YSM Issue 93.4 Full Magazine
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Yale Scientific
THE NATION’S OLDEST COLLEGE SCIENCE PUBLICATION • ESTABLISHED IN 1894
DECEMBER 2020 VOL. 93 NO. 4 • $6.99
22
SEASONS ON
THE SAVANNA
NO MORE STRIKING
10
OUT WITH STROKES
SURVIVING
14
MASS EXTINCTIONS
ADJUSTING
19
FOR MISTAKES
THE SECRET OF
28
SALTED CARAMEL
ABLE O F
VOL. 93 ISSUE NO. 4
COVER
22
A R T
I C L E
Seasons on the Savanna
Angelica Lorenzo
A Yale researcher has confirmed the effects of dietary strategies on herbivore populations of the
African savannas. This new finding will impact the way ecologists view population dynamics and
the conservation of savanna ecosystems.
12 A Molecular Whodunit in the Liver
Alice Huang
What are the root causes of type 2 diabetes? Researchers find that accumulation of fatty acids in the
liver may induce hepatic insulin resistance, a discovery that may lead to novel therapies for diabetes.
14 Surviving Mass Extinctions
Lucas Loman
As human activity drives up extinction rates, understanding how mass extinctions affect surviving
organisms has become a pressing and controversial topic.
16 Drugging the Undruggable
Jenny Tan
Do you know what it takes to discover a drug? Take a glimpse of how a team of researchers at the
Yale School of Pharmacology discovered a possible treatment pathway for Duchenne muscular
dystrophy (DMD).
19 Adjusting for Mistakes
Agastya Rana
Can we build a useful quantum computer? A Yale team brings us a step closer to success by
implementing a crucial piece of the puzzle.
2 Yale Scientific Magazine December 2020 www.yalescientific.org
CONTENTS
More articles online at www.yalescientific.org & https://medium.com/the-scope-yale-scientific-magazines-online-blog
4
6
25
34
Q&A
NEWS
FEATURES
SPECIALS
Why did I get sick when my roommate didn't? • Lauren Chong
Can we generate carbon-free energy from small temperature changes? •
Madison Houck
Asphalt's Fault • Victoria Ouyang
The Single Molecule Electret • Kelly Chen
WHO You Talk to Affects HOW You Talk • Eric Linh
Fabrics of the Future • AnMei Little
The Mystery of Molecular Machinery • Selma Abouneameh
Through the Pipes • Phoebe Liu
No More Striking Out with Strokes • Jerry Ruvalcaba
Treat Yourself • Victoria Vera
Planetary Protection • Anavi Uppal
Hunting Ghosts • Murilo Dorion
Metallizing Diamond • Isabel Trindade
The Secret of Salted Caramel • Elisa Howard
The Levels of Learning at Daycare • Alexandra Haslund-Gourley
Curly the Robot • Jenny Mao
Counterpoint: Your COVID-19 Test Result May Be Lying to You • Veronica Lee
Counterpoint: Climate Change is Worse Than You Thought • Charlotte Leakey
Undergraduate Profile: Alex Cohen '21, Kendra Libby '21, Jason Yang '21 •
Alex Dong & Athena Stenor
Science in the Spotlight: Pandemic: How to Prevent an Outbreak • Dilge Buksur
Science in the Spotlight: Owls of the Eastern Ice by Jonathan Slaght •
Annika Salmi
www.yalescientific.org
December 2020 Yale Scientific Magazine 3
WHY DID I GET SICK WHEN
MY ROOMMATE DIDN’T?
By Lauren Chong
CAN WE GENERATE CARBON-
FREE ENERGY FROM SMALL
TEMPERATURE CHANGES?
By Madison Houck
As global temperatures rise, small temperature changes
might provide a new way for us to generate power. A
recent project, headed by Yu Hushino and Teppei Yamada,
has engineered a thermocell—a device that generates electricity
from heat—that might make this source of affordable and efficient
carbon-free energy closer than you think.
The cell uses poly(N-isopropylacrylamide) hydrogels as
affordable materials. A hydrogel is a large molecule that can hold
water. At low temperatures, acids attached to the hydrogels lose
protons to water in the environment. Poly(N-isopropylacrylamide)
hydrogels, however, are special because they clump together and
shut water out when heated. Therefore, at high temperatures, with
less water, protons stay attached to the acids. “The pH shift [due to
the changing concentration of free protons] is the most important
phenomenon we use,” Yu said.
But how does that pH shift generate voltage? The solution also
contains compounds that transfer electrons and protons. So, if
there are more protons on one side of the cell, the compounds lose
electrons, creating a current. “It’s a shift of equilibrium,” Teppei
said. The greater the pH shift, the more voltage is generated.
Solar power is one of the main ways to generate electricity
without fossil fuels. However, solar panels are unable to convert
all of their heat energy into power. That’s where Yu and Teppei’s
thermocell comes in. “Using our device to collect heat from carbonfree
energy is one of the most interesting future applications,” Yu
said. Their device could use otherwise “wasted” heat to create a
temperature change large enough to generate power, improving
the efficiency of carbon-free energy sources. ■
Whether it’s roommates, suitemates, or friends, students
at Yale are constantly in the vicinity of others. Thus,
it’s surprising whenever one person falls ill to viral
infections such as the common cold, yet their roommate, who
shares their personal space to the greatest extent, does not. Why
is that? It is all embedded in a concept of neutrophils, a type of
white blood cell that fights pathogens, and the response of nasal
mediators in the mucosa, the tissue lining the lung.
Researchers at the University College London administered fiftyeight
participants with the respiratory syncytial virus (RSV), a cause
of neutrophilic lung inflammation, then analyzed the immune cells
and proteins in their nasal mucosa. Only fifty-seven percent of the
participants actually displayed symptoms of infection. Those infected
possessed a neutrophilic inflammatory signal beforehand. After
infection, they repressed an early immune response but later released
cytokines, cell signaling proteins, that induced inflammation. In
contrast, those who were not susceptible to infection had much lower
neutrophil levels before infection and had an increased immune
response a couple of days after infection. The researchers tested on
mice and found a similar correlation: neutrophil response prior to
exposure to the virus increased chances of infection.
The researchers propose that their findings might apply to viruses
beyond RSV. In the unprecedented times of SARS-CoV-2, where
individual responses are also known to vary widely, your neutrophilic
inflammation might help determine whether or not you’ll fall sick
when your roommates, friends, or family members do. ■
Habibi, M.S., Thwaites, R.S., Chang, M., Jozwik, A., Paras,
A., Kirsebom, F., Varese, A., Owen, A., Cuthbertson, L.,
James, P., Tunstall, T., Nickle, D., Hansel, T.T., Moffatt,
M.F., Johansson, C., Chiu, C., & Openshaw, P.J.M. (2020).
Neutrophilic Inflammation in the Respiratory Mucosa
Predisposes to RSV Infection. Science, 370(6513), https://
doi.org/10.1126/science.aba9301
Guo, B., Hoshino, Y., Gao, F., Hayashi, K., Miura, Y., Kimizuka, N.,
& Yamada, T. (2020). Thermocells Driven by Phase Transition
of Hydrogel Nanoparticles. Journal of the American Chemical
Society 142(41), 17318–22. https://doi.org/10.1021/jacs.0c08600
Service, R.F. (2020, May 11). New solar panels suck water
from air to cool themselves down. Retrieved November 08,
2020, from https://www.sciencemag.org/news/2020/05/
new-solar-panels-suck-water-air-cool-themselves-down
4 Yale Scientific Magazine December 2020 www.yalescientific.org
e Editor-in-Chief
peaks
AN EVENTFUL YEAR
As we end a year that has been by all measures tumultuous, we can look back
and find comfort in how far we have come together. For many of us on
the Yale Scientific masthead, the rituals that accompany the publication of
each YSM issue—pitch meeting, writers’ meetings, layout week, etc.—have provided
some normalcy to our academic experience, for which we are grateful.
We were pleasantly surprised to find that progress in all areas of science has
continued relatively unabated through this difficult time. We continue to showcase
the very best of science being done at Yale and beyond, from the environmental
impact of asphalt (p. 6), the neuroscience of interpersonal interactions (p. 7), to
the biochemistry of the classic combination of salted caramel (p. 28). Our cover
article by Angelica Lorenzo features a new model that describes how seasonal
diet adaptations and migration, rather than predatory pressure as previously
assumed, drive herbivore population changes on the African savanna (p. 22). This
mathematically driven insight enhances our understanding of an ecology that is
being particularly threatened and transformed by climate change. Another fulllength
tells the story of identifying a single molecule that links fatty liver disease to
diabetes (p. 12); yet another article spotlights efforts at the Yale Quantum Institute
to reduce errors for qubits in quantum computing (p. 19). From minute to vast
time and length scales, each of these research findings strongly impact and inform
our quest to understand and interact with the natural world.
Interspersed throughout the magazine are a few pieces on COVID-19-related
research—how sewage samples aid in measuring COVID-19 progress (p. 9),
immune response features that keep some unaffected by the common cold (p.
4), and the reliability of COVID-19 tests (p. 34). The recent approvals of the
COVID-19 vaccines represent a step forward in our fight against the pandemic,
and also a landmark achievement in the development of the mRNA vaccine
paradigm. Yet, as the nation continues to record new highs in case numbers
every day, a very strong case remains for us to simply follow health guidelines, be
considerate to others, and use (scientifically-driven) common sense.
I would like to end, as with the past two issues, by expressing my deepest
gratitude to our masthead and contributors, in particular to the first-years whose
unmistakable zeal for communicating science make them a welcome force in the
YSM community. A big thank you to our subscribers, Yale departments, and the
Yale Science and Engineering Association for their support, with which the nation’s
oldest college science publication will continue to thrive, through thick and thin.
bout
he Art
Marcus Sak, Editor-in-Chief
This issue’s cover features the balance
between two main players of
the savanna biome: herbivores and
vegetation. In a mix of earth-toned
trees, shrubs, and grasses, the diverse
grazers of savannas can modulate
their feeding habits and thus
their population dynamics.
Sophia Zhao, Cover Artist
MASTHEAD
December 2020 VOL. 93 NO. 4
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OUTREACH
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STAFF
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Elisa Howard
ADVISORY BOARD
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NEWS
Materials Science / Physics
ASPHALT’S FAULT
THE SINGLE
MOLECULE ELECTRET
RESEARCHERS FIND ASPHALT CONTRIBUTES
TO AIR POLLUTION IN URBAN AREAS
BY VICTORIA OUYANG
IMAGE COURTESY OF PXFUEL
Asphalt-based materials are almost everywhere in U.S. urban
areas, whether they are used for road-paving or roofing
applications. A recent Yale study, led by Drew Gentner,
associate professor of Chemical and Environmental Engineering,
found that asphalt-related materials are a significant source of air
pollutants, even days after initial application.
The team of researchers placed asphalt-based materials in controlled
chambers that simulated a range of temperature and sunlight
conditions typically encountered by asphalt in urban areas. They then
recorded and measured the chemical composition of the organic gases
emitted using high resolution analytical chemistry.
The results revealed that asphalt produces larger organic compounds
that lead to the formation of secondary organic aerosols (SOA), a key
component of PM2.5—an air pollutant composed of fine, particulate
matter that poses a great public health risk. Additionally, asphalt-related
emissions showed a strong dependence on temperature, meaning that
asphalt released more harmful chemicals as temperatures rose.
Contributions of traditional combustion-related sources to air
pollution have decreased with successful control of sources like motor
vehicles or power generation. However, that decrease leads to higher
contributions from other anthropogenic sources, such as asphalt.
Genter’s research suggests that emissions from asphalt may increase
with rising urban temperatures, amplifying asphalt’s impact on urban
air quality over time. Genter emphasized that there is still a lot more
information to gather in order to make cities more environmentallyfriendly.
“Asphalt is just one piece of the current-day urban SOA puzzle
with motor vehicles and volatile chemical products, like cleaning
products or paints, also being major contributors,” Genter said. ■
Khare, P., Machesky, J., Soto, R., He, M., Presto, A. A., &
Gentner, D. R. (2020). Asphalt-related emissions are a major
missing nontraditional source of secondary organic aerosol
precursors. Science Advances, 6(36), eabb9785.
McDonald, B. C., De Gouw, J. A., Gilman, J. B., Jathar, S. H.,
Akherati, A., Cappa, C. D., ... & Cui, Y. Y. (2018). Volatile
chemical products emerging as largest petrochemical source
of urban organic emissions. Science, 359(6377), 760-764.
BUILDING FOUNDATIONS FOR
ADVANCED TECHNOLOGY
BY KELLY CHEN
IMAGE COURTESY OF MARK REED
What are the limitations of our current technology?
With current integrated circuit technology, the
fundamental limit is the heat dissipated as transistors
switch; there is a limit to the number of transistors one can
pack onto a chip without melting the chip. One device with the
potential to dissipate less energy is the single molecule electret.
Along with collaborators, Mark Reed, Yale professor of
electrical engineering and applied physics, explored the single
molecule electret, which is a carbon-82 cage-like structure with
a gadolinium atom inside it. By applying an electric field to the
structure and positioning the gadolinium atom in different parts
inside the cage, the atom can interact with the cage and cause
a polarization that persists after the electric field is removed.
“We found that that polarization [of the device] could be
switched,” Reed said. “It doesn’t go on and off, but it changes
the direction of the polarization, changing the way the current
flows through the device.” The single molecule electret acts as
a piece of memory, with one polarization representing a digital
0 in binary computing language and another representing
1. Additionally, a single molecule electret dissipates less heat
than a single transistor, and the size of these electrets are on
the nanoscale, allowing for creation of smaller, more stable
electronics. However, producing these devices is hard; currently,
making the electret only works once out of every fifty tries.
Nonetheless, the ability to create these single molecule
electrets is amazing in itself. “It’s important to first understand
the physics of what’s going on, try to explain that, and then
hopefully we’ll find a way to fabricate [more advanced
technology],” Reed said. ■
Zhang, K., Wang, C., Zhang, M., Bai, Z., Xie, F., Tan, Y., . . .
Wang, B. (2020). A Gd@C82 single-molecule electret.
Nature Nanotechnology, 15(12), 1019-1024. https://doi.
org/10.1038/s41565-020-00778-z
6 Yale Scientific Magazine December 2020 www.yalescientific.org
Psychology / Materials Science
NEWS
ILLUSTRATION COURTESY OF
ANMEI LITTLE
ILLUSTRATION COURTESY OF ANMEI LITTLE
WHO YOU TALK TO
AFFECTS HOW YOU TALK
FASHION FORWARD:
ROBOTIC FABRICS
BRAIN ACTIVITY VARIATION BASED ON OTHERS
BY ERIC LINH
You know that feeling when you’re having a really good
conversation with someone, and it seems like your brains
are on the same wavelength? Well, there’s actually a
term for that. Neural coupling is the mechanism by which we
can measure synchronization in brain activity between two
individuals. In a study done by the Yale School of Medicine,
neuroscientist Joy Hirsch explores the phenomenon, and how it
differs when there is high versus low socioeconomic disparity in
a dyad, a group of two individuals.
The Hirsch lab has developed a novel technique for brain imaging
known as functional near infrared spectroscopy (fNIRS), which
uses wearable headpieces that can sense brain activity of multiple
users. This sharply contrasts the limitations of functional magnetic
resonance imaging (fMRI), which is much less convenient in
gauging human interactions. fNIRS allows neuroscientists to engage
with the brain during social interactions that underpin the majority
of our daily lives. Their revolutionary research paves the way for
future studies in two-person neuroscience.
The social implications of her study are quite interesting. The
dorsolateral prefrontal cortex, which is hypothesized to regulate the
deliberation of our speech, has significantly more activity in high
disparity dyads. Coherence, or the measurement of neural coupling,
was also greater in high disparity dyads. What are the implications?
“We as humans are wired to actually manage our disparity in a
positive way. We can, based on our neurophysiology, maintain or
create positive experiences with people who are different from you.
We have the neuro-ability to embrace diversity,” Hirsch said. ■
Descorbeth, O., Zhang, X., Noah, J., & Hirsch, J. (2020,
September 03). Neural processes for live pro-social
dialogue between dyads with socioeconomic disparity.
Retrieved November 05, 2020, from https://academic.
oup.com/scan/article/15/8/875/5900886
Interview with Dr. Joy Hirsch. (2020, October 29).
www.yalescientific.org
FABRICS OF THE FUTURE
BY ANMEI LITTLE
For centuries, fabrics have been simple, yielding materials,
but Professor Rebecca Kramer-Botillglio and her research
lab, the Yale Faboratory, seek to integrate robotics with
fabric. Recently, Kramer-Botillglio and lead author Trevor
Buckner developed robotic fabrics that can be programmed to
change shape or stiffness. These fabrics have applications from
deployable structures to assistive clothing.
The robotic fabrics consist of three main components. The
first is a flattened wire made of shape memory alloy, allowing
for control over wire bending. For example, one wire in the
fabric wings can be programmed to extend upon electrical
heating. Another wire can be programmed to wrap the wing
around the plane body. Specific heating controls whether
plane wings are extended or wrapped.
The second component is variable stiffness fibers created with
Field’s metal mixed in epoxy. This material allows the fabric
to hold its shape, becoming softer in warm temperatures and
stiffer in cool temperatures. Kramer-Botillglio and Buckner
demonstrated this through a flat fabric that transforms into a
table-like conformation upon heating (~100 °C). Rapid cooling
stiffens the fabric into a load-bearing structure.
The last component of the fabric is electrically conductive
ink, which attaches sensors to the fabric to detect curvature and
resistance to stretch. The lab demonstrated this “smart” fabric by
developing a fabric that compresses if a fiber is damaged, thus
providing immediate medical assistance.
