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Yale Scientific Magazine
VOL. 90 ISSUE NO. 3
CONTENTS
APRIL 2017
NEWS 6
FEATURES 25
ON THE COVER
12
15
IT’S NOT JUST IN
YOUR HEAD
Scientists have developed a
method of identifying prenatally
damaged neurons that become
susceptible to mental disorders
after birth.
18
Diabetes is caused by the immune
system’s attack on its own beta cells.
Yale researchers have uncovered
a population of beta cells resistant
to these immune attacks, providing
hope for those with Type I diabetes
20
IF IT’S BROKE, DON’T
FIX IT
Research suggests that carcinogenic
mutations most current therapies
aim to repair can instead
serve as selecting agents for better
drug targeting with DNA repair inhibitors
A “BETA” WAY TO
TREAT DIABETES
STUDY OF THE
CENTER OF THE
EARTH
Scientists may soon model magnetic
fields more efficiently thanks to
the development of eGaIn, a magnetic
liquid metal with unprecedentedly
high magnetic and conductive
properties
CHILLING PRECISION
22
Researchers at Yale have developed
a technique to cool down and levitate
molecules in space, enabling new
experiments that could revolutionize
our understanding of fundamental
physics
More articles available online at www.yalescientific.org
April 2017
Yale Scientific Magazine
3

q a
&
►BY MATTHEW KEGLEY
Sleep is one of our most important
bodily functions. In its absence,
we experience cognitive disruption,
depression, and other chronic symptoms.
How does evolution explain our
need for sleep? Some theories suggest
sleep plays a role in energy restoration
and information consolidation.
Many studies focus on the synaptic
homeostasis hypothesis, which says
that during sleep, the brain decreases
the strength of brain cell connections
to counteract the increase that occurs
during wakeful brain activity, thus
promoting balance and efficiency in
the brain.
Synaptic downscaling, or the weakening
of brain cell connections, opposes
upscaling, which refers to the
strengthening of neuronal connections
as we learn. László Acsády from
►BY JOSHUA PEREZ-CRUET
Scientists have always regarded turtles’
curious ability to hide in their shells as a
protective adaptation, but a study from the
Jurassica Museum in Switzerland suggests
that the adaptation is actually an exaptation,
a preexisting trait that developed a secondary
function. The researchers looked at an
ancestral turtle from the Late Jurassic Period,
Platychelys oberndorferi, to provide evidence
against the widely-accepted model
of protective adaptation. They generated
two models of Platychelys head retraction:
a conservative model where all the relevant
joints maintained contact and an extreme
model where some joints could dislocate
and the turtle could retract its head further.
Neither model allowed the turtle to retract
its head enough to provide sufficient security
against predators.
Instead of using retraction for defense,
the researchers believe Platychelys devel-
Why is sleep important?
IMAGE COURTESY OF PIXABAY
►These spines contain receptors that could form
connections with other cells. During sleep, they
decrease in size as part of synaptic downscaling.
the Institute of Experimental Medicine
of the Hungarian Academy of Sciences,
an expert on the homeostasis hypothesis,
explained why downscaling
is necessary. “Memory and information
systems may break down because
of the overload of neuronal actions,”
Acsády said. “In conditions of continually
strengthening neurons, the brain
would soon become epileptic.” Thus,
downscaling prevents damage to the
brain, saving energy and space.
So why exactly do we need sleep for
downscaling to occur? During wakeful
learning, neuronal processes increase
in size. In contrast, sleep prevents
learning, so upscaled neurons
can be downscaled in appropriate
proportions to achieve homeostasis.
This promotes memory and removes
unneeded connections in the brain.
Why did turtles come out of their shells?
IMAGE COURTESY OF FLICKR
►Ancestors of the mata-mata turtle (shown above)
may have first used partial retraction to capture
aquatic prey more easily.
oped partial retraction to spring forward
and capture unsuspecting prey, a mechanism
used by modern-day snapping and
mata-mata turtles. Retraction evolved independently
in two ancestral groups of
turtles—one of which evolved the ability
to vertically retract its head, while the
other developed mainly lateral retraction.
Natural selection directed further retraction
for a protective advantage from this
primary mechanism in Cryptodires, one
of the two ancestral groups.
Although this hypothesis requires further
testing, the team’s research emphasizes
a prevalent issue in the field: creating theories
not firmly rooted in fact. “Our study is
constructed in three layers: facts, interpretation,
and hypothesis,” said Jérémy Anquetin,
lead author on the study. This type
of innovative thinking reconsiders accepted
norms in biological evolution.

F R O M T H E E D I T O R
Innovating for the Future
Where do you see the world in 2030?
The progress of the world is inextricably tied with the progress of scientific innovations.
Scientists improve the world by adapting creative breakthroughs in the lab to our own
lives, through drugs that help us “forget” cocaine’s addiction (pg. 7) or reversing hearing
loss (pg. 8). There is cutting edge research in identifying addictions even prior to birth (pg.
15) and in helping diabetes patients regain the production of insulin (pg. 18). Applying
bench research to practical circumstances is the epitome of innovation.
These innovations excite the world when they first are announced, but they quickly fade
into the status quo. It’s hard to imagine our lives without instant access to knowledge and
affordable pain-relief drugs. This year, our masthead has decided to spotlight a new application
every issue through our “Innovation Station” (pg. 35). This issue’s article explores
a stable production mechanism for solar cells, a technology that drives the growth of a
200,000-person renewable energy industry. We look forwards to cover the latest breakthroughs
with you in the issues to come.
Our cover story this issue tells the story of an innovative new cancer treatment that
prevents DNA repair in only cancerous cells (pg. 12). By exploiting the cancer’s own vulnerabilities,
this inhibitor causes cell death and could lead to clinical trials. Even as we celebrate
humanity’s advancing understanding of the world, we remember that none of these
breakthroughs happen in a vacuum. Instead, they rely on past discoveries that build up
our knowledge of the natural world, piece by piece. Improved observations of molecules at
very small energies can lead to better GPS systems (pg. 22) while the creation of new exotic
chemicals could lead to better computational resources (pg. 27). Even research that might
not seem relevant today, like instruments looking for dark matter (pg. 9) or simulations of
the Earth’s core (pg. 20), could lead to improvements in our daily lives soon.
With the crucial role of scientific research in our daily lives, many scientists have been
very worried about proposed budget cuts to science funding agencies. As of print, there
have been almost 10 billion dollars in proposed cuts to departments like the National Institutes
of Health, the National Oceanic and Atmospheric Administration, the Department
of Energy, and the Environmental Protection Agency. Scientists have reacted in shock to
this news, organizing a “March for Science” on Earth Day this year to celebrate science.
Understanding how this research connects to our lives is crucial in shaping our future.
Whatever your interests, we invite you into the pages of the Yale Scientific to continue
exploring our majestic world. Let us use our current knowledge and creativity to find more
breakthroughs, imagining a better future together.
APRIL 2017 VOL. 90 NO. 3 | $6.99
IF IT’S NOT BROKEN...
...DON’T FIX IT
A B O U T T H E A R T
Chunyang Ding
Editor-in-Chief
This issue’s cover story addresses the role of DNA repair in a novel
cancer therapy and illustrates the complicated nature of correcting
biological processes gone awry. In more ways than one,
maintaining normal cellular function is as difficult as controlling
the weather—minute imbalances and tiny deviations from established
patterns can have huge consequences. On the (literal)
road to proper gene expression, environmental disruptions can
alter or halt normal processes as severely as a thunderstorm can
block transportation. In unfavorable conditions, negligible flaws
in the DNA sequence can become devastating as quickly as patchy
dirt paths and dented fences can become impassable swamps
and splintered wood. The cover illustration serves as a colorful,
straightforward portrayal of this complex biological concept.
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Please send questions and comments to ysm@yale.edu.

NEWS
in brief
PHOTOGRAPHY BY DANYA LEVY
►Professor Paul Turner’s lab
investigates how environmental
changes impact viral evolution.
Deadlier Diseases
By Allie Forman
If you get an annual flu vaccine, you probably
know that new strains of the virus emerge
each year. All viruses, from influenza to Ebola,
undergo genetic changes to adapt to their environments.
Understanding the evolutionary
patterns of viruses is vital for public health, allowing
preemptive measures against disease.
“You can start to create therapies that
are necessary in the future by understanding
more details of emerging virus pathogen
problems,” said Yale Ecology and Evolutionary
Biology professor Paul Turner, whose lab
investigated how environmental changes such
as deforestation or climate change affect viral
patterns of evolution. The results, published
in February in the journal Evolution, suggest
that rates of environmental change greatly impact
viral evolution.
The Turner lab studied Sindbis virus (SINV),
a rapidly mutating RNA virus transmitted by
mosquitoes, as a model for evolution dynamics.
The scientists changed the type of host
cells available to the virus, either suddenly or
gradually, and used genomic sequencing to
track viral changes over time.
For sudden environmental changes, highly
beneficial mutations only occurred in the
virus at the beginning of the experiment. In
the gradually changing environment, however,
beneficial mutations occurred throughout
the experiment. This suggests that a slowly
changing environment may allow viruses to
optimize their machinery and become more
dangerous. Such a pattern of evolution has
far-reaching consequences—HIV is an RNA
virus that adapts slowly to its changing human
body environment, eventually targeting
different target host cell-types within the human
body.
The researchers hope that their work will
ultimately help anticipate and prevent future
disease outbreaks. “The kind of research we
do gets at the predictive power of evolution,”
said Turner.
When Junk Food Finds Samoans
By Maria Wu
IMAGE COURTESY OF WIKIMEDIA
►The McDonald’s drive-thru greeting
sign in Samoan. In recent decades, a
modernized diet high in saturated fats
and red meat has been on the rise.
Obesity isn’t just a problem for
Americans. Recent modernization in
Samoa, a previously isolated island state
in the South Pacific, has resulted in a shift
in dietary habits. Now, Samoans tend to
exercise less and eat a modern Western
diet, which consists of processed foods
and higher amounts of saturated fats and
carbohydrates. Upward trends of heart
disease, Type II diabetes, and metabolic
syndrome—which includes a combination
of high blood pressure, blood sugar, and
body fat—have occurred in the population.
Researchers at Yale and the University of
Michigan have identified three different
types of dietary patterns in Samoa: a modern
diet, a primarily traditional diet with some
modern foods, and a primarily modern diet
with some traditional foods. They found
this by conducting a survey of over 2,500
adult Samoans, half of which suffered from
some type of metabolic syndrome. Using
metrics such as waist circumference, blood
glucose, fat, and cholesterol levels, the
researchers found that those who consumed
a mixed-modern diet were the healthiest.
First author Dongqing Wang has several
explanations for this surprising result.
First, the relatively small amount of red
meat consumed offers some health benefits
without its negative effects. Second, the
intake of coconut oil in the mixed-modern
diet also provides benefits to the heart and
metabolism.
“The primary takeaway from this study
is that this is the first time these mixeddietary
patterns have been observed in the
Samoan population,” said Wang. In future
research, Wang wants to understand why
more traditional foods are on the decline,
as well as how factors such as education,
occupation, and socio-economic position
influence dietary styles. Such research
will elucidate how Western influences are
impacting the health of other communites
around the world.
6 Yale Scientific Magazine April 2017 www.yalescientific.org

in brief
NEWS
Forgetting Cocaine
By Lily Wu
How can medical treatments control
addiction to cocaine? In a Yale study, scientists
Amber Dunbar and Jane Taylor found that
a drug called Garcinol can block memories
associated with cocaine and decrease drugseeking
behavior in rats. The researchers
trained a group of rats to self-administer
cocaine, pairing administration of the drug
with a cue to later be remembered, and found
that the animals could be made to “forget”
these drug-associated memories if Garcinol
was administered. If Garcinol works
similarly on humans, it could have a huge
impact on cocaine addiction rehabilitation.
Postdoctoral Research Fellow Melissa
Monsey explained the motivation behind
the study: “We’re interested in finding
different ways to disrupt memories that
are associated with drug use. By studying
cocaine-associated memories, the lab hopes
to sustain abstinence and potentially help
prevent cravings in human addicts.”
Garcinol is derived from the fruit of the
Kokum tree, and according to Monsey,
was used primarily for culinary purposes
in coastal India before it caught scientists’
attention. Scientists have previously studied
Garcinol’s effects on fear memory. Basing
their work on the previously published
literature, Dunbar and Taylor found that
Garcinol could specifically affect cocainerelated
memories. Specificity is essential
because a person undergoing rehabilitative
treatment would not want to experience loss
or impairment of other memories.
Dunbar and Taylor are currently
continuing research with rodents to figure
out the underlying molecular mechanisms
of Garcinol. They want to elucidate its
neuronal effects and molecular mechanism.
In the future, their lab hopes to collaborate
with the clinical psychiatry department
to potentially move this drug into clinical
trials.
IMAGE COURTESY OF YALE
►Professor Taylor’s research uses
Garcinol, a substance derived from the
Kokum fruit, to help rats forget about
cocaine.
Has road salt ever saved you from slipping
on ice? While the salt might have saved you
from a fall, human interference in the natural
habitat can lead to detrimental effects in
our neighborhood animal populations.
Researchers at the Yale School of Forestry
and Environmental Studies have found that
road salt causes frog sex ratios to change.
The researchers reared frogs in multiple
500-liter tanks containing various levels of
road salt and leaf litter to mimic a typical
forest pond. In the absence of salt, frogs
show a female-biased sex ratio of 63 percent
female. They found that when frogs are
exposed to road salt, the percentage of
females can decrease by up to 10 percent.
Not only are there fewer females, but the
remaining females are smaller and likely
carry fewer eggs. This could be triggered
by the binding of elements such as sodium
to cell receptors, which mimics testosterone
and triggers masculinization.
Millions of tons of salt are dumped on
Sex-Switching Frogs
By Milana Bochkur Dratver
roads in the United States every year to
prevent freezing snow or rain from causing
car accidents, and this can cause permanent
alterations in the frog population. Lead
author of the study and F&ES graduate
student Max Lambert explained that these
results have implications beyond frog sex
ratios: “The conclusions point to the fact that
daily use chemicals are altering sex-hormone
pathways.” In a broader health perspective,
this means that “benign” chemicals can have
relevant hormonal effects. For instance,
repeated exposure to chlorine, commonly
found in tap water and swimming pools, is
associated with hypothyroidism in people.
The findings of this study point to the
importance of understanding the chemicals
in our surroundings, as they can affect
multiple physiological pathways in the body,
whether human or frog. As for helping out
our frog neighbors, possible solutions would
be to reduce salt usage or find alternatives
during the winter.
PHOTO BY MAX LAMBERT
►Road salt can change the sex-ratio
of adult frogs, leading to fewer females
in the frog population.
www.yalescientific.org
April 2017
Yale Scientific Magazine
7

