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VOLUME 11, <strong>2018</strong><br />


written in the<br />

(dead) stars<br />

The Black Hole Information<br />

Paradox<br />


+ Bioengineering Methods to<br />

Foster Neonatal Care<br />

+ Mechanobiology of Lung Cancer<br />

Cells During Metastasis

FROM THE<br />

Editor<br />

Dear Reader,<br />

Welcome to the eleventh annual edition of <strong>Catalyst</strong>,<br />

Rice’s premier Undergraduate Science Research Journal.<br />

We are a peer-edited publication founded to showcase<br />

student perspectives on popular science topics and<br />

scientific research. For the past eleven years, we have<br />

been committed to fostering interdisciplinary interest<br />

in scientific writing and dialogue at Rice and beyond.<br />

We are passionate about making science accessible and<br />

engaging, whether you’re a Ph.D. research scientist or<br />

a casual reader. In this year’s publication, you can find<br />

articles about fields as diverse as quantum computing,<br />

cancer therapy and marine forensics.<br />


Rishi Sinha<br />

Ruchi Gupta<br />

Shashank Mahesh<br />

Rachita Pandya<br />

Staff<br />


Elaine Hu, Activities Chair<br />

Sanket Mehta, Editor-in-Chief<br />


Lin Guo<br />

Juliana Wang [ASSISTANT]<br />


Jacob Mattia<br />


Kseniya Anishchenko<br />

This year, <strong>Catalyst</strong> has grown tremendously, both<br />

inside and outside of the Rice hedges. We began<br />

the year with several goals in mind: to improve our<br />

internal organization in response to our growing<br />

member body and growing reach, to better assess<br />

writer development, and to develop and extend our<br />

non-print platforms, such as podcast and blogs. This<br />

year was about achieving those goals, but it was also<br />

about strengthening old connections and forging new<br />

ones, both among <strong>Catalyst</strong> members and with our<br />

partners. It was about creating several initiatives to<br />

increase cohesiveness within the organization, including<br />

study breaks and social events all throughout the<br />

year. The year also marked the launch of the <strong>Catalyst</strong><br />

Research Fair, a well-attended university-wide event<br />

that connected students interested in undergraduate<br />

research directly with lab positions advertised by<br />

graduate students and postdocs. And it was about<br />

continued leadership at the university level, as <strong>Catalyst</strong><br />

worked alongside the Center for Civic Leadership and<br />

the Dean’s Office to help organize Rice Inquiry Week, a<br />

celebration of inquiry-based pedagogy and research at<br />

the university, particularly by undergraduates and their<br />

faculty mentors.<br />



Jack Trouvé<br />


Brianna Garcia, Meredith<br />

Brown, Jason Lee,<br />

Mahesh Krishna, Kelsey<br />

Sanders, Anna Croyle<br />


Albert Truong, Kalia<br />

Pannell, Vatsala<br />

Mundra, Roma Nyaar,<br />

Pujita Munnangi, Axel<br />

Ntamatungiro, Deepu<br />

Karri<br />



Ajay Subramanian<br />


Olivia Zhang, Rishab Ramapriyan,<br />

Jenny Wang, Shrey Agarwal<br />


Nigel Edward, Avanthika<br />

Mahendrababu, Shikha Avancha, Tom<br />

Wang<br />

The progress and expansion we have undergone this<br />

year would not have been possible without the support<br />

of the Rice community, our partners, our mentors, and<br />

our absolutely amazing staff. In particular, we would<br />

like to thank the Rice Center for Civic Leadership,<br />

the Rich Endowment, the Program in Writing and<br />

Communication, and the Student Activities President’s<br />

Programming Fund for their continued generous<br />

support of Rice <strong>Catalyst</strong>’s endeavors. Of course, we also<br />

want to especially thank Dr. Dan Wagner, our faculty<br />

sponsor who has provided us with invaluable advice<br />

and guidance throughout this entire process.<br />

We are proud of how far <strong>Catalyst</strong> has come this year<br />

and we are excited for our growth in the years to come.<br />

From the entire <strong>Catalyst</strong> staff, we hope you enjoy our<br />

latest issue as much as we enjoyed making it!<br />

Sanket Mehta<br />

Editor-in-Chief<br />

2 | CATALYST<br />


Katrina Cherk, Christina Tan, Kaitlyn Xiong, Evelyn Syau<br />


Sara Ho, Nancy Cui, NamTip Phongmekhin, Maddy Tadros, J. Riley<br />

Holmes, Sahana Prabhu, Priscilla Li, Jenny Wang, Anna Croyle,<br />

Jessica Lee<br />


Natasha Mehta, Kaitlyn Xiong, Krithika Kumar, Pujita Munnangi,<br />

Priyansh Lunia, Emre Yurtbay, Shruti Shah, Evelyn Syau<br />


Dr. Daniel Wagner<br />

Cover Image by Ute Kraus from Space Time Travel Gallery

TABLE OF<br />

Contents<br />

4<br />

6<br />

9<br />

10<br />

12<br />

13<br />

14<br />

15<br />

16<br />

18<br />

20<br />

22<br />

24<br />

26<br />

27<br />

28<br />

30<br />

32<br />

34<br />

36<br />

38<br />

40<br />

44<br />

47<br />

48<br />


SCI-FI TO DIY: The Evolution of Genetic Engineering // Dora Huang<br />

WRITTEN IN THE (DEAD) STARS: The Black Hole Information Paradox // Jenny L. Wang<br />

HIGH-ALTITUDE SULFUR INJECTION: Insane or Insanely Genius? // Meredith Brown<br />

PHOTOSYNTHETIC BACTERIA: Shining Light on Heart Disease // Swathi Rayasam<br />

WHO’S SAVING LIVES? Robots // Jenny S. Wang<br />

MIRROR NEURONS: Unlocking the Mind // Samantha Chao<br />

CHAGAS DISEASE: A Silent Killer // Maishara Muquith<br />

CPR For the Vaquita // Celina Tran<br />

QUANTUM COMPUTING: A Leap Forward in Processing Power // Valerie Hellmer<br />


ROBOTS AND MEDICINE: A Connection of Many Degrees // Alan Ji<br />

AMPing Up the Defense System // Preetham Bachina<br />

CREATING GLOBAL CHANGE: Bioengineering Methods to Foster Neonatal Care // Pujita Munnangi<br />

MITOCHONDRIAL HEALTH: Implications for Breakthrough Cancer Treatment // Sarah Kim<br />

THE WATERWORKS: Drinking Water for All // Andrew Mu<br />

LIGHT SHOW: Using Light-Activated Metal Complexes to Combat Alzheimer’s // Oliver Zhou<br />

Sumo Wrestling With Heart Diseases // Amna Ali<br />

SONGBIRDS, AGING, AND AUTISM: The Exciting New Field of Neurogenesis // Christine Tang<br />

Water Security in the Middle East // Sree Yeluri<br />


Methods of Mosquito Vector Surveillance and Population Control // Owais Fazal<br />

The Emergence of Number Theoretic Questions from a Geometric Investigation // Jacob Kesten<br />

The Effect of Dasatinib on Mechanobiology of Lung Cancer Cells During Metastasis // Shaurey<br />

Vetsa et al.<br />

BIODIVERSITY IN A DROP OF WATER: A Glance into Marine Forensics // Elaine Shen<br />

Reviewing the Relationship Between Inflammatory Bowel Disease and Primary Sclerosing<br />

Cholangitis // Mahesh Krishna<br />


Science of Beauty // Krithika Kumar<br />

THE TICKING TIME BOMB: Hereditary Cancer Syndromes // Shruti Shah<br />


SCI-FI<br />

TO<br />

d.i.y. :<br />

Kac created Alba’s<br />

glow through a feat of<br />

genetic engineering:<br />

synthetic mutation of<br />

the green fluorescent<br />

protein (GFP) gene<br />

from the jellyfish type<br />

Aequorea victoria<br />

Genetic engineering is an area of<br />

science that never fails to intrigue<br />

people, mainly because the field<br />

seems like something directly<br />

out of a sci-fi flick or a superhero comic.<br />

Although the practice has been around<br />

since the 1970s, the intricacy involved in<br />

genetic engineering has recently made a<br />

splashing impact in the world of science<br />

and technology, as well as in our daily lives.<br />

Through the mediums of bio-art, biohacking,<br />

human genetic engineering, and GMOs,<br />

genetic engineering is paving its way towards<br />

becoming a staple within our culture, and we<br />

may not be far from a world where this “scifi”<br />

becomes a scientific standard.<br />

In order to trace the history of genetic<br />

engineering, we must examine its origins:<br />

GMOs. GMO stands for genetically modified<br />

organisms, and they are commonly seen in<br />

the form of produce at local supermarkets<br />

or in angry online posts lamenting about the<br />

downfall of health standards. These GMOs<br />

were created by removing DNA from one<br />

plant and inserting it into a separate plant,<br />

giving rise to new abilities, such as herbicide<br />

tolerance and self-sustaining insecticide.<br />

Despite its polarizing connotation, GMOs<br />

are relevant to industry and to our own<br />

consumption, as much of purchased<br />

produce, including corn, soybeans, cotton,<br />

are genetically modified. 1<br />

GMOs can prove to be beneficial for<br />

generations to come, as seen in a study<br />

at the University of Washington, where<br />

researchers have been working since the<br />

early ‘90s to develop poplar plants that<br />

can clean up pollutants found in both the<br />

ground and the air. 2,3 Their genetically<br />

engineered poplar plants can take in 91% of<br />

trichloroethylene, which is the most common<br />

groundwater contaminant in the U.S.. 2,3<br />

In Japan, another team of researchers<br />

is working with Mammalian cytochrome<br />

P450, which is a gene found in mammal<br />

livers. They are implementing this gene into<br />

rice plants, allowing them to degrade and<br />

detoxify herbicides. 2 A detoxifying poplar<br />

and rice plants provides evidence of the use<br />

of genetic engineering in creating GMOs for<br />

the environmentalist movement, yielding an<br />

interesting solution to a pressing issue.<br />

Moving beyond studying plants, genetic<br />

engineers began to experiment on animals.<br />

Though this move sparked controversy in<br />

the scientific community, researchers were<br />

able to create unique organisms in a new<br />

artistic field known as Bio-Art. Brazilian artist<br />

Eduardo Kac sparked the movement of Bio-<br />

Art, a new brand of innovation that combines<br />

the skills of scientists and engineers with<br />

the creativity of artists. Kac rose to fame<br />

due to his project “Alba,” a bunny that glows<br />

green in the dark. 5 Collaborating with a team<br />

of scientists in France, Kac created Alba’s<br />

glow through a feat of genetic engineering:<br />

synthetic mutation of the green fluorescent<br />

protein (GFP) gene from the jellyfish type<br />

Aequorea victoria. 4,5 In Aequorea victoria, a<br />

protein releases a blue light when it bonds<br />

with calcium. 4 The GFP gene then absorbs<br />

this blue light, and green light is emitted. 4<br />

An enhanced version of the GFP gene was<br />

inserted into Alba, amplifying fluorescence in<br />

mammalian cells. 5 Alba and other transgenic<br />

animals provoke feelings of astonishment,<br />

indignation, and curiosity, and it will be<br />

interesting to see what technology the world<br />

of bio-art will embrace next.<br />

Along with being an integral part of the<br />

Bio-Art movement, genetic engineering was<br />

also used in more environmental studies,<br />

such as with the invention of Enviropigs in<br />

Canada. 6 As with all living organisms, pigs<br />

require phosphorus in their food, but have<br />


the EVOLUTION of<br />


By Dora Huang<br />

the inability to digest phytase, an enzyme<br />

that is used to digest the phosphorus found<br />

in the grains and seeds they consume. 6,7<br />

Therefore, they must intake a supplement<br />

of these phytase enzymes, which have<br />

been found to be ineffective, causing<br />

phosphorous to get flushed out as waste. 6,7<br />

However, with Enviropig, the need for<br />

ingesting phytase supplements is eliminated,<br />

because the pig would ideally generate its<br />

own phosphorus-dissolving enzyme. 6,7 This<br />

genetically engineered pig has urine and<br />

feces that contain 40-65% less phosphorus,<br />

which is beneficial for cutting maintenance<br />

and cleaning costs for pig farmers, as well<br />

as “[complying] with the “zero discharge”<br />

rules...that allow no nitrogen or phosphorus<br />

runoffs from animal operations,” as they can<br />

cause dead zones in nearby water sources. 6,7<br />

Though the operation was terminated<br />

after just two years due to loss of funding,<br />

Enviropigs remain a unique solution to an<br />

environmentally threatening problem, and<br />

remains a useful product of genetically<br />

modification.<br />

Scientists have modified plant and animals,<br />

and it was only a matter of time before<br />

humans started genetically modifying<br />

themselves. Just this last summer, the first<br />

human embryos were edited in Portland,<br />

Oregon, involving the changing of DNA of<br />

one-cell embryos using the gene-editing<br />

technique CRISPR. 9,10 CRISPR is a system that<br />

“target[s] specific stretches of genetic code<br />

and... edit[s] DNA at precise locations.” 8<br />

Researchers can use CRISPR to modify the<br />

genes in living organisms and precisely<br />

correct mutations in the human genome. 8<br />

In using CRISPR on editing human embryos,<br />

scientists can change the genetics of a<br />

family for generations to come, as the<br />

genetically modified child would pass down<br />

the modifications to their future offspring. 9,10<br />

Although these “designer babies” have faced<br />

intense backlash due to concerns that this is<br />

a new form of eugenics, CRISPR and human<br />

genetic engineering are relevant because<br />

they have the potential to eliminate fatal<br />

illnesses and genetic mutations before<br />

birth. 9,10 In such cases, it is important to<br />

weigh the costs and benefits of performing<br />

this research, as well as the ethics behind the<br />

entire operation.<br />

In a realm of pure recreational use,<br />

biohackers have begun taking over the<br />

genetic engineering industry using the<br />

CRISPR technique in their own homes and<br />

communities. 11, 12 Biohackers are a group of<br />

amateur and largely untrained biologists that<br />

work together in community laboratories to<br />

create “DIY” genetically modified organisms,<br />

such as growing organs, fiddling with<br />

yeast, and creating vegan cheese. 11 Most of<br />

these experiments are innocuous and help<br />

cultivate and promote scientific research<br />

for those who never believed they would be<br />

scientists, expanding science as a fun, leisure<br />

activity. These clever inventions have largely<br />

been tame and innocently curious, but there<br />

is always a chance for biohacking to be taken<br />

to the next level as the knowledge and use of<br />

CRISPR expands.<br />

Genetic engineering is a controversial topic,<br />

and it can be uncomfortable to think about.<br />

However, with its growing emergence into<br />

our everyday lives, genetic engineering is a<br />

topic that is influencing our future and will<br />

continue to grow in prominence as we look<br />

towards genetic engineering for the answers<br />

to our medical and environmental issues.<br />

Works Cited<br />

[1] Benbrook, C. Summary of Major Findings and Definitions<br />

of Important Terms. http://news.cahnrs.wsu.edu/blog/<br />

article/summary-of-major-findings-and-definitions-ofimportant-terms/<br />

(accessed Oct. 20, 2017).<br />

[2] Hines, S. Scientists ramp up ability of poplar plants<br />

to disarm toxic pollutants. http://www.washington.edu/<br />

news/2007/10/15/scientists-ramp-up-ability-of-poplarplants-to-disarm-toxic-pollutants/<br />

(accessed Oct. 20, 2017).<br />

[3] Choi, C. Genetically Engineered Plants Could Clean<br />

Humanity’s Messes. https://www.livescience.com/1959-<br />

genetically-engineered-plants-clean-humanity-messes.html<br />

(accessed Oct. 20, 2017).<br />

[4] Green Fluorescent Protein. https://www.conncoll.edu/<br />

ccacad/zimmer/GFP-ww/GFP-1.htm (accessed Oct. 7, 2017).<br />

[5] Slawson, K. Eduardo Kac’s GFP Bunny, a Work of<br />

Transgenic Art, or, It’s not Easy Being Green. http://www.<br />

ekac.org/slawson%203.html (accessed Oct. 7, 2017).<br />

[6] Minard, A. Gene-Altered “Enviropig” to Reduce Dead<br />

Zones? https://news.<br />

nationalgeographic.com/news/2010/03/100330-bacon-pigsenviropig-dead-zones/<br />

(accessed Oct. 20, 2017).<br />

[7] Maglona, M. Enviropig: A Genetically Engineered Pig.<br />

https://wordpress.philau.<br />

edu/thevoice/2016/04/enviropig-a-genetically-engineeredpig/#_ftnref5<br />

(accessed Oct. 20, 2017).<br />

[8] Questions and Answers about CRISPR. https://www.<br />

broadinstitute.org/what-broad/<br />

areas-focus/project-spotlight/questions-and-answers-aboutcrispr<br />

(accessed Oct. 20, 2017).<br />

[9] Connor, S. First Human Embryos Edited in U.S. https://<br />

www.technologyreview.com/s/608350/first-human-embryosedited-in-us/<br />

(accessed Oct. 20, 2017).<br />

[10] Belluck, Pam. In Breakthrough, Scientists Edit a<br />

Dangerous Mutation From Genes in Human Embryos. The<br />

New York Times [Online], Aug. 2, 2017. https://www.nytimes.<br />

com/2017/08/02/science/<br />

gene-editing-human-embryos.html?_r=0 (accessed Oct. 20,<br />

2017).<br />

[11] Ledford, H. Biohackers gear up for genome editing.<br />

http://www.nature.com/news<br />

/biohackers-gear-up-for-genome-editing-1.18236 (accessed<br />

Oct. 20, 2017).<br />

[12] Ossola, A. Biohackers are Now Using CRISPR. Popular<br />

Science [Online], Aug. 26, 2015. https://www.popsci.com/<br />

biohackers-are-now-using-crispr (accessed Oct. 20, 2017).<br />

Design By Kaitlyn Xiong<br />

Edited by Jason Lee<br />


written in the (dead) stars:<br />

the black hole<br />

information paradox<br />

by Jenny L Wang<br />

From Nolan’s Interstellar to Muse’s<br />

2006 hit single, black holes serve<br />

as some of the most widely fantasized<br />

plot devices and symbols in popular<br />

culture. Perhaps our fixation with black<br />

holes stems from our lack of scientific<br />

understanding about them. After<br />

all, black holes pose one of the most<br />

contentious dilemmas facing modern<br />

physicists: the black hole information<br />

paradox. Arising from a contradiction<br />

between several fundamental physical<br />

principles, this paradox continues to<br />

challenge not only astrophysicists, but<br />

also our tenuous assumptions and<br />

ideas about how the universe really<br />

works.<br />

Let’s begin by examining black<br />

holes identifying several of their<br />

properties. In simple terms, a black<br />

hole is an enormous amount of<br />

matter concentrated within a relatively<br />

small volume. Most black holes are<br />

classified as “stellar” and form when<br />

a massive star dies and collapses<br />

upon itself, resulting in a supernova<br />

that ejects most of the star’s mass yet<br />

mysteriously retains a black hole in the<br />

center. 1 In addition to stellar, mini and<br />

supermassive black holes also exist.<br />

While their origins are more ambiguous,<br />

scientists hypothesize that their<br />

formation is tied to the very beginning<br />

of the universe. 1<br />

Black holes pose one<br />

of the most contentious<br />

dilemmas facing modern<br />

physicists: the black hole<br />

information paradox.<br />

Although NASA estimates that as many<br />

as ten million to one billion stellar black<br />

holes populate the Milky Way alone,1<br />

the vast majority remain difficult to<br />

observe with current technology due in<br />

part to a black hole’s incredibly strong<br />

gravitational field. As predicted by<br />

general relativity, the center of a black<br />

hole collapses into a “gravitational<br />

singularity” around which space-time<br />

curves. This forms a sort of sphere<br />

around a black hole with an outer<br />

boundary known as the black hole’s<br />

event horizon. 2 The event horizon of<br />

a black hole represents the “point of<br />

no return” beyond which nothing, not<br />

even light, can escape. 2 Past the event<br />

horizon, the black hole’s gravity is so<br />

strong that it renders direct observation<br />

of a black hole using telescopes and<br />

other electromagnetic radiationmeasurement<br />

devices useless. Instead,<br />

scientists must infer the position and<br />

behavior of black holes by observing the<br />

ways a black hole impacts surrounding<br />

stars and gases. 1<br />

Another interesting phenomenon<br />

that results from a black hole’s<br />

incredible gravity is time dilation. To<br />

an observer outside the event horizon,<br />

time seems to slow down relative to<br />

time experienced by an object falling<br />

towards the black hole. The Stanford<br />

Encyclopedia of Philosophy illustrates<br />

time dilation with the example of<br />

watching someone who, “while falling<br />

[into a black hole]...flashes a light<br />

signal to us every time her watch hand<br />


ticks.” 2 While the falling person would<br />

not feel as if time slows down as she<br />

approaches the event horizon, to us<br />

(outside observers), the time interval<br />

between each successive light would<br />

appear to increase. When the falling<br />

person finally crosses the event horizon,<br />

light no longer reaches our eyes and<br />

the person would suddenly appear to<br />

freeze, seemingly stuck on the black<br />

hole’s surface. 2<br />

The black hole information<br />

paradox arises from a<br />

contradiction between<br />

two foundational physical<br />

theories: quantum<br />

mechanics and general<br />

relativity.<br />

Prior to the 1970s, black hole theory<br />

assumed that when something was<br />

pulled into a black hole, all of the<br />

object’s features (every particle, the<br />

quality of every particle, and the<br />

probability of future behavior of<br />

every particle) became inaccessible to<br />

anything outside the event horizon. 3<br />

According to quantum mechanics,<br />

information must be preserved in<br />

a similar fashion as energy. Thus,<br />

scientists hypothesized that as objects<br />

fall into a black hole, their quantum<br />

information is simply stored away<br />

somewhere inside, unreachable yet still<br />

preserved.<br />

However, in 1975, Stephen Hawking<br />

observed that black holes evaporate<br />

over time through a process called<br />

Hawking radiation. 3 Hawking proposed<br />

that the universe is filled with “virtual<br />

particles”: particle-antiparticle pairs<br />

which constantly pop in and out of<br />

existence, appearing and rapidly<br />

cancelling one another out. 4 However,<br />

near the event horizon of a black hole,<br />

instead of being annihilated by its<br />

particle or antiparticle counterpart,<br />

one virtual particle could fall into the<br />

black hole while the other, along with<br />

a miniscule fraction of the black hole’s<br />

mass, escapes as thermal energy known<br />

as Hawking radiation.<br />

The discovery of Hawking radiation<br />

introduced one of the most urgent<br />

and contentious issues that continues<br />

to puzzle theoretical physicists today:<br />

the black hole information paradox.<br />

In simplified terms, the black hole<br />

information paradox arises from a<br />

contradiction between two foundational<br />

physical theories: quantum mechanics<br />

and general relativity, proposed by<br />

Einstein in 1915. 6 As Clara Moskowitz<br />

summarized on behalf of Scientific<br />

American in 2015, black holes “invoke<br />

two different theories of nature—<br />

quantum mechanics, which governs the<br />

subatomic world, and general relativity,<br />

which describes gravity and reigns on<br />

large cosmic scales.” 7 While quantum<br />

mechanics asserts that information<br />

cannot be created or destroyed, classical<br />

general relativity states that information<br />

cannot escape a black hole. If Hawking<br />

radiation follows principles of general<br />

relativity, then black holes do not<br />

emit information while evaporating.<br />

However, this implies that after a black<br />

hole dissipates completely into random<br />

radiation, the information of everything<br />

that it swallowed vanishes as well: a<br />

contradiction of quantum mechanics. 8<br />

At best, this incongruity causes a<br />

headache for a few star-crossed<br />

astrophysicists. At worst, the paradox<br />

compromises decades of progress<br />

in quantum mechanics and general<br />

relativity.<br />

Since the discovery of Hawking<br />

radiation, scientists continue to debate<br />

and propose solutions to the black<br />

hole information paradox. Theoretical<br />

physicist Sabine Hossenfelder sorts<br />

tentative solutions into four general<br />

categories: 9<br />

1 1<br />

1 2<br />

1 3<br />

1 4<br />

Information is somehow encoded<br />

in Hawking radiation and escapes<br />

as the black hole dissolves. This<br />

statement contradicts Hawking’s<br />

original conclusions about the<br />

radiation being random and<br />

introduces yet another paradox<br />

called the “firewall” paradox.<br />

Information is stored in or on<br />

the surface of a black hole. The<br />

formation of baby universes,<br />

the holographic principle, and<br />

Hawking’s most recent “soft<br />

hair” explanation fall into this<br />

category.<br />

Information actually is destroyed,<br />

and quantum mechanics requires<br />

serious modification.<br />

There is no black hole, and<br />

information never crosses its<br />

boundary. General relativity,<br />

which predicts the existence<br />

and behavior of the black hole,<br />

requires serious modification.<br />


Of course, many other proposed<br />

solutions fall outside of these mentioned<br />

categories. Each come with their own<br />

associated strengths and shortcomings,<br />

but all challenge previously-held<br />

assumptions about the field and<br />

contribute to a growing body of literature<br />

about the black hole information paradox.<br />

However, in spite of this progress, it will<br />

likely take many more years to observe<br />

what actually happens to information in a<br />

black hole, since current technology limits<br />

our ability to measure Hawking radiation<br />

and quantitatively observe the behavior<br />

of black holes. 8<br />

Instead of viewing the<br />

paradox as a conflict<br />

between quantum mechanics<br />

and general relativity, many<br />

regard it as an opportunity<br />

to reconcile the two<br />

foundational theories.<br />

Despite these challenges, the implications<br />

of the black hole information paradox<br />

remain profound. Instead of viewing the<br />

paradox as a conflict between quantum<br />

mechanics and general relativity,<br />

many regard it as an opportunity to<br />

reconcile the two foundational theories.<br />

As Moskowitz writes, the black hole<br />

information paradox urges a deeper<br />

need to “describe gravity according to<br />

quantum rules” and perhaps suggests the<br />

existence of another theory which unites<br />

the other two. Most scientists agree that<br />

discovering such a unifying theory of<br />

quantum gravity could marry quantum<br />

mechanics and general relativity, offering<br />

a satisfying resolution to the information<br />

paradox and inspiring a “conceptually<br />

new understanding of nature.” 3<br />

In the meantime, by improving scientific<br />

instruments, conducting research, and<br />

reexamining our underlying assumptions<br />

about the physical world, we can refine<br />

our existing theories about the black<br />

hole information paradox and develop<br />

new ones. Although the final answer<br />

remains ambiguous, we advance with<br />

tireless inquiry and curiosity about the<br />

mystique of space. In the process, our<br />

understanding—like our universe—<br />

inevitably continues to grow.<br />


[1] Nagaraja, M. Black Holes. [Online] n.d. NASA. https://<br />

science.nasa.gov/astrophysics<br />

/focus-areas/black-holes (accessed Oct. 8, 2017).<br />

[2] Curiel, E.; Bokulich, P. Singularities and Black<br />

Holes. [Online] 2012, Fall 2012 Edition, n.p. Stanford<br />

Encyclopedia of Philosophy. https://plato.stanford.<br />

edu/entries/spacetime-singularities/ (accessed Oct. 28,<br />

2017).<br />

[3] Hossenfelder, S. Forbes. [Online] 2017. https://www.<br />

forbes.com/sites/startswithabang<br />

/2017/01/24/nobody-knows-where-a-black-holesinformation-goes/#7f04ed73767a<br />

(accessed Nov. 11,<br />

2017).<br />

[4] Baez, J.; Schmelzer, I. UCR Mathematics. [Online]<br />

1997. http://math.ucr.edu/home<br />

/baez/physics/Relativity/BlackHoles/hawking.html<br />

(accessed Oct. 28, 2017).<br />

[5] Cain, F. Universe Today. [Online] 2015. https://www.<br />

universetoday.com/119794/howdo-black-holes-evaporate/<br />

(accessed Oct. 29, 2017).<br />

[6] Toth, V. Forbes. [Online] 2017. https://www.forbes.<br />

com/sites/quora/2017/04/13/whydo-general-relativity-and-quantum-mechanics-need-tobe-unified/#3d650734aa2c<br />

(accessed Nov. 8, 2017).<br />

[7] Moskowitz, C. Scientific American. [Online] 2015.<br />

https://www.scientificamerican.<br />

com/article/stephen-hawking-hasn-t-solved-the-blackhole-paradox-just-yet/<br />

(accessed Nov. 8, 2017).<br />

[8] Strassler, M. Of Particular Significance. [Online] 2014.<br />

https://profmattstrassler.com/<br />

articles-and-posts/relativity-space-astronomy-andcosmology/black-holes/black-hole-information-paradoxan-introduction/<br />