The challenge with working with fabric, Buckner argues, is
optimizing its load capacity since the material is so thin. Once
optimized, however, its structural and assistive applications in
robotics could drastically expand. The lab’s next project is to create
a robotic fabric that can walk and carry its own battery. ■
Buckner, T. L., Bilodeau, R. A., Kim, S. Y., & Kramer-Bottiglio, R.
(2020). Roboticizing fabric by integrating functional fibers.
Proceedings of the National Academy of Sciences, 117(41),
25360–25369. https://doi.org/10.1073/pnas.2006211117
December 2020 Yale Scientific Magazine 7
NEWS
Microbiology
THE MYSTERY OF
MOLECULAR
MACHINERY
Understanding the
Bacterial Flagellar Motor
BY SELMA ABOUNEAMEH
It may seem like a simple concept—bacteria have to be able to move
in order to infect their host. However, for decades, scientists have
been scratching their heads, attempting to uncover the intricate
workings of the molecular motor mechanisms that allow bacteria to
move in their signature “run-and-tumble” pattern. The complex that
allows bacteria to achieve this movement, known as the bacterial
flagellar motor, is of particular importance due to the effect it has on
the ability of potentially life-threatening bacteria to infect organisms.
In a paper recently published in Nature Structural & Molecular Biology,
researchers proposed a novel mechanism by which they believe the
spirochete Borrelia burgdorferi, the causative agent of Lyme Disease,
switches the rotation of its flagellar motor from counterclockwise
(which allows bacteria to move in long runs), to clockwise (which
allows bacteria to randomly tumble).
In this study, researchers were able to visualize high-resolution
flagellar motor structures in two mutant strains of B. burgdorferi. The
strains of bacteria, ∆cheX and ∆cheY3, were mutant for two types of
chemotaxis proteins, which regulate the direction of flagellar rotation. In
each of these mutants, the bacteria were locked in counterclockwise or
clockwise rotations, respectively. In order to resolve the structures of the
bacterial flagellar motor, as well as to visualize the changes that occurred
when the chemotaxis proteins were subjected to varying conditions,
the researchers used a combination of cryo-ET imaging, subtomogram
averaging, and genetic modification of the bacterial cells.
After visualizing the flagella motor structures, the researchers
noticed that their results contradicted previous findings. “Before we
resolved the high-resolution flagellar motor structures, we had some
expectations on the structures based on the previous publications,”
said Yunjie Chang, a researcher at Yale University who authored
the paper. Chang pointed out a few major surprises. First, the team
noticed that the flagellar rotor ring subunits form a “hand-in-hand”
structure at the base, as opposed to a “donut structure” that had been
proposed in previous work. In addition, Chang noted that the stator
unit, the part of the flagella that powers the motor, remains the same
regardless of the direction of rotation. This finding contradicted
previous research, which had suggested that the conformation of
the stator unit changed along with the direction of rotation of the
IMAGE COURTESY OF CDC/UNSPLASH
flagella. In the end, these novel pieces of structural information led
researchers to propose a novel mechanism. “I think [that] is really
the intriguing part of doing structural biology research,” Chang said.
The mechanism proposed by the authors is as follows: the
phosphorylation of CheY3 to CheY3-P proteins promotes binding
to FliM, a switch protein that forms the rotor of the bacterial flagella.
This complex then interacts with two other chemotaxis proteins,
CheY and CheZ; these domains interact with other components of
the motor that are able to determine the direction of flagellar rotation
as either clockwise or counter-clockwise. This contact then induces
the remodeling of another switch protein, FliG2. The conformational
changes in FliG2 result in an inward flow of H+ ions causing the torque
generator of the bacterial flagella to rotate. The interaction between the
torque generator and the switch complex allows the flagella to switch
rotational direction. While scientists previously had observed that the
binding of the cheY protein to the FliM switch protein induced the shift
from counterclockwise to clockwise rotation, the exact mechanism
behind the rotational switching was unknown.
While this is indeed a fascinating mechanism, the researchers
acknowledge that much more work is needed in order to confirm or deny
this theory of rotational switching in bacterial flagella. If proven true,
this theory ultimately helps us to understand the mechanism behind
one of the most interesting and efficient pieces of molecular machinery.
“The flagellar motor itself is a complex and fascinating nanomachine,
which can convert the electrochemical potential difference across the
cell membrane into mechanical work with almost [full] efficiency, and
can rotate as fast as 1,700 revolutions per second, which is much faster
than that of a Formula One racing car engine,” Chang said. By better
understanding this intriguing mechanism, scientists may be able to
better understand bacterial virulence and invasion of host organisms. ■
Chang, Y., Zhang, K., Carroll, B.L., Zhao, X., Charon, N.W.,
Norris, S.J., Motaleb, M.A., Li, C., & Liu, J. (2020). Molecular
mechanism for rotational switching of the bacterial flagellar
motor. Nature Structural & Molecular Biology, 27, 1041–7.
https://doi.org/10.1038/s41594-020-0497-2
8 Yale Scientific Magazine December 2020 www.yalescientific.org
Public Health
NEWS
THROUGH
THE PIPES
Wastewater Treatment
and COVID-19
BY PHOEBE LIU
ILLUSTRATION COURTESY OF KAREN LIN
Most people would turn away at the mention of sewage
sludge, the semi-solid residual material that’s left
behind after wastewater has been processed at a water
treatment plant. But a team of researchers led by Yale Professor
of Chemical and Environmental Engineering Jordan Peccia has
found that the presence of SARS-CoV-2 RNA in wastewater
sludge can track community infection dynamics—and do so a
few days in advance of test results.
The study, published in Nature Biotechnology, found a
correlation between viral concentrations in wastewater and
testing and hospitalization data in New Haven over ten weeks
of sampling, from March 19 to June 1. The study showed that
wastewater sludge is a reliable indicator—and even predictor—
of rates of coronavirus infection. The team continues to sample
sewage sludge daily from six water treatment plants across
Connecticut. Their research currently informs the statewide
coronavirus response plan, with data made publicly available on
the YaleCOVIDwastewater.com website.
“Not only are you able to see this increase in wastewater
concentrations during an outbreak that you might not necessarily
see in the cases quite yet, but we can take that case data and
we can adjust it, so that you can kind of predict what’s going to
[happen] and get a week’s head start on things,” Peccia said.
Through their research, the team found that sludge results led the
number and percentage of positive tests by date of specimen collection
by zero to two days, hospital admissions by one to four days, and the
number of positive tests by report date by six to eight days.
Peccia explained that there is a history of looking to sewage
sludge for the presence of pathogens, most recently to monitor
polio infections, because pathogens are often passed from humans
to their wastewater. Early on in the coronavirus pandemic, testing
shortages and delays made it difficult to accurately represent
true rates of coronavirus infection, and wastewater is widely
representative of large populations. Nearly everyone’s sewage
ends up at a centralized water treatment plant—New Haven’s plant
alone, for example, serves two hundred thousand people. Further,
according to Peccia, coronavirus had been detected in wastewater
www.yalescientific.org
through other, unrelated, projects. Thus, using sewage sludge to
track coronavirus infections was “only natural,” Peccia said.
It typically takes the research team about twelve hours for the
team to get from a sewage sludge sample to a number of copies
of viral RNA present in that sample, with daily sampling and
deliveries four times a week, according to Peccia. On delivery
days, before 7 a.m., the team’s courier drives around the state
to pick up sewage sludge samples from each site—an almostthree-hundred-mile
route that includes New Haven, Stamford,
Hartford, Norwich, Bridgeport and New London—before the
samples are dropped off at the lab around 11 a.m. Then, it takes
four to five hours to extract RNA from the samples through a
complex filtration process. Isolated RNA pellets are dissolved
in ribonuclease-free water, and total RNA concentration is
calculated by spectrophotometry, a type of electromagnetic
spectroscopy that tests how much a chemical substance absorbs
light to determine the amount present. Using qRT–PCR, the team
then measures the presence of SARS-CoV-2 RNA and calculates
a final number, in copies per milliliter, by late that evening.
According to Peccia, data from sludge results come a week
in advance of testing reports because infected individuals start
shedding pathogens into wastewater before they even “know
to get tested”—and when they do get tested, it takes days for
results to be reported back to them. Peccia added that the
current wastewater data is an alarming indicator of yet another
wave of coronavirus infections in Connecticut.
Monitoring sewage sludge, according to the paper, is a “broadly
applicable strategy.” Currently, the team shares its data with state
officials and their virus response teams to inform the state’s
sampling, analysis and monitoring of the virus. The team is also
funded by the CDC to inform additional broader projects. ■
Peccia, J., Zulli, A., Brackney, D.E. et al. Measurement of SARS-
CoV-2 RNA in wastewater tracks community infection
dynamics. Nat Biotechnol 38, 1164–1167 (2020). https://
doi.org/10.1038/s41587-020-0684-z
December 2020 Yale Scientific Magazine 9
NEWS
Medicine
NO MORE STRIKING OUT
WITH STROKES
A New Hope for Patients
of Acute Ischemic Stroke
BY JERRY RUVALCABA
ILLUSTRATION COURTESY OF ELLIE GABRIEL
FAST: face drooping, arm weakness, speech difficulty, time. This allows for many individuals who faced an unsuccessful traditional
acronym has been ingrained in us for the simple reason that it mechanical thrombectomy, or had the method pre-evaluated to
saves lives. Recognizing the signs of a stroke and immediately be infeasible, a different opportunity for treating the stroke.
seeking emergency care is the first step in the right direction. But then
what? In the case of acute ischemic stroke, a stroke caused by blockage
of blood flow to the brain, medical practitioners have relied on the
use of a lifesaving procedure known as mechanical thrombectomy.
This amazing procedure relies on the insertion of thin instruments to
suction out the occlusion at the source of the anterior cerebral artery.
Traditionally, this procedure functions on accessing the
blocked artery through a rather circuitous manner. At what
is known as a percutaneous transfemoral access point (near
the groin area), an incision is made to insert a set of wire-like
instruments into the blood vessels. With the help of a contrast
agent directly injected into the arteries, surgeons can then guide
the wires through the vessels starting at this groin area up to the
affected anterior artery, located in the head region.
Although seemingly anfractuous, this odd method of approach
has noteworthy benefits. “Most interventions for many, many
years, were performed through the femoral artery in the leg,
where if it’s damaged, your body can generally tolerate it very
well without major issue,” said Charles Matouk, a neurosurgeon
at the Yale School of Medicine with extensive experience on the
procedure. This way, the relatively simple design of the femoral
artery and the redundancy of collateral pathways in this access
point allow errors in the procedural execution to be less serious
than if the procedure were performed at a different access point.
Still, there are limitations to this method of execution—most
notably the dependence on a relatively clear path from the
femoral entry point to the cerebral anterior artery. “The bigger
issue comes when, as I say, the road is bumpy, or if you can
Despite the larger opportunity for error due to the complex
nature of the artery, Matouk found that when put in practice,
he very infrequently experienced errors. “It’s actually relatively
straightforward, which I think is its beauty,” Matouk said. The
process is very similar in approach to traditional, femoral mechanical
thrombectomy in that it involves the extraction of the obstruction via
a set of wires carefully maneuvered through the blood vessels. It differs
in its extra precautions necessary: “We like the patients to be asleep
with a tube in their mouth, so they’re intubated under an anesthetic
because one of the complications that can arise when you puncture
any blood vessel is that the closure doesn’t take and it can bleed.”
With this approach, the build-up of blood in the neck can subject
the patient to compression of the windpipe and possible closure of
the airway, leading to asphyxiation. This intubation, plus the careful
positioning of the patient’s head, is crucial for a successful operation.
When tested on patients unfit for a femoral approach, this
alternative method proved to be extremely effective, with sixteen of
the nineteen patients treated exhibiting the successful reoxygenation
of affected tissue, where blood access had been thwarted. Additionally,
after twenty-four hours, patients displayed smaller infarct, or dead
tissue, volumes; they also had an increased likelihood for a lower and
thus better mRS score, signifying that these patients were more fit
according to the Modified Rankin Scale for Neurologic Disability.
In the future, Matouk hopes to see this approach become more
widespread and more accessible to the many individuals for which
femoral mechanical thrombectomy is unworkable. He and his
colleagues are also looking into formalizing a concrete method to test
for whether or not traditional thrombectomy works for an individual. ■
predict the road is going to be bumpy from the leg,” Matouk
said. In these cases, traditional mechanical thrombectomy is not
possible and is a waste of critical time.
Cord, B. J., Kodali, S., Strander, S., Silverman, A., Wang, A.,
With this, Matouk and colleagues sought to evaluate the Chouairi, F., Koo, A. B., Nguyen, C. K., Peshwe, K., Kimmel,
feasibility and effectiveness of other pathways, and, in a recent
A., Porto, C. M., Hebert, R. M., Falcone, G. J., Sheth, K. N.,
Sansing, L. H., Schindler, J. L., Matouk, C. C., & Petersen,
study, they tested and brought to light the efficacy of a carotid N. H. (2020). Direct carotid puncture for mechanical
puncture as an alternative technique. The carotid arteries are large thrombectomy in acute ischemic stroke patients with
blood vessels in the neck that supply the brain, neck, and face
with their blood supply. Because of their immediate proximity to
prohibitive vascular access. Journal of Neurosurgery, 1(aop),
1–11. https://doi.org/10.3171/2020.5.JNS192737
the affected arteries of ischemic stroke patients, this entry point
10 Yale Scientific Magazine December 2020 www.yalescientific.org
TREAT
Y URSELF
Neuroscience
NEWS
Connecting the
Brain’s Reward System
and Obesity
BY VICTORIA VERA
ILLUSTRATION COURTESY OF ELLIE GABRIEL
A
silent killer lies among younger populations across
the United States: childhood obesity. For children and
adolescents aged two through nineteen, the prevalence of
obesity stands at around 18.5 percent, with twelve- to nineteenyear-olds
being the most affected subset of that group. It is known
that childhood obesity is a predictor of obesity later in life, and
as such, previous work has largely focused on analyzing the
relationship between rewards-related brain regions, unhealthy
eating behaviors, and health outcomes. This led researchers at
Yale University to focus on how the nucleus accumbens (NAcc)—
part of the reward center of the brain—tissue microstructure can
predict waist circumference after one year.
The study is based on data collected over the first year of a longitudinal
study. In this ten-year Adolescent Brain Cognitive Development
(ABCD) study, researchers across many institutions are currently
following over twelve thousand nine and ten-year-olds. Researchers
at Yale are following 5,366 in particular. The main hypothesis was
built on existing data showing instances of neuroinflammation in the
NAcc of animal models with diet-induced obesity.
In order to study this phenomenon in humans, researchers tracked
the movement of water within the brain using magnetic resonance
imaging (MRI) technology. This particular method is known as
diffusion imaging, and it allows the user to functionally discern
where water is being held within the brain, and, as a result, determine
where there are higher cellular densities. By looking at the patterns
of water movement, one can determine exactly which types of cells
are found in that area. In this particular study, researchers focused
on the glial (support) cells found in the NAcc. This conglomeration
of cells can be attributed to an inflammatory response from the
body. “This effect was not only massive, but it was very specific to
this region (the NAcc),” said Kristina Rapuano, a researcher focusing
more on the neurological aspects of this research.
When the team followed up on their baseline participants
a year later, there was increased waist circumference in 2,133
participants, which led them to believe that the increased amount
of inflammation in the NAcc serves as a predictor of further weight
gain in obese patients. The senior author of the paper, Richard Watts,
expressed just how significant these findings were, specifically
mentioning the traditionally smaller sample sizes available for
MRI studies and how important it was to get this amount of data
out of the baseline sample. Despite confounding factors that might
www.yalescientific.org
COOKIE & TREE IMAGES COURTESTY OF PIXABAY
contribute to both BMI and waist sizes, such as puberty, genetics,
or socioeconomic background, the numbers nevertheless showed
a strong correlation and should not be dismissed. These findings
use data solely from the first year of the study. However, the second
year of data has very recently become available. Researchers hope
to gather further findings from this second set of data, as the first
set did not make use of any MRI scans.
Both Watts and Rapuano emphasized that conclusions from
this research are still speculative. “We can kind of look at it both
ways. How is the weight gain driving the changes in cellularity
in this area, and then how is that then further promoting weight
gain?” Rapuano said. Essentially, there is not one distinct
resolution to this overarching relationship between obesity and
the NAcc. In this way, using the most recent data, this team hopes
to focus on how the participants’ NAcc tissue microstructure
has changed (or not) within thøe past two years, and see how
that correlates with changing waist measurements and body
mass index (BMI) values. They hope to further strengthen
the existing hypotheses mentioned above, and possibly puzzle
together how all these parts come into play.
The bigger study which this particular study borrows from has
its own long-term goals. To name some, the ABCD study plans
to study the impacts on drug use, how these might play into the
aforementioned reward systems, and overall quality of life. At the
moment, we know of some of the negative effects of obesity—
ranging from secondary health problems to struggles with mental
health. Hence, in order to provide a better solution, we must
better understand the many mechanisms at work. Hopefully, as
time goes on, we will begin to understand the basis behind these
behaviors that affect such a large portion of the population. ■
Rapuano, K. M., Laurent, J. S., Hagler, D. J., Hatton, S. N.,
Thompson, W. K., Jernigan, T. L., . . . Watts, R. (2020). Nucleus
accumbens cytoarchitecture predicts weight gain in children.