NEWS
cell biology
HEAR AND NOW
Pioneering Research at the Yale Ear Lab
►BY ALAN LIU
What are the sounds you treasure the most? Perhaps
a loved one’s voice, a gentle piano melody, or the soft
meows of a kitten? Unfortunately, sounds like these can
fade away for us as we age. Studies have shown that after
the age of 65, one in three adults has difficulties with
hearing. This statistic increases to one in two adults after
the age of 75. With modern medicine, the life expectancy
in developed areas of the world is gradually increasing,
meaning that among other potential health issues, many
more adults will be susceptible to hearing loss.
Although hearing loss during old age has many possible
causes, Alla Ivanova’s research at the Yale Ear Lab
has pinpointed one cause. Using specially bred mice, she
linked a form of hearing loss to defective mitochondria
in the cochlear region. She also identified an antioxidant-based
treatment for this problem.
Mitochondria act as the engine of your ear, always running
even when you’re asleep. Just as an engine of a car
needs tune-ups, these mitochondria also need proper
care and nutrition. To test just how vital these organelles
are, Ivanova generated mice with a genetic mitochondrial
defect—removing a critical component from the
engine. Scientists then measured the hearing ability of
the mice over the course of their short lifespan of about
nine months to a year, replicating the aging process of
the human body. At five months—equivalent to a young
adult—mice with damaged mitochondria had impaired
hearing. After a few more months, they couldn’t hear at
all.
“Although mitochondria are hurt by excessive noise
and toxins normally as you age, in these mice, [Ivanova]
has enhanced the damage that occurs and exposed the
relevance of mitochondria towards hearing loss and aging,”
professor Joe Santos-Sacchi of the Yale Ear Lab explained.
Using this model, Ivanova was able to pinpoint
exactly how much hearing loss was expected at certain
ages when mitochondria are sick.
Ivanova’s research has focused not just in identifying
the role of mitochondria, but also in repairing them
when injured. She found that treating the mice with antioxidants,
which remove potentially harmful oxidizing
chemicals from damaging components of the cell, effectively
reduced the strain on mitochondria and allow
them to work for much longer—similar to giving a car
engine an oil change. The mice that were treated with
certain antioxidants, such as N-Acetyl-Cysteine (NAC),
did not lose their hearing even as the other mice all became
deaf. But unfortunately, just as any number of
oil changes wouldn’t fix a broken engine, antioxidants
couldn’t restore hearing in mice that were already deaf.
Although naturally occurring antioxidants like NAC
are already available over-the-counter at pharmacies,
they have not been linked before to preventing mitochondrial
mutations that cause age-related hearing loss.
Their use in human clinical trials could go a far way in
enhancing our hearing and quality of life in old age.
One of the challenges of the experiment was figuring
out how much the mice were able to hear. Unlike humans,
mice cannot directly tell us how clearly they heard
a word or a sound. The researchers utilized a methodology
to address this problem based on the fact that our
ears are always listening, even when we’re asleep. The
mice were first put to sleep using anesthesia. By placing
electrodes directly onto the mice’s skulls, they measured
electrical signals from the nerve cells triggered by
sounds entering their ears. Sounds caused visible peaks
in activity within those nerve cells. Afterwards, the researchers
could compare the activity graphs to identify
and compare hearing loss caused by mitochondria.
Solving the role of mitochondria in the cochlear system
of the ear is only part of addressing the causes of
age related hearing loss. “The challenge is to separate the
neural, immune and cochlear systems and figure out the
impact of each component,” Ivanova said. Her future research
will study other effects of these mitochondria in
the aging process such as in the onset of Alzheimer’s.
PHOTOGRAPHY BY NATASHA ZALIZNYAK
►Dr. Alla Ivanova and Dr. Winston Tan examine defective
mitochondria in mice to better understand hearing loss.
8 Yale Scientific Magazine April 2017 www.yalescientific.org

particle physics
NEWS
FINDING A NEEDLE IN A HAYSTAC
The Search for Dark Matter
►BY ELIZABETH RUDDY
PHOTOGRAPHY BY JESSICA HONG
►The HAYSTAC axion detector probes the universe for axions,
a potential candidate for dark matter.
Imagine searching for a needle in a haystack. The needle
weighs about 100 billion times less than an electron
and has no charge. It acts like a wave rather than a particle,
and the haystack is the size of our universe. Needles
like this may exist in the tens of trillions in every cubic
centimeter of space—the trick is proving that they’re
there.
That is the mission of the HAYSTAC Project at Yale,
which stands for the Haloscope at Yale Sensitive To Axion
Cold Dark Matter. HAYSTAC is a collaboration between
Yale University, University of California, Berkeley and
University of Colorado, Boulder. The project is based in
the Wright Laboratory, led by professor Steve Lamoreaux
and a team of Yale scientists and graduate students. The
scientists began their project about five years ago and released
their first results this past February in the Physics
Review Letters. The first author was Yale graduate student
Ben Brubaker.
“The goals of the experiment are to detect dark matter,
or failing that, to at least rule out some possible models
for what dark matter is,” explained Brubaker. “In simplest
terms, dark matter started out as an astrophysics question:
that is, there is more mass in the universe than can
be accounted for by the mass we can see [through] all the
wavelengths we can detect: visible light, radio waves, ultraviolet.”
Dark matter is the “invisible” matter.
The HAYSTAC project is dedicated specifically to the
detection of the axion, a subatomic particle that was proposed
in 1983 as a likely candidate for dark matter. Like
the aforementioned needle, axions are theorized to have
almost miniscule mass, no charge, and no spin. Based
on the gravitational movement of stars and galaxies, we
know that 80 percent of the matter in our universe is dark
matter, but axions interact with other matter so weakly
they become almost impossible to detect. Because they
are so light, they have very little energy and behave more
like waves than particles. As a result, the scientists must
employ an unusual identification strategy to find them.
The HAYSTAC detection device essentially produces a
magnetic field that converts the axions to photons. The
frequency of oscillation of the photons is determined by
the mass of the axion. Therefore, when the detector is
tuned to one specific frequency at a time, it can amplify
these oscillations to make them detectable.
“Our detector is in essence a tunable radio receiver, and
we painstakingly tune the receiving frequency, looking
for an increase in noise. It is like driving through a desert
looking for a station on the car radio: you tune slowly in
hopes of finding something,” said Professor Lamoreaux,
the head of the project.
In the February report, the team demonstrated its recent
breakthroughs in design: they had achieved sufficient
sensitivity to test out much higher frequencies in
the potential mass range than ever before. By incorporating
technology from other fields like quantum electronics,
Lamoreaux and his colleagues have made the detector
colder and quieter than any of its contemporaries, eliminating
as much of the background noise as possible. According
to Brubaker, the device is kept at approximately
0.1 degree Celsius above absolute zero, the unattainable
temperature at which atoms physically stop moving.
Freezing temperatures are critical for sensitivity because
a major source of noise is thermal radiation: photons being
shed by matter and interfering with the detection of
axions.
According to Professor Lamoreaux, their detector is
currently the most sensitive radio receiver ever built.
“Imagine a match lit on the surface of the Moon. The rate
of energy entering the pupil of your eye when the match
is viewed from the Earth is about the level of sensitivity
we achieve,” said Lamoreaux.
The size of the detector scales inversely with the mass
range being tested, so the Wright Lab instrument will
only be able to search a small portion of the wide range
of possible dark matter masses. However, the team has
proven they have a design with the sensitivity capability
necessary to perform these sweeps. Their design is a pioneering
model for the future.
www.yalescientific.org
April 2017
Yale Scientific Magazine
9

NEWS
neuroscience
MINDREADING THROUGH BRAIN IMAGING
Predicting human behavior using the brain’s signature
►BY JOSHUA MATHEW
Following centuries of curiosity and uncertainty about the human
brain, a recent neuroimaging study will provide us with a
way to study the live human brain non-invasively. Prior to the advent
of neuroimaging, neuroscientists relied solely on post-mortem,
or after death, autopsies to gain insight into the workings of
the brain. By contrast, neuroimaging employs a variety of techniques
to structurally or functionally image the brain without surgical
intervention. A multidisciplinary team of Yale researchers
has developed connectome-based predictive modeling (CPM),
a computational model capable of predicting human behavior
based on how one’s brain is wired.
Some commonly used brain imaging techniques include computed
tomography (CT) scanning, function magnetic resonance
imaging (fMRI), and electroencephalography (EEG). fMRI measures
brain activity by detecting changes in oxygenated blood flow
through specific areas of the brain. Specifically, the ability to detect
these changes by fMRI takes advantage of the difference in
the magnetic properties of oxygenated and deoxygenated blood.
CPM uses fMRI to observe activity in specific regions of the brain
and subsequently derive brain connectivity data for use in predicting
an individual’s behavior.
The human connectome is a network of neural connections between
regions of the brain. These connections can be determined
by identifying regions with simultaneous activity in the brain. The
model developed by Yale researchers can characterize these neural
connections more comprehensively by utilizing a connectivity
matrix acquired from fMRI data. In a nutshell, each row in this
matrix represents one of 300 regions of interest in the brain, and
the data within each row describe the functional relationships between
this region and the remaining 299 regions. Since humans
have unique brain connectivity, and thus unique connectivity matrices,
your brain’s functional connectivity can be used to predict
various aspects of your behavior. CPM provides a way to extract
that information and interpret it in meaningful ways.
The predictive model is constructed by gathering connectivity
matrices from many people, and is then used to predict behavioral
traits of a new person based on their connectivity matrix. The
predictive power of CPM has immense clinical significance. Matrix
data can be used to predict and analyze whether an individual
has paranoia, delusions, schizophrenic symptoms, and other
conditions. Additionally, psychiatric disorders could be more effectively
diagnosed with the help of CPM. The current diagnostic
protocol for such disorders, the Diagnostic and Statistical Manual
of Mental Disorders, Fifth Edition (DSM-5), has been met with
mixed results since categorization of patients is based solely on
identifiable symptoms. Implementing CPM for diagnostic purposes
could allow for more thorough and scientific categorization
that could ultimately improve the quality of mental health care.
Although CPM has not yet reached the stage of clinical application,
future directions for this research are boundless. According
to Professor Todd Constable, senior author of the study, one
such direction could include identifying circuits that function aberrantly
in certain diseases. Mechanistically understanding these
diseases would in turn contribute to the development of more
personalized and targeted treatments. “CPM has already been
demonstrated to predict one’s fluid intelligence and attentive performance,”
said Constable, who believes that many other traits
can be similarly predicted. Another question is how the brain’s
connectivity changes over time with aging and development. In
contrast to DNA, our genetic code which is relatively static in
comparison, brain connectivity is much more dynamic. This dynamism
further challenges our efforts to study the brain.
The novelty of CPM lies in the fact that it is the first whole-brain
connectome study of its kind. Up until recently, a major limitation
for connectivity research had been an inadequate amount of
individual connectome data from which to develop models for
predicting complex behaviors. While previously only local brain
connectivity could be studied given the amount of data available,
the launch of the Human Connectome Project (HCP) in 2009 has
supplied a mass of connectome data that allows whole-brain connectivity
studies to be done for the first time. HCP is a large-scale
effort to collect and share human connectome data in order to
address fundamental questions about the functional connectivity
of the human brain. To further this goal, the Yale researchers have
published an algorithm for implementing CPM to build predictive
models. This provides researchers around the world with the
tools to contribute to the ongoing study of the human brain using
predictive modeling.
IMAGE COURTESY OF WIKIPEDIA
►A 3D visualization of the brain’s neural networks.
10
Yale Scientific Magazine April 2017 www.yalescientific.org

paleontology
NEWS
SPINY SLUGS
New fossil discovery sheds light on mollusk evolution
►BY SARAH ADAMS
IMAGE COURTESY OF JAKOB VINTER
►Paleontologist Jakob Vinther (Yale PhD ‘11) led research on
Calvapilosa in mollusk evolution.
Smooth, slimy, and anything but spiny are qualities that
come to mind when one thinks of slugs. Slugs are part of the
phylum Mollusca, a large group of invertebrate organisms
with soft, unsegmented bodies. Originating 520 million
years ago in the Cambrian Explosion—a period in Earth’s
history when a great diversity of plants and animals developed—mollusks
include a wide variety of species beyond
the familiar garden snails and slugs. Types of mollusks include
those with shell plates, like clams, or with radula, a
tongue-like structure found in squids. The incredible diversity
of mollusks arose during a surprisingly short time
period of 20 million years after the Cambrian Explosion.
The two main stem groups of mollusks that have developed
since then are Aculifera, scale-bearing mollusks, and Conchifera,
shell-bearing mollusks. Scientists have long pondered
what a common ancestor of those groups would have
resembled.
A recent discovery of the fossil Calvapilosa kroegeri, led
by paleontologist and former Yale doctoral student Jakob
Vinther and funded by a grant from the National Science
Foundation and the Yale Peabody Museum of Natural History,
has helped researchers model the earliest common
ancestor of mollusks. This organism is 480 million years
old and was found in the Ordovician Fezouata Formation,
a fossil-rich deposit in Morocco. It measures roughly four
inches long. It most likely ate algae off of rocks, implied by
how its jaw is lined with over 125 rows of tiny teeth. Complete
fossils of the adult and juvenile were found, and the
mollusk was reconstructed in enough detail to show what
it looked like: a “hairy scalp” with a slightly balding spot in
the middle. Thus the organism was given its name, Calvapilosa,
or “hairy scalp.” It has spines extending over its entire
upper body and a helmet shell on its head. In particular,
the spines of Calvapilosa are more mineralized and consequently
harder than those of earlier mollusks. However, its
radula and shell potential satisfy the general criteria to be
classified as a mollusk.
Calvapilosa is similar to two other older fossils of mollusks:
Orthrozanclus, found in Canada, and Halkieria,
found in Greenland. “However, Orthrozanclus and Halkieria
are controversial in determining mollusk evolution,
due their lack of certain unequivocal mollusc characteristics,”
said Vinther. However, Calvapilosa’s definitively mollusk
characteristics allowed Vinther to place Orthrozanclus
and Halkieria more firmly onto the tree of life due to their
similarities to Calvapilosa. Meanwhile, to clarify how Calvapilosa
evolved its unique characteristics, scientists used
phylogenetic analyses and mathematical models to estimate
which tree of life the mollusk evolved from. They found two
main branches of mollusk characteristics: one defined by
shell plates and scales, and one with no scales but a single
shell plate. Calvapilosa is the only known mollusk that has
characteristics of both main branches.
With this new discovery, stronger hypotheses can be
made about how mollusks diversified so quickly following
the Cambrian Explosion. Ancestral mollusks were previously
thought to be soft and shell-less. However, data from
Calvapilosa suggests otherwise. In order to account for the
newly found species, scientists hypothesize that the last
common ancestor of the two main stem groups of mollusks,
Aculifera and Conchifera, had a more flexible body plan.
Rather than having the previously inferred characteristics,
the common ancestor had radula with rows of differentiated
teeth, non-biomineralized bristles, and a single calcareous
shell. This body plan allowed for great morphological
diversity to evolve later in mollusks, and fits with the already
discovered species.
The discovery of Calvapilosa revolutionizes current
knowledge on the common ancestor of mollusks, but does
not end the story of mollusk evolution. “We must be constantly
open to new discoveries that may support or refute
our current hypotheses,” said Vinther. “In the meantime, we
should look for as many fossils as possible to continue our
search on mollusk evolution.” With Calvapilosa, scientists
were able to come up with the best explanation based on
current fossil data. It will be exciting to see how future fossil
discoveries tie other pieces of evidence together, building
and changing this evolutionary tale.
www.yalescientific.org
April 2017
Yale Scientific Magazine
11

