YSM Issue 89.4

Yale Scientific
Established in 1894
THE NATION’S OLDEST COLLEGE SCIENCE PUBLICATION
OCTOBER 2016 VOL. 89 NO. 4 | $6.99
A CLEAN TOUCH TO ART
GECKO

The Economy Doesn’t
Affect Our Quality.

Yale Scientific Magazine
VOL. 89 ISSUE NO. 4
CONTENTS
OCTOBER 2016
NEWS 6
FEATURES 25
ON THE COVER
16 DECO
GECKO
Yale scientists team up with art
conservators to preserve fine art
with a new gecko-inspired material.
12
BRAIN DAMAGE
BEFORE BIRTH
Researchers shed light on how the
Zika virus causes microcephaly and
sparked the worst epidemic since
Ebola.
14
HOW TO EAVESDROP
ON A SYNAPSE
Novel imaging technique developed
at the Yale PET Center allows us to
view synaptic connections in the
living brain.
18
NEW ENERGY:
OLD RULE
Can vibrating membranes reveal
fundamental truths? An extension
of the adiabatic theorem may lead
to improved control of systems.
“CRYSTALS UP CLOSE”
PHOTO BY NATASHA ZALIZNYAK
21
MIND THE GAP:
A MEDICAL MYSTERY
With such disagreement among
psychiatrists and such variety among
patients, the search continues for the
best approach to treat mental illness.
More articles available online at www.yalescientific.org
October 2016
Yale Scientific Magazine
3

q a
&
►BY JOE KIM
After the Rio Olympics, interest in cupping,
a traditional Chinese therapy, spiked.
Many sufferers of chronic pain, often those
with immune, metabolic, or cardiovascular
disease, are trying cupping therapy, and
some are even reporting positive results.
Although different methods of cupping
exist, the common “dry cupping” refers
to using fire to heat the air within a
glass cup and create suction on the treatment
area. But, does it work? One study,
which filtered previous research based on
credibility, found cupping therapy was effective.
Physiologically, cupping may alleviate
inflammation, reduce the blood sugar
of people with diabetes, and increase
pain thresholds. No severe adverse effects
are currently associated with cupping, although
bruising, muscle soreness, and increased
pain sensitivity in treatment areas
are relatively common.
Most scientists are skeptical about cup-
IMAGE COURTESY OF PIXABAY
►Surprisingly little evidence exists to support
the beneficial effects of cupping therapy.
Does cupping work?
ping therapy, doubting its potential benefits
as an alternative or complimentary
to more traditional pain management
regiments. Some cite the lack of unbiased
experiments, emphasizing how methodologically
poor many of the published experiments
are. Others highlight the temporary
nature of any beneficial effects.
Clearly, more robust research on
cupping is necessary to evaluate its effectiveness.
To aid the research process
and promote the safe practice of cupping,
the Chinese government and several
other research groups are aiming
to standardize cupping therapy methods
by setting guidelines for cup placement,
heating time, and size. Ideally,
future research on the short term and
long term benefits, as well as the complications
of cupping therapy, will help
people decide if this particular treatment
is right for them.
What causes pruney fingers?
►BY LAUREN TELESZ
You may remember staring at your hands
after a bath as a little kid, intrigued by how
your small, smooth hands had transformed
into a wrinkled pair. “Look Mom, I have
Grandma’s hands,” you might have said.
For centuries, “pruney fingers,” or what
scientists call water-immersion wrinkling,
was a mystery. No one knew exactly how it
occurred or why. Many scientists attributed
the wrinkles to osmosis, claiming that the
skin was becoming waterlogged. However,
two recent important observations undercut
this common answer. First, water-immersion
wrinkling only occurs in two places on
the body, the hands and feet. Secondly, when
a particular nerve is cut, the skin no longer
becomes pruney after exposure to water. The
selectivity of water-immersion wrinkling
and the connection to the nervous system
suggests another, more complex answer.
In 2003, neurologist Einar Wilder-Smith
IMAGE COURTESY OF THE BRITISH COUNCIL
►The pruning of our fingers is actually due to
the constriction of blood vessels.
found that water-immersion wrinkling is
driven by the constriction of blood vessels.
He found that as water diffused through
sweat glands in the hands and feet, the concentration
of ions in skin tissue changes
and this triggers a reflex that constricts certain
vessels. When these vessels constrict,
wrinkles appear.
Might this curious phenomena have
a purpose? Observing that the grooves
formed on our fingers closely resemble
“tire treads,” neurobiologist Mark Changizi
postulated that this wrinkling gives our
hands a better grip on objects, akin to how
tire treads give cars a better grip by channeling
water away. Indeed, a 2013 study
found that the wrinkling did allow people
to handle wet objects more quickly. How
big an advantage this conferred as our ancestors
adapted to their natural habitat remains
the subject of future research.

3
Science pops up in places where we least expect it.
Crawling lizards and art don’t seem to go well together. But we see on the
cover of this issue how researchers at Yale drew inspiration from the ability of
geckos to cling on to just about any surface and engineered a material that’s
poised to leave their mark in the art world and beyond. Composed of millions
of microscopic columns, this novel film clings to dust without adhering to the
surface underneath, giving conservators a boost as they work to present artwork
at its best (pg. 16).
High-tech swimsuits made a splash in the 2008 Olympics, as swimmers sporting
Speedo’s full-body suit slashed world records and prompted the International
Swimming Federation to ban the swimsuit. Closer to home, new research
may soon find itself into the clothing we wear. Sporting tiny openings 100,000
times the thickness of human hair, the nano-porous fabric allows both sweat
and infrared radiation to escape, not only increasing comfort but also potentially
decreasing energy consumption from air conditioning (pg. 27).
And at a time when cybersecurity has grabbed headlines, Yale researchers are
also making progress on quantum communication techniques that will make
information transfers safe from eavesdropping. By transmitting signals in the
form of quantum information, the sender ensures that any attempt to listen in
would inevitably disrupt the wave pattern of the signal and be detected immediately
(pg. 6).
Some areas of science command more attention, and understandably so. In
this issue, we celebrate advancements in the life sciences, from the discovery of
how the Zika virus caused the terrible disease (pg. 12) to innovative approaches
to cancer treatment (pg. 30) to the development of engineered blood vessels that
provide hope to patients with kidney disease (pg. 6). Medicine touches our lives
when we’re at our most vulnerable and its impact is highly visible.
At the same time, it’s easy to overlook how science is intricately woven into
our daily lives. This fall, we invite you on a journey to marvel at the many ways,
big and small, in which science is transforming the world we live in.
“I believe in science,” Hillary Clinton said in her nomination speech this July.
So do we, and we hope this issue will give you that same optimism.
Yale Scientific
Established in 1894
THE NATION’S OLDEST COLLEGE SCIENCE PUBLICATION
OCTOBER 2016 VOL. 89 NO. 4 | $6.99
GECKO
A CLEAN TOUCH TO ART
F R O M T H E E D I T O R
A B O U T T H E A R T
Lionel Jin
Editor-in-Chief
A day gecko presses his foot against the cover of 89.4,
in this mosaic artwork designed by arts editor Ashlyn
Oakes. Researchers in the School of Engineering and
Applied Science, working in collaboration with Yale’s
Institute for the Preservation of Cultural Heritage, have
developed new polymers for cleaning priceless works of
art. By mimicking the surface architecture of a gecko’s
foot, these new materials are able to grip and remove dust
from the surface of paintings without damaging the underlying
patina, just as geckos are able to cling to smooth
surfaces.
Editor-in-Chief
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NEWS
in brief
Securing Our Cybersecurity
By Michelle Lim
PHOTO BY KENDRICK UMSTATTD
►A chip engineered by professor Hong
Tang preserves the quantum states of
photons transmitted during quantum
communication.
In the nascent age of quantum information,
Yale researchers are striving to make
unhackable systems a reality. Yale Professor
of Electrical Engineering & Physics
Hong Tang will lead a National Science
Foundation initiative in engineering to interface
with researchers on quantum communication.
Why is quantum information more secure?
Unlike classical information, which
is transmitted via amplified signals that
can be received by any party, quantum
information cannot be duplicated. Only
one party can receive information meant
for one receiver. First, the sender encodes
a beam of light particles, called photons,
into a wave pattern, which is then sent to
the receiver. The receiver then retrieves
the waves using a coding pattern unique
to the sender and receiver. By observing,
or attempting to observe, the wave of information,
eavesdroppers automatically
alter the wave’s pattern and are detected
immediately.
Tang’s team will work to engineer a semiconductor
device to allow communication
using these light waves at room temperature
without loss of information. Tang will
collaborate with professor Liang Jiang,
who is developing efficient protocols to
extend the range of quantum communication.
Their findings will bring us closer
to having a completely secure communication
system for all spheres of society. One
day, we may enjoy secure bank accounts
for personal use, secure business transactions
for commerce, and secure government
communications for the military.
Urban Heat Islands in China and the US
By Kathryn Ward
PHOTO BY JARED PERALTA
►Yale researchers take rooftop
measurements as part of a comparative
study on air quality in the US and
China.
This summer, city-dwellers from all over
the world fled to the country for weekends
and vacations to escape the heat. A study
recently published by a Yale-based research
team examined these so called Urban
Heat Islands (UHI), urban areas that are
hotter than the surrounding rural areas.
By surveying dozens of cities throughout
China, researchers discovered that UHIs in
China arise due to different reasons than
their North American counterparts.
In the US and Canada, lack of vegetation is
the leading cause of UHIs, but in China, the
heat increases are due to particles of dust,
chemicals, and other aerosols that create
murky haze. Aerosol particles produced in
industrial Asia are larger in diameter than
those particles found in Western aerosols.
Yale professor Xuhui Lee emphasized that
limiting environmental aerosol exposure
has local climate implications in addition to
health implications.
Chang Cao, the study’s first author
and a visiting PhD student from Nanjing
University of Information Science and
Technology, explained that the UHI
effect is largest in the arid areas of China
due to a loss of the modulating effects of
coastal humidity on increased dust from
construction.
Cao emphasized the need for awareness
of the different sources and effects of haze
in different places. The study drew on
methodology initially used to survey UHIs
in Los Angeles and was modified to fit the
different types of pollution and climates in
China. The authors hope that highlighting
this public health concern may lead to
meaningful changes in the way we plan our
cities.
6 Yale Scientific Magazine October 2016 www.yalescientific.org

in brief
NEWS
Designer Blood Vessels in Regenerative Medicine
By Viola Kyoung A Lee
The use of made-to-order, personalized blood
vessels may soon become a reality. In professor
Laura Niklason’s laboratory, bioengineered blood
vessels are making medical history, demonstrating
enhanced durability and reduced risk of medical
complications compared to synthetic vessels.
Niklason has studied connective tissue
for more than two decades. Her goal was to
develop minimally invasive artificial tissue that
does not trigger the body’s immune response,
while avoiding the pitfalls of purely synthetic
options such as Teflon vessels, which are prone
to infection and clotting. Inserting a piece of
plastic into the human body poses a large risk of
inflammation and infection, as the body often
perceives and attacks the synthetic blood vessel as
a foreign invader. Niklason’s bioengineered blood
vessels are different. “Based on the physiology of
blood vessels, we strived to replicate the [body’s]
environment. The process involved ‘coaxing’ the
cells to activate a program that would allow them
to make new tissue. The host would then have the
ability to remodel the vessel, using cells from the
host to repopulate the graft as needed,” Niklason
said.
The researchers had to overcome several hurdles
in order to ensure the manufactured vessels
possessed the requisite mechanical strength and
biological properties needed for proper function.
For example, the protocol, initially developed
using animal cells, had to be modified to ensure
human cell compatibility.
Niklason’s work represents an important step
forward in a rapidly developing field of mounting
clinical impact. While the precise nature of the
next big discovery in bioengineering is unknown,
it is clear that the field, much like the tissue it aims
to engineer, will only continue to grow.
PHOTO BY JARED PERALTA
►Bioengineered blood vessels exhibit
greater durability and reduced
risk of infection compared to synthetic
vessels.
Why Human Egg Cells Need to Breathe
By Diyu Pearce-Fisher
Over the last several decades, women
have shed the cult of domesticity and
acquired new social and economic roles,
shifting the primary focus of many
women’s twenties from children to careers.
However, this shift in interests has delayed
many women’s plans to start families,
giving birth to a new problem: problems
with fertility due to egg cell aging.
A woman’s egg cells begin to decline
in quality as early as when she is 37 or
38 years old, leading to problems in
fertility. After age 40, women will likely
face difficulties in having children. The
mechanisms responsible for egg cell aging
and fertility problems have been unclear
up until recently, when researchers in
Yale professor Pasquale Patrizio’s lab
concluded that egg cell aging is related to
hypoxia, or a lack of oxygen. Each egg cell,
or oocyte, has surrounding cells called
cumulus cells, which support oocyte
growth and maturation. The researchers
were able to identify certain RNA markers,
or precursors to protein expression, that
indicate egg cell aging in cumulus cells
of older patients. These RNA markers
are present in cumulus cells, which are
normally harvested but thrown away
in the process of in vitro fertilization, a
common procedure used to help couples
with fertility problems. With knowledge
of these markers, doctors could make use
of these cumulus cells by searching for
signs of hypoxia and modifying protocols
of ovarian stimulation. They could remove
oocytes from the follicles before too much
damage has been done by hypoxia. The
new research could vastly improve the
effectiveness of in vitro fertilization.
PHOTO BY EDWARD WANG
►Professor of Obstetrics, Gynecology,
and Reproductive Sciences
Pasquale Patrizio leads Yale’s Fertility
Center.
www.yalescientific.org
October 2016
Yale Scientific Magazine
7