Proceedings of the National Academy of Sciences, 117(43),
26977-26984. https://doi.org/10.1073/pnas.2007918117
Childhood Obesity Facts. (2019, June 24). Retrieved
November 08, 2020, from https://www.cdc.gov/obesity/
data/childhood.html
Adult Obesity Facts. (2020, June 29). Retrieved November 08,
2020, from https://www.cdc.gov/obesity/data/adult.html
December 2020 Yale Scientific Magazine 11
FOCUS
Biochemistry
A MOLECULAR
WHODUNIT
IN THE LIVER
What molecules cause hepatic insulin resistance?
BY ALICE HUANG
IMAGE COURTESY OF SHUTTERSTOCK
What happens to the carbs we eat?
Carbohydrates are one of the
main sources of energy for cells
in the human body. After eating a meal,
carbohydrates pass through the digestive
system, traveling from the stomach to the
small intestines, and are broken down into
their basic unit, the monosaccharide (such
as glucose, fructose, and galactose), along
the way. Upon their arrival in the small
intestines, monosaccharides are transported
into the bloodstream, increasing glucose
concentrations in the blood and prompting
the pancreas to secrete the essential hormone
insulin to promote tissue glucose uptake and
suppress endogenous glucose production.
This process provides tissues access to glucose
for energy production and storage as well as
maintains a healthy concentration of blood
glucose to prevent hyperglycemia.
Hyperglycemia, or abnormally high blood
sugar levels, can become dangerous since the
body will turn to excessively breaking down
fats when glucose cannot be accessed by
tissues for energy production. This process
of rapid fat breakdown produces excessive
ketones, the buildup of which could be lifethreatening.
Additionally, hyperglycemia
can cause damage to multiple tissues, such
as the retina, kidneys, limb extremities,
and cardiovascular system, which could
lead to severe downstream complications,
including vision loss, renal diseases, limb
extremity necrosis and amputation, and
cardiovascular diseases. Disruption of
the insulin signaling pathway may lead
to hyperglycemia in type 2 diabetes, a
condition where the body not only exhibits
lowered response to insulin but also does
not produce enough insulin in chronic
conditions. Researchers have conducted
many studies investigating the pathways
responsible for the development of insulin
resistance. Recently, the Shulman Lab
at Yale has come forth with a potential
mechanism for the development of insulin
resistance in the liver, also known as hepatic
insulin resistance (HIR).
Significance of the study
The Shulman Lab, led by Gerald Shulman,
the George R. Cowgill Professor of Medicine
and Cellular & Molecular Physiology at
Yale, has been extensively studying HIR
and its contribution to type 2 diabetes for
the past few years. “Insulin resistance is
the primary determinant of whether or not
someone develops type 2 diabetes. [Type 2
diabetes] is going to impact half a billion
people within ten years’ time and is the
leading cause of blindness and end-stage
renal disease, as well as a huge economic
cost to society,” Shulman said. His research
team has been dedicated to investigating
the role of liver fat accumulation in insulin
action disruption and hepatic insulin
resistance. In a paper recently published
in Cell Metabolism, the Shulman Lab
presented its newest discovery: a possible
pathway by which certain molecules,
called diacylglycerols (DAGs), might be
responsible for inducing HIR. Kun Lyu, a
graduate student in the Shulman Lab and
first author of the paper, explains that the
pathway had been discovered step-bystep
from decades of work, and that with
its history, had had its fair share of debate
and controversy. “Over the past two or
three years, we have developed new tools
and models to specifically address this
controversy,” Lyu said.
Major results
The pathway the team discovered describes
how accumulation of plasma membrane sn-
1,2-diacylglycerols (PM sn-1,2-DAGs) leads
to HIR. These DAGs are a group of plasma
(cell) membrane-bound stereoisomers
(compounds composed of the same atoms
differing only in their orientations) of DAG
that was found to activate the Protein Kinase
C- (PKCε) pathway, which has the ability to
disrupt insulin signaling. PKCε activation
results in phosphorylation—a type of
chemical tagging—of a critical amino acid
residue (a specific chemical building block of
a protein) on insulin receptor kinase (IRK).
By tagging this amino acid residue, PKCε
then disrupts the downstream signaling
pathway and can lead to insulin resistance.
The research team was able to establish
the role of DAGs in inducing HIR by
removing functioning copies of an enzyme
called DGAT2, which converts DAGs to
triglycerides, in mice—a model known as
DGAT2 knockdown (KD). To determine the
effects of high DAG content on liver insulin
action, the researchers subjected regular
chow-fed rats to a treatment that decreases
DGAT2, allowing DAG to accumulate. They
then subjected these acute hepatic DGAT2
KD rats to a hyperinsulinemic-euglycemic
clamp, a method used to infuse high levels
of insulin (“hyperinsulinemia”) to mimic
insulin levels after ingestion of carbohydrates
while maintaining normal blood-glucose
concentrations (“euglycemia”). The
researchers found that this model impaired
insulin’s suppression of endogenous glucose
production by impairing the insulin
signaling pathway, suggesting that DAGs
could play a role in HIR.
12 Yale Scientific Magazine December 2020 www.yalescientific.org
Biochemistry
FOCUS
The study cemented the association of
high levels of PM sn-1,2-DAGs with HIR
in both rats and humans. The researchers
analyzed DAG stereoisomer content
in multiple subcellular compartments
(endoplasmic reticulum, plasma
membrane, mitochondria, lipid droplets,
and cytosol). The focus on examining
these compartments is significant as
past studies have shown that only DAG
accumulation in certain compartments
is associated with HIR. In rats subjected
to acute hepatic DGAT2 KD, they found
higher sn-1,2-DAG content, particularly
in the plasma membrane. In the liver
tissues of human individuals with HIR,
researchers discovered about five times
higher levels of liver PM sn-1,2-DAGs
than in humans without HIR. These
higher levels of PM sn-1,2-DAGs also
correlated with about three times higher
levels of IRK-T1160 phosphorylation.
From these results, the researchers drew
the association of high levels of PM
sn-1,2-DAGs with HIR, revealing that
targeting this particular stereoisomer
could ameliorate the effects of HIR.
Considering this potential target, the
Shulman Lab found that knocking down
PKCε specifically in the liver ameliorated
HIR caused by a high-fat diet and DGAT2
KD. After treating the rats to decrease
PKCε content in the liver, the researchers
fed the rats a high-fat diet for four days
to induce acute hepatic steatosis (fat
buildup in the liver) and HIR. During a
hyperinsulinemic-hyperglycemic clamp,
they found that the PKCε KD improved
insulin’s suppression of endogenous
glucose production and resulted in a two
times higher rate of insulin-stimulated
hepatic glycogen synthesis compared
with the control. They also observed
improved downstream signaling in the
insulin signaling pathway and lower
levels of IRK-T1160 phosphorylation in
these rats. Essentially, the liver-specific
PKCε KD ameliorated the effects of
high fat feeding and acute DGAT2 KD
on causing HIR. These results indicate
that not only are PKCε and PM sn-1,2-
DAG associated with HIR, but also that
they are directly responsible in mediating
HIR, increasing their promise as an
effective target in therapies aiming to
reverse insulin resistance.
So, the researchers had shown that PKCε
is necessary for PM sn-1,2-DAG-mediated
www.yalescientific.org
HIR, but is it sufficient? To test this,
researchers treated healthy and lean rats to
overexpress constitutively active PKCε. The
constitutively active nature of these particular
PKCε allowed for total PKCε content in the
liver to increase significantly with six times
greater translocation, which induces directly
observable, correlated results. This treatment
resulted in two times higher IRK-T1160
phosphorylation, impairing downstream
signaling. Thus, the conclusion was that
hepatic PKCε activation is both necessary
and sufficient in mediating HIR, leading to
hyperglycemia and hyperinsulinemia.
Novelty of approach
The Shulman Lab developed a range of
new techniques and tools in their pursuit
of these discoveries. One technique crucial
to this study, liquid chromatographytandem
mass spectrometry (LC-MS/MS),
was developed by the lab to quantify DAG
stereoisomers, such as the sn-1,2-DAG. “It
took the whole team a lot of manpower and
troubleshooting. We had to optimize the
conditions using new tools with thousands
of data points of testing and eventually
came to this final product that is reliable
and efficient to distinguish and quantify
different DAG stereoisomers. It reflects
tremendous work,” Lyu said. This new
technique, together with the novel method
measuring molecule levels in subcellular
compartments, allowed the team to measure
DAG content in subcellular compartments
in order to draw the associations between
DAG content and distribution with HIR.
Additionally, the team had to develop a
way to recognize the phosphorylation of
IRK-T1160, which is mediated by PKCε.
Although mass spectrometry had been
sufficient in previous studies using purified
proteins, the process of detecting this
phosphorylation event proved much more
ABOUT THE AUTHOR
complicated in vivo, or in the organism. To
address this issue of recognition, the team
turned to monoclonal antibodies, which are
proteins that are used to target and bind to
specific substances in the body, mimicking
the way the immune system normally
targets foreign substances. “The key tool
was to develop a monoclonal antibody that
would recognize the phosphorylation of this
1160 position in vivo… Now we have a tool
that [Lyu] was able to show worked in both
animal and human liver to show that this
key site is the target for PKCε, to ascribing
hepatic insulin resistance,” Shulman said.
What comes next?
Armed with this new information, the
Shulman Lab continues to investigate and
develop this new model. The discoveries
they made can be applied to other tissues,
such as skeletal muscle, white adipose
tissue, and others that are responsive
to insulin. They also aim to investigate
unknown factors in their model, including
how the DAGs translocate to the plasma
membrane and why similar accumulation
is not observed in other subcellular
compartments in acute short-term models.
With this deeper understanding of the
molecular basis of insulin resistance, new
therapies can be developed to better target
and treat the symptoms of hyperglycemia.
“Right now, every drug that we are using
to treat diabetes is pretty much treating
the symptom of hyperglycemia, not really
the root cause of insulin resistance…If
we understand the molecular basis, we
can identify the best targets to treat it,”
Shulman said. This study indicates that a
significant root cause of hepatic insulin
resistance is PM sn-1,2-DAG and PKCε
activation, and suggests that new therapies
that target these molecules in the liver may
help reverse insulin resistance. ■
ALICE HUANG
ALICE HUANG is a junior in Pierson College majoring in Biomedical Engineering. In addition to writing
for YSM, she is an active participant in Yale’s Design for America chapter and Christian Union Lux. She
also studies fibroblast activation profiles and their contribution to the tumor microenvironment.
THE AUTHOR WOULD LIKE TO THANK Professor Gerald Shulman and Kun Lyu for their time and
enthusiasm in sharing their research.
FURTHER READINGS
Samuel, V. T. & Shulman, G. I. (2012). Mechanisms for Insulin Resistance: Common Threads and Missing
Links. Cell, 148(5), 852-871. https://doi.org/10.1016/j.cell.2012.02.017
Samuel, V. T. & Shulman, G. I. (2016). The pathogenesis of insulin resistance integrating signaling pathways
and substrate flux. The Journal of Clinical Investigation, 126(1), 12-22. https://doi.org/10.1172/JCI77812
December 2020 Yale Scientific Magazine 13
SURVIVIN
EXTINCTIO
FOCUS
Paleontology
HOW DOES LIFE RECOVER?
BY LUCAS
LOMAN
Examining the Fossil Record
Throughout Earth’s history, five
major mass extinction events
have occurred, including the
well-known Cretaceous-Tertiary (K-T)
mass extinction, which wiped out over
seventy-five percent of living organisms
at the time, including the dinosaurs.
However, some scientists see the
present as a sixth, human-caused mass
extinction, as today’s extinction rates
are thousands of times greater than the
natural rate. Consequently, it has become
increasingly urgent for researchers to
understand how mass extinction events
impact populations and how species
respond to them.
While previous mass extinction events
occurred millions of years ago, geologists
can consult the fossil record to study
them. Analyzing physical characteristics
of fossils enables geologists to identify
now-extinct organisms, predict the
planet’s climate patterns over millions
of years, and discover ecological
relationships that may still exist today.
Geologists can also estimate the ages
of fossils through investigation of
radioactive decay in the rocks that
encase them. By noting the ages of
fossils belonging to the same species,
researchers can piece together timelines
of origination and extinction for those
species. When many species disappear
from the fossil record at around the
same time, geologists can conclude that
a mass extinction has occurred.
The Early Burst Model
While studying the mass extinctions
themselves is important, it is also necessary
to examine the behavior of the species
that remain after the events. Immediately
following mass extinction events, many
niches, or areas within an ecosystem in
which organisms specialize, are vacated.
For instance, a mass extinction of lions
would open up a larger niche occupied by
cheetahs, since lions and cheetahs occupy
the same area and target the same prey.
Mass extinctions therefore provide the
surviving species considerable opportunity
to differentiate with new traits that allow
them to fill other niches.
The commonly accepted representation of
such development is the early burst model,
a hypothesis originating in the 1940s where
survivors of mass extinctions quickly radiate
into many new morphologies (physical
forms) to fill the now-empty niches in the
environment. A key example is after the K-T
mass extinction, when surviving mammals
began to differentiate very quickly to fill
the open ecospace. By adapting traits to
better suit various conditions, different
groups of mammals were able to expand
into their respective niches. There are now
thousands of mammal species currently
alive, dominating far more ecospace than
they had before the K-T extinction.
Diversity and Disparity
Christopher Whalen, a researcher at the
Yale Department of Earth and Planetary
Sciences, sought to put the early burst
model to the test using ammonoids,
an extinct group of marine molluscs
related to octopi and squids. Whalen
investigated two main characteristics of
the ammonoid populations: diversity (the
number of species a group of organisms
contains) and disparity (the extent to
which morphology differs from species
to species). By examining the physical
shape of ammonoid fossils from directly
after mass extinctions, Whalen was able
to judge how unique each species was
from one another and determine whether
disparity indeed increases rapidly in
relation to diversity after mass extinctions,
as the early burst model predicts.
Specifically, the researchers factored
in various dimensions of the spiral
ammonoid shell to quantify morphological
differences among specimens. This was
a key advantage to using ammonoids
to study disparity patterns: ammonoid
shells come in relatively simple geometric
shapes, allowing for a straightforward
method of calculating disparity among
species. Also, since the shell accounts
for the majority of the ecological fitness
of the organism due to its effect on the
hydrodynamics of the ammonoids,
measuring shell dimensions allows the
researchers to study a characteristic that is
at the focal point of ammonoid evolution.
So, if the early burst model argues
that disparity increases quickly after
mass extinction events, then where does
diversity fit into the equation? As the
number of species increases, it becomes
14 Yale Scientific Magazine December 2020 www.yalescientific.org
G MASS
NS
ART BY MIRIAM
KOPYTO
Paleontology
FOCUS
more difficult for a new species to
develop a morphology that is different
from all others. It is then necessary
to take into account the number of
species currently present to temper the
expectation for disparity at that time.
“As in rolling dice, the more times you
do it, the more times you are going to
repeat,” Whalen said. “When you have
fewer species, differences among them
are easier to achieve.”
To factor in diversity, Whalen developed
a null model to predict disparity patterns
based on diversity patterns throughout
history. The model randomly assigned
morphologies to each species and
calculated the resulting ammonoid
disparity over time. This simulation was
repeated thousands of times, shuffling
morphologies among species to produce
a new, slightly different disparity pattern
each time. Whalen then calculated the
median disparity pattern to predict how
disparity was expected to look given the
diversity pattern. By comparing the actual
ammonoid disparity over time to the null
model’s expected disparity, the researchers
could find whether disparity increased
sharply after mass extinctions events, as
predicted by the early burst model.
Results and Implications
If the early burst model held true, the
actual disparity would outpace the null
model’s expected disparity after each mass
extinction event. However, Whalen instead
discovered a surprising trend: ammonoid
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disparity after most mass extinctions
actually lagged behind diversity. The early
burst model not only failed to explain
ammonoid population behavior, but it
predicted the exact opposite of the true
outcome. These findings are especially
noteworthy given the characteristics
of ammonoids. As an r-selected group,
meaning they rapidly reproduce in high
quantities and follow “boom and bust”
population dynamics, ammonoids are
particularly adept at recovering quickly
from mass extinctions. Therefore, Whalen
suggested that ammonoids are a group
that should be favorable for supporting
the early burst model. “The fact that the
model does not hold up [for ammonoids]
is good evidence that it is suspect in many,
if not all situations,” he said.
However, Whalen does offer one
caveat: we may simply not be looking in
ABOUT THE AUTHOR
the right place. It is possible that studying
too general of a group of organisms leads
to no clearly identifiable early burst
trend, which could still appear in specific
subsets of that same group. “It is possible
that early burst could exist at those finer
levels, but that is not something you
can determine based on this ammonoid
data,” Whalen said.
As gaps in the fossil record have been
filled through the decades following the
development of the early burst model, so
too have gaps in our knowledge about
ancient organisms. By studying Earth’s
past mass extinction events, we can draw
a clearer picture of what the aftermath
of human impact on ecosystems will
look like. We may also be able to more
accurately predict how vulnerable
species will recover from the sixth major
mass extinction, if at all. ■
LUCAS LOMAN
LUCAS LOMAN is a first-year student in Morse College. In addition to writing for YSM, Lucas serves in
the Public Health Center of the Yale Roosevelt Institute, Yale’s public policy think tank.
THE AUTHOR WOULD LIKE TO THANK Christopher Whalen for his time and enthusiasm in
discussing his research.
FURTHER READINGS
Whalen, Christopher D., et al. “Paleozoic Ammonoid Ecomorphometrics Test Ecospace
Availability as a Driver of Morphological Diversification.” Science Advances, vol. 6, no. 37, 2020,
doi:10.1126/sciadv.abc2365.
