[Catalyst 2018]

VOLUME 11, 2018
RICE UNDERGRADUATE SCIENCE RESEARCH JOURNAL
written in the
(dead) stars
The Black Hole Information
Paradox
ALSO IN THIS ISSUE:
+ Bioengineering Methods to
Foster Neonatal Care
+ Mechanobiology of Lung Cancer
Cells During Metastasis

FROM THE
Editor
Dear Reader,
Welcome to the eleventh annual edition of Catalyst,
Rice’s premier Undergraduate Science Research Journal.
We are a peer-edited publication founded to showcase
student perspectives on popular science topics and
scientific research. For the past eleven years, we have
been committed to fostering interdisciplinary interest
in scientific writing and dialogue at Rice and beyond.
We are passionate about making science accessible and
engaging, whether you’re a Ph.D. research scientist or
a casual reader. In this year’s publication, you can find
articles about fields as diverse as quantum computing,
cancer therapy and marine forensics.
EXECUTIVE EDITORS
Rishi Sinha
Ruchi Gupta
Shashank Mahesh
Rachita Pandya
Staff
CO-PRESIDENTS
Elaine Hu, Activities Chair
Sanket Mehta, Editor-in-Chief
DIRECTORS OF DESIGN
Lin Guo
Juliana Wang [ASSISTANT]
OUTREACH DIRECTOR
Jacob Mattia
BlOG DIRECTOR
Kseniya Anishchenko
This year, Catalyst has grown tremendously, both
inside and outside of the Rice hedges. We began
the year with several goals in mind: to improve our
internal organization in response to our growing
member body and growing reach, to better assess
writer development, and to develop and extend our
non-print platforms, such as podcast and blogs. This
year was about achieving those goals, but it was also
about strengthening old connections and forging new
ones, both among Catalyst members and with our
partners. It was about creating several initiatives to
increase cohesiveness within the organization, including
study breaks and social events all throughout the
year. The year also marked the launch of the Catalyst
Research Fair, a well-attended university-wide event
that connected students interested in undergraduate
research directly with lab positions advertised by
graduate students and postdocs. And it was about
continued leadership at the university level, as Catalyst
worked alongside the Center for Civic Leadership and
the Dean’s Office to help organize Rice Inquiry Week, a
celebration of inquiry-based pedagogy and research at
the university, particularly by undergraduates and their
faculty mentors.
EDITORS
TREASURER
Jack Trouvé
ATTRACTIONS
Brianna Garcia, Meredith
Brown, Jason Lee,
Mahesh Krishna, Kelsey
Sanders, Anna Croyle
BREAKTHROUGHS
Albert Truong, Kalia
Pannell, Vatsala
Mundra, Roma Nyaar,
Pujita Munnangi, Axel
Ntamatungiro, Deepu
Karri
PODCAST EXECUTIVE
PRODUCER
Ajay Subramanian
CONNECTIONS
Olivia Zhang, Rishab Ramapriyan,
Jenny Wang, Shrey Agarwal
DISCOVERIES
Nigel Edward, Avanthika
Mahendrababu, Shikha Avancha, Tom
Wang
The progress and expansion we have undergone this
year would not have been possible without the support
of the Rice community, our partners, our mentors, and
our absolutely amazing staff. In particular, we would
like to thank the Rice Center for Civic Leadership,
the Rich Endowment, the Program in Writing and
Communication, and the Student Activities President’s
Programming Fund for their continued generous
support of Rice Catalyst’s endeavors. Of course, we also
want to especially thank Dr. Dan Wagner, our faculty
sponsor who has provided us with invaluable advice
and guidance throughout this entire process.
We are proud of how far Catalyst has come this year
and we are excited for our growth in the years to come.
From the entire Catalyst staff, we hope you enjoy our
latest issue as much as we enjoyed making it!
Sanket Mehta
Editor-in-Chief
2 | CATALYST
SENIOR DESIGNERS
Katrina Cherk, Christina Tan, Kaitlyn Xiong, Evelyn Syau
DESIGNERS
Sara Ho, Nancy Cui, NamTip Phongmekhin, Maddy Tadros, J. Riley
Holmes, Sahana Prabhu, Priscilla Li, Jenny Wang, Anna Croyle,
Jessica Lee
BLOGGERS
Natasha Mehta, Kaitlyn Xiong, Krithika Kumar, Pujita Munnangi,
Priyansh Lunia, Emre Yurtbay, Shruti Shah, Evelyn Syau
FACULTY ADVISOR
Dr. Daniel Wagner
Cover Image by Ute Kraus from Space Time Travel Gallery

TABLE OF
Contents
4
6
9
10
12
13
14
15
16
18
20
22
24
26
27
28
30
32
34
36
38
40
44
47
48
ATTRACTIONS
SCI-FI TO DIY: The Evolution of Genetic Engineering // Dora Huang
WRITTEN IN THE (DEAD) STARS: The Black Hole Information Paradox // Jenny L. Wang
HIGH-ALTITUDE SULFUR INJECTION: Insane or Insanely Genius? // Meredith Brown
PHOTOSYNTHETIC BACTERIA: Shining Light on Heart Disease // Swathi Rayasam
WHO’S SAVING LIVES? Robots // Jenny S. Wang
MIRROR NEURONS: Unlocking the Mind // Samantha Chao
CHAGAS DISEASE: A Silent Killer // Maishara Muquith
CPR For the Vaquita // Celina Tran
QUANTUM COMPUTING: A Leap Forward in Processing Power // Valerie Hellmer
BREAKTHROUGHS
ROBOTS AND MEDICINE: A Connection of Many Degrees // Alan Ji
AMPing Up the Defense System // Preetham Bachina
CREATING GLOBAL CHANGE: Bioengineering Methods to Foster Neonatal Care // Pujita Munnangi
MITOCHONDRIAL HEALTH: Implications for Breakthrough Cancer Treatment // Sarah Kim
THE WATERWORKS: Drinking Water for All // Andrew Mu
LIGHT SHOW: Using Light-Activated Metal Complexes to Combat Alzheimer’s // Oliver Zhou
Sumo Wrestling With Heart Diseases // Amna Ali
SONGBIRDS, AGING, AND AUTISM: The Exciting New Field of Neurogenesis // Christine Tang
Water Security in the Middle East // Sree Yeluri
CONNECTIONS
Methods of Mosquito Vector Surveillance and Population Control // Owais Fazal
The Emergence of Number Theoretic Questions from a Geometric Investigation // Jacob Kesten
The Effect of Dasatinib on Mechanobiology of Lung Cancer Cells During Metastasis // Shaurey
Vetsa et al.
BIODIVERSITY IN A DROP OF WATER: A Glance into Marine Forensics // Elaine Shen
Reviewing the Relationship Between Inflammatory Bowel Disease and Primary Sclerosing
Cholangitis // Mahesh Krishna
DISCOVERIES
Science of Beauty // Krithika Kumar
THE TICKING TIME BOMB: Hereditary Cancer Syndromes // Shruti Shah
CATALYST | 3

SCI-FI
TO
d.i.y. :
Kac created Alba’s
glow through a feat of
genetic engineering:
synthetic mutation of
the green fluorescent
protein (GFP) gene
from the jellyfish type
Aequorea victoria
Genetic engineering is an area of
science that never fails to intrigue
people, mainly because the field
seems like something directly
out of a sci-fi flick or a superhero comic.
Although the practice has been around
since the 1970s, the intricacy involved in
genetic engineering has recently made a
splashing impact in the world of science
and technology, as well as in our daily lives.
Through the mediums of bio-art, biohacking,
human genetic engineering, and GMOs,
genetic engineering is paving its way towards
becoming a staple within our culture, and we
may not be far from a world where this “scifi”
becomes a scientific standard.
In order to trace the history of genetic
engineering, we must examine its origins:
GMOs. GMO stands for genetically modified
organisms, and they are commonly seen in
the form of produce at local supermarkets
or in angry online posts lamenting about the
downfall of health standards. These GMOs
were created by removing DNA from one
plant and inserting it into a separate plant,
giving rise to new abilities, such as herbicide
tolerance and self-sustaining insecticide.
Despite its polarizing connotation, GMOs
are relevant to industry and to our own
consumption, as much of purchased
produce, including corn, soybeans, cotton,
are genetically modified. 1
GMOs can prove to be beneficial for
generations to come, as seen in a study
at the University of Washington, where
researchers have been working since the
early ‘90s to develop poplar plants that
can clean up pollutants found in both the
ground and the air. 2,3 Their genetically
engineered poplar plants can take in 91% of
trichloroethylene, which is the most common
groundwater contaminant in the U.S.. 2,3
In Japan, another team of researchers
is working with Mammalian cytochrome
P450, which is a gene found in mammal
livers. They are implementing this gene into
rice plants, allowing them to degrade and
detoxify herbicides. 2 A detoxifying poplar
and rice plants provides evidence of the use
of genetic engineering in creating GMOs for
the environmentalist movement, yielding an
interesting solution to a pressing issue.
Moving beyond studying plants, genetic
engineers began to experiment on animals.
Though this move sparked controversy in
the scientific community, researchers were
able to create unique organisms in a new
artistic field known as Bio-Art. Brazilian artist
Eduardo Kac sparked the movement of Bio-
Art, a new brand of innovation that combines
the skills of scientists and engineers with
the creativity of artists. Kac rose to fame
due to his project “Alba,” a bunny that glows
green in the dark. 5 Collaborating with a team
of scientists in France, Kac created Alba’s
glow through a feat of genetic engineering:
synthetic mutation of the green fluorescent
protein (GFP) gene from the jellyfish type
Aequorea victoria. 4,5 In Aequorea victoria, a
protein releases a blue light when it bonds
with calcium. 4 The GFP gene then absorbs
this blue light, and green light is emitted. 4
An enhanced version of the GFP gene was
inserted into Alba, amplifying fluorescence in
mammalian cells. 5 Alba and other transgenic
animals provoke feelings of astonishment,
indignation, and curiosity, and it will be
interesting to see what technology the world
of bio-art will embrace next.
Along with being an integral part of the
Bio-Art movement, genetic engineering was
also used in more environmental studies,
such as with the invention of Enviropigs in
Canada. 6 As with all living organisms, pigs
require phosphorus in their food, but have
4 | CATALYST

the EVOLUTION of
GENETIC ENGINEERING
By Dora Huang
the inability to digest phytase, an enzyme
that is used to digest the phosphorus found
in the grains and seeds they consume. 6,7
Therefore, they must intake a supplement
of these phytase enzymes, which have
been found to be ineffective, causing
phosphorous to get flushed out as waste. 6,7
However, with Enviropig, the need for
ingesting phytase supplements is eliminated,
because the pig would ideally generate its
own phosphorus-dissolving enzyme. 6,7 This
genetically engineered pig has urine and
feces that contain 40-65% less phosphorus,
which is beneficial for cutting maintenance
and cleaning costs for pig farmers, as well
as “[complying] with the “zero discharge”
rules...that allow no nitrogen or phosphorus
runoffs from animal operations,” as they can
cause dead zones in nearby water sources. 6,7
Though the operation was terminated
after just two years due to loss of funding,
Enviropigs remain a unique solution to an
environmentally threatening problem, and
remains a useful product of genetically
modification.
Scientists have modified plant and animals,
and it was only a matter of time before
humans started genetically modifying
themselves. Just this last summer, the first
human embryos were edited in Portland,
Oregon, involving the changing of DNA of
one-cell embryos using the gene-editing
technique CRISPR. 9,10 CRISPR is a system that
“target[s] specific stretches of genetic code
and... edit[s] DNA at precise locations.” 8
Researchers can use CRISPR to modify the
genes in living organisms and precisely
correct mutations in the human genome. 8
In using CRISPR on editing human embryos,
scientists can change the genetics of a
family for generations to come, as the
genetically modified child would pass down
the modifications to their future offspring. 9,10
Although these “designer babies” have faced
intense backlash due to concerns that this is
a new form of eugenics, CRISPR and human
genetic engineering are relevant because
they have the potential to eliminate fatal
illnesses and genetic mutations before
birth. 9,10 In such cases, it is important to
weigh the costs and benefits of performing
this research, as well as the ethics behind the
entire operation.
In a realm of pure recreational use,
biohackers have begun taking over the
genetic engineering industry using the
CRISPR technique in their own homes and
communities. 11, 12 Biohackers are a group of
amateur and largely untrained biologists that
work together in community laboratories to
create “DIY” genetically modified organisms,
such as growing organs, fiddling with
yeast, and creating vegan cheese. 11 Most of
these experiments are innocuous and help
cultivate and promote scientific research
for those who never believed they would be
scientists, expanding science as a fun, leisure
activity. These clever inventions have largely
been tame and innocently curious, but there
is always a chance for biohacking to be taken
to the next level as the knowledge and use of
CRISPR expands.
Genetic engineering is a controversial topic,
and it can be uncomfortable to think about.
However, with its growing emergence into
our everyday lives, genetic engineering is a
topic that is influencing our future and will
continue to grow in prominence as we look
towards genetic engineering for the answers
to our medical and environmental issues.
Works Cited
[1] Benbrook, C. Summary of Major Findings and Definitions
of Important Terms. http://news.cahnrs.wsu.edu/blog/
article/summary-of-major-findings-and-definitions-ofimportant-terms/
(accessed Oct. 20, 2017).
[2] Hines, S. Scientists ramp up ability of poplar plants
to disarm toxic pollutants. http://www.washington.edu/
news/2007/10/15/scientists-ramp-up-ability-of-poplarplants-to-disarm-toxic-pollutants/
(accessed Oct. 20, 2017).
[3] Choi, C. Genetically Engineered Plants Could Clean
Humanity’s Messes. https://www.livescience.com/1959-
genetically-engineered-plants-clean-humanity-messes.html
(accessed Oct. 20, 2017).
[4] Green Fluorescent Protein. https://www.conncoll.edu/
ccacad/zimmer/GFP-ww/GFP-1.htm (accessed Oct. 7, 2017).
[5] Slawson, K. Eduardo Kac’s GFP Bunny, a Work of
Transgenic Art, or, It’s not Easy Being Green. http://www.
ekac.org/slawson%203.html (accessed Oct. 7, 2017).
[6] Minard, A. Gene-Altered “Enviropig” to Reduce Dead
Zones? https://news.
nationalgeographic.com/news/2010/03/100330-bacon-pigsenviropig-dead-zones/
(accessed Oct. 20, 2017).
[7] Maglona, M. Enviropig: A Genetically Engineered Pig.
https://wordpress.philau.
edu/thevoice/2016/04/enviropig-a-genetically-engineeredpig/#_ftnref5
(accessed Oct. 20, 2017).
[8] Questions and Answers about CRISPR. https://www.
broadinstitute.org/what-broad/
areas-focus/project-spotlight/questions-and-answers-aboutcrispr
(accessed Oct. 20, 2017).
[9] Connor, S. First Human Embryos Edited in U.S. https://
www.technologyreview.com/s/608350/first-human-embryosedited-in-us/
(accessed Oct. 20, 2017).
[10] Belluck, Pam. In Breakthrough, Scientists Edit a
Dangerous Mutation From Genes in Human Embryos. The
New York Times [Online], Aug. 2, 2017. https://www.nytimes.
com/2017/08/02/science/
gene-editing-human-embryos.html?_r=0 (accessed Oct. 20,
2017).
[11] Ledford, H. Biohackers gear up for genome editing.
http://www.nature.com/news
/biohackers-gear-up-for-genome-editing-1.18236 (accessed
Oct. 20, 2017).
[12] Ossola, A. Biohackers are Now Using CRISPR. Popular
Science [Online], Aug. 26, 2015. https://www.popsci.com/
biohackers-are-now-using-crispr (accessed Oct. 20, 2017).
Design By Kaitlyn Xiong
Edited by Jason Lee
CATALYST | 5

written in the (dead) stars:
the black hole
information paradox
by Jenny L Wang
From Nolan’s Interstellar to Muse’s
2006 hit single, black holes serve
as some of the most widely fantasized
plot devices and symbols in popular
culture. Perhaps our fixation with black
holes stems from our lack of scientific
understanding about them. After
all, black holes pose one of the most
contentious dilemmas facing modern
physicists: the black hole information
paradox. Arising from a contradiction
between several fundamental physical
principles, this paradox continues to
challenge not only astrophysicists, but
also our tenuous assumptions and
ideas about how the universe really
works.
Let’s begin by examining black
holes identifying several of their
properties. In simple terms, a black
hole is an enormous amount of
matter concentrated within a relatively
small volume. Most black holes are
classified as “stellar” and form when
a massive star dies and collapses
upon itself, resulting in a supernova
that ejects most of the star’s mass yet
mysteriously retains a black hole in the
center. 1 In addition to stellar, mini and
supermassive black holes also exist.
While their origins are more ambiguous,
scientists hypothesize that their
formation is tied to the very beginning
of the universe. 1
Black holes pose one
of the most contentious
dilemmas facing modern
physicists: the black hole
information paradox.
Although NASA estimates that as many
as ten million to one billion stellar black
holes populate the Milky Way alone,1
the vast majority remain difficult to
observe with current technology due in
part to a black hole’s incredibly strong
gravitational field. As predicted by
general relativity, the center of a black
hole collapses into a “gravitational
singularity” around which space-time
curves. This forms a sort of sphere
around a black hole with an outer
boundary known as the black hole’s
event horizon. 2 The event horizon of
a black hole represents the “point of
no return” beyond which nothing, not
even light, can escape. 2 Past the event
horizon, the black hole’s gravity is so
strong that it renders direct observation
of a black hole using telescopes and
other electromagnetic radiationmeasurement
devices useless. Instead,
scientists must infer the position and
behavior of black holes by observing the
ways a black hole impacts surrounding
stars and gases. 1
Another interesting phenomenon
that results from a black hole’s
incredible gravity is time dilation. To
an observer outside the event horizon,
time seems to slow down relative to
time experienced by an object falling
towards the black hole. The Stanford
Encyclopedia of Philosophy illustrates
time dilation with the example of
watching someone who, “while falling
[into a black hole]...flashes a light
signal to us every time her watch hand
6 | CATALYST

ticks.” 2 While the falling person would
not feel as if time slows down as she
approaches the event horizon, to us
(outside observers), the time interval
between each successive light would
appear to increase. When the falling
person finally crosses the event horizon,
light no longer reaches our eyes and
the person would suddenly appear to
freeze, seemingly stuck on the black
hole’s surface. 2
The black hole information
paradox arises from a
contradiction between
two foundational physical
theories: quantum
mechanics and general
relativity.
Prior to the 1970s, black hole theory
assumed that when something was
pulled into a black hole, all of the
object’s features (every particle, the
quality of every particle, and the
probability of future behavior of
every particle) became inaccessible to
anything outside the event horizon. 3
According to quantum mechanics,
information must be preserved in
a similar fashion as energy. Thus,
scientists hypothesized that as objects
fall into a black hole, their quantum
information is simply stored away
somewhere inside, unreachable yet still
preserved.
However, in 1975, Stephen Hawking
observed that black holes evaporate
over time through a process called
Hawking radiation. 3 Hawking proposed
that the universe is filled with “virtual
particles”: particle-antiparticle pairs
which constantly pop in and out of
existence, appearing and rapidly
cancelling one another out. 4 However,
near the event horizon of a black hole,
instead of being annihilated by its
particle or antiparticle counterpart,
one virtual particle could fall into the
black hole while the other, along with
a miniscule fraction of the black hole’s
mass, escapes as thermal energy known
as Hawking radiation.
The discovery of Hawking radiation
introduced one of the most urgent
and contentious issues that continues
to puzzle theoretical physicists today:
the black hole information paradox.
In simplified terms, the black hole
information paradox arises from a
contradiction between two foundational
physical theories: quantum mechanics
and general relativity, proposed by
Einstein in 1915. 6 As Clara Moskowitz
summarized on behalf of Scientific
American in 2015, black holes “invoke
two different theories of nature—
quantum mechanics, which governs the
subatomic world, and general relativity,
which describes gravity and reigns on
large cosmic scales.” 7 While quantum
mechanics asserts that information
cannot be created or destroyed, classical
general relativity states that information
cannot escape a black hole. If Hawking
radiation follows principles of general
relativity, then black holes do not
emit information while evaporating.
However, this implies that after a black
hole dissipates completely into random
radiation, the information of everything
that it swallowed vanishes as well: a
contradiction of quantum mechanics. 8
At best, this incongruity causes a
headache for a few star-crossed
astrophysicists. At worst, the paradox
compromises decades of progress
in quantum mechanics and general
relativity.
Since the discovery of Hawking
radiation, scientists continue to debate
and propose solutions to the black
hole information paradox. Theoretical
physicist Sabine Hossenfelder sorts
tentative solutions into four general
categories: 9
1 1
1 2
1 3
1 4
Information is somehow encoded
in Hawking radiation and escapes
as the black hole dissolves. This
statement contradicts Hawking’s
original conclusions about the
radiation being random and
introduces yet another paradox
called the “firewall” paradox.
Information is stored in or on
the surface of a black hole. The
formation of baby universes,
the holographic principle, and
Hawking’s most recent “soft
hair” explanation fall into this
category.
Information actually is destroyed,
and quantum mechanics requires
serious modification.
There is no black hole, and
information never crosses its
boundary. General relativity,
which predicts the existence
and behavior of the black hole,
requires serious modification.
CATALYST | 7

Of course, many other proposed
solutions fall outside of these mentioned
categories. Each come with their own
associated strengths and shortcomings,
but all challenge previously-held
assumptions about the field and
contribute to a growing body of literature
about the black hole information paradox.
However, in spite of this progress, it will
likely take many more years to observe
what actually happens to information in a
black hole, since current technology limits
our ability to measure Hawking radiation
and quantitatively observe the behavior
of black holes. 8
Instead of viewing the
paradox as a conflict
between quantum mechanics
and general relativity, many
regard it as an opportunity
to reconcile the two
foundational theories.
Despite these challenges, the implications
of the black hole information paradox
remain profound. Instead of viewing the
paradox as a conflict between quantum
mechanics and general relativity,
many regard it as an opportunity to
reconcile the two foundational theories.
As Moskowitz writes, the black hole
information paradox urges a deeper
need to “describe gravity according to
quantum rules” and perhaps suggests the
existence of another theory which unites
the other two. Most scientists agree that
discovering such a unifying theory of
quantum gravity could marry quantum
mechanics and general relativity, offering
a satisfying resolution to the information
paradox and inspiring a “conceptually
new understanding of nature.” 3
In the meantime, by improving scientific
instruments, conducting research, and
reexamining our underlying assumptions
about the physical world, we can refine
our existing theories about the black
hole information paradox and develop
new ones. Although the final answer
remains ambiguous, we advance with
tireless inquiry and curiosity about the
mystique of space. In the process, our
understanding—like our universe—
inevitably continues to grow.
WORKS CITED
[1] Nagaraja, M. Black Holes. [Online] n.d. NASA. https://
science.nasa.gov/astrophysics
/focus-areas/black-holes (accessed Oct. 8, 2017).
[2] Curiel, E.; Bokulich, P. Singularities and Black
Holes. [Online] 2012, Fall 2012 Edition, n.p. Stanford
Encyclopedia of Philosophy. https://plato.stanford.
edu/entries/spacetime-singularities/ (accessed Oct. 28,
2017).
[3] Hossenfelder, S. Forbes. [Online] 2017. https://www.
forbes.com/sites/startswithabang
/2017/01/24/nobody-knows-where-a-black-holesinformation-goes/#7f04ed73767a
(accessed Nov. 11,
2017).
[4] Baez, J.; Schmelzer, I. UCR Mathematics. [Online]
1997. http://math.ucr.edu/home
/baez/physics/Relativity/BlackHoles/hawking.html
(accessed Oct. 28, 2017).
[5] Cain, F. Universe Today. [Online] 2015. https://www.
universetoday.com/119794/howdo-black-holes-evaporate/
(accessed Oct. 29, 2017).
[6] Toth, V. Forbes. [Online] 2017. https://www.forbes.
com/sites/quora/2017/04/13/whydo-general-relativity-and-quantum-mechanics-need-tobe-unified/#3d650734aa2c
(accessed Nov. 8, 2017).
[7] Moskowitz, C. Scientific American. [Online] 2015.
https://www.scientificamerican.
com/article/stephen-hawking-hasn-t-solved-the-blackhole-paradox-just-yet/
(accessed Nov. 8, 2017).
[8] Strassler, M. Of Particular Significance. [Online] 2014.
https://profmattstrassler.com/
articles-and-posts/relativity-space-astronomy-andcosmology/black-holes/black-hole-information-paradoxan-introduction/
(accessed Nov. 12, 2017).
DESIGN BY Katrina Cherk
EDITED BY Kelsey Sanders
BLACK HOLE REGIONS
ergosphere
event
horizon
quiet region:
negligible
gravitational
influence
gravitational
spacetime
distortion
singularity
8 | CATALYST

