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Vox: DACA boosted immigrants’ education, labor force participation, productivity

It also cut teen pregnancy.

Journalist Matthew Yglesias with the website Vox covered the research of SMU government policy expert Elira Kuka. Her working paper, “Do Human Capital Decisions Respond to the Returns to Education? Evidence from DACA,” was released in February by the National Bureau of Economic Research.

Kuka, an assistant professor in the SMU Department of Economics, and her colleagues found that the Deferred Action for Childhood Arrivals program under fire by the Trump Administration has significantly changed the lives of young people who came to the United States illegally as children.

Kuka’s research focus is on understanding how government policy effects individual behavior and well-being, the extent to which it provides social insurance during times of need, and its effectiveness in alleviation of poverty and inequality.

Her current research topics include the potential benefits of the Unemployment Insurance (UI) program, the protective power of the U.S. safety net during recessions and various issues in academic achievement.

Read the full story.

EXCERPT:

By Matthew Yglesias
Vox

The Deferred Action for Childhood Arrivals program changed the lives of young people who came to the United States illegally as children in incredible ways — boosting high school graduation rates and college enrollment, while slashing teen births by a staggering 45 percent.

That’s according to timely new research from Elira Kuka, Na’ama Shenhav, and Kevin Shih that uses the program to study a larger question that’s of interest to economists — when education becomes more available, do people go get more of it? The DACA results suggest that the answer is yes, at least when there’s a clear upside. The program itself, in other words, was a smashing success in terms of bringing people out of the shadows and letting them contribute more to American society.

Oscar Hernandez, a DACA recipient, explained to Vox’s Dara Lind how things changed.

”The discussion in my house was, ‘You don’t get noticed. Because if you do something awesome and great, you might get noticed, and if you do get noticed, they might find out that we’re here undocumented, and if they find we out we could get separated.’ It was never a discussion we had, but that was the unwritten rule for our house. You don’t do bad things, but you also don’t do good things. You stay under the radar, you work, and that’s it.”

DACA changed that. Suddenly, recipients got to experience what US citizens take for granted — that to excel is good.

Canceling DACA almost certainly won’t reduce the overall size of the unauthorized population living in the United States, but it will meaningfully reduce the educational attainment and economic productivity of the undocumented population. That’s bad for the DREAMers, but also America as a whole.

DACA eligibility led to a lot more schooling
One of DACA’s provisions was that to qualify, you had to get a high school degree if you were old enough. That’s an unusual incentive to stay in school, and using a difference-in-differences design to compare the eligible to non-eligible population over time (you can do this because you had to have arrived within a specific time and age window to qualify) they show that DACA-eligibility increased high school graduation rates by 15 percent and brought teen births down by 45 percent.

Read the full story.

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Solving the dark energy mystery: A new sky survey assignment for a 45-year-old telescope

SMU and other members of a scientific consortium prepare for installation of the Dark Energy Spectroscopic Instrument to survey the night sky from a mile-high mountain peak in Arizona

As part of a large scientific consortium studying dark energy, SMU physicists are on course to help create the largest 3-D map of the universe ever made.

The map will emerge from data gathered by the Dark Energy Spectroscopic Instrument (DESI) being installed on the Nicholas U. Mayall Telescope atop a mountain in Arizona.

The map could help solve the mystery of dark energy, which is driving the accelerating expansion of the universe.

DESI will capture about 10 times more data than a predecessor survey of space using an array of 5,000 swiveling robots. Each robot will be carefully choreographed to point a fiber-optic cable at a preprogrammed sequence of deep-space objects, including millions of galaxies and quasars, which are galaxies that harbor massive, actively feeding black holes.

“DESI will provide the first precise measures of the expansion history of the universe covering approximately the last 10 billion years,” said SMU physicist Robert Kehoe, a professor in the SMU Department of Physics. “This is most of the 13 billion year age of the universe, and it encompasses a critical period in which the universe went from being matter-dominated to dark-energy dominated.”

The universe was expanding, but at a slowing pace, until a few billion years ago, Kehoe said.

“Then the expansion started accelerating,” he said. “The unknown ‘dark energy’ driving that acceleration is now dominating the universe. Seeing this transition clearly will provide a critical test of ideas of what this dark energy is, and how it may tie into theories of gravitation and other fundamental forces.”

The Mayall telescope was originally commissioned 45 years ago to survey the night sky and record observations on glass photographic plates. The telescope is tucked inside a 14-story, 500-ton dome atop a mile-high peak at the National Science Foundation’s Kitt Peak National Observatory – part of the National Optical Astronomy Observatory.