NEWS
molecular biology
CRISPER CRISPR
An improved gene editing technology
►BY AMY XIONG
Just as one uses a pair of scissors to cut and reshape a piece
of paper, biologists can use CRISPR to turn off certain genes
and modify the genome. A group of Yale researchers led by
Qin Yan, Associate Professor of Pathology at the Yale School
of Medicine, have created a novel gene editing system using
the CRISPR-Cas9 mechanism that silences several genes
simultaneously and works more efficiently than previously
designed systems.
CRISPR consists of short segments of DNA—the universal
hereditary material. It was first identified in bacteria as an
acquired immune system, methods that allow bacteria to
attack foreign substances like viruses. CRISPR associated
proteins (Cas) cut and destroy the viral genomes, defending
the bacteria against infection. Researchers only elucidated
CRISPR’s mechanism about five years ago and are now using
CRISPR to work on mammalian genomes. “This technique
has revolutionized biomedical research, because it makes
genome editing much easier than before,” said Jian Cao,
associate research scientist of pathology and first author of
the study.
There are two main components involved in the CRISPR
system. One is a protein called Cas9, which cuts the DNA,
and the other is a sequence complementary to the DNA
called sgRNA, which leads Cas9 to the target site. Cas9 is like
a hand with a pair of scissors, and sgRNA the brain and eyes,
directing Cas9 to the cut-site.
The Yan lab designed an inducible CRISPR system with
several advantages: high efficiency, multiplex targeting,
and fewer off-target effects. As a cancer epigenetics lab,
the research group studies a protein family called KDM5s,
which includes proteins incoded by oncogenes—genes
with the potential to turn a normal cell into a tumor cell.
Many families of genes, including KDM5, have functional
compensation, meaning deletion of only one of the genes
would not affect the function of the intended target protein.
Therefore, the researchers want to turn off all the genes in the
family simultaneously.
The researchers also knew that shutting the oncogenes
down immediately would kill the oncogene-dependent
tumor cells, and they would have no stable cell line to study.
Therefore, they created an inducible multiplex system, which
the researchers could turn on with the addition of certain
drugs. Thus, they generated a stable cell line first and then
tested how turning several oncogenes off affected the tumor
cells.
Furthermore, the direct consequences of turning off
genes are more clearly observed in an inducible system. If
Cas9 is expressed from the beginning, researchers could
not distinguish among early and late responses of the cell.
However, in an inducible system, the scientists can study
what happens in the short time after Cas9 expression is
turned on. Furthermore, the inducible system reduces offtarget
effects, since turning off the system when not needed
reduces the number of times sgRNA matches and directs
Cas9 to cut incorrect DNA.
This toolbox is extremely efficient compared to CRISPR
systems used in the past. In previous studies, researchers had
to insert the vector system into a mixture of cells and then
select for single cells to create a cell line for functional studies.
This process would take three to four weeks. “Our approach
is more efficient, so that we can achieve nearly complete
silencing of the target genes, even in a mixed population. We
do not have to pick up a single clone, so that saves a lot of
time,” Cao said.
This system is already in high demand by many research
groups. The Yale researchers have received requests for the
reagents from all over the world, including labs studying
cancer, infectious diseases, and stem cell biology. This
toolbox could theoretically target any gene by switching the
recognition site using the appropriate sgRNA molecule.
As for future directions for the lab’s research on this
CRISPR system, Cao said that they hope to make the system
even more efficient. Developing a plasmid that contains both
the sgRNA and the Cas9, instead of using one plasmid for
each as in the current toolbox, would further speed up the
process of generating a stable cell line.
The lab is now going to utilize this CRISPR system in their
functional studies. “We are applying this toolbox in our
cancer research, especially identifying oncogenes and tumor
suppressor genes that have the potential to serve as drug
targets.”
IMAGE COURTESY OF QIN YAN
►Dr. Qin Yan (front right) pictured with members of his lab at
the Yale School of Medicine.
8 Yale Scientific Magazine October 2016 www.yalescientific.org

astronomy
NEWS
BEYOND GOLDILOCKS
Refining and redefining humanity’s quest for Earth 2.0
►BY SOPHIA SÁNCHEZ-MAES
www.yalescientific.org
IMAGE COURTESY OF MEREDITH HOLGERSON
►Planets form through the accretion of material from the
protoplanetary disk, which is made of gas and dust and is
leftover from star formation.
Just over 20 years ago, our solar system was alone in the
universe, and we thought we knew it all. According to theory,
gas giant planets form and stay beyond an ice line—the
distance from the sun beyond which liquid water freezes,
while small rocky planets dominate the inner circles. Then
came the discovery of 51 Peg b in 1995, a hot gas planet larger
than Jupiter that orbits far closer to its star than we would
expect. Since then, the exoplanet community has discovered
thousands of planets, including worlds like Luke Skywalker’s
Tatooine that dance around a binary sunset. The
field has theorized planets made of diamond and found
planets light as cork or dense as lead. These worlds are unbound
by the limits of imagination, so Yale researchers Debra
Fischer and John Brewer set out to constrain them using
the laws of physics.
For years, the dominant line of thinking about the search
for Earth 2.0 has been in terms of a Goldilocks zone, an area
of ‘just right’ between the “too cold” of faraway Neptune and
the scorching “too hot” of Mercury; it is the region around a
star where an Earth-like planet can possess liquid water. But
Yale scientists are challenging this definition of habitability.
Though a rocky planet may be in its star’s Goldilocks zone, it
cannot be Earth 2.0 if its star has the wrong chemical abundances
for Earth-like geology to form.
Planets are formed by the accretion of material from the
disk of gas and dust that created their star. Brewer and Fischer
studied these planet-forming conditions by analyzing stellar
spectra to correlate stellar properties such as temperature,
surface gravity, and elemental abundances with properties
of their planets. With this approach, they can draw conclusions
about the planets that could form, based on their starting
stellar material. For example, the team found diamond
planets to be highly improbable, since no star in their large
sample had a sufficient carbon to oxygen ratio for one to
form. “But perhaps it’s good,” Brewer noted, “that we don’t
live on a diamond planet.”
That is good for the quest for Earth 2.0. Carbon-oxygen
bonds are some of the fastest to form, but the next strongest
bonds happen between magnesium, silicon and oxygen,
which dominate the mineralogy of planets around stars with
carbon-oxygen ratios like that of our sun. Earth’s geology is
unique to this high magnesium to silicon ratio. Brewer and
Fischer also showed that the peak of the abundance distribution
was similar to our sun’s, and 60% of their large stellar
sample could theoretically support Earth-like geology.
But disk abundances are not enough to point towards an
Earth-like planet. Not all planets in the Goldilocks zone will
be habitable; much depends on their composition and geology.
Jun Korenaga, a Yale professor of Geology and Geophysics,
works on the latter dependence in a recent study.
Greenhouse gases, which warm our planet, are released
into the atmosphere from volcanoes; however, they can return
to the deep mantle in the Earth through plate tectonics.
On Earth, this deep carbon cycle is essential for maintaining
the long-term temperature necessary to support life. “The
planet we have now is the result of billions of years of geological
activities,” notes Korenaga. “Plate tectonics controls
almost all aspects of geologic activities, so much so that geologists
take it for granted.”
However, tectonic plates are not the norm even in our solar
system. Venus and Mars, our closest neighbors, formed
from the same material as Earth, but both have a stagnant
lid, the entire surface is covered by a single rigid shell. There
is no long-term sink for greenhouse emissions, creating the
extreme heat detected on Venus. Dr. Korenaga suggests that
plate tectonics is far from normal. His study goes still farther,
showing that mantle convection is not self-regulating
as was long postulated, it does not create a temperature stabilizing
feedback loop. This means that a planet’s temperature
depends not only on its physical location, as per the traditional
Goldilocks model, but also on its starting internal
temperature.
These studies represent a larger shift in the field of exoplanets,
going beyond planet hunting towards planet exploration
and expanding the notion of the habitable zone
beyond Goldilocks. Dr. Korenaga points out, “The important
question isn’t just finding an earth-like planet; it’s understanding
why we’ve got that kind of system out there.” It
is about looking up, and looking down, to better understand
and contextualize ourselves and our planet in the universe.
October 2016
Yale Scientific Magazine
9

NEWS
neuroscience
CALM UNDER NEURAL FIRE
Dynamic brain activity may indicate resilience under stress
►BY EVALINE XIE
All college students are familiar with those fateful days when
alarms “don’t work” and we fall back asleep, prompting a mad
dash in front of angry, honking cars to arrive on time, and a
whole cascade of terrible events. When it comes time to vent
about the day’s trials and tribulations, there is only one word that
characterizes the struggle: stressful. A quintessential part of our
everyday vocabulary, we use stress to talk about everything from
long-term struggles to brief run-ins with danger. Despite how
casually we talk about stress, however, we still know remarkably
little about the actual neural mechanisms involved. How does the
brain control how we reason through high-pressure situations,
solve problems, and exercise control over our actions during
stress?
As a result of the work published this summer by researchers
at the Yale Stress Center, we may have more insight into these
questions. Researchers used functional magnetic resonance
imaging (fMRI) to map brain activity by measuring changes in
blood flow and oxygenation. They discovered more dynamic
activation patterns, dramatic changes in oxygen levels in certain
regions of the brain, in response to sustained exposure to images of
violence, disgust, victimization, and mutilation, when compared
to neutral images of buildings and objects. The study cited this
as evidence of “neuroflexibility,” what allows for resilience in
coping with stress. Professor Rajita Sinha, the lead author of the
paper, describes neuroflexibility as a kind of adaptability. “The
ability to pull back, divert your attention, and let other pieces of
information come into your consciousness and awareness.” The
brain accomplishes this through active changes in neural signals
over time.
While previous studies examined the brain’s response to stress,
the work by Sinha’s team is unique in the presentation of the
visual stimuli—the stressful or threatening images—for extended
periods of time, rather than brief moments. As a result, the
researchers were able to uncover how the brain was processing
stress not only immediately after it began, but also over time.
For example, previous neuroimaging studies found that initially
after stress is applied, there is increased activation in the limbicstriatal
region, which deals with our emotional and behavioral
reactivity, and decreased activation in the ventromedial prefrontal
cortex (VmPFC), which is responsible for persistence in the face
of failure, processing of risk and fear, and regulation of anxiety.
However, Sinha’s study found that these effects were only the first
steps in an entire behavioral coping network.
Previous studies have already revealed much of the brain’s
immediate stress responses, which are the first two parts of what
Sinha describes as a three-part circuit. The first part of this circuit
involves regions of the brain that respond to arousal during
stress. For example, the amygdala, which processes fear and other
emotions, becomes alert to stressful imagery; the hippocampus,
which is involved in memory, remembers threatening images;
lastly, the striatum system, a motor region of the brain, prepares
for action. Sinha’s group identified a second part of this network
focused more on adaptation, where regions of the brain with
initial high activation lowered their response, possibly to reduce
distress and continue to survive under stress. Finally, the Yale
researchers discovered that beyond this, there was evidence of a
third, later stage of active resilient coping: an increase in VmPFC
activation again after the initial early stage drop in activity.
What is so important about the rising and falling activation of
these small parts of the brain? The researchers discovered that this
neuroflexibility—the brain’s ability to change its response to stress
over time—was linked to how well participants were able to cope
in real life. People with less dynamic activity in the VmPFC tended
to participate in binge drinking, emotional eating, and arguments
and fights. In other words, they have trouble with healthy coping
during stress.
Consequently, this study could have major clinical applications.
“It creates a new frame of reference for helping us understand
stress-related illnesses,” Sinha explains. The researchers at the
Stress Center are already working on follow-up experiments to
explore these clinical implications, looking specifically at bingeheavy
drinkers and, in the future, emotional eaters and patients
who have been exposed to trauma.
“There will always be bad things that happen that can cause
stress,” Sinha said. However, with a growing body of knowledge
about how the brain responds to stress, we may be able to start
thinking about how we can increase resilience and strengthen our
coping mechanisms.
IMAGE COURTESY OF RAJITA SINHA
►The regions of the brain indicated by red and yellow show
significantly increased activity during stress compared to under neutral
conditions, and decreased activity in the VmPFC (shown in blue).
10 Yale Scientific Magazine October 2016 www.yalescientific.org

environmental science
NEWS
HARVESTING HEAT
Renewable Energy for the Future?
►BY NOAH KRAVITZ
PHOTO BY KENDRICK UMSTATTD
►The Elimelech lab uses nanobubbles and nanofibers to
experimentally show that heat can be captured to generate
electricity.
What do wind turbines, dams, and solar panels have in common?
They all harness naturally occurring imbalances—moving
air, flowing water, and electrons excited by photons in sunlight—to
generate electrical energy that we can use to power our
everyday lives. We currently obtain electricity from a wide range
of sources, but we have yet to tap effectively into one that surrounds
us: heat. Yale researchers, however, have recently developed
a new technology that converts low-grade heat energy into
electricity.
There have long been methods for harvesting so-called highand
medium-grade heat characterized by temperatures over 243
°C, but it has proven more difficult to exploit low-grade heat,
which makes up the majority of industrial heat waste. Existing
thermoelectric technologies for harvesting low-grade heat
are expensive to produce, inefficient, and limited in their ability
to respond to even small temperature fluctuations. The Yale
team, led by professor Menachem Elimelech in the Department
of Chemical & Environmental Engineering, collaborated with
Ngai Yin Yip of Columbia University, Shihong Lin of Vanderbilt
University, and Jongho Lee in the Elimelech Lab at Yale to
design a versatile and environmentally friendly process for harvesting
low-grade heat. Their method uses membranes about
half the thickness of a human hair that can generate electricity
when placed between two water sources differing by as little as
20 °C.
This new “nanobubble membrane” technology takes advantage
of a process called thermo-osmotic energy conversion
(TOEC). The higher temperature on the warm side of the membrane
causes water to evaporate and travel across tiny air pores;
the water then condenses on the cold side of the membrane. The
increased pressure in this cold reservoir drives a turbine, which
in turn generates electricity.
The key to making TOEC work is maintaining the air pores
even under high water pressure. To accomplish this, the researchers
made the membrane using highly water-repellent, or
hydrophobic, nanofibers. “We were the first ones to show experimentally
that this sort of membrane could be used in a pressurized
process,” said Anthony Straub, a doctoral student in the
Elimelech Lab who worked on TOEC as part of his dissertation
research. “That was a main objective: making sure water didn’t
get into the pores.”
The current system is estimated to capture up to seven percent
of the energy from the temperature gradient, or around fifty-eight
percent of the highest theoretical yield. The researchers,
however, are confident that they can continue to fine-tune
their design. First, they are explorinEg new methods for creating
more uniform nanopores that would let water vapor travel with
less obstruction. In addition, they seek to reduce the parasitic
energy consumption from operating the technology, analogous
to the calories the human body burns just to digest food. They
also believe that replacing water with a different fluid could be a
game-changer for efficiency. “We are currently working on developing
improved membranes which, with the right structure,
could more than double the power output per surface area,”
Elimelech said. But what really is the potential of this new technology?
Industrial heat waste alone is estimated to constitute up to half
of the total industrial energy input, so recovering some of this
loss would be a major environmental accomplishment. Furthermore,
because its only waste product is water, TOEC leaves a
small environmental footprint. There are also natural geothermal
sources such as hot springs, especially in the American
West, that would be amenable to harvesting by the TOEC process.
“Many possible energy sources have been overlooked because
they are at low temperatures,” Elimelech said. “We hope
our new technology can start developing these untapped resources.”
Yet it is doubtful that in 10 years our houses will be
running on thermoelectric power. When low-grade heat sources
are readily available, TOEC can save energy in areas where
energy is difficult to generate by supplementing existing infrastructure,
but it lacks the scope to replace a nuclear power plant.
Straub is optimistic about expanding the applications of his
findings outside of electricity generation. “Now we’re using
these pressurized hydrophobic membranes for power generation,
but in the future we might also be able to use them for desalination
or other similar processes.”
www.yalescientific.org
October 2016
Yale Scientific Magazine
11

