apply.

The Journal of Chemical Theory and Computation published the resulting algorithm and software, which the researchers have named PEACH — an acronym for “partition-enabled analysis of cluster histograms” and a nod to the method’s development in Georgia at Emory University.

“Our method will allow computational chemists to make better predictions in simulations for a wide range of complex reactions — from how aerosols form in the atmosphere to how proteins come together to form amyloid filaments implicated in Alzheimer’s disease,” says James Kindt, an Emory professor of computational chemistry, whose lab led the work.

Previously it would require at least a week of computing time to do the calculations needed for such predictions. The PEACH system reduces that time to seconds by using tricks derived from number theory.

“Our tool can use a small set of data and then extrapolate the results to a large-system case to predict the big picture,” Kindt says.

“What made this project so fun and interesting is the cross-cultural aspects of it,” he adds. “Computational chemists and theoretical mathematicians use different languages and don’t often speak to one another. By working together we’ve happened onto something that appears to be on the frontiers of both fields.”

The research team includes Lara Patel and Xiaokun Zhang, who are both PhD students of chemistry in the Kindt lab, and number theorists Olivia Beckwith and Robert Schneider, Emory PhD candidates in the Department of Mathematics and Computer Science. Chris Weeden, as an Emory undergraduate, contributed to early stages of the work.

The equilibrium constant is a basic concept taught in first-year college chemistry. According to the Law of Mass Action, at a given temperature, no matter how much of a product and a reactant are mixed together — as long as they are at equilibrium — a certain ratio of product to reactant will equal the equilibrium constant.

“That equation always holds true at equilibrium for huge numbers of molecules,” Kindt says. “It doesn’t matter if it’s applied to a bucket of water or to a single drop of water — which consists of about a billion trillion molecules.”

At much smaller scales of around dozens of molecules, however, the Law of Mass Action breaks down and does not apply.

The Kindt lab uses computers to simulate the behavior of molecules, in particular how they self-assemble into clusters. Sodium octyl sulfate, or SOS, is one of the compounds the lab uses as an experimental model. SOS is a surfactant that can act as a detergent. It forms little clusters in water that can encapsulate oil and grease. Simulations of how SOS molecules come together can predict the distribution of sizes of clusters formed under different conditions, in order to improve the design of soaps and detergents, and to better understand biological processes such as how bile salts break down globules of fat during the digestive process.

In a key test of their model, the lab needed to make sure that the equilibrium for the assembly reaction of SOS molecules into clusters matched up with experiments.

“If we were to run simulations with huge numbers of molecules, we could count the clusters that were formed of each size, count the molecules that remained free of the clusters, and use this information to calculate the equilibrium constant for forming each size cluster,” Kindt says. “The challenge we faced was that it would take too long for the computers to perform simulations of sufficiently huge numbers of molecules to get this to work, and for the numbers of clustering molecules we could practically handle — around 50 — the Law of Mass Action wouldn’t work.”

Kindt decided to approach the problem by considering all the different ways the molecules in a reaction could group into clusters of different sizes in order to arrive at an average. After doing some reading, he realized that these different ways of molecules grouping were what number theorists call integer partitions.

A partition of a number is a sequence of positive integers that add up to that number. For instance, there are five partitions of the number 4 (4 = 3+1 = 2+2 = 2+1+1 = 1+1+1+1). The partition numbers grow at an incredible rate. The amount of partitions for the number 10 is 42. For the number 100, the partitions explode to more than 190,000,000.

That same explosion of possibilities occurs for the ways that molecules can cluster.

Lara Patel and Xiaokun Zhang worked on a “brute force” method to get a computer to run through every single way to combine 10 molecules of one type with 10 molecules of another type. The problem was it took one computer working a couple of days to do a single analysis. And the computational time needed if just a few more molecules were added to the analysis went up exponentially.

The computational chemists had hit a wall.

Kindt reached out to Ken Ono, a world-renowned number theorist in Emory's Mathematics and Computer Science Department, to see if any of his graduate students would be interested in taking a crack at the problem.