SMU researchers have conducted observing with the Mayall. Decommissioning of that telescope allows for building DESI in it’s place, as well as reusing some parts of the telescope and adding major new sytems. As part of DESI, SMU is involved in development of software for operation of the experiment, as well as for data simulation to aid data anlysis.

“We are also involved in studying the ways in which observational effects impact the cosmology measurements DESI is pursuing,” Kehoe said. SMU graduate students Govinda Dhungana and Ryan Staten also work on DESI. A new addition to the SMU DESI team, post-doctoral researcher Sarah Eftekharzadeh, is working on the SMU software and has studied the same kinds of galaxies
DESI will be measuring.

Now the dome is closing on the previous science chapters of the 4-meter Mayall Telescope so that it can prepare for its new role in creating the 3-D map.

The temporary closure sets in motion the largest overhaul in the telescope’s history and sets the stage for the installation of the Dark Energy Spectroscopic Instrument, which will begin a five-year observing run next year.

“This day marks an enormous milestone for us,” said DESI Director Michael Levi of the Department of Energy’s Lawrence Berkeley National Laboratory , which leads the project’s international collaboration. “Now we remove the old equipment and start the yearlong process of putting the new stuff on.”

More than 465 researchers from about 71 institutions are participating in the DESI collaboration.

The entire top end of the telescope, which weighs as much as a school bus and houses the telescope’s secondary mirror and a large digital camera, will be removed and replaced with DESI instruments. A large crane will lift the telescope’s top end through the observing slit in its dome.

Besides providing new insights about the universe’s expansion and large-scale structure, DESI will also help to set limits on theories related to gravity and the formative stages of the universe, and could even provide new mass measurements for a variety of elusive yet abundant subatomic particles called neutrinos.

“One of the primary ways that we learn about the unseen universe is by its subtle effects on the clustering of galaxies,” said DESI collaboration co-spokesperson Daniel Eisenstein of Harvard University. “The new maps from DESI will provide an exquisite new level of sensitivity in our study of cosmology.”

Mayall’s sturdy construction is perfect platform for new 9-ton instrument
The Mayall Telescope has played an important role in many astronomical discoveries, including measurements supporting the discovery of dark energy and establishing the role of dark matter in the universe from measurements of galaxy rotation. Its observations have also been used in determining the scale and structure of the universe. Dark matter and dark energy together are believed to make up about 95 percent of all of the universe’s mass and energy.

It was one of the world’s largest optical telescopes at the time it was built, and because of its sturdy construction it is perfectly suited to carry the new 9-ton instrument.

“We started this project by surveying large telescopes to find one that had a suitable mirror and wouldn’t collapse under the weight of such a massive instrument,” said Berkeley Lab’s David Schlegel, a DESI project scientist.

Arjun Dey, the NOAO project scientist for DESI, explained, “The Mayall was precociously engineered like a battleship and designed with a wide field of view.”

The expansion of the telescope’s field-of-view will allow DESI to map out about one-third of the sky.

DESI will transform the speed of science with automated preprogrammed robots
Brenna Flaugher, a DESI project scientist who leads the astrophysics department at Fermi National Accelerator Laboratory, said DESI will transform the speed of science at the Mayall Telescope.

“The telescope was designed to carry a person at the top who aimed and steered it, but with DESI it’s all automated,” she said. “Instead of one at a time we can measure the velocities of 5,000 galaxies at a time – we will measure more than 30 million of them in our five-year survey.”

DESI will use an array of 5,000 swiveling robots, each carefully choreographed to point a fiber-optic cable at a preprogrammed sequence of deep-space objects, including millions of galaxies and quasars, which are galaxies that harbor massive, actively feeding black holes.

The fiber-optic cables will carry the light from these objects to 10 spectrographs, which are tools that will measure the properties of this light and help to pinpoint the objects’ distance and the rate at which they are moving away from us. DESI’s observations will provide a deep look into the early universe, up to about 11 billion years ago.

DESI will capture about 10 times more data than a predecessor survey
The cylindrical, fiber-toting robots, which will be embedded in a rounded metal unit called a focal plate, will reposition to capture a new exposure of the sky roughly every 20 minutes. The focal plane assembly, which is now being assembled at Berkeley Lab, is expected to be completed and delivered to Kitt Peak this year.

DESI will scan one-third of the sky and will capture about 10 times more data than a predecessor survey, the Baryon Oscillation Spectroscopic Survey (BOSS). That project relied on a manually rotated sequence of metal plates – with fibers plugged by hand into pre-drilled holes – to target objects.