FOCUS
medicine
BRAIN DAMAGE
BEFORE
BIRTH:
by Anson Wang | art by Yanna Lee
How Zika Causes
Microcephaly
In the summer of 2015, an alarming
wave of mothers delivering babies with
small, abnormal heads hit Brazil’s medical
wards. Doctors were baffled. Then, a few
officials noticed that the outbreak coincided
with a rise in Zika virus infections. The
urgency of this medical mystery prompted
the World Health Organization to declare
a public health emergency. Pregnant mothers
were warned not to travel to tropical regions,
and news outlets began declaring an
“epidemic of birth defects” that threatened
the globe. As Brazil prepared for its Summer
Olympic Games, Zika virus stole the
spotlight as the biggest epidemic since the
2014 Ebola outbreak.
By 2016, the birth condition known as
microcephaly was labeled as “congenital
Zika syndrome.” The rare condition results
from insufficient brain growth in the developing
fetus, which causes the baby to be
born with a small head without a forehead.
Zika is a virus related to West Nile, Dengue,
and yellow fever and is commonly
found in tropical, equatorial regions of the
globe. The virus spreads via a mosquito
vector, most commonly the female Aedes
aegypti mosquito. Although multiple case
studies pointed to Zika as the culprit for
the rise in microcephalic births, there was
little hard evidence to connect the virus to
the disease.
A collaborative effort
A team of researchers at the Yale School
of Medicine established some of the first
fundamental links between Zika virus infection
and microcephaly. Drs. Nenad Sestan,
Tamas Horvath, and Brett Lindenbach,
as well as their colleagues from the Departments
of Neuroscience and Microbial
Pathogenesis, came together and combined
their expertise to uncover some of the molecular
mechanisms behind congenital
Zika syndrome.
Through carefully conducted
experiments, the
researchers demonstrated
that the
Zika virus
preferentially
infects
neuroepithelial
stem (NES) cells, the earliest
line of developing neurons. The virus also
inhibits cell division in the developing
brain by redirecting crucial enzymes to
incorrect targets during mitosis.
In addition, the team
stumbled upon a potential
antiviral drug
that inhibits Zika
virus replication.
Remarkably, the
team of researchers
unveiled
not
only crucial
molecular
pathways
12 Yale Scientific Magazine October 2016 www.yalescientific.org

medicine
FOCUS
necessary for early brain development, but
also a possible path to treatment.
The study and its results came together
rapidly, advancing from conception to publication
in a matter of months. “It was very
exciting,” Sestan said. “Here was something
that posed an immediate biomedical threat
to society, and whoever we called for advice
was already thinking, or doing something,
about it.”
Sestan and his colleagues had been
studying NES cells in their lab for many
years. Meanwhile, Lindenbach’s lab, located
on the same floor in an adjacent building
on Yale’s medical campus, studied the
replication of positive-sense RNA stranded-viruses,
a class of viruses that includes
Zika virus. Recognizing that the emergence
of Zika virus raised multifaceted questions
spanning multiple fields, the two labs
teamed up to contribute their respective
expertise to an investigation of the mysterious
Zika virus and how it led to microcephalic
babies.
“We were just socializing before we realized,
‘Wow, maybe we can work together
on this interesting problem,’” Sestan said.
A molecular understanding of Zika
The first half of their research, published
in Cell Reports, addressed Zika virus’ capability
to infect neuronal stem cells. The researchers
showed that Zika virus preferentially
infects both NES cells and radial glial
cells, important cells that provide structure
for the developing brain. The team replicated
their findings in both mouse and human
cell cultures. Infected radial glial cells were
also detected in tissue samples obtained
from prenatal microcephalic brain tissue in
a Zika-infected mother. This critical anomaly
in growth not only resulted in cell death,
but also led to an “architectural disruption”
of the glial cell scaffold that is necessary for
proper brain development.
The researchers now knew that Zika preferentially
infects early neuronal stem cells.
But how did this lead to microcephaly?
Once again, the social and collaborative
aspects of research made all the difference.
Horvath researches metabolic cell functions
and was working with a molecule
known as TANK binding kinase 1 (TBK1),
a crucial enzyme for innate immune signaling
and cell proliferation. Under normal
conditions, TBK1 is important for
the proper functioning of the centrosome,
a component of cells that drives cell division.
The team discovered that following
Zika infection, TBK1 was redirected to the
mitochondria instead, robbing the centrosome
of an essential enzyme and halting
cell division. “Essentially what you are left
with is a chimeric cell, with multiple nuclei
and centrosomes but no cell division,” Sestan
said. Although it is unknown exactly
how or why TBK1 is necessary for mitosis,
a crucial molecular process of Zika virus
that gives rise to microcephaly had been
uncovered for the very first time.
In addition, the researchers observed
that other viruses known as TORCH
(toxoplasma, other agents, rubella virus,
cytomegalovirus, and herpes simplex virus)
syndrome pathogens also caused brain
defects in the developing brain. However,
since numerous vaccines have been developed
to prevent many TORCH pathogen
infections, microcephaly was rarely observed
until the recent outbreak of Zika in
2015. Since Zika may not be so unique, after
all, in its ability to cause microcephaly,
the natural question was to determine how
we may be able to neutralize this virus, just
as we have done with the other viruses of
this class.
In the past, antiviral drugs, such as nucleoside
chain terminators, have been effectively
used against other flaviviruses, which
includes hepatitis C and Zika virus. Now,
the investigators have found that in cell
cultures, the antiviral drug, Sofosbuvir, not
only protects NES cells from Zika-induced
cell death, but also inhibits the misdirection
of TBK1. While the toxicity and pharmacology
of these molecules are unknown,
these findings present promising new leads
for the future of Zika virus treatment.
One piece of the puzzle
Have researchers discovered the missing
link between Zika and microcephaly?
While the study is a major step in understanding
Zika virus, many questions remain
unanswered. It remains unknown
why Zika virus preferentially infects NES
cells and radial glial cells or how exactly
the virus penetrates both the uterus and
the developing brain, two highly protected
areas under normal conditions. The molecular
functions of TBK1 also require further
investigation, and the researchers hope to
derive mice models that lack this crucial
enzyme. If TBK1 is necessary for mitosis
in the developing brain, these mice should
be microcephalic. Meanwhile, the absence
of microcephaly in Zika cases in Colombia,
as well as in related virus cases, such as
Dengue fever, need to be addressed. “This
paper is a rock solid brick in the wall of understanding,”
Lindenbach said. “However,
there are many more bricks that need to be
put in place.”
Beyond discerning a piece of the Zika
puzzle, the group’s research also illustrates
the fruits of collaborative research.
The researchers acknowledged that such
an extensive, multidisciplinary study
would have been impossible to accomplish
through a single lab. Sestan observed that,
as his lab works in brain development, they
would never have looked into the virology
methods ultimately used to study Zika.
“That’s what I like about science. Every day
is different, and that’s what motives me,” he
said. It is that sense of optimism that drives
important discoveries with the potential to
bring health improvements to suffering regions
around the world.
ABOUT THE AUTHOR
ANSON WANG
ANSON WANG is a senior in Davenport College majoring in Molecular
Biophysics & Biochemistry. He currently works in the lab of Dr. Charles Greer
studying the organization and morphological characteristics of axonal growth
cones in the olfactory system. Outside of the sciences, he plays the clarinet
for the Yale Concert Band and dances Bhangra on Yale Jashan Bhangra.
THE AUTHOR WOULD LIKE TO THANK Dr. Nenad Sestan, Dr. Brett
Lindenbach, Dr. Marco Onorati, Dr. Andre M.M. Sousa, Fuchen Li and Zhen
Li for participating in the interview and gathering the figures for this article, as
well as for their enthusiastic research.
www.yalescientific.org
October 2016
Yale Scientific Magazine
13

FOCUS
neuroscience
The 100 trillion synapses in our brain contain a wealth of
information about health and disease in the brain. Scientists
at the Yale PET Center have recently developed a novel
imaging technique to view synaptic connections in the living
brain.
BY CHRISTINE XU
ART BY ISA DEL TORO
Imagine you could shrink yourself to
the size of a neuron and explore the
pathways inside the human brain.
You could map the networks between
neurons and listen to the secret molecular
conversations occurring constantly at the
connections between them. Based on what
the neurons are saying, you could gather
inside information about whether or not
the brain is healthy. Unfortunately, from an
outside perspective, these conversations are
hard to make out.
The human brain is incredibly complex
and mysterious—it contains about 100
billion neurons that encode all our thoughts
and movements. These billions of neurons
are wired together by an estimated 100
trillion synaptic connections. At synapses,
neurons talk to each other, using chemical
messengers called neurotransmitters to
send a variety of signals and information.
Now for the first time, we can eavesdrop on
live neurons, thanks to a technique developed
by professor Richard Carson and
postdoctoral fellow Sjoerd Finnema at the
Yale PET center.
Imaging synaptic density can provide
a wealth of information on the processes
occurring inside the brain. Synapse loss
has been linked to a number of neurocognitive
disorders including Alzheimer’s,
Parkinson’s, autism, depression, and schizophrenia.
In the past, the only way to image
synaptic density was by examining brain
tissue during an autopsy. Now, Carson,
Finnema, and their team of researchers
have developed a novel method of synaptic
imaging that can be used in living patients.
This minimally invasive method has huge
potential in diagnosing and monitoring the
progress of neurocognitive disorders.
The new method developed by Carson
and Finnema uses positron emission topography
(PET), a technique commonly used
by neuroscientists, to observe the activity of
the living brain. During a PET scan, a radioactive
tracer such as a glucose-like molecule
is injected into the patient, and the areas
of localization of the tracer reveal where
the brain is active. The PET Center team
developed a new tracer called [11C]UCB-J,
which binds to a protein found in synapses
and thus reveals where neurons are talking.
A new blade
PET imaging is a flexible technique with
a number of clinical applications. It can be
used to monitor the activity of the body and
detect abnormalities such as cancer, heart
disease, and neurocognitive dysfunction.
Depending on the type of radioactive tracer
used, PET can target a wide range of tissues
in the body, making it a multipurpose tool.
“PET is like a Swiss Army knife,” Carson
said. “With one technique, you can perform
many different functions, depending on
which radioactive material you inject.
Now we’ve added a new blade to our
knife, using a new molecule to perform a
different task.” Carson explained that with
each blade added to the knife—with each
new molecule developed—the Swiss Army
knife becomes a more powerful device.
With improved imaging techniques, scientists
and clinicians will be able to better
understand not just the normal function
of the brain, but also what goes wrong in a
diseased state.
“If you find the right molecule, you
can image anything—so our goal was to
develop a novel radio-pharmaceutical that
can target a specific process in the human
body,” Carson said. The new molecule
that the researchers discovered, [11C]
UCB-J, targets a protein called SV2A found
specifically in the synapses of the brain.
Neurons communicate with each other at
synapses through the action of chemical
neurotransmitters. One neuron releases a
vesicle containing neurotransmitters into
the synaptic cleft, and these neurotransmitters
are picked up by its neighbor. SV2A is
a protein that is embedded in presynaptic
vesicle membranes. Because SV2A shows
up consistently in all synapses of the living
brain, PET imaging and quantification of
SV2A can be used to determine synaptic
density.
14 Yale Scientific Magazine October 2016 www.yalescientific.org

neuroscience
FOCUS
confirmed that the new technique was sensitive
enough to pick up differences in synaptic
density between healthy patients and patients
with a neurocognitive disease.
The future of synaptic imaging
Testing the technique
To make sure that their new technique
presented an accurate measure of synaptic
density, the researchers performed a number
of studies involving both animal and human
subjects. They first injected [11C]UCB-J into
olive baboons (Papio anubis). Within a few
minutes of injection, radioactivity rose within
the brain, with the signal highest in synapserich
gray matter and lowest in synapse-poor
white matter.
The researchers wanted to confirm that
their new technique yielded similar results
to previous postmortem techniques. They
dissected the brains of the baboons and determined
the levels of both SV2A and another
synaptic protein that is considered the gold
standard for measuring synaptic density.
As expected, the levels of the two proteins
correlated well. Furthermore, SV2A levels
were similar whether determined by PET
imaging or postmortem analysis, suggesting
that PET is an accurate measure of where a
protein is localized.
Five healthy human subjects were recruited
to test the PET imaging technique. As with
the trials with baboons, radioactivity rose in
the brains of the human subjects within a few
minutes of injection. Once again, the signal
was highest in gray matter and lowest in white
matter.
Repeating the procedure in three epilepsy
patients, the researchers found that these
patients displayed an asymmetric uptake of
the radioligand with a loss of signal in the
hippocampus and amygdala, two brain structures
where the patients had suffered damage
due to their epilepsy. This exciting finding
In its healthy state, the brain is constantly
re-wiring itself, trimming out some synapses
and strengthening others. Synaptic pruning,
for instance, is a process occurring throughout
and after adolescence wherein neurons shed
old connections to reinforce the efficiency of
essential ones. When the brain makes mistakes
in regulating its synaptic connections, disease
can result. Synapses are destroyed in a number
of neurocognitive diseases, and scientists are
still seeking to fully comprehend the connection
between synapse loss and disease.
Carson emphasized the importance of
the new synaptic imaging technique for
improving our understanding of neurocognitive
disorders. “Alzheimer’s, Parkinson’s,
schizophrenia, Huntington’s, autism, depression,
traumatic brain injury, alcohol abuse…
these are just some of the disorders where
synaptic loss has been implicated,” Carson
said. “We want to combine information from
many imaging techniques to understand
disease and disease progression.”
One of the researchers’ biggest targets is
Alzheimer’s, Carson stated. The pathology
of Alzheimer’s has been fairly well characterized:
Alzheimer’s patients have abnormal
structures called amyloid plaques and neurofibrillary
tangles in their brains, and PET
imaging techniques have been developed that
target these specific structures. As the loss
of synapses is also tied to loss of function in
IMAGE COURTESY OF RICHARD CARSON
►Amyloid plaques and neurofibrillary tangles
can be found in the brains of Alzheimer’s
patients. PET imaging techniques have been
developed to detect these.
Alzheimer’s patients, Carson believes that
synaptic imaging will add a new technique
to the diagnostic toolbox, a new blade to the
Swiss Army knife. “The addition of our tracer
will help improve diagnostics. We would like
to use multiple tracers to follow the progression
of the disease over time, and this will be
very valuable in both diagnosing and treating
patients.”
However, more research is needed to validate
the consistency and accuracy of the technique
before it can be used widely. Carson
envisions a greater number of clinical trials on
larger patient populations in the near future.
He hopes that the technique will soon be used
not just by research scientists, but also by
physicians, neurosurgeons, and pharmaceutical
researchers. In the meantime, he is optimistic
about collaboration to further develop
the technique and hone this new addition to
the Swiss Army knife of neurological diagnosis.
“Many other PET centers around the
world are working on this,” Carson said. “We
look forward to working with them.”
ABOUT THE AUTHOR
CHRISTINE XU
CHRISTINE XU is a junior in Saybrook College majoring in Molecular, Cellular,
and Developmental Biology. She currently works in a neurodevelopment lab
at Yale studying axon growth in the olfactory system. Besides writing for Yale
Scientific Magazine, she enjoys playing classical piano and a cappella.
THE AUTHOR WOULD LIKE TO THANK Dr. Carson for his time and his
enthusiasm in sharing his work.
FURTHER READING
Garrett, Mario D. “Complexity of Our Brain.” Psychology Today.12 Feb. 2014.
.
www.yalescientific.org
October 2016
Yale Scientific Magazine
15