(accessed Nov. 12, 2017).<br />

DESIGN BY Katrina Cherk<br />

EDITED BY Kelsey Sanders<br />


ergosphere<br />

event<br />

horizon<br />

quiet region:<br />

negligible<br />

gravitational<br />

influence<br />

gravitational<br />

spacetime<br />

distortion<br />

singularity<br />



by Meredith Brown<br />

I<br />

f global warming increases the temperature<br />

of the Earth by more than two degrees<br />

Celsius, there will be catastrophic<br />

consequences - major flooding will wipe out<br />

homes, businesses, and ecosystems. 1 Sulfur<br />

dioxide may hold the answer to combating the<br />

threat of global warming. Although aerosols<br />

and sulfur dioxide are detrimental to the<br />

ozone layer and human health, studies have<br />

shown that sulfur dioxide increases both plant<br />

growth and the overall reflectivity of solar<br />

radiation of the Earth’s atmosphere, known as<br />

the Earth’s albedo. 2 Scientists hypothesize that<br />

by injecting sulfur dioxide into the atmosphere,<br />

we could combat the gradual temperature<br />

increase without harming human and plant<br />

life.<br />

The negative consequences of aerosols<br />

and sulfur dioxide are well documented.<br />

Both are banned in large quantities by the<br />

MARPOL regulations and by the National<br />

Ambient Air Quality Standards enforced by<br />

the Environmental Protection Agency.3 The<br />

most harmful aerosols found in hairspray<br />

cans and other products were made illegal in<br />

the United States in the 1970s. 2 Additionally,<br />

atmospheric sulfur dioxide precipitates as<br />

acid rain, negatively affecting plants and<br />

ecosystems. Furthermore, sulfur emissions<br />

are responsible for a large percentage of<br />

particulate matter, a class of air pollutants that<br />

is responsible for approximately two million<br />

deaths per year globally due to respiratory<br />

problems. 4 Sulfur dioxide and aerosols also<br />

play key roles in the destruction of the ozone<br />

layer, the main component of the atmosphere<br />

that protects humans from harmful UV rays. 3<br />

In order to utilize sulfur dioxide to counteract<br />

greenhouse gases, these negative impacts<br />

must be mitigated.<br />

Despite these numerous risks, aerosols<br />

and sulfur dioxide have potential that<br />

encourage scientists to look beyond their<br />

negative qualities. Although sulfur dioxide is<br />

a particulate matter pollutant, it also acts as a<br />

cloud catalyst in certain layers of<br />

the atmosphere.<br />

In this<br />

insane or insanely genius?<br />

phenomenon, water vapor in the air is able<br />

to cling to sulfur dioxide molecules more<br />

easily than to salt crystals or to other water<br />

molecules, resulting in a larger and brighter<br />

cloud cover. This is desirable because larger<br />

and brighter clouds reflect more solar<br />

radiation than smaller and dimmer clouds that<br />

lack sulfur. More solar radiation is reflected<br />

back into space, and thus, less solar energy is<br />

Water vapor in the air is able to<br />

cling to sulfur dioxide molecules<br />

more easily, causing clouds to be<br />

larger, more frequent, and brighter.<br />

available for greenhouse gases to trap near<br />

the Earth’s surface. Also, sulfur dioxide plays a<br />

critical role in plant growth. When a solar ray<br />

cuts through Earth’s atmosphere, it generally<br />

travels in a straight line. But if the ray hits the<br />

large sulfur dioxide particles, the light scatters.<br />

This scattered light is able to reach more plants<br />

on the ground, allowing plants to grow larger.<br />

Larger plants are desirable because the leaves<br />

have a greater surface area and are thus able<br />

to absorb more carbon dioxide, removing this<br />

potent greenhouse gas from the atmosphere.<br />

Dr. David Keith, a professor of physics and<br />

public policy at Harvard University, has<br />

outlined one cheap method of using sulfur<br />

dioxide to combat global temperature<br />

increases: high altitude injection. 3 He proposes<br />

that specialized planes could fly annually and<br />

inject one million tons of sulfur dioxide to<br />

create a thin atmospheric layer intended to<br />

reflect one percent of solar rays. These planes<br />

would fly 20 kilometers high, beyond the cloud<br />

formation point, to avoid contributing to acid<br />

rain, while still reflecting solar radiation before<br />

it ever hits Earth’s surface. Therefore, this<br />

solar radiation is unable to become trapped<br />

by greenhouse gases, thereby slowing Earth’s<br />

temperature increase. In fact, this concept was<br />

underscored by a mega-volcanic eruption in<br />

1991, where a major increase in sulfur caused<br />

a decrease in global temperature by half a<br />

degree Celsius for two years. 5<br />

However, this solution still has some<br />

flaws. Scientists fear disruptions in<br />

precipitation patterns,<br />

reductions in<br />

atmospheric ozone, and obstacles in logistics<br />

regarding “who will inject the sulfur, where<br />

will they inject the sulfur, and who will pay<br />

for this?” Furthermore, the molecular size<br />

of sulfur dioxide causes the particle to<br />

have a short atmospheric life, so gas would<br />

have to be continuously pumped into the<br />

atmosphere, costing billions of dollars and<br />

acting as a mere band-aid for our emissions<br />

problems. 6 Scientists argue against this<br />

tactic by suggesting that if the world were to<br />

develop low-emissions energy systems and<br />

transportation methods, such steps would fix<br />

the greenhouse gas problem in a cheaper and<br />

more sustainable manner in the long-run. Al<br />

Gore denounced this geo-engineering plan,<br />

calling it “insane, utterly mad and delusional in<br />

the extreme.” 7<br />

While high altitude sulfur dioxide injections<br />

are possible with current technology, there<br />

is not enough information to determine the<br />

full scope of the environmental impact. Many<br />

scientists have simply suggested decreasing<br />

emissions to combat the source of the<br />

problem instead of putting on the “bandaid”<br />

of high-altitude sulfur dioxide injection.<br />

However, most scientists can agree that<br />

something must be done to mitigate our air<br />

pollution problem, but global warming is a<br />

challenge that we must tackle immediately.<br />


[1] Aton, ClimateWire Adam. “Earth Almost Certain to Warm<br />

by 2 Degrees Celsius.” Scientific American, 1 Aug. 2017, www.<br />

scientificamerican.com/article/earth-almost-certain-to-warmby-2-degrees-celsius/.<br />

[2] “Sulfur Dioxide: Its Role in Climate Change.” Institute for<br />

Global Environmental Strategies >> Sulfur Dioxide: Its Role<br />

in Climate Change, esseacourses.strategies.org/module.<br />

php?module_id=168.<br />

[3] “Setting and Reviewing Standards to Control SO2<br />

Pollution.” EPA, Environmental Protection Agency, 13 Oct.<br />

2017, www.epa.gov/so2-pollution/setting-and-reviewingstandards-control-so2-pollution#standards.<br />

[4] Physics, Institute of. Researchers Estimate over Two Million<br />

Deaths Annually from Air Pollution, www.iop.org/news/13/jul/<br />

page_60518.html.<br />

[5] Rotman, D. A Cheap and Easy Plan to Stop Global Warming<br />

. MIT Technology Review. https://www.technologyreview.<br />

com/s/511016/a-cheap-and-easy-plan-to-stop-global-warming/<br />

(accessed Nov 7, 2017).<br />

[6] Stephen et al. Self, pubs.usgs.gov/pinatubo/self/.<br />

[7] Hansman, Heather. “Is This Plan to Combat Climate<br />

Change Insane or Insanely Genius?”Smithsonian.com,<br />

Smithsonian Institution, 14 May 2015, www.smithsonianmag.<br />

com/innovation/is-this-plan-combat-climate-change-insaneinsanely-genius-180955258/.<br />

DESIGN BY Katrina Cherk<br />

EDITED BY Anna Croyle<br />

+<br />



Shining Light on Heart Disease<br />

Swathi Rayasam<br />

F<br />

lashing lights. Chest compressions.<br />

A cry of “clear!” We commonly<br />

associate heart attacks with this<br />

frantic mental picture. However, a heart<br />

attack will only develop into fatal heart<br />

rhythms through a cascade of cardiac<br />

events. Before we explore the evolution of<br />

a basic heart attack into cardiac death, we<br />

need a broad overview of heart disease.<br />

The leading cause of death worldwide,<br />

cardiovascular disease is costly – both in<br />

terms of money and in terms of years of<br />

life. 1 Although several recent advances<br />

have explored repair and regeneration<br />

after significant cardiac trauma, 2-3<br />

tackling cardiac injury closer to its onset<br />

would minimize serious damage due to<br />

treatment delay.<br />

A heart attack is characterized by an<br />

obstruction that prevents proper blood<br />

Scientists at Stanford<br />

University have explored<br />

the possibility of<br />

introducing other<br />

photosynthetic agents<br />

into the body to provide a<br />

source of oxygen for<br />

cardiac cells.<br />

flow to the heart. 4 While this is certainly<br />

serious on its own, the cascade of<br />

events that are triggered more largely<br />

contributes to patient death. First, the<br />

blockage of circulation can cause a lack of<br />

oxygen in the heart, known as ischemia. 5<br />

This condition can lead to cardiac cell<br />

death if present for an extended period<br />

of time, as in the case of delayed CPR and<br />

transport to the hospital. If the human<br />

body had an alternate route to bypass the<br />

roadblock and deliver oxygen to the heart,<br />

then there would likely be less heart<br />

tissue injury and improved survival.<br />

The fact that trees generate oxygen<br />

may imply that introducing plant cells<br />

internally might prevent and resolve<br />

ischemia. Photosynthetic processes in<br />

such a situation would merely rely on a<br />

light source and chemical compounds<br />

abundant in the human body to engineer<br />

oxygen production in ischemic areas. 6<br />

This new oxygen source would also<br />

lessen the immediate need for proper<br />

blood flow. However, while maintaining<br />

internal plant cells is not exactly feasible,<br />

scientists at Stanford University have<br />

explored the possibility of introducing<br />

other photosynthetic agents into the body<br />

to provide a source of oxygen for cardiac<br />

cells.<br />

Stanford cardiovascular surgeon Dr.<br />

Joseph Woo recently began a research<br />

study to bring this fantasy to fruition.<br />

He initially limited his efforts to plants,<br />

by grinding kale and spinach to obtain<br />

chloroplasts, plant organelles that<br />

perform photosynthesis. 6 When these<br />

structures did not survive outside of the<br />

plant cell itself, Dr. Woo and his colleagues<br />

found an alternate option. They identified<br />

Synechococcus elongatus, originally<br />

used to study circadian rhythms, 7-8 as<br />

a viable photosynthetic cyanobacteria<br />

for introduction into the body. The<br />

team considered S. elongatus an ideal<br />

candidate because they could easily<br />

engineer it to produce more metabolites,<br />

such as oxygen or glucose. 9-10<br />

To test whether this cyanobacterium<br />

could immediately deliver oxygen to a<br />

tissue, the researchers induced ischemia<br />

in several rodents. They then randomly<br />

grouped these rodents and injected<br />

their hearts with S. elongatus in the<br />

light, S. elongatus in the dark, or saline.<br />

The researchers prevented any light<br />

exposure in the dark group but exposed<br />

the other two groups directly to light to<br />

examine any differences in oxygenation<br />

levels due to photosynthesis. Originally,<br />

baseline oxygen levels were comparable<br />

between the groups and dropped close<br />

to zero when ischemia was induced. At<br />

reassessment 10 and 20 minutes after<br />

injection, S. elongatus caused a 25-fold<br />

increase in oxygen from the onset of<br />

ischemia in the light group. This was<br />

astounding when compared to the merely<br />

3-fold increase in oxygen levels in the<br />

other two treatment groups. This finding<br />

supports the idea that injection with<br />

S. elongatus in light leads to enhanced<br />

oxygenation in ischemic conditions,<br />

suggesting improved metabolism and<br />

cardiac function. 11<br />

Dr. Woo and his team next aimed to<br />

evaluate the metabolic state of the<br />

heart in the living rodent body, using<br />

temperature as an indicator of activity.<br />

Using a form of videography, they found<br />


Cardiac ischemia<br />

was induced in<br />

rodents<br />

Rodents were<br />

injected with<br />

photosynthetic<br />

cyanobacteria<br />

After exposure to<br />

light, rodents had<br />

higher oxygen<br />

levels and increased<br />

heart activity<br />

no difference in left ventricular surface<br />

temperature between the groups at<br />

baseline and at 10 minutes. However,<br />

at 20 minutes, the S. elongatus-treated<br />

group exhibited improved preservation of<br />

surface temperature in the area lacking<br />

oxygen. Furthermore, the saline-treated<br />

group demonstrated a decrease in<br />

surface temperature in this area over<br />

time, while the S. elongatus-treated group<br />

had an increase in surface temperature<br />

over time. This finding indicates that S.<br />

elongatus enhances metabolic activity in<br />

ischemic areas, unlike in the unassisted<br />

The study’s findings<br />

present S. elongatus as an<br />

ideal agent for mitigating<br />

cardiac injury in patients<br />

experiencing ischemia.<br />

heart. Furthermore, cardiac output – the<br />

amount of blood that the heart pumps<br />

in a minute – had a greater increase<br />

from time of ischemia in the light group<br />

than the dark or the saline group. This<br />

provides further support that only<br />

actively photosynthesizing S. elongatus<br />

bacteria offer these benefits. The team<br />

conducted further testing to explore<br />

long-term effects of S. elongatus injection.<br />

Magnetic resonance imaging (MRI) of<br />

the heart four weeks after therapy in<br />

the light group demonstrated enhanced<br />

cardiac performance associated with<br />

photosynthetic therapy. 11<br />

The study’s findings present S. elongatus<br />

as an ideal agent for mitigating<br />

cardiac injury in patients experiencing<br />

ischemia. However, other effects of the<br />

cyanobacterial species on the human<br />

body should also be considered; it would<br />

not be sensible to assume only health<br />

benefits by introducing an unknown<br />

agent. Dr. Woo and his team conducted<br />

tests with the rodent models and found<br />

no sign of infection, unintended bacterial<br />

growth, or immune response in the<br />

organisms after introduction of S. elongatus.<br />

By the 24-hour point after injection, only a few<br />

injected bacterial cells remained. Four weeks<br />

after therapy, the team euthanized the rodents<br />

to examine their hearts and found no abscess<br />

formation or residual S. elongatus. Overall,<br />

these findings suggest that S. elongatus is nontoxic<br />

when injected. 11<br />

Though the findings are promising,<br />

researchers have yet to conduct human trials,<br />

and the bacteria could potentially exhibit<br />

a different effect in the human body. Such<br />

differences may be due to varying physiology,<br />

such as the thicker cardiac muscle of humans<br />

in comparison to rats. 12 Other obstacles could<br />

also block widespread use of the therapy,<br />

due to issues with availability in the absence<br />

of a medical professional. In this case, a few<br />

factors to consider are the safety of personal<br />

access to S. elongatus injections, the feasibility<br />

of injection maintenance and self-use in the<br />

home, and the criteria to qualify for injection<br />

access. Nonetheless, current research<br />

indicates S. elongatus therapy has immense<br />

potential. The cyanobacteria could even be<br />

useful in ischemic tissues outside of the heart<br />

and in procedures such as cardiopulmonary<br />

bypass surgery. Overall, this therapy aims<br />

to tackle the root of sudden cardiac death;<br />

while S. elongatus may not be a plant, it could<br />

blossom into a solution all the same.<br />


[1] Heart Disease. Centers for Disease Control and Prevention,<br />

Centers for Disease Control and Prevention, Aug. 24, 2017.<br />

www.cdc.gov/heartdisease/facts.htm (accessed Oct. 15, 2017).<br />

[2] Tian, Y. et al. Science Translational Medicine 2015, 7 (279).<br />

[3] Polizzotti, B. D. et al. Science Translational Medicine 2015,<br />

7 (281).<br />

[4] What Is a Heart Attack? National Heart Lung and Blood<br />

Institute, U.S. Department of Health and Human Services,<br />

Jan. 27, 2015. www.nhlbi.nih.gov/health/health-topics/topics/<br />

heartattack (accessed Oct. 15, 2017).<br />

[5] Silent Ischemia and Ischemic Heart Disease. www.heart.<br />

org/HEARTORG/Conditions/HeartAttack/Treatmentofa-<br />

HeartAttack/Silent-Ischemia-and-Ischemic-Heart-Disease_<br />

UCM_434092_Article.jsp#.Wfy8GrpFyuU (accessed Oct. 18,<br />

2017).<br />

[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/<br />

(accessed Oct. 19, 2017).<br />

[7] Espinosa, J. et al. Proceedings of the National Academy of<br />

Sciences 2015, 112 (7), 2198–2203.<br />

[8] Kondo, T. et al. Science 1997, 275 (5297), 224–227.<br />

[9] Shih, P. M. et. al. J. Biol. Chem. 2014, 289 (14), 9493–9500.<br />

[10] Niederholtmeyer, H. et al. Appl. Environ. Microbiol. 2010,<br />

76 (11), 3462–3466.<br />

[11] Cohen, J. E. et al. Science Advances 2017, 3 (6).<br />

[12] Price, M. Light-activated bacteria protect rats from<br />

heart attacks. Science, June 14, 2017. http://www.sciencemag.org/news/2017/06/light-activated-bacteria-protect-rats-heart-attacks<br />