FOCUS
genetics
IF IT’S
BROKE
DON’T
FIX IT
BY CHARLIE MUSOFF
ART BY RACHEL STEWART
12 Yale Scientific Magazine April 2017 www.yalescientific.org

genetics FOCUS
The barn door is on its last legs. Creaky hinges, rusty lock, maggot-infested wood, you name it. Thunder spooks
the horses, and they rush out into the rain, trampling the door in their path. The farmer is worried his livestock
won’t make it out in the open; he knows he needs to corral them before they gallop too far away. So, he grabs his
hammer and nails and starts reinforcing the beams of the door that gave way. Pause. That won’t work. Just as fixing
a broken door won’t bring back horses that have already escaped, fixing problems in the cell that result in cancer
after they have done their harm won’t cure the cancer either. If cancerous molecules have already been released
into the body, why spend time repairing the mutation that produced them?
At the Yale Cancer Center, Peter
Glazer and Ranjit Bindra TC
’98 attacked this problem. Cellular
mutations that disrupt
two genes called IDH1 and
IDH2 break the barn door,
so to speak, and release a tumor-causing
molecule called
2HG. Glazer and Bindra found
that cells with these mutations
were more susceptible to an existing
class of drugs called PARP
inhibitors. Instead of attempting to
repair the door and reverse the mutation,
as many current therapies do, PARP
inhibitors exploit this cellular weakness by
preventing DNA repair. Beyond establishing
a new link between IDH mutations and DNA
repair, the research paves the way for a highly
promising cancer therapy.
Broken Brakes
Though it has a single name, cancer is no one
disease. Rather, it refers to any time a population
of cells in the body begins to divide uncontrollably
and spread. This definition may seem
counterintuitive. Obviously, we need our cells
to divide, or else we’d still be single-celled; we
need different populations of cells to migrate,
or else we’d never fight off infection or heal
wounds. Normal cells, however, know when
and where to proliferate because the cell cycle,
the process by which cells divide, is tightly
regulated. The body makes new cells as needed
and no more. When this mechanism goes
awry, cells will continue to proliferate
past the point of necessity and often
form tumors.
A major switch that triggers
this dysregulation of
the cell cycle is mutation,
a change in a cell’s DNA
sequence. Not just any
mutation will result in
cancer. Relevant genes
are those already implicated
in cell division.
Genes that normally
promote proliferation
can be mutated to become
overactive, causing
cancer. IDH2 mutations
fall into a second category,
where mutations deactivate
tumor-suppressing genes.
BRCA’s buddy
The tumor-causing 2HG
molecules produced when the IDH genes are
mutated are called oncometabolites. The prefix
onco- means tumor, and metabolite means
that it is involved with cellular processes. Taken
together, an oncometabolite is an unintended
product of cellular processes that can disrupt
the cell cycle and drive tumor formation. 2HG
is like smoke coming out of an engine—something
had to go wrong in the car for it to be
produced, and the smoke further pollutes the
air. Most current approaches to treating cancer
through this mechanism aim to target IDH1/2
mutations and stop the oncometabolite from
being produced. Drugs that operate under this
logic are currently in clinical trials and were
widely accepted as the cutting edge of cancer
research. However, when Glazer and Bindra
worked together to tackle this same problem,
they saw it from a completely new angle.
The two doctors’ relationship traces back to
2006, when Bindra was an MD/PhD student
in Glazer’s lab. They studied DNA repair under
hypoxia, in which cells are oxygen-deprived;
hypoxic conditions frequently spur cancer
formation. After completing his residency
and fellowship at Memorial Sloane Kettering
Hospital in New York, Bindra returned to New
Haven in 2012 and was given his own lab in
Glazer’s department. By 2013, Bindra had
looked for specific genetic defects in tumors
that could serve as targets for drug therapies,
identifying the IDH1/2 mutations as prime
targets. Computer models of the mutant genes
showed that PARP inhibitor drugs could be
used to distinguish between normal cells and
those with IDH1/2 mutations. At this point,
Glazer realized the potential of this project and
rejoined forces with Bindra. “We realized that
if this was true, it was probably going to change
clinical practice,” Glazer said.
A common treatment for breast and ovarian
cancer, PARP inhibitors target mutations in
the BRCA1 and BRCA2 genes. Angelina Jolie’s
famous disclosure that her maternally inherited
copy of mutant BRCA1 was the reason for
her double mastectomy piqued women’s inter-
www.yalescientific.org
April 2017
Yale Scientific Magazine
13

FOCUS
genetics
est in their own vulnerability. Both referrals to
genetic testing facilities and questions about
preventative surgery significantly increased
in a phenomenon now termed the “Angelina
Jolie effect.” BRCA1/2 mutations render cells
incapable of putting their DNA back together,
which made them susceptible to carcinogenic
mutations. Instead of reversing the mutation’s
effects, PARP inhibitors further unstitch the
DNA to the point where tumor cells simply
fall apart. When Glazer and Bindra found that
IDH1/2 mutations were associated with PARP
inhibition, they reasoned that these genes
could do something similar to BRCA1/2.
Back to basics
To identify potential targets for PARP inhibiton,
the researchers developed the criterion
“BRCAness,” or similarity of a given gene to the
BRCA1/2 genes. A mutation with high BRCAness
is heavily implicated in deficient DNA
repair and, thus, a strong candidate target for
PARP inhibitors. Bindra and Glazer knew that
IDH1/2 mutants produced the oncometabolite
2HG, but it was still unclear how the gene mutations
blocked DNA repair. To isolate the mutation,
the team turned to classical genetics, the
basic patterns of gene inheritance discovered
by Gregor Mendel. Past IDH1/2 research had
not been very selective in choosing tumor cell
lines, using any cells that happened to contain
the relevant mutations. They chose not to have
a delicately engineered model for two reasons:
first, this approach is quick—one can screen for
the mutation and, if it is present, immediately
begin experimenting. Second, a human tumor
cell line with a naturally occurring IDH1/2
mutation is more relevant to actual cancer patients
than one with a more refined genome.
Yet Bindra and Glazer took the time to cross
cells over many generations and grow a single
gene mutation culture of cells. As a result, they
were able to study its specific effects without
worrying about confounding variables.
Once they established this solid foundation,
the rest fell right into place. The results they observed
were so robust that even at a glance, the
statistical significance was clear. The first string
of results strongly suggested that cells with the
IDH1/2 mutation cannot repair breaks in DNA
and are targeted by PARP inhibitors. Next, the
team demonstrated that 2HG was responsible
for both these properties. “It created an unsuspected
vulnerability, like an Achilles heel,” said
Glazer. Even though the unchecked result of
IDH1/2 mutations is cancer, 2HG’s susceptibility
to PARP inhibitors is a chink in the armor
that gives medicine a chance to intervene. Now
that the team had established baseline results
in their classically crafted cell line, they repeated
their tests in samples of brain tumor cells,
which yielded similar results. Finally, they administered
an FDA-approved PARP inhibitor
called olparib to mice with the IDH1 mutation,
and saw cell death in brain tumors increase 50-
fold. Considering that unchecked cell proliferation
causes cancer, this striking halt in tumor
growth holds great promise for the future of
cancer treatment.
Beneficial breaks
When Glazer and Bindra first published
their findings, they were met with resistance.
Reviewers couldn’t fathom how other scientists
had glossed what appeared to be a conceptually
straightforward idea and were hesitant to
publish findings that so directly undermined
the norm in this branch of cancer drugs. Once
the story was out, however, it quickly received
major recognition. The team has received calls
from PARP inhibitor companies, patient advocates,
and patient support groups, among
others. “The story wasn’t just kicking the can
down the road,” said Bindra. He reflected that
the team’s achievement is a prime example of
why the NIH funds academic science—without
the leeway to truly delve into the biology,
such progress would not have occurred.
Moving forward, Glazer and Bindra have
scheduled clinical trials for olparib, which
is currently only used on ovarian cancer patients,
in 35 different medical centers nationwide.
They hope to expand its use to brain
IMAGE COURTESY OF CREATIVE COMMONS
►Cells with IDH mutations have broken DNA
and, thus, often form tumors.
cancer, liver cancer, leukemia, and more.
There is also potential for 2HG to be used as a
biomarker for a cancer patient’s sensitivity to
PARP inhibitors. Since 2HG is not specific to
one type of tumor, its use as a biomarker can
be extended to many different types of cancer.
Both these applications are the result of a
major breakthrough in our understanding of
how cancer develops. “You spend a lot of time
in a lab either talking to biology or listening
to it,” said Bindra. “This is one of those moments
where you hit something and biology
just started talking like crazy.”
ABOUT THE AUTHOR
CHARLIE MUSOFF
CHARLIE MUSOFF is a freshman in Davenport College and a prospective
molecular, cellular, and developmental biology major. Besides being Yale
Scientific’s Outreach Designer, Charlie enjoys running with Yale Club Running,
singing with the Baker’s Dozen, and teaching with Community Health Educators
THE AUTHOR WOULD LIKE TO THANK Drs. Peter Glazer and Ranjit Bindra
for their time and insights.
FURTHER READING
Corso, Christopher D., MD PhD, and Ranjit S. Bindra, MD PhD. “Success and
Failures of Combined Modalities in Glioblastoma Multiforme: Old Problems
and New Directions.” Seminars in Radiation Oncology 26 (2016): 281-98.
Science Direct. Web.
14 Yale Scientific Magazine April 2017 www.yalescientific.org

IT’S NOT
JUSTIN YOUR
HEAD
new method for identifying
prenatally damaged neurons
that become susceptible to
mental disorders after birth
by Eileen Norris
art by Sonia Ruiz

FOCUS
biotechnology
Imagine two college students; let’s call them John and Jack. They are both in an especially
hard lecture class with a not-so-forgiving professor. They spend days preparing
for their midterm to no avail—both do poorly. From the outside, John and Jack
are both generally happy people. But, while John picks himself back up and works harder
for the next exam, Jack falls victim to depression. So what’s the difference between
John and Jack? Most would assume that Jack is mentally weaker—he just gave up. Perhaps
it’s more than just psychological; what if Jack was born more vulnerable to stress?
Past studies have demonstrated how exposure
to drugs, radiation, or poisons in the
womb, or prenatal exposure, can damage cells.
These children tend to be more vulnerable to
mental disorders associated with cellular stress,
as if these disorders were pre-programmed
during early development.
So, looking at a group of people or animals,
how can one tell who is vulnerable? A team of
researchers at Yale, led by Professor of Neuroscience
Pasko Rakic, has developed a way to
identify and visualize these at-risk cells using
fluorescent markers. This new identification
system may lead to further advancements in
the research of the development and treatment
of mental disorders, such as epilepsy, autism,
and schizophrenia, some of which are caused
by prenatal exposure to environmental stress.
A cell’s response to stress
Heat shock factor 1 (HSF1) is a part of a signaling
pathway induced by cellular stress. Heat
shock factors are transcriptional activators,
which means they bind to DNA at specific
locations to turn genes on and off, regulating
the quantity of heat shock proteins produced.
Heat shock factors are key to analyzing a cell’s
response to stress; therefore, by studying heat
shock factors, scientists aim to learn more
about how mental disorders may develop in
response to stress.
In earlier studies by other scientists, cells
were grown in tissue cultures and divided into
groups that were exposed to heat and normal
controls. Researchers found that many cells
exposed to heat generated a much higher level
of one specific protein, dubbed heat shock
protein (HSP), before they died. The surviving
cells had increased levels of heat shock factor,
which served as their protector. “It’s not just
that one could be exposed to too much heat—a
lot of people are confused by the name heat
shock factor. However, the same cell reaction
could occur after overexposure to anything;
you could have too many x-rays; you could
drink too much gin; you could eat too much
mercury from fish,” said Rakic.
Rakic and his colleagues observed that when
pregnant mice were exposed to harmful agents
such as alcohol, x-rays, and methyl mercury,
some fetuses died while others appeared normal.
“The fetuses that survived had developed
just the right amount of heat-shock factor that
prevents their death,” explained Rakic. “When
the cells survive, they look normal, but when
you expose those animals a second time to
harmful conditions postnatally, they are more
vulnerable to brain disorders.” The same is true
in humans—people who are exposed prenatally
to drugs could appear normal, yet be more
vulnerable when exposed to stress after birth.
Glow up before growing up
IMAGE COURTESY OF PASKO RAKIC
►Red fluorescence in neurons exposed to
heat shock (HS), as indicated by the arrows.
Because they observed a relationship between
the level of HSF1 and the development
of mental disorders after a second exposure to
harmful elements or stress, the research team
used the presence of HSF1 to identify vulnerable
brain cells that may contribute to the development
of disorders. A specific sequence of
DNA that produces Red Fluorescent Protein
(RFP) was inserted into the mouse DNA next
to the gene that coded for heat-shock factor.
This insertion results in a protein that emits a
bright red fluorescent “glow” when exposed to
high-energy light—moreover, the fluorescence
would only be present in cells producing the
heat-shock factor. Thus, this technique enables
the identification of the more vulnerable cells
that produce stress-induced heat shock factor.
“What we did is attach red fluorescent
protein, so that the cells with heat-shock factor
appear red under the microscope. That
is why it is called a reporter system,” said
Rakic. This system was tested by introducing
the gene for the fluorescent protein into
mice and analyzing the amount of red fluorescence
under various conditions, such as
the absence of heat shock factor and the mutation
of the reporter system.
Mice that didn’t have the HSF1 didn’t display
red fluorescence, confirming the reliability
and specificity of the reporter system. The
scientists determined that the reporter system
specifically detects the presence of the heat
shock factor and thus can be used to label cells
vulnerable to stress with a bright red color.
After the reporter system was validated,
the researchers developed live mice and
cell cultures with the red fluorescent reporter
DNA inserted. The use of mice was key
to the implications of their results, as mice
are model organisms that can give insight
into how biological processes occur in humans.
“This reporter system may provide a
powerful tool for exploring the pathogenesis
and treatment of multiple disorders caused
by exposure to environmental stress before
symptoms become manifested, exacerbated,
and/or irreversible,” said Masaaki Torii, visiting
assistant professor of neuroscience at
Yale and principal investigator at the Children’s
Research Institute.
Finding the odd ones out
Two methods were used to detect and characterize
vulnerable neurons: first, experiments
were conducted in petri dishes with
reporter brain cells in order to analyze the
behavior of the vulnerable cells compared to
normal cells when exposed to stress. Second,
experiments were conducted with the live re-
16 Yale Scientific Magazine April 2017 www.yalescientific.org

cell biology
FOCUS
porter mice to analyze the effects of stress on
vulnerable brain cells.
Preliminary experiments with reporter
cell cultures were performed under various
concentrations of alcohol, to simulate alcohol
intake during pregnancy, and various
temperatures. Rakic and his colleagues observed
that higher concentrations of alcohol,
higher temperatures, and longer exposures
of heat corresponded to greater red fluorescence
in the cells. This indicated that, as the
amount of physical or chemical stress placed
on the cells increased, the amount of cellular
stress response also increased.
Diagnosing the red cells
Finally, and most importantly, the researchers
observed that these vulnerable neuronal
cells were different structurally and behaviorally
than normal neurons. “The trickiest part
was to confirm that the cells identified by the
reporter really show abnormal physiological
properties. We addressed this by analyzing the
physical cell forms, and cell migratory behavior
and electrical properties,” said Torii.
When exposed to alcohol and heat, red fluorescent
neurons with the increased HSF1 were
observed to have shorter signaling branches,
called axons, which are responsible for conducting
electrical signals from neuron to neuron.
Additionally, in mice exposed to alcohol
during early development, the vulnerable cells
were observed to move more slowly than the
surrounding normal cells. This suggests that
damaged neurons behave differently due to the
environmental stress faced during early stages
of brain development, which may have implications
in further studies of mental disorders.
The reporter system serves as a window into
the cellular basis of mental disorders. “Some
cells are vulnerable. They are more sensitive;
and it’s not just to one thing. They may have increased
sensitivity to stressors like losing a job,
or exposure to alcohol or drugs. They are just
not quite as resistant,” said Rakic.
This new ability to distinguish vulnerable
cells from normal cells has implications for
the identification of individuals who are more
susceptible to mental disorders. Children born
to mothers who were using drugs or alcohol
during pregnancy are likely more vulnerable
IMAGE COURTESY OF PASKO RAKIC
►Cellular damage was imaged using the fluorescent reporter system in control mice (left) and mice exposed to alcohol during prenatal
development (right). Damaged cells are shown by the red fluorescence.
Later experiments in mice models involved
exposing mice to alcohol and other environmental
stressors including hyperglycemia, an
excess of sugar in the blood stream, and asphyxia,
oxygen deprivation, during prenatal
development. After they were born, these mice
had increased red fluorescence in the cortex,
the frontal, outer layer of the brain, suggesting
that these red cells had an activated stress response
and increased levels of HSF1. “We sacrificed
the mouse and saw in slices of brain tissue
that some neurons had a red color due to
the reporter. These neurons otherwise looked
normal, but we knew that they were vulnerable
due to the red labeled HSF1,” said Rakic.
The team of researchers also saw red fluorescence
in damaged cells in other organs of
alcohol-treated mice, suggesting that the reporter
system can be used in other tissues
and organ systems, a finding that may be
important to future studies of other diseases
that develop due to exposure to harmful
agents during early development. “We can
now study… how and why some people react
more strongly to stress,” said Rakic.
to developing disorders later in life. “Identifying
damaged cells before serious symptoms
arise is similar to finding small cracks in a wall
or foundation of your house, which can cause
serious destruction. The earlier you fix such
small cracks before they can grow, the easier
and better the repairs will be. The new reporter
system helps early finding of such small cracks
in humans,” said Torii.
ABOUT THE AUTHOR
EILEEN NORRIS
EILEEN NORRIS is a freshman prospective Biomedical Engineering Major
in Ezra Stiles College. She is the production manager for the Yale Scientific
Magazine and works in Professor Kavathas’ lab studying neoantigen-specific
T cell responses in NSCLC patients undergoing immunotherapy.
THE AUTHOR WOULD LIKE TO THANK Dr. Rakic and Dr. Torii for their
enthusiasm to share their research.
FURTHER READING
Torii, M., Sasaki, M., Chang, Y., Ishii, S., Waxman, S. G., ... Hashimoto-Torii,
K. (2017). Detection of vulnerable neurons damaged by environmental insults
in utero. Proceedings of the National Academy of Sciences, 114(9), 2367-2372.
www.yalescientific.org
April 2017
Yale Scientific Magazine
17