All of DESI’s six lenses, each about a meter in diameter, are complete. They will be carefully stacked and aligned in a steel support structure and will ultimately ride with the focal plane atop the telescope.

Each of these lenses took shape from large blocks of glass. They have criss-crossed the globe to receive various treatments, including grinding, polishing, and coatings. It took about 3.5 years to produce each of the lenses, which now reside at University College London in the U.K. and will be shipped to the DESI site this spring.

Precise measurements of millions of galaxies will reveal effects of dark energy
The Mayall Telescope has most recently been enlisted in a DESI-supporting sky survey known as the Mayall z-Band Legacy Survey, which is one of four sky surveys that DESI will use to preselect its targeted sky objects. SMU astrophysicists carried out observing duties on that survey, which wrapped up just days ago on Feb. 11, to support the coming DESI scientific results.

Data from these surveys are analyzed at Berkeley Lab’s National Energy Research Scientific Computing Center, a DOE Office of Science User Facility. Data from these surveys have been released to the public at http://legacysurvey.org.

“We can see about a billion galaxies in the survey images, which is quite a bit of fun to explore,” Schlegel said. “The DESI instrument will precisely measure millions of those galaxies to see the effects of dark energy.”


Levi noted that there is already a lot of computing work underway at the Berkeley computing center to prepare for the stream of data that will pour out of DESI once it starts up.

“This project is all about generating huge quantities of data,” Levi said. “The data will go directly from the telescope to the Berkeley computing center for processing. We will create hundreds of universes in these computers and see which universe best fits our data.”

Installation of DESI’s components is expected to begin soon and to wrap up in April 2019, with first science observations planned in September 2019.

“Installing DESI on the Mayall will put the telescope at the heart of the next decade of discoveries in cosmology,” said Risa Wechsler, DESI collaboration co-spokesperson and associate professor of physics and astrophysics at SLAC National Accelerator Laboratory and Stanford University. “The amazing 3-D map it will measure may solve some of the biggest outstanding questions in cosmology, or surprise us and bring up new ones.” — Berkeley Lab and SMU

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SMU study finds earthquakes continue for years after gas field wastewater injection stops

High rates of injection and large volumes can perturb critically stressed faults, triggering earthquakes years after wastewater wells are shut in.

Efforts to stop human-caused earthquakes by shutting down wastewater injection wells that serve adjacent oil and gas fields may oversimplify the challenge, according to a new study from seismologists at Southern Methodist University, Dallas.

The seismologists analyzed a sequence of earthquakes at DFW Airport and found that even though wastewater injection was halted after a year, the earthquakes continued.

The sequence of quakes began in 2008, and wastewater injection was halted in 2009. But earthquakes continued for at least seven more years.

“This tells us that high-volume injection, even if it’s just for a short time, when it’s near a critically stressed fault, can induce long-lasting seismicity,” said SMU seismologist Paul O. Ogwari, who developed a unique method of data analysis that yielded the study results.

The earthquakes may be continuing even now, said Ogwari, whose analysis extended through 2015.

The study’s findings indicate that shutting down injection wells in reaction to earthquakes, as some states such as Oklahoma and Arkansas are doing, may not have the desired effect of immediately stopping further earthquakes, said seismologist Heather DeShon, a co-author on the study and an associate professor in the SMU Earth Sciences Department.

“The DFW earthquake sequence began on Halloween in 2008 — before Oklahoma seismicity rates had notably increased,” said DeShon. “This study revisits what was technically the very first modern induced earthquake sequence in this region and shows that even though the wastewater injector in this case had been shut off very quickly, the injection activity still perturbed the fault, so that generated earthquakes even seven years later.”

That phenomenon is not unheard of. Seismologists saw that type of earthquake response from a rash of human-induced earthquakes in Colorado after wastewater injection during the 1960s at the Rocky Mountain Arsenal near Denver. Similarly in that case, injection was started and stopped, but earthquakes continued.

Such a possibility has not been well understood outside scientific circles, said DeShon. She is a member of the SMU seismology team that has studied and published extensively on their scientific findings related to the unusual spate of human-induced earthquakes in North Texas.

“The perception is that if the oil and gas wastewater injectors are leading to this, then you should just shut the injection wells down,” DeShon said. “But Paul’s study shows that there’s a lot to be learned about the physics of the process, and by monitoring continuously for years.”