Whalen, Christopher D., and Derek E. G. Briggs. “The Palaeozoic Colonization of the Water
Column and the Rise of Global Nekton.” Proceedings of the Royal Society B: Biological Sciences,
vol. 285, no. 1883, 2018, p. 20180883., doi:10.1098/rspb.2018.0883.
Whalen, C., Hull, P., & Briggs, D. (2020, September 01). Paleozoic ammonoid ecomorphometrics
test ecospace availability as a driver of morphological diversification.
December 2020 Yale Scientific Magazine 15
FOCUS
Biochemistry
DRUGGING
THE
UNDRUGGABLE
IMAGE COURTESY OF PIXABAY
The
journey
of drug
discovery
BY
JENNY
TAN
Duchenne muscular dystrophy (DMD) is
a genetically linked disorder caused by
a mutation of the protein dystrophin.
The dystrophin protein transfers muscle
contractions from inside of a muscle cell
outward. In other words, it connects the center of a muscle
cell outwards. Without functional dystrophin proteins,
muscle cells are not intact, leading to muscle degeneration
and weakness, and eventually bringing on the loss of heart
and skeletal muscles. With no cures for DMD, an optimistic
life expectancy for those with DMD is in the early thirties.
Anton Bennett, Dorys McConnell Duberg Professor of
Pharmacology and Professor of Comparative Medicine at
Yale, and his team discovered a possible treatment pathway
for DMD. They found this pathway while researching
mitogen-activated protein kinases and its phosphatases.
16 Yale Scientific Magazine December 2020 www.yalescientific.org
Biochemistry
FOCUS
A micrograph of skeletal muscle cells.
How the Cell Propagates Information
Mitogen-activated protein kinase
(MAPK) are a family of proteins that play
an important role in signal cascades, a
series of reactions that occur one after
the other, responding to an activation
event. Like all proteins, MAPKs consist
of a chain of amino acids, or residues,
which fold into specific conformations
based on the interactions between the
different types of amino acids. MAPKs
are activated by the phosphorylation of
tyrosine and threonine residues, which
are located on the activation loop of the
protein. Phosphorylation involves adding
a phosphate group to the protein, often
activating a function. This activation is
often in response to an outside signal, such
as a ligand binding to a signal receptor
within the cell membrane of a cell.
After activation, MAPKs phosphorylate
subsequent substrates (the targets of
an enzyme), initiating a signal cascade.
These signal pathways elicit a large
range of cellular responses such as gene
transcription, cellular differentiation,
metabolism rate, apoptosis and more.
Mitogen-activated protein kinase
phosphatases (MKPs) offer an additional
layer of control by regulating MAPKs.
They do this by dephosphorylating the
tyrosine and threonine residues at the
activation loops. Without phosphate
groups, MAPK return back to their
inactive forms. MKPs are thought of as
belonging to different sub-families, each
www.yalescientific.org
of which regulates a specific group of
MAPKs. For example, a group of MKPs
which includes MKP5, MKP7, and
DUSP8 targets stress-activated MAPKs.
This specificity allows MKPs to closely
regulate their respective kinase proteins,
providing the cell finer control of its
molecular machinery.
The Undruggable MKP5
IMAGE COURTESY OF WIKIMEDIA COMMONS
While MKPs are essential for signal
regulation, recent research suggests that
they may also have roles in disorders.
Specifically, studies suggest that MKP5
disrupts muscle myogenesis, or the
formation of muscle tissue. When
skeletal muscle cannot regenerate
through myogenesis, they are replaced
with fibrotic, or connective, tissues.
In this sense, MKP5 seems to be the
perfect target to treat this disorder.
However, the phosphatase is tricky to
inhibit as most identified inhibitors attack
the active site of the phosphatase, which
is positively charged. Like the attraction
between the north and south poles of
a magnet, to attach to the positively
charged site, the inhibitor compounds
are often negatively charged. However,
charged molecules are undesirable for
drug use as these molecules cannot pass
through the cell membrane. In light of
these challenges, many deemed MKP5
to be “undruggable.” Furthermore,
inhibiting a member of the MKP family
is further complicated by the similarity
of phosphatase structures. A molecule
that inhibits MKP5 may also inhibit
other MKP molecules, disrupting other
mechanisms within the body. Thus,
the specificity of the molecule adds
an additional layer of difficulty when
developing a suitable inhibitor.
To target MKP5, Bennett implemented
a novel strategy: to look for inhibitors
that could deactivate the enzyme without
targeting the active site, also known as
allosteric inhibitors. “That was really the
breakthrough strategy,” Bennett said.
Screening
The first step to finding inhibitor
molecules was to test a large set of
molecules to determine if any of them
loosely inhibited MKP5. There are two
main ways to screen for molecules:
physically or computationally. “We did a
real, physical screen where we screened
over a hundred thousand compounds
using automation with [many] compounds
in well plates,” said Zachary Gannam, a
The path to a workable drug requires
meticulous and thorough work.
December 2020 Yale Scientific Magazine 17
FOCUS
Biochemistry
postdoctoral fellow and the first author of
the study published in Science Signaling.
Alternatively, virtual screenings use
structural biological information to
create docking sites on a desired protein.
Then, simulations can dock millions of
compounds to test their interactions.
Both screening methods have their
benefits and drawbacks. Physical
screening requires a significant amount
of protein, an optimized experiment,
and is also more expensive and time
intensive than computational methods.
However, when you get a hit, you
know the compound is an inhibitor.
On the other hand, computational
screenings require researchers to have
an idea of the protein structure and
the structure of the sites where small
molecules can interact. After conducting
computational models, researchers are
required to eventually physically test
the compounds with the most promise.
A positive is not necessarily guaranteed
to be an inhibitor, and the highest hit
rates are still fairly low. With insufficient
information about docking sites on
MKP5 for computational screenings, the
research team opted to conduct physical
screenings. The screening tests revealed
that a molecule, denoted by Compound
1, showed promise in inhibiting MKP5.
The How’s and the Why’s
With initial screenings showing the
inhibitory properties of Compound 1,
Bennett’s team wanted to find out how
the molecule interacts with MKP5.
Understanding the molecular interactions
between MKP5 and Compound 1 required
acquiring a crystal structure—a repeated
lattice of stable protein interactions—
of the two interacting molecules, which
would help researchers determine the
structure of the proteins and their
interaction. “This was the first crystal
structure of an MKP in a complex with a
small molecule,” Gannam said. The lack of
previous procedures for crystallography
meant that the team had to test out the
MKP5-Compound 1 complex in solutions
of various combinations of buffers, salts
and precipitants. “It’s very idiosyncratic
and there are not many set rules to follow,”
Gannam said. Rounds and rounds of
screening for crystallization were required
to finally develop the crystal structure.
The structure revealed that Compound
1 fundamentally shifts the shape of
MKP5. Notably, a distinct allosteric site
on the protein shifts to interact with
Compound 1. These shifts cause the
volume of the active site to decrease by
eighteen percent. Analyzing the specific
residues which Compound 1 interacts
with also showed its selectivity for
MKP5 as opposed to other MKPs within
the molecule family. Specifically, the
research team showed that methionine
and threonine residues on MKP5’s
allosteric site were unique to it. Further
tests revealed that Compound 1 was less
effective at inhibiting a mutated MKP5
with altered methionine and threonine
residues. Thus, Compound 1 seems to
selectively bind to MKP5 due to these
two residues.
Moving to Cells
So far, research on Compound 1
had been conducted outside of the
cell. To make sure that Compound 1
behaves predictably within a biological
context, the team investigated the
effect of Compound 1 in mice cells.
Since MKP5 inhibits MAPK and
JNK, introducing Compound 1 would
inhibit MKP5, therefore increasing the
phosphorylation of MAPK and JNK. Not
only did Compound 1 increase MAPK
ABOUT THE AUTHOR
and JNK activities, it had no effect on
other kinases such as ERK1/2, which is
not regulated by MKP5. These results
showed that even in a cellular context,
Compound 1 seems to only inhibit
MKP5, displaying the specificity that is
crucial for viability as a drug.
What’s Next?
Discovering Compound 1 represents
the crucial first step to developing a
treatment for DMD. However, there
is still a long way to go to produce a
viable drug. “Essentially, we have a
drug development project to make a
compound that is ideally highly potent,
orally viable and fits the once-a-day pill
treatment,” Bennett said.
Compound 1 may also have applications
beyond DMD. Compound 1 targets the
pathway leading to tissue fibrosis or the
thickening of scarring on tissue. For
example, postoperative fibrosis is a type of
complication that occurs after surgeries,
involving excess tissue scarring as a result
of the surgery. “Fibrosis accounts for
forty-five percent of deaths worldwide in
various clinical presentations,” Bennett
said. These include cardiac, lung, liver,
and kidney fibrosis. Compound 1 can
potentially address these fibrosis diseases
and complications.
The path to a workable drug requires
meticulous and thorough work. It allows
for innovations like Compound 1 to have
the potential to help millions. ■
JENNY TAN
JENNY TAN is a sophomore in Saybrook majoring in Chemistry. She is from northern Virginia just
outside of Washington D.C. Outside of school, she likes baking and listening to music.
THE AUTHOR WOULD LIKE TO THANK Zachary Gannam and Anton Bennett for their time and
illuminating discussions about their research.
FURTHER READING
AM;, M. (n.d.). Loss of MKP-5 promotes myofiber survival by activating STAT3/Bcl-2 signaling during
regenerative myogenesis. Retrieved November 26, 2020, from https://pubmed.ncbi.nlm.nih.
gov/29047406/
Bennett, A. M. (2019, January 01). MKP5 in Dystrophic Muscle Disease. Retrieved November 26, 2020,
from https://grantome.com/grant/NIH/R01-AR066003-05
Gannam, Z. T., Min, K., Shillingford, S. R., Zhang, L., Herrington, J., Abriola, L., . . . Bennett, A. M. (2020).
An allosteric site on MKP5 reveals a strategy for small-molecule inhibition. Science Signaling, 13(646).
doi:10.1126/scisignal.aba3043
Zhang, W., & Liu, H. (n.d.). MAPK signal pathways in the regulation of cell proliferation in mammalian
cells. Retrieved November 26, 2020, from https://www.nature.com/articles/7290105
18 Yale Scientific Magazine December 2020 www.yalescientific.org
ADJUSTING
Quantum Coupling
FOCUS
FOR
Achieving Imperative Error Correction
in Quantum Computers
By Agastya Rana
MISTAKES
Just a couple of decades ago, a
functional quantum computer lay
firmly in the realm of fantasy; the
prospect of creating one was rife
with challenges both theoretical and
practical. Yet, given its unbounded potential
to solve problems that are unsolvable by
conventional computers, scientists have
persevered, tirelessly chipping away at the
barriers that lay in their way. A recent paper
in Nature from a team at Yale University
sees us inch even closer towards this goal.
They have successfully implemented a
critical technique to extend the lifetime
of quantum data that could be used in a
quantum computer.
Image courtesy of Pixabay.
www.yalescientific.org
December 2020 Yale Scientific Magazine 19
FOCUS
Quantum Coupling
of different such QEC codes have
been theorized, but not all have been
practically implemented.
Revisiting The GKP Algorithm
IMAGE COURTESY OF THE YALE QUANTRONIC LABS
A photograph of Yale’s Quantronic Laboratory (QLab) Team
All the hype (and troubles) surrounding
quantum computers stems from the
fundamentally different manner in which
a quantum computer operates. While your
laptop (a ‘classical’ computer) uses the
principles of classical physics to operate,
a quantum computer exploits seemingly
unintuitive quantum phenomena to
perform its computations. Investigating
how these quantum phenomena can be
leveraged in a quantum computer is at the
heart of the mission of Yale’s Quantronics
Laboratory (QLab). “The laws of quantum
physics are radically different from the
laws of classical physics, so quantum
computers pose new challenges that
one does not encounter with classical
computers,” said Michel Devoret, F.W.
Beinecke Professor of Applied Physics,
QLab principal investigator, and coauthor
of the research.
Correcting Errors in Quantum Computing
Among the most significant of these
challenges that the QLab attempts to tackle
arises due to the curious phenomenon of
quantum decoherence, wherein quantum
information is lost. Just as classical
computers store information using bits
(binary values of 0 and 1), quantum
computers utilize qubits (quantum
bits). Unintuitively, these qubits can
take on a combination (superposition)
of binary values which are encoded
by their wavefunctions; it is these
wavefunctions that are manipulated
while performing computations.
‘When a qubit is encoded in a physical
system, its wavefunction interacts with
the environment, and the information it
stores tends to get corrupted in a process
known as quantum decoherence,” said
Alec Eickbusch, the co-lead author and
a graduate student at the QLab. Since it
is impossible in practice to completely
isolate a qubit, quantum decoherence
tends to quickly scramble the qubit,
destroying its information in a matter of
microseconds. “In a quantum computer,
we need to find a way to give a qubit a
longer lifetime,” Eickbusch said.
Unsurprisingly, prolonging a qubit’s
lifetime is much easier said than done. This
goal is the focus of quantum error correction
(QEC), which seeks to correct for errors
stemming from quantum decoherence
and other sources. In classical computers,
error correction, in the very unlikely
circumstance that it is required, is relatively
simple: all one needs is redundant copies
of bits. Any error causing a bit to change
value is easily detected and rectified by
observing the values of its copies.
Alas, quantum physics does not allow
for such a straightforward solution.
The aptly named ‘no-cloning theorem’
disallows the creation of independent,
identical copies of quantum states. Even
more frustratingly, checking whether
the encoded information in a qubit has
changed requires one to measure that
state of the qubit, which itself alters the
qubit. With such enormous roadblocks,
QEC seemed an impossible feat, until
MIT professor Peter Shor developed a
roundabout technique (a “code”), which
corrected errors in a “logical qubit” that
was made of a collection of ordinary
(“physical”) qubits. Since then, a number
The QLab team chose to focus on a
particular code devised in 2001 called
the GKP code, rather creatively named
after the initials of its theorists: Daniel
Gottesman, Alexei Kitaev and John
Preskill. “The GKP algorithm was a
very ingenious form of error correction,
developed ahead of its time,” Devoret
said. It relies on the principle that
quantum noise - the cause of errors in a
qubit - is local: it affects different parts
of a system differently. Therefore, if
information is stored non-locally, it
can be recovered in spite of noise.
Devoret uses an analogy to explain
the basis behind the GKP algorithm:
“Suppose you have two boxes put close
together, with a hole in them to allow
them to ‘communicate.’ If a bit is stored
by placing a ball in either the left (0) or
the right (1) box, then shaking the system
(introducing ‘noise’) may cause the ball
to move between boxes, thus changing
the bit stored. However, if the boxes are
placed far away (‘non-local storage’), then
the ball will remain in its box and the bit
will be preserved in spite of the system
being shaken. Similarly, the GKP code
provides a way to put the 0 and 1 of a
logical qubit as far apart in ‘phase space’
as possible, therefore preventing errors to
as large an extent as possible.
Although the GKP code has been around for
nearly two decades, it was believed to be too
impractical to physically realize in a laboratory
setting. However, in the decades since, the
development of better instrumentation has
allowed the QLab team to recognize that
implementing the GKP code was “very
possible, using tricks of superconducting
circuits”—the quantum mechanical apparatus
that hosts the qubits they manipulate.
Eickbusch outlined the two-year research
journey by separating it into three rough
stages. First, the team set about crafting
simulations to determine whether their
idea would work in practice. Then, they
spent time in the cleanroom, building,
tweaking, and debugging their quantum
superconducting circuits. Finally, with
20 Yale Scientific Magazine December 2020 www.yalescientific.org
Quantum Coupling
FOCUS
their system working, they wrote the code
to carry out measurements and extract
meaningful information from their setup.
From start to finish, the team donned the
roles of theoretical physicists, electrical
engineers and computer scientists to
work on the different theoretical and
experimental facets that were needed to
get their research up-and-running.
To implement these GKP code states
in a quantum circuit, the QLab employed
state-of-the-art technology, “assembled
from scratch and constructed completely
in-house.” For example, the experiment
collected data by analyzing weak microwave
signals that emerged from their setup using
extremely sensitive amplifiers. “[These
amplifiers are so sensitive that] if you were on
the Moon and called home with a telephone,
we’d be able to hear you,” Devoret said.
Employing incredibly precise technology
also necessitates equally precise feats of
engineering. “The biggest challenge
in the research process was
engineering the exact parameters
of the device that we needed. It took
six or seven tries for us to get it right,”
Eickbusch said. The superconducting
circuits used in the QLab need to be cooled
to extremely low temperatures, making
this debugging process all the more
cumbersome. “It would take two days
to cool down the device to test it. Then,
we’d realize that a parameter was off, and
it would take another two days to warm
back up”, Eickbusch said. Malfunctioning
apparatus also added to the team’s woes.
Co-lead author Philippe Campagne-
Ibarcq, now on the faculty of the National
Institute for Research in Digital Science
and Technology in France, recalled the
late nights that these technical difficulties
often brought. “In the middle of our
experimental work, our cryostat started to
die. We were on a race against time, and,
after some completely crazy nights, ended
up implementing an important variation
of our code in just one week,” he said.
Reaping the Rewards in Error Correction
Their painstaking efforts were
eventually rewarded—using the GKP
code, the QLab team was able to extend
the lifetime of a logical qubit by a factor
of two, showing that their quantum error
www.yalescientific.org
correction had successfully mitigated
the impact of quantum decoherence
on a qubit. “This research is a proof-ofconcept
that GKP codes can be practically
stabilized using quantum superconducting
circuits,” Eickbusch said. However, the
improvement in qubit lifetime provided by
the GKP code could be further extended.