a “Beta” way
T O
T R E A T
Type I Diabetes
a sweet
DISCOVERY
by JESSICA TRINH
art by ISA DEL TORO MIJARES
When you eat sugar, your body does more than enjoy the
sweet taste: it gets right to work breaking down the sugar
molecules, digesting the starch that you find in foods such
as potatoes into tiny molecules called glucose, a form of
sugar that your body can convert into energy. If there is too
much sugar in the bloodstream, insulin is responsible for
transferring glucose from the bloodstream into cells. A disruption
to this system, however, has drastic consequences.
Researchers at Yale University, led
by professor of immunobiology
Kevan Herold, studied Type I diabetes,
an autoimmune disorder in
which a body’s own immune system
turns against itself, targeting
its own beta cells. These beta cells
are found in the pancreas and
produce the hormone insulin,
which normally
responds to changes
in levels of glucose in
the blood. In some individuals
with Type I
diabetes, the immune
system destroys its
own beta cells. However,
a number of
beta cells manage to
evade these self-killing
mechanisms. Herold and
his team’s study focused
on this unexplained question
of beta cell survival.
Their research presented
an astonishing discovery:
a unique subpopulation
of beta cells
emerges following diabetes
onset that show
prolonged survival to
immune attack. These
findings provide hope
for those with Type
I diabetes.
A NOD in the right direction
Despite advancements in research on Type
I diabetes, much remains unknown. Specifically,
it is unclear why beta cells are killed off
at different rates in Type I diabetics. In addition,
why these cells are not totally destroyed
in some individuals with Type I also remains
unclear. To better understand the changes that
occur at the molecular level during diabetes
onset, the researchers studied non-obese diabetic
(NOD) mice, a strain of mice that spontaneously
develops diabetes at around ten weeks
of age, and which are considered the gold standard
for studying diabetes.
Researchers noticed that among four-weekold
NOD mice, a small population of beta cells
expressed fewer glucose containing pockets
than other beta cells did. Even more notably: as
time progressed, the population of these lower-glucose
cells increased compared to other
types of beta cells, comprising up to half of all
beta cells by the time the mice were 12 weeks
old. The researchers found that these so-called
“bottom beta cells” produced less insulin than
other beta cells and responded less to the presence
of glucose. But just what were these cells,
and what was their function?
Getting to the bottom of it
To confirm that these bottom beta cells were
still functioning, researchers tested their ability
to produce insulin, the defining characteristic
of beta cells. They inserted the insulin gene into
NOD mice along with a fluorescent gene. The
fluorescent gene emitted a green light, enabling
the scientists to detect insulin production. The
intensity of fluorescent light would correlate to
the amount of insulin produced. Both non-diabetic
and Type I diabetic mice displayed fluorescent
light, indicating that they still produced
insulin. “This means cells are transcribing insulin,
which we took to mean they are beta
cells,” said Herold.
www.yalescientific.org

cell biology
FOCUS
Having determined that the bottom beta
cells were beta cells, the researchers were interested
in studying how they differed from normal
beta cells at the genetic level. To test this,
they sequenced the genes of both normal beta
cells and bottom beta cell populations, identifying
457 genes in which differences were
found between populations. What they found
was astonishing: bottom beta cells displayed
traits characteristic of stem cells, capable of
proliferating and differentiating into various
specialized cell types. “This raises a question
that maybe these cells represent another type
of cell, such as a stem cell, and have now acquired
qualities of a beta cell,” said Herold.
Unlike other cells, stem cells are known for
their ability to reproduce through numerous
cycles of cell division, a process in which their
genetic material, called DNA, is replicated. To
test the stem-cell-like quality of these beta cells,
researchers studied the frequency at which
both normal and bottom beta cells underwent
cell division. Their results indicated that bottom
beta cells replicate DNA more frequently
and thereby proliferate more than other beta
cells. In addition, bottom beta cells exhibit several
cell markers characteristic of stem cells.
This finding suggests these cells actually express
fewer qualities unique to beta cells, leaving
the researchers to wonder whether this is
the reason behind their ability to survive immune
attack.
Duck and cover
In addition to harnessing qualities of stem
cells, researchers found bottom beta cells avoid
immune attack by lowering their expression of
surface markers that are marked as foreign by
the body’s immune system. “In essence, they
‘duck and cover’ from the body’s own self-targeting
immunological responses,” said Herold.
This finding indicates that bottom beta cells
are resistant to autoimmune attacks characteristic
of Type I diabetes. “The biggest surprise
is finding that the beta cells are not just waiting
there helplessly to be recognized and killed;
instead they can hide from immune attacks in
order to survive,” said Joyce Rui, an associate
scientist who contributed to the study.
Following the discovery that bottom beta
cells can survive diabetes in mice, the researchers
were interested in whether this subpopulation
of beta cells was present in human cells.
They cultured pancreatic cells from both Type
I diabetic and healthy patients, and introduced
foreign cells to mirror the immune stress that
occurs in the body when the immune system
targets its own cells. Their results indicated
both types of cells—disease-infected and
healthy, normal cell cultures—developed a
subpopulation of beta cells, suggesting human
cells produced these cells just as the diabetic
mice did. “These changes may account for
the chronicity of the disease and the long-term
survival of beta cells in some patients,” said Rui.
Promising news
Together, Herold and his team have revealed
a subpopulation of beta cells that arise during
autoimmune attack preceding Type I diabetes.
These cells show potential as breakthrough
treatments for diabetics: it may be possible to
IMAGE COURTESY OF LUCY WALKER LAB
►In patients with T1D, pancreatic cells are infiltrated by leukocytes (in green), which surround
the beta cells.
someday revert these bottom beta cells back to
normal beta cells to produce sufficient levels of
insulin Type I patients lack. “We have evidence
that the beta cell subpopulation occurs in beta
cells in humans exposed to inflammatory mediators.
But whether or not this occurs in humans
with type 1 diabetes remains unknown,”
said Herold. It still remains unclear the origin
behind these bottom beta cells. Their research
opens numerous pathways for future research,
including whether this subpopulation of beta
cells can be differentiated into functional beta
cells, which would provide a major breakthrough
for diabetic patients lacking these insulin-producing
cells. It is a sweet discovery
that may shift the way clinicians treat diabetes.
ABOUT THE AUTHOR
JESSICA TRINH
JESSICA TRINH is a freshman and prospective biomedical engineering
major in Branford College. She is the Vice President of Synapse and works
in Dr. Jiangbing Zhou’s lab studying nanoparticle treatment for brain tumors
as well as Dr. Kamil Detyniecki’s lab studying pediatric seizure clusters.
THE AUTHOR WOULD LIKE TO THANK Dr. Kevan Herold and Dr. Jinxiu
Rui for their time and enthusiasm for sharing their research.
FURTHER READING
Herold, K.C., Vignali, D.A.A., Cooke, A., Bluestone, J. 2013. “Type 1 diabetes:
translating mechanistic observations into effective clinical outcomes.” Nature
Reviews Immunology 13, 243-256.
www.yalescientific.org
April 2017
Yale Scientific Magazine
19

study of the
CENTER
of the Earth
by
SONIA WANG
art by
ISA DEL TORO MIJARES
What would you do with two
million dollars? Chances are
dim that your first answer would
be to build and buy enough liquid
sodium to fill a three-meter
radius spherical tank. But
for some scientists, this investment—the
University of Maryland
Three Meter dynamo experiment—paid
off, serving as
a key step to understanding the
age-old question of how Earth’s
magnetic field is generated.
Earth’s magnetic field not only shields us
from the sun’s damaging radiation, but also
helps us navigate the Earth. Geophysicists
have long studied the magnetic field created
by Earth’s liquid core, but attempts to re-create
them in the lab have previously been unsuccessful
due to the prohibitively high costs of
building equipment to do so.
However, in a study published in January, a
team of Yale researchers in Mechanical Engineering
Professor Eric Brown’s lab developed
a method for producing liquid metal with improved
magnetic properties. The researchers
created a protocol to create these Magnetic
Liquid Metals (MLM) after studying a suspension
of magnetic iron particles in eGaIn,
a liquid alloy of indium and gallium. Such a
technique could enable researchers to conduct
dynamo experiments, which model the generation
of Earth’s magnetic field, on a far smaller
size scale.
The magnetic field’s liquid beginnings
By studying earthquake as they travel
through the planet, seismologists know that
the Earth has a fluid outer core surrounding
a solid iron inner core. The liquid outer
core, made of iron, is crucial to the creation of
Earth’s magnetic field which is an example of
a magnetohydrodynamic (MHD) phenomenon—magnetic
properties resulting from an
electrically conductive fluid. Movement of the
outer core in the presence of Earth’s magnetic
field induces electrical currents, which then
create their own magnetic field aligning with
Earth’s overall magnetic field. This process sustains
itself and allows for the maintenance of
Earth’s magnetic field over the years.
Magnetohydrodynamic phenomena only
occur at a high magnetic Reynolds number,
which describes the magnetohydrodynamic
properties of an object; at a high Reynolds
number, MHD phenomena are more likely.
The magnetic Reynolds number depends on
several properties, such as the system size, the
fluid velocity, electrical conductivity, and magnetic
susceptibility—the response of the fluid
to a magnetic influence. Something as large as
a planet would have an extremely high Reynolds
number, making MHD phenomena more
natural. However, re-creating such phenomena
in a laboratory setting is extremely difficult,
requiring materials with high magnetic and
electrical properties.
Traditional studies of MHD have used liquid
metals and plasmas because they have the
highest electric conductivities of any known
materials. Liquid sodium has the highest conductivity
and has been used to create a dynamo
experiment in the past, but is both expensive
and dangerous; sodium reacts explosively with
water and needs to be heated above its high
melting temperature. Looking for a safer and
easier alternative, the researchers sought to use
a different liquid metal base for the study.
However, as noted before, other factors such
as the magnetic susceptibility also affect the
Reynolds number. Despite having a good electrical
conductivity, pure eGaIn has a low magnetic
susceptibility and therefore a low Reynolds
number. To boost the Reynolds number,
www.yalescientific.org

geophysics
FOCUS
the researchers proposed creating a new material
by suspending magnetic particles in liquid
metals to increase their magnetic susceptibility
and take advantage of the liquid metals' natural
high conductivity.
Acid’s key role
While scientists have previously attempted
to suspend magnetic particles in liquid metals,
they have not been very successful because of
metallic oxidation. The oxidation of the metal
causes a new “rusted” oxidation layer on the
liquid metal with its own set of properties. As
this layer is more solid, it prevents some of the
delicate suspension effects.
Initially, stirring iron particles into the liquid
eGaIn failed to create a successful suspension,
since a solid oxide layer formed at the surface
of the liquid upon exposure to air. Despite vigorous
stirring to break the oxide skin, the particles
clung to the oxide skin due to the strength
of the interactions between the two layers.
To solve this problem, the scientists used
hydrochloric acid (HCl), at a dangerously
low pH of 0.69 capable of corroding skin,
as a chemical cleaner or purifying agent; in
eGaIn, hydrochloric acid removes the oxide
layer on the liquid metal and iron particles, allowing
for more liquid-like properties in the
metal and increasing the conductivity of the
iron particles. The suspension process was
successful after the researchers added enough
HCl to cover the metals and prevent further
contact with air.
Design your own fluid
The new material has increased magnetohydrodynamic
properties compared to the
original eGaIn. The resulting MLM had a
Reynolds number over five times higher than
that of pure liquid metal, or two times higher
than liquid sodium. Thus, a dynamo experiment
that would previously have required a
three-meter radius tank might be possible on a
much smaller size scale—ten square centimeters
rather than three meters. “Until this study,
no one thought about doing dynamo experiments
with eGaIn because the quantity needed
for these experiments make it cost prohibitive,”
said Florian Carle, the lead author of the paper.
Furthermore, certain properties of the MLM
can be customized for different purposes and
different applications. As long as the conductivity
of the iron particles you would like to
suspend is higher than that of the liquid metal
base, nearly any material can be used for the
IMAGE COURTESY OF FLORIAN CARLE
►EGaIn has higher conductive and magnetic
properties than traditional liquid metals due
to the iron particles in the suspension.
liquid and suspended particles. “It’s basically
Design Your Own Fluid…you can suspend
silver, graphene, diamond…you can tune the
size of the particles within this huge range,”
said Carle. Changing the quantity of iron particles
in eGaIn will modify the material viscosity—the
more particles, the more viscous the
fluid. Furthermore, changing the type of particle
used can further affect the conductivity
and magnetic properties of the material; using
highly conductive particles will increase
conductivity, and using magnetic particles like
iron or steel can increase magnetic properties.
The applications are myriad. Separately controlling
the viscosity and the magnetic properties
of the material will allow scientists to
isolate the effects of magnetohydrodynamics,
which is indicated by the Reynolds number,
and turbulence, a measure affected by fluid viscosity
and velocity that indicates how chaotic
the flow of the material is.
Carle designed the paper to be easily accessible,
so that even a scientist without special
training could re-create the material. He hopes
that more scientists will apply the procedure
to their research: “Now that we can tune the
properties…hopefully people will start picking
up on that and be able to use that. I hope in the
near future we will see more and more experiments
using MLMs,” said Carle.
Of sustainability and superfluids
Though Carle has moved on to work at the
Yale Quantum Institute, research continues in
the Brown lab on eGaIn. One challenge the
group is investigating is in keeping the magnetic
liquid metals fresh during storage: after
six months of storage, samples exhibited a loss
in magnetic susceptibility as the hydrochloric
acid slowly ate away at the iron particles.
“It’s a bit of a conflict, since you need to protect
the eGaIn with HCl, but then the HCl
will eat the iron,” said Carle. Further research
is being done to develop storage methods for
eGaIn, including solidifying the samples or removing
HCl to allow formation of a protective
oxide layer on the surface of the fluid.
Carle further speculates that there are applications
beyond MHD and dynamo experiments,
since it is a customizable new material.
And perhaps an MLM could eventually be
created out of sodium, which has the highest
electric conductivity of any known liquid metal.
Adding magnetic particles to that suspension
could allow scientists to attain a Reynolds
number off the charts. “You would have a superfluid…maybe
we would see phenomena
we haven’t seen anywhere before,” said Carle.
ABOUT THE AUTHOR
SONIA WANG
SONIA WANG is a junior Molecular Biophysics and Biochemistry major
in Jonathan Edwards College. She is the managing editor for the Yale
Scientific Magazine and works in Professor Joan Steitz’s lab studying
microRNA degradation. She was previously a News Editor and Advertising
Manager for the magazine and loves brainbows.
THE AUTHOR WOULD LIKE TO THANK Dr. Florian Carle for his
enthusiastic and detailed explanations of eGaIn.
FURTHER READING
Carle, F., Bai, K., Casara, J., Vanderlick, K., & Brown, E. (2017). Development
of magnetic liquid metal suspensions for magnetohydrodynamics.
Physical Review Fluids, 2(1).
www.yalescientific.org
April 2017
Yale Scientific Magazine
21