Deco
Gecko
A CLEAN
TOUCH
TO ART
The purpose of art is
washing the dust of
daily life off our souls.
– Pablo Picasso
Dust. Formed from particles
in the atmosphere weathered
from sources as varied
as soil, shed skin cells, paper fibers,
and burnt meteorite particles, it
can be found almost anywhere on
Earth—and often where we don’t
want it. While dust is the bane of humanity
during spring cleaning, it also
causes problems for art conservators
trying to restore fine art and artifacts
to their original state. Many cleaning
methods that effectively remove dust
run the risk of damaging sensitive patinas
underneath.
Researchers at the Vanderlick Lab
at Yale have found a novel way to
clean dust from solid surfaces, using
modified materials inspired by,
of all things, gecko feet. Their study
demonstrated that the material they
developed—a thin polymer layer
comprised of millions of microscopic
columns—effectively cleans dust
from almost any solid surface. The
new material shows promise not only
for thoroughly and nondestructively
cleaning artwork, but also for removing
dust from sensitive surfaces
in fields like electronics and medical
implants where pristine surfaces are
highly desirable.
Building bridges
The Vanderlick Lab was looking to
design a project for art conservation.
“My general research area, which
I’ve been in for decades, has been
related to interfaces, thin films, and
properties related to surfaces,” said
T. Kyle Vanderlick, Dean of the Yale
School of Engineering and Applied
Science (SEAS) and principal investigator
of the lab that produced the paper.
“Many of those problems related
to art preservation are problems related
to surfaces—the chemistry and
physics of surfaces—and so there’s a
natural connection to my research
interests.”
by Andrea Ouyang
art by Laurie Wang
As the Dean of SEAS, Vanderlick
was interested in showing how engineering
could connect to different
parts of campus and the various
fields of study they represent. “I believe
engineering is a real connector,
a real bridge between science and the
humanities, science and the arts, and
so on,” Vanderlick said. With that in
mind, she hired a post-doctoral fellow,
Hadi Izadi, who had experience
in research related to surfaces.
The Institute for the Preservation
of Cultural Heritage (IPCH) on West
Campus played a pivotal role in linking
the engineering lab to the conservation
work being performed in galleries
and museums across campus.
The IPCH put Izadi in touch with
conservators with whom he could
collaborate in developing a project.
“The IPCH is a group of conservation
scientists, scientists who have
been working on art and conservation
problems, and in that way we

materials science
FOCUS
speak both languages,” said Paul Whitmore,
senior research scientist and chemistry and director
of the Aging Diagnostics Lab at IPCH.
“We speak both the language of conservation
and art history and the language of the scientist
and the technical expert.” Though sometimes
the IPCH provides technical expertise,
other times the scientists reach out to those
in various other fields to collaborate on projects,
acting as both matchmakers and advisors
and bridging the gaps between research being
done in the sciences and the arts, according to
Whitmore.
With the aid of the IPCH, Izadi collaborated
directly with art conservators from various
art galleries across campus. “I went and visited
many different museums on campus. I went
to the British Art Museum, I went to the Art
Gallery, and I went to the Peabody,” Izadi said.
Izadi discussed different problems with art
conservation that conservators were having
with their everyday work and collaborated
directly with them on projects aimed at using
materials science to produce new technologies
and methods to make art conservation easier
and more efficient.
Geckos at the get-go
Izadi’s background in materials science and
research in surface properties included studies
on the properties of gecko-inspired adhesives.
Geckos, with their ability to climb almost any
surface—even glass placed at almost a 90-degree
angle—have long been a source of fascination
for scientists and engineers. The ridged
pads of gecko feet are covered by tiny hair-like
structures called setae, which then branch into
nanoscopic tips called septulae. The millions
of septulae on a gecko’s foot allow it to adhere
even to very smooth surfaces via electrostatic
intermolecular interactions.
“During my PhD research, I [realized] one
thing about gecko-inspired adhesives is that
this kind of material gets a large amount of
surface charge when it touches other materials,”
Izadi said. “When you rub a balloon
against your hair, it’s the same mechanism.”
Particles as small as dust are also easily affected
by electric charges and the resulting
electrostatic interactions, so Izadi was drawn
to the possibility of using adhesives modeled
after the properties of gecko feet. Using
polydimethylsiloxane (PDMS), a soft polymer,
he created a thin film covered in microfibrils:
slender, microscopic columns similar
to the hair-like septulae on a gecko’s foot. The
PDMS film was then placed against a layer
of polymethyl methacrylate (PMMA) substrate
covered in silica particles—stand-ins
for dust—only a few micrometers in diameter.
The researchers then separated the layers
and analyzed the amount of silica particles left
on the PMMA layer. While flat, unstructured
PDMS films removed the silica particles poorly
from the PMMA layer, the gecko foot structure
of the microfibril-covered films cleaned
off almost all of the simulated dust.
PDMS is ideal for cleaning because it is a
soft polymer, Izadi said, meaning that it can
develop a large surface area of contact with
dust particles, maximizing the adhesion force
between the silica and the film and therefore
effectively removing the “dust.” The use of
PMMA, the base material in acrylic painting,
helped serve as an early indicator for whether
or not the PDMS film could be effective in
cleaning artwork containing acrylic paint.
In modifying the PDMS film, the research
group actually moved away from the traditional
model of a gecko-inspired adhesive,
which is exactly that: adhesive. Gecko adhesives
are actually very similar to Scotch tape,
which forms physical bonds with surfaces.
However, the soft, “sticky” layer of microfibrils
in Scotch tape is damaged when it is pulled
away from the surface. Additionally, when
most gecko-inspired adhesives are brought
into contact with a surface, or substrate, they
remove not only dust particles, but also parts
of the surface itself. For objects as sensitive
and delicate as artwork or artifacts, both the
stickiness of traditional gecko-inspired adhesives
and their inability to be reused is problematic.
In that sense, the film developed by
the research group is more than a gecko-inspired
adhesive, because, while it incorporates
the same microfibrillary structure, it does not
stick to surfaces and can effectively remove
dust from a surface nine times its size, making
it perfect for the delicate job of cleaning artwork.
Making a clean sweep
The success of the modified PDMS as a
duster was surprising to Izadi, who hadn’t expected
it to become so popular so quickly. He
attributes the effectiveness of the method to
its simplicity. “[Our method is] faster, more
accurate, and much cheaper than the other
methods,” Izadi said. “You just need one simple
roller, a hand roller, that you can just […] drag
over the surface, and it can completely clean up
all dust particles.” Other methods of removing
dust often require large machinery, such as laser
cleaners or ultrasonic baths. While effective
at removing dust, these methods are expensive
and risk damaging sensitive materials.
Future directions for this research include
refining the material so it can remove smaller
particles and particles of different shapes.
Currently, the PDMS film can effectively
clean particles between 10 micrometers and
200 nanometers in diameter, but the ultimate
goal is to remove particles smaller than 100
nanometers. In other words, the researchers’
method can already effectively clear a material
of particles at the very boundaries of light microscopy,
since visible light wavelengths only
extend to about 400 nanometers. To achieve
the scientists’ goals, the film must be able to
remove particles the size of a single HIV virus
or smaller. Thus far, the film only removes
spherical particles. The researchers hope to
eventually be able to remove dust of all shapes
to provide an even more thorough clean.
The partnership between conservators and
academic scientists remains essential in continuing
the project, as conservators are helping
the researchers design projects in which
the effectiveness of the film can be tested on
surfaces similar to those of actual artwork,
rather than just PMMA. This collaboration
between conservators and scientists in this
project was part of what made it so extraordinary,
both Izadi and Vanderlick emphasized.
Like the microfibrils, the close-knit structure
of research communities at Yale allows for
meaningful interactions across various fields.
Yale’s big impact, despite its small size, is precisely
due to its extraordinarily collaborative
and interdisciplinary nature, Vanderlick said.
ABOUT THE AUTHOR
ANDREA OUYANG
ANDREA OUYANG is a sophomore and prospective MCDB major in
Davenport College.
THE AUTHOR WOULD LIKE TO THANK Dean T. Kyle Vanderlick and Drs.
Hadi Izadi and Paul Whitmore for their time and enthusiasm about their
research.
FURTHER READING
Izadi, H. “Removal of Particulate Contamination from Solid Surfaces Using
Polymeric Micropillars.” American Chemical Society, vol. 8, no. 26, 2016.
www.yalescientific.org
October 2016
Yale Scientific Magazine
17

FOCUS
medicine
TRANSFERRING NEW
ENERGY to an
OLD RULE
PUSHING THE BOUNDARIES
OF CLASSICAL PHYSICS by Chunyang Ding
Time after time, brilliant scientists make claims about science’s future
that prove completely wrong. In a quote often misattributed to Lord
Kelvin, Albert Michelson famously declared that “there is nothing new
to be discovered in physics now; all that remains is more and more
precise measurement.”
18 Yale Scientific Magazine October 2016 www.yalescientific.org

physics
FOCUS
Classical mechanics, the tradition of
physics that originated with Newton,
Kepler, and Galileo, is often seen as
something we already understand, and something
we have understood for a long time. This
is simply not true. Even today, new discoveries
made with classical mechanics are transforming
the world of science as we know it.
In a recent breakthrough, a Yale physics lab
shows new behaviors in a phenomenon that
some had considered fully understood. Associate
professor of physics Jack Harris and
post-doctoral researcher Haitan Xu report in
Nature their use of ultra-precise lasers and tiny
vibrating sheets that appear to violate classical
predictions. Their experiment, transferring
danced “clockwise,” return you to the same position,
but when danced “counter-clockwise,”
present you with a new partner. This non-symmetrical
form has serious implications for any
system, and offers a new way that scientists
could control these systems.
The research provides an extension of the
adiabatic theorem, a theorem that governs
how systems change as the parameters of the
systems change. These parameters can be any
controlled quality of the system—the dance
moves performed, the tension in a wire, or the
controls in a computer. The adiabatic theorem
says that if the parameters are slowly restored
to their original state, the system will appear to
have not changed at all. This is very powerful
by assuming such systems would behave very
similarly to those without friction. What physicists
did not expect, however, was that the system
could change completely. Although mathematicians
predicted anomalies using what
they called “exceptional points,” physicists
were unable to see these anomalies in actual
systems—until now.
Tiny vibrating membranes
energy by very slowly tuning the vibrations,
has major implications for a decades-old theorem
in mechanics: the adiabatic theorem. This
newly discovered phenomenon occurs in all
systems with friction,and may fundamentally
shift the way physicists view systems.
A dance for the ages
Although Xu’s research focuses on how energy
can be transferred between two different
regions, the core of this new research deals
with systems, a very general way of describing
things that interact. Most things in the world
are systems: the traffic through a busy city, the
movement of the planets, or even a large ballroom
dance.
In a ballroom dance, each person on the
dance floor obeys the rules of the dance, and
as they move, they interact with other people
harmoniously. There might be a set number of
dance moves that eventually bring them back
to the starting point. Essentially, Xu’s research
found that there are certain moves that when
in physics because for a certain experiment on
a system, scientists can restore previous states
without being concerned about how exactly
the parameters have changed. Yet, it is not very
exciting. After all, you only end up where you
begin.
Imagine for a moment that we had a small
dial allowing us to change the masses of Jupiter
and the Sun. Through our understanding
of the laws of gravity, we could predict how
the orbits of the planet change if Jupiter became
more massive and if the Sun became less
massive. The paths of the planets may become
chaotic, but the adiabatic theorem provides a
simple solution: when all of the parameters are
back to where they began, the system would
appear to have never changed.
However, there is one caveat to the above
examples. The only way that the adiabatic theorem
has been proven is through assuming
systems that do not have any friction, or energy
loss. Only in those cases does the adiabatic
theorem work as expected. Still, physicists
applied this theorem to systems with friction
While the previous systems may be simple
to imagine, they would be nearly impossible to
actually control and measure. In order to actually
see the effects of the adiabatic theorem,
Xu’s research involved vibrating a tiny membrane
between two mirrors while using lasers
both to control and to measure the vibrations
of the membrane. The reason this is considered
a system is because the membrane has
two vibrational modes, or methods of vibration,
and the frequency of each vibration can
be controlled by the laser. Vibrational modes
are like vertical and horizontal waves that pass
by each other, and can be thought of as two
separate strings, each vibrating independently.
Vibrating strings are familiar to anyone
who has played a string instrument, whether
it be a guitar, a violin, or an erhu. When you
pluck a single string, the other strings do not
react, as each string has a different resonating
frequency. However, if you tune two strings
to have the same resonating frequency, the vibrating
energy can transfer from one string to
the other. In this experiment, the resonating
frequencies are being changed so that the two
different strings are first tuned together, and
then returned to their original resonating frequencies.
If we then apply the adiabatic theorem,
we would predict that whatever vibra-
www.yalescientific.org
October 2016
Yale Scientific Magazine
19

FOCUS
physics
PHOTOGRAPHY BY GEORGE ISKANDER
tions are in the strings now are the same as the
vibrations in the strings that we started with.
However, Xu’s research group discovered
that this is not always the case in a system
that has some amount of friction. In rare situations
that involve the “exceptional point”
in parameter space, the energy can end up
transferring from the first string to the second
string. Every time the parameters were
changed counter-clockwise around the exceptional
point, they found drastic changes to
the final systems. They found that whenever
the parameters created a path that encircled
the exceptional point, this change happened,
regardless of the actual shape of the path.
Teleporting between different sheets
Exceptional points are fairly difficult to
imagine for a good reason: They are the result
of two 2D sheets intersecting each other in a
4D space. One way to picture these exceptional
points is a fire pole connecting two floors of
a fire station. While each floor is distinct, they
“meet” at the fire pole. However, oddly, when
you walk counter-clockwise around the pole
on the first floor, you would find yourself on
the second floor, without having climbed the
pole at all! The phenomenon here is due to the
bizarre spatial geometry, similar to shapes like
a Mobius strip or a Klein bottle. The exceptional
points are mathematically similar, connecting
surfaces that appear to be separated.
The example with the fire station may be
hard to visualize, but the actual experiment
is even more abstract, as there is no actual
movement around anything. Instead, when
the parameters of the vibrations travel in this
loop, the energy of the system shifts. The experimental
group was able to quantitatively
measure the energy differences in this single
membrane by spying on the vibrations with a
low-powered laser even as a high-powered laser
changed the parameters. This research, the
first of its type, provides solid evidence that
the mathematicians were right: Exceptional
points exist in parameter space, and physicists
can utilize them to control the system.
In the same issue of Nature, a separate
group also published on this topic, but the
group used a completely different method.
While the Yale group was able to dynamically
change the vibrations using the laser, a group
from the Vienna University of Technology led
by Jorg Doppler found similar effects through
pre-fabricated waveguides, which are equally
impressive in the ability to control waves. Together
with Xu's research, these experiments
provide the first empirical proof of exceptional
points.
Taking control of our world
The most powerful implication of this
new research may be in its application for
controlling systems. The adiabatic theorem,
as well as this extension of the theorem, is
particularly robust. They do not seem to
care what path you take, as long as you return
to the same position. This property is
analogous to blindly driving through a dark
two-lane icy tunnel, but finding that you always
end up on the right side of the road
at the end. These robust theorems are extremely
helpful for experiments, especially
in preventing disruptions to the system.
“It’s a new type of control over really pristine
systems,” Harris said.
Even the classical adiabatic theorem and
its offshoots are being used to predict magnetic
effects and provide a deeper understanding
for many quantum phenomena.
This new extension of the adiabatic theorem
will provide insight for physicists as
they apply it to other systems, like NMRs
and MRIs. In fact, this extended adiabatic
theorem, as a fundamental physical theorem,
could be more broadly applied to any
system—so this research could theoretically
be applied to anything that can be modeled
as a system. However, this isn’t the end
of the line on this research for the Harris
lab; they have a paper forthcoming regarding
the application of this technique to very
different kinds of vibrations.
Our understanding of every branch of
science is constantly evolving and changing.
Just when we think we understand everything
about a field, we realize that particles
can interact with themselves, that the fabric
of space and time can stretch, and that the
universe is expanding. Classical mechanics
is no different; the extended adiabatic
theorem from this study shows just that.
At a certain point, we might as well expect
to be surprised. If you find yourself walking
around a fire pole on the first floor and
ending up on the second, don’t be alarmed.
Bizarre Twilight Zone scenarios like that
are what can help physicist control, bend,
and structure our world—no matter how
strange those truths may be.
ABOUT THE AUTHOR
CHUNYANG DING
CHUNYANG DING is a sophomore Intensive Physics major in Saybrook. He
serves as Operations Manager for the Yale Scientific and as Yale’s co-Head
Delegate to the Ivy Council, and is always boundlessly curious about our
remarkable world.
THE AUTHOR WOULD LIKE TO THANK Professor Harris for his time and
enthusiasm in discussing his research.
FURTHER READING
Doppler, Jörg et al. “Dynamically Encircling an Exceptional Point for
Asymmetric Mode Switching.” Nature 537.7618 (2016): 76–79. Web.
20 Yale Scientific Magazine October 2016 www.yalescientific.org