Ogwari, DeShon and fellow SMU seismologist Matthew J. Hornbach reported the findings in the peer-reviewed Journal of Geophysical Research in the article “The Dallas-Fort Worth Airport Earthquake Sequence: Seismicity Beyond Injection Period.”

Known DFW Airport quakes number more than 400
The DFW Airport’s unprecedented earthquake clusters were the first ever documented in the history of the North Texas region’s oil-rich geological system known as the Fort Worth Basin. The quakes are also the first of multiple sequences in the basin tied to large-scale subsurface disposal of waste fluids from oil and gas operations.

The DFW Airport earthquakes began in 2008, as did high-volume wastewater injection of brine. Most of the seismic activity occurred in the first two months after injection began, primarily within .62 miles, or 1 kilometer, from the well. Other clusters then migrated further to the northeast of the well over the next seven years. The quakes were triggered on a pre-existing regional fault that trends 3.7 miles, or 6 kilometers, northeast to southwest.

Ogwari, a post-doctoral researcher in the SMU Roy M. Huffington Earth Sciences Department in Dedman College, analyzed years of existing seismic data from the region to take a deeper look at the DFW Airport sequence, which totaled 412 earthquakes through 2015.

Looking at the data for those quakes, Ogwari discovered that they had continued for at least seven years into 2015 along 80% of the fault, even though injection was stopped after only 11 months in August of 2009.

Rate of quakes declined, but magnitude has never lessened
In another important finding from the study, Ogwari found that the magnitude of the DFW Airport earthquakes didn’t lessen over time, but instead held steady. Magnitude ranged from 0.5 to 3.4, with the largest one occurring three years after injection at the well was stopped.

“What we’ve seen here is that the magnitude is consistent over time within the fault,” Ogwari said. “We expect to see the bigger events during injection or immediately after injection, followed by abrupt decay. But instead we’re seeing the fault continue to produce earthquakes with similar magnitudes that we saw during injection.”

While the rate of earthquakes declined — there were 23 events a month from 2008 to 2009, but only 1 event a month after May 2010 — the magnitude stayed the same. That indicates the fault doesn’t heal completely.

“We don’t know why that is,” Ogwari said. “I think that’s a question that is out there and may need more research.”

More monitoring needed for human-induced quakes
Answering that question, and others, about the complex characteristics and behavior of faults and earthquakes, requires more extensive monitoring than is currently possible given the funding allotted to monitor quakes.

Monitoring the faults involves strategically placed stations that “listen” and record waves of intense energy echoing through the ground, DeShon said.

The Fort Worth Basin includes the Barnett shale, a major gas producing geological formation, atop the deep Ellenberger formation used for wastewater storage, which overlays a granite basement layer. The ancient Airport fault system extends through all units.

Friction prevented the fault from slipping for millions of years, but in 2008 high volumes of injected wastewater disturbed the Airport fault. That caused the fault to slip, releasing stored-up energy in waves. The most powerful waves were “felt” as the earth shaking.

“The detailed physical equations relating wastewater processes to fault processes is still a bit of a question,” DeShon said. “But generally the favored hypothesis is that the injected fluid changes the pressure enough to change the ratio of the downward stress to the horizontal stresses, which allows the fault to slip.”

Earthquakes in North Texas were unheard of until 2008, so when they began to be felt, seismologists scrambled to install monitors. When the quakes died down, the monitoring stations were removed.

“As it stands now, we miss the beginning of the quakes. The monitors are removed when the earthquakes stop being felt,” DeShon said. “But this study tells us that there’s more to it than the ‘felt’ earthquakes. We need to know how the sequences start, and also how they end. If we’re ever going to understand what’s happening, we need the beginning, the middle — and the end. Not just the middle, after they are felt.”

Innovative method tapped for studying earthquake activity
Monitors the SMU team installed at the DFW Airport were removed when seismic activity appeared to have died down in 2009.

Ogwari hypothesized he could look at historical data from distant monitoring stations still in place to extract information and document the history of the DFW Airport earthquakes.

The distant stations are a part of the U.S. permanent network monitored and maintained by the U.S. Geological Survey. The nearest one is 152 miles, 245 kilometers, away.

Earthquake waveforms, like human fingerprints, are unique. Ogwari used the local station monitoring data to train software to identify DFW earthquakes on the distant stations. Ogwari took each earthquake’s digital fingerprint and searched through years of data, cross-correlating waveforms from both the near and regional stations and identified the 412 DFW Airport events.

“The earthquakes are small, less than magnitude three,” DeShon said. “So on the really distant stations it’s like searching for a needle in a haystack, sifting them from all the other tiny earthquakes happening all across the United States.”