(accessed Oct. 19, 2017).<br />

Image from freepik.com.<br />

DESIGN BY Sara Ho<br />

EDITED BY Brianna Garcia<br />


who’s saving lives?<br />

R B TS<br />

by jenny s wang<br />

R<br />

obot-assistance has been on the<br />

rise in the medical field in recent<br />

years and its applications in surgical<br />

procedures are showing significant<br />

advantages compared to the standard<br />

of practice. In particular, this technology<br />

has been integrated with retroperitoneal<br />

oncological surgery because it overcomes<br />

some of the shortcomings of traditional<br />

surgery practices, which can be imprecise,<br />

more painful, and lead to slower recovery<br />

time, in order to potentially improve<br />

postoperative outcomes.<br />

The retroperitoneal space, or<br />

retroperitoneum, is the anatomical<br />

space in the abdominal cavity behind the<br />

peritoneum, which is the tissue that lines<br />

the abdominal wall. In other words, the<br />

space contains the organs related to the<br />

urinary system that urological surgeons<br />

operate on. These organs include the<br />

kidneys, ureters, and adrenal glands. 1 Due<br />

to the limitations of operative space in the<br />

retroperitoneum, traditional procedures<br />

usually required a substantial incision, a<br />

disruption of soft internal organs, and a<br />

lengthy recovery period. 2 Due to this, renal<br />

surgeons have since adopted a minimally<br />

invasive technique known as laparoscopic<br />

technology, which overcomes the space<br />

limitations that hindered early surgeons. 2<br />

The technology has evolved quickly and<br />

has proven more beneficial for patients<br />

than previous approaches.<br />

The introduction of robot-assisted<br />

surgery was one such turning point in<br />

laparoscopic technology. Progress in the<br />

field of robotics has allowed for evolution<br />

from the first ‘master-slave’ robotic<br />

systems, which allowed surgeon control<br />

of the robot from afar but had limited<br />

functionality, to systems capable of more<br />

precision and complex procedures. In<br />

2000, the first robot-assisted laparoscopic<br />

surgery was performed and the practice<br />

has become increasingly popular over<br />

the past two decades in renal surgery. 1<br />

Today, robot assistance is favored over<br />

pure laparoscopy due to technical ease<br />

and comfort for the surgeon because<br />

it provides clearer 3D visualization and<br />

magnified imaging compared to the<br />

human eye. 1 Additional advantages<br />

12 | CATALYST<br />

include a greater range of motion and a<br />

shorter training time compared to pure<br />

laparoscopy, allowing for greater precision<br />

and ease of use. 1<br />

Robot-assisted approaches have been<br />

developed for multiple surgical procedures<br />

involved in removal of a tumor mass in<br />

the retroperitoneal space. For example,<br />

in stage 1 of kidney cancer when the<br />

tumor mass is small, the procedures<br />

intend to remove the tumor with the<br />

goal of preserving the rest of the kidney<br />

and surrounding tissue 1 . This technique,<br />

a partial nephrectomy, is the standard<br />

approach in removal of small renal<br />

tumors. It has similar survival outcomes<br />

as produced by radical nephrectomy, in<br />

which the entire kidney associated with<br />

the tumor is removed during surgery.<br />






However, renal functionality is generally<br />

improved for patients undergoing partial<br />

nephrectomy as compared to those<br />

undergoing radical nephrectomy. The<br />

introduction of robot-assisted partial<br />

nephrectomy (RAPN), which has allowed<br />

for a shorter operative time, faster return<br />

to normal function, and less invasion, has<br />

increased in popularity as even larger,<br />

more complex renal tumors have been<br />

successfully treated. 1 Moreover, the 5-year<br />

survival rates of patients who underwent<br />

the procedure have been outstanding and<br />

have thus made this approach a standardof-care<br />

therapy. 1<br />

For later stages that involve larger and<br />

more complex tumors, other procedures<br />

utilizing robot assistance have also<br />

been compared to typical approaches.<br />

A prospective comparison between the<br />

laparoscopic form and the robot-assisted<br />

form of radical nephrectomy, a procedure<br />

typically used for stage 2 kidney cancer<br />

tumors. The study demonstrated that the<br />

operative time and survival outcomes<br />

are similar. However, the robot-assisted<br />

procedure is more expensive. 1 For<br />

treatment of especially invasive tumors<br />

that have not yet spread from the upper<br />

urinary tract, radical nephroureterectomy<br />

(RNU) is favored. The benefits of robotassisted<br />

RNU are decreased operative time<br />

and postoperative complications, but the<br />

disadvantage is that the cost is greater<br />

than laparoscopic nephroureterectomy<br />

operations alone. Overall, survival<br />

outcomes are similar in both open and<br />

robot-assisted approaches in RNU, but<br />

advancement of the robot-assisted<br />

technique over time will prove if there are<br />

additional benefits and risks.<br />

The comparisons of robot-assisted<br />

and standard laparoscopic approaches<br />

demonstrate that the robot-assisted<br />

approach has proven useful in reducing<br />

operation time, discomfort to the patient,<br />

and post-surgery complications. Though<br />

this technology is still facing barriers<br />

of high cost and associated risks, the<br />

continual advancement and improvements<br />

for the surgeon and patients have<br />

demonstrated that we should be optimistic<br />

about what lies in the future for the<br />

growing application of robot-assisted<br />

oncological surgery in the retroperitoneal<br />

space as well as other sites.<br />


[1] Ludwig, W. W. et al. Frontiers in robot-assisted<br />

retroperitoneal oncological surgery. Nature Reviews<br />

Urology [Online]. September 12, 2017, p 1-11. https://<br />

www.nature.com/articles/nrurol.2017.149<br />

[2] Velanovich, V. et al. Laparoscopic vs open surgery:<br />

a preliminary comparison of quality-of-life outcomes.<br />

National Center for Biotechnology Information [Online],<br />

January 14, 2000, p 16-21. https://www.ncbi.nlm.nih.gov/<br />

pubmed/10653229<br />

DEsign bY Nancy Cui<br />

edited by Kelsey Sanders

F<br />

Mirror Neurons: Unlocking the Mind<br />


ilm, music, and literature capitalize on<br />

conveying emotion to an audience. These<br />

forms of art crate emotions by crafting<br />

narratives that their audiences connect with<br />

and believe in. Most people would place the<br />

agency of this emotional transaction on the<br />

movie, song, or book. However, the audience<br />

must also be receptive to the story. In other<br />

words, the audience must have the capacity<br />

to empathize with the emotions portrayed by<br />

the art. This fascinating ability for audience<br />

members to ‘feel’ an external stimulus as<br />

if they were experiencing it themselves is<br />

mediated by a newly discovered type of<br />

neuron, the mirror neuron.<br />

Mirror neurons were first discovered in<br />

the 1980s in macaque monkeys when<br />

neurophysiologists at the University of<br />

Parma, Italy, studied neurons specialized for<br />

hand and mouth control. 1 They discovered<br />

that certain neurons in the monkeys’<br />

premotor cortices lit up in the same pattern<br />

both when monkeys picked up food for<br />

themselves and when they merely observed<br />

other monkeys pick up food. This fascinating<br />

discovery led to a new area of study that<br />

focuses on the brain’s ability to adapt and<br />

respond to its environment. Using functional<br />

neuroimaging, which attempts to associate<br />

cortices of the brain to certain functions,<br />

other scientists have discovered similar<br />

mirror neurons in the human<br />

somatosensory cortex<br />

that allow people to<br />

vicariously experience<br />

emotions when<br />

others perform or<br />

experience different<br />

actions. 4<br />

“Mirror neurons<br />

constantly dictate our<br />

social responses, even<br />

without our knowledge.”<br />

Mirror neurons<br />

constantly dictate<br />

our social responses,<br />

even without our<br />

knowledge. For instance,<br />

many moviegoers cry at<br />

the heartbreaking ending of<br />

the movie ‘Titanic’, which exhibits the power<br />

of mirror neurons to create a false sense of<br />

personal reality. A more concrete example<br />

of the power of mirror neurons is when Rose<br />

attempts to free Jack from a pair of handcuffs<br />

with an axe. The audience cringes as Rose<br />

swings the axe at Jack’s hand, as if their own<br />

hands are in danger.<br />

These examples fall in line with a classic<br />

experiment performed in the study of mirror<br />

neurons. 2 During the study, participants hid<br />

their hands behind a divide, then watched<br />

as a fake, rubber hand was simultaneously<br />

stroked along with their own, real hands.<br />

Halfway through the experiment, without<br />

warning, the rubber hand is smashed<br />

with a hammer. Nearly all participants<br />

recoiled in surprise and fear because they<br />

established “a feeling of ownership of [a]<br />

fake [rubber] hand”. 2 Functional magnetic<br />

resonance imaging (fMRI) scanned<br />

each participant’s brain activity and<br />

revealed “evidence that cells in<br />

the premotor cortex respond<br />

both when a specific area of<br />

the body is touched and when<br />

an object is seen approaching<br />

that area”. 3<br />

It is easy to see the benefits<br />

that mirror neurons<br />

provide. New models of<br />

human perception are<br />

currently forming around<br />

the concept of mirror neurons,<br />

which may have broad implications in<br />

the field of psychology and the study of<br />

the human mind. This in turn may lead<br />

to the development of novel methods of<br />

interpersonal interaction, which has a heavy<br />

hand in the business and marketing world.<br />

Though the world currently knows little<br />

about these fascinating neurons and their<br />

mechanism of action, their far-reaching<br />

significance may have much to contribute to<br />

future human development and innovation.<br />

The mirror neuron is a relatively new<br />

finding and requires much more testing and<br />

experimentation before it can be labeled as<br />

an official hallmark of human physiology.<br />

However, even with limited information, it<br />

is abundantly clear that the neuron sparks<br />

a rich debate regarding the world’s current<br />

understanding of psychological study and<br />

evaluation. Through further study, we may<br />

be able to better understand the social<br />

component of human nature. Perhaps<br />

mirror neurons can even answer the age-old<br />

question of why people love the humanities:<br />

people enjoy being spectators.<br />

Works Cited<br />

[1] Winerman, L. American Psychological Association. 2005,<br />

36, 48.<br />

[2] Ehrsson, H. H. et al. J. Neurophysiol. 2000, 83, 528–536.<br />

[3] Acharya, S. et al. J Nat Sci Biol Med. 2012, 3, 118-124.<br />

[4] Kilner, J. M. et al. Curr Biol. 2013, 23, 1057-1062.<br />

Design by: Anna Croyle<br />

Edited by: Meredith Brown<br />




S<br />

by Maishara Muquith<br />

ilent. Deadly. With an estimated 6 to<br />

7 million people affected worldwide,<br />

Chagas disease is a neglected tropical<br />

disease found mainly in Latin American<br />

countries¹. Classified as a disease of<br />

poverty, Chagas perpetuates inequality by<br />

creating a disease burden in the poorest<br />

economies². The total annual cost to<br />

society stemming from healthcare and<br />

lost productivity due to the disease is<br />

$4,059 annually in Latin America for each<br />

individual afflicted². Since Chagas causes<br />

such a massive economic burden, more<br />

attention needs to be paid to this lifethreatening<br />

disease.<br />

Chagas disease is transmitted by the blood<br />

sucking triatomine bug, also known as the<br />

kissing bug due to bites near the mouth or<br />

the eyes³. As the bug bites and defecates<br />

near the wound site, the protozoan<br />

parasite, Trypanosoma Cruzi (T. Cruzi),<br />

enters the body from the infected feces or<br />

urine.In Latin American towns, the kissing<br />

bug is found mostly in adobe houses or<br />

enters through cracks of poorly constructed<br />

houses¹. Other modes of infection include<br />

mother to child transmission, consumption<br />

of contaminated food, and blood<br />

transfusions.<br />

Chagas disease has two phases: acute and<br />

chronic. The acute phase, is characterized<br />

by muscle pain, fever, enlarged lymph<br />

nodes, and headaches⁴. Despite this, some<br />

people are asymptomatic. In all acute<br />

phases, however, there is a large<br />

amount of parasite circulating<br />

in the blood. As the<br />

disease develops<br />

into the<br />

chronic stage, the parasites hide in the<br />

heart and the digestive tract and, as a<br />

result, are hard to detect. Thus, people<br />

who progress to chronic Chagas may not<br />

show any symptoms, and this may result<br />

in sudden death due to inflammation and<br />

cardiac arrest years later¹.<br />

Current treatment of Chagas include only<br />

two drugs: benznidazole and nifurtimox.<br />

While benznidazole is FDA approved,<br />

nifurtimox is not. Although these drugs<br />

are most effective in young patients and<br />

patients with acute Chagas, the drugs have<br />

shown a low cure rate in the chronic phase⁴.<br />

Furthermore, both drugs have adverse<br />

side effects including anorexia, headache,<br />

nausea, and neuropathy⁵. They also pose a<br />

barrier to vulnerable populations who have<br />

limited access to healthcare since these<br />

drugs have a long regimen (benznidazole is<br />

taken for 60 days and nifurtimox for 60-90<br />

days) and require constant blood work<br />

to ensure that there is no adverse side<br />

effects. Currently, there are no vaccines<br />

against Chagas. Thus, the need for novel<br />

therapeutic treatments and vaccines is<br />

paramount.<br />

One of the leading research institute for<br />

Chagas, the Sabin Vaccine Institute, is<br />

currently working hard to develop a human<br />

vaccine against Chagas⁶. With this vaccine,<br />

researchers hope to improve Chagas<br />

prognosis, lower treatment cost, decrease<br />

treatment duration, and slow disease<br />

progression. They have already developed<br />

a successful vaccine candidate which<br />

can either act as a vaccine alone or be<br />

combined with benznidazole as a form of<br />

chemotherapy, demonstrating potential as<br />

both a preventive and a therapeutic agent.<br />

Chagas disease is<br />

transmitted by<br />

the blood sucking<br />

triatomine bug,<br />

also known as the<br />

kissing bug<br />

Early animal studies of these vaccines have<br />

shown promising results:mouse models<br />

treated with the vaccine have shown potent<br />

immune response, increased host survival,<br />

diminished cardiac fibrosis and pathology,<br />

and reduced cardiac parasite loads⁶.<br />

Another potential vaccine uses recombinant<br />

adenovirus carrying sequences of the<br />

T-cruzi parasite’s proteins. Essentially these<br />

viruses cannot replicate in the body, but<br />

they still produce viral proteins. Since these<br />

viruses have T-cruzi DNA integrated into<br />

them, they produce the T-cruzi proteins as<br />

well. The body recognizes these elements<br />

as foreign and mounts an immune<br />

response against all parasite remnants.<br />

Results from this study show that these<br />

vaccines are effective in inciting an immune<br />

response and decreasing parasitic load in<br />

both the acute and the chronic phase of<br />

Chagas⁷. The study also demonstrates that<br />

this vaccine can be used therapeutically<br />

to delay disease progression and reverse<br />

heart tissue damage.<br />

Chagas disease is a serious condition<br />

with little attention given to the disease.<br />

Moreover, current treatments for this<br />

disease are few in number and pose various<br />

adverse side effects. Current research<br />

focuses on novel vaccine candidates aimed<br />

at both preventing and treating the disease.<br />

As scientists continue to focus more on this<br />

neglected disease, a possible cure might be<br />

on the horizon.<br />

Works Cited<br />

[1] Chagas disease (American trypanosomiasis). (2017). In<br />

WHO. Retrieved from http://www.who.int/mediacentre/<br />

factsheets/fs340/en/<br />

[2] Lee BY et al. Lancet. 2013, 13, 342-348<br />

[3] Montgomery, S. P. et al. Am. J. Trop. Med. 2014, 90, 814-<br />

815.<br />

[4] Sales, P. A., Jr. et al. Am. J. Trop. Med. 2014, 97, 1289-<br />

1303.<br />

[5] Castro, J. A., et al. Human Exp.Toxicol. 2006, 25, 471-479.<br />

Barry, M. A. et al. Human Vac. Immunotherapeutics. 2016,<br />

[6] 12, 976-987.<br />

[7] Pereira, I. R. et al. (2015). PLoS Pathogens, 11(1),<br />

e1004594. http://doi.org/10.1371/journal.ppat.1004594<br />

design by Madeleine Tadros<br />

edited by Mahesh Krishna<br />



Celina Tran<br />

A<br />

ndrea, Fathom, Katrina, and Splash.<br />

These were the names of the four U.S.<br />

Navy-trained dolphins which bore<br />

the responsibility of saving their distant<br />

porpoise relatives, the vaquita, from<br />

extinction. 1<br />

The vaquita are the porpoises that live in<br />

the Gulf of California, the little pocket of<br />

sea neighbored on the west by the Baja<br />

California peninsula and on the east by the<br />

Mexico mainland. At their largest, they are<br />

five feet long and have characteristic dark<br />

“eyeliner” rings around each of their eyes.<br />

There are an estimated fewer than thirty of<br />

them left, 2 largely due to totoaba fishing.<br />

The totoaba is a species of fish that shares<br />

the same habitat as the vaquita - in the<br />

Gulf of California. It is highly coveted for its<br />

bladder, similar to how a rhino is coveted<br />

for its ivory horns. The bladder is used<br />

by the Chinese in a soup called fish maw,<br />

which is believed to boost fertility. The<br />

bladders are smuggled into the United<br />

States, and then shipped to China to be<br />

sold. Even though totoaba fishing has been<br />

banned by the Mexican government, the<br />

activity is still worth the risk because each<br />

bladder can yield up to ten thousand dollars<br />

or more. 3 The fishermen use gill nets to<br />

catch the totoaba, unintentionally also<br />

trapping the vaquita as bycatch. Tangled in<br />

the nets, because they cannot resurface, the<br />

oxygen-deprived vaquita drown.<br />

On April 3, 2017, the government of Mexico<br />

made an announcement: $3 million would<br />

be given to the VaquitaCPR initiative; CPR<br />

stands for conservation, protection and<br />

recovery. 4 This ambitious, high-risk plan<br />

aims to save the last few remaining vaquita.<br />

As a part of this project, dolphins Andrea,<br />

Fathom, Katrina, and Splash would use<br />

echolocation to seek out the shy vaquita<br />

so that they can be captured. They would<br />

then be gathered and transported to a<br />

holding pen on the west side of the gulf,<br />

which would keep the vaquita away from<br />

the gill nets that have been otherwise lethal<br />

to them. 4 It was hoped that the vaquita<br />

would adapt to captivity, breed, and their<br />

population would grow large enough to be<br />

eventually released back into the wild.<br />

At least, that was the plan. Because the<br />

vaquita had never been captured live<br />

before, little could be done to predict<br />

how they might handle the stress, which<br />

scientists learned the hard way. The first<br />

animal that was successfully captured was<br />

a juvenile female. She had to be quickly<br />

released because she was under too much<br />

stress. The second, a female of reproductive<br />

age, died in captivity. Just a few hours after<br />

being placed in the pen, she most likely<br />

suffered from a heart attack. 5 For the<br />

already-tiny population, the death was a<br />

huge loss. As a consequence, VaquitaCPR<br />

was suspended, and the decision to cease<br />

the capture portion of the operation was<br />

unanimous. It was just November.<br />

The fate of the vaquita<br />

is in the hands of law<br />

enforcement.<br />

Now what? The fate of the vaquita is in<br />

the hands of law enforcement. Poachers<br />

must be stopped, even if they do not<br />

target the vaquita. At the same time, any<br />

solution must be tailored to benefit both<br />

humans and vaquitas, as conservation<br />

biology is intertwined with local economies<br />

and communities. Illegal fishing must be<br />

replaced with an alternative source of<br />

livelihood for the fishermen. 5 Currently,<br />

VaquitaCPR is working on identifying<br />

the last few vaquita, using the markings<br />

on their fins that are unique to each<br />

individual. Acoustic recording devices<br />

track and monitor the ranges of these<br />

unique porpoises. Veterinarians assess<br />

blood samples from the lab, to determine<br />

what part of the plan - capture, transport,<br />

or enclosure - made the vaquita panic. 5<br />

Hopefully, the “panda of the sea” can be<br />

saved from extinction. It serves as a story<br />

that has greater implications, highlighting<br />

how conservation is about balancing the<br />

ecological concerns and the needs of the<br />

community.<br />

Works Cited<br />

[1] Joyce, C. Chinese Taste for Fish Bladder Threatens Rare<br />

Porpoise in Mexico. NPR, Feb. 9, 2016. https://www.npr.<br />

org/466185043/ (accessed Jan. 17, <strong>2018</strong>).<br />

[2] Grens, K. US Navy Dolphins to Capture Vaquitas to Save<br />

Them from Extinction. The Scientist, Oct. 6, 2017. https://<br />

www.the-scientist.com/?articles.view/articleNo/50580/title/<br />

US-Navy-Dolphins-to-Capture-Vaquitas-to-Save-Themfrom-Extinction/<br />

(accessed Jan. 17, <strong>2018</strong>).<br />

[3] Albeck-Ripka, L. 30 Vaquita Porpoises Are Left. One<br />

Died in a Rescue Mission. The New York Times, Nov. 11,<br />

2017. https://nyti.ms/2hsMV5j (accessed Jan. 17, <strong>2018</strong>).<br />

[4] Nicholis, H. A Last-Ditch Attempt to Save the World’s<br />

Most Endangered Porpoise. Nature, Apr. 7, 2017. http://<br />

dx.doi.org/10.1038/nature.2017.21791 (accessed Jan. 17,<br />

<strong>2018</strong>).<br />

[5] Brulliard, K. A final bid to save the world’s rarest<br />

porpoise ends in heartbreak. Is extinction next?<br />

The Washington Post, Nov. 9, 2017. https://www.<br />

washingtonpost.com/news/animalia/wp/<br />

2017/11/09/a-final-bid-to-save-the-worlds-rarestporpoise-ends-in-heartbreak-is-extinction-next/?utm_<br />

term=.79abaa181c86 (accessed Jan. 17, <strong>2018</strong>).<br />

Images courtesy of Pixabay<br />

Vectors courtesy of chiccabubble and Xihn<br />

Studio<br />

Designed By J. Riley Holmes<br />

Edited By Anna Croyle<br />


Quantum Computing<br />

A Leap Forward in Processing Power<br />

W<br />

e live in the information age, defined<br />

by the computers and technology that<br />

reign over modern society. Computer<br />

technology progresses rapidly every year,<br />

enabling modern day computers to process<br />

data using smaller and faster components<br />

than ever before. However, we are quickly<br />

approaching the limits of traditional<br />

computing technology.<br />

Typical computers process<br />

data with transistors. 1<br />

Transistors act as tiny<br />

switches in one of<br />

two definite states:<br />

ON or OFF. 2<br />

These states are<br />

represented<br />

by binary digits<br />

known as “bits,”<br />

1 for ON and 0 for<br />

OFF. 2 Combinations<br />

of bits let us describe<br />

more complex data,<br />

which ultimately becomes<br />

the basis for a computer.<br />

For instance, a 2-bit computer<br />

has four possible bit combinations at<br />

any given time: 11, 10, 01, and 00. Every<br />

additional bit doubles the number of<br />

possible combinations and increases the<br />

computer’s ability to store and process<br />

data. 3 Shrinking the size of transistors<br />

allows more transistors to fit on a single<br />

chip, giving us greater processing power<br />

per chip. However, modern transistors<br />

are reaching the size of only a few atoms. 4<br />

We will soon reach the physical limit to<br />

how small and fast a transistor can be.<br />

Since 1975, the computer chip industry<br />

has followed Moore’s Law, the notion<br />

that the number of transistors on a chip<br />

will double every two years, but recently,<br />

delays in advancements have caused some<br />

to announce the death of Moore’s Law. 5<br />

Though we may not be capable of making<br />

transistors much smaller, we can push past<br />

their limits with a new type of computer:<br />

the quantum computer.<br />

Quantum computers use quantum bits,<br />

or “qubits,” rather than bits. Qubits are<br />

incredibly tiny particles that experience<br />

by Valerie Hellmer<br />

Superposition<br />

and entanglement<br />

allow quantum<br />

computers to process<br />

data faster than<br />

traditional<br />

computers<br />

quantum effects like superposition and<br />

entanglement due to their small size. 2 A<br />

qubit is in superposition when it is in a<br />

combination of two states simultaneously.<br />

So while a normal bit must be either 1 or<br />

0, a qubit can be both 1 and 0. 2 This can<br />

be difficult to imagine since it goes against<br />

everything we encounter throughout our<br />

lives; a flipped coin can either land on<br />

heads or tails, not both sides<br />

at once. Yet qubits seemingly<br />

defy our reality and do just<br />

that. A 2-qubit computer still<br />

possesses the four original<br />

bit combinations, only<br />

now the qubits can<br />

simultaneously hold<br />

all four combinations. 6<br />

The qubits have a<br />

probability of being in<br />

each of the four states,<br />

but the qubits’ actual<br />

combination is revealed only<br />

after being observed, which<br />

collapses the superposition. 6<br />

Even stranger than superposition,<br />

quantum entanglement is when<br />

the state of one qubit affects the state of<br />

another instantaneously over any distance. 7<br />

For instance, if two qubits are entangled in<br />

opposites states, then when<br />

one qubit changes from 1 to<br />

0, the other changes from<br />

0 to 1 without any delay.<br />

This switch allows<br />

information to travel<br />

incredibly quickly<br />

in a quantum<br />

computer. But<br />

that is not all<br />

entanglement<br />

has to offer;<br />

entanglement<br />

also lets you receive<br />

information on a group<br />

of entangled qubits by<br />

checking the state of only<br />

one qubit. 3 Superposition<br />

and entanglement allow quantum<br />

computers to process data faster than<br />

traditional computers such that a 56-qubit<br />

computer would contain more processing<br />

power than any traditional computer<br />

A 56-qubit<br />

computer would<br />

contain more<br />

processing power than<br />

any traditional<br />

computer ever<br />

built<br />

ever built. 8 This achievement is known<br />

as quantum supremacy over traditional<br />

computing--an impressive feat considering<br />

modern supercomputers can perform<br />

93,000 trillion calculations per second. 8-9<br />

Today’s top tech companies are getting<br />

incredibly close to the quantum supremacy<br />

milestone.<br />

IBM has been researching quantum<br />

computers for over 35 years, and has<br />

recently shown rapid progress. 2 In May<br />

2016, IBM released access to a 5-qubit<br />

quantum computer online, where anyone<br />

can develop and run their own quantum<br />

algorithms. 1 This quantum computer has<br />

created opportunities for both scientists<br />

and enthusiasts to interact with qubits and<br />

has already been used for over 1.7 million<br />

public experiments. 10 IBM then established<br />

a new quantum computing division called<br />

“IBM Q” in March 2017. 1 And more recently,<br />

in January <strong>2018</strong>, the company developed a<br />

50-qubit quantum computer prototype. 10<br />

While these computers cannot beat any<br />

classical machine at present, IBM has their<br />

vision set on a future powered through<br />

quantum computing. 1<br />

Another computer company, D-Wave<br />

Systems, is known for advancing<br />

quantum computing with<br />

a different approach. The<br />

company made headlines in<br />

2013 by selling a 512-qubit<br />

computer called the<br />

D-Wave Two to NASA<br />

and Google. 11 And in<br />

2017, the company<br />

released a 2000-qubit<br />

computer called<br />

the D-Wave 2000Q,<br />

which can run certain<br />

algorithms 100 million<br />

times faster than an average<br />

classical computer. 11-12 While<br />

these numbers make it sound<br />

as if D-Wave Systems has easily<br />

achieved quantum supremacy, this is not<br />

necessarily the case. D-Wave Systems’<br />

computers have faced a lot of controversy<br />

since they use a “quantum annealing”<br />


approach which have minimal control<br />

of their qubits.” 12-13 As a result, D-Wave<br />

Systems’ “quantum annealing” systems can<br />

only be applied to optimization problems,<br />

as compared to IBM’s “gate-based” systems,<br />

which have a much wider<br />

scope of applications. 14-15<br />

Despite the fact D-Wave<br />

Systems is not<br />

considered to have<br />

achieved quantum<br />

supremacy, the<br />

company has<br />

certainly pushed<br />

forward the<br />

boundaries of<br />

computing. 16<br />

quantum<br />

computers may<br />

revolutionize<br />

the fields of<br />

machine learning<br />

and artificial<br />

intelligence<br />

While quantum<br />

computing promises<br />

to dramatically increase<br />

processing power, there<br />

are still limitations to its potential. For one,<br />

a quantum computer cannot replace your<br />

laptop anytime soon. Quantum computers<br />

are extremely task specific, meaning that<br />

even with IBM’s gate-based approach, those<br />

ultra-high processing speeds will only work<br />

best on certain types of problems. 16 In<br />

addition, qubits are very unstable particles;<br />

to be used in a computer, they have to be<br />

kept at a temperature just a fraction of a<br />

degree above absolute zero while shielded<br />

from nearly all light and Earth’s magnetic<br />

field. 16 Even the smallest vibration could<br />

disrupt their state. Consequently, quantum<br />

computers’ extreme operating conditions<br />

currently confine their use to research<br />

companies or data centers instead of<br />

households. Likewise, the fragility of qubits<br />

means they produce a lot of error. 16 Some<br />

experts estimate that checking the results<br />

of one qubit will require 100 additional<br />

qubits, meaning that even when quantum<br />

supremacy is reached, more qubits will<br />

be necessary to make the computers<br />

practical. 16 More realistically, quantum<br />

computers could be used in conjunction<br />

with traditional computers to yield<br />

interesting results.<br />

Despite its limitations, quantum computing<br />

has the potential to transform the world.<br />

One potential application is improving<br />

chemical and biological models, which<br />

need a lot of processing power to fully<br />

represent the complex characteristics<br />

of molecules. 16 Driven by quantum<br />

computers, improvements in these models<br />

could revolutionize our understanding<br />

of chemistry, physics, and medicine. 16<br />

Furthermore, experts believe that quantum<br />

computers may revolutionize the fields of<br />

machine learning and artificial intelligence,<br />

which in turn could impact just about<br />

every aspect of society. 16 However, some<br />

companies and governments are also<br />

preparing their defenses for “Y2Q,” the<br />

year when a large-scale quantum computer<br />

could bring down our current system of<br />

encryption, which protects everything from<br />

credit-card numbers to nationally guarded<br />

secrets. 16 While some experts predict Y2Q<br />

could occur as soon as 2026, it is difficult<br />

to predict how security systems will change<br />

alongside developments in computing, and<br />

what the true impact of quantum<br />

computers will be.<br />

Works Cited<br />

Much like how no one could<br />

have predicted the future<br />

of computers in the<br />

1960s, we cannot tell<br />

how much quantum<br />

computing will shape<br />

our lives in the coming<br />

decades. However, with<br />

every technology come<br />

risks and benefits, and no<br />

matter what, researchers<br />

will continue to push the<br />

boundaries of human capability.<br />

[1] Murphy, M. IBM Thinks It’s Ready to Turn Quantum<br />

Computing into an Actual Business. Quartz, Mar. 05,<br />

2017. https://qz.com/924433/ibm-thinks-its-ready-to-turnquantum-computing-into-an-actual-business/<br />

(accessed<br />

Oct. 20, 2017).<br />

[2] Castelvecchi, D. Quantum computers ready to leap<br />

out of the lab in 2017. Nature News [Online], Jan. 03,<br />

2017. Nature Publishing Group. http://www.nature.com/<br />

news/quantum-computers-ready-to-leap-out-of-the-labin-2017-1.21239<br />

(accessed Nov. 17, 2017).<br />

[3] Steane, A. Quantum computing. Rep. Prog. Phys. 1998,<br />

61, 117-173.<br />

[4] Markoff, J. Smaller, Faster, Cheaper, Over: The Future<br />

of Computer Chips. The New York Times [Online], Sept. 26,<br />

2015. https://www.nytimes.com/2015/09/<br />

27/technology/smaller-faster-cheaper-over-the-future-ofcomputer-chips.html<br />

(accessed Oct. 20, 2017).<br />

[5] Novet, J. Intel Shows off Its Latest Chip for Quantum<br />

Computing as It Looks past Moore’s Law. CNBC, Oct. 10,<br />

2017. https://www.cnbc.com/2017/10/10/intel- delivers-<br />

17-qubit-quantum-computing-chip-to-qutech.<br />

html (accessed Oct. 20, 2017).<br />

[6] Lochan, K.; Singh, T. Nonlinear quantum<br />

mechanics, the superposition principle,<br />

and the quantum measurement<br />

problem, 2010, arXiv:0912.2845 [quantph]<br />

(accessed Jan. 19, <strong>2018</strong>).<br />

[6] Raimond, J. et al. Manipulating<br />

quantum entanglement with atoms<br />

and photons in a cavity. Rev. Mod.<br />

Phys. 2001, 73, 565-582.<br />

[8] Kim, Mark. Google’s quantum<br />

computing plans threatened by<br />

IBM curveball. New Scientist,<br />

Oct. 20 2017. https://<br />

www.newscientist.com/<br />

article/2151032-googlesquantum-computingplans-threatened-by-ibmcurveball/<br />

(accessed Jan.<br />

19, <strong>2018</strong>).<br />

[9] Dongarra, J. China<br />

builds world’s most<br />

powerful computer.<br />

BBC News [Online],<br />

June 20 2016.<br />

http://www.bbc.<br />

com/news/<br />

technology-36575947 (accessed Jan. 19, <strong>2018</strong>).<br />

[10] Morse, J. IBM’s quantum computer could change the<br />

game, and not just because you can play Battleship on it.<br />

Mashable, Jan. 08, <strong>2018</strong>. http://mashable.com/<strong>2018</strong>/01/08/<br />

ibm-quantum-computer-ces-201i8/#NewKKb33GOqh<br />

(accessed Jan. 19, <strong>2018</strong>).<br />

[11] Jones, N. Google and NASA Snap Up Quantum<br />

Computer D-Wave Two. Scientific American [Online], May<br />

17, 2013. https://www.scientificamerican.com/article/<br />

google-nasa-snap-up-quantum-computer-dwave-two/<br />

(accessed Nov. 17, 2017).<br />

[12] Gibney, E. D-Wave upgrade: How scientists are using<br />

the world’s most controversial quantum computer.<br />

Nature News [Online], Jan. 24, 2017. Nature Publishing<br />

Group https://www.nature.com/news/d-wave-upgradehow-scientists-are-using-the-world-s-most-controversialquantum-computer-1.21353<br />

(accessed Nov. 17, 2017).<br />

[13] Denchev, V. et al. Phys. Rev. X. 2016, 6, 031015.<br />

[14] Michielsen, K. et al. Benchmarking gate-based<br />

quantum computers, 2017. arXiv:1706.04341 [quant-ph]<br />

(accessed Nov. 17, 2017).<br />

[15] Marchenkova, A. What’s the difference between<br />

quantum annealing and universal gate quantum<br />

computers?. Medium, Feb. 28, 2017. https://medium.com/<br />

quantum-bits/what-s-the-difference-between-quantumannealing-and-universal-gate-quantum-computersc5e5099175a1<br />