HIGH-ALTITUDE SULFUR INJECTION
by Meredith Brown
I
f global warming increases the temperature
of the Earth by more than two degrees
Celsius, there will be catastrophic
consequences - major flooding will wipe out
homes, businesses, and ecosystems. 1 Sulfur
dioxide may hold the answer to combating the
threat of global warming. Although aerosols
and sulfur dioxide are detrimental to the
ozone layer and human health, studies have
shown that sulfur dioxide increases both plant
growth and the overall reflectivity of solar
radiation of the Earth’s atmosphere, known as
the Earth’s albedo. 2 Scientists hypothesize that
by injecting sulfur dioxide into the atmosphere,
we could combat the gradual temperature
increase without harming human and plant
life.
The negative consequences of aerosols
and sulfur dioxide are well documented.
Both are banned in large quantities by the
MARPOL regulations and by the National
Ambient Air Quality Standards enforced by
the Environmental Protection Agency.3 The
most harmful aerosols found in hairspray
cans and other products were made illegal in
the United States in the 1970s. 2 Additionally,
atmospheric sulfur dioxide precipitates as
acid rain, negatively affecting plants and
ecosystems. Furthermore, sulfur emissions
are responsible for a large percentage of
particulate matter, a class of air pollutants that
is responsible for approximately two million
deaths per year globally due to respiratory
problems. 4 Sulfur dioxide and aerosols also
play key roles in the destruction of the ozone
layer, the main component of the atmosphere
that protects humans from harmful UV rays. 3
In order to utilize sulfur dioxide to counteract
greenhouse gases, these negative impacts
must be mitigated.
Despite these numerous risks, aerosols
and sulfur dioxide have potential that
encourage scientists to look beyond their
negative qualities. Although sulfur dioxide is
a particulate matter pollutant, it also acts as a
cloud catalyst in certain layers of
the atmosphere.
In this
insane or insanely genius?
phenomenon, water vapor in the air is able
to cling to sulfur dioxide molecules more
easily than to salt crystals or to other water
molecules, resulting in a larger and brighter
cloud cover. This is desirable because larger
and brighter clouds reflect more solar
radiation than smaller and dimmer clouds that
lack sulfur. More solar radiation is reflected
back into space, and thus, less solar energy is
Water vapor in the air is able to
cling to sulfur dioxide molecules
more easily, causing clouds to be
larger, more frequent, and brighter.
available for greenhouse gases to trap near
the Earth’s surface. Also, sulfur dioxide plays a
critical role in plant growth. When a solar ray
cuts through Earth’s atmosphere, it generally
travels in a straight line. But if the ray hits the
large sulfur dioxide particles, the light scatters.
This scattered light is able to reach more plants
on the ground, allowing plants to grow larger.
Larger plants are desirable because the leaves
have a greater surface area and are thus able
to absorb more carbon dioxide, removing this
potent greenhouse gas from the atmosphere.
Dr. David Keith, a professor of physics and
public policy at Harvard University, has
outlined one cheap method of using sulfur
dioxide to combat global temperature
increases: high altitude injection. 3 He proposes
that specialized planes could fly annually and
inject one million tons of sulfur dioxide to
create a thin atmospheric layer intended to
reflect one percent of solar rays. These planes
would fly 20 kilometers high, beyond the cloud
formation point, to avoid contributing to acid
rain, while still reflecting solar radiation before
it ever hits Earth’s surface. Therefore, this
solar radiation is unable to become trapped
by greenhouse gases, thereby slowing Earth’s
temperature increase. In fact, this concept was
underscored by a mega-volcanic eruption in
1991, where a major increase in sulfur caused
a decrease in global temperature by half a
degree Celsius for two years. 5
However, this solution still has some
flaws. Scientists fear disruptions in
precipitation patterns,
reductions in
atmospheric ozone, and obstacles in logistics
regarding “who will inject the sulfur, where
will they inject the sulfur, and who will pay
for this?” Furthermore, the molecular size
of sulfur dioxide causes the particle to
have a short atmospheric life, so gas would
have to be continuously pumped into the
atmosphere, costing billions of dollars and
acting as a mere band-aid for our emissions
problems. 6 Scientists argue against this
tactic by suggesting that if the world were to
develop low-emissions energy systems and
transportation methods, such steps would fix
the greenhouse gas problem in a cheaper and
more sustainable manner in the long-run. Al
Gore denounced this geo-engineering plan,
calling it “insane, utterly mad and delusional in
the extreme.” 7
While high altitude sulfur dioxide injections
are possible with current technology, there
is not enough information to determine the
full scope of the environmental impact. Many
scientists have simply suggested decreasing
emissions to combat the source of the
problem instead of putting on the “bandaid”
of high-altitude sulfur dioxide injection.
However, most scientists can agree that
something must be done to mitigate our air
pollution problem, but global warming is a
challenge that we must tackle immediately.
WORKS CITED
[1] Aton, ClimateWire Adam. “Earth Almost Certain to Warm
by 2 Degrees Celsius.” Scientific American, 1 Aug. 2017, www.
scientificamerican.com/article/earth-almost-certain-to-warmby-2-degrees-celsius/.
[2] “Sulfur Dioxide: Its Role in Climate Change.” Institute for
Global Environmental Strategies >> Sulfur Dioxide: Its Role
in Climate Change, esseacourses.strategies.org/module.
php?module_id=168.
[3] “Setting and Reviewing Standards to Control SO2
Pollution.” EPA, Environmental Protection Agency, 13 Oct.
2017, www.epa.gov/so2-pollution/setting-and-reviewingstandards-control-so2-pollution#standards.
[4] Physics, Institute of. Researchers Estimate over Two Million
Deaths Annually from Air Pollution, www.iop.org/news/13/jul/
page_60518.html.
[5] Rotman, D. A Cheap and Easy Plan to Stop Global Warming
. MIT Technology Review. https://www.technologyreview.
com/s/511016/a-cheap-and-easy-plan-to-stop-global-warming/
(accessed Nov 7, 2017).
[6] Stephen et al. Self, pubs.usgs.gov/pinatubo/self/.
[7] Hansman, Heather. “Is This Plan to Combat Climate
Change Insane or Insanely Genius?”Smithsonian.com,
Smithsonian Institution, 14 May 2015, www.smithsonianmag.
com/innovation/is-this-plan-combat-climate-change-insaneinsanely-genius-180955258/.
DESIGN BY Katrina Cherk
EDITED BY Anna Croyle
+
CATALYST | 9

PHOTOSYNTHETIC BACTERIA:
Shining Light on Heart Disease
Swathi Rayasam
F
lashing lights. Chest compressions.
A cry of “clear!” We commonly
associate heart attacks with this
frantic mental picture. However, a heart
attack will only develop into fatal heart
rhythms through a cascade of cardiac
events. Before we explore the evolution of
a basic heart attack into cardiac death, we
need a broad overview of heart disease.
The leading cause of death worldwide,
cardiovascular disease is costly – both in
terms of money and in terms of years of
life. 1 Although several recent advances
have explored repair and regeneration
after significant cardiac trauma, 2-3
tackling cardiac injury closer to its onset
would minimize serious damage due to
treatment delay.
A heart attack is characterized by an
obstruction that prevents proper blood
Scientists at Stanford
University have explored
the possibility of
introducing other
photosynthetic agents
into the body to provide a
source of oxygen for
cardiac cells.
flow to the heart. 4 While this is certainly
serious on its own, the cascade of
events that are triggered more largely
contributes to patient death. First, the
blockage of circulation can cause a lack of
oxygen in the heart, known as ischemia. 5
This condition can lead to cardiac cell
death if present for an extended period
of time, as in the case of delayed CPR and
transport to the hospital. If the human
body had an alternate route to bypass the
roadblock and deliver oxygen to the heart,
then there would likely be less heart
tissue injury and improved survival.
The fact that trees generate oxygen
may imply that introducing plant cells
internally might prevent and resolve
ischemia. Photosynthetic processes in
such a situation would merely rely on a
light source and chemical compounds
abundant in the human body to engineer
oxygen production in ischemic areas. 6
This new oxygen source would also
lessen the immediate need for proper
blood flow. However, while maintaining
internal plant cells is not exactly feasible,
scientists at Stanford University have
explored the possibility of introducing
other photosynthetic agents into the body
to provide a source of oxygen for cardiac
cells.
Stanford cardiovascular surgeon Dr.
Joseph Woo recently began a research
study to bring this fantasy to fruition.
He initially limited his efforts to plants,
by grinding kale and spinach to obtain
chloroplasts, plant organelles that
perform photosynthesis. 6 When these
structures did not survive outside of the
plant cell itself, Dr. Woo and his colleagues
found an alternate option. They identified
Synechococcus elongatus, originally
used to study circadian rhythms, 7-8 as
a viable photosynthetic cyanobacteria
for introduction into the body. The
team considered S. elongatus an ideal
candidate because they could easily
engineer it to produce more metabolites,
such as oxygen or glucose. 9-10
To test whether this cyanobacterium
could immediately deliver oxygen to a
tissue, the researchers induced ischemia
in several rodents. They then randomly
grouped these rodents and injected
their hearts with S. elongatus in the
light, S. elongatus in the dark, or saline.
The researchers prevented any light
exposure in the dark group but exposed
the other two groups directly to light to
examine any differences in oxygenation
levels due to photosynthesis. Originally,
baseline oxygen levels were comparable
between the groups and dropped close
to zero when ischemia was induced. At
reassessment 10 and 20 minutes after
injection, S. elongatus caused a 25-fold
increase in oxygen from the onset of
ischemia in the light group. This was
astounding when compared to the merely
3-fold increase in oxygen levels in the
other two treatment groups. This finding
supports the idea that injection with
S. elongatus in light leads to enhanced
oxygenation in ischemic conditions,
suggesting improved metabolism and
cardiac function. 11
Dr. Woo and his team next aimed to
evaluate the metabolic state of the
heart in the living rodent body, using
temperature as an indicator of activity.
Using a form of videography, they found
10 | CATALYST

Cardiac ischemia
was induced in
rodents
Rodents were
injected with
photosynthetic
cyanobacteria
After exposure to
light, rodents had
higher oxygen
levels and increased
heart activity
no difference in left ventricular surface
temperature between the groups at
baseline and at 10 minutes. However,
at 20 minutes, the S. elongatus-treated
group exhibited improved preservation of
surface temperature in the area lacking
oxygen. Furthermore, the saline-treated
group demonstrated a decrease in
surface temperature in this area over
time, while the S. elongatus-treated group
had an increase in surface temperature
over time. This finding indicates that S.
elongatus enhances metabolic activity in
ischemic areas, unlike in the unassisted
The study’s findings
present S. elongatus as an
ideal agent for mitigating
cardiac injury in patients
experiencing ischemia.
heart. Furthermore, cardiac output – the
amount of blood that the heart pumps
in a minute – had a greater increase
from time of ischemia in the light group
than the dark or the saline group. This
provides further support that only
actively photosynthesizing S. elongatus
bacteria offer these benefits. The team
conducted further testing to explore
long-term effects of S. elongatus injection.
Magnetic resonance imaging (MRI) of
the heart four weeks after therapy in
the light group demonstrated enhanced
cardiac performance associated with
photosynthetic therapy. 11
The study’s findings present S. elongatus
as an ideal agent for mitigating
cardiac injury in patients experiencing
ischemia. However, other effects of the
cyanobacterial species on the human
body should also be considered; it would
not be sensible to assume only health
benefits by introducing an unknown
agent. Dr. Woo and his team conducted
tests with the rodent models and found
no sign of infection, unintended bacterial
growth, or immune response in the
organisms after introduction of S. elongatus.
By the 24-hour point after injection, only a few
injected bacterial cells remained. Four weeks
after therapy, the team euthanized the rodents
to examine their hearts and found no abscess
formation or residual S. elongatus. Overall,
these findings suggest that S. elongatus is nontoxic
when injected. 11
Though the findings are promising,
researchers have yet to conduct human trials,
and the bacteria could potentially exhibit
a different effect in the human body. Such
differences may be due to varying physiology,
such as the thicker cardiac muscle of humans
in comparison to rats. 12 Other obstacles could
also block widespread use of the therapy,
due to issues with availability in the absence
of a medical professional. In this case, a few
factors to consider are the safety of personal
access to S. elongatus injections, the feasibility
of injection maintenance and self-use in the
home, and the criteria to qualify for injection
access. Nonetheless, current research
indicates S. elongatus therapy has immense
potential. The cyanobacteria could even be
useful in ischemic tissues outside of the heart
and in procedures such as cardiopulmonary
bypass surgery. Overall, this therapy aims
to tackle the root of sudden cardiac death;
while S. elongatus may not be a plant, it could
blossom into a solution all the same.
WORKS CITED
[1] Heart Disease. Centers for Disease Control and Prevention,
Centers for Disease Control and Prevention, Aug. 24, 2017.
www.cdc.gov/heartdisease/facts.htm (accessed Oct. 15, 2017).
[2] Tian, Y. et al. Science Translational Medicine 2015, 7 (279).
[3] Polizzotti, B. D. et al. Science Translational Medicine 2015,
7 (281).
[4] What Is a Heart Attack? National Heart Lung and Blood
Institute, U.S. Department of Health and Human Services,
Jan. 27, 2015. www.nhlbi.nih.gov/health/health-topics/topics/
heartattack (accessed Oct. 15, 2017).
[5] Silent Ischemia and Ischemic Heart Disease. www.heart.
org/HEARTORG/Conditions/HeartAttack/Treatmentofa-
HeartAttack/Silent-Ischemia-and-Ischemic-Heart-Disease_
UCM_434092_Article.jsp#.Wfy8GrpFyuU (accessed Oct. 18,
2017).
[6] White, T. About Scope. Scope Blog, June 14, 2017. scopeblog.stanford.edu/2017/06/14/solar-powered-heart-stanford-scientists-explore-using-photosynthesis-to-help-damaged-hearts/
(accessed Oct. 19, 2017).
[7] Espinosa, J. et al. Proceedings of the National Academy of
Sciences 2015, 112 (7), 2198–2203.
[8] Kondo, T. et al. Science 1997, 275 (5297), 224–227.
[9] Shih, P. M. et. al. J. Biol. Chem. 2014, 289 (14), 9493–9500.
[10] Niederholtmeyer, H. et al. Appl. Environ. Microbiol. 2010,
76 (11), 3462–3466.
[11] Cohen, J. E. et al. Science Advances 2017, 3 (6).
[12] Price, M. Light-activated bacteria protect rats from
heart attacks. Science, June 14, 2017. http://www.sciencemag.org/news/2017/06/light-activated-bacteria-protect-rats-heart-attacks
(accessed Oct. 19, 2017).
Image from freepik.com.
DESIGN BY Sara Ho
EDITED BY Brianna Garcia
CATALYST | 11

who’s saving lives?
R B TS
by jenny s wang
R
obot-assistance has been on the
rise in the medical field in recent
years and its applications in surgical
procedures are showing significant
advantages compared to the standard
of practice. In particular, this technology
has been integrated with retroperitoneal
oncological surgery because it overcomes
some of the shortcomings of traditional
surgery practices, which can be imprecise,
more painful, and lead to slower recovery
time, in order to potentially improve
postoperative outcomes.
The retroperitoneal space, or
retroperitoneum, is the anatomical
space in the abdominal cavity behind the
peritoneum, which is the tissue that lines
the abdominal wall. In other words, the
space contains the organs related to the
urinary system that urological surgeons
operate on. These organs include the
kidneys, ureters, and adrenal glands. 1 Due
to the limitations of operative space in the
retroperitoneum, traditional procedures
usually required a substantial incision, a
disruption of soft internal organs, and a
lengthy recovery period. 2 Due to this, renal
surgeons have since adopted a minimally
invasive technique known as laparoscopic
technology, which overcomes the space
limitations that hindered early surgeons. 2
The technology has evolved quickly and
has proven more beneficial for patients
than previous approaches.
The introduction of robot-assisted
surgery was one such turning point in
laparoscopic technology. Progress in the
field of robotics has allowed for evolution
from the first ‘master-slave’ robotic
systems, which allowed surgeon control
of the robot from afar but had limited
functionality, to systems capable of more
precision and complex procedures. In
2000, the first robot-assisted laparoscopic
surgery was performed and the practice
has become increasingly popular over
the past two decades in renal surgery. 1
Today, robot assistance is favored over
pure laparoscopy due to technical ease
and comfort for the surgeon because
it provides clearer 3D visualization and
magnified imaging compared to the
human eye. 1 Additional advantages
12 | CATALYST
include a greater range of motion and a
shorter training time compared to pure
laparoscopy, allowing for greater precision
and ease of use. 1
Robot-assisted approaches have been
developed for multiple surgical procedures
involved in removal of a tumor mass in
the retroperitoneal space. For example,
in stage 1 of kidney cancer when the
tumor mass is small, the procedures
intend to remove the tumor with the
goal of preserving the rest of the kidney
and surrounding tissue 1 . This technique,
a partial nephrectomy, is the standard
approach in removal of small renal
tumors. It has similar survival outcomes
as produced by radical nephrectomy, in
which the entire kidney associated with
the tumor is removed during surgery.
THE ROBOT-ASSISTED APPROACH
HAS PROVEN USEFUL IN REDUCING
OPERATION TIME, DISCOMFORT TO
THE PATIENT, AND POST-SURGERY
COMPLICATIONS
However, renal functionality is generally
improved for patients undergoing partial
nephrectomy as compared to those
undergoing radical nephrectomy. The
introduction of robot-assisted partial
nephrectomy (RAPN), which has allowed
for a shorter operative time, faster return
to normal function, and less invasion, has
increased in popularity as even larger,
more complex renal tumors have been
successfully treated. 1 Moreover, the 5-year
survival rates of patients who underwent
the procedure have been outstanding and
have thus made this approach a standardof-care
therapy. 1
For later stages that involve larger and
more complex tumors, other procedures
utilizing robot assistance have also
been compared to typical approaches.
A prospective comparison between the
laparoscopic form and the robot-assisted
form of radical nephrectomy, a procedure
typically used for stage 2 kidney cancer
tumors. The study demonstrated that the
operative time and survival outcomes
are similar. However, the robot-assisted
procedure is more expensive. 1 For
treatment of especially invasive tumors
that have not yet spread from the upper
urinary tract, radical nephroureterectomy
(RNU) is favored. The benefits of robotassisted
RNU are decreased operative time
and postoperative complications, but the
disadvantage is that the cost is greater
than laparoscopic nephroureterectomy
operations alone. Overall, survival
outcomes are similar in both open and
robot-assisted approaches in RNU, but
advancement of the robot-assisted
technique over time will prove if there are
additional benefits and risks.
The comparisons of robot-assisted
and standard laparoscopic approaches
demonstrate that the robot-assisted
approach has proven useful in reducing
operation time, discomfort to the patient,
and post-surgery complications. Though
this technology is still facing barriers
of high cost and associated risks, the
continual advancement and improvements
for the surgeon and patients have
demonstrated that we should be optimistic
about what lies in the future for the
growing application of robot-assisted
oncological surgery in the retroperitoneal
space as well as other sites.
WORKS CITED
[1] Ludwig, W. W. et al. Frontiers in robot-assisted
retroperitoneal oncological surgery. Nature Reviews
Urology [Online]. September 12, 2017, p 1-11. https://
www.nature.com/articles/nrurol.2017.149
[2] Velanovich, V. et al. Laparoscopic vs open surgery:
a preliminary comparison of quality-of-life outcomes.
National Center for Biotechnology Information [Online],
January 14, 2000, p 16-21. https://www.ncbi.nlm.nih.gov/
pubmed/10653229
DEsign bY Nancy Cui
edited by Kelsey Sanders

F
Mirror Neurons: Unlocking the Mind
SAMANTHA CHAO
ilm, music, and literature capitalize on
conveying emotion to an audience. These
forms of art crate emotions by crafting
narratives that their audiences connect with
and believe in. Most people would place the
agency of this emotional transaction on the
movie, song, or book. However, the audience
must also be receptive to the story. In other
words, the audience must have the capacity
to empathize with the emotions portrayed by
the art. This fascinating ability for audience
members to ‘feel’ an external stimulus as
if they were experiencing it themselves is
mediated by a newly discovered type of
neuron, the mirror neuron.
Mirror neurons were first discovered in
the 1980s in macaque monkeys when
neurophysiologists at the University of
Parma, Italy, studied neurons specialized for
hand and mouth control. 1 They discovered
that certain neurons in the monkeys’
premotor cortices lit up in the same pattern
both when monkeys picked up food for
themselves and when they merely observed
other monkeys pick up food. This fascinating
discovery led to a new area of study that
focuses on the brain’s ability to adapt and
respond to its environment. Using functional
neuroimaging, which attempts to associate
cortices of the brain to certain functions,
other scientists have discovered similar
mirror neurons in the human
somatosensory cortex
that allow people to
vicariously experience
emotions when
others perform or
experience different
actions. 4
“Mirror neurons
constantly dictate our
social responses, even
without our knowledge.”
Mirror neurons
constantly dictate
our social responses,
even without our
knowledge. For instance,
many moviegoers cry at
the heartbreaking ending of
the movie ‘Titanic’, which exhibits the power
of mirror neurons to create a false sense of
personal reality. A more concrete example
of the power of mirror neurons is when Rose
attempts to free Jack from a pair of handcuffs
with an axe. The audience cringes as Rose
swings the axe at Jack’s hand, as if their own
hands are in danger.
These examples fall in line with a classic
experiment performed in the study of mirror
neurons. 2 During the study, participants hid
their hands behind a divide, then watched
as a fake, rubber hand was simultaneously
stroked along with their own, real hands.
Halfway through the experiment, without
warning, the rubber hand is smashed
with a hammer. Nearly all participants
recoiled in surprise and fear because they
established “a feeling of ownership of [a]
fake [rubber] hand”. 2 Functional magnetic
resonance imaging (fMRI) scanned
each participant’s brain activity and
revealed “evidence that cells in
the premotor cortex respond
both when a specific area of
the body is touched and when
an object is seen approaching
that area”. 3
It is easy to see the benefits
that mirror neurons
provide. New models of
human perception are
currently forming around
the concept of mirror neurons,
which may have broad implications in
the field of psychology and the study of
the human mind. This in turn may lead
to the development of novel methods of
interpersonal interaction, which has a heavy
hand in the business and marketing world.
Though the world currently knows little
about these fascinating neurons and their
mechanism of action, their far-reaching
significance may have much to contribute to
future human development and innovation.
The mirror neuron is a relatively new
finding and requires much more testing and
experimentation before it can be labeled as
an official hallmark of human physiology.
However, even with limited information, it
is abundantly clear that the neuron sparks
a rich debate regarding the world’s current
understanding of psychological study and
evaluation. Through further study, we may
be able to better understand the social
component of human nature. Perhaps
mirror neurons can even answer the age-old
question of why people love the humanities:
people enjoy being spectators.
Works Cited
[1] Winerman, L. American Psychological Association. 2005,
36, 48.
[2] Ehrsson, H. H. et al. J. Neurophysiol. 2000, 83, 528–536.
[3] Acharya, S. et al. J Nat Sci Biol Med. 2012, 3, 118-124.
[4] Kilner, J. M. et al. Curr Biol. 2013, 23, 1057-1062.
Design by: Anna Croyle
Edited by: Meredith Brown
CATALYST | 13