Each path is unique for every earthquake, and seismologists record each wave’s movement up and down, north to south, and east to west. From that Ogwari analyzed the evolution of seismicity on the DFW airport fault over space and time. He was able to look at data from the distant monitors and find seismic activity at the airport as recent as 2015.

“Earthquakes occurring close in space usually have a higher degree of similarity,” Ogwari said. “As the separation distance increases the similarity decreases.”

To understand the stress on the fault, the researchers also modeled the location and timing of the pressure in the pores of the rock as the injected water infiltrated.

For the various earthquake clusters, the researchers found that pore pressure increased along the fault at varying rates, depending on how far the clusters were from the injection well, the rate and timing of injection, and hydraulic permeability of the fault.

The analysis showed pore-pressure changes to the fault from the injection well where the earthquakes started in 2008; at the location of the May 2010 quakes along the fault; and at the northern edge of the seismicity.

Will the DFW Airport fault continue to slip and trigger earthquakes?

“We don’t know,” Ogwari said. “We can’t tell how long it will continue. SMU and TexNet, the Texas Seismic Network, continue to monitor both the DFW Airport faults and other faults in the Basin.” — Margaret Allen, SMU

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Study: Cells of three aggressive cancers annihilated by drug-like compounds that reverse chemo failure

Wet-lab experiments confirm the accuracy of an earlier computational discovery that three drug-like compounds successfully penetrate micro-tumors of advanced cancers to aid chemo in destroying the cancer.

Researchers at Southern Methodist University have discovered three drug-like compounds that successfully reverse chemotherapy failure in three of the most commonly aggressive cancers — ovarian, prostate and breast.

The molecules were first discovered computationally via high-performance supercomputing. Now their effectiveness against specific cancers has been confirmed via wet-lab experiments, said biochemistry professors Pia Vogel and John G. Wise, who led the study.

Wise and Vogel report the advancement in the Nature journal Scientific Reports.

The computational discovery was confirmed in the Wise-Vogel labs at SMU after aggressive micro-tumors cultured in the labs were treated with a solution carrying the molecules in combination with a classic chemotherapy drug. The chemotherapy drug by itself was not effective in treating the drug-resistant cancer.

“Nature designs all cells with survival mechanisms, and cancer cells are no exception,” said Vogel, a professor in the SMU Department of Biological Sciences and director of SMU’s Center for Drug Discovery, Design and Delivery. “So it was incredibly gratifying that we were able to identify molecules that can inhibit that mechanism in the cancer cells, thereby bolstering the effectiveness of chemotherapeutic drugs. We saw the drugs penetrate these resistant cancer cells and allow chemotherapy to destroy them. While this is far from being a developed drug that will be available on the market anytime soon, this success in the lab gives us hope for developing new drugs to fight cancer.”

The current battle to defeat cancer is thwarted by chemotherapy failure in advanced cancers. Cancer cells initially treated with chemotherapy drugs ultimately evolve to resist the drugs. That renders chemotherapy ineffective, allowing cancers to grow and spread.

Key to cancer cell resistance are often certain proteins typically found in all cells — cancerous or otherwise — that are outfitted with beneficial mechanisms that pump away toxins to ensure a cell’s continued survival. Nature has set it up that these pumps are prevalent throughout the body, with some areas naturally having more of the pumps than others.

“The cancer cell itself can use all these built-in defenses to protect it from the kinds of things we’re using to try to kill it with,” Wise said.

The most common of these beneficial defense mechanisms is a pump protein, P-glycoprotein or P-gp, as it’s called. Another is one seen in breast and many other cancers, called breast cancer resistance protein, BCRP. In the case of cancer cells on the first round of treatment, these pumps are typically not produced in high levels in the cells, which allows chemotherapy to enter most of the cells in the tumor. This often gives what looks like a good result.

Unfortunately, in the cancer cells that don’t die, the chemotherapeutic often changes the cell, which then adapts to protect itself by aggressively multiplying the production of its defensive pumps.

Upon subsequent rounds of chemo, the P-gp and BCRP pumping mechanisms have proliferated. They effectively resist the chemotherapy, which now is much less successful, or not successful at all.

“if enough of the pumps are present, the cancer isn’t treatable anymore,” said Wise, associate professor in the SMU Department of Biological Sciences. Researchers in the field have searched unsuccessfully for compounds to inhibit the pumps that could be used in the clinic as well.

The molecules that Wise and Vogel discovered stopped the pumps.