“We have not yet attained the ‘break-even
point’, in that this GKP state does not last
longer than the best possible encoding
of quantum information [that does not
use GKP codes]. Our goal for the future
is to beat the break-even point by orders
of magnitude”, Devoret said. In fact,
armed with a government grant from
the Department of Energy, this is
one of the goals towards which the
QLab is now working.
Even if the lifetime of qubits could be
extended by orders of magnitude, according
to Devoret, there is still much to be done
before a quantum computer could become
reality. “What we have shown in this
paper is prolonging memory. The next
step involves fault-tolerant computation:
showing that quantum error correction
ABOUT THE AUTHOR
IMAGE COURTESY OF PIXABAY
can be implemented while performing an
operation on a qubit,” Devoret and Eichbusch
said. Progress also needs to be made on
the technological front to improve the
superconductors, insulators and electronics
that form the physical quantum device.
“Our Lego bricks are still not optimum and
perfectly functioning. Part of the work in
our lab seeks to develop the Lego bricks we
need to build more complicated devices in
the future,” Devoret said.
With all that remains to tackle ahead,
it’s no surprise that Campagne-Ibarcq
thinks that this is an exciting time to be
active in the field of quantum computing.
“There is always room for new ideas,” he
said. Teams across the globe are working
on different, innovative solutions to
similar problems, collaborating and
sharing ideas among one another in what
Devoret describes as a “highly stimulating
environment.” In fact, Campagne-
Ibarcq recounts that the QLab was
also a direct beneficiary of this
kind of collaboration. “Our friendly
competitors working with trapped
ions (an alternative to superconducting
circuits to store qubits) presented their
results in a seminar at Yale, describing
an easier way to stabilize the GKP code.
This prompted fruitful discussion, during
which the protocol we used in our research
was devised,” Campagne-Ibarcq said.
“In just a decade from now, we should
have a good idea of whether a quantum
computer can ever be built, what it will
look like, and how useful it is,” said
Devoret. But for such a machine to be
realized, it will need some form of error
correction, and how that is implemented
will no doubt be, in part, due to this work. ■
AGASTYA RANA
AGASTYA RANA is a first-year interested in Physics and Mathematics in Davenport College. In
addition to writing for the YSM, he enjoys organizing events as part of the YCC Events Committee
and swimming with Yale Club Swim. In his free time, he loves reading about the latest science
research, listening to a wide assortment of music and playing basketball with friends.
THE AUTHOR WOULD LIKE TO THANK Prof. Michel Devoret, Dr. Philippe Campagne-Ibarcq
and Alec Eichbusch for their time and enthusiasm in sharing their research, as well as James
Han for his constructive feedback on this manuscript.
FURTHER READING
Campagne-Ibarcq, P., A. Eickbusch, S. Touzard, E. Zalys-Geller, N. E. Frattini, V. V. Sivak, P.
Reinhold, et al. (2020). Quantum Error Correction of a Qubit Encoded in Grid States of an
Oscillator. Nature, 584(7821), 368–72. https://doi.org/10.1038/s41586-020-2603-3.
December 2020 Yale Scientific Magazine 21
EASONS
BY ANGELICA LORENZO
ART BY ANMEI LITTLE
ON
THE
HOW SEASONAL DIET CHANGES
IMPACT POPULATION SIZES OF
SAVANNA HERBIVORES
AVANNA
Ecology
FOCUS
consume, and nonmigratory grazers suffer
from the lack of plant abundance. Not only
is grass less abundant during the dry season,
but it is also less nutritious, leading species
that switch between grass and tree diets to
be more likely to obtain their food from
trees during the dry season. Because of their
reluctance to change diets, nonmigratory
grazers experience a substantial decline
in population sizes during droughts. “The
two types of herbivores that actually do
become abundant—mixed feeders and
migratory grazers—do so by… actively
[having] strategies to ensure that they
have a better dry season than they would
otherwise,” Staver said.
Theoretical Models
A breathtaking landscape of the Kruger National Park.
If you have ever seen Disney’s timehonored
family feature The Lion
King, you likely have a good picture
of what an African savanna looks like.
The African savanna ecosystem is home
to a large and diverse community of
megafauna, or large terrestrial mammals,
whose populations have undergone
serious declines as a result of many
complex factors, such as predator-prey
relationships, disease, and drought.
While the impact of these variables on
the population dynamics of savanna
herbivores have been well-studied by
ecologists, the dietary strategies of these
communities have only just recently been
investigated as a determining factor of
population abundances.
Seeking to better understand this
determinant, Carla Staver, Associate
Professor of Ecology and Evolutionary
Biology at Yale University, and Gareth
P. Hempson, a postdoctoral fellow
at the University of Witwatersrand
Johannesburg, examined the effects that
seasonal dietary changes have on the
populations of savanna herbivore species.
After composing two different theoretical
mathematical models and evaluating
data from several African savanna parks,
Staver and Hempson found that species
that switch their diets seasonally, in
www.yalescientific.org
addition to species that migrate to find
better forage, have increased population
sizes and dominate the savannas.
Grazing and Browsing
IMAGE COURTESY OF WIKIMEDIA COMMONS
The savannas of Africa, characterized
by trees and grasslands, boast biodiverse
habitats that support herbivores such as
browsers, who feed on tree leaves and
shrubs, grazers, who feed on grass and
other low-lying vegetation, and mixed
feeders, who alternate between browsing
and grazing depending on the season.
Browsers, such as giraffes, and grazers, such
as zebras and wildebeests, are considered
specialists because of their efficiency at
eating a particular, albeit limited, diet.
On the other hand, mixed feeders, such
as impala and elephants, are defined as
generalists because of their ability to adapt
and survive off a varied diet.
Savannas are highly seasonal systems,
meaning they alternate between a wet season
with heavy rainfalls and a dry season with
little to no rainfall. During the wet season,
grazers enjoy bountiful plant growth. But
in the dry season, when grass is sparse,
herbivores of the savanna tend to undertake
three different practices: mixed feeders alter
their food source and switch to browsing,
migratory grazers locate new foliage to
Reinforcing their theory that migratory
grazers and mixed feeders maintain
higher population abundances compared
to nonmigratory specialists, Staver and
Hempson presented two mathematical
models in a paper published in Science
Advances that illustrate the role that
dietary strategies play in population
dynamics. The first model, a discretetime
population model, takes into account
the variance of population sizes between
wet and dry season and finds the overall
rate that the populations of herbivores
increase by. Specifically, the model uses
the geometric mean—a form of averaging
found by multiplying rather than adding
numbers—of wet and dry season growth
rates to establish the comprehensive
growth rate of a population.
PHOTOGRAPH COURTESY OF PROFESSOR STAVER
This photograph captures a group of impala, a
classic example of a mixed feeder herbivore.
December 2020 Yale Scientific Magazine 23
FOCUS
Ecology
This model incorporates a few assumptions
about vegetation and diet switching; first,
it is assumed that grass is more ample and
nutritious in the wet season while browse
vegetation, such as twigs and leaves, are
more bountiful and nourishing in the dry
season; second, it is assumed that there is an
efficiency cost associated with generalism.
Whereas specialists have a particular
anatomy that allows them to be very skilled
at eating certain types of food, mixed
feeders may not be as proficient as grazers at
consuming grass or browsers at consuming
trees. This raises the question: how does
the cost of being less efficient at eating a
particular diet compare to the benefits of
being able to switch between diets? Staver’s
results show that as long as the comparative
benefits of grazing in the wet season and
browsing in the dry season make up for the
costs of switching, then mixed feeders are
more successful than specialists at achieving
larger population sizes.
The second model, an application of the
well-studied Lotka-Volterra consumerresource
model, represents the interactions
between predators and prey, or in this case,
the dynamics between herbivores and food
resources. While the previous model took
for granted the availability of grass and
trees and only considered the quality of
vegetation, this model couples herbivore
population abundance with vegetation
availability. What sets this model apart from
traditional consumer-resource models is
the inclusion of alternating seasons. In
accordance with the changing seasons,
it was observed that plant and herbivore
abundance endure cyclic patterns. While
there is some dependence on seasonal
vegetation productivity and herbivore
digestive and intake efficiency, the model
showed that “any type of seasonal diet
change, whether from grazing to browsing
or a preferred grass forage to a forage
reserve will lead to both larger populations
and more herbivore biomass,” Staver said.
Results and Implications
Given these results that mixed feeders
and migratory specialists experience
population increases as a result of seasonal
dietary strategies, what can we expect
for the field of ecology and evolutionary
biology? Whereas ecologists in the past
have predominantly focused on the effects
IMAGE COURTESY OF WIKIMEDIA COMMONS
The grasslands and trees of the savanna support the diets of both grazers like the wildebeest and zebras, and
browsers like the giraffes.
of predators on herbivores, this study
represents a “renewed focus on mixed
feeders and their implication for vegetation
dynamics and the conservation of African
savanna ecosystems,” said Staver.
One issue Staver raised is that
herbivores of the savannas are
increasingly confined to small protected
areas that limit the ability for specialists
to migrate. “As reserves become smaller
and more fenced and more divorced from
the matrix around them, the potential for
migration potentially decreases, as it has
already,” Staver said. As a result, mixed
feeding species, such as impala, are able
to feed more effectively and become the
ABOUT THE AUTHOR
dominant herbivore in a lot of these
diverse African savanna systems.
Especially in the time of the
COVID-19 pandemic, Staver’s study
demonstrates a profound lesson we
as humans can learn from the mixed
feeders of the savanna. From developing
new business models to altering the way
we learn and communicate, businesses
and individuals alike are faced with
the task of adapting to our new shared
reality. While specialization has been
historically valued and rewarded in our
society, the impala demonstrate that
ultimately, in our ever-evolving world,
generalists may prevail. ■
ANGELICA LORENZO
ANGELICA LORENZO is a sophomore in Grace Hopper College majoring in Biomedical
Engineering. In addition to writing for YSM, Angelica is a percussionist in the Yale
Symphony Orchestra, serves as Publicity Chair for the Society of Women Engineers, and
volunteers with Yale Undergraduates at Connecticut Hospice.
THE AUTHOR WOULD LIKE TO THANK Prof. Carla Staver for her time and thoughtful
discussion about her research.
FURTHER READING
Staver, A. C., & Hempson, G. P. (2020, October 2). Seasonal dietary changes increase
the abundances of savanna herbivore species. Science Advances, 6 (40). https://doi.
org/10.1126/sciadv.abd2848
Staver, A.C. (n.d.). Seasonal dietary changes increase the abundances of savanna herbivore
species. Staver Lab. https://staverlab.yale.edu/sites/default/files/files/StaverHempson_
SciAdv.mp4
24 Yale Scientific Magazine December 2020 www.yalescientific.org
Planetary Science
FOCUS
PLANETARY
PROTECTION
HOW THE ANCIENT
MOON SHIELDED
EARTH’S ATMOSPHERE
BY ANAVI UPPAL
ART BY ANMEI LITTLE
The Moon has been the Earth’s companion since long before
humans have lived on Earth. But new research shows that several
billion years ago, the Moon played a far more important role.
Researchers from the National Aeronautics and Space Administration
(NASA), University of Maryland, and Princeton University found that
the Moon may have helped protect the young Earth.
Our Sun, like other stars, spits harmful particles and radiation into
the space around it. However, the Sun used to be more volatile than it
is today. “Just like a baby, when the Sun is young, it’s energetic; when it
grows old, it becomes less energetic. Go back to four billion years ago
when the Sun was very energetic, and it emitted high stellar radiation
and intense particle fluxes,” said Princeton University astrophysicist
Chuanfei Dong. These particles and radiation have the power to strip
away a planet’s atmosphere, so in order for a young planet to keep its
atmosphere, it must be protected.
Planets use their magnetic fields to deflect most solar particles and
radiation around and away from them, kind of like a planetary umbrella.
The Earth has a protective magnetic field, but the Moon currently does
not. However, a recent reexamination of lunar samples from the Apollo
missions indicates that this wasn’t always the case. “Research was coming
out from the Apollo rocks indicating that the Moon had a magnetic field
in the past, and I really wanted to model it to determine what it was
going to look like,” said James Green, NASA’s Chief Scientist.
Green’s team found that the Moon had a considerable magnetic field
around four billion years ago that protected the young Earth. The Moon’s
magnetic field acted as a second shield to protect the Earth’s atmosphere
from the volatile young Sun. This finding has important implications for
the search for extraterrestrial life outside of our solar system. Exoplanets
with moons would be provided extra protection from their active stars,
which means that they could be located closer to more volatile stars and
still maintain life-supporting conditions.
In addition, the interaction between the Moon’s and the Earth’s early
magnetic fields would have caused some of the Earth’s atmosphere
to transfer to the Moon. Some of the Earth’s atmosphere would have
traveled along the connected magnetic field lines and added to the
early lunar atmosphere. While the Moon doesn’t have an atmosphere
today, remnants of this combined atmosphere could be preserved in
permanently shadowed craters on the Moon called cold traps. The Sun
hasn’t shined in these craters since they were created billions of years
ago, making them one of the coldest places in the solar system. Gas
that traveled from the Earth to the Moon would have been attracted
to these cold traps and should still be trapped there today. This means
that by studying the Moon today, we can figure out what Earth’s early
atmosphere was composed of. “It’s interesting to think that the early
Earth atmosphere—which was almost impossible for us to figure out—
could actually be waiting for us to discover on the Moon,” Green said.
The results of this study will help determine a research focus of NASA’s
Artemis program. Artemis is anticipated to begin next year and will
land the first woman and the next man on the Moon by 2024. With the
Artemis program, NASA plans to establish sustainable lunar exploration
by the end of the decade. “In the Artemis program, what we need to do
is go into these permanently shadowed craters and take ice cores. Not
only would water be [in those cores], but so would elements of the early
atmosphere of both the Earth and the Moon. In fact, current thinking
is that there’s probably anywhere from a hundred, two hundred, maybe
three hundred million tons of water in these craters, and a significant
portion of that may have come from the Earth,” Green said.
Green also stressed the fact that this type of space research is crucial
to understanding Earth. Our solar system has given us the unique
opportunity to see other terrestrial planets such as Venus and Mars
near us and at radically different points in their planetary evolutions.
“It gives us an opportunity to compare, understand, and recognize what
the fate and evolution of our own planet are all about,” Green said. By
studying other planets and uncovering Earth’s past, we can gain a better
understanding of where Earth currently is in its evolutionary path, and
where it’s headed in the future. ■
IMAGE COURTESY OF STEELE HILL/NASA
A visualization of how a planet’s magnetic field acts like an umbrella against
particles and radiation from the Sun.
www.yalescientific.org
Dunbar, B. (n.d.). Artemis. Retrieved November 08, 2020,
from https://www.nasa.gov/specials/artemis/
Green, J., Draper, D., Boardsen, S., & Dong, C. (2020). When
the Moon had a magnetosphere. Science Advances,
6(42), 865–879. https://doi.org/10.1126/sciadv.abc0865
Landau, E. (2020, October 14). Earth and Moon Once
Shared a Magnetic Shield. Retrieved November 08,
2020, from https://www.nasa.gov/feature/earth-andmoon-once-shared-a-magnetic-shield-protectingtheir-atmospheres
December 2020 Yale Scientific Magazine 25
FOCUS
Neuroscience
HUNTING
GHOSTS
THE FUTURE OF TINNITUS TREATMENT
BY MURILO DORION
ART BY MAYA GERADI
IMAGE COURTESY
OF PXFUEL
Seven years before he finished translating the Bible, Martin
Luther started hearing a loud buzz. The sound was so
distracting that, whenever it started, he had to put his
work aside and wait for the torment to go away. “The Devil had
something to do with it,” he concluded in a letter.
Although this passage is almost five centuries old, the suffering
it communicates still resonates with many today: an estimated fifty
million Americans suffer from tinnitus, a highly heterogeneous
disorder that manifests as phantom ringing in the ear. Although it
can be ignored by some, five percent of those affected report severe
impacts in their lives, ranging from concentration problems to
difficulty socializing or even depression. Finding a solution to these
problems can be challenging, as even identifying the source can
be difficult: For some, the sound can come from a physical source
such as muscles in their ears, while for others, ringing originates
from signal mismatches inside the brain. The former is rare and
can sometimes be treated with surgery, while patients with the
latter variety are left with the few and often ineffective treatments
that are available. Cognitive behavioral therapy can help cope with
the discomfort, but there are no approved interventions to reduce
the intensity of the perceived sound.
A clinical trial published in Science Translational Medicine,
however, is changing that landscape. And the researchers are using
a rather unexpected technique: a headphone that also shocks your
tongue. The organ was chosen in part due to the high number
of nerve endings on its surface. According to tinnitus specialist
Berthold Langguth, who is chief physician at the Department of
Psychiatry and Psychosomatic Medicine at Germany’s University
of Regensburg Hospital, hearing and sensitivity in the tongue are
actually very closely related. “You have very intense connections
between the tongue and the trigeminal nerve, and the trigeminal
nerve is strongly connected with the central auditory pathway,”
Langguth said. By stimulating those overlapping senses, the team
hoped to activate only the relevant parts of the brain and drive
neuroplasticity—literally rewiring the brain to reduce symptoms.
This hypothesis has been in the works for some time, with
promising studies in animals and smaller human cohorts. However,
Langguth warns that early positive results may not translate into an
effective treatment. “Frequently new treatments have very positive
pilot studies [with] twenty or thirty patients. But then it is not
possible to replicate these effects,” he said. This study, however,
is different. Not only did they have over three hundred patients,
but the impact of the treatment was overwhelmingly positive. “We
don’t have a response in all patients, but the majority of patients
who participated in the study reported relevant improvement that
held for twelve months,” Langguth said.