CHAGAS CHAGAS DISEASE: DISEASE:
A A SILENT SILENT KILLER KILLER
S
by Maishara Muquith
ilent. Deadly. With an estimated 6 to
7 million people affected worldwide,
Chagas disease is a neglected tropical
disease found mainly in Latin American
countries¹. Classified as a disease of
poverty, Chagas perpetuates inequality by
creating a disease burden in the poorest
economies². The total annual cost to
society stemming from healthcare and
lost productivity due to the disease is
$4,059 annually in Latin America for each
individual afflicted². Since Chagas causes
such a massive economic burden, more
attention needs to be paid to this lifethreatening
disease.
Chagas disease is transmitted by the blood
sucking triatomine bug, also known as the
kissing bug due to bites near the mouth or
the eyes³. As the bug bites and defecates
near the wound site, the protozoan
parasite, Trypanosoma Cruzi (T. Cruzi),
enters the body from the infected feces or
urine.In Latin American towns, the kissing
bug is found mostly in adobe houses or
enters through cracks of poorly constructed
houses¹. Other modes of infection include
mother to child transmission, consumption
of contaminated food, and blood
transfusions.
Chagas disease has two phases: acute and
chronic. The acute phase, is characterized
by muscle pain, fever, enlarged lymph
nodes, and headaches⁴. Despite this, some
people are asymptomatic. In all acute
phases, however, there is a large
amount of parasite circulating
in the blood. As the
disease develops
into the
chronic stage, the parasites hide in the
heart and the digestive tract and, as a
result, are hard to detect. Thus, people
who progress to chronic Chagas may not
show any symptoms, and this may result
in sudden death due to inflammation and
cardiac arrest years later¹.
Current treatment of Chagas include only
two drugs: benznidazole and nifurtimox.
While benznidazole is FDA approved,
nifurtimox is not. Although these drugs
are most effective in young patients and
patients with acute Chagas, the drugs have
shown a low cure rate in the chronic phase⁴.
Furthermore, both drugs have adverse
side effects including anorexia, headache,
nausea, and neuropathy⁵. They also pose a
barrier to vulnerable populations who have
limited access to healthcare since these
drugs have a long regimen (benznidazole is
taken for 60 days and nifurtimox for 60-90
days) and require constant blood work
to ensure that there is no adverse side
effects. Currently, there are no vaccines
against Chagas. Thus, the need for novel
therapeutic treatments and vaccines is
paramount.
One of the leading research institute for
Chagas, the Sabin Vaccine Institute, is
currently working hard to develop a human
vaccine against Chagas⁶. With this vaccine,
researchers hope to improve Chagas
prognosis, lower treatment cost, decrease
treatment duration, and slow disease
progression. They have already developed
a successful vaccine candidate which
can either act as a vaccine alone or be
combined with benznidazole as a form of
chemotherapy, demonstrating potential as
both a preventive and a therapeutic agent.
Chagas disease is
transmitted by
the blood sucking
triatomine bug,
also known as the
kissing bug
Early animal studies of these vaccines have
shown promising results:mouse models
treated with the vaccine have shown potent
immune response, increased host survival,
diminished cardiac fibrosis and pathology,
and reduced cardiac parasite loads⁶.
Another potential vaccine uses recombinant
adenovirus carrying sequences of the
T-cruzi parasite’s proteins. Essentially these
viruses cannot replicate in the body, but
they still produce viral proteins. Since these
viruses have T-cruzi DNA integrated into
them, they produce the T-cruzi proteins as
well. The body recognizes these elements
as foreign and mounts an immune
response against all parasite remnants.
Results from this study show that these
vaccines are effective in inciting an immune
response and decreasing parasitic load in
both the acute and the chronic phase of
Chagas⁷. The study also demonstrates that
this vaccine can be used therapeutically
to delay disease progression and reverse
heart tissue damage.
Chagas disease is a serious condition
with little attention given to the disease.
Moreover, current treatments for this
disease are few in number and pose various
adverse side effects. Current research
focuses on novel vaccine candidates aimed
at both preventing and treating the disease.
As scientists continue to focus more on this
neglected disease, a possible cure might be
on the horizon.
Works Cited
[1] Chagas disease (American trypanosomiasis). (2017). In
WHO. Retrieved from http://www.who.int/mediacentre/
factsheets/fs340/en/
[2] Lee BY et al. Lancet. 2013, 13, 342-348
[3] Montgomery, S. P. et al. Am. J. Trop. Med. 2014, 90, 814-
815.
[4] Sales, P. A., Jr. et al. Am. J. Trop. Med. 2014, 97, 1289-
1303.
[5] Castro, J. A., et al. Human Exp.Toxicol. 2006, 25, 471-479.
Barry, M. A. et al. Human Vac. Immunotherapeutics. 2016,
[6] 12, 976-987.
[7] Pereira, I. R. et al. (2015). PLoS Pathogens, 11(1),
e1004594. http://doi.org/10.1371/journal.ppat.1004594
design by Madeleine Tadros
edited by Mahesh Krishna
14 | CATALYST

CPR FOR THE VAQUITA
Celina Tran
A
ndrea, Fathom, Katrina, and Splash.
These were the names of the four U.S.
Navy-trained dolphins which bore
the responsibility of saving their distant
porpoise relatives, the vaquita, from
extinction. 1
The vaquita are the porpoises that live in
the Gulf of California, the little pocket of
sea neighbored on the west by the Baja
California peninsula and on the east by the
Mexico mainland. At their largest, they are
five feet long and have characteristic dark
“eyeliner” rings around each of their eyes.
There are an estimated fewer than thirty of
them left, 2 largely due to totoaba fishing.
The totoaba is a species of fish that shares
the same habitat as the vaquita - in the
Gulf of California. It is highly coveted for its
bladder, similar to how a rhino is coveted
for its ivory horns. The bladder is used
by the Chinese in a soup called fish maw,
which is believed to boost fertility. The
bladders are smuggled into the United
States, and then shipped to China to be
sold. Even though totoaba fishing has been
banned by the Mexican government, the
activity is still worth the risk because each
bladder can yield up to ten thousand dollars
or more. 3 The fishermen use gill nets to
catch the totoaba, unintentionally also
trapping the vaquita as bycatch. Tangled in
the nets, because they cannot resurface, the
oxygen-deprived vaquita drown.
On April 3, 2017, the government of Mexico
made an announcement: $3 million would
be given to the VaquitaCPR initiative; CPR
stands for conservation, protection and
recovery. 4 This ambitious, high-risk plan
aims to save the last few remaining vaquita.
As a part of this project, dolphins Andrea,
Fathom, Katrina, and Splash would use
echolocation to seek out the shy vaquita
so that they can be captured. They would
then be gathered and transported to a
holding pen on the west side of the gulf,
which would keep the vaquita away from
the gill nets that have been otherwise lethal
to them. 4 It was hoped that the vaquita
would adapt to captivity, breed, and their
population would grow large enough to be
eventually released back into the wild.
At least, that was the plan. Because the
vaquita had never been captured live
before, little could be done to predict
how they might handle the stress, which
scientists learned the hard way. The first
animal that was successfully captured was
a juvenile female. She had to be quickly
released because she was under too much
stress. The second, a female of reproductive
age, died in captivity. Just a few hours after
being placed in the pen, she most likely
suffered from a heart attack. 5 For the
already-tiny population, the death was a
huge loss. As a consequence, VaquitaCPR
was suspended, and the decision to cease
the capture portion of the operation was
unanimous. It was just November.
The fate of the vaquita
is in the hands of law
enforcement.
Now what? The fate of the vaquita is in
the hands of law enforcement. Poachers
must be stopped, even if they do not
target the vaquita. At the same time, any
solution must be tailored to benefit both
humans and vaquitas, as conservation
biology is intertwined with local economies
and communities. Illegal fishing must be
replaced with an alternative source of
livelihood for the fishermen. 5 Currently,
VaquitaCPR is working on identifying
the last few vaquita, using the markings
on their fins that are unique to each
individual. Acoustic recording devices
track and monitor the ranges of these
unique porpoises. Veterinarians assess
blood samples from the lab, to determine
what part of the plan - capture, transport,
or enclosure - made the vaquita panic. 5
Hopefully, the “panda of the sea” can be
saved from extinction. It serves as a story
that has greater implications, highlighting
how conservation is about balancing the
ecological concerns and the needs of the
community.
Works Cited
[1] Joyce, C. Chinese Taste for Fish Bladder Threatens Rare
Porpoise in Mexico. NPR, Feb. 9, 2016. https://www.npr.
org/466185043/ (accessed Jan. 17, 2018).
[2] Grens, K. US Navy Dolphins to Capture Vaquitas to Save
Them from Extinction. The Scientist, Oct. 6, 2017. https://
www.the-scientist.com/?articles.view/articleNo/50580/title/
US-Navy-Dolphins-to-Capture-Vaquitas-to-Save-Themfrom-Extinction/
(accessed Jan. 17, 2018).
[3] Albeck-Ripka, L. 30 Vaquita Porpoises Are Left. One
Died in a Rescue Mission. The New York Times, Nov. 11,
2017. https://nyti.ms/2hsMV5j (accessed Jan. 17, 2018).
[4] Nicholis, H. A Last-Ditch Attempt to Save the World’s
Most Endangered Porpoise. Nature, Apr. 7, 2017. http://
dx.doi.org/10.1038/nature.2017.21791 (accessed Jan. 17,
2018).
[5] Brulliard, K. A final bid to save the world’s rarest
porpoise ends in heartbreak. Is extinction next?
The Washington Post, Nov. 9, 2017. https://www.
washingtonpost.com/news/animalia/wp/
2017/11/09/a-final-bid-to-save-the-worlds-rarestporpoise-ends-in-heartbreak-is-extinction-next/?utm_
term=.79abaa181c86 (accessed Jan. 17, 2018).
Images courtesy of Pixabay
Vectors courtesy of chiccabubble and Xihn
Studio
Designed By J. Riley Holmes
Edited By Anna Croyle
CATALYST | 15

Quantum Computing
A Leap Forward in Processing Power
W
e live in the information age, defined
by the computers and technology that
reign over modern society. Computer
technology progresses rapidly every year,
enabling modern day computers to process
data using smaller and faster components
than ever before. However, we are quickly
approaching the limits of traditional
computing technology.
Typical computers process
data with transistors. 1
Transistors act as tiny
switches in one of
two definite states:
ON or OFF. 2
These states are
represented
by binary digits
known as “bits,”
1 for ON and 0 for
OFF. 2 Combinations
of bits let us describe
more complex data,
which ultimately becomes
the basis for a computer.
For instance, a 2-bit computer
has four possible bit combinations at
any given time: 11, 10, 01, and 00. Every
additional bit doubles the number of
possible combinations and increases the
computer’s ability to store and process
data. 3 Shrinking the size of transistors
allows more transistors to fit on a single
chip, giving us greater processing power
per chip. However, modern transistors
are reaching the size of only a few atoms. 4
We will soon reach the physical limit to
how small and fast a transistor can be.
Since 1975, the computer chip industry
has followed Moore’s Law, the notion
that the number of transistors on a chip
will double every two years, but recently,
delays in advancements have caused some
to announce the death of Moore’s Law. 5
Though we may not be capable of making
transistors much smaller, we can push past
their limits with a new type of computer:
the quantum computer.
Quantum computers use quantum bits,
or “qubits,” rather than bits. Qubits are
incredibly tiny particles that experience
by Valerie Hellmer
Superposition
and entanglement
allow quantum
computers to process
data faster than
traditional
computers
quantum effects like superposition and
entanglement due to their small size. 2 A
qubit is in superposition when it is in a
combination of two states simultaneously.
So while a normal bit must be either 1 or
0, a qubit can be both 1 and 0. 2 This can
be difficult to imagine since it goes against
everything we encounter throughout our
lives; a flipped coin can either land on
heads or tails, not both sides
at once. Yet qubits seemingly
defy our reality and do just
that. A 2-qubit computer still
possesses the four original
bit combinations, only
now the qubits can
simultaneously hold
all four combinations. 6
The qubits have a
probability of being in
each of the four states,
but the qubits’ actual
combination is revealed only
after being observed, which
collapses the superposition. 6
Even stranger than superposition,
quantum entanglement is when
the state of one qubit affects the state of
another instantaneously over any distance. 7
For instance, if two qubits are entangled in
opposites states, then when
one qubit changes from 1 to
0, the other changes from
0 to 1 without any delay.
This switch allows
information to travel
incredibly quickly
in a quantum
computer. But
that is not all
entanglement
has to offer;
entanglement
also lets you receive
information on a group
of entangled qubits by
checking the state of only
one qubit. 3 Superposition
and entanglement allow quantum
computers to process data faster than
traditional computers such that a 56-qubit
computer would contain more processing
power than any traditional computer
A 56-qubit
computer would
contain more
processing power than
any traditional
computer ever
built
ever built. 8 This achievement is known
as quantum supremacy over traditional
computing--an impressive feat considering
modern supercomputers can perform
93,000 trillion calculations per second. 8-9
Today’s top tech companies are getting
incredibly close to the quantum supremacy
milestone.
IBM has been researching quantum
computers for over 35 years, and has
recently shown rapid progress. 2 In May
2016, IBM released access to a 5-qubit
quantum computer online, where anyone
can develop and run their own quantum
algorithms. 1 This quantum computer has
created opportunities for both scientists
and enthusiasts to interact with qubits and
has already been used for over 1.7 million
public experiments. 10 IBM then established
a new quantum computing division called
“IBM Q” in March 2017. 1 And more recently,
in January 2018, the company developed a
50-qubit quantum computer prototype. 10
While these computers cannot beat any
classical machine at present, IBM has their
vision set on a future powered through
quantum computing. 1
Another computer company, D-Wave
Systems, is known for advancing
quantum computing with
a different approach. The
company made headlines in
2013 by selling a 512-qubit
computer called the
D-Wave Two to NASA
and Google. 11 And in
2017, the company
released a 2000-qubit
computer called
the D-Wave 2000Q,
which can run certain
algorithms 100 million
times faster than an average
classical computer. 11-12 While
these numbers make it sound
as if D-Wave Systems has easily
achieved quantum supremacy, this is not
necessarily the case. D-Wave Systems’
computers have faced a lot of controversy
since they use a “quantum annealing”
16 | CATALYST

approach which have minimal control
of their qubits.” 12-13 As a result, D-Wave
Systems’ “quantum annealing” systems can
only be applied to optimization problems,
as compared to IBM’s “gate-based” systems,
which have a much wider
scope of applications. 14-15
Despite the fact D-Wave
Systems is not
considered to have
achieved quantum
supremacy, the
company has
certainly pushed
forward the
boundaries of
computing. 16
quantum
computers may
revolutionize
the fields of
machine learning
and artificial
intelligence
While quantum
computing promises
to dramatically increase
processing power, there
are still limitations to its potential. For one,
a quantum computer cannot replace your
laptop anytime soon. Quantum computers
are extremely task specific, meaning that
even with IBM’s gate-based approach, those
ultra-high processing speeds will only work
best on certain types of problems. 16 In
addition, qubits are very unstable particles;
to be used in a computer, they have to be
kept at a temperature just a fraction of a
degree above absolute zero while shielded
from nearly all light and Earth’s magnetic
field. 16 Even the smallest vibration could
disrupt their state. Consequently, quantum
computers’ extreme operating conditions
currently confine their use to research
companies or data centers instead of
households. Likewise, the fragility of qubits
means they produce a lot of error. 16 Some
experts estimate that checking the results
of one qubit will require 100 additional
qubits, meaning that even when quantum
supremacy is reached, more qubits will
be necessary to make the computers
practical. 16 More realistically, quantum
computers could be used in conjunction
with traditional computers to yield
interesting results.
Despite its limitations, quantum computing
has the potential to transform the world.
One potential application is improving
chemical and biological models, which
need a lot of processing power to fully
represent the complex characteristics
of molecules. 16 Driven by quantum
computers, improvements in these models
could revolutionize our understanding
of chemistry, physics, and medicine. 16
Furthermore, experts believe that quantum
computers may revolutionize the fields of
machine learning and artificial intelligence,
which in turn could impact just about
every aspect of society. 16 However, some
companies and governments are also
preparing their defenses for “Y2Q,” the
year when a large-scale quantum computer
could bring down our current system of
encryption, which protects everything from
credit-card numbers to nationally guarded
secrets. 16 While some experts predict Y2Q
could occur as soon as 2026, it is difficult
to predict how security systems will change
alongside developments in computing, and
what the true impact of quantum
computers will be.
Works Cited
Much like how no one could
have predicted the future
of computers in the
1960s, we cannot tell
how much quantum
computing will shape
our lives in the coming
decades. However, with
every technology come
risks and benefits, and no
matter what, researchers
will continue to push the
boundaries of human capability.
[1] Murphy, M. IBM Thinks It’s Ready to Turn Quantum
Computing into an Actual Business. Quartz, Mar. 05,
2017. https://qz.com/924433/ibm-thinks-its-ready-to-turnquantum-computing-into-an-actual-business/
(accessed
Oct. 20, 2017).
[2] Castelvecchi, D. Quantum computers ready to leap
out of the lab in 2017. Nature News [Online], Jan. 03,
2017. Nature Publishing Group. http://www.nature.com/
news/quantum-computers-ready-to-leap-out-of-the-labin-2017-1.21239
(accessed Nov. 17, 2017).
[3] Steane, A. Quantum computing. Rep. Prog. Phys. 1998,
61, 117-173.
[4] Markoff, J. Smaller, Faster, Cheaper, Over: The Future
of Computer Chips. The New York Times [Online], Sept. 26,
2015. https://www.nytimes.com/2015/09/
27/technology/smaller-faster-cheaper-over-the-future-ofcomputer-chips.html
(accessed Oct. 20, 2017).
[5] Novet, J. Intel Shows off Its Latest Chip for Quantum
Computing as It Looks past Moore’s Law. CNBC, Oct. 10,
2017. https://www.cnbc.com/2017/10/10/intel- delivers-
17-qubit-quantum-computing-chip-to-qutech.
html (accessed Oct. 20, 2017).
[6] Lochan, K.; Singh, T. Nonlinear quantum
mechanics, the superposition principle,
and the quantum measurement
problem, 2010, arXiv:0912.2845 [quantph]
(accessed Jan. 19, 2018).
[6] Raimond, J. et al. Manipulating
quantum entanglement with atoms
and photons in a cavity. Rev. Mod.
Phys. 2001, 73, 565-582.
[8] Kim, Mark. Google’s quantum
computing plans threatened by
IBM curveball. New Scientist,
Oct. 20 2017. https://
www.newscientist.com/
article/2151032-googlesquantum-computingplans-threatened-by-ibmcurveball/
(accessed Jan.
19, 2018).
[9] Dongarra, J. China
builds world’s most
powerful computer.
BBC News [Online],
June 20 2016.
http://www.bbc.
com/news/
technology-36575947 (accessed Jan. 19, 2018).
[10] Morse, J. IBM’s quantum computer could change the
game, and not just because you can play Battleship on it.
Mashable, Jan. 08, 2018. http://mashable.com/2018/01/08/
ibm-quantum-computer-ces-201i8/#NewKKb33GOqh
(accessed Jan. 19, 2018).
[11] Jones, N. Google and NASA Snap Up Quantum
Computer D-Wave Two. Scientific American [Online], May
17, 2013. https://www.scientificamerican.com/article/
google-nasa-snap-up-quantum-computer-dwave-two/
(accessed Nov. 17, 2017).
[12] Gibney, E. D-Wave upgrade: How scientists are using
the world’s most controversial quantum computer.
Nature News [Online], Jan. 24, 2017. Nature Publishing
Group https://www.nature.com/news/d-wave-upgradehow-scientists-are-using-the-world-s-most-controversialquantum-computer-1.21353
(accessed Nov. 17, 2017).
[13] Denchev, V. et al. Phys. Rev. X. 2016, 6, 031015.
[14] Michielsen, K. et al. Benchmarking gate-based
quantum computers, 2017. arXiv:1706.04341 [quant-ph]
(accessed Nov. 17, 2017).
[15] Marchenkova, A. What’s the difference between
quantum annealing and universal gate quantum
computers?. Medium, Feb. 28, 2017. https://medium.com/
quantum-bits/what-s-the-difference-between-quantumannealing-and-universal-gate-quantum-computersc5e5099175a1
(accessed Jan. 19, 2018).
[16] Nicas, J. How Google’s Quantum Computer Could
Change the World. The Wall Street Journal [Online], Oct.
16, 2017. Dow Jones & Company. https://www.wsj.com/
articles/how-googles-quantum-computer-could-changethe-world-1508158847
(accessed Oct. 20, 2017).
design by Namtip Phongmekhin
edited by Brianna Garcia
CATALYST | 17

ROBOTS AND MEDICINE: A CO
F
rom completing common household
activities to performing dangerous tasks
on the International Space Station,
the modern day robot has become more
notably human-centered, picking up where
humanity’s physical capabilities have left off.
As they continue to become more applicable
to human life, the functionalities of robots
have expanded to cover many different fields
of study, including biomedicine, where a
robot’s practicality has been scaled down to
the molecular level.
Dr. Lydia Kavraki, a professor and
researcherat Rice University’s School of
Engineering, is one of the pioneers pursuing
the connections between the two domains
of robotics and bioinformatics. As a young
graduate student, Dr. Kavraki became
interested in robotics when she realized
how helpful robots can be for humans. She
remembers, “there were robots in these labs
and they didn’t do anything! They were just
static! And I was fascinated and said, okay,
these robots should do something and I
should work on motion planning.” As it is
defined today, the motion planning problem
is the problem of moving our “robot,” no
matter how small the size, from one place to
another while avoiding obstacles and walls.
Dr. Kavraki’s motion-planning algorithm
was developed many years ago, but it has
provided a foundation for modern-day
projects and research to expand upon. To
understand the algorithm, the concept of
“degrees of freedom” must be introduced.
These degrees can be thought of as the range
or mobility of certain mechanical systems,
such as the arm of a robot. More complex
robots would require systems with a greater
number of degrees of freedom and would be
much more difficult to plan a path for. A valid
motion can only be achieved by performing
actions that are feasible, or in other words,
within the specified degrees of freedom and
the robot’s physical constraints. 1
The complexity of this problem involves
determining the solution space, which is
defined as the set of all solutions that satisfy
the problem’s constraints. Previous methods
used in the robotics community have tried to
plan a path by partitioning the solution space
into its free parts, where the robots could
move, and forbidden parts, areas that were
obstacles and infeasible for motion. However,
Dr. Kavraki’s algorithm, called the Probabilistic
Roadmap Method (PRM), actually takes
samples of the space to test the mobility
of the robot. After sampling the solution
space, the algorithm then finds connections
among the different configurations of the
robots, and captures this connectivity in
a series of queues, forming approximate
maps of the free space. 2 The effects of Dr.
Kavraki’s research are prominent throughout
the robotics and biological industries, and
these sampling-based motion planners have
since been implemented in a variety of her
projects. Dr. Kavraki’s Open Motion Planning
Library (OMPL) has not only been used in
60 different robotics systems, but has also
become a fundamental component of the
Robot Operating System, the conventional
framework for writing robot software. 3
Ultimately, this computational approach
has become the basis for more complex
problems brought up within the robotics
and bioinformatics communities, regardless
of the dimensions of the solution space. In
the words of Dr. Kavraki, “We [now] have
efficient techniques for a very large number
of robots that [were] just impossible before
the invention of the sampling space and the
motion planning algorithms.” Furthermore,
these techniques can be scaled down to the
molecular level, where even motions of 1000
degrees of freedom can be measured. 1
It turns out that some of
the algorithmics that we
use for modeling robots
and modeling motion can
be used and adapted to
reason about shape and
function of molecules.
While working on her research, Dr. Kavraki
discovered a remarkable relationship
between robots and another kind of machine
billions of times smaller that resides in
our bodies - the protein. “It turns out that
some of the algorithmics that we use for
modeling robots and modeling motion can
be adapted to reason about shape and
function of molecules,” Dr. Kavraki explains.
She also expresses the idea that there is
an “underlying theoretical component” that
connects these two domains, which prompted
her to work on projects integrating both
fields.
Perhaps the most significant application in
the robotics domain is with the NASA Johnson
Space Center. The Robonaut 2 (R2), which
is currently up in the International Space
Station, was designed and created by NASA
in collaboration with Dr. Kavraki’s team.
18 | CATALYST