Olivia Beckwith and Robert Schneider jumped at the chance.

“The Kindt lab’s computer simulations show that classical theorems from partition theory actually occur in nature, even for small numbers of molecules,” Schneider says. “It was surprising and felt very cosmic to me to learn that number theory determines real-world events.”

“It was definitely unexpected,” adds Beckwith. “In theoretical math we tend to work in isolation from physical phenomena like the interaction of molecules.”

The chemists and mathematicians began meeting regularly to discuss the problem and to learn one another’s terminology. “I had to pull out my son’s high school chemistry book and spend a weekend reading through it,” Schneider says.

“It happened so organically,” Patel says of the process of blending their two specialties. “Olivia and Robert would write equations on the board and as soon as a formula made sense to me I’d start thinking in my head, ‘How can we code this so that we can apply it?’”

The two mathematicians suggested a strategy that could make the problem much easier to calculate, based on a theorem known as FaĆ  di Bruno’s Formula.

“It was surprising,” Zhang says, “because it was an idea that never would have occurred to me. They helped us get unstuck and to find a way to push our research forward.”

“They helped us find a shortcut so that we didn’t have to generate all the partitions for ways that the molecules could clump together,” Kindt adds. “Their algorithm is a much more elegant and simple way to find the entire average overall.”

Patel and Zhang used this new algorithm to put together a piece of software to analyze data from the computer simulations. The resulting system, PEACH, speeds up calculations that previously took two hours to just one second. After demonstrating how PEACH simplifies simulations of SOS assemblages, the research team is moving on to simulate this process for a range of other molecules.

“We’re interested in describing how molecular structures dictate assembly in any type of scenario, such as the early stages of crystal formation,” Kindt says. “We’re also working on quantifying just where the Law of Mass Action breaks down. We could then refine the PEACH strategy to make it even more efficient.”

New theories reveal the nature of numbers

Friday, January 26, 2018

Chimpanzee studies highlight disease risk to all endangered wildlife

Famed primatologist Jane Goodall with Emory disease ecologist Thomas Gillespie, who is working with the Jane Goodall Institute to study the health of chimpanzees in Tanzania's Gombe National Park.

The American Journal of Primatology just published a special edition bringing together experts who have contributed to the understanding of chimpanzee health at Gombe National Park in Tanzania and beyond. Gombe is the site where Jane Goodall pioneered her behavioral research of chimpanzees. Goodall’s work at Gombe began in 1960, and continues today through the Jane Goodall Institute, making it the longest field study of any animal.

Thomas Gillespie, associate professor in Emory’s Department of Environmental Sciences, was a guest editor of the special journal edition, along with fellow scientists Dominic Travis and Elizabeth Lonsdorf. Gillespie works at the interface of biodiversity conservation and global health. Much of his research examines how and why anthropogenic influences within tropical forests alter disease dynamics and place wild primates, people and other animals in such ecosystems at increased risk of pathogen exchange.

Following is an interview with Gillespie about the special journal issue and why research on chimpanzee health is important.

What is the current status of chimpanzees?

Both the common chimpanzee and the bonobo, the two chimpanzee subspecies, are endangered. Chimpanzees are the most closely related species to humans and we see them declining precipitously due to habitat loss and poaching. Typical estimates for the chimpanzee population are in the hundreds of thousands. That’s far less than the number of people in Atlanta for the entire chimpanzee species spread across all of Africa. There is a real risk of chimpanzees going locally extinct in core parts of their habitat. Chimpanzee communities in West Africa, for instance, have very little habitat left. They’re often found living in scraps of habitat between villages.

How important is health to conservation? 

Wildlife health is a critical conservation issue, but that’s something that’s only recently been recognized. Wildlife populations already dealing with poaching and habitat loss are more vulnerable to being knocked out by disease. It becomes even more difficult when they are exposed to new pathogens, from humans or domesticated animals.

On top of that, primates are dealing with shifts in the dynamics of pathogens like Ebola. Ebola’s been around for a long time in natural systems but now we’re seeing big mortality events in wild chimpanzees and other apes. The Lowland Gorillas are actually listed as critically endangered due to Ebola.