FOCUS
applied physics
CHILLING
PRECISION
cooling & trapping
molecules
with lasers
by Will Burns | art by Catherine Yang
22 Yale Scientific Magazine April 2017 www.yalescientific.org

applied physics
FOCUS
Ten thousand scientists and engineers from over one hundred countries. Over one thousand
superconducting magnets, each more than fifty feet in length. Thirteen billion
dollars. One thirty-eight-thousand-ton tunnel. This is what it took to build the Hadron
Collider over the course of its ten-year construction. It was the largest and most powerful
experimental facility built. The aim of the endeavor was to discover new particles—notably,
the Higgs boson—by smashing protons together at speeds nearing the speed of light. But
what if this same feat could be achieved on a tabletop using a gas chamber and a few lasers?
Researchers in Professor of Physics
Dave DeMille’s group at Yale have improved
a complex technique in atomic
physics to explore this exciting physical
topic. The technique, called laser cooling
and trapping, combines atomic spectroscopy
with the mechanics of light to change
the properties of gaseous atoms and molecules.
By shining lasers at gas molecules
from several directions, researchers were
able to cool the molecules to near absolute
zero and levitate them in space, allowing
for extremely precise measurements for a
wide array of applications.
Cooling Atoms With Lasers
The concept of shining a laser at an object
to cool it down is not intuitive, especially
since we usually think of lasers as
heat sources. Laser cancer treatment, 3D
printing, and laser cutting all use the high
energy of laser light. Using a laser as a
cooling agent, however, seems odd, since
it is difficult to imagine using high-energy
laser light to decrease the energy of a
group of atoms or molecules.
Temperature is a measure of the average
velocities of atoms or molecules, so in essence,
to cool something is to slow down
its atoms and molecules. But to slow an
atom down, the atom needs to be pushed
in the opposite direction of its motion.
This can be achieved on an atomic scale by
making use of the properties of atoms and
light. The photons of laser light carry momentum
and energy, and when they hit an
atom moving in the opposite direction, the
momentum is transferred from the photon
to the atom, slowing the atom down.
When enough photons hit the atom, the
atom could stop moving altogether.
However, the photons in laser light only
interact with an atom if they have a certain,
extremely precise frequency. This is
complicated by the fact that atoms are in
constant motion. The trick of laser cooling
is to deliberately adjust the frequency of
laser light so that the frequency is slightly
smaller than the frequency that would
be needed to excite an atom that is at rest.
This creates what is called a Doppler shift,
more commonly known to affect the way
sound waves are perceived. For example,
if an object emitting sound moves away
from a listener, he or she will hear a lower
pitch, whereas if the object moves toward
the listener, he or she will hear a higher
pitch. This principle holds true for light as
well. If an atom is moving toward a laser,
the atom experiences a frequency slightly
higher than the frequency of the laser
light, causing the atom to absorb the photon.
If an atom is moving away from a laser,
the atom experiences a frequency too
low for photon absorption. “If the laser is
calibrated such that it has a frequency too
low to excite an atom at rest, but such that
if that atom starts moving toward the laser,
the Doppler shift makes the atom ‘see’
the correct frequency, then an electron
transition can occur and the photon will
be absorbed,” said DeMille.
Once enough photons from one laser
hit an atom, the atom will slow down and
eventually stop moving. Once stopped, the
atom also ceases to absorb photons, because
the atom only absorbs photons when
moving toward the laser. For this process to
work, several lasers are placed around the
collection of atoms. Any given laser only
slows down atoms moving toward that laser.
But since atoms travel in all directions,
each atom needs to be individually Doppler
shifted using several lasers. The net result
is that all of the atoms stop moving. Since
the speed of an atom is directly related to
its temperature, this technique can chill the
atoms to less than a thousandth of a degree
above absolute zero.
A Magneto-Optical Trap for Molecules
The process of cooling atoms with lasers
is only useful if they can be simultaneously
confined in space such that researchers
can study their properties. To achieve
this, researchers now use a technique in
cold-atom physics called the magneto-optical
trap (MOT), which combines laser
cooling with restoring forces that compress
a cloud of gaseous atoms into a tight
ball. “The magneto-optical trap technique
is so ubiquitous that pretty much anything
you do in the field of atomic physics uses
it. It is really that revolutionary. These systems
are now the best controlled systems
in the world,” said Matthew Steinecker, a
fourth-year graduate student at Yale.
The magneto-optical trap has been used
to simultaneously cool atoms down and
levitate them in space for over three decades.
David DeMille’s group, however,
was the first group in the world to use the
magneto-optical trap to cool and confine
molecules. Molecules, unlike atoms, have
more complex internal structures, which
pose additional technical challenges when
trying to confine them using magneto-optical
trapping. Molecules have additional
properties, notably vibration and rotation,
which makes it challenging to apply the
same technique for molecules as was previously
used for atoms.
Researchers in the DeMille group used
a modified version of MOT to generate
ultracold, trapped strontium monofluoride
(SrF) molecules. The new technique,
called radio-frequency magneto optical
trap (RF-MOT), rapidly and simultaneously
reverses the polarization of the
lasers and the magnetic field of the system
to counteract the challenges in controlling
molecular movement when molecules
vibrate and rotate. SrF molecules
have less potent vibrational and rotation-
www.yalescientific.org
April 2017
Yale Scientific Magazine
23

FOCUS
applied physics
al motions, making them easier to study.
Refining this technique, researchers have
been able to trap SrF molecules at a much
greater density than has previously been
achieved and at molecular temperatures
as low as 250 microkelvin—4,000 times
colder than the Boomerang Nebula, the
coldest naturally occurring place in the
universe.
Beyond the Lab
The emergence of MOT technology
has given rise to a number of exciting
applications for ultracold matter. First,
ultracold atoms and molecules allow for
extremely precise measurements, making
them ideal candidates for high-resolution
spectroscopy, quantum measurements,
and precision tests on the fundamental
laws of nature. Ultracold atomic physics
has already given rise to high-accuracy
atomic clocks, which are the heart
of satellite and GPS systems, quantum
sensors, and precision measurements of
well-known constants in nature such as
the acceleration of gravity. We now know
the value of the gravitational constant a
million times more accurately using laser
cooling and trapping than from previous
experiments. MOT technology can detect
and measure very small quantities of rare
isotopes, so doctors can now measure the
amounts of rare isotopes of calcium in
the bones of patients with certain types of
bone degeneration.
The Heisenberg-Uncertainty Principle
states that the energy and time of a particle
cannot be simultaneously measured
with high precision. The longer amount
of time an object can be observed, the
more effectively one can measure its energy.
Using MOT technology—which
simultaneously confines molecules in
space and cools them down—the energy
of atoms, and now molecules, can be
measured with extreme precision. The
DeMille group has recently embarked
on an experiment using RF-MOT to
trap molecules and observe very subtle
changes in energy of molecules that are
caused by elemental particles—the building
blocks of the universe, including the
Higgs boson. This could even lead to the
discovery of new elementary particles.
The complex and information-rich nature
of molecules is opening the door to a
number of exciting new experiments using
laser cooling and trapping technology. The
unique properties of molecules enhance
researchers’ ability to test our understanding
of fundamental physics. Researchers
are currently hunting for the permanent
electric dipole moment of the electron.
Since molecules have electric dipoles, they
interact strongly through electric fields
even when they are far apart. DeMille
suggests that when a group of molecules
is cooled to low enough temperatures, it
will form states of matter with properties
not yet observed. “There’s a lot of interest
in studying these exotic phases of matter
IMAGE COURTESY OF MATTHEW STEINECKER
►The DeMille group has built a network of lasers adjusted to very precise frequencies to
decrease the spread of random velocities of a group of molecules and exert forces on the
molecules to confine them in space.
where the pieces of the gas interact with
each other pretty strongly even when they
are far apart,” said DeMille.
Advancements in RF-MOT technology
in the DeMille group could potentially
revolutionize our understanding of
fundamental physics. “There are certain
observations that we can make about the
universe that we don’t understand given
the laws of physics. This is one area
where we can look to see how our understandings
of the laws of physics are subtly
wrong,” said Steinecker. Laser cooling
and trapping technology is on the verge
of making a truly extraordinary catch.
ABOUT THE AUTHOR
WILL BURNS
WILL BURNS is a freshman Molecular Biophysics & Biochemistry major in
Morse College. He is the copy editor for the Yale Scientific Magazine and
works in Professor Forscher’s lab studying cytoskeletal dynamics underlying
growth cone motility in neurons.
THE AUTHOR WOULD LIKE TO THANK Professor DeMille and Matthew
Steinecker for their passion and dedication to their research.
FURTHER READING
Steinecker, M. H., McCarron, D. J., Zhu, Y., & DeMille, D. (2016, November
08). Improved Radio-Frequency Magento-Optical Trap of SrF Molecules.
Retrieved April 09, 2017.
24 Yale Scientific Magazine April 2017 www.yalescientific.org

astronomy
FEATURE
►BY ANDREW RICE
LIFE FROM WITHIN?
Organic materials stemming from Ceres’ interior
IMAGE COURTESY OF NASA
►Photo of Ceres’ surface. Each crater is the result of an impact
by an exterior body.
Are we alone in the universe? The hunt for extraterrestrial life
is a complex search leading in many directions. What is certain
among researchers involved in this hunt, however, is the dependence
of life on organic elements. Life as we know it evolved
from organic compounds, molecules composed of primarily
carbon and hydrogen—and where there are organics, there is a
possibility of life. The process by which planets acquire organics
has been studied for centuries, the most prominent theory being
that planets are exposed to organics through impacts from
exterior bodies such as comets and asteroids. Now, a recent discovery
on the dwarf planet Ceres shows that planets don’t always
acquire organics from exterior impacts, but instead can form
these materials in their interiors.
Approximately 4.6 billion years ago, our solar system was
formed. During the period of planet formation, small bodies,
such as comets and asteroids, were ubiquitous and bombarded
newly-forming planets. Frequent collisions allowed for molecules
such as water and organic compounds to make their way
to different planets, acting as passengers on these smaller bodies.
This phenomenon is how many believe Earth acquired its
organic materials some four and a half billion years ago. As the
Earth continued to mature, it cooled down, developed an atmosphere,
and began harboring the evolution of life.
This same process of smaller bodies colliding with other planets
is very common throughout the universe, far beyond our solar
system. Now, researchers are able to analyze craters left behind
from these impacts by examining their radioactive decay.
This method of analysis determines a crater’s age and composition,
painting a history of the planet. And, as observed on the
dwarf planet Ceres, this analysis can lead to major conclusions
about the origins of different elements on these planets.
In early February 2017, the Dawn Spacecraft, first launched
by NASA in 2007, gathered data about Ceres from its spectrometer
that shows organic-rich areas on the surface of the
dwarf planet. The spectrometer measures different wavelengths
of light, including visible and infrared, which are plotted
to reveal important information about the object emitting
or reflecting that light. When plotted, the infrared spectra
show absorption bands—wavelengths of light that are absorbed
only if certain organic compounds are present on areas
of Ceres’ surface. The highest concentrations of these organics
occur in a heavily-cratered and fresh region, partly on the
southwest floor of the Ernutet crater.
Researchers are ruling out the possibility of an external origin
for these organics because they lie in a heavily-impacted
region. For organics to survive, they need to be in a stable environment,
so the presence of high concentrations in a freshly-cratered
region means another source must be supplying
the organic materials. “We think the organics in the subsurface
were concentrated somehow, perhaps by hydrothermal
activity, and then exhumed by impacts,” said Harry McSween,
a University of Tennessee geophysicist involved in the study.
This idea that Ceres’ core is hydrothermally active suggests
that Ceres may have been able to independently form organics
in its interior, while impacts from asteroids or comets exposed
these organics to the surface.
Although scientists have now found strong evidence to support
the idea that planets can form their own organic elements,
there are several obstacles to overcome before applying this to
the search for extraterrestrial life. Kanani Lee, a mineral physicist
at Yale, explains that four conditions are necessary for life
to form: the proper elements, a burst of energy, shelter, and an
environment conducive to formation of life. “Even though we
know Ceres has the right elements, it is too small to produce
a significant magnetic field capable of protecting it from radiation,
and it doesn’t have a safe environment for life to evolve
because it is frequently impacted by smaller bodies,” Lee said.
Despite Ceres’ failure as a legitimate contender for harboring
life, this discovery broadens how we think about extraterrestrial
life. “Ceres already contained processed organic matter,
so the ingredients for life were there in molecular form—life
did not have to start from scratch with elements,” McSween
said. With further research on dwarf planets in our solar system
and on exoplanets, researchers will begin to learn more
about the patterns of interiorly-formed organics and the planets
that harbor them, narrowing the search for life elsewhere
in the universe.
www.yalescientific.org
April 2017
Yale Scientific Magazine
25