A MEDICAL MYSTERY
MIND THE GAP
BY JESSICA SCHMERIER • ART BY CATHERINE YANG

FOCUS
public health
Depression, anxiety, bipolar
disorder, schizophrenia. We
all recognize these terms, and
we all know someone struggling with
some form of mental illness. According
to the National Alliance on Mental
Illness (NAMI), mental illness affects
one in five adults in America and threequarters
of these cases begin by the age
of 24. Eighteen percent of American
adults live with anxiety disorders and
seven percent live with depression. In
fact, depression is the leading cause
of disability worldwide. Despite these
startling statistics, no treatment has
proven 100 percent effective in treating
mental illnesses, and because of a lack of
consensus among medical professionals,
patients are suffering.
There are a variety of causes for this
lack of consensus regarding treatment.
For one, there is a lack of consistency in
how different clinical trials measure the
success of various medications. Clinical
trials attempt to quantify the severity of
mental illness as a whole, but they would
be more informative if they evaluated
specific symptoms. It does not help that
the definitions of mental illnesses tend
to be broad and that the presentation
of mental illness varies from patient
to patient. In order to understand why
diagnostic criteria are so inclusive and
the impact this has on treatment, it is
important to consider the history of
categorizing and treating certain mental
illnesses.
Depression medication
Ambiguity with regard to treatment
of depression is particularly striking.
Descriptions of depression date back
millennia. The Ancient Greek physician
Hippocrates described the symptoms
of “melancholia,” and Sigmund Freud
expanded this description in his 1917
paper Mourning and Melancholia. But
it was only in 1980 that the term major
depressive disorder (MDD) was added to
the third edition of the Diagnostic and
Statistical Manual of Mental Disorders
(DSM-III). This marked a departure
from the previous editions that simply
made reference to “depressive reaction”
or to “depressive neurosis,” and came
amid increasing awareness of depression’s
biological underpinnings.
Drugs developed in the 1950s were
known as “tricyclics” for their threering
structure, and although they led
to improvement in 60 to 80 percent
of patients, they came with severe
side effects. Because of this high risk,
scientists were highly motivated to seek
out safer alternatives. The hypothesis
that the neurotransmitter serotonin
played a role in depression led to a new
generation of antidepressants hitting the
market. These antidepressants, known as
selective serotonin reuptake inhibitors
(SSRIs), had far fewer serious side effects
and were massively successful.
Since the arrival of SSRIs, there
have been various other classes of
antidepressants developed, each
associated with their own benefits
and risks, ranging from weight gain
and insomnia to anxiety and sexual
dysfunction. With the development of
these safer classes, antidepressant use
increased 400 percent between 1988
and 2008. Even then, all prescription
antidepressants still come marked with a
black box warning—the strictest warning
the FDA can give—due to the possibility
of increased suicide risk.
Anxiety medication
This treatment ambiguity is also seen
with regard to the treatment of anxiety.
Generalized anxiety disorder (GAD)
was also added to the DSM-III in 1980,
having been subsumed under “anxiety
neurosis” in previous editions of the
manual. References to anxiety date back
to Hippocrates’ descriptions of “hysteria,”
but the modern conception of anxiety
arose with Freud’s theory that anxiety
is a physiological response to unsettling
stimuli.
Prior to the shift of psychiatry to a
biological model in the 1950s and 1960s,
treatments for anxiety mirrored those
used for depression, and many patients
turned to religion, using confession, for
example, to ease their anxiety. But with
the revolution in drug development,
doctors began marketing tranquilizers to
anxiety patients. However, tranquilizers
associated with dependence and severe
side effects including cardiac arrest.
Consequently, another class of anxiolytic
drugs, the benzodiazepines (“benzos”),
soon replaced tranquilizers as the
prescription of choice.
Although tranquilizers and benzos
directly target anxiety, it has also
been shown that many classes of
antidepressants, particularly SSRIs,
also have antianxiety effects. This is
especially important given than anxiety
and depression often co-occur. However,
the side-effects of antidepressants mean
that these treatments are not always the
best option for anxiety patients.
Alternatives to medication
Due to the potentially serious side
effects, many psychiatrists advise
considering non-pharmacological
treatments first. These alternatives, while
technically safer, are accompanied by
their own advantages and disadvantages
depending on the patient, further
complicating the dialogue regarding
optimal treatment methods. Some
common alternative treatments that
have been shown to be effective are talk
therapy, exercise, dietary changes and
yoga or meditation.
Studies have shown that in many
cases, talk therapy can be just as
effective as medication. Research has
also demonstrated the effectiveness
of lifestyle changes in treating mental
illness. Cochrane, a non-government
organization that compiles medical
information, periodically releases
reports through its Depression, Anxiety
and Neurosis Review Group. According
to the most recent report in 2013,
when compared to psychological or
pharmacological therapies, exercise
is equally effective. However, patients
often fail to realize that lifestyle changes
such as exercise need to be treated just
like medication. Too much or too little
exercise or failure to establish a consistent
routine can significantly reduce the
benefits provided by lifestyle changes. In
other words, just as with drugs, dosage
and compliance matters.
Why drugs?
Both medical and sociocultural
factors are important in explaining
why medication tends to be the favored
option. The safety profile of drugs
have made huge advances over the
past decades. Modern antidepressants
22 Yale Scientific Magazine October 2016 www.yalescientific.org

have far fewer side effects, and modern
antianxiety drugs carry a much lower risk
of addiction. As such, doctors are more
comfortable prescribing, and patients
are more comfortable with taking these
comparatively safer medications.
Media also plays a large role.
Pharmaceutical giants spend billions of
dollars on drug advertising, and these
ads are designed to highlight the benefits
while speeding through the risks. The
general population sees these ads and
sees miracle cures for mental health
problems.
A final major consideration in the
choice between medication and lifestyle
change is time and money. Patients have
the choice between taking a pill, which
takes two seconds and costs them next
to nothing thanks to modern insurance
coverage, and spending hours each week
exercising or hundreds of dollars on
therapy sessions.
A patient-centric approach
The lack of consensus regarding the
optimal treatment for mental illnesses
makes it difficult to give concrete
recommendations. This lack of consensus
stems partially from the inconsistencies
in how improvement due to any given
intervention is measured. For example,
previous drug company-sponsored
research on medications showed that
only 44 percent of antidepressant trials
resulted in significant improvements in
patients’ symptoms. However, a 2015
report pointed out the fact that these
trials used the Hamilton Depression
Rating Scale (HDRS), a 17-item scale
that was developed in the 1950s and
is thus rather outdated. When the
team re-analyzed the data, looking for
changes in only one element of the scale,
depressed mood, it was shown that 91
percent of trials resulted in significant
improvement.
A similar problem arises when
physicians attempt to determine which
treatment would be most appropriate
for a given patient. “[Psychiatrists]
understand that there is no unitary
solution for whatever a person presents
with… and it is rare that one thing
works perfectly,” said Michael Sernyak, a
professor of psychiatry at Yale and CEO
of the Connecticut Mental Health Center.
www.yalescientific.org
T h e
DSM-
5 lists
n i n e
s y m p t o m s
of major
depression, and a
patient must meet five
to qualify for a diagnosis.
For a diagnosis of GAD, a
patient must meet only three of six
listed symptoms. Given the countless
possible combinations of symptoms, it is
clear that not all depression or anxiety
is equal. As such, it makes sense that
different treatments might be more
effective for different patients. Very little
research has been done on the effects of
medications on specific symptoms, and
research has shown that many patients
benefit from a multifactorial approach
to treatment consisting of medication,
psychotherapy and lifestyle changes.
Treatments for mental illnesses are not
one-size-fits-all. Each patient presents
with a specific combination of symptoms
and may respond to certain treatments
more than
others. When
considering moving
forward with a treatment
plan, patients should be presented
with all options, and physicians should
tailor decisions based on the unique
characteristics of each patient rather
than on statistics from studies that are
broad-based and thus not necessarily
applicable to the patient. In other words,
for the best results, doctors should
always think of the patient, not the
numbers.
October 2016
Yale Scientific Magazine
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astronomy
FEATURE
RAIN ON BLACK HOLES
Exploring what feeds black holes
►BY URMILA CHADAYAMMURI
Nearly every observed galaxy has a giant black hole at its
center. Clues lead us to believe that these monsters, weighing
as much as a billion suns, consume copious amounts of gas
from their environment and occasionally spew out some of
it as powerful jets, bubbles, or heat. How exactly they do
this, however, has been a mystery.
“For over half a century, people have simplified
supermassive black hole accretion as a smooth spherical
inflow of very hot plasma,” said Grant Tremblay, a
postdoctoral researcher at Yale. This was not necessarily a
bad idea: gas that falls into a gravitational field gets heated
up, and the stronger the gravity, the higher the temperature.
For a dense region like a cluster of galaxies, this temperature
is over a hundred million degrees Celsius, ten times the
temperature of the Sun’s core. At these temperatures, the gas
is mostly ionized and is called plasma. Since the black hole
is at the cluster center, plasma surrounds it on all sides, so it
is reasonable to assume that the plasma falls into the black
hole from all sides. Consequently, warm, spherical accretion
sounds like a credible explanation.
But there is another phenomenon to consider, called
thermal bremsstrahlung or “braking radiation.” In hot
plasma, electrons zoom freely around until they come close
to positively charged ions; then, they change trajectories and
lose energy. Because of lost energy, hot and dense gases don’t
stay hot indefinitely, so no long-term reservoir of warm gas
exists to feed a black hole. We can observe the lost energy
by measuring the X-ray emissions from galaxy clusters.
“The cluster had to lose energy to give us this photon,” said
Tremblay. “Every X-ray observation of a galaxy cluster is
actually a direct measurement of galaxy cooling.”
In fact, Professor Megan Donahue of Michigan State
University, who is a co-author on the paper, explained that
the gas near the center of galaxies should actually be cooling
rapidly. “The gas near the centers of galaxies is very dense,”
she explained. As the gas is so dense, electrons in the cloud
should collide more frequently with positive ions, emitting
X-ray radiation and cooling down. The cluster cores should
thus be brimming with cold gas, which in turn should form
many stars. Instead, astronomers found that the core was
mysteriously warm and starless. This discovery motivated
theorists to propose a new model, in which central black
holes spit energy back into their environment; they named
these black holes active galactic nuclei.
So, if hot gas doesn’t feed black holes, what does? Donahue
says the key is realizing that not all gas is the same, neither
uniformly warm nor uniformly cold gas feeds the black
hole. Instead, cold clouds precipitate out of the warm gas,
and these clouds can then rain down on the black hole.
“It’s like this big rain cloud that can produce raindrops that
cool very rapidly,” said Donahue. Just as raindrops falling
through the Earth’s atmosphere don’t heat up and evaporate,
so too can the cold clouds maintain their structure all the
way from where they formed to the cluster core. Donahue’s
team designed the model by observing galaxy clusters but
could not detect the drops—until now.
In a paper published in Nature this June, the team
reported observing the elusive drops from the Atacama
Large Millimeter Array (ALMA), a collection of telescopes
located in the Atacama Desert. ALMA can accurately
measure the position and velocity of celestial objects. The
telescope’s resolution is so fine it could see a dime held up
in New Haven from where it stands in Chile. Working off of
Donahue’s idea that the cold and warm gas lived together,
the team tried to observe the cold, star-forming gas in the
galaxy cluster Abell 2597.
The supermassive black hole in the center of this galaxy
accumulates a lot of matter but can only do so at a limited
rate. The remaining material settles in a large disk around
the black hole. Different layers of this rotating disk generate
friction as they rub against each other, releasing light and
heat. The center of the galaxy cluster should have been as
bright as a light bulb, but it was obscured by a shadow.
These shadows were cast by the elusive cold gas clumps,
which absorb certain wavelengths of light. “This is one of
the first really big pieces of unambiguous evidence for cold
molecular clouds that are falling towards a supermassive
black hole,” says Tremblay.
The clouds absorbed different wavelengths of light
depending on how fast they were moving relative to the
black hole. Tremblay was thus able to determine that the
clouds were descending towards the black hole at about
67,000 miles an hour. “These things are basically on ballistic
trajectories falling towards the black hole,” said Tremblay.
This Nature paper is just the first step towards answering
broader questions. How is cold, star-forming gas distributed
in galaxies? How is this process shaped by active galactic
nuclei? Donahue’s research demonstrated that this gas exists
in little clouds, but there’s one last fascinating detail—the
clouds themselves are arranged in extended filaments as
long as the cluster itself.
Tremblay thinks pasta is a better analogy for the underlying
physics. After the first round of cold gas falls into the black
hole, the galactic nucleus releases jets and bubbles of energy.
These bubbles, he says, “drag cold gas out of the center of the
galaxy, like pulling spaghetti out of hot water.”
www.yalescientific.org
October 2016
Yale Scientific Magazine
25