(accessed Jan. 19, <strong>2018</strong>).<br />

[16] Nicas, J. How Google’s Quantum Computer Could<br />

Change the World. The Wall Street Journal [Online], Oct.<br />

16, 2017. Dow Jones & Company. https://www.wsj.com/<br />

articles/how-googles-quantum-computer-could-changethe-world-1508158847<br />

(accessed Oct. 20, 2017).<br />

design by Namtip Phongmekhin<br />

edited by Brianna Garcia<br />



F<br />

rom completing common household<br />

activities to performing dangerous tasks<br />

on the International Space Station,<br />

the modern day robot has become more<br />

notably human-centered, picking up where<br />

humanity’s physical capabilities have left off.<br />

As they continue to become more applicable<br />

to human life, the functionalities of robots<br />

have expanded to cover many different fields<br />

of study, including biomedicine, where a<br />

robot’s practicality has been scaled down to<br />

the molecular level.<br />

Dr. Lydia Kavraki, a professor and<br />

researcherat Rice University’s School of<br />

Engineering, is one of the pioneers pursuing<br />

the connections between the two domains<br />

of robotics and bioinformatics. As a young<br />

graduate student, Dr. Kavraki became<br />

interested in robotics when she realized<br />

how helpful robots can be for humans. She<br />

remembers, “there were robots in these labs<br />

and they didn’t do anything! They were just<br />

static! And I was fascinated and said, okay,<br />

these robots should do something and I<br />

should work on motion planning.” As it is<br />

defined today, the motion planning problem<br />

is the problem of moving our “robot,” no<br />

matter how small the size, from one place to<br />

another while avoiding obstacles and walls.<br />

Dr. Kavraki’s motion-planning algorithm<br />

was developed many years ago, but it has<br />

provided a foundation for modern-day<br />

projects and research to expand upon. To<br />

understand the algorithm, the concept of<br />

“degrees of freedom” must be introduced.<br />

These degrees can be thought of as the range<br />

or mobility of certain mechanical systems,<br />

such as the arm of a robot. More complex<br />

robots would require systems with a greater<br />

number of degrees of freedom and would be<br />

much more difficult to plan a path for. A valid<br />

motion can only be achieved by performing<br />

actions that are feasible, or in other words,<br />

within the specified degrees of freedom and<br />

the robot’s physical constraints. 1<br />

The complexity of this problem involves<br />

determining the solution space, which is<br />

defined as the set of all solutions that satisfy<br />

the problem’s constraints. Previous methods<br />

used in the robotics community have tried to<br />

plan a path by partitioning the solution space<br />

into its free parts, where the robots could<br />

move, and forbidden parts, areas that were<br />

obstacles and infeasible for motion. However,<br />

Dr. Kavraki’s algorithm, called the Probabilistic<br />

Roadmap Method (PRM), actually takes<br />

samples of the space to test the mobility<br />

of the robot. After sampling the solution<br />

space, the algorithm then finds connections<br />

among the different configurations of the<br />

robots, and captures this connectivity in<br />

a series of queues, forming approximate<br />

maps of the free space. 2 The effects of Dr.<br />

Kavraki’s research are prominent throughout<br />

the robotics and biological industries, and<br />

these sampling-based motion planners have<br />

since been implemented in a variety of her<br />

projects. Dr. Kavraki’s Open Motion Planning<br />

Library (OMPL) has not only been used in<br />

60 different robotics systems, but has also<br />

become a fundamental component of the<br />

Robot Operating System, the conventional<br />

framework for writing robot software. 3<br />

Ultimately, this computational approach<br />

has become the basis for more complex<br />

problems brought up within the robotics<br />

and bioinformatics communities, regardless<br />

of the dimensions of the solution space. In<br />

the words of Dr. Kavraki, “We [now] have<br />

efficient techniques for a very large number<br />

of robots that [were] just impossible before<br />

the invention of the sampling space and the<br />

motion planning algorithms.” Furthermore,<br />

these techniques can be scaled down to the<br />

molecular level, where even motions of 1000<br />

degrees of freedom can be measured. 1<br />

It turns out that some of<br />

the algorithmics that we<br />

use for modeling robots<br />

and modeling motion can<br />

be used and adapted to<br />

reason about shape and<br />

function of molecules.<br />

While working on her research, Dr. Kavraki<br />

discovered a remarkable relationship<br />

between robots and another kind of machine<br />

billions of times smaller that resides in<br />

our bodies - the protein. “It turns out that<br />

some of the algorithmics that we use for<br />

modeling robots and modeling motion can<br />

be adapted to reason about shape and<br />

function of molecules,” Dr. Kavraki explains.<br />

She also expresses the idea that there is<br />

an “underlying theoretical component” that<br />

connects these two domains, which prompted<br />

her to work on projects integrating both<br />

fields.<br />

Perhaps the most significant application in<br />

the robotics domain is with the NASA Johnson<br />

Space Center. The Robonaut 2 (R2), which<br />

is currently up in the International Space<br />

Station, was designed and created by NASA<br />

in collaboration with Dr. Kavraki’s team.<br />



R2 is incredibly dexterous, having a total<br />

of 34 degrees of freedom in its main body,<br />

and is able to perform simple tasks such<br />

as using human tools, fetching cargo bags<br />

and measuring the quality of the air tank.<br />

Furthermore, this humanoid robot takes over<br />

repetitive and potentially life threatening<br />

procedures that the astronauts on board can<br />

avoid. 3 For example, it inspects the outside<br />

of the space station and aids the docking of a<br />

shuttle to a space station that is in continual<br />

orbit. 4 This difficult procedure relies on<br />

identifying and calculating the degrees of<br />

freedom of both the shuttle and docking<br />

platform. “You really want a robot to do this<br />

job. You don’t want humans out to get all<br />

the radiation as they inspect the outside of<br />

the space station,” Dr. Kavraki comments.<br />

Looking forward, she says, “NASA is interested<br />

in robotics applications for caretaking<br />

operations for astronauts, for future missions<br />

to Mars, for establishing habitats that would<br />

later be populated by humans.”<br />

In the biomolecular domain, Dr. Kavraki’s<br />

algorithm has enabled researchers to<br />

determine the structures and motions of<br />

molecules. It has also helped develop handson<br />

techniques that have become integral<br />

in medical procedures, such as the closing<br />

of wounds by tying knots used in surgical<br />

suturing. 3 In the past, suturing techniques<br />

were extremely challenging and required<br />

precise measurements to perform, but<br />

by applying Dr. Kavraki’s motion planning<br />

research, robotic surgical systems were able<br />

to determine a motion pathway for directing<br />

the surgical needle to specific locations that<br />

minimize the interaction forces between the<br />

needle and tissue. This has allowed suturing<br />

to become more automated and precise.<br />

In addition, her work has led to an efficient<br />

way of analyzing molecular binding<br />

conformations, another form of docking,<br />

where interactions between molecules such<br />

as those between a ligand and receptor can<br />

be modeled to design new therapeutics.<br />

Ligand docking can be determined in a<br />

manner similar to shuttle docking. A motion<br />

space is first explored. Then, depending on<br />

the size of the ligand--the larger and more<br />

flexible the ligand is, the more degrees of<br />

freedom these large molecules have--docking<br />

can be modeled computationally. These<br />

interactions are often more challenging,<br />

as the motion space for a large ligand has<br />

increased dimensionality. 5 By undergoing<br />

dimension-reducing techniques that use the<br />

PRM as a foundation, Dr. Kavraki’s research<br />

is able to simplify the process of obtaining a<br />

valid motion space.<br />

Dr. Kavraki’s research in the molecular<br />

domain has led to applications in the<br />

medical field, specifically the Kavraki Lab’s<br />

immunotherapy project in collaboration<br />

with MD Anderson. While the medical labs<br />

perform the actual experiments, the Kavraki<br />

Lab helps design the receptors involved<br />

in immunotherapy and does modeling to<br />

narrow down the many possible receptor<br />

conformations for them to test. In other<br />

words, they perform the experiments from a<br />

computational perspective. 3 “We try to show<br />

them how different proteins and receptors<br />

and peptides dock, that is, what is the relative<br />

position when they interact,” Dr. Kavraki says.<br />

Currently, Kavraki and her lab are trying to<br />

understand the mechanics of the motions of<br />

these large molecules using techniques that<br />

have already been established by the PRM.<br />

In the future, Kavraki hopes to see her work<br />

being implemented for constructing robots<br />

that aid people with special needs and<br />

accomplish tasks that are beyond physical<br />

reach. She also looks forward to progress<br />

on the immunotherapy project, where the<br />

applications of her research can help patients<br />

with severe medical conditions. “To improve<br />

the quality of life, “ Dr. Kavraki says, is the<br />

main objective of her passion and dedication<br />

to these studies.<br />


[1] Teodoro, M. L. et al. IEEE International<br />

Conference on Robotics and Automation<br />

2011, 1, 960-966.<br />

[2] Kavraki, L. et al. IEEE Transactions on<br />

Robotics and Automation 1998, 14, 166-171.<br />

[3] Kavraki Lab. kavrakilab.org (accessed Nov.<br />

05, 2017)<br />

[4] Robonaut.robonaut.jsc.nasa.gov/R2<br />

(accessed Nov. 05, 2017)<br />

[5] Dhanik, Ankur. et al. BMC Structural<br />

Biology 2012, 13, 48-55<br />

DESIGN BY Christina Tan<br />

EDITED BY Albert Truong<br />

by Alan Ji<br />

Dr. Lydia Kavraki<br />

Lydia E. Kavraki is the<br />

Noah Harding Professor of<br />

Computer Science, professor<br />

of Bioengineering, professor<br />

of Electrical and Computer<br />

Engineering, and professor<br />

of Mechanical Engineering at<br />

Rice University. She received<br />

her B.A. in Computer Science<br />

from the University of Crete<br />

in Greece and her Ph.D.<br />

in Computer Science from<br />

Stanford University. Her<br />

research contributions are in<br />

physical algorithms and their<br />

applications in robotics (robot<br />

motion planning, hybrid<br />

systems, formal methods in<br />

robotics, assembly planning,<br />

micromanipulation, and<br />

flexible object manipulation),<br />

as well as in computational<br />

structural<br />

biology,<br />

translational bioinformatics,<br />

and biomedical informatics<br />

(modeling of proteins and<br />

biomolecular interactions,<br />

large-scale functional<br />

annotation of proteins,<br />

computer-assisted drug<br />

design, and the integration<br />

of biological and biomedical<br />

data for improving human<br />

health).<br />


AMP<br />

ing up the<br />

defense system<br />


A<br />

rguably one of the greatest achievements<br />

in modern medicine has been the<br />

discovery and creation of antibiotics to help<br />

the human body combat bacterial infections.<br />

However, the overuse of antibiotics has led<br />

to the development of another crisis: growing<br />

bacterial resistance to antibiotics as evidenced<br />

by the growing strains of Methicillin-resistant<br />

Staphylococcus aureus, or MRSA, and other<br />

similar organisms. This phenomenon of<br />

antibiotic resistance is an unfortunate result<br />

of the natural process of evolution. As more<br />

antibiotics are used, the nonresistant strains<br />

of bacteria will succumb to the antibiotic<br />

while the resistant strains will proliferate<br />

at a high rate. There is a dire need for the<br />

development of novel antibiotics and other<br />

similar treatments. 4 Fortunately, a new class<br />

of antibiotics has recently been discovered<br />

that may serve as a potential solution to<br />

antibiotic resistance. Because they were<br />

just recently discovered and have not been<br />

used extensively in modern medicine, most<br />

bacterial strains have not developed any form<br />

of resistance to these new antibiotics making<br />

them very promising therapeutic agents in the<br />

future.<br />

This new class of antibiotics, called antimicrobial<br />

peptides (AMPs), works to kill<br />

bacteria by destroying their lipid membranes. 2<br />

A cell is defined by its ability to maintain a<br />

this new class of antibiotics, called anti-microbial peptides (amps), works<br />

to kill bacteria by destroying their lipid membranes...when the membrane<br />

is structurally attacked and subsequently compromised, the cell becomes<br />

dysfunctional and dies.<br />

separate environment inside from the outside<br />

via a lipid membrane; when the membrane<br />

is structurally attacked and subsequently<br />

compromised, the cell becomes dysfunctional<br />

and dies. A large subset of AMPs work by<br />

creating holes in the bacteria’s membrane<br />

while other AMPs work by leaking selective<br />

ions to kill the bacteria. On the other hand,<br />

20 | CATALYST<br />

conventional antibiotics, like penicillin, act Dr. Huang and his team developed and<br />

on bacterial proteins in order to hijack the modified methods to study such a unique<br />

bacteria’s internal machinery to prevent cell system. “It’s so thin, just 40 Å thick. How do<br />

wall formation and mitigate bacterial growth. 9 you study this structure? It cannot be optical;<br />

While conventional antibiotics have been it’s far too thin for that … For the detail, we<br />

researched extensively, AMPs still hold many end up relying on x-rays and neutron in-plate<br />

mysteries that researchers are still trying to scattering. These methods use x-rays or<br />

explain.<br />

neutrons and send them as a beam and see<br />

“It’s [the membrane] so thin, just 40 Å thick. How do you study this<br />

structure? It cannot be optical; it’s far too thin for that…For the<br />

detail, we end up relying on x-rays and neutron in-plate scattering.”<br />

how they are scattered. From these scatter<br />

Dr. Huey Huang, a professor of physics at patterns we can extrapolate structure,” Dr.<br />

Rice University, has spent much of his career Huang explains. In order to study the effect of<br />

studying membrane biophysics and the AMPs on a cell membrane without having to<br />

effect of drugs like AMPs on the membrane. deal with living bacterial cells every time, Dr.<br />

Dr. Huang was drawn to the membrane, Huang uses giant unilamellar vesicles (GUVs),<br />

because unlike other biological systems, the which are large cell membranes without cell<br />

membrane is relatively physical, in nature. organelles inside. According to Dr. Huang,<br />

Moreover, membranes are extremely difficult using GUVs with a similar composition to<br />

to study due to their small size, as evidenced bacterial cell membranes in order to study<br />

by their thickness of just 40 Angstroms (4 the effects of AMPs is far easier than using<br />

10-9 m), as well as the fact that membranes actual living bacteria since the bacteria will<br />

must be studied in an aqueous setting. inevitably die during the course of the study.<br />

Dr. Huang was attracted to the challenges Using these methods, Dr. Huang has been<br />

studying cellular membranes posed and has able to elucidate the mechanism behind the<br />

spent much of his career developing tools membrane-active variety of AMPs. By placing<br />

and methods to do so. These challenges are AMPs into a giant unilamellar vesicle and<br />

using neutron scattering, Dr. Huang found<br />

that for the AMP to successfully attack the<br />

membrane and create pores, the AMP must<br />

be on both sides of the GUV membrane.<br />

To enter the interior of the vesicle, the<br />

AMP binds to the GUV membrane from the<br />

outside, which allows a minuscule amount<br />

of AMPs to diffuse into the interior. Once a<br />

particular ratio of AMP to phospholipids in the<br />

best exemplified by the amount of scientific membrane is exceeded, pores are formed and<br />

progress that has occurred in the study of the membrane is destroyed. 3<br />

proteins. While over 12,000 soluble proteins<br />

have been crystallized, only a little over 500 Recently, Dr. Huang was part of a team<br />

membrane proteins have been crystallized that discovered the mechanism of action<br />

to have their structure revealed, despite behind daptomycin, an AMP drug that<br />

representing somewhere between 20 and had been approved by the Food and Drug<br />

30% of all proteins in an organism. 1,3 Administration despite its mode of action

AMPs<br />

Giant unilamellar vesicle<br />

AMPs bind and diffuse inside the vesicle,<br />

destroying the vesicle’s membrane<br />

To enter the interior of the vesicle, the AmP binds to the guv membrane from the outside, which allows<br />

a minuscule amount of AmPs to diffuse into the interior. Once a particular ratio of AmP to phospholipids<br />

in the membrane is exceeded, pores are formed and the membrane is destroyed.<br />