FEATURE
molecular biology
SUGAR’S SAVING GRACES:
Reducing the strain of an active lifestyle
►BY MAYA CHANDRA
Humans love sugar. It’s delicious and energizing, and our bodies
use it for a variety of activities. In an interspecies competition for
the biggest sweet tooth, however, we’re losing big time to nectarivores,
a group of animals that expend huge amounts of energy flying,
hovering, and sucking the sugar-rich nectar out of plants. In a
new study released in Science in February 2017, researchers found
that these species need sugar to power an ancient pathway that produces
antioxidants and enables their active lifestyles.
Nectarivores, such as hummingbirds, bees, butterflies and hawk
moths, are unique due to both their taxing aerobic lifestyle and their
high-sugar diets. The nectar they consume is essentially pure sugar.
In fact, a single meal for a hawkmoth is approximately equivalent to
80 bottles of soda for a human. According to Eran Levin, a researcher
at Tel Aviv University and the first author on the study, sugar is
“magic” in that it can be transformed into all the body’s basic building
blocks, from amino acids to DNA. While the multi-purpose nature
of nectar makes it an attractive fuel source for these species, the
energy expenditure required to collect it from flowers is high.
For most pollinators, nectar collection involves a lot of flying,
which requires a high oxygen intake. By using oxygen from the
air in aerobic metabolism, the sugar molecules split to create usable
energy, but this process is imperfect because a small percentage
of the oxygen involved becomes free radicals, or atoms with
unpaired electrons. These free radicals, in their need to complete
their missing electrons, have the capacity to attack lipids, proteins,
DNA, and other vital cell components and cause what is known as
oxidative damage. Antioxidants are the body’s best defense against
oxidative damage, donating electrons to free radicals and rendering
them harmless. Nectar, however, contains no antioxidants. So how
do pollinators combat oxidative damage, if they are not getting anti-oxidants
from their diet?
This team of researchers suggests that nectarivores use cellular
processes to generate antioxidants outside of their diet, allowing
them to be highly active. “This is why hummingbirds can hover and
fly the way they do,” Levin said. In order to measure oxidative damage,
the researchers tested hawk moths for lipid and protein damage.
They found that moths fed a high-sugar diet had lower oxidative
damage than those who were not. The challenge then became
to identify the structure that was using sugars to create antioxidants.
Glucose is traditionally broken down inside mitochondria in a
pathway called the Krebs cycle, but most organisms also have another
mechanism, known as the Pentose Phosphate Pathway
(PPP), through which glucose breakdown can occur. To confirm
that hawk moths were using this pathway, the researchers fed them
glucose labeled with a trackable isotope. They discovered that these
insects were sending sugars through the PPP and through this
pathway, they generated the antioxidants necessary to prevent oxidative
damage and produced fewer free radicals. The PPP is a biological
relic from a time when there was little oxygen in the atmosphere.
The Krebs cycle cannot occur in the absence oxygen, so
PPP was necessary as an alternative pathway during this time. PPP
is already known to produces a few vital compounds, yet this paper
was the first to demonstrate that its secondary role—creating antioxidants—has
permitted high-metabolic-rate, nectar-feeding animals
to evolve and persist.
The project focused on nectarivores, particularly hawk moths,
but the PPP is found in all animals, including humans. The researchers
hope that further studies will illuminate how the PPP
functions in a variety of organisms with different diets. Research
has already shown that humans with a PPP deficiency suffer higher
levels of oxidative damage; however, they are also less likely to
suffer from cancer or blood parasites. This research opens the door
for further work into the evolution of metabolic systems across the
biological kingdoms, and it raises a wide range of questions on topics
ranging from evolutionary history to modern human diet and
exercise. Only further scientific inquiry, carried out by the paper’s
authors and other interested scientists, will reveal the full breadth of
the paper’s impact.
IMAGE COURTESY OF PIXABAY
► Hummingbirds and other nectarivores use sugar in the
Pentose Phosphate Pathway to create antioxidants from sugar,
repairing their bodies rapidly.
26 Yale Scientific Magazine April 2017 www.yalescientific.org

physical chemistry
FEATURE
KNOCKING AROUND ATOMS: A CHEMICAL
►BY ISAAC WENDLER
Synthesizing for the quantum age
ART BY SIDA TANG
►Researchers at IBM were able to construct the elusive
triangulene by manipulating single atoms with a scanning probe
microscope.
Conventional methods have allowed organic chemists to make
many molecules with complex three-dimensional structures, but
one particular triangle-shaped molecule called triangulene has
presented some difficulty. Its instability has prevented previous
chemists from isolating it, but a research team at IBM has recently
synthesized this elusive molecule. Its successful synthesis could
mark an interesting development in the quantum age of technology,
as this new technique for chemical synthesis has many potential
applications.
In traditional chemical synthesis, chemists follow a synthetic
pathway, or a series of sequential steps such as mixing or heating
chemicals, to carry out chemical reactions and transform the
original reactants into a desired product. All attempts made so
far to synthesize triangulene—whose triangle-shape consists of
six attached rings, each made of six-carbons, with two unpaired
electrons on the middle rings—have been unsuccessful. This is
because these unpaired electrons are extremely reactive, and any
triangulene molecule produced from a conventional synthetic
pathway is ephemeral—it usually isn’t sufficiently stable to exist
long enough for practical use. The bulk of the practical value of
triangulene comes from the very same properties that make it
so unstable: its two unpaired electrons give it potential for use in
quantum technologies, which have yet to be explored.
The team at IBM decided to put the traditional method on the
back-burner and opted instead for a new technique: atomic manipulation.
In atomic manipulation, a scanning probe microscope
or other extremely fine instrument is used to physically manipulate
atoms or molecules and to change their chemical structure
manually, without the use of conventional chemical reactions.
To produce the molecule, the team at IBM first obtained a sample
of dihydrotriangulene—a molecule that looks identical to triangulene
except it lacks unpaired electrons, which are instead replaced
with hydrogen atoms. They then added this molecule to
the surfaces of three solids: sodium chloride, copper, and xenon.
Adhering dihydrotriangulene to these surfaces provided structural
stability to the molecule and therefore improved the accuracy of
the next step, in which the team placed the needle of the scanning
probe microscope above two hydrogen atoms and delivered pulses
of electricity to separate them from dihydrotriangulene, leaving
an electron behind. The result was triangulene, characterized by
its two unpaired electrons on two sides of the carbon “triangle.”
The team is undoubtedly excited about their first-ever synthesis
of triangulene. Lead researcher Leo Gross told Nature reporter
Philip Ball, “Triangulene is the first molecule that we’ve made that
chemists have tried hard, and failed, to make already.”
This synthesis of triangulene may have practical applications
in the realm of electronics and quantum technologies, including
quantum computers, sensors, and data transmitters. The research
in this field is ongoing and promising, suggesting that this
new kind of technology will be able to store more memory and
compute mathematical calculations with greater speed than do its
classical counterparts.
The challenges that researchers have faced in synthesizing triangulene
are also what makes it most promising for quantum
technologies. Triangulene’s unpaired electrons have a fundamental
quantum property called spin, which is very relevant for modern
spintronics, as it uses electron spins to manage memory. Because
the spins of the two unpaired electrons are aligned, they can
be manipulated to store information in a more efficient manner.
Not only can this improve modern electronics, such as hard drive
read heads, but it may also unlock new fields within quantum
computation.
Especially promising is the fact that the team’s research suggests
that triangulene, even with its unpaired electrons, is relatively unreactive
on solid copper. This is positive news for triangulene’s
practicality, as copper is a valuable constituent of many electronic
technologies; if the two were reactive, it would be extremely challenging
to incorporate triangulene into quantum technology that
also has copper.
Perhaps more far-reaching and important than triangulene itself
is its method of synthesis. The work of this IBM team shows
that atomic manipulation can indeed be used to work around the
limitations of conventional chemical synthesis and produce synthetic
targets that are not able to be produced otherwise.
This new method of synthesis, and the end-product molecule
itself, are good signs for the future of technology—especially as
the world makes the leap from classical to quantum.
www.yalescientific.org
April 2017
Yale Scientific Magazine
27

FEATURE
geology and geophysics
Dramatic landscapes invite wonder. The sheer
stark rock of Devil’s Tower, the vast emptiness of
the Utah salt flats, and the deep plunge of the Grand
Canyon all seem to be beyond our limited human
imaginations. One such landscape can be found in
Southeastern India, in a region known as the Deccan
traps. The Deccan traps are one of the world’s largest
volcanic plateaus, stretching across over half a million
square kilometers and covering an area larger
than Washington and Oregon combined. Sixty-five
million years ago, this region became very geologically
active. Volcanic eruptions shook the Earth,
adding layer after layer to the Earth and stretching
several kilometers into the sky. Some scientists
have even suggested that these eruptions were a
major contributing factor to the Cretacious-Tertiary
extinction event, which wiped out the dinosaurs.
Such an impressive geological feature must have
had an equally impressive geological cause, but
unlike the easy-to-see traps, these causes are buried
deep—deep below the surface, and deep in the
past. The Deccan traps were certainly created by a
hotspot, or a large upwelling of hot magma in the
mantle. The previously-accepted theory says that the
Deccan traps were caused by the Reunion hotspot,
located a thousand miles to the east of Madagascar.
As the subcontinent of India moved from near
Antarctica up into the Eurasian continent, it passed
over this hotspot and formed these Deccan traps.
But now, Petar Gilsovic and Alessandro Forte, professors
at the University of Quebec at Montreal,
have created more accurate models, predicting that
a second hotspot also fed into these volcanic eruptions.
In the journal Science, they published a new
back-and-forth time integration method to create a
more accurate model of the whole Earth, possibly
unlocking a better understanding of our Earth’s
dynamic past.
The Earth is an incredibly complex and dynamic
object, as rocks swirl and churn deep below our
feet. Understanding the Earth’s interior today takes
complex instrumentation and research, but looking
backward in time is even harder. The physical laws
that govern how the Earth changes are as chaotic
and nonlinear as the butterfly effect, where a flap
of a butterfly’s wings in the Amazon could cause a
hurricane off the coast of France. “The Earth is profoundly
nonlinear,” said Forte, one of the coauthors
of this report. That nonlinearity causes errors to cascade
and multiply, especially when viewed over the
span of millions of years.
Even basic physics seems to stack the deck against
the prediction of the Earth’s past. One basic physical
force that shapes the Earth is thermal diffusion, the
distribution of heat throughout the Earth—whether
in magma pockets in the mantle or in cooling vents
near the crust. However, thermal diffusion is often a
one-way process, always moving forward in time. A
simple example can be found in your morning habit
of drinking a cup of coffee with cream. As you stir
cream into the coffee, the cream quickly dissipates
throughout the coffee. It would be nearly impossible
to trace back the exact location where you began
pouring the cream, given only the final state of the
coffee.
Despite these challenges, many geophysicists have
still tried synthesizing all the data they can collect
on the past to create a model for a past Earth.
Then, to see if their guesses hit the mark, they apply
known physical laws such as thermal diffusion and
fluid dynamics to time-evolve the modeled Earth to
its present state. If their model matches our current
Earth, then the initial prediction was somewhat
accurate. But, because of the nonlinearity of these
physical laws, it becomes incredibly difficult to make
accurate predictions past roughly thirty million
years ago.
The new research takes a different approach.
Instead of synthesizing data from the past, they use
the most up-to-date data of the present Earth to
make predictions for the past. They apply physical
laws to time-evolve forward to the present day and
check if any errors showed up. An algorithm then
seeks the smallest possible modification that can
reduce these errors, creating a slightly modified
model. With this new model, just rinse and repeat.
As the model tangos through time, it sweeps back
and forth, and back and forth, checking for errors
28 Yale Scientific Magazine April 2017 www.yalescientific.org

and making tiny corrections. Eventually, one of the predictions
exactly matches our present Earth.
To even begin this process, an in-depth understanding of our
Earth is required. Although we can’t just look through the ground
and see everything, there are very clever instruments that map
the Earth. Adventurers of the past may have hiked up mountains
IMAGE COURTESY OF THE SCRIPPS INSTITUTE
►The Indian subcontinent was once closer to the Antarctica and
African plates, but has since shifted towards the Eurasian plate. As it
moved across the Reunion and Comores hotspots in the Indian ocean,
the Deccan traps were formed.
to measure their altitudes, but today, scientists can also use GPS
and other satellite technologies to determine the Earth’s topography.
To image the inside of the Earth, seismologists use earthquakes
as light sources and measure how they bounce and reflect.
Like x-rays that reveal our bones and tissues, earthquakes reveal
detailed structures within the core and mantle. Further data—for
example, measuring how the Earth distorts gravity—enables even
more precision in measuring.
Armed with a detailed understanding of today’s Earth, scientists
are still investigating why this method works. Is this not just
a case of a student with an answer key, trying to guess the correct
steps without understanding the question? The fundamental difference
is that under this method, physical laws are being applied
and evaluated. One place where this can be best seen is with the
velocity of tectonic plates. As the churning of the mantle below
the crust moves tectonic plates on the surface, the plates gain
different velocities. However, the relationship between mantle
and crust is very complex, depending on viscosity and thermodynamics.
Many other models simply use known data, gathered from other
sources, to assign velocities to each of the plates. “We referred
to this procedure flippantly as the ‘Hand of God,’ because there
wasn’t anything predicted based on what was going on inside the
geology and geophysics
FEATURE
Earth,” said Forte. Using a more advanced physical model, Forte
removed the Hand of God from these models to better understand
how the Earth really was. Professor Jun Korenaga from
Yale’s Department of Geology and Geophysics, another expert on
mantle dynamics, has reservations on models predicting further
than 100 million years ago, especially because of the complexities
of viscosity. “Nobody really knows how to simulate plate tectonics,”
said Korenaga. But, even with these shortcomings, Forte and
Gilsovic were able to find very interesting results.
The researchers applied this technique to the Deccan traps to
understand their origin. Although the Reunion hotspot has long
been thought to have been the only driving force of this catastrophic
force of nature, Forte and Gilsovic discovered a smaller
hotspot that also fed the volcanos. The Comoros hotspot is several
hundred kilometers northeast of the Reunion hotspot, but
the models of the Earth show that they also contributed greatly
to the Deccan traps 65 million years ago. Although these regions
appear separate today, they were once joined below the surface,
giving rise to a fearsome display of fire and lava. “We think of
eruptions [such as Mount Saint Helens] as being fantastic volcanic
eruptions today, but they are literally a pinprick when
compared to the amount of lava erupted in forming these Deccan
traps,” said Forte.
‘‘They are literally a pinprick
when compared to the
amount of lava erupted in
Dr.
forming these Deccan traps.
Alessandro Forte
Hopefully, the Deccan traps mark only the start of the story. The
researchers plan to continue using this method to make further
predictions on other interesting geological features, including the
creation of the North Atlantic Ocean 55 million years ago. If further
developed, this could be another tool to understand the awe-inspiring
and wonderful forces that shaped the place we know as our home.
www.yalescientific.org
April 2017
Yale Scientific Magazine
29

FEATURE
cell biology
NO CELL LEFT BEHIND
mapping the human body
by Bryan Ho|art by Sida Tang
Imagine walking into the doctor’s office, preparing for the worst.
The doctor brings up surgery, vaguely motions to a chart on the
wall, and points to certain printed organs. But what if he could
show you which cells needed removal, what they looked like, and
even why they caused your condition? Scientists may now have
the means to determine the precise cellular structure of human
organs, which could improve researchers’, doctors’, and patients’
understanding of human diseases.
Researchers at the Weizmann institute in Israel, led by Ido Amit
and Shalev Itzkovitz, reconstructed the cellular structure of the liver
in a Nature article published in February 2017. Their research
team is a part of the Human Cell Atlas project, whose mission is
to “create comprehensive reference maps of all human cells.” These
maps, which organize cells by their genomes, will help researchers
and medical professionals to better understand how and why cellular
structures lead to organ functions.
While researchers have long been interested in cellular maps, the
ability to determine the locations of cells and their genomic blueprints
has been limited by available molecular biology techniques.
Sequencing DNA, the alphabet of our genes, has traditionally been
expensive and time-consuming. The cells must be extracted from
the body before DNA can be harvested, destroying the spatial location
of the cell.
Researchers also want to know the RNA profile of different cell
types, which would reveal which genes are expressed as proteins.
Ultimately, they would like to determine the proteome, or the entire
set of expressed proteins, of each type of cell. However, this
is still an emerging research field. Determining the levels of just
50 proteins in a cell is already a cumbersome task, let alone of the
thousands of proteins actually present. The RNA profile serves as a
simpler proxy for the proteome because modern advances in molecular
biology, such as Next Generation Sequencing, have allowed
researchers to quickly determine the DNA and RNA content of a
cell. However, this process still requires the isolation of each cell
prior to sequencing and sacrifices the cell’s spatial context in exchange
for its genomic content.
30 Yale Scientific Magazine April 2017 www.yalescientific.org