NNECTION OF MANY DEGREES
R2 is incredibly dexterous, having a total
of 34 degrees of freedom in its main body,
and is able to perform simple tasks such
as using human tools, fetching cargo bags
and measuring the quality of the air tank.
Furthermore, this humanoid robot takes over
repetitive and potentially life threatening
procedures that the astronauts on board can
avoid. 3 For example, it inspects the outside
of the space station and aids the docking of a
shuttle to a space station that is in continual
orbit. 4 This difficult procedure relies on
identifying and calculating the degrees of
freedom of both the shuttle and docking
platform. “You really want a robot to do this
job. You don’t want humans out to get all
the radiation as they inspect the outside of
the space station,” Dr. Kavraki comments.
Looking forward, she says, “NASA is interested
in robotics applications for caretaking
operations for astronauts, for future missions
to Mars, for establishing habitats that would
later be populated by humans.”
In the biomolecular domain, Dr. Kavraki’s
algorithm has enabled researchers to
determine the structures and motions of
molecules. It has also helped develop handson
techniques that have become integral
in medical procedures, such as the closing
of wounds by tying knots used in surgical
suturing. 3 In the past, suturing techniques
were extremely challenging and required
precise measurements to perform, but
by applying Dr. Kavraki’s motion planning
research, robotic surgical systems were able
to determine a motion pathway for directing
the surgical needle to specific locations that
minimize the interaction forces between the
needle and tissue. This has allowed suturing
to become more automated and precise.
In addition, her work has led to an efficient
way of analyzing molecular binding
conformations, another form of docking,
where interactions between molecules such
as those between a ligand and receptor can
be modeled to design new therapeutics.
Ligand docking can be determined in a
manner similar to shuttle docking. A motion
space is first explored. Then, depending on
the size of the ligand--the larger and more
flexible the ligand is, the more degrees of
freedom these large molecules have--docking
can be modeled computationally. These
interactions are often more challenging,
as the motion space for a large ligand has
increased dimensionality. 5 By undergoing
dimension-reducing techniques that use the
PRM as a foundation, Dr. Kavraki’s research
is able to simplify the process of obtaining a
valid motion space.
Dr. Kavraki’s research in the molecular
domain has led to applications in the
medical field, specifically the Kavraki Lab’s
immunotherapy project in collaboration
with MD Anderson. While the medical labs
perform the actual experiments, the Kavraki
Lab helps design the receptors involved
in immunotherapy and does modeling to
narrow down the many possible receptor
conformations for them to test. In other
words, they perform the experiments from a
computational perspective. 3 “We try to show
them how different proteins and receptors
and peptides dock, that is, what is the relative
position when they interact,” Dr. Kavraki says.
Currently, Kavraki and her lab are trying to
understand the mechanics of the motions of
these large molecules using techniques that
have already been established by the PRM.
In the future, Kavraki hopes to see her work
being implemented for constructing robots
that aid people with special needs and
accomplish tasks that are beyond physical
reach. She also looks forward to progress
on the immunotherapy project, where the
applications of her research can help patients
with severe medical conditions. “To improve
the quality of life, “ Dr. Kavraki says, is the
main objective of her passion and dedication
to these studies.
WORKS CITED
[1] Teodoro, M. L. et al. IEEE International
Conference on Robotics and Automation
2011, 1, 960-966.
[2] Kavraki, L. et al. IEEE Transactions on
Robotics and Automation 1998, 14, 166-171.
[3] Kavraki Lab. kavrakilab.org (accessed Nov.
05, 2017)
[4] Robonaut.robonaut.jsc.nasa.gov/R2
(accessed Nov. 05, 2017)
[5] Dhanik, Ankur. et al. BMC Structural
Biology 2012, 13, 48-55
DESIGN BY Christina Tan
EDITED BY Albert Truong
by Alan Ji
Dr. Lydia Kavraki
Lydia E. Kavraki is the
Noah Harding Professor of
Computer Science, professor
of Bioengineering, professor
of Electrical and Computer
Engineering, and professor
of Mechanical Engineering at
Rice University. She received
her B.A. in Computer Science
from the University of Crete
in Greece and her Ph.D.
in Computer Science from
Stanford University. Her
research contributions are in
physical algorithms and their
applications in robotics (robot
motion planning, hybrid
systems, formal methods in
robotics, assembly planning,
micromanipulation, and
flexible object manipulation),
as well as in computational
structural
biology,
translational bioinformatics,
and biomedical informatics
(modeling of proteins and
biomolecular interactions,
large-scale functional
annotation of proteins,
computer-assisted drug
design, and the integration
of biological and biomedical
data for improving human
health).
CATALYST | 19

AMP
ing up the
defense system
BY PREETHAm BACHINA
A
rguably one of the greatest achievements
in modern medicine has been the
discovery and creation of antibiotics to help
the human body combat bacterial infections.
However, the overuse of antibiotics has led
to the development of another crisis: growing
bacterial resistance to antibiotics as evidenced
by the growing strains of Methicillin-resistant
Staphylococcus aureus, or MRSA, and other
similar organisms. This phenomenon of
antibiotic resistance is an unfortunate result
of the natural process of evolution. As more
antibiotics are used, the nonresistant strains
of bacteria will succumb to the antibiotic
while the resistant strains will proliferate
at a high rate. There is a dire need for the
development of novel antibiotics and other
similar treatments. 4 Fortunately, a new class
of antibiotics has recently been discovered
that may serve as a potential solution to
antibiotic resistance. Because they were
just recently discovered and have not been
used extensively in modern medicine, most
bacterial strains have not developed any form
of resistance to these new antibiotics making
them very promising therapeutic agents in the
future.
This new class of antibiotics, called antimicrobial
peptides (AMPs), works to kill
bacteria by destroying their lipid membranes. 2
A cell is defined by its ability to maintain a
this new class of antibiotics, called anti-microbial peptides (amps), works
to kill bacteria by destroying their lipid membranes...when the membrane
is structurally attacked and subsequently compromised, the cell becomes
dysfunctional and dies.
separate environment inside from the outside
via a lipid membrane; when the membrane
is structurally attacked and subsequently
compromised, the cell becomes dysfunctional
and dies. A large subset of AMPs work by
creating holes in the bacteria’s membrane
while other AMPs work by leaking selective
ions to kill the bacteria. On the other hand,
20 | CATALYST
conventional antibiotics, like penicillin, act Dr. Huang and his team developed and
on bacterial proteins in order to hijack the modified methods to study such a unique
bacteria’s internal machinery to prevent cell system. “It’s so thin, just 40 Å thick. How do
wall formation and mitigate bacterial growth. 9 you study this structure? It cannot be optical;
While conventional antibiotics have been it’s far too thin for that … For the detail, we
researched extensively, AMPs still hold many end up relying on x-rays and neutron in-plate
mysteries that researchers are still trying to scattering. These methods use x-rays or
explain.
neutrons and send them as a beam and see
“It’s [the membrane] so thin, just 40 Å thick. How do you study this
structure? It cannot be optical; it’s far too thin for that…For the
detail, we end up relying on x-rays and neutron in-plate scattering.”
how they are scattered. From these scatter
Dr. Huey Huang, a professor of physics at patterns we can extrapolate structure,” Dr.
Rice University, has spent much of his career Huang explains. In order to study the effect of
studying membrane biophysics and the AMPs on a cell membrane without having to
effect of drugs like AMPs on the membrane. deal with living bacterial cells every time, Dr.
Dr. Huang was drawn to the membrane, Huang uses giant unilamellar vesicles (GUVs),
because unlike other biological systems, the which are large cell membranes without cell
membrane is relatively physical, in nature. organelles inside. According to Dr. Huang,
Moreover, membranes are extremely difficult using GUVs with a similar composition to
to study due to their small size, as evidenced bacterial cell membranes in order to study
by their thickness of just 40 Angstroms (4 the effects of AMPs is far easier than using
10-9 m), as well as the fact that membranes actual living bacteria since the bacteria will
must be studied in an aqueous setting. inevitably die during the course of the study.
Dr. Huang was attracted to the challenges Using these methods, Dr. Huang has been
studying cellular membranes posed and has able to elucidate the mechanism behind the
spent much of his career developing tools membrane-active variety of AMPs. By placing
and methods to do so. These challenges are AMPs into a giant unilamellar vesicle and
using neutron scattering, Dr. Huang found
that for the AMP to successfully attack the
membrane and create pores, the AMP must
be on both sides of the GUV membrane.
To enter the interior of the vesicle, the
AMP binds to the GUV membrane from the
outside, which allows a minuscule amount
of AMPs to diffuse into the interior. Once a
particular ratio of AMP to phospholipids in the
best exemplified by the amount of scientific membrane is exceeded, pores are formed and
progress that has occurred in the study of the membrane is destroyed. 3
proteins. While over 12,000 soluble proteins
have been crystallized, only a little over 500 Recently, Dr. Huang was part of a team
membrane proteins have been crystallized that discovered the mechanism of action
to have their structure revealed, despite behind daptomycin, an AMP drug that
representing somewhere between 20 and had been approved by the Food and Drug
30% of all proteins in an organism. 1,3 Administration despite its mode of action

AMPs
Giant unilamellar vesicle
AMPs bind and diffuse inside the vesicle,
destroying the vesicle’s membrane
To enter the interior of the vesicle, the AmP binds to the guv membrane from the outside, which allows
a minuscule amount of AmPs to diffuse into the interior. Once a particular ratio of AmP to phospholipids
in the membrane is exceeded, pores are formed and the membrane is destroyed.
being unknown. Using a combination of
imaging techniques, Dr. Huang and his team
found that daptomycin binds to a certain
component of the GUV membrane called
phosphatidylglycerol (PG). 4 He and his team
also found that daptomycin’s mechanism
of action depends on the concentration
of extracellular calcium, an important ion
that the cell regulates carefully. 4 After a
certain calcium concentration is exceeded,
daptomycin begins to bind to the membrane
and makes it permeable to potassium. 4 This
permeability to potassium prevents the
bacteria from maintaining the proper ion
concentrations it needs to survive. The exact
moment in which this permeability is induced
appears to be when there is a daptomycin/
calcium ratio of 2:3 and a daptomycin/PG
ratio close to 1:1. 4
According to Dr. Huang, much work in
the study of AMPs remains to be done as
the “[it is] a young field and [is] growing in
importance.” One of Dr. Huang’s main goals
is: to find general groups of AMPs that have
similar mechanisms of actions. Finding these
general groups would make development
of newer AMP-based antibiotics a much
easier task and allow for greater variety in
therapeutic products. Another major aim is
to find classes of AMPs that are effective at
differentiating between human and bacterial
cells; this is a difficult process because AMPs
target the cell membrane, which is shared
by both organisms., However, these cell
membranes have some minor compositional
differences, and drugs like daptomycin can
bind to components unique to bacteria, like
PG. 2 In order for AMPs to be more effective
in a clinical context, Dr. Huang hopes to find
other AMPs like daptomycin and study them
to determine how this specificity is achieved.
Dr. Huang is not alone in his research
on AMPs. Many other researchers and
corporations around the world are trying
to discover or create new AMPs in order to
combat the growing problem of antibiotic
resistance. According Dr. Huang, “Lots of
people are trying to develop AMPs for clinical
use; the money incentive is always there.
Some have succeeded, like daptomycin has.
Relatively fewer people are trying to figure out
the exact mechanism.” However, collaboration
with the pharmaceutical companies that
are trying to develop AMP drugs hasn’t
One of dr. huang’s main goals is to find general groups of Amps that have
similar mechanisms of actions. Finding these general groups would make
development of newer AmP-based antibiotics a much easier task and allow
for greater variety in therapeutic products.
always been easy. “I have talked to many
biotechnology companies,” says Dr. Huang.
“They are sort of interested in mechanisms,
that’s why they talk to me but they don’t
give me much detail of their clinical trials or
anything. They consider that to be business
secrets.” This lack of collaboration makes it
difficult for progress in the field of AMPs since
information sharing allows researchers to
build upon the work of others and inspire new
experiments. 5
As the nuances of AMPs are further
researched and discovered, this class of drug
may soon become a viable alternative to
antibiotics. With continued innovation as well
as exponential advances in technology, we
will be able to mitigate and eventually cure
the ever-evolving problem of antibacterial
resistance, and the answer to this debilitating
issue lies in the foundation of AMPs. By
harnessing the power of AMPs and their
exploitable capacity to kill bacteria while
facing no resistance, we will be able to solve
the problem of antibacterial resistance, once
and for all.
WORKS CITED
[1] Carpenter, E. P., et al. Curr Opin Struct Biol. 2008, 5,
581-586.
[2] Epand, R. M., et al. Mol Biosyst. 2009, 1788, 289-294
[3] Huang, H. W., et al. Phys Rev Lett. [Online] 2004, 92,
198304. http://hwhuang.rice.edu/pdfs/Huang2004.pdf
(accessed Feb. 21, 2018)
[4] Lee, MT., et al. Biophys J. 2017, 113, 82-90
[5] Mahlapuu, M., et al. Front Cell Infect Microbiol. [Online]
2016, 6, 194. https://www.frontiersin.org/articles/10.3389/
fcimb.2016.00194/full (accessed
Feb. 21, 2018).
[6] Parker, Joanne L., et al. Adv Exp Med Biol. 2016, 922, 61-72.
[7] World Health Organization. http://www.who.int/
mediacentre/news/releases/
2017/running-out-antibiotics/en/ (accessed December 22,
2017).
[8] USGS. https://www2.usgs.gov/datamanagement/share/
guidance.php (accessed Dec. 22, 2017).
[9] Yocum, R. R., et al. J Biol Chem. 1980, 255, 3977-3986
DESIGN BY
EDITED BY
Evelyn Syau
Vatsala Mundra
CATALYST | 21

Creating Global
Bioengineering Methods to Foste
A
round the world, more than 3
million children under the age
of 5 die every year from acute
respiratory infections 1 , most of which are
in the developing world. However, the
development of accessible and low-cost
technology in low-resource settings can
easily save these children’s lives. Recently,
a team of engineers at Rice University
led by Dr. Maria Oden has developed the
Pumani CPAP (Continuous Positive Airway
Pressure) machine, a novel mechanism
featuring cost-effective methods to solve
the problem of acute respiratory infections
in infants in low-resource settings.
Dr. Maria Oden, the director of the
Oshman Engineering Design Kitchen
(OEDK) and a professor in the department
of bioengineering at Rice University, guides
undergraduate students to create devices
solving global health issues. Dr. Oden
was inspired to research these types of
technologies to provide interesting design
projects for bioengineering students,
especially since “babies around the world
are dying needlessly from conditions that
we treat easily in the developed setting,
[and] something [can be done] to prevent
these types of deaths.”
The CPAP machine solves one of these
problems, helping newborn infants breathe
by treating acute respiratory infections.
By continuously pumping pressurized
flow into the lungs, the machine ensures
air sacs do not deflate, making it easier
to breathe for the infant. According to Dr.
Oden, the CPAP system works by keeping
an infant’s lungs inflated, since premature
infants often have lungs that collapse or
are too small. By blowing pressurized air
into lungs, the machine has helped bring
newborn survival up from 24% previously
to 65% currently.
The design process necessary to create the
CPAP machine was extensive, requiring
Dr. Oden and her colleague Dr. Richards-
Kortum to travel to Malawi to talk to
physicians about their technological needs.
Through interviews and observation, they
learned that almost 50% of the babies who
are prematurely born have respiratory
By continuously pumping pressurized flow into the lungs, the
cpap machine ensures air sacs do not deflate, making it easier to
breathe for the infant.
distress. But there was an even bigger
problem. The systems available at the time
cost $8,000 each, making them difficult to
access in places that needed them most,
low-resource settings.
Dr. Oden and her colleagues saw this
as an opportunity to engage senior
bioengineering design students. According
to Dr. Oden, “the student team worked
over the course of the year and came up
with a really amazing design.” Despite
its lack of aesthetic appeal (Dr.
Oden says it looked like a
plastic shoebox from
Target), the students
were able to achieve
pressures and flows
similar to that of
the expensive
system used at
Texas Children’s
Hospital. The
student project
also cost about
$140 - more than 50
times less than the
industry cost. Upon
testing, the student
project matched the flows
and pressures of existing CPAP
machines. With this promising data,
the system was taken to Malawi, where it
received user feedback and suggestions
for improvement, all culminating in a unit
ready for clinical trial.
Looking back at the experience, Dr. Oden’s
favorite recollection was during the start of
clinical trials. “We were training the nurses
on how to use the system, and we got a
call from one of our physician-colleagues
who was on call at the emergency room
in the hospital, and he said: “I have a
baby here that really needs CPAP. Are
you guys ready?” Dr. Oden and her team
were excited to put their machine to the
test, finally being able to use it to help the
sick baby who had a low oxygen
saturation and whose eyes
were rolled up in her
head. After putting
the baby on CPAP,
the baby became
alert within the
hour; she was
able to nurse
and breathe
comfortably.
Dr. Oden could
see the impact
this design had
on its users: “I
felt directly the
work was impacting
this baby’s life.” But
she also realized the
impact of her guidance and
mentorship. She saw greegone
of the student designers of the CPAP,
who had taken a job with the Rice
bioengineering team that ran the clinical
trial, watch her device save a baby. For Dr.
22 | CATALYST

Change
r Neonatal Care
by Pujita Munnagi
Oden, “the product of [her] work is the
baby that was saved but also this former
student who had a growth experience and
is capable of doing many amazing things
beyond that. And we’ve seen her do that
now. So for me, that one moment was just
unbelievable.”
that’s really our focus
now - how do you
implement an entire
neonatal nursery? what
we’re trying to do is
create that same kind
of neonatal intensive
care unit, but that is
appropriate for the
world’s poorest places
The Pumani CPAP project is one of several
completed by the Rice 360° Global Health
program. In her time in the program, Dr.
Oden has worked with colleagues and
students to fulfill most needs of neonates
and infants. Even though the CPAP
machine will
help premature
infants breathe,
they cannot survive
without right amount of
heat, the right fluids, or the
right nutrition. Since they are
prone to so many issues, they need
a comprehensive care unit that addresses
all of their needs. According to Dr. Oden,
“That’s really our focus now - how do you
implement an entire neonatal nursery?
What we’re trying to do is create that same
kind of neonatal intensive care unit, but
that is appropriate for the world’s poorest
places.”
For Dr. Oden, a big part of her work is
collaborating with colleagues of different
disciplines and cultures and making sure
engineers use their skills to help the
world at-large. Dr. Oden hopes the future
also involves creating neonatal intensive
care units (also known as NEST systems)
and implementing them in hospitals all
around the world. If successful, at least
half a million lives a year would be saved,
according to Dr. Oden. Another future
area of focus is maternal health: care
throughout pregnancy, gestation, and the
delivery period. In the words of Dr. Oden,
such care is critical because “if the babies
have a safer delivery and birth, they’re
more
likely
to survive.
And if the
mom has a safer
delivery, she’s more likely
to survive to be able to raise that baby
well.” In addition to creating NEST systems
and teaching students how to solve
problems that impact global health, she
enjoys knowing the students she instructs
will go on to have influences in several
ways. According to her, it’s about enabling
engineers to ensure that they can and
should make a difference.
Works Cited
[1] Denny FW, Loda FA. Acute respiratory infections are
the leading cause of death in children in developing
countries. The American Journal of Tropical Medicine
and Hygeine 1986, 35, 1-2. https://www.ncbi.nlm.nih.gov/
pubmed/3946732 (accessed November 15, 2017).
[2] Rice 360° Institute for Global Health. bCPAP
Continuous Positive Airway Pressure. http://www.rice360.
rice.edu/bcpap (accessed November 15, 2017).
Design By Madeleine Tadros
Edited By Deepu Karri
infant
tubing port
water
bottle
total flow
meter
O2 flow
o2 inlet
meter
port CATALYST | 23

Mitochondrial Health
IMPLICATIONS FOR BREAKTHROUGH CANCER TREATMENT
SARAH KIM
B
eginning in the late 1980s, health
disorders and genetic diseases have
become increasingly attributed to the
mitochondria. Current research projects
use model organisms to understand the
implications of mitochondrial health on the
whole organism. Some of the most fruitful
research has been performed using the
model organism Caenorhabditis elegans, or
C. elegans. C. elegans is a type of nematode
(roundworm) that is only 1 millimeter in
length. Most viewers peer into a microscope
of these nematodes and see modest, squirmy
lines. Dr. Natasha Kirienko peers into the
microscope and sees limitless potential for
discovery. In an attempt to redefine disease
treatment at a global level, Dr. Kirienko
studies mitochondria surveillance pathways
and their implications on genetics and cancer
medicine.
Dr. Kirienko was brought to Rice University
by a $2 million grant from the Cancer
Prevention Research Institute of Texas
(CPRIT). As an undergraduate and graduate
student in Russia, Dr. Kirienko didn’t have
the opportunities or equipment to pursue
the research she was interested in. Coming
to America, however, she found herself with
access to advanced lab equipment and a
relatively enormous stipend—compared
to her maximum stipend of $12/month in
Russia—with which she could do whatever
she wanted. “Suddenly, the sky is your limit,”
she declared, as a sure smile reached her
eyes. “I didn’t need any encouragement to
work hard.” Dr. Kirienko’s mindset has been
infectious, as it has definitely motivated
Elissa Tjahjono, a graduate student currently
working in the Kirienko Lab. Dr. Kirienko
elaborates on how “hardworking and
motivated” Ms. Tjahjono was during her
studies and how her determination has led
her into graduate school, allowing her “to do
substantial amount of work in a year or so.”
Ms. Tjahjono was the first author of a recent,
monumental paper in Dr. Kirienko’s lab on a
mitochondrial surveillance pathway important
in the pathogenesis of Pseudomonas
aeruginosa, a bacteria that affects cell iron
availability and causes organism death. 1
Dr. Kirienko’s fascination with the
mitochondria began in graduate school.
She had read about a particular gene motif,
or a distinct sequence of DNA, called the
Ethanol Stress Response Element (ESRE).
This motif had been identified by different
scientists seven different times, and it was
shown to be upregulated (expressed more
as a gene) by ethanol-induced heat shock
(heat shock occurs when a cell is subjected
to a higher temperature than ideal). 1 During
Mitochondrial
diseases have
now become
the number
one genetic
disorder
her PhD studies, Dr. Kirienko discovered an
anomaly: a genetic mutant that was actually
supposed to reduce expression of the ESRE
gene instead caused upregulation. Further,
she found that the mutant was sensitive
to not just one , but multiple stressors. So,
“there was this puzzle [relating to ESRE]
that [involved] multiple conditions that
were different from each other.” She began
asking the questions: what is the underlying
mechanism? What triggers ESRE activation?
This led into her postdoctoral studies, during
which she researched interactions between
C. elegans and its accompanying pathogen,
Pseudomonas aeruginosa. During that time,
Dr. Kirienko and her colleagues found a
siderophore (iron carrier) called pyoverdine,
produced by P. aeruginosa, kills C. elegans by
causing severe mitochondrial damage. Almost
all living organisms require iron for their
survival, but it is difficult to acquire iron from
the environment. Animals have complicated
immune systems that limit the ability of
pathogens to acquire iron during infection. 2
Pyoverdine has evolved to surmount this
difficulty, and it is capable of getting inside
of host cells, taking away iron, and bringing
it back to bacteria. Pyoverdine, she found,
can remove up to a third of iron (III), which
is about 20-25% of iron within the host. This
results in organismal death. 1
How are the two distinct concepts of ESRE
and pyoverdine related, one may ask? At Rice,
Dr. Kirienko found that the ESRE pathway
was also upregulated after exposure to
pyoverdine, leading her to understand that
pyoverdine exposure and heat shock are
two very different stressors. It also led her
to draw the connection between ESRE and
mitochondrial damage. ESRE is upregulated
in mutants that are affected by a variety of
stressors. Pyoverdine is a direct stressor
that upregulates ESRE in the mitochondria.
According to the two previous statements,
there must be some kind of association
between ESRE and mitochondrial damage.
With this juncture acting both as a conclusion
and a foundation, the Kirienko lab took the
next step. They used small molecule drugs
such as rotenone and antimycin (known
mitochondrial poisons) to test the possibility
of the effects of ESRE on mitochondrial
damage. After much experimentation in the
lab, they “were able to link this presence of
[ESRE] in the promoter of effector genes of
mitochondrial damage.”
Now, the Kirienko lab is working on
understanding how pyoverdine is produced
in bacteria. Testing for drugs that may inhibit
this pyoverdine factor, the lab recently
found small molecules that can prevent
pyoverdine synthesis or function. The tests
are on a path to success, and a collaborator is
24 | CATALYST

currently testing the drugs in mice. Beyond
these projects, Dr. Kirienko has a broad
vision for the future implications of her
lab’s work. One of those is developing
future medicine for patients with cystic
fibrosis, a disease tied deeply to excessive
inflammation influenced by pyoverdine
presence. 3 Another goal to understand how
to “leverage mitochondrial dysfunction
[in] cancer.” Dr. Kirienko knows that
cancers, in general, tend to accumulate
lots of mutations, and the mutation rate in
mitochondria is noticeably higher, due to
less checkpoint mechanisms. This means
that mitochondria become dysfunctional
much faster than, for example, nuclear
DNA. 4 Accordingly, the lab was able to
identify a subset of cancer cells that are
most sensitive to mitochondria-damaging
chemotherapeutics. They are now using
C. elegans to find exactly which mutations
cause the sensitivity. If this research
succeeds, then the lab “will be able to
get a step closer to personalized cancer
medicine.”
“Mitochondrial diseases [have] now
[become the] number one genetic
disorder,” Dr. Kirienko states.
Mitochondrial diseases have a variety
of phenotypes, spanning from subtle
muscle fatigue to complete nonfunctional
muscles and neurons. The severity, she
hypothesizes, depends on how pathways
mitigate mitochondrial damage. If these
pathways, like the ESRE pathway, are
performing well, then patients with
affected mitochondria can have a much
better healthspan, she extrapolates.
Thus, if her lab can find the “members
of the pathway,” they can find drugs that
work with molecules activated within
dysfunctional mitochondria. “Being able
to transfer that to human health is a big
thing,” she commented. The Kirienko
lab is in the process of finding specific
transcription factors that bind to ESRE.
They carry the hope of developing future
medicine that will specifically target
mitochondrial-related cancers.
Works Cited
[1] Tjahjono E., Kirienko NV. PLoS Genetics. 2017, 6,
http://journals.plos.org/plosgenetics/
article?id=10.1371/journal.pgen.1006876 (accessed Jan.
28, 2018).
[2] Our Need for Iron. http://www.irondisorders.org/
our-need-for-iron/ (accessed February 20, 2018), Iron
Disorders Institute.
[3] National Cancer Institute Dictionary of Cancer Terms.
https://www.cancer.gov/publications/
dictionaries/cancer-terms (accessed January 28, 2018),
National Institutes of Health.
[4] All About Mitochondria. http://www.lhsc.on.ca/
Patients_Families_Visitors/Genetics/
Inherited_Metabolic/Mitochondria/ (accessed February
20, 2018), London Health Sciences Centre.
E
E
E
ESRE
GFP
3XESRE::GFP
The ESRE motif is activated by
mitochondrial damage. Sequence
of the Ethanol and Stress
Response Element (top).
Activation of ESRE-controlled GFP
expression after exposure to a
mitochondria-damaging drug
rotenone (bottom).
Images by Photoroylaty at Freepik
Design By J. Riley Holmes
Edited By Kalia Pannell
CATALYST | 25