FEATURE
medicine
ANTIBODIES AGAINST ALZHEIMER’S
New approach shows promise in phase I trials
►BY NATALIA ZALIZNYAK
Approximately every minute, someone in the United
States develops Alzheimer’s disease. With over five million
Americans currently diagnosed, Alzheimer’s is the
sixth leading cause of death in the United States and is
associated with declines in memory and cognitive function.
The disease takes an immense physical, emotional,
and monetary toll on patients and their caregivers, with
hardship only increasing as the illness progresses.
There is no cure for Alzheimer’s disease, and until recently
the outlook for treatment was grim. In a recent
study led by researchers at Biogen, a biotechnology company
focused on treating neurological diseases, scientists
used a human antibody to target and destroy amyloid-β,
a large molecule associated with the neurological symptoms
of Alzheimer’s. Within the brains of Alzheimer’s
patients, amyloid-β molecules aggregate in two different
forms: large, insoluble plaques and smaller, soluble
complexes. Of these, the latter have been demonstrated
to be neurotoxic and causative of cognitive dysfunction.
These soluble complexes bind to the junctions between
neurons, called synapses, and interfere with their ability
to communicate with other cells. Furthermore, binding
by amyloid-β may elicit an adverse immune response,
causing the body to destroy its own non-communicating
neurons.
Previous attempts at harnessing the disease-fighting
ability of the immune system to treat Alzheimer’s have
been ineffective. Aducanumab, the antibody developed
by researchers, binds effectively to both soluble and insoluble
aggregates of amyloid-β and appears to successfully
reduce plaque size in human clinical trials. These
amyloid-β plaques are not implicated as the primary
cause of Alzheimer’s symptoms, but their size corresponds
to the amount amyloid-β in a patient’s brain.
Since plaque size is more easily measured than the concentration
of soluble amyloid-β complexes, researchers
use plaques to monitor disease progression. In fact, the
aducanumab-induced decreases in plaque size observed
in this study were accompanied by astounding changes
in disease progression.
After initial biochemical experiments demonstrated
that the antibody could bind to amyloid-β, researchers
tested aducanumab in mice. The mouse trials confirmed
that the antibody was able to enter the brain and clear
amyloid-β aggregates. After obtaining these encouraging
results, researchers began human clinical trials. The recently
completed phase-one trials included a relatively
small number of participants but appeared to show noteworthy
results. After receiving aducanumab for one year,
patients showed significant reductions in amyloid-β
plaque size and maintained their cognitive abilities and
memory better than those given a placebo.
Since the trial’s conclusion of in 2015, Biogen’s aducanumab
research has increased in scale; researchers
are currently testing the therapy in two large clinical
trials. They aim to gather more information about the
antibody, including its ideal dosage and potential side
effects. Christopher Van Dyck, director of Yale’s Alzheimer’s
Disease Research Center and the principal investigator
for aducanumab trials at Yale, believes that aducanumab
will likely enter the medical market if the same
efficacy of treatment can replicated in these larger trials.
“I think that these results were unprecedented in many
ways in our field, and I think that they are game-changing,”
Van Dyck explained.
Although the initial clinical trial was a small, early-phase
study, it accomplished something groundbreaking.
It provided solid evidence for the effectiveness of
immunotherapy against Alzheimer’s disease. Future
medical and pharmacological research will undoubtedly
incorporate this valuable insight in the battle against
Alzheimer’s.
IMAGE COURTESY OF WIKIMEDIA COMMONS
►Plaques in the brain of a senile patient are consistent with the
characteristics of amyloid-β.
26 Yale Scientific Magazine October 2016 www.yalescientific.org

materials science
FEATURE
A CLOTHING COOL DOWN
Innovative textile facilitates heat loss
►BY CAROLINE AYINON
IMAGE COURTESY OF WIKIMEDIA COMMONS
►Polyethylene, the material used for food packaging, was the
inspiration for the nanoporous textile design.
After another sweltering summer, a group of Stanford engineers
may have finally found a way to beat the heat. The research
team, working in collaboration with several laboratories,
has developed a new low-cost, plastic-based fabric that, when
used in clothing, can cool the wearer’s skin. In addition to increasing
comfort in high heat, the material may also decrease
energy consumption by allowing people to rely less on air conditioning.
Up to this point, engineers have focused on designing fabrics
that allow perspiration to evaporate. Although breathability
does improve comfort, it does not eliminate the heat trapped
between skin and the fabric. Our bodies naturally emit heat in
the form of infrared radiation, invisible and benign waves of
energy that we feel as heat. On a typical day indoors, infrared
radiation contributes to about 50 percent of total body heat.
The newly designed fabric lets perspiration evaporate, as many
other fabrics already do, but it also allows infrared radiation to
escape.
The innovative textile was inspired by polyethylene (PE), the
plastic material found in kitchen wrap. The PE in plastic wrap,
however, is unsuitable for clothing; it is transparent and impermeable
to moisture. To address these issues, the team proposed
nano-porous PE, a variant of polyethylene with pores comparable
in size to the wavelength of visible light. Introduction of
these pores into PE resulted in a material that is opaque, but
still lets infrared radiation pass through. Next, they further engineered
the nano-pores to better resemble a clothing material
and to improve water and air permeability. Finally, they created
a better textile by layering nano-PE with a cotton mesh, giving
the fabric more thickness and strength.
The researchers explored the properties of nano-PE by comparing
it to cotton cloth. They placed samples of each material
on a device simulating human skin and measured the amount
of heat each fabric trapped. “Bare skin’ with no textile has a
temperature of 33.5 °C, and with cotton the temperature rises
to 37.0 °C. With Nano-PE, it only rises 0.8 [degrees] to 34.3 °C,”
explained Alex Song, a leading scientist on the project. These
results are promising; the newly engineered textile is able to
keep the skin-simulating device several degrees cooler than the
cotton cloth.
Nano-PE could significantly increase the comfort of outdoor
workers, athletes, and people living in hot climates. In fact, it
could lower the risk of heat-related illnesses including heat exhaustion
and heat stroke. However, the researchers are more
focused on the fabric’s potential in indoor use, where it could
be important to resolving the world’s growing energy concerns.
The researchers predict that wearing clothing made from their
new textile would decrease a person’s need to turn on fans and
air conditioners. Previous research has found that a 1 ° to 4 °C
increase in set point temperature can save 7 to 45 percent of
energy consumed by air conditioning. If the new product becomes
widely used, it might give commercial buildings the opportunity
to turn down central air conditioning, reducing energy
consumption on a large scale.
Technology-to-market has always been a major focus of the
project, according to Song, so the research team is continuing
to modify the fabric, adding more colors and textures. Before
the product is made commercially available, the team must
also reduce the cost of mass-production. The team is currently
working with industrial partners to push forward the technology,
so hopefully it will be available on the market soon.
Though relatively simple in design, the group’s innovation
has revolutionized the field of textile engineering. By targeting
trapped heat, instead of perspiration, they have presented a new
solution to an old problem. As they further adapt and build on
their design, we may soon find ourselves relying less on air conditioners
and more on clothing that can literally cool.
IMAGE COURTESY OF WIKIMEDIA COMMONS
►The nanoporous fabric allows infrared radiation to pass
through, while absorbing visible light.
www.yalescientific.org
October 2016
Yale Scientific Magazine
27

FEATURE
engineering
The Octobot
By Claire Carroll
Art by Sida Tang
a robot with a softer touch
28 Yale Scientific Magazine October 2016 www.yalescientific.org

The Robot” dance is all about restricted, unnatural motion.
Robotic systems are often mocked for their painful inability
to comprehend nuance or intent in logical rules. In the Star
War’s universe, AT-ATs move inexorably forward, yet are tripped up
by their inability to adapt. Robots, in our fiction and in our factories,
have always been rigid. Yet emerging research in the field of softrobotics
hints that truly flexible robots could be on the horizon.
This harbinger of soft-robotics, the Octobot, looks like a children’s
toy. It is a squishy, colorful plastic octopus that is about the size of
a pack of gum. It even waves its arms in a rudimentary dance. Yet
this friendly fellow, designed at the Wyss Institute for Biologically
Inspired Engineering at Harvard University, is a proof-of-concept
grown from years of research that could revolutionize the ways we
can use robots. The design was not a mere accident but an homage
to the animal it resembles. “We knew early on that this would be a
legged system. We do not claim to mimic the behavior of the complex
creature, but, because it serves as an inspiration for the entire field of
soft-robotics, we wanted to use this form as a tribute to the endlessly
fascinating creature,” said Michael Wehner, a research fellow at Wyss
and co-first author of the paper.
Before the Octobot, the best soft-robotocists could hope for was a
soft-shelled robotic system containing traditional silicon and metal
circuitry or a soft robot tethered to an external battery. Traditional
power supplies and logic circuits are always made of hard materials,
which is why the Octobot required massive innovation. The Octobot
is constructed from entirely soft components and is autonomous.
To accomplish this, designers utilized a pressure-based hydrogen
peroxide circuit, instead of a traditional electrical circuit and power
supply; instead of electricity powering the Octobot, rising gaseous
pressure pushes the action forward. The research team, led by
professors Robert Wood and Jennifer Lewis, has been working on the
Octobot for about three years, perfecting its imaginative fuel system,
logic circuit, and fabrication.
Researchers fabricated the Octobot using cutting-edge 3D-printing
technology. Previous methods of 3D printing could not fulfill
their needs: soft sensors and circuits are notoriously difficult to
manufacture and involve labor-intensive production and multistep
insertion into the robot. But Ryan Truby, a graduate student
at Wyss and the other co-first author of the Octobot paper, led
Professor Lewis’s lab to pioneer a new technology called embedded
3D-printing (EMB3D). EMB3D uses conductive carbon-based inks
to draw circuits into silicon, using a needle-based setup reminiscent
of a tattoo gun. The conductive ink can carry electricity like wires,
but, in this case, it is embedded with a slight tunnel to enable gas to
travel. With EMB3D, Octobot researchers could draw-in circuits after
finishing the main body piece, enabling precise, smooth lines to form
the Octobot. Wehner intially had doubts about the Octobot design,
citing difficulties in manufacturing, but according to Wehner, “Ryan
[Truby] was confident that he could build what we needed. Together,
we moved forward to develop the Octobot.”
The Octobot could not run on traditional electrical power, since
that would require hard components. Researchers turned to the
microfluid logic circuit, a circuit developed by Wyss professor George
Whitesides, which relies on pressure instead of electricity. Within the
circuit, a slow chemical reaction converts liquid hydrogen peroxide
into hydrogen and oxygen gases, creating a pressure from the gas that
inflates channels in the Octobot’s legs. The logic circuit acts like a road
map and allows the Octobot to move a certain set of legs at a time,
engineering
FEATURE
based on the pressure. The peroxide is stored in two reservoirs, and
when it comes in contact with platinum embedded in the circuit, the
peroxide turns to gas in a typical redox reaction. Separate channels
direct the gas to the different limbs of the robot, allowing it to perform
its dance.
The logical channels are analogous to wires, and the fuel reservoirs
are similar to batteries. The channels in the microfluidic logic were
100x100 micron, compared to electrical circuits which can be built
1000x smaller. Wehner compared the fueling process to filling a
car’s gas tank: “We have a supply of the hydrogen peroxide fuel. We
attach two tubes to the Octobot, fill the Octobot with fuel, and finally
remove the tubes. When the bot is empty, it can be refilled using the
same process.” The Octobot can run for approximately eight minutes
on one milliliter of fuel. While this seems like a small capacity, it is
actually large and cumbersome when compared with electronics; the
channels in the microfluidic logic are 100x100 micron, compared to
electrical circuits which can be built 1000x smaller.
The current circuit is simple, so the Octobot’s motions are not
very precise. When pressure builds up in one half of the circuit, it
triggers the reaction in the second half. The Octobot exists in one
of two states, with one half of its legs ‘raised’ or the other, depending
on the pressure from its fuel reservoirs. Creating more complicated
soft-robots using this technology will be no small task, but Wehner
is confident that the soft-robotics community is up to the challenge,
since there have been large community advances in embedded
systems. “One of the primary advantages of this fabrication technique
is that it allows embedded microfluidics…We hope that, in addition
to our future efforts, the rest of the community will use this approach
to build novel devices that we can’t even imagine.” At this time, the
Wood and Lewis labs plan to continue collaborating but are open to
other partnerships. “We love working with others. It is the best way
to develop even more complex systems and learn even more than we
could alone,” said Wehner.
The Octobot is a triumph for soft-robotics, but it is not a solution.
In order to create an Octobot that can perform complex tasks,
researchers must overcome space constraints, increase the complexity
of the logic circuit, direct the gas release more precisely, and speed
up the peroxide circuit, which is currently quite slow. The team at
Wyss is already at work improving the Octobot to incorporate sensors
and a more precise control strategy. They hope to generate more
sophisticated behavior and even create a soft robot capable of reacting
to the environment.
But, for now, this cute little harbinger is content to keep dancing.
IMAGE COURTESY OF LORI SANDERS
►This cute little bot is powered by the release of pressurized gases.
www.yalescientific.org
October 2016
Yale Scientific Magazine
29

FEATURE
microbiology
BY DIANE RAFIZADEH
ART BY ANUSHA BISHOP
PATHOGEN
PROTECTOR?
OR
SALMONELLA SLAMS CANCER
30 Yale Scientific Magazine October 2016 www.yalescientific.org