The researchers at the Weizmann Institute were able to overcome
this problem by combining the RNA sequencing results from Next
Generation Sequencing with cellular locations determined by fluorescence.
They then used computer algorithms to determine which
RNA profile corresponded to which cellular location.
To do this, the researchers first determined the locations of several
different cell types in the liver. One of the largest organs in the
body, the liver is responsible for digesting nutrients and detoxifying
dangerous substances. The cells in a subunit of the liver are differentiated
into layers expanding radially from a central vein, and
those closest to the vein are most accessible to the nutrients and
oxygen carried in the bloodstream. The cells in each layer express
a set of different genes, so the RNA profiles, which tell us which
genes are expressed, differ between each layer.
They then identified six “landmark” genes that are known to
be expressed differently in each layer. They designed probes that
would bind to each gene’s specific mRNA, a type of RNA that is
translated into protein. With a technique called single molecule
fluorescent in situ hybridization, the researchers determined
which cells in each layer expressed which genes. “Each little dot
corresponds to an mRNA,” said Thomas Pollard, a professor of
Molecular, Cellular and Developmental Biology at Yale. A brighter
dot signifies more copies of that gene’s mRNA. The Weizmann researchers
now had data on six of the thousands of genes expressed
in liver cells.
The next step was to find the entire RNA expression profile —the
complete collection of different RNAs—or each layer. They turned
to single cell-RNA sequencing to quickly identify the thousands
of different RNAs within each cell. In this technique, RNA from
each cell is harvested and amplified many times to allow it to be
sequenced. Armed with this knowledge, the researchers compared
the RNA expression levels of the six genes measured earlier. Since
they knew the approximate expression levels of six of the genes
from the previous experiment, they could match the RNA profiles
to each cellular location from these six genes. For example, if
landmark gene A was expressed highly in one RNA profile, then
it would have to had come from a cell from a layer that fluoresced
brightly for gene A’s mRNA.
Their maps showed that of the 7,277 genes expressed in liver
cells, 3,496 of them va ry non-randomly by spatial location. For
example, genes in energy-demanding pathways were expressed the
most near the central vein, which provides the cells with oxygen
and nutrients. Cells near the vein also strongly expressed genes
coding for secreted proteins; their placement near the vein allows
cells to efficiently transport their secretory proteins through the
vein. This finding confirmed the long-standing biological principle
that structure leads to function.
Researchers would still like to dig further and determine the
proteomes of different cells in addition to RNA profiles. Knowing
which proteins are expressed at what levels in each cell would further
illustrate the role of each cell in our body. “RNA expression
profiles don’t give you protein levels,” Pollard explained. “Sometimes
low mRNA levels can give you a lot of proteins, or a lot of
mRNA can give you a few proteins. It also depends on the lifespan
of the protein.”
Scott Holley, another professor of Molecular, Cellular, and Developmental
Biology, agrees. “It’s a caveat of the experiment,” Holley
said. However, identifying the thousands of proteins in each
cell biology
FEATURE
IMAGE COURTSY OF WIKIMEDIA COMMONS
►A representative RNA sequencing chip. Each dot represents one
letter of DNA, and the color indicates the letter.
cell requires thousands of antibodies to recognize and bind to each
protein. This can be very difficult because researchers still do not
know every protein our cells make. Finding every protein and producing
antibodies for each one could take years.
Moreover, reference maps for other organs may not prove so
easy. The cells in the liver are arranged in concentric circles, allowing
the Weizmann researchers to assign cellular locations with
as few as six genes. More complex structures, such as the brain, do
not have such a simple geometry, making the reference map more
complicated.
Nevertheless, cell maps will give researchers and medical professionals
a new outlook on the human body. Embryo cell lineage
mapping, a related technique used since the early 20th century, was
a successful predecessor: it revealed the development of each cell
in the embryos of various organisms. It has already provided important
information about how organs and structures develop and
given researchers the ability to manipulate embryonic organisms.
The Human Cell Atlas project hopes to continue to empower scientists
and medical professionals, especially in cancer treatment.
Rather than generalizing cancer to a whole organ, such as breast
or lung cancer, this new blueprint may allow doctors and scientists
to understand the inherent variation within each tumor. They can
then more accurately monitor tumor growth and identify which
therapy would be best suited for which cancers.
The lab at Weizmann is but one of many groups attempting to
provide researchers with detailed maps of where each of the thousands
of types of cells is located in the human body. The project
is an international effort, with member laboratories in the United
States, United Kingdom, Sweden, and Israel. Meanwhile, other
mapping projects are also in the works. Cancer Research UK announced
last month that a project to create an interactive virtual-reality
map of breast cancers would receive up to $25 million.
In the United States, the National Institute of Mental Health is preparing
to announce grant awards for mapping mouse brains later
this year.
There is still a long way to go to map out all 37 trillion cells in the
human body, but with these advances in sequencing and imaging,
it has never been easier to see our cells where they belong.
www.yalescientific.org
April 2017
Yale Scientific Magazine
31

FEATURE
ecology
Providing shelter to millions of exotic and colorful marine
species, coral reefs are some of the most diverse ecosystems
on the planet. From microscopic, photosynthetic algae to
large, predatory sharks, a wide variety of organisms live within and
among the coral polyps that compose these reefs. People flock from
around the world to view these spectacular habitats, and local economies
earn billions of dollars from tourism and fishing. Beyond its
economic advantages, coral reefs also protect against the erosion
of coastlines and serve as a source of chemicals currently used in
medicine.
Coral reefs are valuable and beautiful, but they are also particularly
fragile, currently endangered by climate change, pollution,
ocean acidification, and disease. One of these threats, however,
may have a natural solution. Research recently published in Science
found that seagrass meadows reduce the abundance of pathogenic
bacteria, mitigating disease in coral reefs and preventing the spread
of waterborne human diseases.
In recent years, incidences of coral disease have increased around
the world, from sites in the Caribbean to those in the Pacific and
Indian Oceans, resulting in decreases in coral cover—the proportion
of a reef’s surface that is covered by live coral. A variety of
known microorganisms are associated with coral diseases, yet the
pathogenesis behind several of these illnesses is complex and not
fully understood. Multiple bacteria interact to cause some of these
diseases, such as black band disease, a condition characterized
by a band of bacteria that travels over coral and leaves behind a
white skeleton. While current research struggles to understand the
mechanisms behind coral diseases, the most recent study, led by
Joleah Lamb of Cornell University, took a different approach and
investigated how another ecosystem had been alleviating the problem
all along.
Studying seagrass meadows, which grow in the sedimentary
areas of land near shores, this team of researchers centered their
research near four islands in the Indonesian Spermonde Archipelago.
They chose sites with similar characteristics, monitoring
the temperature, pH, and salinity of seawater from each site, and
paired them so the only major difference in each pair was the presence
or absence of a nearby meadow. At these sites, the researchers
monitored bacterial levels in the seawater from four locations:
the shore, the intertidal flats, the coral reefs, and the open water
between islands.
The researchers first tested each location for Enterococci, a
genus of bacteria often used to test for fecal contamination since
32 Yale Scientific Magazine April 2017 www.yalescientific.org

ecology
FEATURE
IMAGE COURTESY OF NOAA
►Seagrass meadows can reduce the amount
of bacterial pathogens within seawater.
IMAGE COURTESY OF WIKIMEDIA COMMONS
►Black band disease is a bacterial disease
that causes the destruction of coral reefs.
IMAGE COURTESY OF PIXNIO
►Enterococci, a bacteria in wastewater, was
used to monitor water quality.
it is found in human wastewater. Levels of
Enterococcus were low in the open water,
indicating that the bacterial source was
wastewater pollution that had diffused
from the islands. Closer to shore, Enterococcus
levels were significantly affected by
the presence of seagrass. Seawater samples
collected at coral reefs with neighboring
meadows had half the amount of Enterococcus
as those taken from coral reefs without
them. Furthermore, seawater collected at
intertidal flats without seagrass had three
times more Enterococcus than did the
seawater sampled at seagrass meadows.
Since Enterococcus is found in human
wastewater, its detection often indicates
the presence of other pathogenic bacteria.
Knowing this, the researchers decided to
analyze whether seagrass meadows affected
the levels of other bacteria using a process
called high-throughput amplicon sequencing.
In this technique, segments of genetic
material, called amplicons, are artificially
amplified, purified, and sequenced. The
procedure has several useful applications,
since it can sequence a region of interest
for multiple targets simultaneously. After
sequencing, researchers can analyze the
genetic variation within a sample after it
has been sequenced or determine which
organisms are present by comparing the
sequences they obtained to a database.
Amplicon sequencing is commonly used
for bacterial identification. When studying
bacteria, researchers often use sequences
from a particular gene, 16S rRNA, because
it is present in most bacteria and its size
is appropriate for the technique. In this
study, the researchers used this rRNA gene
to analyze the composition of bacteria
in their seawater samples. They took all
sequences identified as bacterial, clustered
similar sequences together, and compared
their most abundant sequences to those
within literature to classify the bacteria.
They detected the presence of twenty-seven
bacterial genera that are pathogenic to
humans, marine fishes, and/or invertebrates.
Of these, nine of the sequences were
only found at the islands’ shores, so the
team decided to analyze only the remaining
eighteen. Again, they found that the relative
abundance of pathogens was lower at sites
with seagrass meadows than at locations
without them.
With this information, the researchers
decided to monitor how seagrass meadows
affected the health of adjacent coral reefs by
visually comparing the reefs in their paired
sites. They looked for visual characteristics
of diseased coral, including growth anomalies,
eroding bands, and white syndromes—
patches of dead, bone-colored coral skeletons.
Based on their examinations, coral
disease was twice as prevalent on reefs
without an adjacent seagrass meadow. Two
types of coral disease, white syndrome
and black band disease, were particularly
common within these reefs. The team’s
results demonstrate that seagrass meadows
help to alleviate disease in nearby coral reefs
by reducing the concentration of pathogens
within seawater.
Reducing bacterial load at these sites also
keeps other organisms healthy. Several
bacteria whose concentrations were
reduced are also pathogenic for humans,
fish, and other marine species. For example,
the seawater samples included Vibrio,
species of which can contaminate seafood
and infect the humans that eat it, causing
gastroenteritis—an inflammation of
the gastrointestinal tract that results in
diarrhea, vomiting and abdominal pain.
Certain Vibrio species can also cause cellulitis,
an infection of the skin resulting in
hot, painful rashes.
With this publication, we now understand
how important seagrass meadows
are for the vitality of coral reefs. This
study is the first to evaluate the ability
of seagrass meadows to remove pathogens
from seawater, but it is only one step
towards understanding the complex and
interacting ecosystems of the coast. Future
research must determine the mechanisms
involved. Lamb’s research team speculates
that seagrass retains sediment and blocks
sediment-associated bacteria from reaching
nearby coral reefs, but this idea is still
a hypothesis. Furthermore, discovering the
pathogen-removing abilities of seagrass
meadows does not solve the current problem
of coral reef destruction.
Outbreaks of disease in reefs are only
getting worse, as current trends toward
higher global temperatures pose a threat
to coral reefs in many ways. Increased
temperatures may increase pathogen virulence,
inhibit corals’ ability to fight against
disease, and facilitate opportunistic infections.
Seagrass meadows may currently
protect some reefs against disease, but these
ecosystems are also being lost at alarming
rates. More than a quarter of the world’s
seagrass ecosystems have disappeared in
the last 135 years, and rates of destruction
are increasing with coastal development.
Coastal ecosystems, from seagrass meadows
to coral reefs, are fragile and easy to
overlook, but they are economically and
ecologically essential. They provide habitats
for a diverse community of marine
organisms and support the livelihoods of
millions of people who depend on income
from fishing and tourism. Research continues
to unveil how organisms within these
ecosystems interact. The question is, how
do humans fit into the picture?
www.yalescientific.org
April 2017
Yale Scientific Magazine
33

COUNTERPOINT
OXYTOCIN — NOT JUST FOR WOMEN
►BY STEPHANIE SMELYANSKY
Everybody eventually catches the love bug or the cuddle monster.
As great as that strong feeling of love and attraction is, it can largely
be attributed to just one molecule: oxytocin. Oxytocin is a hormone
and neurotransmitter that is active in reproductive and attractionbased
signaling systems. It’s probably best known for its function
in childbirth, during which oxytocin induces delivery and later
lactation; however, the hormone also plays a crucial role in both
genders in pathways such as sexual activity, social bonding, and
stress. New research has shown that this typically maternal molecule
is active in helping fathers bond with their children as well.
Previous research has shown that oxytocin affects the behavior of
men who are in a relationship. In addition to being a key hormone
in sexual activity, oxytocin also seems to play an important role in
bonding between romantic partners. In one study, a group of men in
monogamous heterosexual relationships were dosed with oxytocin
and then shown either photos of their partner or photos of random
women. Under MRI imaging, the brain showed significantly higher
activity when the men looked at photos of their own partners rather
than at photos of other women. Later on, in a similar study, men
were dosed with either oxytocin or a placebo and were then led into
IMAGE COURTESY OF WIKIMEDIA COMMONS
►Oxytocin, a typically maternal molecule, has been shown to play a
role in helpin fathers bond with their children as well.
a room where they interacted with an attractive female researcher.
Unsurprisingly, the men who were both treated with oxytocin and
already in monogamous relationships felt more comfortable when
the attractive researcher stood at a greater distance away from them.
These experiments, among many others, suggest that oxytocin plays
a critical role in monogamy for men.
Oxytocin’s effects on male monogamy might occur because the
molecule heightens a person’s ability to empathize and feel emotions.
Some studies even suggest that high levels of oxytocin actually make
people overly empathetic, recognizing a greater intensity of emotions
in others. There is also evidence that the increased emotional
sensitivity caused by oxytocin can help couples communicate. In
one study, couples were dosed with oxytocin or a placebo and then
led into a disagreement. Couples who had been dosed with oxytocin
were able to communicate more effectively and to better de-escalate
the situation than couples who had received the placebo. In healthy
couples, physical contact such as kissing, touching, and cuddling can
actually stimulate the release of oxytocin in both partners, creating a
positive feedback loop that improves trust and emotional sensitivity
between partners.
Considering these studies, it’s not revolutionary that there is also a
link between oxytocin and the way fathers bond with their toddlers,
as shown in a recent study. “There is now evidence that oxytocin
can increase in men who become fathers. Other labs have also
shown that giving men additional, exogenous oxytocin intranasally
stimulates positive paternal behaviors,” said James Rilling, professor
at Emory University and one of the authors of this study. Building
on this previous research, Rilling and his team at the Laboratory for
Darwinian Neuroscience have demonstrated that oxytocin levels
may be a factor in how involved fathers are in caregiving. Fathers
of toddlers between the ages of one and two were dosed with either
oxytocin or a placebo and then shown pictures of their toddler, a
random toddler, and a random adult. Using MRI imaging, the
researchers measured brain activity in response to each photograph.
Like in other studies, the fathers dosed with oxytocin showed a
much greater neural response to their own child than to the other
photographs of random individuals, suggesting that oxytocin plays a
critical part in these close, familial social interactions.
“Oxytocin acts on targets of the brain’s dopamine reward system
to render child stimuli more rewarding, which may increase the
motivation to interact with the child,” Rilling said. As with romantic
partners, spending time with their children can stimulate the release
of oxytocin in fathers, which then contributes to the brain’s reward
system, encouraging similar behavior. Thus, what was previously
considered a maternal hormone serves a similar purpose when men
interact with their kids. At the end of the day, however, what really
matters isn’t a parent’s hormonal make-up, but is that every child
receives the love and care they deserve.
34 Yale Scientific Magazine April 2017 www.yalescientific.org