“They effectively bring the cancer cells back to a sensitivity as if they’d never seen chemotherapy before,” said Vogel. “And our data indicated the molecules aren’t cancer specific. They can be used to treat all kinds of cancers because they inhibit not just the P-gp pump, but also the breast cancer protein pump.”

To test the compounds, the researchers used amounts of chemotherapeutic that would not kill these multi-drug resistant cancers if the pumps were not blocked.

“We wanted to make sure when using these really aggressive cancers that if we do knock out the pump, that the chemotherapy goes in there and causes the cell to die, so it doesn’t just stop it temporarily,” Wise said. “We spent a fair amount of time proving that point. It turns out that when a cell dies it goes through very predictable morphological changes. The DNA gets chopped up into small pieces, and we can see that, and so the nucleus becomes fragmented, and we can see that. Under the microscope, with proper staining, you can actually see that these highly drug-resistant prostate cancer cells, for example, are dead.”

The Scientific Reports article, “Targeted inhibitors of P-glycoprotein increase chemotherapeutic-induced mortality of multidrug resistant tumor cells,” is available open access at this link.

Other co-authors are SMU Ph.D. doctoral candidate Amila K. Nanayakkara, and Courtney A. Follit and Gang Chen, all in the SMU Department of Biological Sciences; and Noelle S. Williams, Department of Biochemistry, UT Southwestern Medical Center, Dallas.

Getting at the heart of the problem
Unique to the experiment is that the molecules were also tested on three-dimensional micro-tumors. That is a departure from the usual cell-culture experiments, which are a two-dimensional film.

In two-dimensional experiments, every cell is exposed to the chemotherapeutic because the film is just one layer of cells thick. That method ignores one of the key challenges to reversing tumors — how to get drugs into the middle of a tumor, not just on its surface.

“We show that with the help of our inhibitor compounds, we actually make the tumor penetrable to chemotherapeutic,” Vogel said. “We can kill the cells in the middle of the tumor.”

A pathway to personalized medical treatments
Chemotherapy’s harmful side effects on non-cancerous organs is well-known. The discovery of molecules that target a specific pump may mitigate that problem.

A patient’s tumor can be sampled to see which pump is causing the drug resistance. Then the molecule that knocks out that specific pump can be added to the chemotherapy.

“That means you don’t open the door wide to toxins in the central nervous system,” Wise said. “That has some real implications for the future and for personalized medicine. In most of the previous clinical trials, inhibitors have opened the brain up to toxins. From what we can tell so far, our inhibitors do not increase the toxicity of chemotherapeutics in normal cells.”

An audacious discovery
P-gp is present in one form or another in everything that lives.

“It’s in your dog, it’s in your cat, it’s in yeast cells, it’s in bacteria, it’s everywhere,” Wise said. “Why is it everywhere? Because it’s a really wonderful solution to the problem of getting toxins out of a cell. P-gp is a tremendously sophisticated evolutionary solution to that problem. And as with most things in biology that work well, everybody gets it, because if you don’t have it, you didn’t survive.”

Biologists say that P-gp can pump out 95 of 100 chemotherapeutics, indicating it can grab almost any drug and throw it out of a cell.

“So there’s a certain audacity to say that we can use a computer and target one part of this protein — the motor — and totally avoid the part of the protein that has evolved to pump almost anything that looks like a drug out of the cell,” Wise said. “That’s an audacious claim and the findings surprised us.”

In their computational and wet-lab experiments, Wise and Vogel searched for molecules that inhibit ATP hydrolysis — the chemical energy reaction that powers the P-gp pump.

“We targeted the motor of the pump instead of the pump part of the pump because almost all the clinical trial failures in other studies were actually compounds that targeted the pump part of the pump — and they would just slow down the pumping of the chemotherapeutic,” Vogel said. “The time was ripe to do these structural models. We hypothesized that we could completely avoid the pumping mechanism and just target the motor.”

Computational method highly predictive
The wet-lab experiments confirmed the accuracy of the computational findings, Vogel said.

“The predictiveness of the computational methods was really high,” she said. “It completely exceeded my expectations. We had selected certain molecules that were predicted in those computational experiments to interact with the pump in certain ways and not in others, and we could show in our wet-lab experiments that the predictions were spot on.”

Fascinated by the novel approach to the research, the National Institute of General Medical Sciences funded much of the research.

Wise and Vogel tapped the high-performance computing power of SMU’s Maneframe, one of the most powerful academic supercomputers in the nation. Wise sorted through 15 million commercially available drug-like compounds made publically available in digital form from the pharmacology database Zinc at the University of California, San Francisco.