The team also randomized patients in three groups to test which
device configurations were most effective. The two main differences
between the groups were the frequency of the sound and the length
of delays—the amount of time between the sound being played and
the stimulus on the tongue. Although delays improved outcomes
in animals, humans showed better long-term improvement with
synchronized activity. These observations allow future trials to have
a better baseline for which to configure the device.
Those results also sketch a better future for the field of tinnitus
research. “Twenty years ago there was very little tinnitus research. I
think it’s the merit of philanthropic effort from non-profits [...] and
some patient organizations to help attract academic researchers to the
field,” Langguth said. Now, public agencies have gained interest in the
disorder, but the same cannot be said about the private sector yet. “There
is not so much investment at the moment because there’s no success
story,” he said. This clinical trial was funded by Neuromod, a private
company for which Langguth serves on the Scientific Advisory Board,
perhaps signaling changing tides for financing tinnitus treatment.
In spite of this development, Langguth stresses that prevention
is still the best choice. “We have none, or only very few, wellestablished
treatment options at the moment; however, what is very
well established [...] is that it’s possible to prevent tinnitus,” Langguth
said. The condition is associated with hearing loss, but waiting for
symptoms to appear is dangerous, as they might indicate that the
damage is irreversible. Thus, early prevention methods as simple as
avoiding loud noises and taking care of one’s hearing are crucial; after
all, even though tinnitus care is improving, it is best to not need it. ■
American Tinnitus Organization. (n.d.). Understanding the Facts.
American Tinnitus Association. Retrieved November 2, 2020,
from https://www.ata.org/understanding-facts#nhnes
Bikson, M., Brunoni, A. R., Charvet, L. E., Clark, V. P., Cohen, L.
G., Deng, Z.-D., Dmochowski, J., Edwards, D. J., Frohlich, F., &
Kappenman, E. S. (2018). Rigor and reproducibility in research
with transcranial electrical stimulation: An NIMH-sponsored
workshop. Brain Stimulation, 11(3), 465–480.
Conlon, B., Langguth, B., Hamilton, C., Hughes, S., Meade,
E., Connor, C. O., Schecklmann, M., Hall, D. A., Vanneste,
S., & Leong, S. L. (2020). Bimodal neuromodulation
combining sound and tongue stimulation reduces
tinnitus symptoms in a large randomized clinical study.
Science Translational Medicine, 12(564).
Langguth, B., Kreuzer, P. M., Kleinjung, T., & De Ridder, D. (2013).
Tinnitus: Causes and clinical management. The Lancet Neurology,
12(9), 920–930.
Morgenstern, L. (2005). The bells are ringing: Tinnitus in their own
words. Perspectives in Biology and Medicine, 48(3), 396–407
26 Yale Scientific Magazine December 2020 www.yalescientific.org
METALLIZING BY ISABEL TRINDADE
USING MACHINE LEARNING
TO ALTER DIAMOND
DIAMOND
Chemical Engineering
FOCUS
For centuries, alchemists have been seeking ways to convert
substances into one another. While water to wine or metal to
gold may not be possible yet, a research team has identified a
method of converting diamond to metal solely through mechanical
strain. The team, led by Suba Suresh, Ju Li, and Ming Dao, used
quantum mechanical and machine learning simulations to identify
a method of reversible metallization in diamond nanoneedles.
Under enough mechanical strain, diamond nanoneedles were
converted to metal without undergoing a phase transition, and
without causing structural irregularities in the material.
The team was interested in studying diamond due to its
properties as a semiconductor. “Diamond has a very high
degree of hardness and stiffness, which makes it ideal for a
variety of applications,” Li said. The extreme physical properties
and biocompatibility make diamond applicable to mechanical,
electronic, biomedical, and energy fields.
Previous research on nanoscale diamonds undergoing
mechanical strain demonstrated that diamond nanoneedles of
different geometries (monocrystalline and polycrystalline) and
diameter around three hundred nanometers can be reversibly
deformed under certain conditions, and this study sought
to find out how much metallization could be safely achieved
under those conditions. “Past research on nanoscale diamond
and advancements in machine learning of the electronic and
phonon structures of diamond has created new opportunities to
address new scientific questions,” Li said.
In particular, the team sought to demonstrate whether diamond
could be completely metallized under mechanical strain. They also
wanted to identify the lowest strain energy required to achieve
“safe” metallization—metallization that would not cause “phonon
instability.” A phonon is the uniform vibrational motion of atoms
at a single frequency in a material with a lattice structure, such as
diamond, so phonon instability could cause irregularities in the
properties of diamond. In addition, the team studied diamond
nanoneedles of various geometric structures, to
identify how different crystallographic and
geometric variables would influence
the metallization process.
Frank Shi, a graduate student
working on this research
project, developed a machine
learning algorithm to model
pathways to metallization
for different geometries of
diamond nanoneedles. “For this
project, we used an algorithm based
www.yalescientific.org
ART BY ELLIE GABRIEL
on an artificial neural network approach,” Shi said. The team
developed calculations and simulations for the elastic straining of
diamond, the results of which were used to determine the optimal
properties for metallization of diamond, demonstrating that “safe”
reversible metallization could be achieved under a certain degree
of elastic strain. Further strain, however, would cause phonon
instability in the diamond, which could trigger a phase change
from diamond into graphite, another form of carbon.
Using experimentally-validated simulations, the team found
that the optimal conditions for the metallization of diamond
nanoneedles depend on the geometry of the diamond and the
nanoneedle orientation. In this research, three different nanoneedle
orientations were studied, and each was found to have different
strain possibilities. Beyond the three configurations studied
here, nanoneedles with more complex geometric features can be
designed, simulated, and studied with machine learning, which
would further improve the possibilities of diamond metallization.
“There is a lot of possibility for future research in this field because
more complex needle geometries can be designed,” Li said.
The results of this study offer new possibilities for deliberate
and extreme alteration of the functional properties of diamond
using strain engineering, which could have applications in many
different fields of science, technology, and engineering. “Photons
and excitons are the main tools used for quantum information
processing,” Li said. This means that the results of this research
carry implications for other fields including quantum sensing
and quantum computing. In addition, according to Li, the
demonstration of complete metallization of diamond without
phonon instability is a groundbreaking development for power
electronics, a field in which diamond is widely used due to its
properties as a semiconductor, a material with less conductivity
that a conductor (such as copper), but more than an insulator
(such as glass). When strained, diamond is transformed into
a direct bandgap semiconductor, which means that electrons
have the same momentum in both the valence band (the highest
energy range where electrons are present) and the conduction
band (where electrons “jump” to when excited, allowing
conductivity to occur). Because absorbance increases with the
thickness of a material, a device that converts light energy based
on a direct bandgap semiconductor such as diamond would be
able to absorb visible and infrared light with much less thickness
than other materials, which could improve the design of devices
such as high-efficiency photodetectors. ■
Li, J., & Shi, F. (2020, October 26). [Online interview].
Shi, Z., Dao, M., Tsymbalov, E., Shapeev, A., Li, J., & Suresh,
S. (2020). Metallization of diamond. Proceedings of the
National Academy of Sciences, 117(40), 24634-24639.
doi:10.1073/pnas.2013565117
December 2020 Yale Scientific Magazine 27
FOCUS
Culinary Science
T H E SECRET
O F
SALTED CARAMEL
SODIUM CHLORIDE INTENSIFIES NEURAL FIRING IN RESPONSE
TO GLUCOSE BY ELISA HOWARD | ART BY MAYA GERADI
Imagine the luxurious taste of salted
caramel trickling over an ice cream
sundae, oozing out of a chocolate
candy bar, or glazing popcorn with a
shiny surface of delectable perfection.
In 1977, French chocolatier Henri Le
Roux struck the perfect balance between
sweet and salty in the development of
the amber-colored confection exploding
in popularity across the United States.
But, have you ever wondered why salted
caramel is such a heavenly treat for the
taste buds? Researchers in Japan found
the answer by investigating proteins
found in the kidneys and small intestine.
Taste buds located in papillae—
tiny bumps on the surface of the
tongue—house receptor cells that
generate electrical signals known as
action potentials in response to sweet,
salty, sour, umami, and bitter food
molecules. Fiber bundles known as
IMAGE COURTESY OF WIKIMEDIA COMMONS
The Mallory’s trichrome stain shows the taste buds
of mice viewed through optical microscopy.
the chorda tympani and
glossopharyngeal nerves
relay action potentials to the
nucleus of the solitary tract
for subsequent transmission to
the cortex. A group of proteins
classified as T1R receptors is
responsible for detecting artificial
sweeteners or natural sugars like glucose
and sucrose. However, in 2003, a study
led by Sami Damak found that mice
deprived of T1R3s maintained sugardetecting
abilities, thereby suggesting
alternate pathways for the perception of
sweet compounds.
Following this discovery, a team of
Japanese and American researchers
turned their attention to sodiumglucose
cotransporters (SGLTs),
protein molecules commonly found in
nephrons and small intestine mucosa.
SGLTs couple the favorable movement
of sodium ions with the uptake of
glucose molecules into the intracellular
space. All the while, sodiumpotassium
pumps maintain proper ion
concentrations inside and outside the
cell. Interestingly, the SGLT1 proteins
were recently discovered in the inner
lining of the mouth. To investigate
the role of these proteins in sugarresponsive
taste cells, professor Keiko
Yasumatsu of Tokyo Dental Junior
College and colleagues recorded the
neural activity in the chorda tympani
and glossopharyngeal nerves of eight to
twenty-week old laboratory mice. The
researchers prepared glucose and
sucrose solutions mixed with sodium
chloride (NaCl), a chemical commonly
known as table salt. The mice were
knocked unconscious through
anesthetic injections, and the solutions
were applied on their tongues. Then,
the mice were treated with phlorizin,
a glucoside acting as a competitive
inhibitor of SGLTs.
The researchers found that the chorda
tympani and glossopharyngeal nerves
of the mice fired more frequently in
response to glucose-NaCl solutions
than pure sugar solutions. All the while,
mixtures of table salt and artificial
sweeteners, citric acid, quinine, or other
taste compounds failed to generate
such enhanced activity. Indeed, the
combination of glucose and table salt
plays a decisive role in sweet taste
detection, as the SGLT1 receptors utilize
two sodium ions for the transport of
one glucose molecule into taste cells.
“In the presence of sugar molecules, the
increase in NaCl content of saliva allows
for the increased generation of action
28 Yale Scientific Magazine December 2020 www.yalescientific.org
Culinary Science
FOCUS
IMAGE COURTESY OF PEXELS
Salted caramel apples are a popular autumn dessert
in the United States.
potentials,” Yasumatsu said. Those
potentials are transmitted through
nerve fibers to the brain, producing
the perception of glucose. Even without
additional salt consumption, SGLT1
may play a role every time we consume
sugars, or more broadly carbohydrates.
“Saliva has 5-100 mM NaCl. We may
already enjoy carbohydrates with
NaCl even when we did not add salt,”
Yasumatsu said.
In addition, the researchers
discovered a significant reduction in
the neural firing of mice treated with
phlorizin, a compound commonly
found in apple tree bark. As phlorizin
inhibits SGLTs, the results suggest that
the cotransporters are instrumental
in sweet-sensitive taste cells. To
continue their investigation of SGLT1,
Yasumatsu and researchers analyzed
the relationship between sugar-solution
type and mice consumption behavior.
Conscious mice were given glucose
solutions with and without NaCl. A
lickometer with a laser beam mechanism
was used to record the mean number of
mice licks for the solutions. Mice licked
sugar solutions containing table salt
more frequently than solutions without
salt, suggesting an enhanced preference
for glucose in the presence of NaCl.
Ultimately, the researchers reasoned
that sweet-detecting taste cells exist in
three major forms depending on T1Rs,
SGLTs, or both receptor types. SGLTs
may enable nerve activity in response
to glucose even in the absence of T1R
receptors. This helps explain the findings
of the 2003 research study. At the same
time, the two sweet receptors may work
in conjunction. In the presence of salt,
SGLTs may allow for increased glucose
detection by the T1R receptors. “SGLT1
mediates the deliciousness of sugars,”
Yasumatsu said.
But, what does this study on mice
have to do with humans? While mice
look drastically different from people
in both size and appearance, they have
genomes roughly eighty-five percent
identical to that of human beings. As
mice have similar organs, nervous
systems, and biological development
patterns, Yasumatsu believes that her
findings allow for the development of
hypotheses on sugar detection in the
human body.
Now, let’s return to salted caramel. In the
world of baking, salted caramel is made
with granulated sugar that is boiled into
a brownish-colored liquid. Then, butter,
heavy cream, and vanilla are added. Next
comes the secret ingredient: salt, which
is mixed into the bubbling liquid or
sprinkled atop the cooled concoction.
When the first heavenly bite of caramel
enters your mouth, the salivary amylase
enzyme and disaccharidases on the taste
cell begin to break down the delectable
candy. In SGLT-dependent taste cells, the
cotransporters provide a pathway for the
movement of glucose monosaccharides
aided by the sodium ions of table salt.
With the help of NaCl, the sweetsensitive
taste cells generate enhanced
action potentials retrieved by the brain.
“We can enjoy meals when salt is added
to all dishes including sandwiches or
hamburgers. Carbohydrates plus sodium
chloride offers deliciousness in daily life,”
Yasumatsu said.
To sum it up, this is the secret of salted
caramel: it is the perfect marriage of
sweet and salty that activates SGLT1
proteins for magical perception of the
concoction trickling ice cream, oozing
out of a candy bar, or glazing popcorn
with a shiny surface of delectable
perfection. Is your mouth watering yet? ■
IMAGE COURTESY OF WIKIMEDIA COMMONS
Scientists used mice to observe neural activity and consumption behavior when given sugar solutions
with and without NaCl.
Randall, I. (2020). Why adding salt makes fruit—and candy—sweeter. Retrieved from https://
www.sciencemag.org/news/2020/10/why-adding-salt-makes-fruit-and-candy-sweeter
Yasumatsu, K., Ohkuri, T., Yoshida, R., Iwata, S., Margolskee, R. F., & Ninomiya, Y. (2020). Sodiumglucose
cotransporter 1 as a sugar taste sensor in mouse tongue. Acta Physiologica, n/a,
e13529. https://doi.org/10.1111/apha.13529
www.yalescientific.org
December 2020 Yale Scientific Magazine 29
FOCUS
Microbiology
THE LEVELS
ART BY
NOORA
SAID
BY
ALEXANDRA
HASLUND-GOURLEY
OF LEARNING
AT DAYCARE
UNDERSTANDING THE IMMUNOLOGICAL ADVANTAGES
TO CHILDREN BEING IN NATURE
Imagine yourself in nature. As you
step through the forest, your foot is
cushioned by moist, fertile soil. You
look up to see light streaming through the
verdant canopy above. Breathing in, the
air is layered with wafts of peat moss and
pine needles. As you reach out to touch the
trunk of a pine tree, you feel the stress of
urban life being washed away from you,
and you feel replenished, rejuvenated,
perhaps even healed, by immersing
yourself in nature. Previously, we may have
seen only psychological benefits to being in
nature, but recent research at the University
of Helsinki has identified tremendous
physical and immunological benefits to
connecting with the outdoors.
Whether you are aware of it or not, your
microbiome (the set of bacteria that occupy
your skin, gut and other mucosal areas of
your body) engage in a silent, evolutionarily
engrained conversation with the microbes
in your environment. If you brush against
bushes or run your hand through soil, an
extremely diverse set of bacteria come into
contact with your skin—giving them the
opportunity to become new residents of your
microbiome. Incredibly, even the groundcover
or vegetation around your home,
school or place of work can significantly affect
your microbiome. These resident bacteria
then interact with your immune system—
causing cascades of various immune cells
and cytokines to be released. This extremely
complex web of immunological signals can
become imbalanced when your resident
microbes lack diversity (a state referred to as
dysbiosis) and lead to inflammatory diseases.
This link between the friendly, diverse
bacteria found in nature and our overall
well-being underscores a shocking truth
of modernization and the advancement
of sterile environments. As a result of our
diligent adherence to hygiene, sterilized
foods, pesticides, and use of antibiotics—in
order to eradicate and separate ourselves
from pathogens—we have also destroyed
the bacterial landscape that helps us
maintain homeostasis. We simply couldn’t
live without helpful bacteria. In fact, if you
were to do a genetic analysis of the DNA
within your body, a measly one percent of
the DNA would be yours to claim—leaving
the remaining ninety-nine to the bacteria
which occupy your skin, intestinal tract,
eyes, nose, ears, and mouth. These bacteria
help digest food and protect us from other,
harmful bacteria that could wreak havoc
on our body. Additionally, dysbiosis in the
microbiome of our bodies has been linked
to rheumatoid arthritis, inflammatory bowel
disease (IBD), celiac disease, Type 1 Diabetes,
metabolic syndrome, neurodegenerative
disorder, and malignancy—all diseases
which have become increasingly prevalent
in westernized countries.
In order to quantify this recently
identified relationship between foreign
microbes and our overall well-being,
researchers Marja Roslund and Aki
Sinkkonen performed an intervention
study at Finnish daycares. In their study,
they compared the bacterial communities
and immune systems of children attending
nature-oriented, urban, and intervention
daycare centers. The intervention centers
were urban daycare centers that were
enriched with a forest floor and sod
ground covering. Over a twenty-eightday
period, children in the intervention
daycares were guided through various
activities including planting, crafting
natural materials and playing in the nature
in order to ensure sufficient exposure to
natural microbiota in the soil.
Incredibly, children’s microbial and
immunological profiles underwent
30 Yale Scientific Magazine December 2020 www.yalescientific.org
Microbiology
FOCUS
significant changes just from interacting
with soil. While children from the natureoriented
daycares had much higher
microbial diversity initially, the microbial
diversity of children in the intervention
group increased to nearly comparable levels
by the end of the twenty-eight-day period.