INN VATI N
STATION
Printing Solar Power Generators
►BY AMY XIONG
Solar cell development has been a hot topic in recent years.
First created in the 1950s, solar cell technologies are now
continuously updated to have both improved performance
and an easier manufacturing process. Solar cell production is
currently expensive and very difficult, requiring temperatures
above 500 degrees Celsius. Recently published in Science
in February 2017, researchers at the University of Toronto
made significant advances in alternative solar cell technology,
bringing its production to lower temperatures and making
it compatible with conventional silicon cells—potentially
leading to the commercial-scale manufacturing of solar cells
that are more efficient.
Most solar cells use crystalline silicon as a light-harvesting
material. These solar cells already have an efficiency—the
amount of input energy from sunlight that can be converted
to electricity—of above 26 percent, said Zhenyu Yang,
postdoctoral fellow at the University of Toronto and a coauthor
on the study. “One drawback in existing crystalline
silicon solar cells is that manufacturing is complex and
requires high processing temperatures,” explained Hairen
Tan, postdoctoral researcher at the University of Toronto and
the lead author on the study.
Engineers have recently begun to use metal-halide
perovskite—a class of perovskite-structured crystal composed
of earth-abundant elements such as lead and iodine—as a
new high-efficiency solar cell material. Perovskite cells can be
made thinner and more flexible, allow a lower temperature to
manufacture, and can potentially be combined with a more
rigid silicon cell to harvest more energy. “Among all-solutionprocessed
solar cells, perovskite-based solar cells show
great potential as the new generation photovoltaics,” Yang
said. However, perovskite is known to be less stable than its
inorganic counterparts. Oleksandr Voznyy, research associate
at the University of Toronto and co-author on the study, said
that current research focuses on how to make the material
stable for a long time under operation conditions.
The University of Toronto researchers found a way to bypass
some of the problems of the perovskite solar cells (PSC): they
developed a process that is low-temperature compatible, able
to be run below 200 degrees Celsius. Voznyy added that the
process also allows the electron-extracting layer of the solar
cell to be grown on a flexible polymer substrate. Flexible
substrates, including plastic films and curved surfaces, cannot
withstand high temperatures because they would simply
melt under the heat, and thus couldn’t be used in previous
manufacturing of solar cells.
“The biggest implications of our research are that a lowtemperature
process of producing the solar cells is now
compatible with flexible substrates and that it can be deposited
on top of silicon solar cells to harvest more energy without
damaging them,” said Tan. “Flexible substrates allow you to
print the solar cell like a newspaper, which wasn’t possible
with previous materials and processes.”
The high performance of perovskite has been demonstrated
in the past. For example, Stanford researchers developed
a perovskite solar cell last October with an efficiency of 20
percent, comparable to current silicon solar cells on the market
today. However, scientists are now working to make them
commercially available, which means they have to be more
stable. To achieve this, the researchers improved the electron
selective layer. They added chlorine atoms in between the
perovskite and the titanium, which serve as an effective link
that can bind both materials. This change to the interface of the
two layers reduces positively-charged electron vacancies in the
cell layer, thus improving the stability of the whole solar cell.
“These devices [made with our PSC] will be low-cost,
highly stable, efficient, and solution-processible, and could
be could be further integrated to many types of surfaces—
such as building roofs, walls, windows, and roads—to harvest
light,” Yang said. This PSC technology can be used to create
low-cost, printable solar panels for solar windows that reduce
energy use, as well as for smartphone covers with charging
capabilities. With high thermal and atmospheric stability,
rooftop solar panels, for example, could last decades, rather
than degrading quickly when exposed to moisture or light.
The researchers are continuing their investigation into this
new PSC technology. Tan explained that they are now working
with other labs to develop devices with both crystalline silicon
cells and their new perovskite technology to further improve
cell stability and power conversion efficacy.
www.yalescientific.org
April 2017
Yale Scientific Magazine
35

UNDERGRADUATE PROFILE
JULIAN MENZEL (BR ‘17)
EXPLORING THE FUTURE OF PHYSICS WITH THE PAST
►BY GENA COBLENTZ
PHOTOGRAPHY BY PATRICK HONG
►Menzel, a Cambridge-bound senior in Yale College, combines the
study of physics with his passion for the history of science.
It’s fairly common for college freshmen to enter school without
knowing exactly what they want to pursue, but current senior Julian
Menzel (BR ’17) was a little different. He has known that he
wanted to study physics since the age of fourteen. He first developed
an interest in the subject when he stumbled upon books by
well-known physicists like Stephen Hawking, Brian Green, and
Roger Penrose, but he eventually grew tired of popular science simplifications.
“I hit a point where I got frustrated with frog-in-a-bowl
analogies rather than actual equations,” Menzel said. He decided to
teach himself calculus in high school, even though only two teachers
at his high school were equipped to teach the subject. While
he also enjoyed activities like playing soccer, participating in Boy
Scouts, and practicing the piano, he spent some of his after-school
time struggling through a physics textbook. However, it was not
until college that Menzel discovered his passion for the history of
science.
Menzel’s physics education took off at Yale. Throughout high
school, Menzel had also developed an interest in philosophy and
literature. Once at Yale, he eventually found himself asking the
same set of questions that literature and philosophy provoke, but
about physics. He wondered about issues in physics that physicists
have as of yet failed to answer, such as how the field’s cultural norms
determine who becomes a physicist or how standards of rigor have
changed over time. He was curious about the social world of physicists,
pondered the consequences and purpose of being a physics
student, and developed an interest in how the study of physics in
the United States came to look like it does today. Eventually, Menzel
read Image and Logic by Peter Galison and experienced what he referred
to as a sort of secular “conversion experience;” the book was
a catalyst for his up-and-coming fascination with integrating the
history of science into the study of science itself. “It’s interesting,”
Menzel remarked. “Scientists are often interested in the history of
their disciplines. Right now, there is very little cross-talk between
the humanities and the sciences.”
Menzel is majoring in physics (intensive), but his interdisciplinary
interests are not limited to his fields of study. He has enjoyed the
small class sizes in the Yale physics department, loves to work with
other students to solve problems, and appreciates the collaborative
environment. However, after observing that women and other minorities
were often not included in student-formed study groups,
Menzel formed Iota, an organization that has made strides to reform
the way study groups are created. Iota pushes for basic pedagogical
reform by obtaining peer tutoring for 300-level math classes
and organizing student study groups to increase the amount of support
available to students, as well as pushing to have more course
staff available to students. Menzel is also on the board of directors
of the Telluride Association, a non-profit that offers intensive educational
programs for both high school and college students.
In the future, Menzel plans to go into academia and conduct research
in history of physics. He won’t have to wait very long to realize
his dreams, though: in the coming year, Menzel will head to
Cambridge as a Gates Scholar, partaking in a one-year masters program
in history of philosophy and science. He is looking forward
to thoroughly digging into historical reading, research, and writing.
“I’ve been living two lives, in some sense. I spend most of my
time doing physics with other people—fighting for time by myself
to pursue historical interests,” Menzel said. However, he emphasizes
that his multifaceted interests are important to develop a deep
understanding of physics. “Having an understanding of the history
of the discipline is a good way of getting a baseline cognizance of
it,” Menzel said.
Menzel will continue on to MIT to attain a PhD after he completes
his time at Cambridge, after which he would be interested
in collaborating with a professor to incorporate history of physics
into introductory physics courses; he believes that this is an enriching
component of the curriculum that is oft-forgotten by many
lecturers. “Building up channels of communication would be very
beneficial. Scientists are government advisors. They fill important
positions. They need a working sense of how their work fits into the
broader sociopolitical landscape that they inhabit, so that they can
do their work responsibly and ethically,” Menzel said.
36 Yale Scientific Magazine April 2017 www.yalescientific.org

ALUMNI PROFILE
BESSIE SCHWARZ (FES ‘14)
ON THE ROAD TO RAIN
►BY DAWN CHEN
IMAGE COURTESY OF BESSIE SCHWARZ
►Bessie Schwarz (FES ’14) is the co-founder of Cloud to Street, a
company that uses machine learning techniques to predict climate
change disasters.
Bessie Schwarz (FES ‘14) found her calling in the woods of Maine
when she was 15. “I realized that what I have come to love and recognize
as a beautiful part of the world was really threatened,” Schwarz said.
“It won’t necessarily be around unless it is intentionally preserved.” As
she drove home to suburban New Jersey, the land of concrete and highways,
she decided to dedicate her future to environmental protection
and advocacy. Now, as the co-founder of Cloud to Street (cloudtostreet.
info)—a company that uses machine-learning techniques to predict climate
change disasters—and Communications Strategist at the Yale Project
on Climate Change Communication, Schwarz’s efforts have paid off.
While Schwarz was an undergraduate at Carleton College, she became
a community organizer. She was the environmental senator for the student
government, and she co-hosted a longform radio show called “Recycled
Air” on the campus radio station. The college experience helped
her reorient her vision of how to empower people to protect the environment:
not only does the environment need intentional protection,
she reasoned, but it also requires collective action with everyone working
together. This led her to work in rural Ohio, where she rallied citizens
to call their congressmen weekly about climate issues. However, as
she worked on these campaigns, she quickly realized that simply rallying
was not enough. “We didn’t have enough tools in the toolbox, the world
was rapidly changing environmentally, and we needed to find new types
of tools, strategies and innovations,” Schwarz said. She thus decided to
head to Yale to obtain her Master’s degree in Environmental Studies.
While at Yale, Schwarz attended a talk by Google where she learned
about the sheer amount of data and new technologies that are now available.
“There is a greater wealth of data from satellites, and we now also
have the computing capacity to type into a browser and access 40 years
of data,” Schwarz said. After attending the talk, she felt that these tools
could be used to help marginalized people who are disproportionately
affected by climate change. The poor are hit hardest in weather-related
disasters, and as crop yields decrease, more of the disadvantaged suffer
from malnutrition. So Schwarz had an idea: she created an algorithm in
Google Earth Engine to predict the effects of climate change disasters.
It started off as a fun project. While she was doing field work in rural
Washington, she would spend ten hours at a time programming on her
laptop. The result was an algorithm that could predict physical and social
vulnerability by determining which communities are most likely to
experience loss when hit by natural disasters. Beth Tellman, Schwarz’s
friend at Yale FES who was specializing in hydrology, also co-wrote the
algorithm by helping to predict flood water patterns.
Schwarz’s algorithm can detect flood risk in an area so that, when
combined with social data, it can predict a comprehensive social vulnerability
index. The result looks something like Google Earth but shows regions
that are more prone to flooding and damage that might need to be
evacuated. Schwarz believes that her algorithm can inform governments
and help them decrease damage from climate change disasters.
With so many disasters around us, why aren’t people taking part in the
fight? Schwarz attributes this absence of involvement to a lack of effective
dialogue on this issue. “The major problem with communicating climate
change is that it is distant in space and distant in time. People think
that it will only affect your children’s children, or people in other parts of
the word,” Schwarz said. She thinks that individuals need to communicate
the impacts of climate change in ways that are very personal, such as
by discussing the occurrence of increased droughts and water pollution,
or the impacts climate change will have on the refugee crisis. Talking to
friends and family may seem trivial, but Schwarz believes this is the most
important way of engaging the community.
Looking to the future, Schwarz hopes that her work can help more
people as we experience more extreme weather conditions caused by climate
change. “Exposure to inland flooding alone is expected to double
by the year 2030. We don’t know how to take care of the hundreds of
thousands of people affected today by these disasters, and we live in a
very exciting moment, deciding how we want to re-govern the world,”
Schwarz said.
www.yalescientific.org
April 2017
Yale Scientific Magazine
37

FEATURE
documentary review
SCIENCE IN THE SPOTLIGHT
DOCUMENTARY REVIEW : (DIS)HONESTY: THE TRUTH ABOUT LIES
►BY ELIZABETH RUDDY
A man asks a room full of people, “So, who here has told
a lie since the beginning of this year?” Everyone sheepishly
raises his or her hand. “Who generally thinks of themselves as
a decent, honest person?” he asks. Everyone again raises his
or her hand. “How can it be that at the same time we think of
ourselves as honest, we recognize we are dishonest?”
The man is Dan Ariely, a professor at Duke University, whose
work in behavioral economics inspired the documentary (Dis)
Honesty: The Truth About Lies. The film features clips from an
interactive lecture of Ariely’s, interspersed with reenactments
of his team’s experiments and personal testimonies from
individuals who have faced serious consequences for lying
and cheating. Their stories cover topics ranging from insider
trading to adultery.
Most of reenactments show variations of what Ariely calls
“the matrix experiment,” a key tool that he and other behavioral
economists use to evaluate people’s levels of honesty. A notable
finding from their experiments is that many “little cheaters”
do more damage to society than do the few “big cheaters” that
make headlines for large-scale tax evasion and fraud. Small
acts of dishonesty add up to major costs, such as the IRS being
cheated out of 15 percent of its tax revenue.
Although the film is full of interesting facts and compelling
stories, it lacks cohesiveness and
flow. The insertion of personal
anecdotes often felt choppy, almost
like an afterthought designed to
artificially generate emotional
connection. Even maintaining the
existing structure, director Yael
Melamede would have done well
to more obviously connect these
stories to the phenomena Ariely
describes in his lecture.
The film ends on a clear,
hopeful note despite its sobering
message. Ariely’s team found that
cheating almost disappeared when
participants were reminded of their own morality by having
to sign an honor code or write down the Ten Commandments.
Some schools have already put these findings into practice by
requiring students to sign honor codes before taking exams.
In addition, because Ariely’s team concluded that most people
are dishonest to similar extents and react similarly to various
situations, their findings are widely applicable and may help
move us towards a more honest global society.
DOCUMENTARY REVIEW: LO AND BEHOLD: REVERIES OF A CONNECTED WORLD
►BY ANDREA OUYANG
Werner Herzog’s recent documentary, “Lo and Behold:
Reveries of a Connected World,” takes on one of the most
pressing questions of our generation: what does it mean to
live in a world in which technological capabilities are nearly
outstripping—or perhaps have already outstripped—our
comprehension?
The actual science behind the machines investigated in
the documentary is somewhat sparse, limited to flashes of
chalkboard equations and over-simplified explanations. The
point, it seems, is to have the viewer meditate, rather than
think; the scenes have a dreamy quality, courtesy of Herzog’s
polished directing and the natural visual appeal of machines in
motion. The viewer is left with the impression of experiencing
a reverie of the musings and questions that life in our brave new
technological world inspires. The documentary does a fair job
of representing both the bright and dark sides of technology,
from a community of modern-day hermits living away from
the wireless signals to which they have severe reactions to
scientists testing software that can translate brain activity to
images on a screen.
Herzog is excellent at finding examples of humantechnological
interactions that the average viewer might not
have considered—when was the last time you thought about
how difficult it would be to navigate life with a debilitating
reaction to wireless signals? To that end, it would have been
satisfying to see Herzog’s take on the more sensitive and
controversial topics regarding technology today, such as
drone-enabled warfare, identity theft, “revenge porn,” and
international cyber-hacking.
Herzog briefly touches on related
issues, but leaves something to
be desired; his questions give
the impression of a leaf rippling
the surface of the techno-ethical
pond, rather than a pebble thrown
in. Exploring the possibility (and
consequences) of a trip to colonize
Mars, for instance, is charming,
but admittedly not a high priority
for people not named Elon Musk.
Nevertheless, it was refreshing
to see a documentary that seemed
purposefully removed from the
chaotic pace of everyday life, with
all its difficult questions. One of the most charming scenes was
of a group of monks standing under a tree, heads bent over
their smartphones, with the narrator asking, “Have the monks
stopped meditating? They all seem to be tweeting.” Another
hypnotizing scene shows an android meticulously pushing a
cart to the center of a room, arranging everything on the cart
just so, then carefully unscrewing a canister of orange juice,
pouring it into a cup, and handing it to the nearest human.
Viewers looking for the next hard-science documentary
might be better served elsewhere. However, to those looking
for a charming, thought-provoking evening watch with friends
and family, lo and behold—this is the documentary for you.
38 Yale Scientific Magazine April 2017 www.yalescientific.org

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FEATURE
PRE-MED MOTIVATION @ YALE
►BY EMMA HEALY
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visit 50 Whitney Ave, New Haven, CT 06510

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