being unknown. Using a combination of<br />

imaging techniques, Dr. Huang and his team<br />

found that daptomycin binds to a certain<br />

component of the GUV membrane called<br />

phosphatidylglycerol (PG). 4 He and his team<br />

also found that daptomycin’s mechanism<br />

of action depends on the concentration<br />

of extracellular calcium, an important ion<br />

that the cell regulates carefully. 4 After a<br />

certain calcium concentration is exceeded,<br />

daptomycin begins to bind to the membrane<br />

and makes it permeable to potassium. 4 This<br />

permeability to potassium prevents the<br />

bacteria from maintaining the proper ion<br />

concentrations it needs to survive. The exact<br />

moment in which this permeability is induced<br />

appears to be when there is a daptomycin/<br />

calcium ratio of 2:3 and a daptomycin/PG<br />

ratio close to 1:1. 4<br />

According to Dr. Huang, much work in<br />

the study of AMPs remains to be done as<br />

the “[it is] a young field and [is] growing in<br />

importance.” One of Dr. Huang’s main goals<br />

is: to find general groups of AMPs that have<br />

similar mechanisms of actions. Finding these<br />

general groups would make development<br />

of newer AMP-based antibiotics a much<br />

easier task and allow for greater variety in<br />

therapeutic products. Another major aim is<br />

to find classes of AMPs that are effective at<br />

differentiating between human and bacterial<br />

cells; this is a difficult process because AMPs<br />

target the cell membrane, which is shared<br />

by both organisms., However, these cell<br />

membranes have some minor compositional<br />

differences, and drugs like daptomycin can<br />

bind to components unique to bacteria, like<br />

PG. 2 In order for AMPs to be more effective<br />

in a clinical context, Dr. Huang hopes to find<br />

other AMPs like daptomycin and study them<br />

to determine how this specificity is achieved.<br />

Dr. Huang is not alone in his research<br />

on AMPs. Many other researchers and<br />

corporations around the world are trying<br />

to discover or create new AMPs in order to<br />

combat the growing problem of antibiotic<br />

resistance. According Dr. Huang, “Lots of<br />

people are trying to develop AMPs for clinical<br />

use; the money incentive is always there.<br />

Some have succeeded, like daptomycin has.<br />

Relatively fewer people are trying to figure out<br />

the exact mechanism.” However, collaboration<br />

with the pharmaceutical companies that<br />

are trying to develop AMP drugs hasn’t<br />

One of dr. huang’s main goals is to find general groups of Amps that have<br />

similar mechanisms of actions. Finding these general groups would make<br />

development of newer AmP-based antibiotics a much easier task and allow<br />

for greater variety in therapeutic products.<br />

always been easy. “I have talked to many<br />

biotechnology companies,” says Dr. Huang.<br />

“They are sort of interested in mechanisms,<br />

that’s why they talk to me but they don’t<br />

give me much detail of their clinical trials or<br />

anything. They consider that to be business<br />

secrets.” This lack of collaboration makes it<br />

difficult for progress in the field of AMPs since<br />

information sharing allows researchers to<br />

build upon the work of others and inspire new<br />

experiments. 5<br />

As the nuances of AMPs are further<br />

researched and discovered, this class of drug<br />

may soon become a viable alternative to<br />

antibiotics. With continued innovation as well<br />

as exponential advances in technology, we<br />

will be able to mitigate and eventually cure<br />

the ever-evolving problem of antibacterial<br />

resistance, and the answer to this debilitating<br />

issue lies in the foundation of AMPs. By<br />

harnessing the power of AMPs and their<br />

exploitable capacity to kill bacteria while<br />

facing no resistance, we will be able to solve<br />

the problem of antibacterial resistance, once<br />

and for all.<br />


[1] Carpenter, E. P., et al. Curr Opin Struct Biol. 2008, 5,<br />

581-586.<br />

[2] Epand, R. M., et al. Mol Biosyst. 2009, 1788, 289-294<br />

[3] Huang, H. W., et al. Phys Rev Lett. [Online] 2004, 92,<br />

198304. http://hwhuang.rice.edu/pdfs/Huang2004.pdf<br />

(accessed Feb. 21, <strong>2018</strong>)<br />

[4] Lee, MT., et al. Biophys J. 2017, 113, 82-90<br />

[5] Mahlapuu, M., et al. Front Cell Infect Microbiol. [Online]<br />

2016, 6, 194. https://www.frontiersin.org/articles/10.3389/<br />

fcimb.2016.00194/full (accessed<br />

Feb. 21, <strong>2018</strong>).<br />

[6] Parker, Joanne L., et al. Adv Exp Med Biol. 2016, 922, 61-72.<br />

[7] World Health Organization. http://www.who.int/<br />

mediacentre/news/releases/<br />

2017/running-out-antibiotics/en/ (accessed December 22,<br />

2017).<br />

[8] USGS. https://www2.usgs.gov/datamanagement/share/<br />

guidance.php (accessed Dec. 22, 2017).<br />

[9] Yocum, R. R., et al. J Biol Chem. 1980, 255, 3977-3986<br />



Evelyn Syau<br />

Vatsala Mundra<br />


Creating Global<br />

Bioengineering Methods to Foste<br />

A<br />

round the world, more than 3<br />

million children under the age<br />

of 5 die every year from acute<br />

respiratory infections 1 , most of which are<br />

in the developing world. However, the<br />

development of accessible and low-cost<br />

technology in low-resource settings can<br />

easily save these children’s lives. Recently,<br />

a team of engineers at Rice University<br />

led by Dr. Maria Oden has developed the<br />

Pumani CPAP (Continuous Positive Airway<br />

Pressure) machine, a novel mechanism<br />

featuring cost-effective methods to solve<br />

the problem of acute respiratory infections<br />

in infants in low-resource settings.<br />

Dr. Maria Oden, the director of the<br />

Oshman Engineering Design Kitchen<br />

(OEDK) and a professor in the department<br />

of bioengineering at Rice University, guides<br />

undergraduate students to create devices<br />

solving global health issues. Dr. Oden<br />

was inspired to research these types of<br />

technologies to provide interesting design<br />

projects for bioengineering students,<br />

especially since “babies around the world<br />

are dying needlessly from conditions that<br />

we treat easily in the developed setting,<br />

[and] something [can be done] to prevent<br />

these types of deaths.”<br />

The CPAP machine solves one of these<br />

problems, helping newborn infants breathe<br />

by treating acute respiratory infections.<br />

By continuously pumping pressurized<br />

flow into the lungs, the machine ensures<br />

air sacs do not deflate, making it easier<br />

to breathe for the infant. According to Dr.<br />

Oden, the CPAP system works by keeping<br />

an infant’s lungs inflated, since premature<br />

infants often have lungs that collapse or<br />

are too small. By blowing pressurized air<br />

into lungs, the machine has helped bring<br />

newborn survival up from 24% previously<br />

to 65% currently.<br />

The design process necessary to create the<br />

CPAP machine was extensive, requiring<br />

Dr. Oden and her colleague Dr. Richards-<br />

Kortum to travel to Malawi to talk to<br />

physicians about their technological needs.<br />

Through interviews and observation, they<br />

learned that almost 50% of the babies who<br />

are prematurely born have respiratory<br />

By continuously pumping pressurized flow into the lungs, the<br />

cpap machine ensures air sacs do not deflate, making it easier to<br />

breathe for the infant.<br />

distress. But there was an even bigger<br />

problem. The systems available at the time<br />

cost $8,000 each, making them difficult to<br />

access in places that needed them most,<br />

low-resource settings.<br />

Dr. Oden and her colleagues saw this<br />

as an opportunity to engage senior<br />

bioengineering design students. According<br />

to Dr. Oden, “the student team worked<br />

over the course of the year and came up<br />

with a really amazing design.” Despite<br />

its lack of aesthetic appeal (Dr.<br />

Oden says it looked like a<br />

plastic shoebox from<br />

Target), the students<br />

were able to achieve<br />

pressures and flows<br />

similar to that of<br />

the expensive<br />

system used at<br />

Texas Children’s<br />

Hospital. The<br />

student project<br />

also cost about<br />

$140 - more than 50<br />

times less than the<br />

industry cost. Upon<br />

testing, the student<br />

project matched the flows<br />

and pressures of existing CPAP<br />

machines. With this promising data,<br />

the system was taken to Malawi, where it<br />

received user feedback and suggestions<br />

for improvement, all culminating in a unit<br />

ready for clinical trial.<br />

Looking back at the experience, Dr. Oden’s<br />

favorite recollection was during the start of<br />

clinical trials. “We were training the nurses<br />

on how to use the system, and we got a<br />

call from one of our physician-colleagues<br />

who was on call at the emergency room<br />

in the hospital, and he said: “I have a<br />

baby here that really needs CPAP. Are<br />

you guys ready?” Dr. Oden and her team<br />

were excited to put their machine to the<br />

test, finally being able to use it to help the<br />

sick baby who had a low oxygen<br />

saturation and whose eyes<br />

were rolled up in her<br />

head. After putting<br />

the baby on CPAP,<br />

the baby became<br />

alert within the<br />

hour; she was<br />

able to nurse<br />

and breathe<br />

comfortably.<br />

Dr. Oden could<br />

see the impact<br />

this design had<br />

on its users: “I<br />

felt directly the<br />

work was impacting<br />

this baby’s life.” But<br />

she also realized the<br />

impact of her guidance and<br />

mentorship. She saw greegone<br />

of the student designers of the CPAP,<br />

who had taken a job with the Rice<br />

bioengineering team that ran the clinical<br />

trial, watch her device save a baby. For Dr.<br />


Change<br />

r Neonatal Care<br />

by Pujita Munnagi<br />

Oden, “the product of [her] work is the<br />

baby that was saved but also this former<br />

student who had a growth experience and<br />

is capable of doing many amazing things<br />

beyond that. And we’ve seen her do that<br />

now. So for me, that one moment was just<br />

unbelievable.”<br />

that’s really our focus<br />

now - how do you<br />

implement an entire<br />

neonatal nursery? what<br />

we’re trying to do is<br />

create that same kind<br />

of neonatal intensive<br />

care unit, but that is<br />

appropriate for the<br />

world’s poorest places<br />

The Pumani CPAP project is one of several<br />

completed by the Rice 360° Global Health<br />

program. In her time in the program, Dr.<br />

Oden has worked with colleagues and<br />

students to fulfill most needs of neonates<br />

and infants. Even though the CPAP<br />

machine will<br />

help premature<br />

infants breathe,<br />

they cannot survive<br />

without right amount of<br />

heat, the right fluids, or the<br />

right nutrition. Since they are<br />

prone to so many issues, they need<br />

a comprehensive care unit that addresses<br />

all of their needs. According to Dr. Oden,<br />

“That’s really our focus now - how do you<br />

implement an entire neonatal nursery?<br />

What we’re trying to do is create that same<br />

kind of neonatal intensive care unit, but<br />

that is appropriate for the world’s poorest<br />

places.”<br />

For Dr. Oden, a big part of her work is<br />

collaborating with colleagues of different<br />

disciplines and cultures and making sure<br />

engineers use their skills to help the<br />

world at-large. Dr. Oden hopes the future<br />

also involves creating neonatal intensive<br />

care units (also known as NEST systems)<br />

and implementing them in hospitals all<br />

around the world. If successful, at least<br />

half a million lives a year would be saved,<br />

according to Dr. Oden. Another future<br />

area of focus is maternal health: care<br />

throughout pregnancy, gestation, and the<br />

delivery period. In the words of Dr. Oden,<br />

such care is critical because “if the babies<br />

have a safer delivery and birth, they’re<br />

more<br />

likely<br />

to survive.<br />

And if the<br />

mom has a safer<br />

delivery, she’s more likely<br />

to survive to be able to raise that baby<br />

well.” In addition to creating NEST systems<br />

and teaching students how to solve<br />

problems that impact global health, she<br />

enjoys knowing the students she instructs<br />

will go on to have influences in several<br />

ways. According to her, it’s about enabling<br />

engineers to ensure that they can and<br />

should make a difference.<br />

Works Cited<br />

[1] Denny FW, Loda FA. Acute respiratory infections are<br />

the leading cause of death in children in developing<br />

countries. The American Journal of Tropical Medicine<br />

and Hygeine 1986, 35, 1-2. https://www.ncbi.nlm.nih.gov/<br />

pubmed/3946732 (accessed November 15, 2017).<br />

[2] Rice 360° Institute for Global Health. bCPAP<br />

Continuous Positive Airway Pressure. http://www.rice360.<br />

rice.edu/bcpap (accessed November 15, 2017).<br />

Design By Madeleine Tadros<br />

Edited By Deepu Karri<br />

infant<br />

tubing port<br />

water<br />

bottle<br />

total flow<br />

meter<br />

O2 flow<br />

o2 inlet<br />

meter<br />

port CATALYST | 23

Mitochondrial Health<br />



B<br />

eginning in the late 1980s, health<br />

disorders and genetic diseases have<br />

become increasingly attributed to the<br />

mitochondria. Current research projects<br />

use model organisms to understand the<br />

implications of mitochondrial health on the<br />

whole organism. Some of the most fruitful<br />

research has been performed using the<br />

model organism Caenorhabditis elegans, or<br />

C. elegans. C. elegans is a type of nematode<br />

(roundworm) that is only 1 millimeter in<br />

length. Most viewers peer into a microscope<br />

of these nematodes and see modest, squirmy<br />

lines. Dr. Natasha Kirienko peers into the<br />

microscope and sees limitless potential for<br />

discovery. In an attempt to redefine disease<br />

treatment at a global level, Dr. Kirienko<br />

studies mitochondria surveillance pathways<br />

and their implications on genetics and cancer<br />

medicine.<br />

Dr. Kirienko was brought to Rice University<br />

by a $2 million grant from the Cancer<br />

Prevention Research Institute of Texas<br />

(CPRIT). As an undergraduate and graduate<br />

student in Russia, Dr. Kirienko didn’t have<br />

the opportunities or equipment to pursue<br />

the research she was interested in. Coming<br />

to America, however, she found herself with<br />

access to advanced lab equipment and a<br />

relatively enormous stipend—compared<br />

to her maximum stipend of $12/month in<br />

Russia—with which she could do whatever<br />

she wanted. “Suddenly, the sky is your limit,”<br />

she declared, as a sure smile reached her<br />

eyes. “I didn’t need any encouragement to<br />

work hard.” Dr. Kirienko’s mindset has been<br />

infectious, as it has definitely motivated<br />

Elissa Tjahjono, a graduate student currently<br />

working in the Kirienko Lab. Dr. Kirienko<br />

elaborates on how “hardworking and<br />

motivated” Ms. Tjahjono was during her<br />

studies and how her determination has led<br />

her into graduate school, allowing her “to do<br />

substantial amount of work in a year or so.”<br />

Ms. Tjahjono was the first author of a recent,<br />

monumental paper in Dr. Kirienko’s lab on a<br />

mitochondrial surveillance pathway important<br />

in the pathogenesis of Pseudomonas<br />

aeruginosa, a bacteria that affects cell iron<br />

availability and causes organism death. 1<br />

Dr. Kirienko’s fascination with the<br />

mitochondria began in graduate school.<br />

She had read about a particular gene motif,<br />

or a distinct sequence of DNA, called the<br />

Ethanol Stress Response Element (ESRE).<br />

This motif had been identified by different<br />

scientists seven different times, and it was<br />

shown to be upregulated (expressed more<br />

as a gene) by ethanol-induced heat shock<br />

(heat shock occurs when a cell is subjected<br />

to a higher temperature than ideal). 1 During<br />

Mitochondrial<br />

diseases have<br />

now become<br />

the number<br />

one genetic<br />

disorder<br />

her PhD studies, Dr. Kirienko discovered an<br />

anomaly: a genetic mutant that was actually<br />

supposed to reduce expression of the ESRE<br />

gene instead caused upregulation. Further,<br />

she found that the mutant was sensitive<br />

to not just one , but multiple stressors. So,<br />

“there was this puzzle [relating to ESRE]<br />

that [involved] multiple conditions that<br />

were different from each other.” She began<br />

asking the questions: what is the underlying<br />

mechanism? What triggers ESRE activation?<br />

This led into her postdoctoral studies, during<br />

which she researched interactions between<br />

C. elegans and its accompanying pathogen,<br />

Pseudomonas aeruginosa. During that time,<br />

Dr. Kirienko and her colleagues found a<br />

siderophore (iron carrier) called pyoverdine,<br />

produced by P. aeruginosa, kills C. elegans by<br />

causing severe mitochondrial damage. Almost<br />

all living organisms require iron for their<br />

survival, but it is difficult to acquire iron from<br />

the environment. Animals have complicated<br />

immune systems that limit the ability of<br />

pathogens to acquire iron during infection. 2<br />

Pyoverdine has evolved to surmount this<br />

difficulty, and it is capable of getting inside<br />

of host cells, taking away iron, and bringing<br />

it back to bacteria. Pyoverdine, she found,<br />

can remove up to a third of iron (III), which<br />

is about 20-25% of iron within the host. This<br />

results in organismal death. 1<br />

How are the two distinct concepts of ESRE<br />

and pyoverdine related, one may ask? At Rice,<br />

Dr. Kirienko found that the ESRE pathway<br />

was also upregulated after exposure to<br />

pyoverdine, leading her to understand that<br />

pyoverdine exposure and heat shock are<br />

two very different stressors. It also led her<br />

to draw the connection between ESRE and<br />

mitochondrial damage. ESRE is upregulated<br />

in mutants that are affected by a variety of<br />

stressors. Pyoverdine is a direct stressor<br />

that upregulates ESRE in the mitochondria.<br />

According to the two previous statements,<br />

there must be some kind of association<br />

between ESRE and mitochondrial damage.<br />

With this juncture acting both as a conclusion<br />

and a foundation, the Kirienko lab took the<br />

next step. They used small molecule drugs<br />

such as rotenone and antimycin (known<br />

mitochondrial poisons) to test the possibility<br />

of the effects of ESRE on mitochondrial<br />

damage. After much experimentation in the<br />

lab, they “were able to link this presence of<br />

[ESRE] in the promoter of effector genes of<br />

mitochondrial damage.”<br />

Now, the Kirienko lab is working on<br />

understanding how pyoverdine is produced<br />

in bacteria. Testing for drugs that may inhibit<br />

this pyoverdine factor, the lab recently<br />

found small molecules that can prevent<br />

pyoverdine synthesis or function. The tests<br />

are on a path to success, and a collaborator is<br />


currently testing the drugs in mice. Beyond<br />

these projects, Dr. Kirienko has a broad<br />

vision for the future implications of her<br />

lab’s work. One of those is developing<br />

future medicine for patients with cystic<br />

fibrosis, a disease tied deeply to excessive<br />

inflammation influenced by pyoverdine<br />

presence. 3 Another goal to understand how<br />

to “leverage mitochondrial dysfunction<br />

[in] cancer.” Dr. Kirienko knows that<br />

cancers, in general, tend to accumulate<br />

lots of mutations, and the mutation rate in<br />

mitochondria is noticeably higher, due to<br />

less checkpoint mechanisms. This means<br />

that mitochondria become dysfunctional<br />

much faster than, for example, nuclear<br />

DNA. 4 Accordingly, the lab was able to<br />

identify a subset of cancer cells that are<br />

most sensitive to mitochondria-damaging<br />

chemotherapeutics. They are now using<br />

C. elegans to find exactly which mutations<br />

cause the sensitivity. If this research<br />

succeeds, then the lab “will be able to<br />

get a step closer to personalized cancer<br />

medicine.”<br />

“Mitochondrial diseases [have] now<br />

[become the] number one genetic<br />

disorder,” Dr. Kirienko states.<br />

Mitochondrial diseases have a variety<br />

of phenotypes, spanning from subtle<br />

muscle fatigue to complete nonfunctional<br />

muscles and neurons. The severity, she<br />

hypothesizes, depends on how pathways<br />

mitigate mitochondrial damage. If these<br />

pathways, like the ESRE pathway, are<br />

performing well, then patients with<br />

affected mitochondria can have a much<br />

better healthspan, she extrapolates.<br />

Thus, if her lab can find the “members<br />

of the pathway,” they can find drugs that<br />

work with molecules activated within<br />

dysfunctional mitochondria. “Being able<br />

to transfer that to human health is a big<br />

thing,” she commented. The Kirienko<br />

lab is in the process of finding specific<br />

transcription factors that bind to ESRE.<br />

They carry the hope of developing future<br />

medicine that will specifically target<br />

mitochondrial-related cancers.<br />

Works Cited<br />

[1] Tjahjono E., Kirienko NV. PLoS Genetics. 2017, 6,<br />

http://journals.plos.org/plosgenetics/<br />

article?id=10.1371/journal.pgen.1006876 (accessed Jan.<br />

28, <strong>2018</strong>).<br />

[2] Our Need for Iron. http://www.irondisorders.org/<br />

our-need-for-iron/ (accessed February 20, <strong>2018</strong>), Iron<br />

Disorders Institute.<br />

[3] National Cancer Institute Dictionary of Cancer Terms.<br />

https://www.cancer.gov/publications/<br />

dictionaries/cancer-terms (accessed January 28, <strong>2018</strong>),<br />

National Institutes of Health.<br />

[4] All About Mitochondria. http://www.lhsc.on.ca/<br />

Patients_Families_Visitors/Genetics/<br />

Inherited_Metabolic/Mitochondria/ (accessed February<br />

20, <strong>2018</strong>), London Health Sciences Centre.<br />

E<br />

E<br />

E<br />

ESRE<br />

GFP<br />

3XESRE::GFP<br />

The ESRE motif is activated by<br />

mitochondrial damage. Sequence<br />

of the Ethanol and Stress<br />

Response Element (top).<br />

Activation of ESRE-controlled GFP<br />

expression after exposure to a<br />

mitochondria-damaging drug<br />

rotenone (bottom).<br />

Images by Photoroylaty at Freepik<br />

Design By J. Riley Holmes<br />

Edited By Kalia Pannell<br />


The Wateworks<br />


by Andrew Mu<br />

W<br />

ater is the most abundant natural<br />

resource on Earth , yet clean drinking<br />

water remains inaccessible for almost<br />

one billion people across the globe. 1 This is<br />

because drinking water requires the right<br />

infrastructure, which isn’t always available.<br />

Refugee camps, small islands, and developing<br />

countries are just a few examples of settings<br />

where obtaining clean water is a daily struggle.<br />

Though improving water accessibility is a<br />

hefty task, Dr. Qilin Li, a professor of civil<br />

and environmental engineering, chemical<br />

and biomolecular engineering, and materials<br />

science and nanoengineering at Rice<br />

University isn’t one to shy away from the<br />

challenge. Dr. Li and her team are addressing<br />

issues regarding water accessibility by<br />

developing technologies that harness the<br />

power of the sun to purify water.<br />

One in nine people worldwide do not have<br />

access to clean, safe drinking water, and<br />

these people are closer to home than you<br />

would imagine. 2 Some residents along the<br />

Texas-Mexico border, for example, don’t<br />

have access to municipal water, or any easily<br />

obtained source of water for that matter.<br />

Locals obtain their water from a large tank<br />

that must be transported in and treated onsite<br />

to ensure safety. This water treatment<br />

system is inconvenient. More established<br />

water treatment sites, as present in municipal<br />

water sources, experience a different problem<br />

called biological fouling, a phenomenon in<br />

which bacteria grow on and damage the<br />

membranes that are used to filter water. Li<br />

explains, “This is a very big problem in water<br />

treatment. So, for example, a big seawater<br />

desalination plant in Tampa Bay, Florida was<br />

built many years ago, but when it was built<br />

and designed, they did not consider fouling<br />

of this membrane material. Eventually fouling<br />

got completely out of control so they had to<br />

shut down and completely redesign the plant.”<br />

The lack of portable water treatments systems<br />

and fouling-resistant membrane materials can<br />

make treating water prohibitively expensive.<br />

According to Dr. Li, “We can treat any water,<br />

it's not [an] exaggeration, any water, to<br />

drinking water quality, but ultimately the<br />

problem is the cost.” Dr. Li seeks to provide<br />

clean water to all, utilizing nanophotonicsenabled<br />

solar membrane distillation and<br />

biological fouling-resistant membranes.<br />

Nanophotonics-solar membrane distillation<br />

is a solar desalination technology in which<br />

the energy in a solar cell is used to heat<br />

water into vapor. As sunlight hits the solar<br />

cell, a photothermal process converts photon<br />

energy into heat, which is then concentrated<br />

and used to boil salty, impure water. The<br />

resultant water vapor is then transported<br />

through a thin, porous membrane. Salts and<br />

other contaminants cannot pass through and<br />

are left on one side of the membrane, while<br />

on the other side, the vapor condenses into<br />

pure water. 1 Dr. Li explains that this water<br />

purification method is advantageous because<br />

you can “easily scale it up, and it's modular,<br />

so by adding more solar cells you can enlarge<br />

the capacity of the plant.” This is the first<br />

approach to solar distillation that is scalable,<br />

which makes it suitable for communities in offgrid<br />

locations and allows for greatly reduced<br />

One in nine people<br />

worldwide do not have<br />

access to clean, safe<br />

drinking water, and these<br />

people are closer to home<br />

than you would imagine.<br />

energy costs in desalination. 1 In addition,<br />

because this technology is so portable, it can<br />

be used in military applications. According to<br />

Dr. Li, a surprisingly large number of military<br />

fatalities are the result of transporting water<br />

to the frontlines of a battlefield, so a portable<br />

water purification system could save lives. “In<br />

the past what they used is reverse osmosis,<br />

but then they have to carry heavy pumps and<br />

big batteries. With this, hopefully all they need<br />

to do is unfold the membrane and put it under<br />

the sun and produce clean water wherever<br />

you have any source of water,” Dr. Li explains.<br />

While solar distillation is intended for<br />

communities and military applications,<br />

biological fouling-resistant membranes are<br />

targeted for large water treatment plants.<br />

Dr. Li tackles biological fouling by creating<br />

membranes in which nanoparticles have<br />

been embedded. These nanoparticles contain<br />

antimicrobials that are slowly released and<br />

interfere with biofilm formation. Once the<br />

chemicals are depleted, nanoparticles can<br />

be easily reloaded onto the membrane. 3 Dr.<br />

Li believes that approaching the problem<br />

with slow release mechanisms will present<br />

a longer term control strategy compared to<br />

previous methods. By using fouling-resistant<br />

membranes, large amounts of money and<br />

energy can be saved that would have been<br />

spent pre-treating the water to prevent this<br />

fouling. The development of these foulingresistant<br />

membranes would have a huge<br />

impact on industrial water treatment. This is<br />

particularly significant for Houston because<br />

of the applications of fouling-resistant<br />

membranes to the oil and gas industry. When<br />

drilling for oil and gas, large amounts of<br />

wastewater are produced, which are normally<br />

injected back into the ground. With more<br />

efficient large-scale water treatment, this<br />

wastewater can be repurposed to address<br />

water shortages and supply irrigation systems<br />

in agriculture.<br />

Currently, Dr. Li is working to disseminate<br />

the solar purification and fouling-resistant<br />

membrane technologies developed in<br />

her laboratory. NEWT, the Nanosystems<br />

Engineering Research Center for<br />

Nanotechnology-Enabled Water Treatment, at<br />

Rice is teaming up with industry partners to<br />

commercialize water purification technologies.<br />

One such partner, Localized Water Solutions<br />

Inc., is a company based in Austin committed<br />

to reducing water shortages by building<br />

smarter water systems and has licensed<br />

solar membrane distillation for emergency<br />

response and military applications. Dr. Li<br />

is also part of a startup company called<br />

SOLMEM, which is looking to apply the<br />

technologies to bigger markets--seawater<br />

desalination and industrial wastewater<br />

treatment in the form of zero liquid discharge,<br />

a wastewater management strategy that<br />

eliminates liquid waste, for example. By<br />

studying and applying novel water treatment<br />

technologies, Dr. Li hopes to create a<br />

sustainable water supply for those in need.<br />


[1] Dongare, P. T. et al. Proc. Natl. Acad. Sci. U.S.A. 2017, 114,<br />

6936-6941.<br />

[2] The Water Project. https://thewaterproject.org/waterscarcity/water_stats<br />

(accessed Nov. 9, 2017)<br />

[3] Wu, J. et al. J. Membr. Sci. 2017, 531, 68-76<br />

DESIGN BY Juliana Wang<br />

EDITED BY Albert Truong<br />



By Oliver Zhou<br />

I<br />

magine slowly losing your memory,<br />

motivation, and communication skills—the<br />

things that make you who you are. These<br />

are just a few of the effects of Alzheimer’s<br />

disease, and occur over the course of only a<br />

few years. When someone has Alzheimer’s,<br />

amyloid beta proteins, which are products<br />

of a normal protein recycling process in<br />

their brain, improperly join together to form<br />

long strands called fibrils. 1 Even though the<br />

individual protein monomers are harmless,<br />

these fibrils can then stick together to<br />

become toxic plaques that inhibit neuron<br />

function and cause cell death, thus leading<br />

to the debilitating effects of Alzheimer’s<br />

on the brain. 1 Although the molecular<br />

mechanisms of Alzheimer’s are understood,<br />

the causes of these microscopic failures<br />

are unclear, and no treatment to stop or<br />

reverse its progression currently exists. In<br />

addition, there are no definitive practices<br />

or measures to significantly decrease risk<br />

of developing Alzheimer’s. 2,3 As Alzheimer’s<br />

patients deteriorate over the course of several<br />

years, supportive and palliative care are the<br />

only means of assistance, leading to higher<br />

and higher costs of patient care. Altogether,<br />

Alzheimer’s disease is one of the most costly<br />

and serious diseases 4 that plagues the world<br />

today.<br />

Enter Dr. Angel Martí. An inorganic chemist<br />

from Puerto Rico, Dr. Martí has spent his<br />

whole life dreaming of being a scientist.<br />

Dr. Martí began his career studying the<br />

photophysical properties of metal complexes<br />

at the University of Puerto Rico. In 2004,<br />

he joined a research group at Columbia<br />

University, where he contributed to the<br />

development of fluorescent probes formed<br />

from metal complexes for detection of DNA<br />

and RNA. In 2008, he joined Rice University’s<br />

Department of Chemistry, where he now<br />

combines his past knowledge of metal<br />

complexes and biological proteins for use<br />

in the area of neurodegenerative diseases.<br />

This combination of the building blocks of<br />

inorganic chemistry with the fundamentally<br />

biological issues of proteins and diseases<br />

is what makes his research exciting. As Dr.<br />

Martí put it, since “people don’t tend to study<br />

amyloid beta through the eyes of an inorganic<br />

chemist…being an inorganic chemist allows<br />

me to bring something new to the table,<br />

and that something new is the use of metal<br />

complexes.”<br />

Metal complexes have special photophysical<br />

properties that allow Dr. Martí to study the<br />

amyloid beta buildup of Alzheimer’s in new<br />

ways. A metal complex is essentially a metal<br />

atom, such as iron, or ruthenium, or rhenium,<br />

surrounded by and bound to organic<br />

molecules—a “hybrid of organic and inorganic<br />

materials,” as Dr. Martí describes. An earlier<br />

project of his involved the use of ruthenium<br />

metal complexes, which would increase in<br />

fluorescence over 100 fold when bound to<br />

amyloid beta aggregates. This complex is<br />

useful in the detection and assessment of the<br />

extent of amyloid beta protein aggregation<br />

in the brain, and with its higher visibility and<br />

long lifetime, it holds numerous advantages<br />

over the more commonly used indicator,<br />

thioflavin T.<br />

Ruthenium metal complexes have many great<br />

uses, but Dr. Martí discovered something<br />

even greater. “[When] we changed that<br />

metal [in the metal complex] to rhenium”,<br />

Being an inorganic<br />

chemist allows me<br />

to bring something<br />

new to the table, and<br />

that something new<br />

is the use of metal<br />

complexes<br />

Dr. Martí describes, “very strange and<br />

wonderful things started happening.” Once<br />

irradiated with blue light, rather than merely<br />

fluorescing, the rhenium metal complex<br />

could actually oxidize the parts of the<br />

amyloid beta aggregate that it bound to.<br />

This new discovery is called footprinting,<br />

and it can reveal exactly where hydrophobic<br />

compounds like the rhenium metal complex<br />

bind, making it easier to engineer drugs to<br />

bind to those sites and combat Alzheimer’s.<br />

However, this is not all the rhenium metal<br />

complex can do. When binding to the large<br />

amyloid beta aggregates, the oxidizing effects<br />

of the metal complex were insignificant for<br />

purposes other than simply signaling where<br />

they could bind. However, when bound to the<br />

harmless, monomeric form of amyloid beta,<br />

the oxidation can significantly change their<br />

individual shapes. This is enough to prevent<br />

them from forming fibrils and aggregating<br />

altogether. If there were some way to<br />

preemptively insert and activate this rhenium<br />

metal complex in the brain before symptoms<br />

of Alzheimer’s began to show, the amyloid<br />

Using Light-Activated Metal<br />

Complexes to Combat<br />

Alzheimer’s<br />

beta monomers would never begin to<br />

aggregate at all. This technique could lead to<br />

a potential “vaccine” to prevent Alzheimer’s.<br />

This Alzheimer’s vaccine is the end goal of<br />

Dr. Martí’s research, but there are still many<br />

challenges that the lab faces. Currently, the<br />

only way to activate the metal complexes<br />

after they bind to amyloid beta is by<br />

irradiating them with blue light. This would be<br />

impossible in a human, since our tissues are<br />

not transparent to blue light, only red. Think<br />

about what happens when you shine a light<br />

through your hand—the light appears red. If<br />

the rhenium metal complex could be altered<br />

in a way so that it could be activated by red<br />

light, it would allow for potential use inside<br />

humans. Another challenge is ensuring that<br />

the rhenium metal complexes are not toxic<br />

to humans. This also brings up the question<br />

of how the rhenium metal complexes would<br />

make it to the brain. Most drugs are delivered<br />

via the bloodstream, and the brain is<br />

separated from the blood by a highly selective<br />

blood-brain barrier. Currently, the metal<br />

complex would not be able to get through<br />

this membrane to the brain.<br />

Despite these challenges, Dr. Martí’s research<br />

presents a beacon of hope in the fight against<br />

Alzheimer’s. Knowledge of the binding sites of<br />

hydrophobic substances on the amyloid beta<br />

aggregates is critical in design of future drugs<br />

that may be able to neutralize or disintegrate<br />

them. And if a rhenium metal complex that<br />

can absorb red light and make it into the<br />

brain could be synthesized, the progression<br />

of Alzheimer’s could be stopped or even<br />

prevented altogether.<br />


[1] What Happens to the Brain in Alzheimer’s Disease? National<br />

Institute on Aging [Online], May 16, 2017. https://www.<br />

nia.nih.gov/health/what-happens-brain-alzheimers-disease<br />

(accessed Dec 16, 2017).<br />

[2] More research needed on ways to prevent Alzheimer’s,<br />

panel finds. National Institute on Aging [Online], June 15,<br />

2010. https://www.nia.nih.gov/news/more-research-neededways-prevent-alzheimers-panel-finds<br />

(accessed Jan 7, <strong>2018</strong>).<br />

[3] Alzheimer’s & Dementia Prevention and Risk. Alzheimer’s<br />

Association Research Center [Online]. https://www.alz.<br />

org/research/science/alzheimers_prevention_and_risk.asp<br />

(accessed Jan 7, <strong>2018</strong>).<br />

[4] Latest Alzheimer’s Facts and Figures. Alzheimer’s Association<br />

[Online]. https://www.alz.org/facts/ (accessed Jan 7,<br />

<strong>2018</strong>).<br />

Image from freepik.com<br />

DESIGN BY Sara Ho<br />

EDITED BY Roma Nayyar<br />




by amna ali<br />

H<br />

eart failure. Congenital heart defects. Each<br />

year, both of these diseases take millions<br />

of lives, yet much remains to be learned<br />

about their mechanism and their treatment.<br />

According to the Center for Disease Control<br />

and Prevention (CDC), 6.5 million Americans<br />

have heart failure, a condition in which the<br />

patient’s heart cannot effectively pump blood<br />

throughout the body, and the number of<br />

individuals with heart failure will increase<br />

by 46 percent by the year 2030. 1 In addition,<br />

among people who develop heart failure, half<br />

of them die within five years of the diagnosis. 1<br />

This can be attributed to both an aging<br />

population and the rise of risk factors such as<br />

hypertension, disease, and diabetes. 2 Though<br />

congenital heart defects do not affect nearly<br />

as many individuals as heart failure, they still<br />

pose problems in terms of treatment cost and<br />

infant mortality, especially in underdeveloped<br />

countries. 3 As of 2017, the average cost to<br />

treat a congenital heart defect from infancy<br />

to age 21 is anywhere between $47,500<br />

and $73,600, which is an astronomical cost<br />

in many healthcare settings. 3 In addition,<br />

hospitalizations for these adult patients<br />

have doubled over the past 20 years, with<br />

congenital heart surgery accounting for nearly<br />

20% of these admissions. 4 Although both<br />

heart failure and congenital heart defects have<br />

definitely become more manageable, we have<br />

yet to identify a process through which we can<br />

control these diseases from developing in the<br />

first place.<br />

Dr. Jun Wang, a principal investigator at the<br />

Texas Heart Institute, seeks to discover the<br />

underlying cause behind cardiovascular<br />

abnormalities. His research team is<br />

currently “investigating the mechanisms of<br />

congenital heart defects and heart failure…<br />

[by] examining how cardiomyocyte survival<br />

and death is controlled.” Cardiomyocytes, or<br />

heart cells, undergo cell death when there is a<br />

defect which causes excess production of the<br />

apoptosis-inducing factor (AIF), a protein that<br />

sits in the cell and waits for a “death” signal<br />





28 | CATALYST<br />

from the nucleus. 5 In a typical heart cell, the<br />

nucleus releases this “death” signal when the<br />

cell is somehow injured or too old. 5 Once the<br />

AIF receives this signal, it causes the DNA of<br />

the cell to condense and fragment in order to<br />

prepare for apoptosis, or cell death. 5 In the<br />

heart cells of an individual with heart failure,<br />

too much of the “death” signal is released,<br />

causing a release of too much AIF, leading<br />

to excessive and unnecessary cell death.<br />

Fortunately, certain modification processes<br />

can be used to control levels of AIF.<br />

Dr. Wang’s research team is specifically<br />

examining how a process known as sumo<br />

conjugation, a modification process in which<br />

a small protein known as sumo is attached<br />

and detached from other proteins in the cell,<br />

can regulate AIF. Through sumo conjugation,<br />

various processes in the cell, including the<br />

processes that control cell death, can be<br />

turned on and off. Dr. Wang is exploring how<br />

sumo conjugation can be used to regulate the<br />

production of AIF in the cells of a person with<br />

heart failure. As heart failure involves random<br />

apoptosis of cardiomyocytes, understanding<br />

the signaling process associated with cell<br />

death and its regulation is crucial step in<br />

curing heart failure. Heart failure, however, is<br />

not the only disease that could be potentially<br />

managed through sumo conjugation.<br />

Dr. Wang’s team is also researching how<br />

the processes associated with congenital<br />

heart defects can be regulated via sumo<br />

conjugation. Congenital heart defects,<br />

problems in the structure of the heart at<br />

birth, often involve cells that have either<br />

grown too much or too little. This results<br />

in defects, such as holes in the separating<br />

wall between two chambers when the cells<br />

don’t grow enough, or a heart valve that is<br />

too small when the cells grow too much.<br />

Congenital heart defects originate in the<br />

fetus, where stem cells that have not yet<br />

decided what specific type of organ or tissue<br />

they are going to become undergo a process<br />

known as the hippo pathway, a type of sumo<br />

conjugation. If the hippo pathway is turned<br />

on, the stem cells stop growing; if the hippo<br />

pathway is turned off, the stem cells continue<br />

to differentiate into heart cells. 6 Dr. Wang’s<br />





research team is attempting to determine<br />

precisely which genes are responsible for<br />

controlling the on and off switch of the hippo<br />

pathway. This process is tested by “knocking<br />

out”, or making ineffective, certain genes in<br />

stem cells and determining the effects of<br />

the knock out on the hippo pathway.6 Thus<br />

far, in its preliminary research, Dr. Wang’s

stem cells<br />

no further growth<br />

further differentiation<br />



research team has found that a gene known<br />

as ari3b that may play a crucial role in the<br />

hippo pathway; cells with ari3b “knocked<br />

out” stopped differentiating. In other words,<br />

although further research is required, Dr.<br />

Wang’s research team has possibly found a<br />

way to control incorrect or excessive heart cell<br />

growth that contributes to congenital heart<br />

defects, a potentially crucial step towards<br />

being able to end the disease once and for all.<br />

Dr. Wang hopes that with further research<br />

about sumo conjugation and the hippo<br />

pathway, his work will one day help other<br />

researchers better understand cardiomyocyte<br />

death in heart failure and random<br />

uncontrolled growth in congenital heart<br />

disease. By understanding the mechanisms<br />

that cause these diseases with further<br />

research, Dr. Wang states, rather than treating<br />

the symptoms through surgeries, transplants,<br />

and drugs, we are on the path to possibly<br />

find a cure to the diseases that have afflicted<br />

humanity since the beginning of time.<br />


[1] Thacker, C; Del Barto, J. Latest statistics show heart failure<br />

on the rise; cardiovascular diseases remain leading killer.<br />

American Heart Association, Jan. 26, 2017. http://newsroom.<br />

heart.org/news/latest-statistics-show-heart-failure-on-therise;-cardiovascular-diseases-remain-leading-killer<br />

(accessed<br />

Nov. 3, 2017).<br />

[2] Heart Failure to Increase by Nearly 40 Percent in Next<br />

15 Years. American Heart Association News, Sept. 29 2015.<br />

https://news.heart.org/heart-failure-numbers-to-increase-bynearly-40-percent-in-next-15-years/<br />

(accessed Jan. 8, <strong>2018</strong>).<br />

[3] Congenital Heart Defects (CHD): Data and Statistics.<br />

Division of Birth Defects and Developmental Disabilities,<br />

Center for Disease Control and Prevention, Jan. 8, <strong>2018</strong>.<br />

https://www.cdc.gov/ncbddd/heartdefects/data.html<br />

(accessed Feb. 7, <strong>2018</strong>).<br />

[4] Dmyterko, Kaitlyn. Circ: Pediatric congenital heart surgery<br />

costs more than adult surgery. Cardiovascular Business, Oct.<br />

4, 2011. http://www.cardiovascularbusiness.com/topics/<br />

healthcare-economics/circ-pediatric-congenital-heart-surgerycosts-more-adult-surgery<br />

(accessed Feb. 8, <strong>2018</strong>).<br />

[5] Cande, C; Vahsen, N; Garrido, C; Kroemer, G. Cell Death<br />

and Differentiation. 2004, 11, 591-595.<br />

[6] Yu, F; Guan, K. Cold Spring Harbor Laboratory Press.<br />

[online] 2013, 27, 355-371. http://genesdev.cshlp.org/<br />

content/27/4/355. (accessed November 2017).<br />

Icon from pngtree<br />

DESIGN BY Evelyn Syau<br />

EDITED BY Roma Nayyar<br />


1. Dr. Wang’s favorite procedure to conduct in the lab is injecting of genes, proteins,<br />

or viruses with green fluorescent protein (GFP), which has a fluorescent emission<br />

wavelength in the green region of the visible light spectrum. This means that when the<br />

GFP is exposed to certain wavelengths of light, it will turn a bright green color.<br />

Watching the specimen “light up like stars in the night sky, all under the microscope” is<br />

beautiful, Dr. Wang says.<br />

2. GFP has existed in jellyfish for millions of years, but it has very recently begun to<br />

be used in research labs. Dr. Wang uses GFP to tag “knock out” genes in his samples<br />

so that he can determine which samples can be used in his study.<br />


songbirds,<br />

the exciting<br />

new field of neurogenesis<br />

aging & autism<br />

by Christine Tang<br />

F<br />

or a long time, scientists believed that<br />

humans are born with all the neurons<br />

that they will ever have, and that these<br />

neurons can only die. However, scientific<br />

evidence from the 1960s started to show<br />

that neurogenesis, the production of<br />

neurons from neural stem cells, occurs in a<br />

portion of the brain called the<br />

hippocampus, which is the<br />

center of learning and<br />

memory in the brain.<br />

Though this finding<br />

was received<br />

with skepticism<br />

in the scientific<br />

community,<br />

it was further<br />

confirmed when<br />

researchers found<br />

in the 1980s that<br />

adult songbirds<br />

produced new neurons<br />

when they learned new<br />

today, we know that<br />

each of the two human<br />

hippocampi makes about<br />

700 new neurons each<br />

day<br />

songs. 1 Today, we know that each of the two<br />

human hippocampi makes about 700 new<br />

neurons each day. 2<br />

Neurogenesis is the process by which new<br />

neurons form from primary neural stem<br />

cells (NSCs) in the brain. 3-4 This process starts<br />

very early in development in the womb, but<br />

also occurs in the hippocampus throughout<br />

the lifetime. However, neurogenesis is much<br />

more prominent in a young brain than in an<br />

older brain, and a decrease in neurogenesis<br />

is associated with memory decline and<br />

mood changes. Dr. Mirjana Maletic-Savatic,<br />

an assistant professor and child neurologist<br />

at Baylor College of Medicine and Texas<br />

Children’s Hospital, is investigating this<br />

process of neurogenesis in the hopes of<br />

making the old hippocampus young, so that<br />

older people will still be able to learn and<br />

remember at the same capacity of a young<br />

child. Development of new neurons is not<br />

a simple process, and involves a series of<br />

events called the neurogenesis cascade.<br />

In the subventricular zone (SVZ) of the<br />

hippocampus, a NSC divides into a daughter<br />

cell. Then, the daughter cell produces many<br />

clones, which each have three fates: they<br />

can divide more, differentiate, or die. Dying<br />

neurons are part of a natural process<br />

called pruning, which is the reason<br />

why adults have fewer neurons<br />

than infants do. The cells that are<br />

stimulated to differentiate will<br />

gradually progress into immature<br />

and then mature neurons,<br />

which are integrated into the<br />

hippocampus.<br />

The mother NSC does not die,<br />

but it does have a big limitation. It<br />

can only divide into daughter cells<br />

a few times, which means that the<br />

amount of daughter cells that can originate<br />

from one primary NSC is limited.5 After<br />

dividing several times, the primary<br />

NSC transforms itself into an<br />

astrocyte, which is a type of<br />

glial cell (non-neuronal cell)<br />

that cannot differentiate<br />

into new neurons. Even<br />

though daughter cells can<br />

reproduce, the high death<br />

rate of differentiated cells<br />

and immature neurons<br />

limits the production of new<br />

mature neurons. Therefore,<br />

during aging, there is a decrease<br />

in the number of stem cells, a<br />

decrease in the number of newborn<br />

neurons, and an increase of astrocyte<br />

density in the hippocampus. These factors<br />

contribute to cognitive decline and diseases<br />

as we age. Dr. Fatih Semerci, a postdoctoral<br />

student in her lab, and Dr. Maletic-Savatic<br />

identified a gene called Lunatic fringe that is<br />

a selective marker of NSCs. 6 Lunatic fringe<br />

mediates Notch signaling, which allows for<br />

communication between the mother and<br />

daughter cells and is involved in quiescence<br />

(dormancy) and differentiation of NSCs. This<br />

is a unique mechanism in which progeny<br />

of NSCs can send feedback signals to the<br />

mother NSC to modify its fate. Therefore,<br />

Lunatic fringe is a control step; it allows NSCs<br />

to decide when to divide or stop, as NSCs<br />

can only divide a limited amount of times. In<br />

addition, Dr. Maletic-Savatic and Dr. Semerci<br />

developed a new mouse model with the<br />

Lunatic fringe gene that traces the lineage of<br />

NSCs. 2,6 This allows for future experiments<br />

that investigate other unknown mechanisms<br />

of NSC differentiation or effects of knockout<br />

genes on neuron development and mouse<br />

behavior and cognition.<br />

Research in<br />

neurogenesis could<br />

lead to potential<br />

therapies for many<br />

neurological patterns<br />

or disorders<br />

In addition, Dr. Maletic-Savatic has found<br />

that epilepsy and impaired neurogenesis are<br />

linked. In a joint study with Dr. Juan<br />

Manuel Encinas, she injected<br />

kainic acid, a neuroexcitatory<br />

amino acid,<br />

into the dentate gyrus<br />

of the hippocampus.<br />

They discovered<br />

that high doses of<br />

kainic acid resulted<br />

in neural excitability<br />

and terminal NSC<br />

differentiation into<br />

reactive astrocytes, 7<br />

which are cells that<br />

respond to pathological<br />

conditions such as stroke and<br />

epilepsy. 8 Unfortunately, this results in two<br />

major problems: the NSC population will<br />

decrease over time and reactive astrocytes<br />

can increase inflammation, form scar tissue<br />

and disrupt synaptic connectivity. 9-10 At this<br />


Critical periods of<br />

survival:<br />

Main<br />

(1-4 days)<br />

Secondary<br />

(1-3 weeks)<br />

Stem cells<br />

Neurons<br />

NSCs ANPs Early NBs NBs Immature<br />

neuron<br />

Granule<br />

cell<br />

Learning<br />

Memory<br />

Mood<br />

Granule<br />

Cell Layer<br />

Subgranular<br />

Zone<br />

Apoptotic cells<br />


Images of neural stem cells (NSCs)<br />

differentiating into neurons. NSCs are vital for<br />

learning, memory and mood.<br />

Microglia<br />

Early<br />

Late<br />


The neurogenic cascade, which shows the differentiation of neural stem<br />

cells (NSCs) into amplifying neural progenitor cells (ANPs) and eventually,<br />

into immature neurons and granule cells. Throughout differentiation and<br />

proliferation, cells die by a process called apoptosis and microglia clean up<br />

the dead cells.<br />

time, findings highlight new mechanisms<br />

that may contribute to epilepsy but<br />

do not propose new therapies. In the<br />

future, researchers plan to prevent<br />

epileptic activation of NSC conversion<br />

into reactive astrocytes to stop rapid<br />

depopulation of NSCs.<br />

Dr. Maletic-Savatic is also interested in<br />

early neuronal development and sees<br />

prematurely born babies and autistic<br />

children at a clinic. Neurogenesis in<br />

early periods of life can modulate the<br />

ability to learn, and she is focused on<br />

developing an integrative approach<br />

to the study of early developmental<br />

disorders, such as autism. Behavioral<br />

features of autism include repetitive<br />

thinking and the inability to accept<br />

new environments. Autistic children<br />

like routine and have trouble in new<br />

environments or with new objects in<br />

their environment. Newborn neurons<br />

are involved in pattern separation,<br />

which is a process that helps people<br />

distinguish new and old objects in their<br />

environment. Pattern separation may be<br />

disrupted in autistic children; perhaps<br />

their hippocampal neurogenesis has<br />

something to do with this disruption.<br />

This is important because autism is not<br />

diagnosed until about 2-3 years old, so<br />

an earlier intervention is critical because<br />

the human brain has the most plasticity<br />

in the first two years of life. Dr. Maletic-<br />

Savatic is trying to do that by developing<br />

a image-based model of autism that<br />

could help diagnose autism earlier<br />

through mapping different parts of the<br />

brain using various techniques such<br />

as magnetic resonance imaging (MRI)<br />

and magnetic resonance spectroscopy<br />

(MRS). 11-12<br />

Neurogenesis is a hot field right now<br />

because it is a potential target for new<br />

therapies and drugs. Research in the field<br />

could lead to potential therapies for many<br />

neurological patterns or disorders, such as<br />

age-related cognitive decline, epilepsy and<br />

autism. These projects are interdisciplinary<br />

and often involve collaborations around<br />

the world. In the future, Dr. Maletic-Savatic<br />

hopes to improve human neurological<br />

function and health by elucidating other<br />

mechanisms that are involved with Lunatic<br />

fringe and Notch signaling as well as<br />

epileptic and autistic processes that affect<br />

NSC differentiation.<br />

Works Cited<br />

[1] Blakeslee, S. A Decade of Discovery Yields a Shock<br />

About the Brain. The New York Times, Jan. 4, 2000. http://<br />

www.nytimes.com/2000/01/04/science/a-decade-ofdiscovery-yields-a-shock-about-the-brain.html<br />