Notably, the relative abundance of bacteria
associated with IBD decreased, while the
diversity of bacteria known to help maintain
the lining of our intestines increased.
These shifts in bacterial communities then
initiated significant downstream effects on
the children’s immune systems. While we
are far from understanding the complete
web of interactions that comprise an
immune system, there are a few key markers
that point towards the overall state of one’s
immunological health. For instance, they
tracked the frequency of autoimmune disease
preventing regulatory T cells in children.
Additionally, the researchers investigated
the proportion of the anti-inflammatory
interleukin-10 (IL-10) to the inflammatory
interleukin-17 (IL-17) as well as the amount
of anti-inflammatory cytokine Transforming
growth factor-Beta1 (TGF-β1). In general,
all three of these signaling molecules bind to
different receptors on immune cells which,
in turn, provokes the cells to produce either
pro- or anti- inflammatory proteins.
By the end of the study, children in
the intervention group presented higher
IL-10 to IL-17A ratios, increased levels
www.yalescientific.org
of TGF-β1, and higher frequencies of
regulatory T cells—all signs of a less proinflammatory
immune system. Thus, it
seems that just as the children in daycare
centers were learning how to interact
with others and navigate the world,
their immune systems were receiving an
education of their own. This intervention
study sheds light on the crucial link
between our health and our environment,
providing a glimpse of a future where
deliberate steps could be taken to create
and curate healthy immune systems.
Additionally, in a parallel study focusing
on the qualitative effects of the natural
intervention at daycares, researchers at the
University of Helsinki found that children’s
motivation to learn, activity levels, and
overall well-being also increased.
While millions of dollars have been
justly awarded to fund research seeking to
treat inflammatory diseases that arise from
microbial dysbiosis, recent results have
started to point to possibly inexpensive
and easy ways to prevent such diseases
from occurring at all. For instance, in
another recent study, researchers at the
University of Helsinki designed a widespectrum
microbial inoculation mixture
that could reproduce the slow-growing
and elaborate agglomeration of ancient
microbes in forest soil. Engineered to leave
out any naturally occurring pathogens,
this inoculate could safely be integrated
into our urban soils and landscapes in
order to increase microbial diversity and
potentially mitigate the risk of immunemediated
diseases in urban populations.
Unfortunately, there are ideological
barriers to implementing such programs.
“People are afraid of microbes because
there are some bad microbes,” Posland
said. Intuitively, the thought of bacteria
conjures up ominous images of fuzzy
cylindroids infested with infectious
diseases. “Current legislation requires
that many products do not contain
microbes. Creating policy change
requires collaboration between many
organizations and that the decision
makers understand the science and value
of maintaining a healthy microbiome.
It’s a slow process to change the way
that things are currently done in urban
planning, green infrastructure and so
on, ” Sinkkonen said.
While we have made leaps and bounds
in our scientific understandings of
germs since the days of Louis Pasteur,
trying to conquer disease by completely
eradicating bacteria from our food,
living environments, and bodies may
no longer be the best course of action.
Recent research, coupled with the rise
of immunological disorders in Western
populations, has proven that health is
not always synonymous with sterility. It
seems that we have reached a point of
inflection where science and modern
technology should be used to understand
and reconnect us to—not separate us
from—nature. Perhaps the next era of
medicine and healthcare will engage a
more nuanced conversation with the
lifeforms that have evolved alongside us
for time immemorial, allowing us to step
towards a healthier world. ■
Roslund, M.I., Puhakka, R., Grönroos, M., Nurminen, N., Oikarinen, S., Gazali, A.M.,
Cinek, O., Kramná, L., Siter, N., Vari, H.K., Soininen, L., Parajuli, A., Rajaniemi, J.,
Kinnunen, T., Laitinen, O.H., Hyöty, H., Sinkkonen, A., 2020. Biodiversity intervention
enhances immune regulation and health-associated commensal microbiota among
daycare children. Science Advances.. https://doi.org/10.1126/sciadv.aba2578
December 2020 Yale Scientific Magazine 31
FOCUS
Robotics
CURLY THE ROBOT
ARTIFICIAL INTELLIGENCE ON ICE
BY JENNY MAO
At the 2018 Pyeongchang Winter
Olympics, the South Korean
women's curling team won their
country’s first medal in curling. Before
their shockingly successful run, the
sport was barely known to many South
Koreans. Almost overnight, the country
was swept up in a curling craze.
Curling has been called “chess on ice”
for the high level of strategy involved in
every move. On the surface, the rules of
curling seem simple enough: Two teams
take turns throwing stones across the
ice with the goal of getting it as close to
the bullseye as possible. However, every
throw requires an incredible amount of
calculation to get the ideal velocity, angle,
and direction of curl to knock out their
opponent’s stones while simultaneously
getting their own stone to stop on the
bullseye. Inspired by the sport's need for
quick decision-making and adaptation, a
team of Korean and German researchers
developed a deep learning curling robot
that could hold its own and even win
against top-ranked human teams.
Meet Curly, the artificial intelligence
(AI) curling robot system and star
athlete extraordinaire.
The lean mean curling machine is
made up of two physical parts: skip-
Curly and thrower-Curly. Thrower-
Curly rotates and releases the stone, and
skip-Curly processes the locations and
trajectories of all stones with imaging
techniques. These robots have long necks
to allow them to survey the entire rest of
the ice, giving them a gawky giraffe-like
appearance. However, once the game is
in play, thrower-Curly tucks in its neck,
transforming into a surprisingly agile
athlete equipped with video analysis,
data communication, and throwing
control modules strong enough to
accelerate a hefty curling stone.
While Curly’s physical ability is quite
impressive, the real secret to Curly’s
prowess lies in its curling AI which
acts as a strategy planning model,
curling simulator, and adaptive Deep
Reinforcement Learning (DRL) model.
Reinforcement Learning describes
a learning problem in which the goal
is to maximize a long-term goal or
reward. DRL is an incredibly powerful
technology because it can learn by itself
using a process of trial and error, typically
through virtual simulations. However,
these simulations are typically done in
specific stationary environments, which
means that every time an environment
changes, the DRL model has to go
through the process of relearning. This
ART BY ELAINE CHENG
works for stationary tasks like chess, but
not so much for robotic star athletes.
“Curly learned states from millions
of actions in simulations [...] In the real
world, we may not even be able to perform
hundreds of actions for the purpose of
learning in each case. The system can
never replicate the real world,” said Seong-
Whan Lee, senior author of the study
and Professor of Brain and Cognitive
Engineering at Korea University.
After all, it is one thing to simulate
moves on a chessboard and another to
play a physical sport in live, changing
conditions. Changing conditions in the
real world are one of the largest obstacles
to applying AI outside of the confines
of a controlled lab environment, and
many researchers have done work to try
to reduce the gap between a simulated
32 Yale Scientific Magazine December 2020 www.yalescientific.org
Robotics
FOCUS
environment and a real-world scenario.
This is why the researchers chose to
study DRL in the context of curling.
“Curling is challenging because
it requires precise throwing (robot
control problem) and strategic planning
to win. Moreover, the environmental
characteristics change at every moment,
and every throw has an impact on the
outcome of the match,” Lee said.
Ice is slippery and unpredictable. Over
the course of a single curling match, there
are many differences in the smoothness of
the ice, wear of the pebble, temperature,
and humidity. No two throws have the
same conditions. In fact, if you apply
the exact same direction, force, and curl
to a stone, the stone’s final trajectory
could be far off enough to account for
the difference between a gold medal and
finishing off the podium.
The typical relearning process that
standard DRL models go through to
accommodate these different factors
is impractical in a curling tournament
because of time constraints. That’s
the problem that Lee, in collaboration
with Klaus-Robert Müller of the Berlin
Institute of Technology, set out to solve.
“Our proposed adaptation framework
can compensate for uncertainties and
nonstationarities that are unavoidable
in the curling game by augmenting
standard DRL through temporal features,
which helps to lower the distance gaps
to competitive levels. Specifically, our
framework is that Curly performs
adaptive actions that can respond to
the environment changes that occur
continuously with every shot,” Lee said.
Unlike existing DRL models, their
proposed adaptation framework learns to
compensate for the unknowns over a short
time period. When applied to curling, the
AI is able to recalculate the best throwing
strategy for each turn, making Curly a
formidable force on the ice.
Curly plays through seamless
communication between the skip- and
thrower-Curly. First, skip-Curly uses
active computer vision to identify
where the stones are on the ice and
IMAGE COURTESY OF PROFESSOR SEONG-WHAN LEE
This photograph shows thrower-Curly throwing
the stone.
transmits them to the curling AI. With
the knowledge of where the stones are
and their implications for the game
status, the strategy planning AI figures
out the best strategy to compute the
most optimal throw. The crucial step
occurs when the adaptation DRL model
computes an adaptation to the strategy,
factoring in any uncertainties within
the icy environment. This accomplishes
the overarching aim of Lee and
Müller’s study by incorporating and
adjusting for variability in a real-world
environment. Finally, the information
is communicated to thrower-Curly, who
delivers the stone with a rubber grip.
After more than two years of trial and
error, the researchers and Curly were
ready to test their skills on the big stage.
Curly played four matches against expert
human teams: a top Korean women’s
curling team, and the national wheelchair
reserve curling team. You might notice
that Curly can’t sweep, so these matches
weren’t exactly reflective of an Olympic
match. Still, Lee was surprised at Curly’s
success, as the robot won three out of the
four matches it played against the two
Korean national teams.
Curly also played some collaborative
games in which it showed the human
players the computed throw strategies,
and the human players executed and
swept the stone. The collaboration
between robot and human athletes was
very successful. Compared to the nonadapted
algorithm, the level of error
in distance traveled was significantly
reduced when using the proposed
adaptive DRL framework.
“Even elite players don’t always get
the stone to the target. They can be off
by an average of three to four feet (0.8
meters to 1.3 meters). Curly was able
to match that margin of error. [...] Our
results indicate that the gap between
physics-based simulators and the real
world can be narrowed,” Lee said.
The framework has implications
for the application of AI to changing
environments beyond Curly’s stunning
athletic career. Curly’s success adds
more fuel to the question of the 21st
century: can AI outsmart humanity?
On May 12, 1997, IBM’s Deep Blue
supercomputer defeated Chess world
champion Garry Kasparov. More
recently, in 2016, AlphaGo beat the
legendary Go player Lee Sedol 4–1, a
bit step forward for machine learning,
because Go is exceptionally complex—
there are significantly more possible
board configurations than the number
of atoms in the universe.
After this historic victory, a more
recent iteration of AlphaGo known as
AlphaGo Zero—which, liked Curly,
uses DRL—was introduced in 2017.
In AlphaGo Zero’s case, the computer
started off with a neural network that
had absolutely zero knowledge of
Go. Similar to how Curly learned the
sport of curling through simulations,
AlphaGo Zero was able to learn Go by
playing against itself. After just eight
hours of learning, AlphaGo Zero bested
the former version of itself, AlphaGo.
The performance of AlphaGo Zero
shone a light on the powerful ability of
AI to learn complex tasks using DRL,
unconstrained by the limits of human
knowledge. Curly takes that one step
further by showing that robots have the
potential to adapt to the “real world,”
opening up the door for AI to become
increasingly integrated in our homes,
workplaces, and in
Curly’s case, maybe
even bask in the
glory of a gold
medal finish at
the Olympics. ■
Won, D., Müller, K., & Lee, S. (2020). An adaptive deep reinforcement learning framework enables curling robots with
human-like performance in real-world conditions. Science Robotics, 5(46). doi:10.1126/scirobotics.abb9764
www.yalescientific.org
December 2020 Yale Scientific Magazine 33
COUNTERP
YOUR COVID-19 TEST RESULT
MAY BE LYING TO YOU
JOHNS HOPKINS RESEARCHERS DISCOVER HIGH FALSE NEGATIVE RATE FOR COVID-19 TESTS
BY VERONICA LEE
Accurate COVID test results are critical in guiding hospitals, workplaces, universities, and other institutions to make and implement policies.
IMAGE COURTESY OF PIXABAY
For over half a year, the global pandemic caused by COVID-19 has
left over two million people dead and tens of millions of people
sick. And it’s not slowing down. Without an official vaccine
approved in the US as of the time of writing, most healthcare providers
across the nation have relied on reverse transcriptase polymerase chain
reaction (RT-PCR) tests to detect severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2) in high-risk populations such as nursing
home residents, hospitalized patients, and health care workers. RT-PCR
tests, administered using nasal or throat swabs, work by identifying
viral RNA from patient samples. But can we actually trust them?
In a study published in the , researchers at
Johns Hopkins University addressed this very question. Led by Lauren
Kucirka, an obstetrics and gynecology resident at Johns Hopkins
Medicine, the team studied the sensitivity of respiratory PCR-based tests
and the probability of false negatives during a crucial “window period”
after infection. Sensitivity is a measure of a test’s ability to correctly
identify positive results for people who have the condition. A false
negative occurs when a patient who is actually positive for the condition
receives a negative test result, usually due to very low amounts of virus
in the sample that go undetected.
Accurate test results for COVID-19 are extremely important
because hospitals, workplaces, universities, and other institutions
use them to make decisions and implement policies. “With
limited resources, hospitals use these tests to rule out infection
and conserve personal protective equipment,” Kucirka said.
“When exposed healthcare workers or patients test negative, they
can be cleared to return to work, and certain measures to prevent
the spread of infection can be removed. This poses a major threat
if these tests are not as reliable as we think they are.”
Kucirka and her team applied a statistical model to analyze data
from seven published studies. Their set represented a total of 1330
RT-PCR-tested respiratory samples, collected from patients who
either exhibited symptoms or had known exposure to the virus, with
information on the test’s performance over time.
The team found that one day after initial exposure, the false
negative rate was one-hundred percent. In other words, if you take
the test one day after close contact to COVID, it is essentially useless.
After four days, that rate only decreased to sixty-seven percent. On
the fifth day, the average point of symptom onset, false negatives still
occurred in thirty-eight percent of patients. Never did this rate drop
below twenty percent, revealing the frighteningly low sensitivity
of PCR-based tests for SARS-CoV-2. Put simply, based on the
researchers’ results, at least one in five people who have COVID will
receive a negative result from a respiratory PCR test.
Such results will not necessarily be fixed by improved testing methods,
as there are biological limitations inherent to any viral testing. We can
see similar rates of false negatives with tests for other viruses, such as the
flu. Rather, Kucirka believes these results should be used to educate and
inform policies and protocol, especially regarding high-risk populations.
“I think the most important thing is to understand that the test is a tool,”
Kucirka said. “It’s the best tool we have, but we have to understand that
it’s not perfect and that false negatives are possible. If a patient had a highrisk
exposure or is exhibiting convincing symptoms, the conservative
thing to do is to treat that person as infected.”
Kucirka also stressed that the data were from studies extremely
varied in design and conduct, which may have significantly
affected their results, although the team’s sensitivity analysis
showed consistent results despite this heterogeneity. In the future,
she hopes that more uniform data can be collected to provide
more accurate estimations of the false negative rate.
“That’s why we made our data and statistical code publicly
available,” Kucirka said. “Hopefully as more data comes in,
other researchers will use the code, and the results will be
updated with more accurate numbers.”
Currently, Yale tests its on-campus undergraduate students using these
respiratory PCR-based tests, administered two times a week. However,
the low sensitivity of the test may pose a major threat to the university
and others like it. In response, Kucirka emphasized the importance of
preventative measures like social distancing and wearing masks. Given
the results of her study, it is clear that we must remain conservative and
cautious in our activities to ensure our safety as a community, rather
than rely on testing alone to completely eliminate risk. ■
Kucirka, L. M., Lauer, S. A., Laeyendecker, O., &
Boon, D. (2020). Variation in False-Negative
Rate of Reverse Transcriptase Polymerase Chain
Reaction–Based SARS-CoV-2 Tests by Time Since
Exposure. Annals of Internal Medicine, 173(4),
262-267. https://doi.org/10.7326/M20-1495
DNA IMAGE COURTESY OF PIXABAY
IMAGE COURTESY OF WIKIMEDIA COMMONS
34 Yale Scientific Magazine December 2020 www.yalescientific.org
OINT
CLIMATE CHANGE IS WORSE
THAN YOU THOUGHT
BY CHARLOTTE LEAKEY
IMAGE COURTESY OF PIXABAY
Bramble Cay melomys are the chubbiest brown mice you’ve
never heard of. They lived on a small island on the northern
tip of the Great Barrier Reef until they met their unfortunate
demise in the early 2000s. Scientists worldwide grieved the
extinction of these elusive critters, both for the ecosystems they
left behind and for the dire situation that their extinction brings
to light. “Significantly, this probably represents the first recorded
mammalian extinction due to anthropogenic climate change,” a
2016 Queensland Government report postulated. As modern-day
anthropogenic (human-caused) climate change progresses, other
fauna of the Earth are also projected to suffer immensely. Alas, if
climate-driven extinctions of ancestral human species thousands
of years ago give any indicators about the present, the situation
might be even worse than we thought.
Pasquale Raia’s group at the University of Naples Federico
II studied the fossil records of five extinct human species, such
as Homo erectus and Homo neanderthalensis, in addition to our
own, to see how they reacted to natural changes in climate. The
researchers looked at climatic niches, the conditions in which a
species can survive and thrive. By studying fossil records with
a climate emulator, a computational tool that supplies highresolution
temperature and rainfall data, the researchers estimated
the climatic niches during the time period and in the regions in
which each human species lived. After distributing each species’s
fossil record into respective consecutive time bins—a statistical
technique for discretizing large sets of data—they compared
the niche of each bin to the fully realized climatic niche that the
species encompassed throughout its evolution.