The Wateworks
DRINKING WATER FOR ALL
by Andrew Mu
W
ater is the most abundant natural
resource on Earth , yet clean drinking
water remains inaccessible for almost
one billion people across the globe. 1 This is
because drinking water requires the right
infrastructure, which isn’t always available.
Refugee camps, small islands, and developing
countries are just a few examples of settings
where obtaining clean water is a daily struggle.
Though improving water accessibility is a
hefty task, Dr. Qilin Li, a professor of civil
and environmental engineering, chemical
and biomolecular engineering, and materials
science and nanoengineering at Rice
University isn’t one to shy away from the
challenge. Dr. Li and her team are addressing
issues regarding water accessibility by
developing technologies that harness the
power of the sun to purify water.
One in nine people worldwide do not have
access to clean, safe drinking water, and
these people are closer to home than you
would imagine. 2 Some residents along the
Texas-Mexico border, for example, don’t
have access to municipal water, or any easily
obtained source of water for that matter.
Locals obtain their water from a large tank
that must be transported in and treated onsite
to ensure safety. This water treatment
system is inconvenient. More established
water treatment sites, as present in municipal
water sources, experience a different problem
called biological fouling, a phenomenon in
which bacteria grow on and damage the
membranes that are used to filter water. Li
explains, “This is a very big problem in water
treatment. So, for example, a big seawater
desalination plant in Tampa Bay, Florida was
built many years ago, but when it was built
and designed, they did not consider fouling
of this membrane material. Eventually fouling
got completely out of control so they had to
shut down and completely redesign the plant.”
The lack of portable water treatments systems
and fouling-resistant membrane materials can
make treating water prohibitively expensive.
According to Dr. Li, “We can treat any water,
it's not [an] exaggeration, any water, to
drinking water quality, but ultimately the
problem is the cost.” Dr. Li seeks to provide
clean water to all, utilizing nanophotonicsenabled
solar membrane distillation and
biological fouling-resistant membranes.
Nanophotonics-solar membrane distillation
is a solar desalination technology in which
the energy in a solar cell is used to heat
water into vapor. As sunlight hits the solar
cell, a photothermal process converts photon
energy into heat, which is then concentrated
and used to boil salty, impure water. The
resultant water vapor is then transported
through a thin, porous membrane. Salts and
other contaminants cannot pass through and
are left on one side of the membrane, while
on the other side, the vapor condenses into
pure water. 1 Dr. Li explains that this water
purification method is advantageous because
you can “easily scale it up, and it's modular,
so by adding more solar cells you can enlarge
the capacity of the plant.” This is the first
approach to solar distillation that is scalable,
which makes it suitable for communities in offgrid
locations and allows for greatly reduced
One in nine people
worldwide do not have
access to clean, safe
drinking water, and these
people are closer to home
than you would imagine.
energy costs in desalination. 1 In addition,
because this technology is so portable, it can
be used in military applications. According to
Dr. Li, a surprisingly large number of military
fatalities are the result of transporting water
to the frontlines of a battlefield, so a portable
water purification system could save lives. “In
the past what they used is reverse osmosis,
but then they have to carry heavy pumps and
big batteries. With this, hopefully all they need
to do is unfold the membrane and put it under
the sun and produce clean water wherever
you have any source of water,” Dr. Li explains.
While solar distillation is intended for
communities and military applications,
biological fouling-resistant membranes are
targeted for large water treatment plants.
Dr. Li tackles biological fouling by creating
membranes in which nanoparticles have
been embedded. These nanoparticles contain
antimicrobials that are slowly released and
interfere with biofilm formation. Once the
chemicals are depleted, nanoparticles can
be easily reloaded onto the membrane. 3 Dr.
Li believes that approaching the problem
with slow release mechanisms will present
a longer term control strategy compared to
previous methods. By using fouling-resistant
membranes, large amounts of money and
energy can be saved that would have been
spent pre-treating the water to prevent this
fouling. The development of these foulingresistant
membranes would have a huge
impact on industrial water treatment. This is
particularly significant for Houston because
of the applications of fouling-resistant
membranes to the oil and gas industry. When
drilling for oil and gas, large amounts of
wastewater are produced, which are normally
injected back into the ground. With more
efficient large-scale water treatment, this
wastewater can be repurposed to address
water shortages and supply irrigation systems
in agriculture.
Currently, Dr. Li is working to disseminate
the solar purification and fouling-resistant
membrane technologies developed in
her laboratory. NEWT, the Nanosystems
Engineering Research Center for
Nanotechnology-Enabled Water Treatment, at
Rice is teaming up with industry partners to
commercialize water purification technologies.
One such partner, Localized Water Solutions
Inc., is a company based in Austin committed
to reducing water shortages by building
smarter water systems and has licensed
solar membrane distillation for emergency
response and military applications. Dr. Li
is also part of a startup company called
SOLMEM, which is looking to apply the
technologies to bigger markets--seawater
desalination and industrial wastewater
treatment in the form of zero liquid discharge,
a wastewater management strategy that
eliminates liquid waste, for example. By
studying and applying novel water treatment
technologies, Dr. Li hopes to create a
sustainable water supply for those in need.
WORKS CITED
[1] Dongare, P. T. et al. Proc. Natl. Acad. Sci. U.S.A. 2017, 114,
6936-6941.
[2] The Water Project. https://thewaterproject.org/waterscarcity/water_stats
(accessed Nov. 9, 2017)
[3] Wu, J. et al. J. Membr. Sci. 2017, 531, 68-76
DESIGN BY Juliana Wang
EDITED BY Albert Truong
26 | CATALYST

LIGHT SHOW:
By Oliver Zhou
I
magine slowly losing your memory,
motivation, and communication skills—the
things that make you who you are. These
are just a few of the effects of Alzheimer’s
disease, and occur over the course of only a
few years. When someone has Alzheimer’s,
amyloid beta proteins, which are products
of a normal protein recycling process in
their brain, improperly join together to form
long strands called fibrils. 1 Even though the
individual protein monomers are harmless,
these fibrils can then stick together to
become toxic plaques that inhibit neuron
function and cause cell death, thus leading
to the debilitating effects of Alzheimer’s
on the brain. 1 Although the molecular
mechanisms of Alzheimer’s are understood,
the causes of these microscopic failures
are unclear, and no treatment to stop or
reverse its progression currently exists. In
addition, there are no definitive practices
or measures to significantly decrease risk
of developing Alzheimer’s. 2,3 As Alzheimer’s
patients deteriorate over the course of several
years, supportive and palliative care are the
only means of assistance, leading to higher
and higher costs of patient care. Altogether,
Alzheimer’s disease is one of the most costly
and serious diseases 4 that plagues the world
today.
Enter Dr. Angel Martí. An inorganic chemist
from Puerto Rico, Dr. Martí has spent his
whole life dreaming of being a scientist.
Dr. Martí began his career studying the
photophysical properties of metal complexes
at the University of Puerto Rico. In 2004,
he joined a research group at Columbia
University, where he contributed to the
development of fluorescent probes formed
from metal complexes for detection of DNA
and RNA. In 2008, he joined Rice University’s
Department of Chemistry, where he now
combines his past knowledge of metal
complexes and biological proteins for use
in the area of neurodegenerative diseases.
This combination of the building blocks of
inorganic chemistry with the fundamentally
biological issues of proteins and diseases
is what makes his research exciting. As Dr.
Martí put it, since “people don’t tend to study
amyloid beta through the eyes of an inorganic
chemist…being an inorganic chemist allows
me to bring something new to the table,
and that something new is the use of metal
complexes.”
Metal complexes have special photophysical
properties that allow Dr. Martí to study the
amyloid beta buildup of Alzheimer’s in new
ways. A metal complex is essentially a metal
atom, such as iron, or ruthenium, or rhenium,
surrounded by and bound to organic
molecules—a “hybrid of organic and inorganic
materials,” as Dr. Martí describes. An earlier
project of his involved the use of ruthenium
metal complexes, which would increase in
fluorescence over 100 fold when bound to
amyloid beta aggregates. This complex is
useful in the detection and assessment of the
extent of amyloid beta protein aggregation
in the brain, and with its higher visibility and
long lifetime, it holds numerous advantages
over the more commonly used indicator,
thioflavin T.
Ruthenium metal complexes have many great
uses, but Dr. Martí discovered something
even greater. “[When] we changed that
metal [in the metal complex] to rhenium”,
Being an inorganic
chemist allows me
to bring something
new to the table, and
that something new
is the use of metal
complexes
Dr. Martí describes, “very strange and
wonderful things started happening.” Once
irradiated with blue light, rather than merely
fluorescing, the rhenium metal complex
could actually oxidize the parts of the
amyloid beta aggregate that it bound to.
This new discovery is called footprinting,
and it can reveal exactly where hydrophobic
compounds like the rhenium metal complex
bind, making it easier to engineer drugs to
bind to those sites and combat Alzheimer’s.
However, this is not all the rhenium metal
complex can do. When binding to the large
amyloid beta aggregates, the oxidizing effects
of the metal complex were insignificant for
purposes other than simply signaling where
they could bind. However, when bound to the
harmless, monomeric form of amyloid beta,
the oxidation can significantly change their
individual shapes. This is enough to prevent
them from forming fibrils and aggregating
altogether. If there were some way to
preemptively insert and activate this rhenium
metal complex in the brain before symptoms
of Alzheimer’s began to show, the amyloid
Using Light-Activated Metal
Complexes to Combat
Alzheimer’s
beta monomers would never begin to
aggregate at all. This technique could lead to
a potential “vaccine” to prevent Alzheimer’s.
This Alzheimer’s vaccine is the end goal of
Dr. Martí’s research, but there are still many
challenges that the lab faces. Currently, the
only way to activate the metal complexes
after they bind to amyloid beta is by
irradiating them with blue light. This would be
impossible in a human, since our tissues are
not transparent to blue light, only red. Think
about what happens when you shine a light
through your hand—the light appears red. If
the rhenium metal complex could be altered
in a way so that it could be activated by red
light, it would allow for potential use inside
humans. Another challenge is ensuring that
the rhenium metal complexes are not toxic
to humans. This also brings up the question
of how the rhenium metal complexes would
make it to the brain. Most drugs are delivered
via the bloodstream, and the brain is
separated from the blood by a highly selective
blood-brain barrier. Currently, the metal
complex would not be able to get through
this membrane to the brain.
Despite these challenges, Dr. Martí’s research
presents a beacon of hope in the fight against
Alzheimer’s. Knowledge of the binding sites of
hydrophobic substances on the amyloid beta
aggregates is critical in design of future drugs
that may be able to neutralize or disintegrate
them. And if a rhenium metal complex that
can absorb red light and make it into the
brain could be synthesized, the progression
of Alzheimer’s could be stopped or even
prevented altogether.
WORKS CITED
[1] What Happens to the Brain in Alzheimer’s Disease? National
Institute on Aging [Online], May 16, 2017. https://www.
nia.nih.gov/health/what-happens-brain-alzheimers-disease
(accessed Dec 16, 2017).
[2] More research needed on ways to prevent Alzheimer’s,
panel finds. National Institute on Aging [Online], June 15,
2010. https://www.nia.nih.gov/news/more-research-neededways-prevent-alzheimers-panel-finds
(accessed Jan 7, 2018).
[3] Alzheimer’s & Dementia Prevention and Risk. Alzheimer’s
Association Research Center [Online]. https://www.alz.
org/research/science/alzheimers_prevention_and_risk.asp
(accessed Jan 7, 2018).
[4] Latest Alzheimer’s Facts and Figures. Alzheimer’s Association
[Online]. https://www.alz.org/facts/ (accessed Jan 7,
2018).
Image from freepik.com
DESIGN BY Sara Ho
EDITED BY Roma Nayyar
CATALYST | 27

SUMO WRESTLING
WITH HEART DISEASES
by amna ali
H
eart failure. Congenital heart defects. Each
year, both of these diseases take millions
of lives, yet much remains to be learned
about their mechanism and their treatment.
According to the Center for Disease Control
and Prevention (CDC), 6.5 million Americans
have heart failure, a condition in which the
patient’s heart cannot effectively pump blood
throughout the body, and the number of
individuals with heart failure will increase
by 46 percent by the year 2030. 1 In addition,
among people who develop heart failure, half
of them die within five years of the diagnosis. 1
This can be attributed to both an aging
population and the rise of risk factors such as
hypertension, disease, and diabetes. 2 Though
congenital heart defects do not affect nearly
as many individuals as heart failure, they still
pose problems in terms of treatment cost and
infant mortality, especially in underdeveloped
countries. 3 As of 2017, the average cost to
treat a congenital heart defect from infancy
to age 21 is anywhere between $47,500
and $73,600, which is an astronomical cost
in many healthcare settings. 3 In addition,
hospitalizations for these adult patients
have doubled over the past 20 years, with
congenital heart surgery accounting for nearly
20% of these admissions. 4 Although both
heart failure and congenital heart defects have
definitely become more manageable, we have
yet to identify a process through which we can
control these diseases from developing in the
first place.
Dr. Jun Wang, a principal investigator at the
Texas Heart Institute, seeks to discover the
underlying cause behind cardiovascular
abnormalities. His research team is
currently “investigating the mechanisms of
congenital heart defects and heart failure…
[by] examining how cardiomyocyte survival
and death is controlled.” Cardiomyocytes, or
heart cells, undergo cell death when there is a
defect which causes excess production of the
apoptosis-inducing factor (AIF), a protein that
sits in the cell and waits for a “death” signal
6.5 MILLION AMERICANS HAVE HEART FAILURE, A CONDITION IN
WHICH THE PATIENT’S HEART CANNOT EFFECTIVELY PUMP BLOOD
THROUGHOUT THE BODY, AND THE NUMBER OF INDIVIDUALS WITH
HEART FAILURE WILL INCREASE BY 46 PERCENT BY THE YEAR 2030.
28 | CATALYST
from the nucleus. 5 In a typical heart cell, the
nucleus releases this “death” signal when the
cell is somehow injured or too old. 5 Once the
AIF receives this signal, it causes the DNA of
the cell to condense and fragment in order to
prepare for apoptosis, or cell death. 5 In the
heart cells of an individual with heart failure,
too much of the “death” signal is released,
causing a release of too much AIF, leading
to excessive and unnecessary cell death.
Fortunately, certain modification processes
can be used to control levels of AIF.
Dr. Wang’s research team is specifically
examining how a process known as sumo
conjugation, a modification process in which
a small protein known as sumo is attached
and detached from other proteins in the cell,
can regulate AIF. Through sumo conjugation,
various processes in the cell, including the
processes that control cell death, can be
turned on and off. Dr. Wang is exploring how
sumo conjugation can be used to regulate the
production of AIF in the cells of a person with
heart failure. As heart failure involves random
apoptosis of cardiomyocytes, understanding
the signaling process associated with cell
death and its regulation is crucial step in
curing heart failure. Heart failure, however, is
not the only disease that could be potentially
managed through sumo conjugation.
Dr. Wang’s team is also researching how
the processes associated with congenital
heart defects can be regulated via sumo
conjugation. Congenital heart defects,
problems in the structure of the heart at
birth, often involve cells that have either
grown too much or too little. This results
in defects, such as holes in the separating
wall between two chambers when the cells
don’t grow enough, or a heart valve that is
too small when the cells grow too much.
Congenital heart defects originate in the
fetus, where stem cells that have not yet
decided what specific type of organ or tissue
they are going to become undergo a process
known as the hippo pathway, a type of sumo
conjugation. If the hippo pathway is turned
on, the stem cells stop growing; if the hippo
pathway is turned off, the stem cells continue
to differentiate into heart cells. 6 Dr. Wang’s
DR. WANG’S RESEARCH TEAM IS SPECIFICALLY EXAMINING HOW A
PROCESS KNOWN AS SUMO CONJUGATION, A MODIFICATION PROCESS
IN WHICH A SMALL PROTEIN KNOWN AS SUMO IS ATTACHED AND
DETACHED FROM OTHER PROTEINS IN THE CELL, CAN REGULATE AIF.
research team is attempting to determine
precisely which genes are responsible for
controlling the on and off switch of the hippo
pathway. This process is tested by “knocking
out”, or making ineffective, certain genes in
stem cells and determining the effects of
the knock out on the hippo pathway.6 Thus
far, in its preliminary research, Dr. Wang’s

stem cells
no further growth
further differentiation
IF THE HIPPO PATHWAY IS TURNED ON, THE STEM CELLS STOP GROWING; IF THE HIPPO PATHWAY IS
TURNED OFF, THE STEM CELLS CONTINUE TO DIFFERENTIATE INTO HEART CELLS.
research team has found that a gene known
as ari3b that may play a crucial role in the
hippo pathway; cells with ari3b “knocked
out” stopped differentiating. In other words,
although further research is required, Dr.
Wang’s research team has possibly found a
way to control incorrect or excessive heart cell
growth that contributes to congenital heart
defects, a potentially crucial step towards
being able to end the disease once and for all.
Dr. Wang hopes that with further research
about sumo conjugation and the hippo
pathway, his work will one day help other
researchers better understand cardiomyocyte
death in heart failure and random
uncontrolled growth in congenital heart
disease. By understanding the mechanisms
that cause these diseases with further
research, Dr. Wang states, rather than treating
the symptoms through surgeries, transplants,
and drugs, we are on the path to possibly
find a cure to the diseases that have afflicted
humanity since the beginning of time.
WORKS CITED
[1] Thacker, C; Del Barto, J. Latest statistics show heart failure
on the rise; cardiovascular diseases remain leading killer.
American Heart Association, Jan. 26, 2017. http://newsroom.
heart.org/news/latest-statistics-show-heart-failure-on-therise;-cardiovascular-diseases-remain-leading-killer
(accessed
Nov. 3, 2017).
[2] Heart Failure to Increase by Nearly 40 Percent in Next
15 Years. American Heart Association News, Sept. 29 2015.
https://news.heart.org/heart-failure-numbers-to-increase-bynearly-40-percent-in-next-15-years/
(accessed Jan. 8, 2018).
[3] Congenital Heart Defects (CHD): Data and Statistics.
Division of Birth Defects and Developmental Disabilities,
Center for Disease Control and Prevention, Jan. 8, 2018.
https://www.cdc.gov/ncbddd/heartdefects/data.html
(accessed Feb. 7, 2018).
[4] Dmyterko, Kaitlyn. Circ: Pediatric congenital heart surgery
costs more than adult surgery. Cardiovascular Business, Oct.
4, 2011. http://www.cardiovascularbusiness.com/topics/
healthcare-economics/circ-pediatric-congenital-heart-surgerycosts-more-adult-surgery
(accessed Feb. 8, 2018).
[5] Cande, C; Vahsen, N; Garrido, C; Kroemer, G. Cell Death
and Differentiation. 2004, 11, 591-595.
[6] Yu, F; Guan, K. Cold Spring Harbor Laboratory Press.
[online] 2013, 27, 355-371. http://genesdev.cshlp.org/
content/27/4/355. (accessed November 2017).
Icon from pngtree
DESIGN BY Evelyn Syau
EDITED BY Roma Nayyar
FUN FACTS
1. Dr. Wang’s favorite procedure to conduct in the lab is injecting of genes, proteins,
or viruses with green fluorescent protein (GFP), which has a fluorescent emission
wavelength in the green region of the visible light spectrum. This means that when the
GFP is exposed to certain wavelengths of light, it will turn a bright green color.
Watching the specimen “light up like stars in the night sky, all under the microscope” is
beautiful, Dr. Wang says.
2. GFP has existed in jellyfish for millions of years, but it has very recently begun to
be used in research labs. Dr. Wang uses GFP to tag “knock out” genes in his samples
so that he can determine which samples can be used in his study.
CATALYST | 29

songbirds,
the exciting
new field of neurogenesis
aging & autism
by Christine Tang
F
or a long time, scientists believed that
humans are born with all the neurons
that they will ever have, and that these
neurons can only die. However, scientific
evidence from the 1960s started to show
that neurogenesis, the production of
neurons from neural stem cells, occurs in a
portion of the brain called the
hippocampus, which is the
center of learning and
memory in the brain.
Though this finding
was received
with skepticism
in the scientific
community,
it was further
confirmed when
researchers found
in the 1980s that
adult songbirds
produced new neurons
when they learned new
today, we know that
each of the two human
hippocampi makes about
700 new neurons each
day
songs. 1 Today, we know that each of the two
human hippocampi makes about 700 new
neurons each day. 2
Neurogenesis is the process by which new
neurons form from primary neural stem
cells (NSCs) in the brain. 3-4 This process starts
very early in development in the womb, but
also occurs in the hippocampus throughout
the lifetime. However, neurogenesis is much
more prominent in a young brain than in an
older brain, and a decrease in neurogenesis
is associated with memory decline and
mood changes. Dr. Mirjana Maletic-Savatic,
an assistant professor and child neurologist
at Baylor College of Medicine and Texas
Children’s Hospital, is investigating this
process of neurogenesis in the hopes of
making the old hippocampus young, so that
older people will still be able to learn and
remember at the same capacity of a young
child. Development of new neurons is not
a simple process, and involves a series of
events called the neurogenesis cascade.
In the subventricular zone (SVZ) of the
hippocampus, a NSC divides into a daughter
cell. Then, the daughter cell produces many
clones, which each have three fates: they
can divide more, differentiate, or die. Dying
neurons are part of a natural process
called pruning, which is the reason
why adults have fewer neurons
than infants do. The cells that are
stimulated to differentiate will
gradually progress into immature
and then mature neurons,
which are integrated into the
hippocampus.
The mother NSC does not die,
but it does have a big limitation. It
can only divide into daughter cells
a few times, which means that the
amount of daughter cells that can originate
from one primary NSC is limited.5 After
dividing several times, the primary
NSC transforms itself into an
astrocyte, which is a type of
glial cell (non-neuronal cell)
that cannot differentiate
into new neurons. Even
though daughter cells can
reproduce, the high death
rate of differentiated cells
and immature neurons
limits the production of new
mature neurons. Therefore,
during aging, there is a decrease
in the number of stem cells, a
decrease in the number of newborn
neurons, and an increase of astrocyte
density in the hippocampus. These factors
contribute to cognitive decline and diseases
as we age. Dr. Fatih Semerci, a postdoctoral
student in her lab, and Dr. Maletic-Savatic
identified a gene called Lunatic fringe that is
a selective marker of NSCs. 6 Lunatic fringe
mediates Notch signaling, which allows for
communication between the mother and
daughter cells and is involved in quiescence
(dormancy) and differentiation of NSCs. This
is a unique mechanism in which progeny
of NSCs can send feedback signals to the
mother NSC to modify its fate. Therefore,
Lunatic fringe is a control step; it allows NSCs
to decide when to divide or stop, as NSCs
can only divide a limited amount of times. In
addition, Dr. Maletic-Savatic and Dr. Semerci
developed a new mouse model with the
Lunatic fringe gene that traces the lineage of
NSCs. 2,6 This allows for future experiments
that investigate other unknown mechanisms
of NSC differentiation or effects of knockout
genes on neuron development and mouse
behavior and cognition.
Research in
neurogenesis could
lead to potential
therapies for many
neurological patterns
or disorders
In addition, Dr. Maletic-Savatic has found
that epilepsy and impaired neurogenesis are
linked. In a joint study with Dr. Juan
Manuel Encinas, she injected
kainic acid, a neuroexcitatory
amino acid,
into the dentate gyrus
of the hippocampus.
They discovered
that high doses of
kainic acid resulted
in neural excitability
and terminal NSC
differentiation into
reactive astrocytes, 7
which are cells that
respond to pathological
conditions such as stroke and
epilepsy. 8 Unfortunately, this results in two
major problems: the NSC population will
decrease over time and reactive astrocytes
can increase inflammation, form scar tissue
and disrupt synaptic connectivity. 9-10 At this
30 | CATALYST