Then, again using ManeFrame, Wise ran the compounds through a computer-generated model of P-gp. The virtual model, designed and built by Wise, is the first computational microscope of its kind to simulate the actual behavior of P-gp in the human body, including interactions with drug-like compounds while taking on different shapes. He reported the dynamic functioning of the model in 2015 in the journal Biochemistry in “Multiple drug transport pathways through human P-glycoprotein.”

Process of elimination finds needle in the haystack
Out of 15 million drug-like compounds that were virtually screened, the researchers found 180,000 that in the computer were predicted to interact strongly with the ATP harvesting power plant part of the pump motor. From those, Wise and Vogel eliminated the ones that interact well with the pump part. Roughly 0.15 percent survived — several hundred.

“So that tells you how promiscuous that binding site is for compounds,” Wise said.

From there, they bought and tested in the lab a number of the remaining molecules.

“It was a process of elimination,” Vogel said. “Of the first 38 we tested, we found four. And because of the computational approach we took, it made failure relatively cheap. This is proof of principle that at least in those cases the compounds behave exactly in the lab as predicted in the computer. Which thrills the heck out of me — I never, ever would have thought that.”

The Vogel and Wise research labs are part of the Center for Drug Discovery, Design and Delivery in SMU’s Dedman College. The center’s mission is a novel multi-disciplinary focus for scientific research targeting medically important problems in human health. — Margaret Allen, SMU

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Female students exposed briefly to charismatic career women are inspired to pursue male-dominated field

Easy, inexpensive experiment briefly sent inspiring female role models into intro to econ classes and sharply increased college female interest in the male-dominated, well-paying field of economics.

A low-budget field experiment to tackle the lack of women in the male-dominated field of economics has been surprisingly effective, says the study’s author, an economist at Southern Methodist University, Dallas.

Top female college students were inspired to pursue a major in economics when exposed very briefly to charismatic, successful women in the field, according to SMU economist Danila Serra.

The results suggest that exposing young women to an inspiring female role model succeeds due to the mix of both information and pure inspiration, Serra said.

“The specific women who came and talked to the students were key to the success of the intervention,” she said. “It was a factor of how charismatic and enthusiastic they were about their careers and of how interesting their jobs looked to young women.”

Given the simplicity and low-cost of the intervention, similar experiments could be easily conducted in other male-dominated or female-dominated fields of study to enhance gender diversity.

Serra’s results showed that among female students exposed to the enthusiastic mentors there was a 12-percentage point increase in the percentage of female students enrolling in the upper-level Intermediate Microeconomics course the following year — a 100% increase, or doubling, for that demographic.

Not surprisingly, given that the intervention was targeted to female students, Serra found that the role model visits had no impact on male students.

But astonishingly it had the greatest impact on high-achieving female students.

“If we restrict the analysis to the top female students, the students with a GPA of 3.7 or higher, the impact is remarkable — it is a 26 percentage points increase,” Serra said. “So this intervention was especially impactful on the top female students who perhaps were not thinking about majoring in economics.”

The results were very surprising to Serra, an assistant professor in the SMU Department of Economics in Dedman College who teaches the upper-level class Behavioral and Experimental Economics. Serra’s research relies on laboratory and field experiments, a relatively new methodology in the field of economics. She launched and is co-leader of the Laboratory for Research in Experimental Economics at SMU.

“I didn’t think such limited exposure would have such a large impact,” Serra said. “So this is telling me that one of the reasons we see so few women in certain fields is that these fields have been male-dominated for so long. This implies that it is very difficult for a young woman to come into contact with a woman in the field who has an interesting job in the eyes of young women and is enthusiastic about her major and her work. Young men, on the other hand, have these interactions all the time because there are so many male economics majors out there.”

Co-author on the research is Catherine Porter, associate professor of economics at Heriot-Watt University, Edinburgh, Scotland, and Serra’s former Ph.D. classmate at the University of Oxford.

“The gender imbalance in economics has been in the news a lot lately, and much of the discussion has been very negative,” said Porter. “This study offers something positive: a cheap way of improving the gender balance. The results can hopefully be used by other schools in order to redress the low numbers of women that major in economics – women have a lot to offer and should consider economics as a subject that is interesting and varied for a career.”

Serra reported the findings, “Gender differences in the choice of major: The importance of female role models,” on Jan. 6 in Philadelphia at the 2018 annual meeting of the Allied Social Sciences Association. Hers is one of many findings on gender and gender differences in economics presented at a session organized by the Committee for the Status of Women in the Economics Profession.