Right before their extinction, in the last time bin, three human
species lost a significant proportion of their climatic niche. These
results were consistent across different fossil records and with controls
for various confounding factors, such as species interbreeding and
competition with Homo sapiens. “If you consider the entire history
of a species as a sphere, we thought that the diameter of the sphere of
each bin would be a constant proportion of the entire sphere because
humans are so good at modifying their climatic conditions,” Raia said.
“[Instead], in the last bin, that sphere became very tiny.” Additional
statistical analysis further confirmed that climate change in particular
caused the shrinkage of the bin sphere, accelerating the extinctions.
What does this mean for us, the last prevailing Homo species,
as we face a climate crisis today? There’s good(ish) and bad news.
www.yalescientific.org
The good: “I do not feel that we as humans really risk going extinct
because of future climate change,” Raia said. Though we face drastic
damages to our lifestyle, as a species, we have the ability to create
technology that can let us at least survive just about anything that
climate change has to throw at us. Floods, droughts, drowning
cities, tropical storms, or even ice ages would be devastating, but
they would not be at a scale to completely wipe out the human
race, unlike the fate of the hapless hominids of the past.
The bad news concerns other life on Earth. “[The Homo species]
were endowed with a lot of skills that were quite unnatural, quite
rare. They were able to master fire, produce clothes and spears,
and move over very large distances,” Raia said. “Despite this,
climate change that was not as fast and not as extreme as the
current climate change was enough to wipe them extinct.” This
is very concerning: given this result, it is difficult to envision how
the fauna of the Earth, which are far less technologically advanced
than any Homo species, could possibly survive anthropogenic
climate change—especially considering that it is occurring at a
rate orders of magnitude more quickly than past events.
Exactly how vulnerable are our precious fauna? The
preliminary results look grim. “They have not enough space,
the populations are too small, too isolated, too fragmented,”
Raia said. And humans have been frustratingly slow to help.
“We are doing almost nothing—we are thinking a lot, studying
a lot, trying to do a lot of things,” Raia said. “I think probably a
teenager from Sweden is doing more than politicians have done
in the past twenty years or so.” If these patterns continue, we are
looking towards a disaster, both for the fauna of our planet and
for the modern lifestyle we hold onto. ■
Gynther, I., Waller, N. & Leung, L.K.-P (2016). Confirmation of
the extinction of the Bramble Cay melomys Melomys rubicola
on Bramble Cay, Torres Strait: results and conclusions from a
comprehensive survey in August–September 2014. Unpublished
report to the Department of Environment and Heritage
Protection, Queensland Government, Brisbane.
Raia, P., Mondanaro, A., Melchionna, M., Febbraro, M. D., Diniz-
Filho, J. A., Rangel, T. F., . . . Rook, L. (2020). Past Extinctions
of Homo Species Coincided with Increased Vulnerability
to Climatic Change. One Earth, 3(4), 480-490. https://doi.
org/10.1016/j.oneear.2020.09.007
December 2020 Yale Scientific Magazine 35
NDERGRADU
CELEBRATING YALE’S THREE GOLDWATE
ALEX COHEN ‘21, KENDRA LIBBY ‘21, JASON YANG '21
Established in 1986, the Goldwater
Scholarship has long worked
to recognize sophomores and
juniors who have demonstrated a strong
commitment to and potential in research
in natural sciences, engineering, and
mathematics.
Of the 396 college students awarded the
2020 scholarship across the United States,
three were Yale College juniors: Alex
Cohen, Kendra Libby, and Jason Yang. In
their respective fields of discrete geometry,
biochemistry, and chemical engineering,
each displayed an impressive level of
intellectual vigor, intensity, and passion.
ALEX COHEN
Alex Cohen initially fell in love with pure
math in his first year at Yale from
a class with Professor Yair
Minksy. “The way that we
built up abstract tools over
time and used them to
answer basic questions
was beautiful and
special,” Cohen said.
He then independently
studied math over the
summer, garnering
his own understanding
and appreciation for
the subject while doing
research in computer science and
mathematics in Daniel Spielman’s lab.
Cohen gained interest in his specific
research field, discrete geometry, after
attending the 2019 Baruch Combinatorics
Research Experience for Undergraduates
(REU). Discrete geometry is the study of finite
configurations of objects in a plane. Prior to
the REU, Cohen had never been exposed to
this branch of pure math, but the summer
research program quickly sparked his interest
in a field he had never even considered. “It’s a
fun way to combine combinatorial reasoning
with geometric intuition,” Cohen said.
Cohen’s excitement for discrete geometry
only grew after his summer experience.
His research culminated in his own paper,
“A Sylvester–Gallai Result for Concurrent
Lines in the Complex Plane,” which was
accepted in 2020 by the journal Discrete
and Computational Geometry.
Reflecting on his undergraduate experience,
Cohen first underlined the importance
of a broad foundation as a precursor to a
future path in research. “You need to, as an
undergraduate especially, get a really strong
foundation that’s as wide as possible in the
field, because you really want to know as
much broad context as possible in order to do
more research later,” Cohen said.
He simultaneously emphasized the
importance of being excited and
passionate about your field.
“Letting yourself get
obsessed with some
problem or some
book—letting yourself
go off on tangents
and spending a week
working on a problem
that doesn’t matter—
is really important for
personal and academic
development, which is
a precondition for doing
research,” he said.
Mathematics and research are not
Cohen’s only passions. Outside of his major,
Cohen loves to go on walks, play board
games, and do political work and advocacy on
campus. He cited his largest extracurricular
commitment to be his involvement with the
Yale Endowment Justice Coalition.
After graduating from Yale College with
the Goldwater Scholarship, Cohen plans to
pursue a Ph.D. in mathematics. “The most
important thing is to make sure that research
is fun; if it’s not, then what’s the point?” he
said. Clearly, for Cohen, mathematics will
always mean more than a degree or a job.
KENDRA LIBBY
Kendra Libby is a woman of many
talents. She’s a foxtrotting ballroom dancer,
a horseback rider, and, perhaps most
importantly, a cellular biology researcher. But,
whether it’s offering to take her profile writer
down to her favorite barn for a riding lesson
or showing off the handmade Chewbacca and
Dumbledore replicas she crocheted in her
limited downtime, she’s always eager to share
her passions with others.
After all, when Libby was a young girl,
Yale students shared their passion for
science with her. Growing up in nearby
Branford, Libby participated in the Girls
Science Investigation program, which is
operated by the physics department. On
Saturdays, she would come to campus
and conduct various experiments that left
her with a lasting enthusiasm for science.
“Instead of talking at us, they let us work
through [the explanations] on our own,”
Libby said. She eventually returned to the
program as a project leader.
In high school, Libby researched
inflammatory responses during pregnancy,
sparking her interest in protein biochemistry
and biosignaling. Shortly thereafter, in her
first year at Yale, Libby took Associate Dean
of Science Sandy Chang’s Topics in Cancer
Research seminar, a pivotal moment in
Libby’s intellectual life. When cell biology
professor Xiaolei Su arrived at Yale that
year, Libby jumped at the opportunity to
work in his lab. She’s been there ever since.
Libby’s current research focuses on
improving existing chimeric antigen
receptor (CAR) therapy. T-cells have
protrusions that recognize undesirable cells
for attack by the immune system. However,
36 Yale Scientific Magazine December 2020 www.yalescientific.org
ATE PROFILE
R SCHOLARSHIP WINNERS
BY ALEX DONG &
ATHENA STENOR
cancer cells are unusually good at blending
in. CAR therapy, therefore, seeks to improve
T-cells’ radar for cancerous cells by adding
manmade molecules, CARs. Current CARs
tend to get stuck in the middle of the T-cell,
where they are useless. So, Libby’s been
refining the technique, looking for a way to
get CARs to the cell surface by modifying
membrane proteins.
Libby looks forward to pursuing a
career in academia. That said, she hasn’t
always been completely sure about her
future in science. As a bisexual woman,
it was sometimes challenging to envision
herself in high-level research. This
changed early on in her Yale career, when
through a women in STEM mentorship
program, Libby connected with a
leader of the graduate chapter of Out in
STEM, an organization for LGBT STEM
professionals. Libby, in turn, was inspired
to revive the undergraduate chapter. “It’s
been really fantastic to see someone who’s
actually a queer grad student in STEM
living and doing it, because there’s so
little representation,” Libby said. “Anytime
you’re able to actually see somebody like
you, it gives reassurance that when you
want to go to grad school, you’ll be able to
do it.” It’s only fitting, then, that Libby has
turned out to be a fantastic role model for
young female scientists herself.
www.yalescientific.org
JASON YANG
Jason Yang has had a
chemical engineer’s spirit
his whole life. “When I
was younger, I was always
just really interested in
tinkering around with
chemicals and mixing
things,” he said. His mother,
a mechanical engineering
professor at Northwestern
University, stoked the flames of his
curiosity, taking him to work with her and
exposing him to just how fun science could
be. Yang holds onto fond memories of
pickle electrocutions and other whimsical
experiments he participated in as a kid.
By high school, Yang was an enthusiastic
member of the Science Olympiad team,
where he got to design hovercrafts and
build wind turbines. Being on the team
cemented his love of engineering, allowing
him to really see the connection between
theory and practical problem-solving.
“That critical link between learning and
creating is what inspired me to continue
doing research now,” Yang said.
These days, Yang is an undergraduate
researcher at chemical engineering
professor Menachem “Meny” Elimelech’s
lab, where he’s worked since the summer
after his first year. Yang’s research is
focused on improving membranes for
desalination, the process by which salts and
minerals are removed from saline water
via filtration through a special membrane.
Yang is currently working on tuning the
chemical properties of these membranes
so that they can better distinguish between
ions of similar size, allowing for more
sophisticated filtration.
Yang ultimately hopes that his work
can ultimately contribute to reducing
global water scarcity.
“In the U.S., we
take fresh water for
granted,” Yang said.
His passion for
augmenting the
world’s freshwater
supply can be
traced back to the
summers he spent
in China with his
grandparents, who
had to conserve water
and energy to a degree Yang
had never experienced in America.
Yang’s quest to address this brutal reality
faced by many around the world led him to
the National Renewable Energy Lab, where
he interned this summer. There, he worked on
computational simulations of polymers that let
him better understand their properties. This
experience validated his longstanding desire to
transition from experimental research, a trialand-error
process, to computational research,
which is more intentional. “[Computational
approaches] give you insight into the
mechanism, how ions and molecules move
through membranes, in a way that’s inaccessible
from experimental approaches,” Yang said.
For his graduate research, Yang plans to
further explore computational methods.
One day, he’d like to be a professor, not
only out of a love of research, but out
of a hope that he can provide the same
transformational mentorship that he has
received from Elimelech and his lab team.
Besides science, Yang enjoys practicing
calisthenics, listening to electronic music, and
learning about modern philosophy. He’s also an
avid reader, with a strong preference for fiction
over nonfiction. “I want to see the world in a
different way,” he explained. It’s precisely that
impulse to envision a new world and reimagine
our collective future that sets Yang—like Cohen
and Libby— apart as a researcher and member
of our community. ■
December 2020 Yale Scientific Magazine 37
ANDEMIC: HOW TO
REVENT AN OUTBREAK
Though released in January 2020, several months before
the escalation of our current pandemic, Pandemic: How
to Prevent an Outbreak, a compelling Netflix docu-series,
touches upon terrifying scenes of our reality right now. Pandemic
provides an in-depth analysis of the deadly threat of viruses such
as influenza and Ebola. Its timing was so eerily prescient that in
online forums, viewers have proposed conspiracy theories about
how the producers managed to predict the COVID-19 outbreak.
Ironically, throughout the documentary, scientists, physicians, and
government threat units try to convince the audience that a deadly
virus will soon emerge—the producers did not need to guess
anything, as it was rather scientifically obvious.
The show revolves around different stories of virus-fighting
physicians and scientists from across the world. Bioengineers Jacob
Glanville and Sarah Ives strive towards a universal flu vaccine,
which they hope will immunize everyone against any strain of
the virus. Infectious disease epidemiologist Syra Madad directs
the System-wide Special Pathogens Program at NYC Health +
Hospitals, tirelessly attempting to prepare New York City for the
next infectious outbreak. Dinesh Vijay fights against deadly H1N1
virus in India, while Holly Goracke tries to protect the citizens of
Jefferson County, Colorado. Images throughout the series—the
urgency of the flu season, violence against doctors combating
Ebola in Congo, and the overabundance of patients in India—
drastically impact the audience, devastating us with the sacrifices
of the frontline workers.
BY DILGE BUKSUR
This devastation soon transforms into disappointment over
our country’s ignorance of the show’s warnings. Pandemic clearly
outlined many of the reasons why our world would struggle in
the face of a new form of respiratory virus. It explained the
difficulties of containing the spread of viruses that originate from
bats, the hypothesized source of SARS-CoV-2. The vivid footage
and extensive interviews listed lack of medical replenishments,
rejection of scientific authority, insufficient healthcare workers
in small areas, lack of access to extensive hospitals, and poverty
as potential destroyers of our healthcare systems. Yet, just a
few months later when faced with the COVID-19 pandemic,
government figures chose to ignore these warnings.
This fall, we have struggled with the record highs of coronavirus
cases in the United States. Even though screens and papers tend
to discuss only numbers, these digits represent real people. An
average viewer will not have actually stepped foot inside our
virus-swamped hospitals, but this show will transport them
right to the epicenter, revealing what it is like to deal with a virus
as either a patient or a frontline worker. Numbers and statistics
represent people who are unable to breathe, shiver with fever,
and suffer isolated in hospital rooms.
Just weeks before COVID-19 spread across the whole world, a sixepisode
Netflix show predicted its onset and divulged what we needed
to change. However, we sat back and watched our forthcoming
reality like a sci-fi movie. People are dying for something we should
have been prepared for. There is nobody or nothing else to blame. ■
(2020, January 22). Pandemic: How to Prevent an Outbreak
[Docu-series]. Netflix.
IMAGE COURTESY OF WIKIMEDIA COMMONS
Mask wearing
has become the
new normal with
the COVID-19
pandemic.
SCIENCE IN TH
38 Yale Scientific Magazine December 2020 www.yalescientific.org
IMAGE COURTESY OF WIKIMEDIA COMMONS
A Blakiston’s fish
owl in the snow.
BY JONATHAN SLAGHT
A COMPELLING TALE OF
CONSERVATION AND
INTERNATIONAL FRIENDSHIP
It has fierce yellow eyes and lives in the trunks of massive,
old-growth trees. When the bird takes flight, it can have a
wingspan of over six feet. During its breeding season, its
calls are so in sync with its mate’s that novices often believe
only one bird is hooting. Blakiston’s fish owl is the largest living
species of owl, dwelling in parts of Japan, China, and far east
Russia. Members of the species are difficult to find, especially as
loggers destroy their habit year over year.
Jonathan Slaght has spent his career researching this majestic
creature and fighting to conserve its habitat. In his book Owls of
the Eastern Ice, Slaght narrates his fieldwork in Primorye, east
Russia, searching for the owl. Beyond the story, he also discusses
conserving habitats and cross-cultural science. The result is an
engaging read of crusades through snow and ice.
The book’s events take place over a period of four years, beginning
with the start of Slaght’s Ph.D. project. Blakiston’s fish owls are easiest
to find in the winter, so every time the cold months come around, he
leaves Minnesota for Russia. The book follows his extensive quest
through the snowy wilderness to find, trap, and then tag the fish
owls—his ultimate goal is to use GPS information to decipher the
owl’s preferred habitat and determine what areas to protect.
Finding and trapping is a convoluted process; the birds are rare and avoid
many traps Slaght’s team devises. Eastern Russia is harsh and unforgiving.
Slaght recounts being wet to the bone, trudging through snow for hours,
sleeping in unforgiving conditions, and even a dramatic sequence of events
where he sits in a tractor being carried along a roaring, overflowing river.
BY ANNIKA SALMI
Slaght also faces the difficulty of doing field research in a foreign
land. While Slaght is fluent in Russian, Primorye sees few visitors,
and many are shocked to learn that he is an American and studying
owls, no less. He talks seriously of lasting Cold War difficulties and
counters that wildlife sees no borders. His Russian coworkers seem
outlandish to an American reader. Sergey, his most frequent assistant,
has “an upper row of gold teeth perpetually clenching a cigarette.”
Slaght recounts how his colleagues make fun of him often—for not
knowing how to hold his vodka, for failing to drive a snowmobile
correctly, for wearing fancy outdoor gear, and more. Despite this, he’s
fond of them all. Through his descriptions of his friendships, Slaght
makes a strong argument that science knows no borders. After all,
wildlife doesn’t: salmon that the fish owls hunt are eaten all over Asia,
and wood from Primorye forests goes to North America.
Despite the difficulties he faces, Slaght’s passion for his job leaks
out of every sentence. Even as Slaght campaigns for conservation and
international collaboration, Owls of the Eastern Ice is ultimately about
loving fieldwork. “I was truly comfortable here, alone among the trees,
breathing in the cold air and passing familiar landmarks,” Slaght wrote
about returning to Primorye one year.
Overall, Owls of the Eastern Ice is a worthwhile read, both for
Slaght’s thrilling adventures and for a deeper understanding of
conservation biology. ■
Slaght, J. C. (2020). Owls of the Eastern Ice. S.l.: Penguin Books.
E SPOTLIGHT
www.yalescientific.org
December 2020 Yale Scientific Magazine 39
IMAGE COURTESY OF NASA HUBBLE SPACE TELESCOPE
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