Critical periods of
survival:
Main
(1-4 days)
Secondary
(1-3 weeks)
Stem cells
Neurons
NSCs ANPs Early NBs NBs Immature
neuron
Granule
cell
Learning
Memory
Mood
Granule
Cell Layer
Subgranular
Zone
Apoptotic cells
APOPTOSIS
Images of neural stem cells (NSCs)
differentiating into neurons. NSCs are vital for
learning, memory and mood.
Microglia
Early
Late
PHAGOCYTOSIS
The neurogenic cascade, which shows the differentiation of neural stem
cells (NSCs) into amplifying neural progenitor cells (ANPs) and eventually,
into immature neurons and granule cells. Throughout differentiation and
proliferation, cells die by a process called apoptosis and microglia clean up
the dead cells.
time, findings highlight new mechanisms
that may contribute to epilepsy but
do not propose new therapies. In the
future, researchers plan to prevent
epileptic activation of NSC conversion
into reactive astrocytes to stop rapid
depopulation of NSCs.
Dr. Maletic-Savatic is also interested in
early neuronal development and sees
prematurely born babies and autistic
children at a clinic. Neurogenesis in
early periods of life can modulate the
ability to learn, and she is focused on
developing an integrative approach
to the study of early developmental
disorders, such as autism. Behavioral
features of autism include repetitive
thinking and the inability to accept
new environments. Autistic children
like routine and have trouble in new
environments or with new objects in
their environment. Newborn neurons
are involved in pattern separation,
which is a process that helps people
distinguish new and old objects in their
environment. Pattern separation may be
disrupted in autistic children; perhaps
their hippocampal neurogenesis has
something to do with this disruption.
This is important because autism is not
diagnosed until about 2-3 years old, so
an earlier intervention is critical because
the human brain has the most plasticity
in the first two years of life. Dr. Maletic-
Savatic is trying to do that by developing
a image-based model of autism that
could help diagnose autism earlier
through mapping different parts of the
brain using various techniques such
as magnetic resonance imaging (MRI)
and magnetic resonance spectroscopy
(MRS). 11-12
Neurogenesis is a hot field right now
because it is a potential target for new
therapies and drugs. Research in the field
could lead to potential therapies for many
neurological patterns or disorders, such as
age-related cognitive decline, epilepsy and
autism. These projects are interdisciplinary
and often involve collaborations around
the world. In the future, Dr. Maletic-Savatic
hopes to improve human neurological
function and health by elucidating other
mechanisms that are involved with Lunatic
fringe and Notch signaling as well as
epileptic and autistic processes that affect
NSC differentiation.
Works Cited
[1] Blakeslee, S. A Decade of Discovery Yields a Shock
About the Brain. The New York Times, Jan. 4, 2000. http://
www.nytimes.com/2000/01/04/science/a-decade-ofdiscovery-yields-a-shock-about-the-brain.html
(accessed
Dec. 1, 2017).
[2] Gutierrez, G. Lunatic Fringe gene plays key role in
renewable brain. Baylor College of Medicine [Online], July
19, 2017. https://www.bcm.edu/news/brain/lunatic-fringegene-brain-renewal
(accessed Dec. 1, 2017).
[3] Gage, F. H. Science. 2000, 287, 1433-1438.
[4] Altman, J.; Das, G.D. J. Com. Neurol. 1965, 124, 319-335.
[5] Encinas, J. M. et al. Cell Stem Cell. 2011, 8, 566-579.
[6] Semerci, F. et al. Elife. [Online] 2017, 6. https://
elifesciences.org/articles/24660
[7] Sierra, A. et al. Cell Stem Cell. 2015, 16, 488-503.
[8] Haim, L. B. et al. Front Cell Neurosci. 2015, 9, 278.
[9] Gutierrez, G. Neural stem cells massively turn into
astrocytes in a model of epilepsy. Baylor College of
Medicine [Online], May 7, 2015. https://www.bcm.edu/
news/neuroscience/stem-cells-massively-astrocytesepilepsy
(accessed Dec. 1, 2017).
[10] Sofroniew, M. V. Trends Neurosci. 2009, 32, 638-647.
[11] Ward, A. Solving the mystery of autism. The Houston
Chronicle, Apr. 29, 2013. http://www.chron.com/news/
health/article/Solving-the-mystery-of-autism-4456952.php
(accessed Dec. 1, 2017).
[12] Nace, M. Autism Researchers at Texas Hospital Hunt
For Autism’s Roots. BioNews Texas, Apr. 24, 2013. https://
bionews-tx.com/news/2013/04/24/autism-researchersat-texas-hospital-hunt-for-autisms-roots/
(accessed Dec.
1, 2017).
Designed by NamTip Phongmekhin
EDITED BY Roma Nyaar
CATALYST | 31

BY SREE YELURI
D
espite the Middle East’s abundance
of black gold, it severely lacks
two other resources needed for
stable socioeconomic development.
The limited supplies of and increasing
demands on each of these vital, highly
interdependent resources- food, water,
and energy- is a main point of tension for
countries in this region. In fact, increased
desertification and loss of fertile land,
water scarcity, and climate variability
are all cited by United Nations
Environmental Programme as
having been precursors for
past conflict (specifically in
Darfur, Sudan).¹ Balancing
the demands on these
resources is key to
achieving regional
stability. Looking
specifically at water
stress in the Middle
East, an analytical
lens that can be used
to understand the
challenges in alleviating
this stress and achieving water
security is the Food-Energy-Water (FEW)
Nexus. This FEW nexus can help us break
down the relationship and involvement
of food and energy production on water
security, which (defined by UN-Water)
is the ability to secure enough water--
and the right quality of water-- needed
for sustaining our well-being and
development.²
Mr. Gabriel Collins, J.D., a Baker Botts
Fellow in Energy & Environmental
Regulatory Affairs at the James A. Baker
III Institute for Public Policy, is currently
exploring the environmental, legal, and
economic implications of the FEW Nexus.
His work is primarily water-related and
energy-related, and one of his recent
32 | CATALYST
WATER
SECURITY IS
THE ABILITY TO
SECURE ENOUGH
WATER NEEDED FOR
SUSTAINING OUR
WELL-BEING AND
DEVELOPMENT
publications, titled “Carbohydrates, H2O,
and Hydrocarbons: Grain Supply Security
and the Food-Water-Energy Nexus
in the Arabian Gulf Region”, builds a
comprehensive review of the interactions
between each component of the nexus and
ultimately offers policy recommendations
to maximize resource security.
One aspect of the nexus that Mr. Collin’s
explores in his paper is the fundamental
interaction between water usage and food
production: “[w]ater-thirsty staple food
grains must be irrigated in the region’s
arid climate”.³ Saudi Arabia, one
country Mr. Collins discusses in
his paper, had a challenging time
meeting both the hydrological
and agricultural demands
of its growing population
and “between 1980 and
1999 alone, Saudi Arabian
farms consumed more than
300 billion cubic meters of
water—most of which came
from deep aquifers that do
not recharge—and spent tens of
billions of dollars in a failed attempt
to cultivate wheat on an industrial scale
in its harsh desert climate”.⁴ In fact, the
high economic and environmental costs
of this process were so steep, that Saudi
Arabia completely abandoned wheat
production in 2016, and instead turned to
relying solely on imports.⁵ This situation
of unequal supply and demand is not
unique to Saudi Arabia. As the Middle East
is an arid region, lacking in rainfall, fertile
soil, and adequate humidity,⁶ many of the
countries here face similar challenges in
meeting the food and water demands of
their growing populations.
Another country that is facing a similar
challenge in balancing demands for
food and water is Iran. However, unlike
“
Saudi, Iran is choosing to remain with
their mindset of self-sufficiency and has
reinvigorated efforts to increase domestic
crop production. This encouragement
of domestic wheat production by the
government is concerning because Iran’s
groundwater depletion rate heralds the
possibility that their aquifers (their primary
water source for agriculture) will be
depleted in the next 50 years.⁷ However,
Iran is currently going through severe
water scarcities and droughts that may
have an irreversible impact on current and
future water availability, which Mr. Collins
explains in an apt analogy⁸:
IF YOU HAVE A CAR GOING
TOWARDS A BARRIER AHEAD,
OVER 60 MPH AND IT ATTEMPTS
TO BRAKE GRADUALLY, ENERGY
IS BEING APPLIED GRADUALLY
AND IT’S NOT UNPLEASANT FOR
THOSE IN THE CAR. HOWEVER, IF
THE CAR CONTINUES TOWARD THE
BARRIER AND CRASHES, THE SAME
AMOUNT OF ENERGY IS BEING
DISSIPATED, BUT MUCH MORE
QUICKLY. THE SECOND SCENARIO
IS BAD FOR THE CAR AND WORSE
FOR THE PEOPLE INSIDE. TO
COMPARE THIS TO IRANIANS
MINING GROUNDWATER RESERVES
THAT ARE THOUSANDS OF YEARS
OLD, THE LIKELY FUTURE IS
THAT IF WATER CONSUMPTION
IS NOT MANAGED SUSTAINABLY,
THERE WILL BE A FIGURATIVE
“CRASH” AND EXTREME WATER
SHORTAGES WILL BE A REALITY.
SAUDI ARABIA, ON THE OTHER
HAND, IS WORKING TO MINIMIZE
THE IMPACT OF THAT FIGURATIVE
CRASH AND DEVELOP MORE
SUSTAINABLE PRACTICES.
”

TURKEY
SYRIA
IRAQ
IRAN
EGYPT
SAUDI ARABIA
Another major barrier to achieving water
security is meeting growing energy
demands. The Middle East’s wealth comes
from it’s disproportionate abundance of
petroleum and natural gas; however, its
high investments in energy production
and exportation have severe implications
on water usage. In Saudi Arabia, “energy
production accounts for the second largest
use of water behind agriculture and is
expected to continue rising over the next
15-20 years.”⁹
The connection between water and energy
perhaps isn’t as straightforward as that
between water and food. Water is used in
the generation of electricity, the extraction
and processing of fossil fuels, and in the
production of biofuel.¹⁰ And, energy is
used in water extraction, desalination, and
transportation. From this interdependence
stems the difficulty in separating the
impact of the usage of one resource on
the availability of the other; this difficulty
makes it harder to develop deliberate
and sustainable practices that maximize
effective resource allocation.
Mr. Collins also introduces methods
that can be used to increase resource
security and facilitate the development
of sustainable practices. He discusses
the benefits of more solar and nuclear
powered infrastructure, especially for small
farmers and communities who aren’t using
established power grids. Particularly for
this subgroup of energy consumers, Mr.
Collins believes that there is a lot of merit
in solar-powered groundwater pumping
infrastructure to put in wells. And using
nuclear power, rather than fossil fuels, also
has the added benefit of freeing up gas for
other uses, such as desalination.¹¹
However, questions regarding effective
allocation of resources cannot be
answered easily, and of course there are
differing viewpoints as to what the most
“effective” practice for each country is.
But placing resource conservation at the
forefront of the region’s environmental,
economic, and sociopolitical agendas will
help spark serious efforts to think about
the importance of water security and
sustainability.
Going forward, Mr. Collins plans to
continue to research the FEW nexus in
Sub-Saharan Africa and South America.
The main purpose of his research is to help
introduce sound environmental, economic,
and legal analysis to policy makers to
aid them in creating stronger policies.
His vision is that he and researchers like
him will be able to offer nonpartisan
policy recommendations to policymakers
in the US and abroad.¹² The potential
implications of being able to fully analyze
each component of the nexus will be to
create specific policies that will encourage
the use of clean energy, promote effective
economic/trade policies, and allow each
country to take advantage of the resources
they have while still making sure that
future demand for those resources will be
met.
WORKS CITED
[1] Pedraza, L.E.; and Heinrich, M. Water Scarcity:
Cooperation or Conflict in the Middle East and North
Africa? Foreign Policy Journal. Sept. 2 2016. https://www.
foreignpolicyjournal.com/2016/09/02/water-scarcitycooperation-or-conflict-in-the-middle-east-and-northafrica/
(accessed Feb. 17 2018).
[2] What is Water Security? Infographic. UN Water
[Online]. May 8 2013. http://www.unwater.org/
publications/water-security-infographic/ (accessed Feb.
17 2018).
[3] Collins, G. Carbohydrates, H2O, and Hydrocarbons:
Grain Supply Security, and the Food-Water-Energy
Nexus in the Arabian Gulf Region. Center for Energy
Studies, Baker Institute. June 2017. https://www.
bakerinstitute.org/media/files/files/96136d13/CES-pub-
QLC_Nexus-061317.pdf (accessed Feb. 17 2018).
[4] Ibid.
[5] Ibid.
[6] Ibid.
[7] Senguptajan, S. Warming, Water Crisis, Then Unrest:
How Iran Fits an Alarming Pattern. The New York Times
[Online], Jan. 18 2018.
[8] Interview with Mr. Gabriel Collins.
https://www.nytimes.com/2018/01/18/climate/water-iran.
html (accessed Feb. 17 2018).
[9] Rambo, K.A. et al. Water-Energy Nexus in Saudi Arabia.
Energy Procedia. 2016, 105, 3837- 3843
[10] World Energy Outlook; International Energy Agency,
2012. Ch. 17. http://www.worldenergyoutlook.org/
media/weowebsite/2012/WEO_2012_Water_Excerpt.pdf
(accessed Feb. 17 2018).
[11] Interview with Mr. Gabriel Collins.
[12] Ibid.
DESIGN BY Jessica Lee
EDITED BY Pujita Munnangi
CATALYST | 33

methods of
MOSQUITO VECTOR
SURVEILLANCE
rR
and population control
o w a i s f a z a l
BACKGROUND
A variety of mosquito vector surveillance
and control programs have been instituted
over the past few decades with the intention
of limiting the spread of infectious diseases
such as dengue, malaria, and the Zika virus.
With the major public health threat of
mosquito populations spanning across the
globe, it is imperative that we continue to
develop effective methods of controlling the
mosquito population as well as designing
and implementing novel solutions on an
international scale. While these programs
have displayed varying degrees of success, this
review analyzes various methods that seem
to be effective in combating vector incidence
and prevalence within endemic populations
worldwide. Specifically, we will analyze vector
control initiatives involving Aedes albopictus
populations in Yorke Island off the coast of
Australia as well as the control of Anopheles
gambiae populations in Brazil in order to
determine trends in effective mosquito vector
control systems.
YORKE ISLAND
A particularly successful mosquito vector
surveillance program was implemented in
the recent Yorke island mosquito control
initiative. Consistently low densities of Aedes
albopictus populations have been recorded
six years following the program’s inception in
2005. Following the success of the program,
project leaders have claimed that the use
of insecticides appeared to be the most
important component of their intervention
program, with inspection cycles and public
outreach also playing key roles in limiting
the prevalence of the endemic mosquito
population. 1
SOURCE REDUCTION
Successful vector surveillance programs
rely heavily on the utilization of a process
known as source reduction. 2 Source reduction
essentially involves the systematic removal of
potential mosquito breeding sites, effectively
diminishing the growth rates of endemic
mosquito populations significantly. This
process was heavily used in Yorke Island, as
any containers that could potentially hold
water and support larval development were
removed, destroyed, placed under cover,
34 | CATALYST
or treated with pellets or briquettes of the
insect growth regulator s-methoprene.
The s-methoprene was applied to smaller
containers in the form of 15g pellets at a rate
of one pellet per liter of estimated container
volume. Larger containers, such as rainwater
tanks and wells, were treated with ProLink
XR Briquets applied at one briquet per
5000 liters of water. 3 Containers that could
not be removed had their interior surfaces
also sprayed with the residual pyrethroid
bifenthrin to kill adult mosquitoes that came
in contact with them. 4 Samples of larvae were
collected from infested containers for species
identification on a weekly basis in order to help
monitor the efficacy of the insecticide usage.
Thus, the larval habitats of the local Aedes
mosquito species were totally decimated in
the region and mosquito vector populations
declined by as much as 98% according to
recent estimates in 2016. 5
5
Our increasingly
interconnected global
climate is highly vulnerable
to infectious disease
pandemics spread through
vectors such as mosquitoes,
and we must continue
to refine our mosquito
population control methods
to combat this threat.
ACTIVE SURVEILLANCE
Furthermore, it is also imperative to have
reliable methods of approximating the number
of vectors within specific regions of a target
area. In order to address this issue, the Yorke
Island initiative enlisted the support of local
public health officials in order to conduct active
surveillance of target areas and to obtain an
accurate count of mosquito prevalence in
select regions of the island. 6 For each round of
surveillance, larval densities were expressed as
number of positive containers per 100 houses
for the Aedes albopictus species. Moreover,
local populations in vector endemic regions
were surveyed at regular intervals in order to
corroborate results of any other independent,
ongoing vector density studies. 7 All in all, the
teams conducted sweep-net sampling on a
total of 230 different sites, providing data
on precise locations as well as population
densities of vector groups throughout the
vector endemic regions. 8
VECTOR MONITORING
AND THE CORDON SANITAIRE STRATEGY
One of the most crucial qualities of a
successful mosquito vector surveillance and
control program is to be able to monitor
changes in mosquito vector populations
in response to the usage of specific vector
control tactics. 9 In conjunction with the above
methods, being able to accurately examine
vector trends over the period of time that a
vector control program is in place is key. A
strategy used by Yorke island public health
officials that combines monitoring with some
of the more direct methods of combating
vector populations is the cordon sanitaire
strategy, which is an integrated approach
composed of harborage spraying, source
reduction, insecticide treatment of containers,
lethal tire piles, mosquito population
monitoring and public awareness campaigns
supported by local authorities and local
media. 10
BRAZIL
The eradication of the accidentally introduced
Anopheles gambiae mosquito species
from 54,000 km 2 of largely ideal habitat in
northeast Brazil is regarded as one of the
most effective mosquito control campaigns
in scientific history. 11 This successful program
was implemented in the 1930s and early
1940s through an integrated program that
relied overwhelmingly upon larval control
mechanisms. In the decades following the
implementation of the program, similar
initiatives utilized comparable strategies
in order to successfully combat vector
populations in Egypt as well as rural Zambia. 12
ROUTINE VECTOR INSPECTION CYCLES
The total coverage of the A. gambiae mosquito
population was achieved primarily through
the combination of large numbers of field
workers with strictly enforced task-allocation
and supervision systems. Each individual field
worker, known as a larval inspector, was given
a fixed area in which to identify and treat
potential breeding sites and for which he or

she alone was responsible. 13 All inspectors
were allocated a reasonable area that was
carefully mapped and both the inspectors and
the mosquito populations they faced were
monitored regularly. One key method utilized
during this process involved the use two
flags to mark where the inspectors had left
the road and where they was located at any
time. 14 The campaign was designed to tackle
A. gambiae according to its ecological niche.
A. gambiae prefers sunlit and relatively small
bodies of water as larval habitats and these
had to be identified and monitored rigorously
throughout the countryside. 15
ADMINISTRATION AND
VERTICAL MANAGEMENT METHODS
The core foundation underlying the success
of the Brazilian vector control program was in
the clearly defined and organized nature of its
activities. A cartographic unit was immediately
set up and the infested area was mapped
using aerial photographs. 16 A common
laboratory and epidemiological division
allowed centralised training, surveillance,
and decision-making. Adulticide and
medicinal measures were similarly organized,
in which researchers and local officials
clearly emphasized a central administrative
structure. 15
The work of inspectors in their allocated zones
was also closely scrutinized and managed by
district chief inspectors who were typically
allocated only five zones for which they were
held individually responsible. The zones
and districts were further aggregated and
managed through administrative units termed
posts and divisions, both of which were
headed by medical doctors who could deal
with the clinical aspects of the program in
addition to vector control. 18 A system of flags
and on-site field documentation ensured that
each inspector was monitored on an almost
hourly basis and could be held unambiguously
accountable for any lapses. 19 Notably, the
activities of the anti-larval and anti-adult
control teams were separately reported at
district level so that discrepancies could be
identified, and separate adult capture squads
conducted independent evaluations of all
vector-control activities by knockdown catches
in houses on a monthly basis. 20
CONCLUSION
Thus, we were able to analyze some of
defining characteristics of successful mosquito
vector control programs in diverse ecological
settings based off the coast of Australia in
Yorke Island as well as in Brazil. Key themes
that were observed across both programs
included a heavy reliance on local public
health officials and epidemiologists to obtain
key information regarding the locations
and prevalence of target mosquito vector
populations as well as the employment of
insecticides to decimate these mosquito
populations once locations were precisely
determined. Modern mosquito control
programs based in Sub-Saharan Africa and
the Middle East have also expanded upon
several of the techniques mentioned in this
article to increase the efficacy and efficiency of
these programs. 4 Ultimately, our increasingly
interconnected global climate is highly
vulnerable to infectious disease pandemics
spread through vectors such as mosquitoes,
and we must continue to refine our mosquito
population control methods to combat this
threat.
WORKS CITED
[1.] Worobey J, Fonseca DM, Espinosa C, Healy S, Gaugler R. J
Am Mosq Control Assoc. 2013; 29(1): 78–80.
[2.] Muzari MO, Devine G, Davis J, Crunkhorn B, van den Hurk
A, Whelan P PLOS Negl Trop Dis. 2017; 11(2); 433-9
[3.] Nelder M, Kesavaraju B, Farajollahi A, Healy S, Unlu I,
Crepeau T, et al. Am J Trop Med Hyg. 2010 ;82(5):831–7.
[4.] Benedict MQ, Levine RS, Hawley WA, Lounibos LP. Vector
Borne Zoonotic Dis. 2007;7(1):76–85.
[5.] Kuno G. J Med Entomol. 2012; 49(6):1163–76.
[6.] Lounibos LP, O'Meara GF, Juliano SA, Nishimura N, Escher
RL, Reiskind MH, et al. Ann Entomol Soc Am. 2010;103(5):757–
70.
[7.] Sun D, Williges E, Unlu I, Healy S, Williams GM, Obenauer
P, et al. J Am Mosq Control Assoc. 2014; 30(2): 99–105.
[8.] Ritchie SA, Moore P, Morven C, Williams C. J Am Mosq
Control Assoc. 2006; 22(3): 358–65.
[9.] Rueda LM. Zootaxa. 2004; 589: 1–60.
[10.] Nguyen HT, Whelan PI, Shortus MS, Jacups SP. J Am Mosq
Control Assoc. 2009;25(1):74–82.
[11.] Killeen, G. F., Fillinger, U., Kiche, I., Gouagna, L. C., &
Knols, B. G. The Lancet infect. dis. 2002; 2(10), 618-627.
[12.] Garrett-Jones, C. Nature. 1964; 204: 1173–1175
[13.] Spielman, A, Pollack, RJ, Kiswewski, AE, and Telford III, SR.
Vector Borne Zoonotic Dis. 2001; 1: 3–19
[14.] Guyatt, HL, Gotink, MH, Ochola, SA, and Snow, RW. Trop
Aedes albopictus
Yorke Island
Anopheles gambiae
Brazil
Med Int Health. 2002; 7: 1–12
[15.] Guyatt, HL, Corlett, SK, Robinson, TP, Ochola, SA, and
Snow, RW. Trop Med Int Health. 2002; 7: 298–303
[16.] Molyneux, DH, Floyd, K, Barnish, G, and Fevre, EM.
Parasitol Today. 1999; 15: 238–240
[17.] Buckling, AG, Taylor, LH, Carlton, JM, and Read, AF. Proc
R Soc Lond B Biol Sci. 1997; 264: 553–559
[18.] Shiff, C. Clin Microbiol Rev. 2002; 15: 278–298
[19.] Gimnig, JE, Ombok, M, Otieno, S, Kaufman, MG, Vulule,
JM, and Walker, ED. J Med Entomol. 2002; 39: 162–172
[20.] Charlwood, JD and Edoh, D. J Med Entomol. 1996; 33:
202–204
Fonts from GoogleFonts and DaFont.com
Images from Wikimedia Commons and
Clipground
DESIGN BY Sahana Prabhu
EDITED BY Rishab Ramapriyan
CATALYST | 35