Inspiring the individual is the best tool to recruit and retain
Serra launched the study after SMU was one of 20 U.S. universities randomly chosen by Harvard economics professor Claudia Goldin for the Undergraduate Women in Economics Challenge. The project awarded each university a $12,500 grant to develop a program freely chosen by the universities to test the effectiveness of a deliberate intervention strategy to recruit and retain female majors.

Nationally, there’s only about one woman for every three men majoring in economics. SMU has a large number of economics majors for a school of its size, with 160 a year. The gender imbalance, however, is greater at SMU than the national average, with only one woman to every four men.

Serra developed her intervention based on her own experience as a Ph.D. student at the University of Oxford several years ago.

“I started thinking about role models from my personal experience,” Serra said. “As a student, I had met many female professors in the past, but my own experience taught me that inspiration is not about meeting any female professor — it’s about meeting that one person that has a huge charisma and who is highly inspiring and speaks to you specifically.”

Serra said that’s what she experienced as a graduate researcher when she first met Professor Abigail Barr, who later became her Ph.D. advisor.

“I know for a fact that that is why I decided to do a Ph.D. in economics, because I was greatly inspired by this person, her experiences and her research,” she said. “So I thought it would be interesting to see whether the same could work for a general student population.”

Two inspiring women role models, 15 minutes, four classrooms
Serra asked two of her department’s top undergraduate female economics students to take the lead in choosing the role models.

The students, Tracy Nelson and Emily Towler, sorted through rosters of SMU economics alums and shortlisted 18 men and women that they thought were working in interesting fields – which purposely excluded stereotypical jobs in banking and finance – and then carried out scripted interviews with a subset of who agreed to be interviewed via Skype to get additional information about their career path and to assess their charisma.

The students ultimately found two alumnae, Julie Lutz and Courtney Thompson, to be the most inspiring. Lutz, a 2008 graduate, started her career in management consulting but, shortly after, decided to completely change her career path by going to work for an international NGO in Nicaragua, and then as a director of operations at a toy company based in Honduras. Lutz now works in Operations at a fast-growing candy retail company. Courtney Thompson, class of 1991, has had a stellar career in marketing, becoming the senior director of North American Marketing and Information Technology at a large international communications company, with the unique claim of being not only a female econ major at a time when that was exceedingly rare, but also African American in a white dominated field.

Serra invited each woman to speak during the Spring 2016 semester for 10 to 15 minutes to four Principals of Economics classes that she had randomly selected from a set of 10. The Principles classes are very popular, with about 700 students total from a variety of desired majors, and are typically gender balanced. The imbalance, said Serra, starts the following year with Intermediate Microeconomics, which is a requirement for upper-level economics courses and so is a good indicator of a desire to major in economics.

Serra offered each role model an honorarium for speaking, but each woman declined and indicated they were happy to be back on campus sharing with students. Serra told the speakers nothing of the purpose of the research project, but encouraged each one to explain to the class why they majored in economics and to be very engaging. She directed them to approach the students with the following question in mind: “If you had to convince a student to major in economics, what would you say?”

Thompson, Serra said, during her college days played SMU’s costumed Peruna mascot, and today retains a “bubbly, big personality, that makes her extremely engaging.” In her classroom visits, Thompson described her experience working and being extremely successful in marketing with an economics degree, while being surrounded by business majors. Lutz, being still in her 20s, was very easy for the young women in the classrooms to identify with, and her experience working in the non-profit and in developing countries may have been especially appealing to them.

Young women judge best who will inspire them
Serra believes that a key to the success of the intervention was the fact her two female economics students actively participated in the selection of the role models.

“The most important thing about the project was that I realized I needed current female students to choose the role models,” Serra said. “I’m not that young anymore, so I’m probably not the best person to recognize what is inspiring to young women. I think young female students are in the best position to tell us what is most inspiring to them.”

In November the directors and officers of the International Foundation for Research in Experimental Economics honored Serra as the inaugural recipient of the $50,000 Vernon L. Smith Ascending Scholar Prize. The Smith Prize is described by the foundation as a “budding genius” award.

For her highly cited corruption research, Serra uses lab experiments to study bribery, governance and accountability, questioning long-standing assumptions. Some of her findings are that corruption declines as perpetrators take into account social costs of their illegal activities, and as victims share information about specific bribery exchanges through online reporting. Serra’s current research agenda also includes experimental work on gender differences in preferences, behaviors and outcomes. — Margaret Allen, SMU