(accessed<br />

Dec. 1, 2017).<br />

[2] Gutierrez, G. Lunatic Fringe gene plays key role in<br />

renewable brain. Baylor College of Medicine [Online], July<br />

19, 2017. https://www.bcm.edu/news/brain/lunatic-fringegene-brain-renewal<br />

(accessed Dec. 1, 2017).<br />

[3] Gage, F. H. Science. 2000, 287, 1433-1438.<br />

[4] Altman, J.; Das, G.D. J. Com. Neurol. 1965, 124, 319-335.<br />

[5] Encinas, J. M. et al. Cell Stem Cell. 2011, 8, 566-579.<br />

[6] Semerci, F. et al. Elife. [Online] 2017, 6. https://<br />

elifesciences.org/articles/24660<br />

[7] Sierra, A. et al. Cell Stem Cell. 2015, 16, 488-503.<br />

[8] Haim, L. B. et al. Front Cell Neurosci. 2015, 9, 278.<br />

[9] Gutierrez, G. Neural stem cells massively turn into<br />

astrocytes in a model of epilepsy. Baylor College of<br />

Medicine [Online], May 7, 2015. https://www.bcm.edu/<br />

news/neuroscience/stem-cells-massively-astrocytesepilepsy<br />

(accessed Dec. 1, 2017).<br />

[10] Sofroniew, M. V. Trends Neurosci. 2009, 32, 638-647.<br />

[11] Ward, A. Solving the mystery of autism. The Houston<br />

Chronicle, Apr. 29, 2013. http://www.chron.com/news/<br />

health/article/Solving-the-mystery-of-autism-4456952.php<br />

(accessed Dec. 1, 2017).<br />

[12] Nace, M. Autism Researchers at Texas Hospital Hunt<br />

For Autism’s Roots. BioNews Texas, Apr. 24, 2013. https://<br />

bionews-tx.com/news/2013/04/24/autism-researchersat-texas-hospital-hunt-for-autisms-roots/<br />

(accessed Dec.<br />

1, 2017).<br />

Designed by NamTip Phongmekhin<br />

EDITED BY Roma Nyaar<br />



D<br />

espite the Middle East’s abundance<br />

of black gold, it severely lacks<br />

two other resources needed for<br />

stable socioeconomic development.<br />

The limited supplies of and increasing<br />

demands on each of these vital, highly<br />

interdependent resources- food, water,<br />

and energy- is a main point of tension for<br />

countries in this region. In fact, increased<br />

desertification and loss of fertile land,<br />

water scarcity, and climate variability<br />

are all cited by United Nations<br />

Environmental Programme as<br />

having been precursors for<br />

past conflict (specifically in<br />

Darfur, Sudan).¹ Balancing<br />

the demands on these<br />

resources is key to<br />

achieving regional<br />

stability. Looking<br />

specifically at water<br />

stress in the Middle<br />

East, an analytical<br />

lens that can be used<br />

to understand the<br />

challenges in alleviating<br />

this stress and achieving water<br />

security is the Food-Energy-Water (FEW)<br />

Nexus. This FEW nexus can help us break<br />

down the relationship and involvement<br />

of food and energy production on water<br />

security, which (defined by UN-Water)<br />

is the ability to secure enough water--<br />

and the right quality of water-- needed<br />

for sustaining our well-being and<br />

development.²<br />

Mr. Gabriel Collins, J.D., a Baker Botts<br />

Fellow in Energy & Environmental<br />

Regulatory Affairs at the James A. Baker<br />

III Institute for Public Policy, is currently<br />

exploring the environmental, legal, and<br />

economic implications of the FEW Nexus.<br />

His work is primarily water-related and<br />

energy-related, and one of his recent<br />

32 | CATALYST<br />

WATER<br />








publications, titled “Carbohydrates, H2O,<br />

and Hydrocarbons: Grain Supply Security<br />

and the Food-Water-Energy Nexus<br />

in the Arabian Gulf Region”, builds a<br />

comprehensive review of the interactions<br />

between each component of the nexus and<br />

ultimately offers policy recommendations<br />

to maximize resource security.<br />

One aspect of the nexus that Mr. Collin’s<br />

explores in his paper is the fundamental<br />

interaction between water usage and food<br />

production: “[w]ater-thirsty staple food<br />

grains must be irrigated in the region’s<br />

arid climate”.³ Saudi Arabia, one<br />

country Mr. Collins discusses in<br />

his paper, had a challenging time<br />

meeting both the hydrological<br />

and agricultural demands<br />

of its growing population<br />

and “between 1980 and<br />

1999 alone, Saudi Arabian<br />

farms consumed more than<br />

300 billion cubic meters of<br />

water—most of which came<br />

from deep aquifers that do<br />

not recharge—and spent tens of<br />

billions of dollars in a failed attempt<br />

to cultivate wheat on an industrial scale<br />

in its harsh desert climate”.⁴ In fact, the<br />

high economic and environmental costs<br />

of this process were so steep, that Saudi<br />

Arabia completely abandoned wheat<br />

production in 2016, and instead turned to<br />

relying solely on imports.⁵ This situation<br />

of unequal supply and demand is not<br />

unique to Saudi Arabia. As the Middle East<br />

is an arid region, lacking in rainfall, fertile<br />

soil, and adequate humidity,⁶ many of the<br />

countries here face similar challenges in<br />

meeting the food and water demands of<br />

their growing populations.<br />

Another country that is facing a similar<br />

challenge in balancing demands for<br />

food and water is Iran. However, unlike<br />

“<br />

Saudi, Iran is choosing to remain with<br />

their mindset of self-sufficiency and has<br />

reinvigorated efforts to increase domestic<br />

crop production. This encouragement<br />

of domestic wheat production by the<br />

government is concerning because Iran’s<br />

groundwater depletion rate heralds the<br />

possibility that their aquifers (their primary<br />

water source for agriculture) will be<br />

depleted in the next 50 years.⁷ However,<br />

Iran is currently going through severe<br />

water scarcities and droughts that may<br />

have an irreversible impact on current and<br />

future water availability, which Mr. Collins<br />

explains in an apt analogy⁸:<br />





























TURKEY<br />

SYRIA<br />

IRAQ<br />

IRAN<br />

EGYPT<br />


Another major barrier to achieving water<br />

security is meeting growing energy<br />

demands. The Middle East’s wealth comes<br />

from it’s disproportionate abundance of<br />

petroleum and natural gas; however, its<br />

high investments in energy production<br />

and exportation have severe implications<br />

on water usage. In Saudi Arabia, “energy<br />

production accounts for the second largest<br />

use of water behind agriculture and is<br />

expected to continue rising over the next<br />

15-20 years.”⁹<br />

The connection between water and energy<br />

perhaps isn’t as straightforward as that<br />

between water and food. Water is used in<br />

the generation of electricity, the extraction<br />

and processing of fossil fuels, and in the<br />

production of biofuel.¹⁰ And, energy is<br />

used in water extraction, desalination, and<br />

transportation. From this interdependence<br />

stems the difficulty in separating the<br />

impact of the usage of one resource on<br />

the availability of the other; this difficulty<br />

makes it harder to develop deliberate<br />

and sustainable practices that maximize<br />

effective resource allocation.<br />

Mr. Collins also introduces methods<br />

that can be used to increase resource<br />

security and facilitate the development<br />

of sustainable practices. He discusses<br />

the benefits of more solar and nuclear<br />

powered infrastructure, especially for small<br />

farmers and communities who aren’t using<br />

established power grids. Particularly for<br />

this subgroup of energy consumers, Mr.<br />

Collins believes that there is a lot of merit<br />

in solar-powered groundwater pumping<br />

infrastructure to put in wells. And using<br />

nuclear power, rather than fossil fuels, also<br />

has the added benefit of freeing up gas for<br />

other uses, such as desalination.¹¹<br />

However, questions regarding effective<br />

allocation of resources cannot be<br />

answered easily, and of course there are<br />

differing viewpoints as to what the most<br />

“effective” practice for each country is.<br />

But placing resource conservation at the<br />

forefront of the region’s environmental,<br />

economic, and sociopolitical agendas will<br />

help spark serious efforts to think about<br />

the importance of water security and<br />

sustainability.<br />

Going forward, Mr. Collins plans to<br />

continue to research the FEW nexus in<br />

Sub-Saharan Africa and South America.<br />

The main purpose of his research is to help<br />

introduce sound environmental, economic,<br />

and legal analysis to policy makers to<br />

aid them in creating stronger policies.<br />

His vision is that he and researchers like<br />

him will be able to offer nonpartisan<br />

policy recommendations to policymakers<br />

in the US and abroad.¹² The potential<br />

implications of being able to fully analyze<br />

each component of the nexus will be to<br />

create specific policies that will encourage<br />

the use of clean energy, promote effective<br />

economic/trade policies, and allow each<br />

country to take advantage of the resources<br />

they have while still making sure that<br />

future demand for those resources will be<br />

met.<br />


[1] Pedraza, L.E.; and Heinrich, M. Water Scarcity:<br />

Cooperation or Conflict in the Middle East and North<br />

Africa? Foreign Policy Journal. Sept. 2 2016. https://www.<br />

foreignpolicyjournal.com/2016/09/02/water-scarcitycooperation-or-conflict-in-the-middle-east-and-northafrica/<br />

(accessed Feb. 17 <strong>2018</strong>).<br />

[2] What is Water Security? Infographic. UN Water<br />

[Online]. May 8 2013. http://www.unwater.org/<br />

publications/water-security-infographic/ (accessed Feb.<br />

17 <strong>2018</strong>).<br />

[3] Collins, G. Carbohydrates, H2O, and Hydrocarbons:<br />

Grain Supply Security, and the Food-Water-Energy<br />

Nexus in the Arabian Gulf Region. Center for Energy<br />

Studies, Baker Institute. June 2017. https://www.<br />

bakerinstitute.org/media/files/files/96136d13/CES-pub-<br />

QLC_Nexus-061317.pdf (accessed Feb. 17 <strong>2018</strong>).<br />

[4] Ibid.<br />

[5] Ibid.<br />

[6] Ibid.<br />

[7] Senguptajan, S. Warming, Water Crisis, Then Unrest:<br />

How Iran Fits an Alarming Pattern. The New York Times<br />

[Online], Jan. 18 <strong>2018</strong>.<br />

[8] Interview with Mr. Gabriel Collins.<br />

https://www.nytimes.com/<strong>2018</strong>/01/18/climate/water-iran.<br />

html (accessed Feb. 17 <strong>2018</strong>).<br />

[9] Rambo, K.A. et al. Water-Energy Nexus in Saudi Arabia.<br />

Energy Procedia. 2016, 105, 3837- 3843<br />

[10] World Energy Outlook; International Energy Agency,<br />

2012. Ch. 17. http://www.worldenergyoutlook.org/<br />

media/weowebsite/2012/WEO_2012_Water_Excerpt.pdf<br />

(accessed Feb. 17 <strong>2018</strong>).<br />

[11] Interview with Mr. Gabriel Collins.<br />

[12] Ibid.<br />

DESIGN BY Jessica Lee<br />

EDITED BY Pujita Munnangi<br />


methods of<br />



rR<br />

and population control<br />

o w a i s f a z a l<br />


A variety of mosquito vector surveillance<br />

and control programs have been instituted<br />

over the past few decades with the intention<br />

of limiting the spread of infectious diseases<br />

such as dengue, malaria, and the Zika virus.<br />

With the major public health threat of<br />

mosquito populations spanning across the<br />

globe, it is imperative that we continue to<br />

develop effective methods of controlling the<br />

mosquito population as well as designing<br />

and implementing novel solutions on an<br />

international scale. While these programs<br />

have displayed varying degrees of success, this<br />

review analyzes various methods that seem<br />

to be effective in combating vector incidence<br />

and prevalence within endemic populations<br />

worldwide. Specifically, we will analyze vector<br />

control initiatives involving Aedes albopictus<br />

populations in Yorke Island off the coast of<br />

Australia as well as the control of Anopheles<br />

gambiae populations in Brazil in order to<br />

determine trends in effective mosquito vector<br />

control systems.<br />


A particularly successful mosquito vector<br />

surveillance program was implemented in<br />

the recent Yorke island mosquito control<br />

initiative. Consistently low densities of Aedes<br />

albopictus populations have been recorded<br />

six years following the program’s inception in<br />

2005. Following the success of the program,<br />

project leaders have claimed that the use<br />

of insecticides appeared to be the most<br />

important component of their intervention<br />

program, with inspection cycles and public<br />

outreach also playing key roles in limiting<br />

the prevalence of the endemic mosquito<br />

population. 1<br />


Successful vector surveillance programs<br />

rely heavily on the utilization of a process<br />

known as source reduction. 2 Source reduction<br />

essentially involves the systematic removal of<br />

potential mosquito breeding sites, effectively<br />

diminishing the growth rates of endemic<br />

mosquito populations significantly. This<br />

process was heavily used in Yorke Island, as<br />

any containers that could potentially hold<br />

water and support larval development were<br />

removed, destroyed, placed under cover,<br />

34 | CATALYST<br />

or treated with pellets or briquettes of the<br />

insect growth regulator s-methoprene.<br />

The s-methoprene was applied to smaller<br />

containers in the form of 15g pellets at a rate<br />

of one pellet per liter of estimated container<br />

volume. Larger containers, such as rainwater<br />

tanks and wells, were treated with ProLink<br />

XR Briquets applied at one briquet per<br />

5000 liters of water. 3 Containers that could<br />

not be removed had their interior surfaces<br />

also sprayed with the residual pyrethroid<br />

bifenthrin to kill adult mosquitoes that came<br />

in contact with them. 4 Samples of larvae were<br />

collected from infested containers for species<br />

identification on a weekly basis in order to help<br />

monitor the efficacy of the insecticide usage.<br />

Thus, the larval habitats of the local Aedes<br />

mosquito species were totally decimated in<br />

the region and mosquito vector populations<br />

declined by as much as 98% according to<br />

recent estimates in 2016. 5<br />

5<br />

Our increasingly<br />

interconnected global<br />

climate is highly vulnerable<br />

to infectious disease<br />

pandemics spread through<br />

vectors such as mosquitoes,<br />

and we must continue<br />

to refine our mosquito<br />

population control methods<br />

to combat this threat.<br />


Furthermore, it is also imperative to have<br />

reliable methods of approximating the number<br />

of vectors within specific regions of a target<br />

area. In order to address this issue, the Yorke<br />

Island initiative enlisted the support of local<br />

public health officials in order to conduct active<br />

surveillance of target areas and to obtain an<br />

accurate count of mosquito prevalence in<br />

select regions of the island. 6 For each round of<br />

surveillance, larval densities were expressed as<br />

number of positive containers per 100 houses<br />

for the Aedes albopictus species. Moreover,<br />

local populations in vector endemic regions<br />

were surveyed at regular intervals in order to<br />

corroborate results of any other independent,<br />

ongoing vector density studies. 7 All in all, the<br />

teams conducted sweep-net sampling on a<br />

total of 230 different sites, providing data<br />

on precise locations as well as population<br />

densities of vector groups throughout the<br />

vector endemic regions. 8<br />



One of the most crucial qualities of a<br />

successful mosquito vector surveillance and<br />

control program is to be able to monitor<br />

changes in mosquito vector populations<br />

in response to the usage of specific vector<br />

control tactics. 9 In conjunction with the above<br />

methods, being able to accurately examine<br />

vector trends over the period of time that a<br />

vector control program is in place is key. A<br />

strategy used by Yorke island public health<br />

officials that combines monitoring with some<br />

of the more direct methods of combating<br />

vector populations is the cordon sanitaire<br />

strategy, which is an integrated approach<br />

composed of harborage spraying, source<br />

reduction, insecticide treatment of containers,<br />

lethal tire piles, mosquito population<br />

monitoring and public awareness campaigns<br />

supported by local authorities and local<br />

media. 10<br />

BRAZIL<br />

The eradication of the accidentally introduced<br />

Anopheles gambiae mosquito species<br />

from 54,000 km 2 of largely ideal habitat in<br />

northeast Brazil is regarded as one of the<br />

most effective mosquito control campaigns<br />

in scientific history. 11 This successful program<br />

was implemented in the 1930s and early<br />

1940s through an integrated program that<br />

relied overwhelmingly upon larval control<br />

mechanisms. In the decades following the<br />

implementation of the program, similar<br />

initiatives utilized comparable strategies<br />

in order to successfully combat vector<br />

populations in Egypt as well as rural Zambia. 12<br />


The total coverage of the A. gambiae mosquito<br />

population was achieved primarily through<br />

the combination of large numbers of field<br />

workers with strictly enforced task-allocation<br />

and supervision systems. Each individual field<br />

worker, known as a larval inspector, was given<br />

a fixed area in which to identify and treat<br />

potential breeding sites and for which he or

she alone was responsible. 13 All inspectors<br />

were allocated a reasonable area that was<br />

carefully mapped and both the inspectors and<br />

the mosquito populations they faced were<br />

monitored regularly. One key method utilized<br />

during this process involved the use two<br />

flags to mark where the inspectors had left<br />

the road and where they was located at any<br />

time. 14 The campaign was designed to tackle<br />

A. gambiae according to its ecological niche.<br />

A. gambiae prefers sunlit and relatively small<br />

bodies of water as larval habitats and these<br />

had to be identified and monitored rigorously<br />

throughout the countryside. 15<br />



The core foundation underlying the success<br />

of the Brazilian vector control program was in<br />

the clearly defined and organized nature of its<br />

activities. A cartographic unit was immediately<br />

set up and the infested area was mapped<br />

using aerial photographs. 16 A common<br />

laboratory and epidemiological division<br />

allowed centralised training, surveillance,<br />

and decision-making. Adulticide and<br />

medicinal measures were similarly organized,<br />

in which researchers and local officials<br />

clearly emphasized a central administrative<br />

structure. 15<br />

The work of inspectors in their allocated zones<br />

was also closely scrutinized and managed by<br />

district chief inspectors who were typically<br />

allocated only five zones for which they were<br />

held individually responsible. The zones<br />

and districts were further aggregated and<br />

managed through administrative units termed<br />

posts and divisions, both of which were<br />

headed by medical doctors who could deal<br />

with the clinical aspects of the program in<br />

addition to vector control. 18 A system of flags<br />

and on-site field documentation ensured that<br />

each inspector was monitored on an almost<br />

hourly basis and could be held unambiguously<br />

accountable for any lapses. 19 Notably, the<br />

activities of the anti-larval and anti-adult<br />

control teams were separately reported at<br />

district level so that discrepancies could be<br />

identified, and separate adult capture squads<br />

conducted independent evaluations of all<br />

vector-control activities by knockdown catches<br />

in houses on a monthly basis. 20<br />


Thus, we were able to analyze some of<br />

defining characteristics of successful mosquito<br />

vector control programs in diverse ecological<br />

settings based off the coast of Australia in<br />

Yorke Island as well as in Brazil. Key themes<br />

that were observed across both programs<br />

included a heavy reliance on local public<br />

health officials and epidemiologists to obtain<br />

key information regarding the locations<br />

and prevalence of target mosquito vector<br />

populations as well as the employment of<br />

insecticides to decimate these mosquito<br />

populations once locations were precisely<br />

determined. Modern mosquito control<br />

programs based in Sub-Saharan Africa and<br />

the Middle East have also expanded upon<br />

several of the techniques mentioned in this<br />

article to increase the efficacy and efficiency of<br />

these programs. 4 Ultimately, our increasingly<br />

interconnected global climate is highly<br />

vulnerable to infectious disease pandemics<br />

spread through vectors such as mosquitoes,<br />

and we must continue to refine our mosquito<br />

population control methods to combat this<br />

threat.<br />


[1.] Worobey J, Fonseca DM, Espinosa C, Healy S, Gaugler R. J<br />

Am Mosq Control Assoc. 2013; 29(1): 78–80.<br />

[2.] Muzari MO, Devine G, Davis J, Crunkhorn B, van den Hurk<br />

A, Whelan P PLOS Negl Trop Dis. 2017; 11(2); 433-9<br />

[3.] Nelder M, Kesavaraju B, Farajollahi A, Healy S, Unlu I,<br />

Crepeau T, et al. Am J Trop Med Hyg. 2010 ;82(5):831–7.<br />

[4.] Benedict MQ, Levine RS, Hawley WA, Lounibos LP. Vector<br />

Borne Zoonotic Dis. 2007;7(1):76–85.<br />

[5.] Kuno G. J Med Entomol. 2012; 49(6):1163–76.<br />

[6.] Lounibos LP, O'Meara GF, Juliano SA, Nishimura N, Escher<br />

RL, Reiskind MH, et al. Ann Entomol Soc Am. 2010;103(5):757–<br />

70.<br />

[7.] Sun D, Williges E, Unlu I, Healy S, Williams GM, Obenauer<br />

P, et al. J Am Mosq Control Assoc. 2014; 30(2): 99–105.<br />

[8.] Ritchie SA, Moore P, Morven C, Williams C. J Am Mosq<br />

Control Assoc. 2006; 22(3): 358–65.<br />

[9.] Rueda LM. Zootaxa. 2004; 589: 1–60.<br />

[10.] Nguyen HT, Whelan PI, Shortus MS, Jacups SP. J Am Mosq<br />

Control Assoc. 2009;25(1):74–82.<br />

[11.] Killeen, G. F., Fillinger, U., Kiche, I., Gouagna, L. C., &<br />

Knols, B. G. The Lancet infect. dis. 2002; 2(10), 618-627.<br />

[12.] Garrett-Jones, C. Nature. 1964; 204: 1173–1175<br />

[13.] Spielman, A, Pollack, RJ, Kiswewski, AE, and Telford III, SR.<br />

Vector Borne Zoonotic Dis. 2001; 1: 3–19<br />

[14.] Guyatt, HL, Gotink, MH, Ochola, SA, and Snow, RW. Trop<br />

Aedes albopictus<br />

Yorke Island<br />

Anopheles gambiae<br />

Brazil<br />

Med Int Health. 2002; 7: 1–12<br />

[15.] Guyatt, HL, Corlett, SK, Robinson, TP, Ochola, SA, and<br />

Snow, RW. Trop Med Int Health. 2002; 7: 298–303<br />

[16.] Molyneux, DH, Floyd, K, Barnish, G, and Fevre, EM.<br />

Parasitol Today. 1999; 15: 238–240<br />

[17.] Buckling, AG, Taylor, LH, Carlton, JM, and Read, AF. Proc<br />

R Soc Lond B Biol Sci. 1997; 264: 553–559<br />

[18.] Shiff, C. Clin Microbiol Rev. 2002; 15: 278–298<br />

[19.] Gimnig, JE, Ombok, M, Otieno, S, Kaufman, MG, Vulule,<br />

JM, and Walker, ED. J Med Entomol. 2002; 39: 162–172<br />

[20.] Charlwood, JD and Edoh, D. J Med Entomol. 1996; 33:<br />

202–204<br />

Fonts from GoogleFonts and DaFont.com<br />

Images from Wikimedia Commons and<br />

Clipground<br />

DESIGN BY Sahana Prabhu<br />

EDITED BY Rishab Ramapriyan<br />


the emergence of NUMBER<br />


from a geometric investigation<br />


Taking any regular even-sided polygon, one<br />

can make cross-cuts from each vertex and<br />

connect it to the midpoint of one of the<br />

opposite sides to create a smaller regular<br />

polygon contained within the original. The<br />

ratio between the area of this new polygon<br />

and the original has been shown to have<br />

some interesting values, specifically 1/5 for<br />

squares and 1/13 for hexagons. Building<br />

on this, a general formula that gives the<br />

ratio for an arbitrary regular polygon can<br />

be found. In this paper, we will explore<br />

how to generalize this result even further<br />

by allowing the crosscuts to connect to any<br />

side of the polygon, rather than just to the<br />

opposite side. We then explore the rationality<br />

of this expression, and discover interesting<br />

connections to number theoretic techniques<br />

looking into the relationship between<br />

Chebyshev Polynomials and the minimal<br />

polynomials of cosine.<br />


Recent results have shown that there is an<br />

interesting relationship between the area of a<br />

regular polygon and the area of the polygon<br />

formed through<br />

crosscuts.<br />

Essentially, a<br />

second regular<br />

polygon is<br />

created from<br />

the first by<br />

connecting<br />

each vertex to<br />

the midpoint<br />

of the opposite side. Because even-sided<br />

polygons have two sides that can be opposite<br />

to any vertex, this implies that one side<br />

should be chosen and that direction should<br />

be repeated for every other vertex (See<br />

Figure 1). The area ratio has been calculated<br />

explicitly for squares and hexagons, and were<br />

found to be 1/5 and 1/13, respectively. 1,5,6<br />

In addition, for an odd-sided polygon, the<br />

crosscuts will connect in the center, so that<br />

the ratio will always be 0. After these specific<br />

results, the next question is whether a<br />

generalized formula can be found that agrees<br />

with these, as well as gives ratios for a regular<br />

polygon with an arbitrary number of sides. It<br />

is also important to explore the rationality of<br />

this function, as it is rational ratios that have<br />

motivated this research.<br />

Fig. 1: The crosscut formation of regular polygons when n=3, 4, 6.<br />


The following are some necessary formulas<br />

that will be used later in the paper. The first<br />

is a simplified expression for the ratio of the<br />

areas, which gives R=a S2<br />

/a B2<br />

,where a S<br />

is the<br />

apothem of the smaller polygon, and<br />

a B<br />

is for the original polygon. The<br />

second is an explicit formula that<br />

gives the ratio in terms of only the<br />

number of sides of the polygons: R n<br />

=<br />

1/(1+4cot 2 (θ)) , where θ=π/n. This is<br />

the starting point for this paper, as<br />

this result will be generalized using<br />

similar methods as those used in the<br />

proof of R n<br />

.<br />


We want this new generalization to<br />

allow our crosscut to be connected<br />

to an arbitrary side of the polygon,<br />

instead of requiring that it connect to the side<br />

opposite of the vertex where it started. This<br />

new formula should give the area ratio only in<br />

terms of the number of sides of the polygon,<br />

n, and the number of vertices skipped<br />

before connecting the crosscut, denoted k.<br />

To do this, we first define a coordinate axis<br />

system that is<br />

suitable for our<br />

calculations. This<br />

coordinate axis<br />

can be created<br />

by placing one<br />

vertex and the<br />

center of the<br />

polygon on the<br />

line y=C that<br />

runs parallel to the x-axis. Then, the crosscut<br />

originating from this vertex would create an<br />

angle with this line. Connecting the other<br />

endpoint of the crosscut to the center of the<br />

polygon forms a triangle that has one known<br />

angle, ψ=2πk/n+(1/2)(2π/n)=(π(2k+1))/n, at<br />

the center. (We assume in this proof that<br />

0< ψ≤π, but we will later show that this<br />

formula actually holds for all values of ψ.) In<br />

addition to this known angle, two of the sides<br />

are known, as one, a B<br />

, is the apothem and<br />

another, r, is the radius of the polygon. This<br />

setup is detailed in Figure 2.<br />

As only one angle in this triangle is known, it<br />

is easiest to form two right triangles, so that<br />

known trigonometric formulas more readily<br />

apply. This is accomplished by taking a line<br />

By Jacob Kesten<br />

from E to E’, where is connects to the line<br />

y=Cat a right angle. In Figure 2, this new line<br />

is denoted b. Now using trigonometry, it is<br />

possible to find the slope of the crosscut by<br />

calculating the lengths of b and c. This gives<br />

Fig. 2: A diagram depicting the two triangles used to compute the slope<br />

of the specific crosscut. The first picture shows placement of the triangle<br />