the emergence of NUMBER
THEORETIC QUESTIONS
from a geometric investigation
ABSTRACT
Taking any regular even-sided polygon, one
can make cross-cuts from each vertex and
connect it to the midpoint of one of the
opposite sides to create a smaller regular
polygon contained within the original. The
ratio between the area of this new polygon
and the original has been shown to have
some interesting values, specifically 1/5 for
squares and 1/13 for hexagons. Building
on this, a general formula that gives the
ratio for an arbitrary regular polygon can
be found. In this paper, we will explore
how to generalize this result even further
by allowing the crosscuts to connect to any
side of the polygon, rather than just to the
opposite side. We then explore the rationality
of this expression, and discover interesting
connections to number theoretic techniques
looking into the relationship between
Chebyshev Polynomials and the minimal
polynomials of cosine.
INTRODUCTION
Recent results have shown that there is an
interesting relationship between the area of a
regular polygon and the area of the polygon
formed through
crosscuts.
Essentially, a
second regular
polygon is
created from
the first by
connecting
each vertex to
the midpoint
of the opposite side. Because even-sided
polygons have two sides that can be opposite
to any vertex, this implies that one side
should be chosen and that direction should
be repeated for every other vertex (See
Figure 1). The area ratio has been calculated
explicitly for squares and hexagons, and were
found to be 1/5 and 1/13, respectively. 1,5,6
In addition, for an odd-sided polygon, the
crosscuts will connect in the center, so that
the ratio will always be 0. After these specific
results, the next question is whether a
generalized formula can be found that agrees
with these, as well as gives ratios for a regular
polygon with an arbitrary number of sides. It
is also important to explore the rationality of
this function, as it is rational ratios that have
motivated this research.
Fig. 1: The crosscut formation of regular polygons when n=3, 4, 6.
INITIAL FORMULAS
The following are some necessary formulas
that will be used later in the paper. The first
is a simplified expression for the ratio of the
areas, which gives R=a S2
/a B2
,where a S
is the
apothem of the smaller polygon, and
a B
is for the original polygon. The
second is an explicit formula that
gives the ratio in terms of only the
number of sides of the polygons: R n
=
1/(1+4cot 2 (θ)) , where θ=π/n. This is
the starting point for this paper, as
this result will be generalized using
similar methods as those used in the
proof of R n
.
GENERALIZED EXPRESSION
We want this new generalization to
allow our crosscut to be connected
to an arbitrary side of the polygon,
instead of requiring that it connect to the side
opposite of the vertex where it started. This
new formula should give the area ratio only in
terms of the number of sides of the polygon,
n, and the number of vertices skipped
before connecting the crosscut, denoted k.
To do this, we first define a coordinate axis
system that is
suitable for our
calculations. This
coordinate axis
can be created
by placing one
vertex and the
center of the
polygon on the
line y=C that
runs parallel to the x-axis. Then, the crosscut
originating from this vertex would create an
angle with this line. Connecting the other
endpoint of the crosscut to the center of the
polygon forms a triangle that has one known
angle, ψ=2πk/n+(1/2)(2π/n)=(π(2k+1))/n, at
the center. (We assume in this proof that
0< ψ≤π, but we will later show that this
formula actually holds for all values of ψ.) In
addition to this known angle, two of the sides
are known, as one, a B
, is the apothem and
another, r, is the radius of the polygon. This
setup is detailed in Figure 2.
As only one angle in this triangle is known, it
is easiest to form two right triangles, so that
known trigonometric formulas more readily
apply. This is accomplished by taking a line
By Jacob Kesten
from E to E’, where is connects to the line
y=Cat a right angle. In Figure 2, this new line
is denoted b. Now using trigonometry, it is
possible to find the slope of the crosscut by
calculating the lengths of b and c. This gives
Fig. 2: A diagram depicting the two triangles used to compute the slope
of the specific crosscut. The first picture shows placement of the triangle
on the polygon and coordinate axes. The second shows how the 2 right
triangles were formed, and the third shows how this can be used to
compute the length of the smaller apothem.
the slope of the crosscut as m=(–a B
sin(ψ))/
(r–a B
cos(ψ))=(–cos(θ)sin(ψ))/(1–cos(θ)cos(ψ)).
Knowing the slope makes it possible to
write an equation for the line containing
the crosscut, as well as the equation of
the line perpendicular to the crosscut that
contains aS. These are given by y 1
=mx+mr+C
and y 2
=–x/m+C, respectively. Finding the
intersection of these two lines allows us to
find a S
2
in terms of m and a B2
. Dividing both
sides by a B2
, we get that a S2
/a B
2
= R n,k
= (m 4 +m 2 )/
(cos 2 θ(1+m 2 ) 2 ) = (1–cos 2 (ψ))/(1–2cosψcos θ
+cos 2 θ), where θ=π/n and ψ=(2k+1)θ. Notice
that this formula depends only on n and k, as
desired.
We now check that this formula holds for
values of π < ψ < 2π. This follows from the
fact that for π < ψ < 2π, ψ=π+ψ’ where ψ‘ < π,
and cosψ=cosψ’ so that the formula will be
the same as the one for the corresponding
complement angle. Essentially, the case
where π < ψ < 2π reduces to a case where
ψ≤π by looking at the angle going in the
opposite direction of the obtuse angle. An
example of this is given in Figure 3 using
different crosscut octagons. Flipping the
octagons on the bottom shows that they will
be identical to the ones in the first row, so
that they will produce identical ratios.
Now that we have found the formula R n,k
,we
can check that it matches with the values
already found for specific polygons. One such
example is when the crosscuts connect to the
36 | CATALYST

opposite side of an odd-sided polygon, where
the ratio should be 0. In this case, we have
that k=(n–1)/2, so that we get the following
result: R n,k
= (1–cos 2 π)/(1–2cosπ cosθ+cos 2 θ)
= 0/(1–2cosθ +cos 2 θ) = 0, as expected. In
addition, using n=6 and k=2, we get that
R 6,2
=(1–cos 2 5π/6)/(1–2cos 5π/6 cos π/6 +cos 2
π/6) = (1–(–√3/2) 2 )/(1–2(–√3/2)(–√3/2)+(–√3/2) 2 )
= (1– 3/4)/(1+2(3/4)+3/4) = (1/4)/(1+3/2+3/4)
= (1/4)/(13/4) = 1/13, which is exactly what
Fig. 3: Octagon crosscuts using k=1,2,3,4,5,6. Comparing the
2 lines shows that the octagons using k=1,2,3 are the same as
those using k=4,5,6.
was found in earlier papers. The other known
results can also be checked using a similar
method.
RATIONALITY
Now we try to find which values of n and k
will produce a rational value for R n,k
. We can
easily check different values of n and k and
find that the following are rational: R n,0
, R 4,1
,
R 6,2
, R 6,1
, R 8,2
, R n(odd),(n-1)/2
. However, there are an
infinite number of combinations for n and k,
and there is no straightforward way to prove
that these are or are not the only rational
values of R n,k
. One approach is to look at
different values for the possible parts of the
ratio that could be irrational. For example,
when both cosθ and cosψ are rational, then
R n,k
is rational. This approach works for some
combinations, but a problem arises when
both cos 2 θ and cos 2 ψ are irrational, as there
is no way to tell what will happen with R n,k
.
This is because both the sum and product
of irrational numbers can be rational, thus
even though all components of R n,k
are
irrational, the final output could still be a
rational number. Because this is the majority
of the values that will occur, an approach that
directly applies to this case is needed.
One possible approach is to look at the
polynomial representation for R n,k
and the
minimal polynomials for cosθ. The minimal
polynomial of the value cosθ is the smallest
nonzero, monic polynomial with rational
coefficients that has cosθ as a solution. For
example, the minimal polynomial of √2 is
x 2 –2=0. Note that this polynomial cannot
be reduced, and thus it is the smallest
polynomial with √2 as a solution. All algebraic
numbers have a minimal polynomial, by
definition, and thus for each value of n, cosθ
has a minimal polynomial. 2
First, we use R n,k
to create a polynomial
expression of one variable. Using the multiple
angle formula, we know that cosψ=cos((2k+1)
θ)=cos(sθ)=T s
(cosθ) where T s
(cosθ) is the
s th Chebyshev Polynomial. For example,
cos(4θ)=8cos 4 (θ)–8cos 2 (θ)+1because T 4
(x)=8x 4 –
8x 2 +1. 7 This allows us to express R n,k
as an
expression of θ: R n,k
=(1–T s2
(cosθ))/(1–2T s
(cosθ)
cos θ +cos 2 θ, where s=2k+1. Setting x=cosθ,
and R n,k
=r, where r is a rational value, we get
the polynomial expression P(R n,k
)=1-T s
2(
x) –
r+2rxT s
(x)–rx 2 =0.
It is known that if a certain value solves a
polynomial, then the minimal polynomial
(minpoly) of that value has to be able to divide
the larger polynomial, with a remainder of
0. 4 Thus we want to see what happens when
we use different combinations of n and k,
and see if there is any way to find a pattern
in the remainders of P(R n,k
)/minpoly(cosθ).
In this case, a random collection of values
from within the bounds n≤100 and k1
–1) ∏ ψ2 (x) for n even.
d
d|n, d>2
where ψ n
(x) is the minimal polynomial of
cos(2π/n) multiplied by a constant and d|n
means that d is a divisor of n, so that the
product runs through all the divisors of n. 3
Exploring this relationship in more detail is
an important and rapidly expanding area
of theoretical mathematics, and could be
very helpful in creating a final proof of the
rationality of Rn,k. In our exploration, we
came across a need to understand more
about the relationship between these two
concepts and have seen how a simple
question concerning area ratios can produce
complicated mathematical questions that
are still being explored purely for theory.
This is just one application of the possible
knowledge that can be gained by the abstract
investigation of these two concepts and the
inner workings of their natural connection.
A special thanks to Dr. Zsolt Lengvarszky of
the Louisiana State University, Shreveport,
Mathematics Department for his help and
mentorship in the project.
WORKS CITED
[1] Ash, J.M., et al., Constructing a Quadrilateral Inside
Another One, Mathematical Gazette, 2009, 528, 522–532.
[2] Calcut, J.S., Rationality and the Tangent Function, http://
www2.oberlin.edu/faculty/jcalcut/tanpap.pdf (accessed Feb.
8, 2018).
[3] Gürtaş, Yusuf Z., Chebyshev Polynomials and the Minimal
Polynomial of Cos(2/n), The American Mathematical Monthly,
2017, 124, 74-78.
[4] Leinster, T., Minimal Polynomial and Jordan Form, http://
www.maths.ed.ac.uk/~tl/minimal.pdf (accessed Feb. 8, 2018).
[5] Mabry, R., Crosscut Convex Quadrilaterals, Math Mag,
2011, 84, 16–25.
[6] Mabry, R., One-Thirteenth of a Hexagon, n.d. 1-11.
[7] Mason, J.C., Handscom, D.C., Chebyshev Polynomials;
Chapman and Hall: Boca Raton, 2003; sec 1.2.1.
DESIGN BY Kaitlyn Xiong
EDITED BY Olivia Zhang
CATALYST | 37

THE EFFECT OF DASATINIB ON
MECHANOBIOLOGY OF
LUNG CANCER CELLS DURING
METASTASIS
Shaurey Vetsa, Richard I. Han, Don L. Gibbons, K. Jane Grande-Allen
Department of Bioengineering, Rice University
ABSTRACT
My research has sought to further
characterize the effect of Dasatinib on the
focal adhesion pathway in cancer cells.
While plenty of research exists on how the
cell propagates tumor growth, the results
of this research show how tumor-matrix
interactions drive tumor metastasis. To
resemble the stress that the cell matrix
would face in a lung, we placed the cells in a
static tension environment and recorded the
changes in spatial distribution of the cells in
the presence of Dasatinib. It was found that
Dasatinib induced clustering in cancer cells;
however, further research is required to
show causation rather than correlation of the
clustering.
INTRODUCTION
Among all the cancers that afflict the
American population, lung cancer is
the second most widespread in men
and women. 1 Afflicted lung cancer cells
proliferate through a process called
epithelial to mesenchymal transition (EMT).
Although EMT for healthy cells is important
for embryonic development and other vital
organs, cancer cells become invasive after
EMT. The cells lose cell to cell adhesion and
increase the expression of mesenchymal
cell markers such as vimentin, fibronectin,
N-cadherin, and alpha-smooth muscle actin
(α-SMA). These changes allow cancer cells to
metastasize throughout the cell space. 2
The extracellular matrix (ECM) plays a
significant role in the occurrence of EMT. Two
families of enzymes, microRNA-200 and ZEB1,
regulate EMT using transcription factors.
These families form a double-negative
feedback loop in which ZEB1 activates a
collagen-producing gene to increase collagen
expression in the extracellular matrix.
Another family of enzymes, LOX, creates
greater organization of the collagen due to
the increased expression of crosslinking.
Less randomness in the structure of the ECM
promotes metastasis as cancer cells can
traverse the matrix more easily. 3
The metastasis of cancer strongly depends
not only on processes occurring in the cell,
but also on the regulatory behavior between
the cell and the extracellular matrix. The
focal adhesion pathway is an important
macromolecular assembly that transfers
information from the extracellular matrix
to the cell. Its inhibition can create changes
in cell morphology and organization in lung
cancer cells. The transduction of the focal
adhesion pathway undergoes a secondary
messenger amplification that contains the
proto-oncogene tyrosine-protein kinase
(SRC). Bristol-Myers Squibb Inc. developed an
anti-cancer drug called Dasatinib that inhibits
the SRC protein which controls important cell
processes like movement, proliferation, and
survival. 4
We investigate Dasatinib’s effect on the cell
focal adhesion pathway by incubating 344 SQ
cancer cells with the drug and observing cell
proliferation.
METHODS
The cancer cells that were analyzed are
from a mouse model (metastatic 344 SQ
cell line) donated by the Gibbons Lab at MD
Anderson. 5 These cells have mutations in
the Kras and p53 genes, both of which are
tumor-suppressor genes.
344 SQ cells were mixed with 2 mg/ml
collagen MasterMix and incubated at a
density of 106 cells per ml of solution. 2 ml
aliquots of solution were poured in ten bone
shaped hollow molds, two in each of the five
trays. Prior to use, the trays were dessicated
using an oven. Metal pins extending outward
were inserted inside of the tray to stimulate
static tension. The contraction of the cell mix
caused the pins to be pulled inwards. Four
sawbone cylinders were placed on each of
the pins to increase the pin’s surface area to
prevent the collagen gel mix from tearing on
them during contraction. Media covered the
gels with 50 mm Dasatinib in 200 µl of the
RPMI.
Confocal Imaging
Each day for four days, two gels were
removed from the collagen gel molds and
immersed in 4% paraformaldehyde (PFA). Gel
sections were cut and placed in this buffer to
prevent photobleaching of the samples. Gels
were stained with DAPI for the cell nuclei
and Phalloidin for F-actin and were taken to
confocal microscopy.
Image Processing
DAPI stained images were analyzed using
ImageJ and Cell Profiler, image processing
tools that cleaned for noise and conjoined
looking cells. The end result was a binary
mask, an image representing cells in white
and everything else in black, of all the cells.
The NND ImageJ plugin was then used to
find the distance between the centroid of
each cell and the nearest centroid to it. Cell
Profiler additionally returned the x and y
coordinates of the centroids and object
numbers of the first and second closest cells
to each cell object.
RESULTS
Confocal Imaging
DAPI and Phalloidin staining revealed that
the cells cluster as time progresses (Figure 2).
The panel shows the progression of image
analysis that was undertaken to produce
binary masks for the image analysis software
(Figure 1).
The first column shows an overlay of the
DAPI and Phalloidin channels. The next
column shows the DAPI channel extracted
from the multichannel raw image. Column
three has processed binary masks of the
38 | CATALYST

Figure 1: Panel of Image Processing: The boundaries of the nuclei are
separated from the raw image to conduct NND testing. The scale bar is 50
µm and is applicable for all images.
Figure 2: Nearest Neighbor Distance for Cells treated with 50 nM Dasatinib
over the course of four days. The green lines each indicate the median of
the distribution of distances for one day (Day 1: 46.36 µm, Day 2: 31.77 µm,
Day 3: 21.49 µm, and Day 4: 13.72 µm). The red horizontal lines indicate the
interquartile ranges for each distribution. Two stars indicate a significance
level of 0.01 and three stars indicate a significance level of 0.001.
DAPI channel, and the last column has
outlines of the binary masks in which each
object is numbered for reference. This
processing was conducted for all images in
Day 1, 2, 3, and 4 sets. The general qualitative
trend in DAPI from Day 1 to 4 is that there
are more cells and more of them are
clustered. Increased intensity in phalloidin
staining from Day 1 to Day 4 shows actin
expression increasing with time.
Each object’s NND was calculated and plotted
(Figure 2). Cell Profiler also returned NND
calculations identical to ImageJ plugin’s data.
The values for Day 1 have a statistically
significant difference from those of Day 2,
Day 3, and Day 4 (Figure 2). Day 2 and Day 4
also had a statistically significant difference.
DISCUSSION
Confocal Imaging
Image processing results show that the cells
appear clustered in response to Dasatinib.
This is seen in the statistically significant drop
in the mean NND over the course of the four
days.
There is a possibility that the clustered
cells replicated in the same area. Dasatinib
inhibits the focal adhesion pathway, which
controls important processes such as actin
polymerization and filopodia formation
that are instrumental to the invasiveness of
cancer cells. 4 Thus, the newly divided cells
would have a diminished ability in moving.
Even if Dasatinib does not cause old cells
to migrate closer to each other, it may slow
down cell movement that otherwise drives
new cells away from each other.
Furthermore, analysis of the binary masks
shows evidence of cell division. Each set of
binary masks had more cells than that of the
previous day. This phenomenon may have
occurred if cells that were not initially in the
viewing frame moved into view or if the cells
already in view divided in place. However,
tracking the movement of cells in real
time would be required to provide further
evidence for this inference.
One limitation of our experiment is that it is
difficult to image the same gel location for
each day. According to the current protocol,
the cells must be fixated before confocal
view, so the experiment operates under the
assumption that the distribution of cells in
the gel at any time is the same. We conclude
that the clustering observed at a different
location on Day 3 suggests that the cells
viewed on Day 2 would have experienced the
same amount of clustering had they been
allowed to live to the next day. However,
we had a sample size of four different gel
locations for each day and observed the
same general characteristics across locations,
providing evidence to assume that the spatial
distribution in one location is representative
enough of the whole cell distribution.
The NND statistical model provided robust
results. The Cell Profiler data and the NND
plugin in ImageJ were identical in terms of
the object number and the calculated NND,
but the Cell Profiler method required fewer
post processing steps, allowing less room for
error.
An area of improvement for our method of
statistical analysis would be to differentiate
between cells organized in a line and
cells clustered in a ball. Our traditional
understanding of clustering involves a
circular cluster but the images showed
clustering in the form of a slanted line.
Because the images are cross sections
in the z direction and several images in a
row showed a line of cells, that indicates
clustering in the form of a slanted plane in
the gel. Both circular and linear distributions
could have the same NND values, but the
present analysis fails to explain different
clustering behaviors. Regardless of spatial
distribution, smaller NNDs occur as an effect
of the treatment applied to the sample.
CONCLUSION
In the presence of Dasatinib there is a
significant decrease in NND over the course
of four days. All the methods used to analyze
the data suggest that cells cluster in the
presence of Dasatinib. Clustering induced
by Dasatinib will induce a reversal of EMT
induced mesenchymal cells into adopting
a more epithelial phenotype. These cell
clusters reduce the progress of metastasis
of the cancer, bringing the patient extended
lifetime. To examine the possibility that
the cell’s decrease in movement causes
clustering in Dasatinib treated cells, scanning
electron microscopy (SEM) imaging can show
diseased cell mechanisms for movement
in the presence of the drug. To determine
whether the cell clustering occurs due
to migration or cell replication, molds
constructed using the engineering design
process will be used for live cell confocal
imaging. Current and ongoing evaluations
of Dasatinib’s properties will define its
effectiveness as a cancer drug.
WORKS CITED
[1] American Cancer Society, https://www.cancer.org/cancer/
small-cell-lung-cancer/about/key-statistics.html (accessed Jan.
4, 2018).
[2] Xiao, D., et al. J Thoracic Dis, 2010, 2, 154-159.
[3] Peng, D. H., et al. Oncogene, 2017, 36, 1925-1938.
[4] Sulzmaier, F. J, et al. Nat Rev Cancer, 2014, 14, 598-610.
[5] Gibbons, D. L., et all. Genes Dev, 2009, 23, 2140-2151.
DESIGN BY: Priscilla Li
EDITED BY: Olivia Zhang
CATALYST | 39

BIODIVERSITY IN
A DROP OF WATER:
A GLANCE INTO
MARINE FORENSICS
ELAINE SHEN
eDNA refers to the
genetic material
organisms shed
as waste in the
environment (e.g.
water, sediment,
ice cores, etc.) that
can be directly
sampled
Introduction
Marine ecosystems are threatened
worldwide by a variety of anthropogenic
stressors which have severe implications
for global biodiversity, economy, and
human health. 1,2 Examining the abundance,
distribution, and diversity of marine
communities is vital to understanding
basic ecological questions pertaining to
conservation and resource management. 2,3
Traditionally, scientists monitor marine
organisms using techniques reliant on
in-situ visual identification and counting
of organisms. These methods, which
include roving diver surveys, trawls, netting,
tagging, electrofishing, and rotenone
poisoning, are expensive, time-consuming,
invasive, limited in scope, and reliant
on taxonomic experts. 3,4 In addition,
such traditional techniques are prone to
produce a significant number of falsenegatives
in which species actually present
in an environment are not seen in the
survey, generally because they are rare
and/or not easily seen. 2 Addressing these
limitations using a molecular approach
may limit the human biases associated with
these sampling methods.
Improvements to DNA sequencing
technology and decreased sequencing costs
have made sampling for environmental
DNA (eDNA) in marine environments
more feasible. eDNA refers to the genetic
material organisms shed as waste in the
environment (e.g. water, sediment, ice
cores, etc.) that can be directly sampled. 4
For the purpose of this review, eDNA
collection from specifically liquid water
samples were considered because they
detect organisms in recent time (on the
order of hours to days) due to their faster
degradation rates in the water. 4 While
ecological applications of eDNA started in
microbial communities in marine sediments
and invasive species in aquatic habitats,
there have been a handful of studies in the
past few years that have sampled for larger
size classes, like macrofauna, from marine
communities. 5-7
Regardless of ecosystem, the “eDNA
metabarcoding” approach allows for
quantification of whole communities using
water sampling (Figure 1). Water samples
are collected, filtered, extracted for DNA,
amplified using specific PCR primers, and
analyzed using next-generation sequencing
for amplicons. Sequencing data is then
compared to a reference database of
partially or fully characterized genomes
of organisms present in that particular
region. Other further applications of DNA
extracts such as quantitative PCR (qPCR)
are also utilized in place of next-generation
sequencing for identification of organisms. 7
40 | CATALYST

Identifying Presence/
Absence of Marine
Macrofauna Across
Spatial Scales
eDNA sampling has been utilized in a
variety of marine ecosystems to detect the
presence of marine macrofauna, including
marine fish and mammal species. In
one of the first studies to sample eDNA
from marine communities, Thomsen
et al. (2012a) found that in comparison
to nine different traditional surveying
techniques, eDNA performed as well or
better than traditional surveying techniques
at detecting commercially important yet
rarely-detected fish species in the Sound of
Elsinore. After multiple trials, the traditional
surveying techniques, were only able to
detect on average 4.3 species using fish
pots to 14.7 species using night-snorkeling.
In comparison, the eDNA samples detected
more, at 15 fish species. In addition, the
eDNA samples detected 4 bird species
that could not have been detected using
traditional surveying techniques. However,
the scope of this study was limited, as
only three half-liter water samples were
examined, and these findings cannot be
reasonably extrapolated to apply over
larger spatial scales.
Port et al. (2015) addressed some of
these limitations and found that eDNA
sampling still outperformed traditional
roving diver surveys in a 2.5 km transect
across kelp forests, rocky reefs, sand
patches, and seagrass habitats. While the
visual surveys identified 12 taxa, the eDNA
samples identified 11 of those and 18
additional taxa that were not detected by
the visual surveys. The sensitivity of eDNA
to detect species indicates that on larger
spatial scales, the false-negative rate of
traditional surveys far exceeds that of eDNA
sampling. 2 In addition to detecting elusive
fish species, they found that eDNA can be
used to determine the spatial patterns of
entire marine communities as well. Within
each habitat, the distribution of species
was more consistent, while across these
habitats, they were markedly different.
This indicates that while ocean water
movement could theoretically move eDNA
to vastly different locations from their point
of origin, eDNA tends to stay localized (in
this case, within 60 meters) of a particular
habitat. 2
However, for organisms with large
home ranges such as cetaceans, eDNA is
dispersed across a wide spatial scale and
becomes less useful in comparison to other
monitoring methods like bioacoustics. 8 For
the harbor porpoise (Phocoena phocoena),
for example, eDNA detection was only
reliable in controlled environments and
performed worse than acoustic detections
in natural environments. However, because
scientists were able to identify a long-finned
pilot whale (Globicephala melas), another
cetacean, in the natural environment
that is rarely sighted, the research group
concluded that further polishing of the
eDNA sampling method could prove to be
promising for monitoring efforts. 8
The relationship between eDNA
abundance, relative abundance, and
biomass has been shown in closed
marine and aquatic systems, but
has yet to be applied successfully in
natural marine habitats.
Current Limitations to
eDNA Applications
The success of eDNA detection is limited by
both site-specific environmental conditions,
sample processing at the molecular level,
and bioinformatics analyses.
1 2 3 4 5 6 7
Sample
collection
DNA
extraction
DNA
amplification
High-throughput
sequencing
Bioinformatic
processing
Species
identification
Ecological
analysis
Figure 1. Simplified representation of a metabarcoding (next-generation sequencing) pipeline.
CATALYST | 41