How did you become involved with Gombe and the Jane Goodall Institute?

Fifteen years ago, as evidence mounted that disease was playing an important role in the population declines observed in Gombe chimpanzees in Tanzania, Dominic Travis and Elizabeth Lonsdorf developed a prospective health monitoring system. They began to collect specific behavioral data on signs of respiratory and gastrointestinal illnesses, combined with body condition scoring on a monthly basis for the chimpanzee communities at Gombe, that paralleled efforts by the Mountain Gorilla Veterinary Project in Rwanda and Uganda.

When I met Dom and Elizabeth at a workshop in Germany in 2004, I was six years into efforts to understand how logging and forest fragmentation in and around Kibale National Park, Uganda, affected disease dynamics in resident primates. My findings in Uganda highlighted that some forms of anthropogenic disturbance can alter the dynamics of natural pathogens in wildlife, such as a legacy of selective logging. It also revealed that other forms of disturbance, such as active forest fragmentation, can lead to opportunities for pathogens to jump between species, including the introduction of pathogens from people and domesticated animals to wild primates.

Dom and Elizabeth asked me to join their effort and expand the scope of their project to a One Health approach. I initiated diagnostic surveillance linked to geographical indicators of species overlap for Gombe’s chimpanzees and baboons, as well as the people and domesticated animals within the Greater Gombe Ecosystems. It serves as a map of all the places these species are interacting, for a greater sense of how transmission may be occurring. Integration of these new data streams, along with the ongoing observational health data and in-depth post-mortem necropsies, have allowed us to establish baselines of health indicators to inform outbreak contingency plans.

Dom, Elizabeth and I now co-direct this effort, which is known as the Gombe Ecosystem Health Project.

How does Gombe fit into the bigger picture of wildlife conservation? 

As a result of Jane Goodall’s initial observations of disease outbreaks impacting Gombe’s chimpanzees, it became apparent that infectious diseases have the capacity to threaten the conservation of endangered species.

Some people call Gombe “a living laboratory.” It’s unique in the sense that it’s a place where there has been long-term data collection on the behavior patterns of chimpanzees, and for the past 15 years we’ve been collecting all this data on their health.

Methods have been developed at Gombe that allow us to monitor chimpanzee health non-invasively, through fecal sampling, so that we don’t have to dart the animals and tranquilize them to take blood samples. Many of the tools and approaches developed at Gombe have the capacity to manage disease-related threats to other wildlife populations globally.

Ashley Sullivan from the Jane Goodall Institute contributed to this report.

Disease poses risk to chimpanzee conservation, Gombe study finds
Sanctuary chimps show high rates of drug-resistant staph

Thursday, January 25, 2018

Studying how genetic differences contribute to addiction

Psychology professor Rohan Palmer has earned a $2.4 million grant to examine why some people become addicted to alcohol or drugs, while others don't. Emory Photo/Video

By April Hunt
Emory Report

Rohan Palmer, an assistant professor of psychology in Emory College, started on the path to becoming a researcher as an undergraduate, when he worked in a lab studying whether female mice could overcome their anxiety to leave the safety of the nest to retrieve babies that he and other researchers had moved away.

Intriguingly, the work showed that some strains of mice performed very differently than others in overcoming their emotions to perform their motherly duties. Moreover, females exposed to more testosterone in the uterus performed worst at this and other maternal tasks.

“It was understanding behavior at its core,” says Palmer, now an expert in the field of behavioral genetics. “What helps us understand what makes us individuals better than looking at the environment and the biology?”

Palmer now runs his own behavioral genetics lab at Emory that turns that question to one of today’s most pressing issues: What makes some people addicted to drugs or alcohol, and not others?

His highly innovative approach, to find and characterize the layer of biology that combines with factors such as environment to find an answer, has earned him a 2017 Avenir Award for Genetics or Epigenetics of Substance Abuse Disorders (DP1) from the National Institutes of Health Director’s Pioneer Award program.