on the polygon and coordinate axes. The second shows how the 2 right<br />

triangles were formed, and the third shows how this can be used to<br />

compute the length of the smaller apothem.<br />

the slope of the crosscut as m=(–a B<br />

sin(ψ))/<br />

(r–a B<br />

cos(ψ))=(–cos(θ)sin(ψ))/(1–cos(θ)cos(ψ)).<br />

Knowing the slope makes it possible to<br />

write an equation for the line containing<br />

the crosscut, as well as the equation of<br />

the line perpendicular to the crosscut that<br />

contains aS. These are given by y 1<br />

=mx+mr+C<br />

and y 2<br />

=–x/m+C, respectively. Finding the<br />

intersection of these two lines allows us to<br />

find a S<br />

2<br />

in terms of m and a B2<br />

. Dividing both<br />

sides by a B2<br />

, we get that a S2<br />

/a B<br />

2<br />

= R n,k<br />

= (m 4 +m 2 )/<br />

(cos 2 θ(1+m 2 ) 2 ) = (1–cos 2 (ψ))/(1–2cosψcos θ<br />

+cos 2 θ), where θ=π/n and ψ=(2k+1)θ. Notice<br />

that this formula depends only on n and k, as<br />

desired.<br />

We now check that this formula holds for<br />

values of π < ψ < 2π. This follows from the<br />

fact that for π < ψ < 2π, ψ=π+ψ’ where ψ‘ < π,<br />

and cosψ=cosψ’ so that the formula will be<br />

the same as the one for the corresponding<br />

complement angle. Essentially, the case<br />

where π < ψ < 2π reduces to a case where<br />

ψ≤π by looking at the angle going in the<br />

opposite direction of the obtuse angle. An<br />

example of this is given in Figure 3 using<br />

different crosscut octagons. Flipping the<br />

octagons on the bottom shows that they will<br />

be identical to the ones in the first row, so<br />

that they will produce identical ratios.<br />

Now that we have found the formula R n,k<br />

,we<br />

can check that it matches with the values<br />

already found for specific polygons. One such<br />

example is when the crosscuts connect to the<br />


opposite side of an odd-sided polygon, where<br />

the ratio should be 0. In this case, we have<br />

that k=(n–1)/2, so that we get the following<br />

result: R n,k<br />

= (1–cos 2 π)/(1–2cosπ cosθ+cos 2 θ)<br />

= 0/(1–2cosθ +cos 2 θ) = 0, as expected. In<br />

addition, using n=6 and k=2, we get that<br />

R 6,2<br />

=(1–cos 2 5π/6)/(1–2cos 5π/6 cos π/6 +cos 2<br />

π/6) = (1–(–√3/2) 2 )/(1–2(–√3/2)(–√3/2)+(–√3/2) 2 )<br />

= (1– 3/4)/(1+2(3/4)+3/4) = (1/4)/(1+3/2+3/4)<br />

= (1/4)/(13/4) = 1/13, which is exactly what<br />

Fig. 3: Octagon crosscuts using k=1,2,3,4,5,6. Comparing the<br />

2 lines shows that the octagons using k=1,2,3 are the same as<br />

those using k=4,5,6.<br />

was found in earlier papers. The other known<br />

results can also be checked using a similar<br />

method.<br />


Now we try to find which values of n and k<br />

will produce a rational value for R n,k<br />

. We can<br />

easily check different values of n and k and<br />

find that the following are rational: R n,0<br />

, R 4,1<br />

,<br />

R 6,2<br />

, R 6,1<br />

, R 8,2<br />

, R n(odd),(n-1)/2<br />

. However, there are an<br />

infinite number of combinations for n and k,<br />

and there is no straightforward way to prove<br />

that these are or are not the only rational<br />

values of R n,k<br />

. One approach is to look at<br />

different values for the possible parts of the<br />

ratio that could be irrational. For example,<br />

when both cosθ and cosψ are rational, then<br />

R n,k<br />

is rational. This approach works for some<br />

combinations, but a problem arises when<br />

both cos 2 θ and cos 2 ψ are irrational, as there<br />

is no way to tell what will happen with R n,k<br />

.<br />

This is because both the sum and product<br />

of irrational numbers can be rational, thus<br />

even though all components of R n,k<br />

are<br />

irrational, the final output could still be a<br />

rational number. Because this is the majority<br />

of the values that will occur, an approach that<br />

directly applies to this case is needed.<br />

One possible approach is to look at the<br />

polynomial representation for R n,k<br />

and the<br />

minimal polynomials for cosθ. The minimal<br />

polynomial of the value cosθ is the smallest<br />

nonzero, monic polynomial with rational<br />

coefficients that has cosθ as a solution. For<br />

example, the minimal polynomial of √2 is<br />

x 2 –2=0. Note that this polynomial cannot<br />

be reduced, and thus it is the smallest<br />

polynomial with √2 as a solution. All algebraic<br />

numbers have a minimal polynomial, by<br />

definition, and thus for each value of n, cosθ<br />

has a minimal polynomial. 2<br />

First, we use R n,k<br />

to create a polynomial<br />

expression of one variable. Using the multiple<br />

angle formula, we know that cosψ=cos((2k+1)<br />

θ)=cos(sθ)=T s<br />

(cosθ) where T s<br />

(cosθ) is the<br />

s th Chebyshev Polynomial. For example,<br />

cos(4θ)=8cos 4 (θ)–8cos 2 (θ)+1because T 4<br />

(x)=8x 4 –<br />

8x 2 +1. 7 This allows us to express R n,k<br />

as an<br />

expression of θ: R n,k<br />

=(1–T s2<br />

(cosθ))/(1–2T s<br />

(cosθ)<br />

cos θ +cos 2 θ, where s=2k+1. Setting x=cosθ,<br />

and R n,k<br />

=r, where r is a rational value, we get<br />

the polynomial expression P(R n,k<br />

)=1-T s<br />

2(<br />

x) –<br />

r+2rxT s<br />

(x)–rx 2 =0.<br />

It is known that if a certain value solves a<br />

polynomial, then the minimal polynomial<br />

(minpoly) of that value has to be able to divide<br />

the larger polynomial, with a remainder of<br />

0. 4 Thus we want to see what happens when<br />

we use different combinations of n and k,<br />

and see if there is any way to find a pattern<br />

in the remainders of P(R n,k<br />

)/minpoly(cosθ).<br />

In this case, a random collection of values<br />

from within the bounds n≤100 and k1<br />

–1) ∏ ψ2 (x) for n even.<br />

d<br />

d|n, d>2<br />

where ψ n<br />

(x) is the minimal polynomial of<br />

cos(2π/n) multiplied by a constant and d|n<br />

means that d is a divisor of n, so that the<br />

product runs through all the divisors of n. 3<br />

Exploring this relationship in more detail is<br />

an important and rapidly expanding area<br />

of theoretical mathematics, and could be<br />

very helpful in creating a final proof of the<br />

rationality of Rn,k. In our exploration, we<br />

came across a need to understand more<br />

about the relationship between these two<br />

concepts and have seen how a simple<br />

question concerning area ratios can produce<br />

complicated mathematical questions that<br />

are still being explored purely for theory.<br />

This is just one application of the possible<br />

knowledge that can be gained by the abstract<br />

investigation of these two concepts and the<br />

inner workings of their natural connection.<br />

A special thanks to Dr. Zsolt Lengvarszky of<br />

the Louisiana State University, Shreveport,<br />

Mathematics Department for his help and<br />

mentorship in the project.<br />


[1] Ash, J.M., et al., Constructing a Quadrilateral Inside<br />

Another One, Mathematical Gazette, 2009, 528, 522–532.<br />

[2] Calcut, J.S., Rationality and the Tangent Function, http://<br />

www2.oberlin.edu/faculty/jcalcut/tanpap.pdf (accessed Feb.<br />

8, <strong>2018</strong>).<br />

[3] Gürtaş, Yusuf Z., Chebyshev Polynomials and the Minimal<br />

Polynomial of Cos(2/n), The American Mathematical Monthly,<br />

2017, 124, 74-78.<br />

[4] Leinster, T., Minimal Polynomial and Jordan Form, http://<br />

www.maths.ed.ac.uk/~tl/minimal.pdf (accessed Feb. 8, <strong>2018</strong>).<br />

[5] Mabry, R., Crosscut Convex Quadrilaterals, Math Mag,<br />

2011, 84, 16–25.<br />

[6] Mabry, R., One-Thirteenth of a Hexagon, n.d. 1-11.<br />

[7] Mason, J.C., Handscom, D.C., Chebyshev Polynomials;<br />

Chapman and Hall: Boca Raton, 2003; sec 1.2.1.<br />

DESIGN BY Kaitlyn Xiong<br />

EDITED BY Olivia Zhang<br />






Shaurey Vetsa, Richard I. Han, Don L. Gibbons, K. Jane Grande-Allen<br />

Department of Bioengineering, Rice University<br />


My research has sought to further<br />

characterize the effect of Dasatinib on the<br />

focal adhesion pathway in cancer cells.<br />

While plenty of research exists on how the<br />

cell propagates tumor growth, the results<br />

of this research show how tumor-matrix<br />

interactions drive tumor metastasis. To<br />

resemble the stress that the cell matrix<br />

would face in a lung, we placed the cells in a<br />

static tension environment and recorded the<br />

changes in spatial distribution of the cells in<br />

the presence of Dasatinib. It was found that<br />

Dasatinib induced clustering in cancer cells;<br />

however, further research is required to<br />

show causation rather than correlation of the<br />

clustering.<br />


Among all the cancers that afflict the<br />

American population, lung cancer is<br />

the second most widespread in men<br />

and women. 1 Afflicted lung cancer cells<br />

proliferate through a process called<br />

epithelial to mesenchymal transition (EMT).<br />

Although EMT for healthy cells is important<br />

for embryonic development and other vital<br />

organs, cancer cells become invasive after<br />

EMT. The cells lose cell to cell adhesion and<br />

increase the expression of mesenchymal<br />

cell markers such as vimentin, fibronectin,<br />

N-cadherin, and alpha-smooth muscle actin<br />

(α-SMA). These changes allow cancer cells to<br />

metastasize throughout the cell space. 2<br />

The extracellular matrix (ECM) plays a<br />

significant role in the occurrence of EMT. Two<br />

families of enzymes, microRNA-200 and ZEB1,<br />

regulate EMT using transcription factors.<br />

These families form a double-negative<br />

feedback loop in which ZEB1 activates a<br />

collagen-producing gene to increase collagen<br />

expression in the extracellular matrix.<br />

Another family of enzymes, LOX, creates<br />

greater organization of the collagen due to<br />

the increased expression of crosslinking.<br />

Less randomness in the structure of the ECM<br />

promotes metastasis as cancer cells can<br />

traverse the matrix more easily. 3<br />

The metastasis of cancer strongly depends<br />

not only on processes occurring in the cell,<br />

but also on the regulatory behavior between<br />

the cell and the extracellular matrix. The<br />

focal adhesion pathway is an important<br />

macromolecular assembly that transfers<br />

information from the extracellular matrix<br />

to the cell. Its inhibition can create changes<br />

in cell morphology and organization in lung<br />

cancer cells. The transduction of the focal<br />

adhesion pathway undergoes a secondary<br />

messenger amplification that contains the<br />

proto-oncogene tyrosine-protein kinase<br />

(SRC). Bristol-Myers Squibb Inc. developed an<br />

anti-cancer drug called Dasatinib that inhibits<br />

the SRC protein which controls important cell<br />

processes like movement, proliferation, and<br />

survival. 4<br />

We investigate Dasatinib’s effect on the cell<br />

focal adhesion pathway by incubating 344 SQ<br />

cancer cells with the drug and observing cell<br />

proliferation.<br />


The cancer cells that were analyzed are<br />

from a mouse model (metastatic 344 SQ<br />

cell line) donated by the Gibbons Lab at MD<br />

Anderson. 5 These cells have mutations in<br />

the Kras and p53 genes, both of which are<br />

tumor-suppressor genes.<br />

344 SQ cells were mixed with 2 mg/ml<br />

collagen MasterMix and incubated at a<br />

density of 106 cells per ml of solution. 2 ml<br />

aliquots of solution were poured in ten bone<br />

shaped hollow molds, two in each of the five<br />

trays. Prior to use, the trays were dessicated<br />

using an oven. Metal pins extending outward<br />

were inserted inside of the tray to stimulate<br />

static tension. The contraction of the cell mix<br />

caused the pins to be pulled inwards. Four<br />

sawbone cylinders were placed on each of<br />

the pins to increase the pin’s surface area to<br />

prevent the collagen gel mix from tearing on<br />

them during contraction. Media covered the<br />

gels with 50 mm Dasatinib in 200 µl of the<br />

RPMI.<br />

Confocal Imaging<br />

Each day for four days, two gels were<br />

removed from the collagen gel molds and<br />

immersed in 4% paraformaldehyde (PFA). Gel<br />

sections were cut and placed in this buffer to<br />

prevent photobleaching of the samples. Gels<br />

were stained with DAPI for the cell nuclei<br />

and Phalloidin for F-actin and were taken to<br />

confocal microscopy.<br />

Image Processing<br />

DAPI stained images were analyzed using<br />

ImageJ and Cell Profiler, image processing<br />

tools that cleaned for noise and conjoined<br />

looking cells. The end result was a binary<br />

mask, an image representing cells in white<br />

and everything else in black, of all the cells.<br />

The NND ImageJ plugin was then used to<br />

find the distance between the centroid of<br />

each cell and the nearest centroid to it. Cell<br />

Profiler additionally returned the x and y<br />

coordinates of the centroids and object<br />

numbers of the first and second closest cells<br />

to each cell object.<br />


Confocal Imaging<br />

DAPI and Phalloidin staining revealed that<br />

the cells cluster as time progresses (Figure 2).<br />

The panel shows the progression of image<br />

analysis that was undertaken to produce<br />

binary masks for the image analysis software<br />

(Figure 1).<br />

The first column shows an overlay of the<br />

DAPI and Phalloidin channels. The next<br />

column shows the DAPI channel extracted<br />

from the multichannel raw image. Column<br />

three has processed binary masks of the<br />


Figure 1: Panel of Image Processing: The boundaries of the nuclei are<br />

separated from the raw image to conduct NND testing. The scale bar is 50<br />

µm and is applicable for all images.<br />

Figure 2: Nearest Neighbor Distance for Cells treated with 50 nM Dasatinib<br />

over the course of four days. The green lines each indicate the median of<br />

the distribution of distances for one day (Day 1: 46.36 µm, Day 2: 31.77 µm,<br />

Day 3: 21.49 µm, and Day 4: 13.72 µm). The red horizontal lines indicate the<br />

interquartile ranges for each distribution. Two stars indicate a significance<br />

level of 0.01 and three stars indicate a significance level of 0.001.<br />

DAPI channel, and the last column has<br />

outlines of the binary masks in which each<br />

object is numbered for reference. This<br />

processing was conducted for all images in<br />

Day 1, 2, 3, and 4 sets. The general qualitative<br />

trend in DAPI from Day 1 to 4 is that there<br />

are more cells and more of them are<br />

clustered. Increased intensity in phalloidin<br />

staining from Day 1 to Day 4 shows actin<br />

expression increasing with time.<br />

Each object’s NND was calculated and plotted<br />

(Figure 2). Cell Profiler also returned NND<br />

calculations identical to ImageJ plugin’s data.<br />

The values for Day 1 have a statistically<br />

significant difference from those of Day 2,<br />

Day 3, and Day 4 (Figure 2). Day 2 and Day 4<br />

also had a statistically significant difference.<br />


Confocal Imaging<br />

Image processing results show that the cells<br />

appear clustered in response to Dasatinib.<br />

This is seen in the statistically significant drop<br />

in the mean NND over the course of the four<br />

days.<br />

There is a possibility that the clustered<br />

cells replicated in the same area. Dasatinib<br />

inhibits the focal adhesion pathway, which<br />

controls important processes such as actin<br />

polymerization and filopodia formation<br />

that are instrumental to the invasiveness of<br />

cancer cells. 4 Thus, the newly divided cells<br />

would have a diminished ability in moving.<br />

Even if Dasatinib does not cause old cells<br />

to migrate closer to each other, it may slow<br />

down cell movement that otherwise drives<br />

new cells away from each other.<br />

Furthermore, analysis of the binary masks<br />

shows evidence of cell division. Each set of<br />

binary masks had more cells than that of the<br />

previous day. This phenomenon may have<br />

occurred if cells that were not initially in the<br />

viewing frame moved into view or if the cells<br />

already in view divided in place. However,<br />

tracking the movement of cells in real<br />

time would be required to provide further<br />

evidence for this inference.<br />

One limitation of our experiment is that it is<br />

difficult to image the same gel location for<br />

each day. According to the current protocol,<br />

the cells must be fixated before confocal<br />

view, so the experiment operates under the<br />

assumption that the distribution of cells in<br />

the gel at any time is the same. We conclude<br />

that the clustering observed at a different<br />

location on Day 3 suggests that the cells<br />

viewed on Day 2 would have experienced the<br />

same amount of clustering had they been<br />

allowed to live to the next day. However,<br />

we had a sample size of four different gel<br />

locations for each day and observed the<br />

same general characteristics across locations,<br />

providing evidence to assume that the spatial<br />

distribution in one location is representative<br />

enough of the whole cell distribution.<br />

The NND statistical model provided robust<br />

results. The Cell Profiler data and the NND<br />

plugin in ImageJ were identical in terms of<br />

the object number and the calculated NND,<br />

but the Cell Profiler method required fewer<br />

post processing steps, allowing less room for<br />

error.<br />

An area of improvement for our method of<br />

statistical analysis would be to differentiate<br />

between cells organized in a line and<br />

cells clustered in a ball. Our traditional<br />

understanding of clustering involves a<br />

circular cluster but the images showed<br />

clustering in the form of a slanted line.<br />

Because the images are cross sections<br />

in the z direction and several images in a<br />

row showed a line of cells, that indicates<br />

clustering in the form of a slanted plane in<br />

the gel. Both circular and linear distributions<br />

could have the same NND values, but the<br />

present analysis fails to explain different<br />

clustering behaviors. Regardless of spatial<br />

distribution, smaller NNDs occur as an effect<br />

of the treatment applied to the sample.<br />


In the presence of Dasatinib there is a<br />

significant decrease in NND over the course<br />

of four days. All the methods used to analyze<br />

the data suggest that cells cluster in the<br />

presence of Dasatinib. Clustering induced<br />

by Dasatinib will induce a reversal of EMT<br />

induced mesenchymal cells into adopting<br />

a more epithelial phenotype. These cell<br />

clusters reduce the progress of metastasis<br />

of the cancer, bringing the patient extended<br />

lifetime. To examine the possibility that<br />

the cell’s decrease in movement causes<br />

clustering in Dasatinib treated cells, scanning<br />

electron microscopy (SEM) imaging can show<br />

diseased cell mechanisms for movement<br />

in the presence of the drug. To determine<br />

whether the cell clustering occurs due<br />

to migration or cell replication, molds<br />

constructed using the engineering design<br />

process will be used for live cell confocal<br />

imaging. Current and ongoing evaluations<br />

of Dasatinib’s properties will define its<br />

effectiveness as a cancer drug.<br />


[1] American Cancer Society, https://www.cancer.org/cancer/<br />

small-cell-lung-cancer/about/key-statistics.html (accessed Jan.<br />

4, <strong>2018</strong>).<br />

[2] Xiao, D., et al. J Thoracic Dis, 2010, 2, 154-159.<br />

[3] Peng, D. H., et al. Oncogene, 2017, 36, 1925-1938.<br />

[4] Sulzmaier, F. J, et al. Nat Rev Cancer, 2014, 14, 598-610.<br />

[5] Gibbons, D. L., et all. Genes Dev, 2009, 23, 2140-2151.<br />

DESIGN BY: Priscilla Li<br />

EDITED BY: Olivia Zhang<br />







eDNA refers to the<br />

genetic material<br />

organisms shed<br />

as waste in the<br />

environment (e.g.<br />

water, sediment,<br />

ice cores, etc.) that<br />

can be directly<br />

sampled<br />

Introduction<br />

Marine ecosystems are threatened<br />

worldwide by a variety of anthropogenic<br />

stressors which have severe implications<br />

for global biodiversity, economy, and<br />

human health. 1,2 Examining the abundance,<br />

distribution, and diversity of marine<br />

communities is vital to understanding<br />

basic ecological questions pertaining to<br />

conservation and resource management. 2,3<br />

Traditionally, scientists monitor marine<br />

organisms using techniques reliant on<br />

in-situ visual identification and counting<br />

of organisms. These methods, which<br />

include roving diver surveys, trawls, netting,<br />

tagging, electrofishing, and rotenone<br />

poisoning, are expensive, time-consuming,<br />

invasive, limited in scope, and reliant<br />

on taxonomic experts. 3,4 In addition,<br />

such traditional techniques are prone to<br />

produce a significant number of falsenegatives<br />

in which species actually present<br />

in an environment are not seen in the<br />

survey, generally because they are rare<br />

and/or not easily seen. 2 Addressing these<br />

limitations using a molecular approach<br />

may limit the human biases associated with<br />

these sampling methods.<br />

Improvements to DNA sequencing<br />

technology and decreased sequencing costs<br />

have made sampling for environmental<br />

DNA (eDNA) in marine environments<br />

more feasible. eDNA refers to the genetic<br />

material organisms shed as waste in the<br />

environment (e.g. water, sediment, ice<br />

cores, etc.) that can be directly sampled. 4<br />

For the purpose of this review, eDNA<br />

collection from specifically liquid water<br />

samples were considered because they<br />

detect organisms in recent time (on the<br />

order of hours to days) due to their faster<br />

degradation rates in the water. 4 While<br />

ecological applications of eDNA started in<br />

microbial communities in marine sediments<br />

and invasive species in aquatic habitats,<br />

there have been a handful of studies in the<br />

past few years that have sampled for larger<br />

size classes, like macrofauna, from marine<br />

communities. 5-7<br />

Regardless of ecosystem, the “eDNA<br />

metabarcoding” approach allows for<br />

quantification of whole communities using<br />

water sampling (Figure 1). Water samples<br />

are collected, filtered, extracted for DNA,<br />

amplified using specific PCR primers, and<br />

analyzed using next-generation sequencing<br />

for amplicons. Sequencing data is then<br />

compared to a reference database of<br />

partially or fully characterized genomes<br />

of organisms present in that particular<br />

region. Other further applications of DNA<br />

extracts such as quantitative PCR (qPCR)<br />

are also utilized in place of next-generation<br />

sequencing for identification of organisms. 7<br />


Identifying Presence/<br />

Absence of Marine<br />

Macrofauna Across<br />

Spatial Scales<br />

eDNA sampling has been utilized in a<br />

variety of marine ecosystems to detect the<br />

presence of marine macrofauna, including<br />

marine fish and mammal species. In<br />

one of the first studies to sample eDNA<br />

from marine communities, Thomsen<br />

et al. (2012a) found that in comparison<br />

to nine different traditional surveying<br />

techniques, eDNA performed as well or<br />

better than traditional surveying techniques<br />

at detecting commercially important yet<br />

rarely-detected fish species in the Sound of<br />

Elsinore. After multiple trials, the traditional<br />

surveying techniques, were only able to<br />

detect on average 4.3 species using fish<br />

pots to 14.7 species using night-snorkeling.<br />

In comparison, the eDNA samples detected<br />

more, at 15 fish species. In addition, the<br />

eDNA samples detected 4 bird species<br />

that could not have been detected using<br />

traditional surveying techniques. However,<br />

the scope of this study was limited, as<br />

only three half-liter water samples were<br />

examined, and these findings cannot be<br />

reasonably extrapolated to apply over<br />

larger spatial scales.<br />

Port et al. (2015) addressed some of<br />

these limitations and found that eDNA<br />

sampling still outperformed traditional<br />

roving diver surveys in a 2.5 km transect<br />

across kelp forests, rocky reefs, sand<br />

patches, and seagrass habitats. While the<br />

visual surveys identified 12 taxa, the eDNA<br />

samples identified 11 of those and 18<br />

additional taxa that were not detected by<br />

the visual surveys. The sensitivity of eDNA<br />

to detect species indicates that on larger<br />

spatial scales, the false-negative rate of<br />

traditional surveys far exceeds that of eDNA<br />

sampling. 2 In addition to detecting elusive<br />

fish species, they found that eDNA can be<br />

used to determine the spatial patterns of<br />

entire marine communities as well. Within<br />

each habitat, the distribution of species<br />

was more consistent, while across these<br />

habitats, they were markedly different.<br />

This indicates that while ocean water<br />

movement could theoretically move eDNA<br />

to vastly different locations from their point<br />

of origin, eDNA tends to stay localized (in<br />

this case, within 60 meters) of a particular<br />

habitat. 2<br />

However, for organisms with large<br />

home ranges such as cetaceans, eDNA is<br />

dispersed across a wide spatial scale and<br />

becomes less useful in comparison to other<br />

monitoring methods like bioacoustics. 8 For<br />

the harbor porpoise (Phocoena phocoena),<br />

for example, eDNA detection was only<br />

reliable in controlled environments and<br />

performed worse than acoustic detections<br />

in natural environments. However, because<br />

scientists were able to identify a long-finned<br />

pilot whale (Globicephala melas), another<br />

cetacean, in the natural environment<br />

that is rarely sighted, the research group<br />

concluded that further polishing of the<br />

eDNA sampling method could prove to be<br />

promising for monitoring efforts. 8<br />

The relationship between eDNA<br />

abundance, relative abundance, and<br />

biomass has been shown in closed<br />

marine and aquatic systems, but<br />

has yet to be applied successfully in<br />

natural marine habitats.<br />

Current Limitations to<br />

eDNA Applications<br />

The success of eDNA detection is limited by<br />

both site-specific environmental conditions,<br />

sample processing at the molecular level,<br />

and bioinformatics analyses.<br />

1 2 3 4 5 6 7<br />

Sample<br />

collection<br />

DNA<br />

extraction<br />

DNA<br />

amplification<br />

High-throughput<br />

sequencing<br />

Bioinformatic<br />

processing<br />

Species<br />

identification<br />

Ecological<br />

analysis<br />

Figure 1. Simplified representation of a metabarcoding (next-generation sequencing) pipeline.<br />