microbiology
FEATURE
Synthetic biology, an emerging and fascinating field at the
crossroads of natural and technical science, once served
only as fodder for sci-fi films. And, while it’s doubtful that
scientists are working on the next Frankenstein, the field has
since progressed rapidly: Researchers are now designing and
manipulating biological molecules, engineering life forms to
do anything from delivering chemicals to producing biofuels.
Most recently, a lab at the University of California, San
Diego (UCSD) engineered Salmonella, a common pathogenic
bacterium often associated with food poisoning, to fight
cancer. It sounds counterintuitive, since we usually think of
Salmonella as dangerous, but the magic of it lies in the science
behind the bacteria’s mode of action.
The researchers used the bacteria to produce and transport
a confirmed anti-cancer chemical, Haemolysin E, to cancerous
cells. Haemolysin E destroys cancer cells, and mammalian
cells in general, by creating pores in the cells to cause them to
lyse, or rupture and release their cellular contents. Since the
bacteria release the chemical directly to the cancer site, this
helps prevent the toxin from spreading to healthy cells. The
researchers programmed Salmonella to produce Haemolysin E
by inserting a plasmid, or a small piece of circular DNA, with
the Haemolysin E gene into the bacterial DNA. The bacteria
could then produce the toxin independently and in sufficient
quantities.
Haemolysin E is not a newly discovered toxin, but the
Salmonella research at the UCSD lab is notable for its use of
bacteria as a vector for drug delivery. Jeff Hasty, who heads the
lab, and his team chose to work with bacteria because of a fairly
recent discovery that bacteria actually live and thrive inside of
tumors. Though scientists aren’t entirely certain why this is the
case, one theory is that developing tumors allow bacteria to
enter through the blood when the tumor is building its system
of blood vessels. The researchers concluded that bacteria could
effectively transport materials because they naturally localize
to tumors, are grown quickly, and can be easily manipulated
by genetic engineering. The bacterial strains they used were
attenuated to be non-pathogenic and had been tested for safety
in human clinical trials.
Once the Salmonella arrive at the treatment site, Haemolysin
E must exit the bacteria to make contact with cancer cells.
To accomplish this, the researchers programmed the cells
to lyse after reaching a minimum population density. They
engineered a sensing system within the cells so that when the
bacteria reached a certain population density, they released
small, diffusible molecules that signaled it was time to lyse.
Lysis releases all of the cells’ contents, including the toxin that
then acts on the tumor. But the process doesn’t stop there, as
a small number of unlysed cells remains to repopulate the site
and repeat the cycle: they proliferate, reach a high population
density, lyse, and recolonize. The bacterial population acts like
a clock, cyclically pulsing up to the threshold population and
back down again at the appropriate times.
Working out the kinks of this cycle was a major challenge for
the researchers who hope to design a better way to stabilize the
circuit. “Ideally, we would want the bacteria to retain the circuit
for a long period of time with a reduced risk of mutations,”
said Omar Din, a UCSD graduate student who performed the
Salmonella research. Bacteria have the potential to mutate
quickly, and these mutations can interfere with their function.
To prove their method was actually effective against cancer,
the researchers first tested the genetically modified bacteria in
vitro, in a culture dish, by growing human cancer cells with the
engineered bacteria. The cancer cells died when the bacterial
cells were lysed, indicating successful toxin delivery. Next, the
researchers tested the agent in mice with liver tumors. Test mice
received either an oral dose of bacteria, chemotherapy, or both
treatments. Though the bacteria-only treatment wasn’t very
effective, mice who received both treatments had less tumor
activity and a greater survival rate than those who received
either single treatment, suggesting that bacterial treatment
is most effective when combined with chemotherapy. Hasty
predicts that combined treatment works best because each
individual treatment targets a different area. Chemotherapy is
most effective in the oxygen-rich environment outside tumors,
while the bacteria inhabit the area inside tumors.
For now, Hasty’s lab found that their engineered Salmonella
decreased tumor sizes in mice for approximately twenty days
before the tumors began to grow again, significantly increasing
the mice’s life expectancies. However, this research has yet
to provide a method for treating cancer in humans, since
additional research must first determine the host’s response
to the treatment and as well as its long-term effectiveness.
The work done in Hasty’s lab is promising because the lysis
steps keep the bacterial population low, minimizing potential
for a negative host response. Their research sets a precedent
for the future of synthetic biology: Hasty’s lab has identified
Salmonella as a platform for delivering chemicals to diseased
cells, exploiting the bacteria’s tendency to localize and flourish
in a cancer-cell environment.
“We hope to highlight the utility of using synthetic biology
to engineer bacteria for therapeutic purposes,” said Din. “This
will ideally include collaboration between groups working
in synthetic biology and cancer research.” Further work
with Salmonella may improve the treatment to maximize
effectiveness and further prove safety. Once that has been done,
scientists can test how best to administer the treatment and
at what dosage. If all of those pieces fall into place, bacterial
therapy could potentially reach human clinical trials in a few
years.
The momentum of bacterial therapy lies in its versatility: it
doesn’t stop at cancer. “Bacteria can theoretically deliver any
protein or molecule they are capable of producing,” said Din.
These molecules could range from toxins like Haemolysin E
to the proteins normally produced in mammalian cells. For
example, bacteria could be engineered to deliver chemokines,
a type of signaling molecule that attracts white blood cells
and other immune system cells to an infected site in the body.
This case presents an interesting paradox: bacteria can treat an
infection instead of causing it.
The Salmonella research at UCSD exemplifies synthetic
biology’s ability to engineer living things to synthesize a
product or get a job done, which is certainly an improvement
from the era of Mary Shelley’s science-fiction masterpiece.
www.yalescientific.org
October 2016
Yale Scientific Magazine
31

FEATURE
biology
HERE COMES THE SUN
by ELLIE HANDLER | art by EMMA HEALY
When the sun creeps up over the horizon at dawn, blanketing
the world in its yellow glow, sunflowers have already
turned to face its morning rays. As it traces its path across
the sky, the plants follow, tracking the sun’s motion from
east to west throughout the day. Only after the sun has
set do they slowly return to their starting positions. This
phenomenon, known as heliotropism, has been observed
in fields of sunflowers for ages. Even Charles Darwin performed
early experiments on the movement of plants. He
hypothesized that when light hits the tip of the plants, it
triggers the release of hormones that guide the direction
of growth. Some experimentation had been done based on
this early idea, but no conclusive evidence for one of many
theories for heliotropism had been found.
More recently, heliotropism in sunflowers piqued the
interest of Stacey Harmer, professor of plant biology at
UC Davis. Harmer studies plant circadian rhythms, the
internal systems that coordinate and time behavior, and
she thought that these rhythms might guide sunflowers’
motions, especially at night. Heliotropism has largely been
explained as a direct response to sunlight, but researchers
have mostly ignored what happens at night, when environmental
signaling is absent. With the help of sunflower expert
Benjamin Blackman, now a professor at UC Berkeley,
Harmer began observing sunflowers, studying how they
track the sun and how they adjust at nighttime. The researchers
also explored the benefits of heliotropism and
related phenomena.
Plants’ motion was previously understood only in the
context of phototropism, a plant’s tendency to grow towards
light. Photoreceptors, the molecules that detect light,
identify light sources and alter the production of auxin, a
growth hormone, within plant cells. Growth is then accelerated
on the shaded side of a stalk, causing a bend towards
the light. A similar process occurs in sunflowers in response
to daily time cycles. “During the day, when the east side
grows faster than the west side, the plant gradually grows to
the west,” said Hagop Atamian, a post-doc in Harmer’s lab.
The opposite pattern occurs at night and reorients the plant
towards the east. This is a well-recorded phenomenon, but
Harmer and Blackman made a new discovery: these patterns,
initially regulated by sunlight, are ingrained into the
plant’s circadian clock. “The plant is running by the clock
and not directly by the light input,” said Atamian. This is
what allows plants to return to facing the east during the
night, when the photoreceptors receive no input.
To study heliotropism, the researchers manipulated the
environments and orientations of cultivated sunflowers.
Atamian initially grew sunflowers outside in a field: “They
were tracking the sun nicely during the day and returning
at night,” he said. Next, the plants were brought inside to
a growth chamber with unidirectional overhead lighting.
“They moved back and forth with the same directions as
in the field,” said Harmer. Remarkably, the plants remembered
the sun’s motion and continued to track that motion
for several days after moving inside. The results corroborated
Harmer’s theory that circadian clocks govern directional
growth and movement.
“One characteristic of the circadian clock is that it can be
trained or reset by the environmental conditions,” noted
Atamian. Plants ceased to exhibit heliotropism after a couple
days spent inside, but when brought back to the field,
they resumed their tracking behavior. The flexibility of
circadian clocks allows plants to adjust their timing to the
season. “The length of the light-dark cycle is adjusting the
clock continuously so that the plant knows that nights are
longer in fall than in spring,” Atamian explained.
The researchers also grew sunflower plants in growth
chambers with different conditions. One group of sunflowers
received only overhead light and grew completely
vertically, demonstrating that tropism depends on an environmental
input. Another sample of plants was grown beneath
an arc of lights that were turned on and off to create
a sun-like motion. Plants grown under these conditions,
and with a 24-hour light-dark cycle, tracked the motion of
the light like those grown outdoors. “If we altered that time,
the plants didn’t track as well,” said Harmer. The need for
a 24-hour clock has been seen in other organisms as well.
“It’s already known for a lot of systems that you have to
have a match between the environment and internal clock,”
Harmer added.
The ability to track the sun appears to significantly impact
plant growth. A sample of plants was grown outside
and turned 180 degrees every morning so they could not
32 Yale Scientific Magazine October 2016 www.yalescientific.org

iology
FEATURE
establish a normal heliotropism pattern. “These plants
didn’t grow as well as normal plants,” said Atamian. Their
leaves were smaller, and they had less overall biomass than
plants whose orientation was undisrupted. Heliotropism is
important to a plant’s growth and success, since maintaining
a specific orientation to the sun’s rays improves energy
absorption.
Yale professor in mechanical engineering, Madhusudhan
Venkadesan, thinks that understanding the energy absorption
of sunflowers could improve solar panel efficiency.
“Solar panels lose 30% of the energy if they don’t track the
sun, so it’s a big deal,” said Venkadesan.
►East-facing sunflowers heat up more rapidly in the morning than do west-facing flowers.
IMAGE COURTESY OF STACEY HARMER
Venkadesan has been conversing with Harmer and Atamian
about the physical motion of sunflowers. He wonders
about the complex motions that might arise from the
sun’s migration from north to south, in addition to east to
west. “This would give a bending-twisting coupling,” said
Venkadesan. Plants might face growth problems from this
motion.
All the researches involved concluded that heliotropism
and overall growth is quite complex. For example, after
sunflowers reach maturity and produce flowers, they do not
track the sun; the flowers all face east. The research team
wondered about the effects of this phenomenon and studied
eastward plant orientation. They grew sunflowers outside
in pots and switched the orientation of half the plants
when they reached maturity. The two groups, one facing
east and one west, were noticeably different in their temperature
and number of pollinator visits. “East-facing heads
warmed up more quickly in the morning,” said Blackman.
After videotaping flowers to count the number of received
pollinators, such as bees and butterflies, researchers discovered
that pollinators visited east-facing flowers much more
frequently, especially in the morning.
Why this discrepancy in pollination exists is still unknown,
but based on heliotropism research in other plants,
researchers hypothesized it might be related to the observed
differences in temperature. To test this, they used
a device that measures the temperature of the east-facing
flowers and correspondingly heats the west-facing flowers.
Afterwards, the west-facing plants had more pollinator visits,
but still fewer than those facing east. “The result was not
exactly what we were expecting, but at least it was in the
right direction,” Blackman said.
This study has helped to shed light on the complexity of
sunflower heliotropism. Going forward, Blackman is interested
in studying why insects prefer to pollinate warmer
flowers and what genetic changes lead to variation in heliotropism.
Harmer is curious about the biological mechanism
that coordinates interactions between circadian clocks and
environmental inputs. “I’m really interested in how this
works at a molecular level,” she said. “Most of what we’ve
done so far was pretty physiological.” She’s hopeful that the
sunflower can be used as a model for understanding how
environmental inputs and the circadian clock constantly
interact with each other and regulate behavior. The new
knowledge from this study will be applied to a host of fields
for further research.
www.yalescientific.org
October 2016
Yale Scientific Magazine
33

FACT-CHECKING
RED
KING
THEORY
SCIENCE
►BY JESSICA TRINH
A queen ant chews through the thorns of the acacia plant. Once
inside, she finds shelter to lay her eggs. Outside the thorn, more
ants smell rich nectar dripping from the leaves, and after tasting
the sweet sap, they are hooked. Soon, the plant houses an entire
colony of ants, providing them with a nesting site and food. In
return, the ants act as the plant’s bodyguards, aggressively fending
off herbivores with their painful stings. These two species are in
a mutualistic relationship—a partnership where each organism
benefits from the other’s activities—and life seems too good to
change.
And maybe life doesn’t change—at least, not rapidly. According
to a scientific theory called the Red King effect, organisms
in mutualistic relationships evolve slowly to maintain their
beneficial relationship. The theory is an offshoot of the Red
Queen Hypothesis, which proposes that organisms must
constantly evolve to survive because of interspecies competition
and predation. For example, if a rabbit population evolves to
better escape foxes, then the foxes must adapt to better catch the
rabbit or go extinct from starvation. The selective pressures on
both species lead to faster evolutionary rates.
While the Red Queen Hypothesis explains predator-prey
relationships, the Red King effect relates specifically to mutualism.
“When two organisms are working together, rather than fighting
each other, then maybe they should be evolving more slowly, so
as not to outrun each other,” said Benjamin Rubin, lead author
of a study at the University of Chicago on the subject. Rubin
studied a mutualistic ant-plant relationship, observing ants that
take shelter in the hollow thorns, trunks, or leafstalks of plants
www.yalescientific.org
IMAGES COURTESY OF ALEX WILD
► Certain species of ants have been known to form mutualistic
relationships with plants. The Red King effect attempts to explain how
these relationships can interact with evolution.
while aggressively patrolling and protecting against herbivores.
According to the Red King effect, Rubin should have witnessed a
slower rate of evolution, but he did not.
Rubin’s team did not originally plan to study the Red King
effect. They were comparing the DNA of several closely-related
mutualist and non-mutualist ant species, when, without even
looking for it, they detected a pattern: the mutualists evolved
faster. “Just trying to explain that pattern, that phenomenon, led
me to explore the Red King effect,” Rubin said.
To explore this phenomenon, Rubin’s team used a field of
biological research called comparative genomics, where they
compared the DNA sequences of different species. Genetic
mutations drive evolution by creating the heritable variation
necessary for natural selection. Therefore, by observing the
number of accumulated sequence changes, or mutations, since
a common ancestor, researchers can predict evolutionary rates.
This type of research would not have been possible 10 years
ago. “Each genome used to cost millions of dollars and years of
effort, but with recent advances in technology, we are now able
to sequence full genomes relatively easily,” said Rubin. “It’s all
done on the computer and through programming. In addition
to needing the sequencing technology, we also need certain
computing technology in order to do any of this.”
Rubin’s discovery directly contradicts the Red King effect.
However, there is not enough information to prove whether
mutualism accelerates or slows evolution, since the underlying
causes are still unknown. Rubin plans to explore potential
mechanisms in future research, but, in the meantime, he has
his theories. For example, the biological interaction between
plants and ants might increase selection pressures: By being in
an intimate, mutualistic relationship, each species must adapt not
only to the selective pressures on them, but with the organisms
they closely interact with, as well. A dietary effect may also
contribute. In this mutualistic relationship, ants rely on the
food resources provided by the plants. The nectar contains an
enzyme called chitinase that inhibits one of the ant’s digestive
proteins, preventing them from breaking down other sources of
sucrose. Due to their reliance on this nectar, the ants must adapt
to accommodate changes in the chemical makeup of their food.
Consequentially, these mutualistic ants seem to accumulate more
mutations and evolve faster.
By challenging the Red King effect, this study has brought
attention to evolutionary relationships and opened the potential
for further research. Rubin plans to continue studying the
effects of behavior on the genome. While the biology behind the
differences observed in mutualist and non-mutualist ant species
is uncertain, one thing is for sure in this co-evolutionary race: it
pays off to help others.
October 2016
Yale Scientific Magazine
34