The five-year, $2.34 million award is among a handful of grants given to recognize “highly creative” scientists from the nation’s top universities and to encourage high-impact approaches to the broad area of biomedical and behavioral science.

“This is a special award, more so because very few beginning investigators receive this honor,” says Ronald Calabrese, the College’s senior associate dean for research.

Read more in Emory Report.

Thursday, January 4, 2018

Aversion to holes driven by disgust, not fear, study finds

Clusters of holes, such as those of a lotus seed pod, may be evolutionarily indicative of contamination and disease — visual cues for rotten or moldy food or skin marred by an infection. (Photo by Peripitus/Wikipedia Commons.)

By Carol Clark

Trypophobia, commonly known as “fear of holes,” is linked to a physiological response more associated with disgust than fear, finds a new study published in PeerJ.

Trypophobia is not officially recognized in the American Psychiatric Association’s Diagnostic and Statistical Manuel of Mental Disorders (DSM). Many people, however, report feeling an aversion to clusters of holes — such as those of a honeycomb, a lotus seed pod or even aerated chocolate.

“Some people are so intensely bothered by the sight of these objects that they can’t stand to be around them,” says Stella Lourenco, a psychologist at Emory University whose lab conducted the study. “The phenomenon, which likely has an evolutionary basis, may be more common than we realize.”

Previous research linked trypophobic reactions to some of the same visual spectral properties shared by images of evolutionarily threatening animals, such as snakes and spiders. The repeating pattern of high contrast seen in clusters of holes, for example, is similar to the pattern on the skin of many snakes and the pattern made by a spider’s dark legs against a lighter background.

“We’re an incredibly visual species,” says Vladislav Ayzenberg, a graduate student in the Lourenco lab and lead author of the PeerJ study. “Low-level visual properties can convey a lot of meaningful information. These visual cues allow us to make immediate inferences — whether we see part of a snake in the grass or a whole snake — and react quickly to potential danger.”

It is well-established that viewing images of threatening animals generally elicits a fear reaction in viewers, associated with the sympathetic nervous system. The heart and breathing rate goes up and the pupils dilate. This hyperarousal to potential danger is known as the fight-or-flight response.

The researchers wanted to test whether this same physiological response was associated with seemingly innocuous images of holes.

They used eye-tracking technology that measured changes in pupil size to differentiate the responses of study subjects to images of clusters of holes, images of threatening animals and neutral images.

Unlike images of snakes and spiders, images of holes elicited greater constriction of the pupils — a response associated with the parasympathetic nervous system and feelings of disgust.

“On the surface, images of threatening animals and clusters of holes both elicit an aversive reaction,” Ayzenberg says. “Our findings, however, suggest that the physiological underpinnings for these reactions are different, even though the general aversion may be rooted in shared visual-spectral properties.”

In contrast to a fight-or-flight response, gearing the body up for action, a parasympathetic response slows heart rate and breathing and constricts the pupils. “These visual cues signal the body to be cautious, while also closing off the body, as if to limit its exposure to something that could be harmful,” Ayzenberg says.

The authors theorize that clusters of holes may be evolutionarily indicative of contamination and disease — visual cues for rotten or moldy food or skin marred by an infection.

The subjects involved in the experiments were college students who did not report having trypophobia. “The fact that we found effects in this population suggests a quite primitive and pervasive visual mechanism underlying an aversion to holes,” Lourenco says.

Since the time of Darwin, scientists have debated the relation between fear and disgust. The current paper adds to the growing evidence that — while the two emotions are on continuums and occasionally overlap — they have distinct neural and physiological underpinnings.

“Our findings not only enhance our understanding of the visual system but also how visual processing may contribute to a range of other phobic reactions,” Ayzenberg says.

A third co-author of the study is Meghan Hickey. She worked on the experiments as an undergraduate psychology major, through the Scholarly Inquiry and Research at Emory (SIRE) program, and is now a medical student at the University of Massachusetts.

How fear skews our spatial perception
Psychologists closing in on claustrophobia