YSM Issue 93.4 Full Magazine

yalescientific

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

EDITORIAL BOARD

Editor-in-Chief

Managing Editors

News Editor

Features Editor

Articles Editor

Online Editors

Copy Editors

Scope Editors

PRODUCTION & DESIGN

Production Manager

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Art Editor

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Webmasters

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BUSINESS

Publisher

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OUTREACH

Synapse Presidents

Synapse Vice President

Outreach Coordinators

STAFF

Selma Abouneameh

Ryan Bose-Roy

Dilge Buksur

Kelly Chen

Elaine Cheng

Lauren Chong

Krishna Dasari

Alex Dong

Murilo Dorion

Matthew Fan

Maya Geradi

Alexandra Haslund-Gourley

Madison Houck

Elisa Howard

ADVISORY BOARD

Priyamvada Natarajan

Sandy Chang

Kurt Zilm, Chair

Fred Volkmar

Stanley Eisenstat

James Duncan

Stephen Stearns

Jakub Szefer

Werner Wolf

John Wettlaufer

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Ayaska Fernando

Elissa Dunn Levy

Alice Huang

Miriam Kopyto

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Veronica Lee

Karen Lin

Eric Linh

AnMei Little

Phoebe Liu

Lucas Loman

Angelica Lorenzo

Victoria Lu

Jenny Mao

Tai Michaels

Victoria Ouyang

Marcus Sak

Kelly Farley

Anna Sun

Xiaoying Zheng

Hannah Ro

James Han

Tiffany Liao

Maria Fernanda Pacheco

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Serena Thaw-Poon

Lorenzo Arvanitis

Brett Jennings

Antalique Tran

Julia Zheng

Ellie Gabriel

Sophia Zhao

Kate Kelly

Siena Cizdziel

Matt Tu

Megan He

Sebastian Tsai

Jenny Tan

Stephanie Hu

Cynthia Lin

Michelle Barsukov

Katherine Dai

Chelsea Wang

Nadean Alnajjar

Blake Bridge

Agastya Rana

Jerry Ruvalcaba

Noora Said

Annika Salmi

Sydney Scott

Ishani Singh

Athena Stenor

Izzi Trindade

Victoria Vera

Anavi Uppal

Kerui Yang

Catherine Zheng

Astronomy

Biological and Biomedical Sciences

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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

www.yalescientific.org

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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