I. Relating Sequence
Abundance to Relative
Abundance
While studying the presence of marine
macrofauna is a novel approach to
understanding many basic ecological
questions, relating the sequence
abundance from a water sample to the
relative abundance of an organism in
a natural community is still difficult to
determine. The relationship between
eDNA abundance, relative abundance,
and biomass has been shown in closed
marine and aquatic systems, but has yet to
be applied successfully in natural marine
habitats. 9,10
II. Environmental
Constraints
As with any field method, eDNA sampling
assumes that the contents of a water
sample are representative of the whole
community. To ensure that a water sample
is homogeneous throughout, scientists
often collect subsamples from larger water
samples in order to determine if there are
significant differences in the sequencing
data between subsamples. 4,9
The degradation rates of eDNA in marine
environments are also important for
determining how long the presence signal
of an organism persists in the environment
(and potentially moves to distant locations
through currents). 3,4,10 Since eDNA shedding
and degradation depends on a variety of
factors based on the environment, target
organisms’ physiology, abiotic and biotic
factors, DNA characteristics, population
size, and more, study-specific degradation
and shedding experiments should be
utilized to calibrate the eDNA signal. 3
eDNA proves to be highly sensitive and
reliable in determining the presence of
marine macrofauna in comparison to
traditional visual/trap-based methods
III. PCR Bias and Primer
Choice
The primer choice during PCR is crucial
to determine the region of DNA that
will be amplified and sequenced from
an eDNA sample and must be validated
using experimental controls or online
programs. 4,7 There are tradeoffs in primer
choice and design - some primers have a
higher affinity to some sequences and not
others, affecting which marine organisms
transmit the largest detection signal. 4
Primer choice introduces amplification
bias, which is influenced by the types of
fishes surveyed and the environmental
conditions of the area. 9,10 For example,
when Kelly et al. (2014) used the 12S
mitochondrial DNA (mtDNA) primers, they
were able to detect bony fishes with a
low false-negative rate, but were not able
to detect the cartilaginous fishes or sea
turtle in the mesocosm tank. For these
organisms, species-specific primers were
needed for detection. Since the community
composition can vary so widely depending
on the primer choice and amplification bias,
researchers may use multiple universal and
species-specific primer sets on the same
DNA extracts to obtain higher resolution
and detection. 4,9
IV. Quality Controlling Reads
and Reliable Reference
Databases
After samples are sequenced, they come
back as raw material known as “reads”
and are processed for quality control and
validation. 7 Known as bioinformatic filtering,
sequences are assigned to samples,
filtered, trimmed and discarded based on a
strict set of criteria. 2,4,9,10 Although detecting
rare, cryptic, or low-abundance species is
desired, strict sequence and taxon filtering
ensures high-confidence reads that could
repeatedly and reliably show presence of
organisms while removing false positives,
or organisms artificially present in the data
(likely from contamination) but not present
in the actual environment. 2
After quality control and validation,
Operational Taxonomic Units (OTUs) are
assigned to sequences and referenced to
known genomic databases for taxonomic
identification. Generally, sequences are
clustered into OTUs and matched to known
genus or species sequences if they are
>99% similar to each other. 2,4,9,10 However,
the proper identification of these marine
organisms relies heavily on the quality of
the reference database. In systems that are
not well-studied, the reference database
42 | CATALYST

may not be reliable.
Conclusion
The future of eDNA as a monitoring tool
for marine macrofauna communities is
possible, but currently limited in scope
due to the methodological constraints that
need to be considered. Current research
indicates that while eDNA proves to be
highly sensitive and reliable in determining
the presence of marine macrofauna in
comparison to traditional visual/trapbased
methods, relating eDNA sequence
abundance to the relative abundance in the
community requires further investigation.
This is due to the fact that eDNA
sequence abundance varies depending
on the particular workflow and sitespecific
environmental factors. However,
establishing multiple avenues to test the
importance of these limitations within an
experiment can help contextualize these
problems. For example, including an
eDNA degradation experiment, multiple
primer sets, and a custom database are all
different methods researchers mentioned
in this review used to address some of
these constraints. Although it is difficult
to control for all of the abiotic, biotic,
and molecular factors, the importance
of accurate monitoring efforts in these
ecosystems cannot be understated.
and 3) to continue building on known
reference databases. Combined, these
considerations will improve the eDNA
sampling and metabarcoding method,
promoting its eventual establishment as
the gold standard for marine community
monitoring, resource management, and
conservation efforts.
References
[1] Halpern, B. S. et al. Science. 2008. 319 (948-952).
[2] Port, J. A. et al. Mol. Ecol. 2015. 25 (527-541).
[3] Sassoubre, L.M. et al. Env. Sci. and Tech. 2016. 50
(10456-10464)
[4] Thomsen, P. F. et al. PLoS ONE. [Online] 2012a. 7.
https://doi.org/10.1371/journal.pone.0041732 (accessed
Nov. 14, 2017)
[5] Díaz-Ferguson, E. E.; Moyer, G. R. Revista de biologia
tropical. 2014. 62.4 (1273-1284).
[6] Thomsen, P. F. et al. Mol. Ecol. 2012b. 21 (2565-2573).
[7] Rees, H. C. et al. J. Applied Ecol. 2014. 51 (1450-1459).
[8] Foote, A. D. et al. PLoS ONE. [Online] 2012. 7. https://
doi.org/10.1371/journal.pone.0041781 (accessed Nov. 14,
2017)
[9] Kelly, R. P. et al. PLoS ONE. [Online] 2014. 9. https://
doi.org/10.1371/journal.pone.0086175 (accessed Nov. 14,
2017)
[10] Lacoursière-Roussel, A. et al. J. Applied Ecol 2016. 53
(1148-1157).
[11] DiBattista, J. D. et al. Coral Reefs. 2017. 36.4 (1245-
1252)
Icons from AFY Studio, Aleksandr Vector,
Jeffrey Qua, Luke Patrick, and Vega Asensio via
the Noun Project
Design by Kaitlyn Xiong
Edited by Jenny Wang
relating eDNA
sequence abundance
to the relative
abundance in the
community requires
further investigation
. . . due to the fact
that eDNA sequence
abundance varies
depending on the
particular workflow
and site-specific
environmental factors.
Thus, further studies utilizing eDNA should
proceed in three ways: 1) to take advantage
of eDNA’s benefits in presence/absence
studies to detect rare, and cryptic species,
2) to refine the methodological details,
including primer design and bioinformatic
analyses, for more reliability and efficiency,
CATALYST | 43

eviewing the relationship between
INFLAMMATORY BOWEL
DISEASE AND PRIMARY
SCLEROSING CHOLANGITIS
by Mahesh Krishna
ABSTRACT
Primary Sclerosing Cholangitis (PSC)
is a chronic and progressive disease
of unknown etiology that affects the
bile ducts in the liver. 1 Inflammatory
Bowel Disease (IBD) is a chronic disease
affecting the gut that comprises of
two classifications: Crohn’s disease
(CD) and ulcerative colitis (UC). 2 The
exact mechanism for both diseases is
unknown, yet as high as 80% of patients
with PSC are also diagnosed with IBD. 3
This suggests that these two diseases
are closely related and may even have a
shared ‘trigger.’ This article provides an
overview of the current research carried
out on the relationship between IBD and
PSC by first focusing on theories of the
pathogenesis of PSC and then explaining
how these theories can explain the
association with IBD.
THEORIES ON PATHOGENESIS
OF PRIMARY SCLEROSING
CHOLANGITIS
Although the exact pathogenesis of PSC is
unknown, there are three main theories
that have been proposed: a) the “leaky
gut”, b) the “gut lymphocyte homing”, and
c) the “toxic bile” theory. The earliest one
has been the ‘leaky gut’ theory, which
proposes that an injury to the mucosa in
the gut would cause a ‘leakage’ of bacteria
into the circulation of the body, eventually
reaching the liver and leading to PSC. 4
The ‘leaky gut’ theory is concerned with
The exact mechanism for
both diseases is unknown,
yet as high as 80% of
patients with PSC are
also diagnosed with IBD.
pro-inflammatory bacteria that escape the
gut due to the increased permeability of
the intestinal walls (‘leaky’). 5 Then, these
bacteria are able to reach the bile ducts
in the liver and upregulate inflammation
through lipopolysaccharides leading to
PSC. 6 Since PSC does not seem to respond
to immunosuppressants, research
suggests that non-immune mechanisms
such as bacterial infections, ischemia,
and toxicity are also important, which
are explored in the ‘leaky gut’ theory. 7
Therefore, genetically susceptible
individuals exposed to bacteria may
start having their hepatic macrophages
produce pro-inflammatory cytokines
such as TNF and chemokines, which in
turn may attract and activate T-cells, B
cells, monocytes, and neutrophils to the
liver and around the bile ducts, causing
damage and thus leading to cholestasis
and PSC. 7 The ‘leaky gut theory’ is an
interesting explanation to explain the
pathogenesis of PSC, but it is not the only
theory.
As more research has been conducted
through genome-wide association studies
(GWAS), a strong connection to the
human leukocyte antigen (HLA) complex
was identified, suggesting an autoimmune
component affecting susceptibility
to PSC. 5 Based on the results of the
GWAS, other models, including the ‘gut
lymphocyte homing’ theory and the ‘bile
acid toxicity theory,’ were developed 1,5 It is
also important to note that environmental
risk for the disease likely contributes
50% in the development of the disease,
therefore, complicating the application of
one particular theory to explain PSC. 5 A
unified model of the various theories has
not yet been proposed.
PSC pathogenesis theories:
1
Leaky Gut
2
Gut Lymphocyte Homing
3
Toxic Bile
44 | CATALYST

Gut microbiota and bile homeostasis
Human mechanistic insights
• Hereditary choleostasis (eg, cystic fibrosis)
• Infection with or without immunodeficiency
• Ischaemia and other causes of secondary
sclerosing cholangitis
Murine mechanistic insights
• Spontaneous models (eg, ABCB4-/-)
• Induced models (eg, lithocholic acid)
Pathological changes
Crohn’s disease
30 loci
Fibrosis
Dysplasia
CCR9
T
α4β1
Inflammatory
bowel disease
103 loci
Ulcerative
colitis
22 loci
7 loci
1
locus
Primary
sclerosing
cholangitis
7 loci
HLA
associations
Inflammation
B
α4β7
VCAM1 CCL25
MADCAM1
Endothelial cell
Genetics and the HLA complex
T-cell homing and autoreactivity
Figure 1. This image shows the complex interactions throughout the body between genetics, the immune system, and the
microbiome that leads to PSC-IBD and harmful changes within the body. From Hirschfield et al.1
The ‘gut lymphocyte homing’ theory
focuses on memory T-cells from the gut
moving into the liver via the chemokine
receptor CCR9 and integrin α4β7,
triggering inflammation once reactivated. 9
Recent research has found evidence of
memory T-cells of common clonal origin in
both the liver and gut of patients with PSC-
IBD.10 CCR9+ α4β7+ T-cells are recruited
to the gut by binding to mucosal vascular
addressing cell adhesion molecule 1
(MAdCAM-1) and chemokine CCL25, which
are usually uniquely expressed in the
gut. 9 MAdCAM-1 and CCL25, however, are
induced in the liver of patients with PSC
due to hepatic inflammation through proinflammatory
cytokines (like TNFα) and
activation of VAP1 in the veins near the
liver. 1 The ‘gut lymphocyte homing’ theory
attempts to explain the pathogenesis of
PSC by incorporating an autoimmune
component.
Finally, the ‘bile acid toxicity’ theory
concerns the failure of mechanisms to
protect biliary epithelial cells against bile.
While bile is an important fluid that aids
in digestion, it is toxic. 11 Cholangiocytes,
the epithelial cells of the bile ducts,
are protected from bile acid toxicity by
a variety of mechanisms including a
bicarbonate layer and a calcium-driven
channel. 5 Therefore, a disturbance in bile
homeostasis is believed to contribute
to the development of PSC. 5 Bile acid
homeostasis regulation, however, is not
completely understood. 12 Currently, the
recommended medication for someone
diagnosed with PSC is ursodeoxycholic
acid, although there are controversial
findings on whether it actually helps or
not. Ursodeoxycholic acid may utilize
bile mechanisms by replacing toxic
hydrophobic bile salts in serum, liver, and
bile, which protects cholangiocytes against
cytotoxicity of the bile acids. 11 Therefore,
this theory is also vital in understanding
the complete picture of the etiology of
PSC.
THEORIES ON PATHOGENESIS
OF INFLAMMATORY BOWEL
DISEASE
Studies have identified IBD in patients
with PSC (PSC-IBD) as a unique entity
compared to those with just IBD. 3 This
is due to different risk genes found
between the two diseases and unique
clinical presentations. 3,13 Additionally,
PSC-IBD patients were found to have a
higher risk of colorectal cancer, yet a less
active form of IBD. 14 75% of cases of IBD
in PSC-IBD is found to be classified as
UC. 15 Similar to PSC, the exact mechanism
for the cause of IBD and a cure have not
been found. Important factors that may
trigger an aberrant immune response
and chronic gut inflammation include the
gut microbiome, infectious agents, stress,
genetics. 16
The gut microbiota, in particular, has
been found to have an impact on the
pathogenesis of IBD. 16 Dysbiosis, an
imbalance in the gut microbiome,
has been shown through clinical and
experimental data as having a pivotal role
Both diseases share
common antibodies that
have a characteristic
perinuclear staining
pattern.
in the pathogenesis of IBD. 16 Therefore,
the presence or lack of an organism in the
gut microbiome may trigger IBD in certain
environmental conditions.
CATALYST | 45

CONNECTION BETWEEN
ULCERATIVE COLITIS AND
PRIMARY SCLEROSING
CHOLANGITIS
Since PSC and IBD have a strong
concurrence, there is a likely connection
between the two diseases. There
have been observations regarding the
occurrence of PSC after a colectomy
and occurrence of IBD after liver
transplantation, which suggests that ‘gut
lymphocyte homing’ might be causing
both PSC and IBD. 17 Both diseases
share common antibodies that have
a characteristic perinuclear staining
pattern. 15 However, PSC and IBD have
been found to have limited genetic
overlap suggesting these diseases
utilize distinct genetic mechanisms. 15 In
addition to the ‘gut lymphocyte homing’
hypothesis, the ‘leaky gut’ hypothesis
also connects the two diseases. The liver
receives a large amount of its blood
supply through the gut. As a result,
the liver is also exposed to molecules
present in the gut microbiome. 15
Therefore, the dysbiosis present in
PSC-IBD patients may alter homing of
gut-specific lymphocytes or cause the
intestine to become more ‘leaky’ to proinflammatory
bacteria. 15 The ‘leaky gut’
and ‘gut lymphocyte homing’ concepts
attempt to provide a connection of PSC
with IBD.
CONCLUSION
The pathogenesis of PSC-IBD is still
unknown, but it is known to involve a
complex mechanism that may overlap
between the two diseases. Of the three
common theories of the etiology of PSC,
two of them (gut lymphocyte homing
and leaky gut) also attempt to explain
its interaction with the gut and IBD.
The ‘gut lymphocyte homing’ theory
attempts to explain the connection
through the aberrant expression of
MAdCAM-1 and CCL25, which are usually
only present in the gut. As a result of
this unusual expression, memory T-cells
with the appropriate homing receptors
(chemokine receptor CCR9 and integrin
Both diseases share
common antibodies that
have a characteristic
perinuclear staining
pattern.
α4β7) may attack liver cells and gut cells,
triggering the inflammation typical of
PSC and IBD. The ‘leaky gut’ hypothesis
justifies the connection between the
two diseases through the portal system.
The liver is constantly exposed to the
intestinal microbiome through the
circulation of blood. Therefore, it is
thought that an imbalanced microbiome
in the gut, which has been implicated in
IBD, may also serve as a trigger in the
development of PSC. The microbiome in
PSC-IBD patients has been the subject of
recent research.
The phenotype of PSC-IBD patients
is very unique and requires further
research to better meet the need of the
patient population. The diagnosis of
PSC and UC for PSC-IBD patients also
occur at a much earlier age than PSConly
and UC-only phenotypes. 15 More
resources are needed to address this
health burden as the costs for patients
of a PSC-IBD phenotype will be much
greater, due to the early age of diagnosis
for PSC and IBD and their debilitating
effects over time. By elucidating the
mechanisms of these diseases, hopefully
a cure for both PSC and IBD can be
developed in the near future.
WORKS CITED
[1] Hirschfield G.M. et al. Lancet. 2013, 382, 1587-
1599.
[2] Nemati S.; Teimourian S. Mid East J Dig Dis. 2017,
9, 69-80.
[3] Chung B.K.; Hirschfield G.M. Curr Opin Gastro.
2017, 33, 93-98.
[4] Karlsen T.H. Gut. 2016, 65, 1579-1581.
[5] Karlsen T.H. et al. J Hepatol. 2017. 67, 1298-1323.
[6] Pontecorvi V. et al. Ann Transl Med. 2016, 4, 512.
[7] Cullen S.; Chapman R. Best Pract Res Clin Gastro.
2001, 15, 577-589.
[8] Aron J.H.; Bowlus C.L. Semin Immunopathol. 2009,
31, 383-397.
[9] Trivedi P.J.; Adams D.H. J Autoimmun. 2013, 46,
97-111.
[10] Henriksen E.K. et al. J Hepatol. 2017, 66, 116-122.
[11] Trauner M. et al. N Engl J Med. 1998, 339, 1217-
1227.
[12] Chiang J.Y. F1000Res. 2017, 6, 2029.
[13] Sano H. et al. J Hepatobiliary Pancreat Sci. 2011,
18, 154-161.
[14] Sokol H. et al. World J Gastro. 2008, 14, 3497-
3503.
[15] Palmela C. et al. Gut Liver. 2018, 12, 17-29.
[16] Nishida A. et al. Clin J Gastro, 2017, 11, 1-10
[17] Nakazawa T. et al. World J Gastro, 2014, 20,
3245-2354.
DESIGN BY: Katrina Cherk
EDITED BY: Shrey Agarwal
46 | CATALYST

the science of beauty
by Krithika Kumar
Henry David Thoreau, in his book Walden, details
his almost two-year excursion of simple living in
the woods of Massachusetts. He viewed nature
as a way to achieve a higher understanding of the
universe, and enjoyed being one with the solitude
and beauty it has to offer. Nature, thus, has a way
of connecting humans to our emotions and eliciting
positive thoughts and feelings. For example, it is
a universal truth that a rainbow after a rainy day
brings a smile to anyone’s face. The aurora borealis,
or Northern Lights, are regarded by many as
breathtaking, a must-see on planet Earth. But how
does nature capture our attention and scintillate
our senses? What are the long-term effects of
spending time in the outdoors?
Beauty in the natural world affects humans
subconsciously: spending time in the outdoors is
connected to overall mental well-being. A simple
stroll through a forest, for example, can allow us
to distance ourselves from our otherwise chaotic
thoughts. We are forced to regard every stimuli
around us, from the sun shining down upon us to
the tall trees shrouding us to the the small squirrels
and insects we are careful not to harm. Compared
to the contemporary world, which forces humans
to live life in the fast lane through the influence
of technology and commerce, nature is Earth at
its most basic level. It allows humans to take a
step back and a breath in, and entices us with its
many facets of simplicity and serenity. Thus, the
environment melts stress and releases endorphins
that can decrease feelings of depression and
fatigue.
Nature’s ability to distract us from the present also
increases creativity and intelligence. David Strayer
of the University of Utah showed that hikers were
able to solve more complex puzzles after a four-day
backpacking trip compared to a control group. The
prefrontal cortex, which controls decision-making
and social behavior, undergoes much strain from
daily usage of technology and multi-tasking. This
area of the brain can take a break when we respond
to purely nature-driven stimulus. Nature allows
the brain to reset so that it can perform tasks with
renewed energy.
A change of environment can also makes humans
kinder and more generous. There is an out-of-body
feeling associated with viewing an awe-inspiring
landscape that makes one feel that one is part of
something bigger than the present. It can make dayto-day
inconveniences seem inconsequential and
remind us that there is more to the world than what
goes on in our lives. Humans are also more likely to
be more ethical when faced with moral dilemmas
after spending time in nature. Experiments
conducted at the University of California, Berkeley,
found that participants playing the Dictator Game
(which measures the degree to which individuals
will act out of self-interest) were more likely to be
generous to their peers after being exposed to
alluring nature scenes.
Planet Earth’s most primitive offerings actually
present us with complex and diverse benefits. A
quick breath of fresh air can melt away feelings of
stress and anxiety, while increasing cognitive focus
and creativity. Perhaps we can create our own
“Walden” and take a break from studying or working
to simply enjoy the outdoors and spend time
appreciating the many sides of our ever-changing
world.
WORKS CITED
[1] “How Nature Can Make You Kinder, Happier, and More Creative.”
Greater Good, greatergood.berkeley.edu/article/item/how_nature_
makes_you_kinder_happier_more_creative.
[2] Louv, Richard. “Ten Reasons Why We Need More Contact with
Nature | Richard Louv.” The Guardian, Guardian News and Media, 12
Feb. 2014, www.theguardian.com/commentisfree/2014/feb/13/10-
reasons-why-we-need-more-contact-with-nature.
[3] “Henry David Thoreau.” Henry David Thoreau, transcendentalismlegacy.tamu.edu/authors/thoreau/.
Vector from Freepik
CATALYST | 47

BOMB:
the
TICKING
hereditary cancer
TIME syndromes
BY SHRUTI SHAH
“Life comes with many challenges. The
ones that should not scare us are the ones
we can take on and take control of.” As
hard as it is to believe, this is a quote from
Angelina Jolie’s book about hereditary
breast cancers where she encourages a
more thorough integration of genomics
into the field of oncology. Recently,
celebrities such as Angeline Jolie have
spoken out about the BRCA genes and
their personal experiences with hereditary
cancer syndromes. Jolie’s doublemastectomy
and the media’s portrayal of
her treatment have helped to drastically
increase the awareness of genetic testing
among the general population.
Hereditary cancer syndromes, and
particularly hereditary breast cancers,
are primarily associated with the genetic
mutations BRCA1 and BRCA2. An
individual with the BRCA genes can have
over a 70% chance of developing cancer
with the right combination of genetic and
environmental factors. With the odds
of developing cancer so high, it seems
obvious that any measure we can take to
lower this penetrance should be fervently
supported by all medical professionals.
Right?
There’s an important ethical dilemma
that arises whenever we think about
using these new technologies. On the one
hand, genomics, the technological aspect
of genetics concerned with sequencing
and analyzing an organism’s genome,
has greatly improved the prognosis for
cancer patients. Genetic profiling can help
individuals with hereditary breast cancers
through every stage of their disease, from
diagnosis to treatment. An interesting
use of genetic profiling is using the BRCA
genes to help classify tumors. Because
patients with the same BRCA mutation
most likely have the same type of tumor,
classifying one individual’s tumor means
you have classified the other’s! More
importantly, by providing a means of
pre-symptomatic testing, patients are
able to utilize precautionary measures
such as estrogen-regulating drugs and
preventative surgeries like mastectomies
(removal of breast tissue).
On the other hand, it is simply not
possible to test every individual for the
BRCA genes. For one, they are extremely
costly. There is no way that a geneticist
can indiscriminately recommend
genetic testing to every patient as DNA
sequencing tests have yet to be covered
by every health insurance plan. Without
insurance, the cost of one of these tests
can range from $475 to over $4000.
Furthermore, the results of such a test
can put an individual at risk for genetic
discrimination. Although GINA, or the
Genetic Information Nondiscrimination
Act, protects from genetic discrimination,
or having to pay an inflated premium
due to genetic test results that reveal
a predisposition for a severe genetic
disease, it only applies to health insurance
and not life insurance. Having young
individuals get tested for the BRCA genes
comes with the possibility of hiking up
their life insurance premiums later in life.
Finally, an individual’s mental wellbeing is
at risk because the fear of one’s diagnosis
can understandably cause anxiety and/or
depression.
So the question remains. Do we
encourage the general public to get
tested for the BRCA genes if they believe
that they have a strong family history of
hereditary cancers? Although there is no
answer to this question that pleases all
medical professionals, one thing is certain:
An ordinary individual can possibly
prevent cancer in his or her family with
the help of genetic testing. When used
cautiously, genetic testing is an invaluable
tool in all stages of cancer treatment and
prevention. It seems clear to me that
advocating for widespread awareness
of the advantages of genetic testing in
reducing cancer penetrance is one of
the most beneficial ways to prevent the
growth of tumors in an individual and to
control inheritance through generations.
Why are we waiting, then? Let’s take
control and not let cancer scare us
anymore.
WORKS CITED
[1] “GINA & Your Health Insurance.” GINAhelp.org - Your
GINA Resource. N.p., n.d. Web. 03 Nov. 2016.
[2] Moyer, Virginia A. “Risk assessment, genetic
counseling, and genetic testing for BRCA-related
cancer in women: US Preventive Services Task Force
recommendation statement.” Annals of internal
medicine 160.4 (2014): 271-281.
[3] Chen, Sining, and Giovanni Parmigiani. “Meta-analysis
of BRCA1 and BRCA2 penetrance.” Journal of Clinical
Oncology 25.11 (2007): 1329-1333.
48 | CATALYST

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