BLAST
from
the
PAST
Ancient Analgesics: A Brief History of Opioids
►BY GRACE NIEWIJK
In 1898, scientists announced the synthesis of a new, allegedly
non-addictive cough suppressant called heroin. Advertisements
proudly proclaimed that heroin was “superior
in all respects” to opium, morphine, and codeine and that users
would be completely free from any chemical dependence.
While these claims have since been proven false, and heroin is
no longer available over-the-counter, modern medicine continues
to have a love-hate relationship with opioid painkillers.
Opioids are a class of drugs derived from opium, a naturally
occurring compound in poppies that produces euphoria, pain
relief, and sedation in humans. These drugs have been used
for centuries, and even though medical professionals now
recognize their side effects and the potential for abuse, they
remain a staple of modern pain management. Now that scientists
have a comprehensive understanding of how opioids
can alter neurons, the field’s current focus is on developing the
next generation of analgesic painkillers, which have a lower
potential for abuse. This research is part of an effort to reduce
the rising worldwide death rate related to opioid use.
Historical accounts show evidence of opium use dating back
to the ancient Sumerian civilization, nearly 5,000 years ago.
While some records indicate recreational consumption, the
drug’s earliest use was primarily linked to religion and mysticism.
Primitive understandings of pain had deep roots in the
spiritual realm, and ingesting or inhaling opium produced an
unexplainable, seemingly transcendent, euphoria in the user.
More recent accounts, relatively speaking, such as the ancient
Egyptian Ebers Papyrus, describe medical uses for opium,
such as calming crying children and performing euthanasia.
Recreational opium use became popular in 17th-century
China after smoking tobacco was outlawed. Opium dens,
in which patrons could buy and smoke the drug, sprang up
across China and later appeared in other countries. By the
time Emperor Jiaqing outlawed the import of opium in 1799,
England had established a robust opium trade with China.
England’s attempts to prevent and circumvent the criminalization
of opium would eventually lead to the First and Second
Opium Wars.
In the mid-19th century, the invention of the syringe enabled
doctors to use opiates in surgery and general pain management,
but painkiller development did not attract significant
interest until the 20th century. The aftermath of both
world wars brought attention to the need for the development
of new approaches to pain management, as modern warfare
had left many soldiers with appalling wounds and chronic
pain. Multiple new drugs arrived on the scene to meet this
new demand. Most of these drugs would eventually be identified
as opioids. Opioids share the ability to mimic the body’s
native opioid peptides, such as the endorphins released by the
pituitary gland after vigorous exercise. Holden Ko, a scientist
developing and testing new painkillers at Wake Forest School
of Medicine, explains that pharmacologists now know that
structures dissimilar to opium derivatives can still bind to the
same opioid receptors, thereby producing many of the same
effects, such as feelings of euphoria and physical well-being.
Robert LaMotte, researcher at the Yale School of Medicine, is
working to better understand the neural mechanisms behind
the sensations of pain. His lab has published numerous papers
on topics such as the causes of increased sensitivity and chronic
cancer pain. Ko, who met with LaMotte while visiting Yale,
recently published promising findings demonstrating the efficacy
of a new opioid drug type that has thus far proven to be
free of abuse potential in primates. Pharmaceutical companies
are looking to develop a related compound so they may soon
realize the centuries-old goal of developing potent, abuse-free
painkillers. When discussing his work, Ko emphasizes the importance
of non-human primates to opioid research. “Their
neurological and physical drug reactions and physiological
anatomy are most similar to humans. Many promising findings
from rodent studies do not translate into primates,” he
said. He adds that researchers design as many non-invasive
procedures as possible to protect primate well-being.
When asked if opioid painkillers are here to stay, Ko agreed
with the widely-held conclusion among pharmacologists that,
“morphine is hard to beat.” “Scientists have made a lot of exciting
discoveries in the past several decades, but, at this moment,
opioid analgesics are still considered a cornerstone of
pain management.”
www.yalescientific.org
October 2016
Yale Scientific Magazine
35

UNDERGRADUATE PROFILE
SOPHIA SANCHEZ (TD’19)
OUT OF THIS WORLD
►BY MICHELLE PHAN
For someone who spends most of her time thinking about outer
space, Sophia Sánchez-Maes is firmly grounded in her research
here on Earth. From examining algae to studying exoplanets, the
burgeoning astrophysicist retains a refreshing curiosity about the
world, something she believes is essential to science. That curiosity is
a driving force in her life, both in and out of the laboratory.
Sánchez-Maes currently studies astrophysics and the exploration
of exoplanets, planets that orbit stars outside of our solar system,
but her scientific career spans several years and subjects. She has
previously worked to improve sustainable energy and create new
computer simulations, but in all disciplines, her work is rooted in
the simple appreciation of science as a force for positive, unfettered
good.
Sánchez-Maes’ first introduction to physics was at an early age.
At 15 years old, she started her first job at the Center for High
Technology Materials, where she worked in optics, a branch of
physics that studies the properties of light. There, she began thinking
about algae as an energy alternative to coal and petroleum. She was
dissatisfied with the current methods of biofuel production, which
used huge amounts of energy, produced high levels of carbon dioxide,
and were often too expensive to be sustainable. “It took more energy
to produce the fuel than the fuel actually contained,” she said. “That
was the problem that I was determined to solve.” Using a computer
simulation, she calculated the optimal conditions for algae growth
and began researching Galdieria sulphuraria, a species of red algae.
She experimented with using subcritical temperatures and catalysts
IMAGE COURTESY OF MICHELLE PHAN
►Sophia Sanchez is a current sophomore in TD College. She is a
founder of Girls Get Tech.
to convert the algae into fuel, hoping to increase the algae’s energy
yield. In time, she demonstrated that this G “pressure-cooking,” also
called hydrothermal liquefaction, of the algae produced net gains in
energy, an improvement over earlier methods.
Although her research on algae earned her numerous accolades
and a meeting with Barack Obama, Sánchez-Maes soon took on
a new challenge: the study of astrophysics. After a local job fair,
she received an offer from NASA’s Jet Propulsion Laboratory and
weighed her options. “One of my friends told me, ‘Sophia, how is
this even a choice? You have this out-of-the world option. Literally
out-of-this-world’,” recalled Sánchez-Maes. Ultimately, her decision
to work at NASA paid off. “I got to do amazing code with amazing
people… it was a really spectacular place.”
At the Jet Propulsion Laboratory, Sánchez-Maes began her
interstellar exploration by creating computational models for the
Curiosity and Mars 2020 rovers. The models simulated the rovers’
mission variables and electronic inputs. By simulating how heat
would transfer through the machine, the program calculated how to
safely operate the machines on Mars.
Last summer, Sánchez-Maes continued her work at NASA, this
time with the Exoplanet Exploration Program, where she worked on
telescope and exoplanet detection technology. She primarily worked
with the radial velocity method of detecting exoplanets, which
involves observing a star’s spectrum to see if if the star “wobbles”
due to the pull of nearby exoplanets. The method is not always
straightforward: “The stars themselves produce radial velocity… the
more active the star, the harder it is to find the mass of the exoplanet,”
Sánchez-Maes explained. She designed code to analyze the effects of
a star’s movement on her results. The code first adds the movement
into an already-analyzed spectrum. Then, it applies the radial velocity
method to the new spectrum. From there, she can see how accurate
the radial velocity is when there is stellar interference.
Despite her scientific achievements and time-consuming projects,
Sánchez-Maes still finds time to think about the social issues in her
field. In particular, Sánchez-Maes hopes to expand scientific spaces
for women and minorities in STEM. In 2015, she launched Girls Get
Tech, a summer program that teaches young Latinas how to code,
in the hopes of making computer science and technology more
accessible.
Clearly, Sánchez-Maes is devoted to her field. A scientist in the
true meaning of the word, she continues to march toward bigger and
brighter innovations in astrophysics. Looking forward, Sánchez-
Maes is determined: “We can do better. Everyone can do better.”
36 Yale Scientific Magazine October 2016 www.yalescientific.org

ALUMNI PROFILE
TSO-PING MA (PHD’74)
SAVING SATELLITES, ONE SEMICONDUCTOR AT A TIME
►BY KENDRICK UMSTATTD
IMAGE COURTESY OF TSO-PING MA
►Ma is excited by the prospect of educating the next generation of
engineers at Yale.
Most of us know that solving a problem, whether it is a question
on an exam or a roadblock encountered in a long research endeavor,
almost always requires a bit of luck. Professor of Electrical Engineering
and Applied Science Tso-Ping Ma, PhD ’74, is no stranger to that
luck. It may, however, come as a surprise that Ma, whose work has
spanned continents and earned him several patents, started research
in his current field by accident.
Ma attributes his initial interest in engineering to his parents. Ma
was born in China, but he and his parents fled to Taiwan following
the Cultural Revolution. “They led a pretty meager life in those days,”
Ma said. Given his parent’s often sporadic employment as civil servants,
Ma sought out a career that would provide him with greater
stability.
Ma attended National Taiwan University, earning a B.S. in electrical
engineering in 1968. In Taiwan, Ma grew accustomed to big-picture
thinking, which he found to be endemic to the Chinese educational
system at that time. When he transitioned to Yale University, where
he completed his master’s and doctorate degrees, Ma was struck by
the contrast between the educational systems of Taiwan and the US:
the emphasis on minute details was unfamiliar to him, and the very
existence of research universities was also new–this type of institution
was largely absent from Taiwan while he was in college.
In the end, it was lucky for Ma that research is so strongly integrated
with learning in American universities. During his time as a Ph.D.
candidate at Yale, Ma often accompanied his wife to her molecular
biology lab, where she was researching the effects of radiation on
bacteria samples. One day, when Ma’s wife took a sample out of the
radiation-emitting machine to observe mutations in the bacteria, Ma
was spellbound by the appearance of the glass tube that contained
the bacteria. The once-clear glass tube was now completely gray.
By this time, Ma had begun to research semiconductors with professor
Richard Barker, his thesis advisor. Semiconductors, materials
with modest electrical conductivity, are essential to electronic devices.
To make a semiconductor, impurities are introduced to the element
silicon in order to provide it with some conductive abilities.
Since electrical devices must function in a sea of radiation, from the
sun’s rays to FM radio-waves, engineers must develop semiconductors
that can filter out unwanted background noise and avoid degradation.
Ma had not initially intended to research radiation. However, when
he saw how radiation affected glass, he wondered what it would do
to silicon-based semiconductors. This initial spark motivated him
to research the effects of radiation on silicon chips and semiconductors.
His historic findings would ultimately aid US security. During
the Cold War, guided missiles deployed by the US needed to resist
the radiation generated by Russian neutron bombs, which emit high
levels of radiation. If they could not, Americans would be in danger,
since the missiles could deviate from their intended course.
Radiation-resistant technologies have applications outside
of American security. Satellites must also be able to withstand
high-levels of radiation. When satellites are deployed, they enter a
radiation-rich environment, and their electrical systems are at risk
of deteriorating. Any resulting malfunctions would interrupt satellite
communication with receiving centers on Earth. Without Ma’s
work, satellites today would have significantly shorter lifespans,
making life saving information and Netflix much harder to access.
“This research highlights that a multidisciplinary approach to work
is the best way to move forward, because you can learn from other
disciplines,” Ma said, referencing his discovery in the molecular
biology lab.
Current engineering students ask Ma how best to prepare themselves
for the ever-changing world of science and technology. In answering,
Ma addresses the fluidity of science today. As innovations
are continually made, technology becomes obsolete quickly. In order
to stay ahead of the curve, Ma advises students to gain a breadth
of knowledge in different subject areas. If an engineer has breadth,
depth, and purpose, the only remaining asset they need is, perhaps,
a bit of luck.
www.yalescientific.org
October 2016
Yale Scientific Magazine
37

FEATURE
book review
SCIENCE IN THE SPOTLIGHT
BOOK REVIEW: THE GENIUS OF BIRDS
►BY SARAH ADAMS
Arising from expressions like “bird brain” and “dumb as a dodo,”
the opinion that birds are unintelligent animals is a common myth,
one that Yale alum Jennifer Ackerman YC ‘80 seeks to debunk in
her new book, The Genius of Birds. Ackerman shares her refreshing
insight into the different varieties of bird intelligence. The book
features research by experts focusing on social, vocal, and even spatial
aspects of cognition. Ackerman explores classic examples of the
exceptional intelligence of parrots, as well as lesser known instances
of aviary acumen found in less exotic birds such as chickadees and
sparrows.
Although her in depth consideration of bird cognition and
intelligence could stand on its own, Ackerman goes further and
relates bird cognition to human cognition. One instance of this
cross-species parallelism highlighted by Ackerman can be found
in vocal learning, the way in which an organism learns and
subsequently reproduces vocalizations. Young zebra finches have
the ability to learn any bird song but are genetically predisposed to
learn their own species’ songs and calls. Similarly, humans possess
a genetic predisposition to learning human speech and language
at a young age. In both birds and humans, the regions of the brain
necessary for speech, or song, production are similarly situation. “I
hope that readers will question what intelligence is and realize that
the different kinds of intelligence are evolutionary stepping stones
for approaching the problems that a variety of organisms face in the
BOOK REVIEW: PATIENT H.M.
►BY ISHAAN SRIVASTAVA
Hoping to cure the epilepsy that had dogged him for 20 years, Henry
Molaison elected to receive a lobotomy in 1953. Neurosurgeon William
Scoville employed a radical procedure for the time, removing significant
portions of Molaison’s hippocampus. After the procedure, the frequency
of Molaison’s seizures decreased. However, Molaison found himself
unable to commit new events to his memory and was soon diagnosed
with anterograde amnesia.
Molaison’s tale is gut-wrenching. It demonstrates the unintended
consequences that often coincide with experimental procedures. It
also illustrates how we rationalize these cases, perhaps perversely, by
considering the scientific advancements they enable. Based on Molaison’s
experiences, neuroscientists concluded that the hippocampus is essential
for memory formation. Molaison was immortalized as “Patient H.M.” in
textbooks and subsequent research.
Luke Dittrich’s new book, Patient H.M.: A Story of Memory, Madness,
and Family Secrets, introduces much needed passion and compassion
into the often overly-academic subject of medical ethics. In 400 pages of
searing prose, Dittrich lays out the implications of capitalizing on such
unfortunate events in excruciating detail.
Dittrich’s work resonates. It is the culmination of not only six years of
work from an award-winning journalist but also a substantial amount of
natural world,” Ackerman said.
In her discussions of intelligence,
Ackerman effectively incorporates
concepts from evolutionary biology to
explain differences in the emergence
of traits among species. Adaptability is
key, and towards the end of the book,
Ackerman addresses how humandriven
environmental changes may
be making it more difficult for some
bird species to adapt and survive.
A particular species of bird may be
“intelligent” in some way, but that
does not automatically improve their
likelihood of survival in novel and
IMAGE COURTESY OF JENNIFER
ACKERMAN
unstable environments, creating the potential for extinction.
Accessible to non-birders and birders alike, The Genius of
Birds has received great praise from a wide audience. “I knew that
birdwatchers were also booklovers, and figured that this book would
strike a chord with them, but it has really taken off and struck a
chord with many other people too,” Ackerman said. Throughout
the book, her explanations of complex studies were understandable
and enjoyable, and are sure to continue helping readers see the
importance of investigating further the intelligence of birds.
introspection. Dittrich’s grandfather was the surgeon who lobotomized
Patient H.M., and his family friend Suzanne Corkin is a prominent MIT
neuroscientist who has researched Patient H.M. for decades.
The most powerful moments of the book come from Dittrich’s intimate
connections to the protagonists of 20th century neuroscience. While
reading about the horrors experienced by Scoville’s mentally ill wife, we
are privy to the reflections of a grandson attempting to understand his
grandfather. When we read about researchers such as Corkin obtaining
“consent” from a lobotomized amnesiac, we realize that Dittrich is not
only critiquing the actions of a prominent neuroscientist, but of someone
who once gossiped with his mother on tin-can telephones.
Dittrich’s allegations of ethical shortcomings against Corkin
have drawn attention from the scientific community. Hundreds of
neuroscientists sought to rebut Dittrich’s claims: specifically, that Corkin
destroyed records relating to Molaison, suppressed findings that opposed
once-firm paradigms of modern neuroscience, and failed to obtain
proper consent for experimentation. Dittrich himself has responded to
these claims, providing documented evidence to support his assertions.
The existence of such arguments in the public sphere reinforces the
ethical stakes of scientific research that we occasionally take for granted.
Patient H.M. insists that we ignore such conversations at our own peril.
38 Yale Scientific Magazine October 2016 www.yalescientific.org

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