I. Relating Sequence<br />

Abundance to Relative<br />

Abundance<br />

While studying the presence of marine<br />

macrofauna is a novel approach to<br />

understanding many basic ecological<br />

questions, relating the sequence<br />

abundance from a water sample to the<br />

relative abundance of an organism in<br />

a natural community is still difficult to<br />

determine. The relationship between<br />

eDNA abundance, relative abundance,<br />

and biomass has been shown in closed<br />

marine and aquatic systems, but has yet to<br />

be applied successfully in natural marine<br />

habitats. 9,10<br />

II. Environmental<br />

Constraints<br />

As with any field method, eDNA sampling<br />

assumes that the contents of a water<br />

sample are representative of the whole<br />

community. To ensure that a water sample<br />

is homogeneous throughout, scientists<br />

often collect subsamples from larger water<br />

samples in order to determine if there are<br />

significant differences in the sequencing<br />

data between subsamples. 4,9<br />

The degradation rates of eDNA in marine<br />

environments are also important for<br />

determining how long the presence signal<br />

of an organism persists in the environment<br />

(and potentially moves to distant locations<br />

through currents). 3,4,10 Since eDNA shedding<br />

and degradation depends on a variety of<br />

factors based on the environment, target<br />

organisms’ physiology, abiotic and biotic<br />

factors, DNA characteristics, population<br />

size, and more, study-specific degradation<br />

and shedding experiments should be<br />

utilized to calibrate the eDNA signal. 3<br />

eDNA proves to be highly sensitive and<br />

reliable in determining the presence of<br />

marine macrofauna in comparison to<br />

traditional visual/trap-based methods<br />

III. PCR Bias and Primer<br />

Choice<br />

The primer choice during PCR is crucial<br />

to determine the region of DNA that<br />

will be amplified and sequenced from<br />

an eDNA sample and must be validated<br />

using experimental controls or online<br />

programs. 4,7 There are tradeoffs in primer<br />

choice and design - some primers have a<br />

higher affinity to some sequences and not<br />

others, affecting which marine organisms<br />

transmit the largest detection signal. 4<br />

Primer choice introduces amplification<br />

bias, which is influenced by the types of<br />

fishes surveyed and the environmental<br />

conditions of the area. 9,10 For example,<br />

when Kelly et al. (2014) used the 12S<br />

mitochondrial DNA (mtDNA) primers, they<br />

were able to detect bony fishes with a<br />

low false-negative rate, but were not able<br />

to detect the cartilaginous fishes or sea<br />

turtle in the mesocosm tank. For these<br />

organisms, species-specific primers were<br />

needed for detection. Since the community<br />

composition can vary so widely depending<br />

on the primer choice and amplification bias,<br />

researchers may use multiple universal and<br />

species-specific primer sets on the same<br />

DNA extracts to obtain higher resolution<br />

and detection. 4,9<br />

IV. Quality Controlling Reads<br />

and Reliable Reference<br />

Databases<br />

After samples are sequenced, they come<br />

back as raw material known as “reads”<br />

and are processed for quality control and<br />

validation. 7 Known as bioinformatic filtering,<br />

sequences are assigned to samples,<br />

filtered, trimmed and discarded based on a<br />

strict set of criteria. 2,4,9,10 Although detecting<br />

rare, cryptic, or low-abundance species is<br />

desired, strict sequence and taxon filtering<br />

ensures high-confidence reads that could<br />

repeatedly and reliably show presence of<br />

organisms while removing false positives,<br />

or organisms artificially present in the data<br />

(likely from contamination) but not present<br />

in the actual environment. 2<br />

After quality control and validation,<br />

Operational Taxonomic Units (OTUs) are<br />

assigned to sequences and referenced to<br />

known genomic databases for taxonomic<br />

identification. Generally, sequences are<br />

clustered into OTUs and matched to known<br />

genus or species sequences if they are<br />

>99% similar to each other. 2,4,9,10 However,<br />

the proper identification of these marine<br />

organisms relies heavily on the quality of<br />

the reference database. In systems that are<br />

not well-studied, the reference database<br />


may not be reliable.<br />

Conclusion<br />

The future of eDNA as a monitoring tool<br />

for marine macrofauna communities is<br />

possible, but currently limited in scope<br />

due to the methodological constraints that<br />

need to be considered. Current research<br />

indicates that while eDNA proves to be<br />

highly sensitive and reliable in determining<br />

the presence of marine macrofauna in<br />

comparison to traditional visual/trapbased<br />

methods, relating eDNA sequence<br />

abundance to the relative abundance in the<br />

community requires further investigation.<br />

This is due to the fact that eDNA<br />

sequence abundance varies depending<br />

on the particular workflow and sitespecific<br />

environmental factors. However,<br />

establishing multiple avenues to test the<br />

importance of these limitations within an<br />

experiment can help contextualize these<br />

problems. For example, including an<br />

eDNA degradation experiment, multiple<br />

primer sets, and a custom database are all<br />

different methods researchers mentioned<br />

in this review used to address some of<br />

these constraints. Although it is difficult<br />

to control for all of the abiotic, biotic,<br />

and molecular factors, the importance<br />

of accurate monitoring efforts in these<br />

ecosystems cannot be understated.<br />

and 3) to continue building on known<br />

reference databases. Combined, these<br />

considerations will improve the eDNA<br />

sampling and metabarcoding method,<br />

promoting its eventual establishment as<br />

the gold standard for marine community<br />

monitoring, resource management, and<br />

conservation efforts.<br />

References<br />

[1] Halpern, B. S. et al. Science. 2008. 319 (948-952).<br />

[2] Port, J. A. et al. Mol. Ecol. 2015. 25 (527-541).<br />

[3] Sassoubre, L.M. et al. Env. Sci. and Tech. 2016. 50<br />

(10456-10464)<br />

[4] Thomsen, P. F. et al. PLoS ONE. [Online] 2012a. 7.<br />

https://doi.org/10.1371/journal.pone.0041732 (accessed<br />

Nov. 14, 2017)<br />

[5] Díaz-Ferguson, E. E.; Moyer, G. R. Revista de biologia<br />

tropical. 2014. 62.4 (1273-1284).<br />

[6] Thomsen, P. F. et al. Mol. Ecol. 2012b. 21 (2565-2573).<br />

[7] Rees, H. C. et al. J. Applied Ecol. 2014. 51 (1450-1459).<br />

[8] Foote, A. D. et al. PLoS ONE. [Online] 2012. 7. https://<br />

doi.org/10.1371/journal.pone.0041781 (accessed Nov. 14,<br />

2017)<br />

[9] Kelly, R. P. et al. PLoS ONE. [Online] 2014. 9. https://<br />

doi.org/10.1371/journal.pone.0086175 (accessed Nov. 14,<br />

2017)<br />

[10] Lacoursière-Roussel, A. et al. J. Applied Ecol 2016. 53<br />

(1148-1157).<br />

[11] DiBattista, J. D. et al. Coral Reefs. 2017. 36.4 (1245-<br />

1252)<br />

Icons from AFY Studio, Aleksandr Vector,<br />

Jeffrey Qua, Luke Patrick, and Vega Asensio via<br />

the Noun Project<br />

Design by Kaitlyn Xiong<br />

Edited by Jenny Wang<br />

relating eDNA<br />

sequence abundance<br />

to the relative<br />

abundance in the<br />

community requires<br />

further investigation<br />

. . . due to the fact<br />

that eDNA sequence<br />

abundance varies<br />

depending on the<br />

particular workflow<br />

and site-specific<br />

environmental factors.<br />

Thus, further studies utilizing eDNA should<br />

proceed in three ways: 1) to take advantage<br />

of eDNA’s benefits in presence/absence<br />

studies to detect rare, and cryptic species,<br />

2) to refine the methodological details,<br />

including primer design and bioinformatic<br />

analyses, for more reliability and efficiency,<br />


eviewing the relationship between<br />




by Mahesh Krishna<br />


Primary Sclerosing Cholangitis (PSC)<br />

is a chronic and progressive disease<br />

of unknown etiology that affects the<br />

bile ducts in the liver. 1 Inflammatory<br />

Bowel Disease (IBD) is a chronic disease<br />

affecting the gut that comprises of<br />

two classifications: Crohn’s disease<br />

(CD) and ulcerative colitis (UC). 2 The<br />

exact mechanism for both diseases is<br />

unknown, yet as high as 80% of patients<br />

with PSC are also diagnosed with IBD. 3<br />

This suggests that these two diseases<br />

are closely related and may even have a<br />

shared ‘trigger.’ This article provides an<br />

overview of the current research carried<br />

out on the relationship between IBD and<br />

PSC by first focusing on theories of the<br />

pathogenesis of PSC and then explaining<br />

how these theories can explain the<br />

association with IBD.<br />




Although the exact pathogenesis of PSC is<br />

unknown, there are three main theories<br />

that have been proposed: a) the “leaky<br />

gut”, b) the “gut lymphocyte homing”, and<br />

c) the “toxic bile” theory. The earliest one<br />

has been the ‘leaky gut’ theory, which<br />

proposes that an injury to the mucosa in<br />

the gut would cause a ‘leakage’ of bacteria<br />

into the circulation of the body, eventually<br />

reaching the liver and leading to PSC. 4<br />

The ‘leaky gut’ theory is concerned with<br />

The exact mechanism for<br />

both diseases is unknown,<br />

yet as high as 80% of<br />

patients with PSC are<br />

also diagnosed with IBD.<br />

pro-inflammatory bacteria that escape the<br />

gut due to the increased permeability of<br />

the intestinal walls (‘leaky’). 5 Then, these<br />

bacteria are able to reach the bile ducts<br />

in the liver and upregulate inflammation<br />

through lipopolysaccharides leading to<br />

PSC. 6 Since PSC does not seem to respond<br />

to immunosuppressants, research<br />

suggests that non-immune mechanisms<br />

such as bacterial infections, ischemia,<br />

and toxicity are also important, which<br />

are explored in the ‘leaky gut’ theory. 7<br />

Therefore, genetically susceptible<br />

individuals exposed to bacteria may<br />

start having their hepatic macrophages<br />

produce pro-inflammatory cytokines<br />

such as TNF and chemokines, which in<br />

turn may attract and activate T-cells, B<br />

cells, monocytes, and neutrophils to the<br />

liver and around the bile ducts, causing<br />

damage and thus leading to cholestasis<br />

and PSC. 7 The ‘leaky gut theory’ is an<br />

interesting explanation to explain the<br />

pathogenesis of PSC, but it is not the only<br />

theory.<br />

As more research has been conducted<br />

through genome-wide association studies<br />

(GWAS), a strong connection to the<br />

human leukocyte antigen (HLA) complex<br />

was identified, suggesting an autoimmune<br />

component affecting susceptibility<br />

to PSC. 5 Based on the results of the<br />

GWAS, other models, including the ‘gut<br />

lymphocyte homing’ theory and the ‘bile<br />

acid toxicity theory,’ were developed 1,5 It is<br />

also important to note that environmental<br />

risk for the disease likely contributes<br />

50% in the development of the disease,<br />

therefore, complicating the application of<br />

one particular theory to explain PSC. 5 A<br />

unified model of the various theories has<br />

not yet been proposed.<br />

PSC pathogenesis theories:<br />

1<br />

Leaky Gut<br />

2<br />

Gut Lymphocyte Homing<br />

3<br />

Toxic Bile<br />


Gut microbiota and bile homeostasis<br />

Human mechanistic insights<br />

• Hereditary choleostasis (eg, cystic fibrosis)<br />

• Infection with or without immunodeficiency<br />

• Ischaemia and other causes of secondary<br />

sclerosing cholangitis<br />

Murine mechanistic insights<br />

• Spontaneous models (eg, ABCB4-/-)<br />

• Induced models (eg, lithocholic acid)<br />

Pathological changes<br />

Crohn’s disease<br />

30 loci<br />

Fibrosis<br />

Dysplasia<br />

CCR9<br />

T<br />

α4β1<br />

Inflammatory<br />

bowel disease<br />

103 loci<br />

Ulcerative<br />

colitis<br />

22 loci<br />

7 loci<br />

1<br />

locus<br />

Primary<br />

sclerosing<br />

cholangitis<br />

7 loci<br />

HLA<br />

associations<br />

Inflammation<br />

B<br />

α4β7<br />

VCAM1 CCL25<br />

MADCAM1<br />

Endothelial cell<br />

Genetics and the HLA complex<br />

T-cell homing and autoreactivity<br />

Figure 1. This image shows the complex interactions throughout the body between genetics, the immune system, and the<br />

microbiome that leads to PSC-IBD and harmful changes within the body. From Hirschfield et al.1<br />

The ‘gut lymphocyte homing’ theory<br />

focuses on memory T-cells from the gut<br />

moving into the liver via the chemokine<br />

receptor CCR9 and integrin α4β7,<br />

triggering inflammation once reactivated. 9<br />

Recent research has found evidence of<br />

memory T-cells of common clonal origin in<br />

both the liver and gut of patients with PSC-<br />

IBD.10 CCR9+ α4β7+ T-cells are recruited<br />

to the gut by binding to mucosal vascular<br />

addressing cell adhesion molecule 1<br />

(MAdCAM-1) and chemokine CCL25, which<br />

are usually uniquely expressed in the<br />

gut. 9 MAdCAM-1 and CCL25, however, are<br />

induced in the liver of patients with PSC<br />

due to hepatic inflammation through proinflammatory<br />

cytokines (like TNFα) and<br />

activation of VAP1 in the veins near the<br />

liver. 1 The ‘gut lymphocyte homing’ theory<br />

attempts to explain the pathogenesis of<br />

PSC by incorporating an autoimmune<br />

component.<br />

Finally, the ‘bile acid toxicity’ theory<br />

concerns the failure of mechanisms to<br />

protect biliary epithelial cells against bile.<br />

While bile is an important fluid that aids<br />

in digestion, it is toxic. 11 Cholangiocytes,<br />

the epithelial cells of the bile ducts,<br />

are protected from bile acid toxicity by<br />

a variety of mechanisms including a<br />

bicarbonate layer and a calcium-driven<br />

channel. 5 Therefore, a disturbance in bile<br />

homeostasis is believed to contribute<br />

to the development of PSC. 5 Bile acid<br />

homeostasis regulation, however, is not<br />

completely understood. 12 Currently, the<br />

recommended medication for someone<br />

diagnosed with PSC is ursodeoxycholic<br />

acid, although there are controversial<br />

findings on whether it actually helps or<br />

not. Ursodeoxycholic acid may utilize<br />

bile mechanisms by replacing toxic<br />

hydrophobic bile salts in serum, liver, and<br />

bile, which protects cholangiocytes against<br />

cytotoxicity of the bile acids. 11 Therefore,<br />

this theory is also vital in understanding<br />

the complete picture of the etiology of<br />

PSC.<br />




Studies have identified IBD in patients<br />

with PSC (PSC-IBD) as a unique entity<br />

compared to those with just IBD. 3 This<br />

is due to different risk genes found<br />

between the two diseases and unique<br />

clinical presentations. 3,13 Additionally,<br />

PSC-IBD patients were found to have a<br />

higher risk of colorectal cancer, yet a less<br />

active form of IBD. 14 75% of cases of IBD<br />

in PSC-IBD is found to be classified as<br />

UC. 15 Similar to PSC, the exact mechanism<br />

for the cause of IBD and a cure have not<br />

been found. Important factors that may<br />

trigger an aberrant immune response<br />

and chronic gut inflammation include the<br />

gut microbiome, infectious agents, stress,<br />

genetics. 16<br />

The gut microbiota, in particular, has<br />

been found to have an impact on the<br />

pathogenesis of IBD. 16 Dysbiosis, an<br />

imbalance in the gut microbiome,<br />

has been shown through clinical and<br />

experimental data as having a pivotal role<br />

Both diseases share<br />

common antibodies that<br />

have a characteristic<br />

perinuclear staining<br />

pattern.<br />

in the pathogenesis of IBD. 16 Therefore,<br />

the presence or lack of an organism in the<br />

gut microbiome may trigger IBD in certain<br />

environmental conditions.<br />






Since PSC and IBD have a strong<br />

concurrence, there is a likely connection<br />

between the two diseases. There<br />

have been observations regarding the<br />

occurrence of PSC after a colectomy<br />

and occurrence of IBD after liver<br />

transplantation, which suggests that ‘gut<br />

lymphocyte homing’ might be causing<br />

both PSC and IBD. 17 Both diseases<br />

share common antibodies that have<br />

a characteristic perinuclear staining<br />

pattern. 15 However, PSC and IBD have<br />

been found to have limited genetic<br />

overlap suggesting these diseases<br />

utilize distinct genetic mechanisms. 15 In<br />

addition to the ‘gut lymphocyte homing’<br />

hypothesis, the ‘leaky gut’ hypothesis<br />

also connects the two diseases. The liver<br />

receives a large amount of its blood<br />

supply through the gut. As a result,<br />

the liver is also exposed to molecules<br />

present in the gut microbiome. 15<br />

Therefore, the dysbiosis present in<br />

PSC-IBD patients may alter homing of<br />

gut-specific lymphocytes or cause the<br />

intestine to become more ‘leaky’ to proinflammatory<br />

bacteria. 15 The ‘leaky gut’<br />

and ‘gut lymphocyte homing’ concepts<br />

attempt to provide a connection of PSC<br />

with IBD.<br />


The pathogenesis of PSC-IBD is still<br />

unknown, but it is known to involve a<br />

complex mechanism that may overlap<br />

between the two diseases. Of the three<br />

common theories of the etiology of PSC,<br />

two of them (gut lymphocyte homing<br />

and leaky gut) also attempt to explain<br />

its interaction with the gut and IBD.<br />

The ‘gut lymphocyte homing’ theory<br />

attempts to explain the connection<br />

through the aberrant expression of<br />

MAdCAM-1 and CCL25, which are usually<br />

only present in the gut. As a result of<br />

this unusual expression, memory T-cells<br />

with the appropriate homing receptors<br />

(chemokine receptor CCR9 and integrin<br />

Both diseases share<br />

common antibodies that<br />

have a characteristic<br />

perinuclear staining<br />

pattern.<br />

α4β7) may attack liver cells and gut cells,<br />

triggering the inflammation typical of<br />

PSC and IBD. The ‘leaky gut’ hypothesis<br />

justifies the connection between the<br />

two diseases through the portal system.<br />

The liver is constantly exposed to the<br />

intestinal microbiome through the<br />

circulation of blood. Therefore, it is<br />

thought that an imbalanced microbiome<br />

in the gut, which has been implicated in<br />

IBD, may also serve as a trigger in the<br />

development of PSC. The microbiome in<br />

PSC-IBD patients has been the subject of<br />

recent research.<br />

The phenotype of PSC-IBD patients<br />

is very unique and requires further<br />

research to better meet the need of the<br />

patient population. The diagnosis of<br />

PSC and UC for PSC-IBD patients also<br />

occur at a much earlier age than PSConly<br />

and UC-only phenotypes. 15 More<br />

resources are needed to address this<br />

health burden as the costs for patients<br />

of a PSC-IBD phenotype will be much<br />

greater, due to the early age of diagnosis<br />

for PSC and IBD and their debilitating<br />

effects over time. By elucidating the<br />

mechanisms of these diseases, hopefully<br />

a cure for both PSC and IBD can be<br />

developed in the near future.<br />


[1] Hirschfield G.M. et al. Lancet. 2013, 382, 1587-<br />

1599.<br />

[2] Nemati S.; Teimourian S. Mid East J Dig Dis. 2017,<br />

9, 69-80.<br />

[3] Chung B.K.; Hirschfield G.M. Curr Opin Gastro.<br />

2017, 33, 93-98.<br />

[4] Karlsen T.H. Gut. 2016, 65, 1579-1581.<br />

[5] Karlsen T.H. et al. J Hepatol. 2017. 67, 1298-1323.<br />

[6] Pontecorvi V. et al. Ann Transl Med. 2016, 4, 512.<br />

[7] Cullen S.; Chapman R. Best Pract Res Clin Gastro.<br />

2001, 15, 577-589.<br />

[8] Aron J.H.; Bowlus C.L. Semin Immunopathol. 2009,<br />

31, 383-397.<br />

[9] Trivedi P.J.; Adams D.H. J Autoimmun. 2013, 46,<br />

97-111.<br />

[10] Henriksen E.K. et al. J Hepatol. 2017, 66, 116-122.<br />

[11] Trauner M. et al. N Engl J Med. 1998, 339, 1217-<br />

1227.<br />

[12] Chiang J.Y. F1000Res. 2017, 6, 2029.<br />

[13] Sano H. et al. J Hepatobiliary Pancreat Sci. 2011,<br />

18, 154-161.<br />

[14] Sokol H. et al. World J Gastro. 2008, 14, 3497-<br />

3503.<br />

[15] Palmela C. et al. Gut Liver. <strong>2018</strong>, 12, 17-29.<br />

[16] Nishida A. et al. Clin J Gastro, 2017, 11, 1-10<br />

[17] Nakazawa T. et al. World J Gastro, 2014, 20,<br />

3245-2354.<br />

DESIGN BY: Katrina Cherk<br />

EDITED BY: Shrey Agarwal<br />


the science of beauty<br />

by Krithika Kumar<br />

Henry David Thoreau, in his book Walden, details<br />

his almost two-year excursion of simple living in<br />

the woods of Massachusetts. He viewed nature<br />

as a way to achieve a higher understanding of the<br />

universe, and enjoyed being one with the solitude<br />

and beauty it has to offer. Nature, thus, has a way<br />

of connecting humans to our emotions and eliciting<br />

positive thoughts and feelings. For example, it is<br />

a universal truth that a rainbow after a rainy day<br />

brings a smile to anyone’s face. The aurora borealis,<br />

or Northern Lights, are regarded by many as<br />

breathtaking, a must-see on planet Earth. But how<br />

does nature capture our attention and scintillate<br />

our senses? What are the long-term effects of<br />

spending time in the outdoors?<br />

Beauty in the natural world affects humans<br />

subconsciously: spending time in the outdoors is<br />

connected to overall mental well-being. A simple<br />

stroll through a forest, for example, can allow us<br />

to distance ourselves from our otherwise chaotic<br />

thoughts. We are forced to regard every stimuli<br />

around us, from the sun shining down upon us to<br />

the tall trees shrouding us to the the small squirrels<br />

and insects we are careful not to harm. Compared<br />

to the contemporary world, which forces humans<br />

to live life in the fast lane through the influence<br />

of technology and commerce, nature is Earth at<br />

its most basic level. It allows humans to take a<br />

step back and a breath in, and entices us with its<br />

many facets of simplicity and serenity. Thus, the<br />

environment melts stress and releases endorphins<br />

that can decrease feelings of depression and<br />

fatigue.<br />

Nature’s ability to distract us from the present also<br />

increases creativity and intelligence. David Strayer<br />

of the University of Utah showed that hikers were<br />

able to solve more complex puzzles after a four-day<br />

backpacking trip compared to a control group. The<br />

prefrontal cortex, which controls decision-making<br />

and social behavior, undergoes much strain from<br />

daily usage of technology and multi-tasking. This<br />

area of the brain can take a break when we respond<br />

to purely nature-driven stimulus. Nature allows<br />

the brain to reset so that it can perform tasks with<br />

renewed energy.<br />

A change of environment can also makes humans<br />

kinder and more generous. There is an out-of-body<br />

feeling associated with viewing an awe-inspiring<br />

landscape that makes one feel that one is part of<br />

something bigger than the present. It can make dayto-day<br />

inconveniences seem inconsequential and<br />

remind us that there is more to the world than what<br />

goes on in our lives. Humans are also more likely to<br />

be more ethical when faced with moral dilemmas<br />

after spending time in nature. Experiments<br />

conducted at the University of California, Berkeley,<br />

found that participants playing the Dictator Game<br />

(which measures the degree to which individuals<br />

will act out of self-interest) were more likely to be<br />

generous to their peers after being exposed to<br />

alluring nature scenes.<br />

Planet Earth’s most primitive offerings actually<br />

present us with complex and diverse benefits. A<br />

quick breath of fresh air can melt away feelings of<br />

stress and anxiety, while increasing cognitive focus<br />

and creativity. Perhaps we can create our own<br />

“Walden” and take a break from studying or working<br />

to simply enjoy the outdoors and spend time<br />

appreciating the many sides of our ever-changing<br />

world.<br />


[1] “How Nature Can Make You Kinder, Happier, and More Creative.”<br />

Greater Good, greatergood.berkeley.edu/article/item/how_nature_<br />

makes_you_kinder_happier_more_creative.<br />

[2] Louv, Richard. “Ten Reasons Why We Need More Contact with<br />

Nature | Richard Louv.” The Guardian, Guardian News and Media, 12<br />

Feb. 2014, www.theguardian.com/commentisfree/2014/feb/13/10-<br />

reasons-why-we-need-more-contact-with-nature.<br />

[3] “Henry David Thoreau.” Henry David Thoreau, transcendentalismlegacy.tamu.edu/authors/thoreau/.<br />

Vector from Freepik<br />


BOMB:<br />

the<br />


hereditary cancer<br />

TIME syndromes<br />


“Life comes with many challenges. The<br />

ones that should not scare us are the ones<br />

we can take on and take control of.” As<br />

hard as it is to believe, this is a quote from<br />

Angelina Jolie’s book about hereditary<br />

breast cancers where she encourages a<br />

more thorough integration of genomics<br />

into the field of oncology. Recently,<br />

celebrities such as Angeline Jolie have<br />

spoken out about the BRCA genes and<br />

their personal experiences with hereditary<br />

cancer syndromes. Jolie’s doublemastectomy<br />

and the media’s portrayal of<br />

her treatment have helped to drastically<br />

increase the awareness of genetic testing<br />

among the general population.<br />

Hereditary cancer syndromes, and<br />

particularly hereditary breast cancers,<br />

are primarily associated with the genetic<br />

mutations BRCA1 and BRCA2. An<br />

individual with the BRCA genes can have<br />

over a 70% chance of developing cancer<br />

with the right combination of genetic and<br />

environmental factors. With the odds<br />

of developing cancer so high, it seems<br />

obvious that any measure we can take to<br />

lower this penetrance should be fervently<br />

supported by all medical professionals.<br />

Right?<br />

There’s an important ethical dilemma<br />

that arises whenever we think about<br />

using these new technologies. On the one<br />

hand, genomics, the technological aspect<br />

of genetics concerned with sequencing<br />

and analyzing an organism’s genome,<br />

has greatly improved the prognosis for<br />

cancer patients. Genetic profiling can help<br />

individuals with hereditary breast cancers<br />

through every stage of their disease, from<br />

diagnosis to treatment. An interesting<br />

use of genetic profiling is using the BRCA<br />

genes to help classify tumors. Because<br />

patients with the same BRCA mutation<br />

most likely have the same type of tumor,<br />

classifying one individual’s tumor means<br />

you have classified the other’s! More<br />

importantly, by providing a means of<br />

pre-symptomatic testing, patients are<br />

able to utilize precautionary measures<br />

such as estrogen-regulating drugs and<br />

preventative surgeries like mastectomies<br />

(removal of breast tissue).<br />

On the other hand, it is simply not<br />

possible to test every individual for the<br />

BRCA genes. For one, they are extremely<br />

costly. There is no way that a geneticist<br />

can indiscriminately recommend<br />

genetic testing to every patient as DNA<br />

sequencing tests have yet to be covered<br />

by every health insurance plan. Without<br />

insurance, the cost of one of these tests<br />

can range from $475 to over $4000.<br />

Furthermore, the results of such a test<br />

can put an individual at risk for genetic<br />

discrimination. Although GINA, or the<br />

Genetic Information Nondiscrimination<br />

Act, protects from genetic discrimination,<br />

or having to pay an inflated premium<br />

due to genetic test results that reveal<br />

a predisposition for a severe genetic<br />

disease, it only applies to health insurance<br />

and not life insurance. Having young<br />

individuals get tested for the BRCA genes<br />

comes with the possibility of hiking up<br />

their life insurance premiums later in life.<br />

Finally, an individual’s mental wellbeing is<br />

at risk because the fear of one’s diagnosis<br />

can understandably cause anxiety and/or<br />

depression.<br />

So the question remains. Do we<br />

encourage the general public to get<br />

tested for the BRCA genes if they believe<br />

that they have a strong family history of<br />

hereditary cancers? Although there is no<br />

answer to this question that pleases all<br />

medical professionals, one thing is certain:<br />

An ordinary individual can possibly<br />

prevent cancer in his or her family with<br />

the help of genetic testing. When used<br />

cautiously, genetic testing is an invaluable<br />

tool in all stages of cancer treatment and<br />

prevention. It seems clear to me that<br />

advocating for widespread awareness<br />

of the advantages of genetic testing in<br />

reducing cancer penetrance is one of<br />

the most beneficial ways to prevent the<br />

growth of tumors in an individual and to<br />

control inheritance through generations.<br />

Why are we waiting, then? Let’s take<br />

control and not let cancer scare us<br />

anymore.<br />


[1] “GINA & Your Health Insurance.” GINAhelp.org - Your<br />

GINA Resource. N.p., n.d. Web. 03 Nov. 2016.<br />

[2] Moyer, Virginia A. “Risk assessment, genetic<br />

counseling, and genetic testing for BRCA-related<br />

cancer in women: US Preventive Services Task Force<br />

recommendation statement.” Annals of internal<br />

medicine 160.4 (2014): 271-281.<br />

[3] Chen, Sining, and Giovanni Parmigiani. “Meta-analysis<br />

of BRCA1 and BRCA2 penetrance.” Journal of Clinical<br />

Oncology 25.11 (2007): 1329-1333.<br />





Rice University Center for Civic Leadership<br />

Program in Writing and Communication<br />

Rich Family Endowment<br />

Wiess School of Natural Sciences<br />

George R. Brown School of Engineering<br />

The Energy Institute High School<br />

Young Women’s College Preparatory Academy

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